Rachael L Fulton

Kennedy R Lees

Erich Bluhmki

Gabriele Biegert

Gregory W Albers

Stephen Davis

Geoffrey A Donnan

James C Grotta

Markku Kaste

Ashfaq Shuaib

Danilo Toni

Jun Lee

Maarten G Lansberg

Michael Mlynash

Matus Straka

Roland Bammer

Jean-Marc Olivot

Stephanie Kemp

UCSD Branko N Huisa

CA La Jolla

David S Liebeskind

UCSD Rema Raman

UCLA Qing Hao

CA Los Angeles

Karin Ernstrom

Brett C Meyer

Dawn M Meyer

Thomas M Hemmen

; Ucsd

Pablo Garcı ´a-Bermejo

Ana I Calleja

Elisa Cortijo-Garcı ´a

Santiago Pe ´rez-Ferna ´ndez

Jose ´m

Del Monte

Nieves Te ´llez

Dulce M Campos

Rosario Ferna ´ndez-Herranz

Juan F Arenillas

W MP1 Selection for Delayed Intravenous Alteplase Treatment Based on Prognostic Score

Background: Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled analysis of RCT suggests that additional patients could benefit but others may be harmed with initiation of alteplase beyond 4.5 hours after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection to be applied first to an existing trial dataset and then validated in the pooled RCT 4.5-6h data. Methods: We selected 500 patients treated by iv alteplase and 500 controls from VISTA, matching Rankin (mRS) outcomes to those from pooled RCT 4.5-6h data. We ranked patients by prognostic score (from age and NIHSS). We iteratively chose lower and upper score limits to exclude patients with extreme predicted outcomes. We generated odds ratios for alteplase treatment effects on mRS distribution within these populations of patients with intermediate prognostic scores; and examined proportions attaining mRS 0-1, and surviving. We chose prognostic score limits to optimise our sample for a net treatment benefit significant at pϭ0.01 by Cochran-Mantel-Haenszel test and by ordinal logistic regression. We also defined more inclusive limits based on pϭ0.05 criteria. After finalising prognostic score limits, for validation we had these applied by an independent statistician to the pooled RCT data for 4.5-6h, testing for net benefit by CMH test, ordinal regression and also by dichotomised outcomes: mRS 0-1, mortality and PH2 bleeds at 5% significance. All analyses were adjusted for age and NIHSS. Results: In the VISTA training dataset, limits of 56-95 on a prognostic score based on 145-0.46*age-2.5*NIHSS retained a population of 714 patients in whom there was net benefit significant at pϭ0.01; limits of 47-104 gave net benefit in 937 patients at pϭ0.05. When applied to the 1120 patients in the pooled RCT 4.5-6h dataset, score limits of 56-95 retained 711 patients and gave OR for improved mRS distribution of 1.13, 95% CI 0.87-1.47, CMH pϭ0.89. More patients achieved mRS 0-1 (OR 1.44, 1.02-2.05, pϭ0.04) but mortality and PH2 bleeds were increased: OR 1.56, 1. pϭ0.04; OR 15.6, pϭ0.0002 respectively. The wider limits of 47-104 gave ordinal OR 1. CMH pϭ0.40, nϭ988). Conclusion: Selection of patients between 4.5 and 6h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

Introduction: Carotid artery stenting (CAS) is a possible method of carotid revascularization for stroke prevention; however cerebral embolism may occur during the procedure. Hypothesis. Cerebral embolism during CAS could be associated with specific morphological and serological patterns. Methods: Consecutive patients with carotid artery stenosis undergoing filterprotected CAS were preoperatively evaluated to identify carotid unstable plaque at duplex ultrasound, complicated aortic plaque at trans-esophageal echocardiography and flogistic status with high sensitivity C-reactive proteins (hs-CRP) serum levels. Aortic arch type, carotid artery tortuosity index, and complexity of the procedure were considered. Cerebral embolism was evaluated by comparing at diffusion weight resonance magnetic imaging (DW-RMI) preoperative and postoperative cerebral lesions (number and volume in mm 3 of total, ipsilateral and contralateral cerebral lesions) and through the analysis of cerebral protection filters obtained from CAS by light and scanning electron microscopy. Results: From January to December 2009, 20 consecutive patients were submitted to CAS with no complications. At least 1 asymptomatic cerebral lesion on DW-MRI was present in 18 (90%) patients. Female gender was associated with higher total and ipsilateral number of cerebral lesions at DW-RMI (18.2Ϯ10.9 vs. 8.3Ϯ8.8 pϭ0.03 and 11.0Ϯ6.9 vs.4.0Ϯ5.3 pϭ0.02 respectively); presence of complicated aortic plaque was associated with higher volume of contralateral cerebral lesions (2350Ϯ2593 vs. 636Ϯ632 mm 3 pϭ0.02). Hs-CRP Ͼ5mg/l was correlated with higher number of total, ipsilateral and contralateral cerebral lesions (16.2Ϯ10.7 vs. 4.3Ϯ3.4 pϭ0.02, 9.3Ϯ6.6 vs. 1.5Ϯ2.3 pϭ0.01 and 6.8Ϯ4.7 vs. 2.8Ϯ1.1 pϭ0.04 respectively). HsCRP Ͼ5mg/l gives an OR 2.6 (C.I. 1.005-6.8) of elevated total number (nϾ5) of cerebral lesions and an OR 3.9 (C.I. 1.1-13.7) of elevated volume (Ͼ1000 mm3) of cerebral lesions. Hs-CRPϾ5 mg/l was also correlated with greater surface involvement by embolic materials in the cerebral protection filters at microscopic analysis (37.0Ϯ5.7 vs. 26.9Ϯ2.5 pϭ0.004). Neither the morphological characteristics of the plaque and of the supraortic vessels, nor the complexity of the procedure correlated with number or volume of new cerebral lesions at DW-RMI. Conclusions: Rather than morphological and technical aspects of the procedure, high levels of Hs-CRP are associated with higher embolic risk during CAS. These results are important in the definition of embolic potential of carotid plaques.

Introduction: Dynamic CT-perfusion (CTP) is frequently used in acute stroke imaging, however there is need for further standardization and harmonization of this technique for reliable quantification of tissue at risk. Perfusion thresholds applied to the entire brain to identify salvageable tissue have been established, but there is evidence for significantly different regional ischemic vulnerability. The purpose of this study was to assess and standardize human regional blood flow parameters in a large sample of non-stroke patients using whole brain dynamic CTP. Methods: Within 30 months, whole brain dynamic CTP was performed in 1050 patients admitted for new-onset acute stroke. In 135 cases, there was no evidence for any perfusion abnormality, persistent symptoms or infarction on follow up imaging. In these cases, CTP maps (cerebral blood-flow [CBF], -volume [CBV], time to peak [TTP] and mean transit time) were calculated and co-registered to standard MNI-152 space (FLIRT5.5). In all normalized CTP maps, a weighted average perfusion value (mean and SD) was calculated for each perfusion parameter in a priori brain regions defined by the anatomical probability distribution in the standardized Harvard Oxford cortical/subcortical atlases (significant differences P Ͻ 0.05 adjusted for multiple comparisons). Results: A total of 68 defined regions in 135 normal brains were evaluated. There were significantly different normalized values of regional perfusion parameters in cortex, subcortical grey matter and white matter. In cortical grey matter the highest mean perfusion values were observed in the Insula, Heschl's gyrus, calcarine gyrus and opercular cortex, the lowest in the temporal and frontal cortex. In subcortical grey matter the highest perfusion values were found in the Putamen, Thalamus, and Hippocampus (Figure 1). Discussion: This study demonstrates the variability of regional perfusion parameters derived from whole brain dynamic CTP in a large population. There are significantly different regional perfusion parameters in cortical and subcortical grey-and white matter and the results are in accord with gold standard PET studies in the past. Regional blood flow thresholds may be a more precise measure of tissue at risk to account for significant variability in regional ischemic vulnerability. Conclusion: A normalized map of dynamic CTP parameters of the whole brain is presented for the first time to target the need for standardization of stroke evaluation and to improve assessment of regional tissue at risk. Background: To date there have been 14 trials of surgery for spontaneous intracerebral haemorrhage. The trials have included different populations and have had equivocal results but have narrowed down the population of patients that may be more likely to benefit from surgery to those with lobar intracerebral haemorrhages and no intraventricular haemorrhage. The STICH II trial began in the autumn of 2006 and is due to complete patient recruitment at the end of August 2011. Methods: This international multicentre pragmatic randomised parallel group trial is being undertaken to establish whether a policy of early surgery improves outcome compared to a policy of initial conservative treatment. Patients with spontaneous ICH should have a superficial lobar haematoma, be within 48 hours of the event, and have a best motor score of 5 or more and a best eye score of 2 or more on the GCS. The treating neurosurgeon should be in clinical equipoise over the risks and benefits of both treatments. The patients may be randomised by telephone or web. If the patient is randomised to surgery the haematoma should be evacuated within 12 hours of randomisation. The primary outcome will be based on extended Glasgow Outcome Scale at six months. Results: By mid April 2010, 300 patients had been randomised into STICH II. The patients came from 21 different countries and 57 centres from around the world, including 16 patients from 5 of the 9 registered USA sites. The patients had a median age of 64 years and a median GCS of 13; 56% were male. More than 50% were recruited within 24 hours of ictus. Their haematoma had a median volume of 36 ml and a median depth from the cortex surface of 1mm. Further results will be presented. Conclusions: This study is necessary to define the most appropriate treatment for patients with lobar ICH. As we approach our last year of recruitment it is essential to encourage all centres who are yet to recruit as well as our active recruiting centres to increase their efforts for one more year. For further information visit: http://research.ncl.ac.uk/stich/.

Introduction: Surgical decompression improves outcome in patients with malignant middle cerebral artery (MCA) infarction when performed early. However, objective parameters that reliably predict a malignant course of MCA infarction have not been determined so far. We hypothesized that stroke volume and pre-stroke subarachnoid space (CSF), which indicates the intracranial volume reserve, are major determinants to develop a malignant MCA infarction. We here present a method which allows prediction of the course of large MCA infarction based on CT imaging at admission including perfusion CT. Methods: Patients with a proximal MCA occlusion and a reduced cerebral blood flow (CBV) involving at least 1/3 of the MCA territory were included. Patients were classified as having a malignant course of MCA infarction (clinical signs of herniation) or a non-malignant course. CCT at admission was used to determine the CSF-volume in the healthy hemisphere and the intracranial volume (IV). Brain parenchyma volume (BV) was defined as the difference of IV and CSF. CT perfusion with use of a 4D adaptive spiral allowed complete coverage of the MCA territory allowing segmentation of the total volume of significantly reduced cerebral blood flow (CBV), which indicates the infarct core. Normalized CSF volume (nCSF) was defined as CSF/IV and the normalized stroke volume (nSV) was defined as CBV/BV. We then calculated the ratio of nSV and nCSF. To determine which variables best predict a malignant course of MCA infarction a ROC analysis was conducted. Results: We included 29 patients (malignant n ϭ 15, non-malignant n ϭ 14). The ROC curve analysis is given in the table. The ratio of nSV and nCSF shows the lowest rate of false negative predictions (7.2%) in combination with a low rate of false positive predictions (6.6%). Conclusions: In this study a malignant course of MCA infarction was best predicted by the ratio of nCBV and nCSF. The suggested method therefore allows early identification of patients for surgical decompression. Since our method only requires CCT and perfusion CT it is particularly feasible in clinical practice.

Introduction: Experimental and human stroke studies suggest that preserved structural and functional integrity of the contralateral to the ischemic stroke hemisphere is strongly correlated with greater degree of subsequent recovery. Increasing fractional anisotropy (FA) values, measured by obtaining MRI diffusion tensor imaging studies, have been shown to correlate with integrity of the white matter. Objectives: To define the FA values in the region of the unaffected hemisphere that is homologous to the ischemic lesion (ROI-UN) at one month after stroke onset, and correlate these values with the clinical neurological scores in patients with ischemic stroke. Main Hypothesis: Elevated FA values in the ROI-UN at 1 month after stroke correlate with a greater NIHSS score improvement from baseline to outcome study (3 months). Methods: We prospectively studied ischemic stroke patients with clinical scores and MRI scans at baseline (1-3 days), 1 month an 3 months. The clinical neurological deficit was graded with NIHSS at each time point. The baseline scan was used for definition of lesion size. Subsequent scans were done in a 3T GE scanner. Multiparametric MRI protocol included: diffusion tensor imaging, T1WI, T2WI and DWI, which were acquired at each time point. The ischemic core was defined as the segment of the baseline ischemic lesion that remained abnormal in the subsequent MRI studies. The ROI-UN was defined after the ischemic core was outlined and flipped over onto the contralateral unaffected hemisphere. The FA values were defined in the infarct core and in the ROI-UN. Spearman's correlation coefficients were computed to assess the association between MR measurements at 1 and 3 months and the NIHSS score improvement from baseline to 3 months. The study was approved by the Institutional IRB. Results: We studied 20 patients, mean age 62 (Ϯ13) years. The mean baseline NIHSS score was 10.1 (Ϯ5.7). The mean 3-month NIHSS score was 4.6 (Ϯ5.3). There was strong correlation between the FA value in the ROI-UN and the NIHSS score improvement from baseline to 3 months (r: 0.624, pϭ0.007). There was however no significant correlation between the 1-month FA value in the ischemic core and the NIHSS score improvement from baseline to 3 months (r:0.194, pϭ0.46). Conclusions: Higher FA values in the unaffected hemisphere correlate with greater improvement in the NIHSS score from baseline to 3 months. These findings indicate that structural axonal integrity in the contralateral to the ischemic stroke hemisphere is one of the significant contributors to clinical recovery after ischemic stroke.

Objective: To describe the presentation, imaging characteristics, management, and outcome of neuroimaging-confirmed craniocervical arterial dissection (CCAD) in children. Methods: A computerized search engine identified all cases of CCAD at Children's Hospital Boston in children under 18 years old from 1994 to 2010. Using neuroimaging diagnostic criteria, 44 cases were identified. Results: There was a male predominance (66%). Spontaneous occurrence was the most frequent etiology (nϭ19; 43%). History of antecedent trauma was common (nϭ17; 39% overall; of these, 35% were intracranial dissection (ICD), 53% were extra-cranial dissection (ECD), 12% both ICD and ECD). The most common presenting symptoms were hemiparesis (nϭ19; 43%), headache or neck pain (nϭ14; 32%) and aphasia (nϭ10; 23%). The most commonly used initial imaging modalities were MR-and catheterangiography in 35(80%) and 5(11%) cases, respectively. Catheter angiography was the most commonly performed confirmatory test. Neuroimaging characteristics of CCAD included anterior circulation location in 28(64%) and left-sided location in 30(68%); 21(47%) were ICD, 18(41%) were ECD and 5 (11%) involved both intra-and extra-cranial vasculature. Most anterior circulation dissections, (nϭ22/28; 79%) involved ICD, while most posterior dissections (nϭ13/16; 81%) were extracranial. Neuroimaging evidence of cerebral ischemia at diagnosis appeared in 29(66%) cases. Of those with follow-up neuroimaging, 25(89%) had persistent arterial changes. Most patients were anticoagulated(nϭ25;56%); the majority (72%) involved ICD. No hemorrhage occurred following anticoagulation treatment. Average follow-up time was 3.3 years. Using Pediatric Stroke Outcome Measure (PSOM) criteria, 38% of children had a normal neurologic exam, while the remaining demonstrated mild-(22%), moderate-(22%) or severe (9%) motor impairment or persistent language dysfunction (9%). Conclusions: This large single-institution cohort of children with CCAD confirms prior findings and provides novel findings. We confirm a male predominance of CCAD, predilection for its occurrence in anterior circulation, and tendencies of ICD and ECD to occur in anterior and posterior circulations, respectively. Novel features found in the current cohort analysis include a high rate of spontaneous occurrence in over 40% of cases, the overall predominance of intracranial vascular location for dissection and neuroimaging signs of cerebral ischemia in only 2/3 of patients. Importantly, the majority of patients in the current cohort were anticoagulated and despite the intracranial location of dissection in 72% of this group, no consequent intracranial hemorrhage was observed. This cohort of pediatric CCAD demonstrated favorable clinical outcome.

Author Disclosures: E.S. Ho: None. A.R. Danehy: None. H.P. Goodkin: None. A.H. Huang: None. R. Robertson: None. N.J. Ullrich: None. M.J. Rivkin: None.

W MP75 Short-term Neurological Outcomes after Childhood Stroke: Results of a Population-based Cohort Study

Christine K Fox, S. Claiborne Johnston, UCSF, San Francisco, CA; Stephen Sidney, Kaiser Permanente Div of Rsch, Oakland, CA; Heather J Fullerton; UCSF, San Francisco, CA Background: Outcome data after childhood stroke have been limited to hospital series and stroke registries, and childhood hemorrhagic stroke outcome data are particularly limited. Previously reported high rates of deficits could reflect referral bias to tertiary care centers. Our objective was to determine neurologic outcomes at hospital discharge in children with stroke from a population-based cohort in Northern California. Methods: We performed a retrospective cohort study of children (29 days-19 years) enrolled in a Northern Californian integrated healthcare plan from 1/93-12/03. Cases of symptomatic ischemic and hemorrhagic stroke were identified through electronic searches of in-patient, out-patient, and radiology databases, and confirmed through independent chart review. Data were abstracted by a medical records analyst and confirmed by a pediatric neurologist. Deficit at discharge was defined as documentation of any abnormal neurological finding at the time of discharge from the acute hospitalization. Analyses were stratified by ischemic versus hemorrhagic stroke. Dichotomous variables were compared using Fisher's exact test. Multivariate logistic regression models including age, gender and clinical symptoms at presentation were used to identify predictors of residual neurological deficits at discharge. Results: In a cohort of 2.3 million children, 124 ischemic and 132 hemorrhagic strokes were identified. Ischemic strokes presented most commonly with hemiparesis (64%), altered mental status (31%), headache (30%) and seizure (28%). Hemorrhagic strokes presented most commonly with headache (60%), followed by altered mental status (58%), hemiparesis (25%) and seizure (18%). Median length of stay was 5.5 days for ischemic and 7 days for hemorrhagic stroke (Pϭ0.5). In hospital mortality was similar between ischemic (4%; 95% CI 0.05%, 7%) and hemorrhagic strokes (5%; 95% CI 1%, 8%). Neurological deficits at discharge were less frequent after hemorrhagic stroke, noted in 47% compared to 65% of ischemic strokes (OR 0.5, 95% CI 0.3, 0.8). On multivariate analysis, after adjusting for age and gender, hemiparesis (OR 6.5, 95% CI 2.0, 21) and altered mental status (OR 5.5, 95% CI 2.1, 14.3) at presentation were associated with neurological deficits at discharge after hemorrhagic stroke. The only predictor of deficits at discharge for ischemic stroke was presentation with hemiparesis (OR 5.4, 95% CI 1.9, 15.3). Neither seizure nor headache at stroke onset was predictive of neurological deficits at discharge. Conclusions: Even in a population-based cohort, children had high rates of neurological deficits at the time of hospital discharge after a pediatric stroke. Residual deficits at discharge were more frequent for ischemic than hemorrhagic stroke. Further studies are needed to determine long-term outcomes.

Background and Purpose -Recent studies have examined the overall cost of pediatric stroke, but there is little data regarding the sources of these costs. If physicians are aware of these sources, they may be able to work towards more cost-effective care. Methods: We examined an administrative database from 24 children's hospitals in the US affiliated with the Child Health Corporation of America to characterize individual patient costs. We searched anonymized records of children older than age 1 month who had no associated trauma codes. Using ICD-9 code searches of the primary diagnosis position, we identified 1,813 discharges, corresponding to 1,667 patients who had a diagnosis of stroke from 2003 to 2009. Total costs were divided into seven categories that were then subdivided into individual costs. Categories were ranked to determine which contributed the most to total cost, and individual costs were subsequently ranked within their categories. We also analyzed costs based upon stroke type. Total costs were adjusted using the annual US Consumer Price Index to compare the rate of increase with inflation. Results: Median total cost was $19,548 (Interquartile Range $10,721). Single admission occurred in 92.7% of the subjects, while 6.4% had two discharges. There were 703 patients (42%) with hemorrhagic strokes and 964 patients (58%) with ischemic strokes. The category "Other/nursing" contributed the most to total cost, followed by imaging, lab, pharmacy, clinical services, and supplies. Brain MRI and CT contributed the most to imaging costs. Inserting endotracheal tubes, continuous invasive mechanical ventilation, ventriculostomy, and brain procedures (diagnostic biopsies, excision of lesions, and brain incisions) were associated with high total cost (75 th percentile or greater). Hemorrhagic strokes (median $24,843,IQR $11,729) were more expensive than ischemic strokes (median $16,954,IQR $10,663). Patients admitted multiple times had a median total cost of $39,451 (IQR $23,859). Total cost increased from 2003 to 2009 but the increase did not exceed the rate of inflation. Conclusions: This is the first detailed analysis of cost for acute pediatric stroke care in multiple US children's hospitals. Our findings support earlier reports that hemorrhage in children accounts for a higher proportion of stroke than with adults, and hemorrhagic stroke is more expensive than ischemic stroke. Inpatient nursing and imaging are the two largest sources of cost. These categories are potential targets for cost containment, yet they are crucial for effective diagnosis and treatment. Necessary yet prudent use of imaging and inpatient stays may be strategies for cost containment.

Introduction: Rho-kinase (ROK)-mediated Ca 2ϩ sensitization of vascular smooth muscle (VSM) plays a pivotal role in cerebral vasospasm (CV). We previously showed that sphingosylphosphorylcholine (SPC), a sphingolipid, induces ROK-mediated Ca 2ϩ sensitization, which is regulated by serum total cholesterol (T-Cho). Here, we link this effect to the vascular tissue cholesterol level. Methods: Adult male Sprague-Dawley rats (400-500 g, nϭ45) received a control diet; a 1% cholesterol diet; or a 1% cholesterol dietϩ5% ␤-cyclodextrin (␤-CD), which depletes VSM cholesterol, for 8 weeks. Changes in the basilar artery diameter were measured using cranial window preparations. Serum T-Cho was measured using an L-type Wako CHO-H kit. T-Cho and phosphatidylcholine (PC) levels in the internal carotid artery (ICA) were measured using Gas Chromatography and Thin Layer Chromatography. Human brain VSM cells (HBVSMCs) were stained with filipin III to visualize cholesterol and counterstained with rhodamine phalloidin to visualize F-actin. The filipin III intensity for each cell was measured using ImageJ. Statistical analysis was by Mann-Whitney U-test. Values are meansϮSD. Results: Serum T-Cho and T-Cho in the ICA were significantly higher in rats fed a cholesterol diet compared to controls (131.8Ϯ20.0 mg/dl, nϭ16 vs. 53.6Ϯ10.7 mg/dl, nϭ24, PϽ0.001; 0.82Ϯ0.24 mg/g, nϭ5 vs. 0.49Ϯ0.09 mg/g, nϭ5, pϭ0.028). SPC (100 ı `mol/L)-induced contraction increased with the cholesterol diet and the extent correlated (r 2 ϭ0.75, nϭ40) with serum T-Cho levels. T-Cho in the ICA was reduced by a ˆ-CD (0.47Ϯ0.06 mg/g, nϭ5, pϭ0.016 vs. cholesterol diet) and the depletion of cholesterol inhibited the SPC-induced contraction. The mean % filipin III intensity of HBVSMCs treated with ␤-CD (5 mmol/L, 2 hr) also displayed a marked decrease (37.7Ϯ12.0%, nϭ35, PϽ0.001 vs. control cells). There were no significant differences in the PC content in the ICA among the three groups. Conclusion: Lipid rafts are cholesterol-enriched membrane microdomains that influence signal transduction. In this study, hypercholesterolemia increased VSM cholesterol (but not PC, a major component of nonraft membranes) and SPC-ROK-mediated VSM contraction. Depletion of VSM cholesterol (but not PC) by ␤-CD inhibited SPC-induced contraction. These results indicate that cholesterol potentiates SPC-ROK-mediated contractions of importance in CV and are compatible with a role for lipid rafts in this process.

Abnormal activation of neuronal and blood vessel cell death pathways are common features in acute stroke, whereas angiogenesis is a key requisite for brain tissue recovery. Spatial and temporal regulation of cytoskeletal dynamics critically modulates this process. A set of cell cycle kinases has been also implicated. Currently, their relationship to brain tissue recovery remains unclear. Our recent findings showed that the pharmacological inhibition of cyclindependent kinase 5 (Cdk5) with kinase inhibitor r-roscovitine and the deregulation of its activators p35/p25 with calpain inhibitor can affect angiogenesis in human brain microvascular endothelial cells (hCMEC/D3). Here, using in vivo cell imaging system (Chip-Man Technologies Ltd) we monitored for 24-72h the effects of stable GFP-Cdk5 over-expression (Cdk5ov) on hCMEC/D3 angiogenesis. Capillary branch chain formation (72h) and migration (24h) were studied in Matrigel and wounding healing assays, respectively. With the use of a hypoxiachamber we mimicked the effects of stroke condition on cell migration. Protein levels were estimated by Western blot. Cdk5/p35 involvement in cytoskeletal organization was investigated by confocal microscope analysis, in spreading or moving untransfected cells (controls). Stable transfection efficiency was defined by GFP fluorescence and cdk5 protein levels in different cell passages. Our results show that over-expression of cdk5 reduced cell adhesion (pϽ0.01 vs controls or empty vector transfectants) but not spreading. This was associated with increased p35 and talin protein levels. Cell migration was increased in Cdk5ov transfectants and this was augmented further in hypoxic condition (pϽ0.05). Notably, Cdk5ov transfectants showed a greater formation of neocapillary branch structures but their appearance was more chaotic. Similar to the controls, cdk5 was distributed with actin fibres alongside the branch structures. Confocal analysis in untransfected cells, demonstrated a co-localization of p35 and activated pTyr(15)Cdk5 with actin fibres in all phases of cell motility. P35 and talin co-localized with activated Cdk5 and integrin beta-1 at the leading edge of moving cells, indicating their interplay in cytoskelatal dynamics during cell motility. Notably, pilot microarray analysis showed reduced expression of pro-angiogenic protein MEF2C and Notch ligand, Jagged-1 in mutated (D144N) Cdk5 transfectants. In conclusion our results suggest that a pathway operating through Cdk5 may critically modulate cell dynamics during hypoxia/brain injury associated condition. Cdk5 over-expression may positively contribute to preserve cell motility, but may require interplay with other pathways to promote microvascular cell differentiation.

Author Disclosures: A. Bosutti: None. S. Matou: None. J. Qi: None. R. Pennucci: None. L. Tsai: None. K. Giese: None. S. Love: None. J. Krupinski: None. S. Kumar: None. M. Slevin: None.

W MP83 White Matter Hyperintensity Burden Accumulation Is Accelerated In Inherited vs. Sporadic Disorders Of Small Cerebral Vasculature

Natalia S Rost, Alessandro Biffi, Massachusetts General Hosp, Boston, MA; Christian Opherk, Ludwig-Maximilians-Universita ¨t Mu ¨nchen, Mu ¨nchen, Germany; Kaitlin M Fitzpatrick, Allison S Kanakis, Anand Viswanathan, Massachusetts General Hosp, Boston, MA; Hugues Chabriat, Univ Paris VII, Paris, France; Karen L Furie, Steven M Greenberg, Jonathan Rosand, Massachusetts General Hosp, Boston, MA; Martin Dichgans; Ludwig-Maximilians-Universita ¨t Mu ¨nchen, Mu ¨nchen, Germany Background: White matter hyperintensities (WMH) are a common radiographic finding in disorders of cerebral small vessels such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cerebral amyloid angiopathy (CAA). However, limited data are available on WMH burden accumulation in cerebral microangiopathy syndromes, including those which can manifest as sporadic ischemic or hemorrhagic strokes. We sought to quantify and compare the burden of WMH in subjects with inherited (CADASIL) vs. predominantly sporadic (acute ischemic stroke [AIS] and intracerebral hemorrhage [ICH]) cerebral small vessels disease. Methods: We conducted a cross-sectional, multicenter study of prospectively enrolled cohorts of consecutive patients (1) admitted to the Emergency Department with a diagnosis of AIS or ICH, and (2) referred to our centers with a diagnosis of CADASIL. Among AIS patients, small vessel (SV) stroke subtype was assigned based on the TOAST criteria. ICH patients were diagnosed with CAA based on the Boston Background and Purpose: Endoglin (ENG) or activin receptor-like kinase 1 (ALK1) mutations cause hereditary hemorrhagic telangiectasia with high prevalence of brain arteriovenous malformations (bAVM). We demonstrated that vascular endothelial growth factor (VEGF) overexpression induced cerebrovascular dysplasia in adult Engϩ/-and Alk1ϩ/-mice. Engϩ/mice had 4-fold higher dysplasia than Alk1ϩ/-mice. However, the phenotype was subtle. We hypothesized that VEGF stimulation with regional homozygous deletion of Alk1 or Eng induces severe dysplasia in the adult mouse brain, more akin to human bAVM. Method: Alk1 2f/2f (exons 4-6 flanked by loxP sites), Eng 2f/2f (exons 5-6 flanked by loxP sites) and wild type (WT) mice (8-10 weeks old) were injected with Ad-Cre (2X10 7 PFU, adenoviral vector expressing Cre recombinase) and AAV-VEGF (2X10 9 genome copies, adeno-associated viral vectors expressing VEGF) into the basal ganglia. At 8 weeks, blood vessels were visualized by microfil and lectin perfusion. Vascular density (capillaries in a 20X objective field) and dysplasia index (number of capillaries Ͼ15m in diameter per 200 capillaries) were counted. Results: Gross vascular irregularities were seen in the Alk1 2f/2f mouse brain injected with Ad-Cre and AAV-VEGF. The vessels were markedly enlarged with abnormal pattern; no gross irregularities were seen in similarly treated Eng 2f/2f or WT mice. Dysplastic capillaries were seen in both Alk1 2f/2f and Eng 2f/2f mice, but not in WT mice. The dysplasia indexes were: 2.9Ϯ0.23 (Alk1 2f/2f ), 1.47Ϯ0.80 (Eng 2f/2f ) and 0.40Ϯ0.19 (WT). Injection of Ad-GFP and AAV-VEGF induced angiogenesis with normal structure. Alk1 2f/2f mice showed a trend towards an increase (353Ϯ95) and Eng 2f/2f mice showed a trend towards a decrease (194Ϯ31) in capillary densities compared to WT mice (248Ϯ72, P values ϭ0.13 and 0.14). Conclusions: After VEGF stimulation and Ad-Cre-mediated regional gene deletion, the Alk1 2f/2f mice had a greater dysplastic response with frank cerebrovascular malformations than Eng 2f/2f mice. This is inexplicably opposite to what we observed in Alk1ϩ/-or Engϩ/-mice. Potential reasons for further study include: (1) Ad-Cre is more effective in Alk1 2f/2f than Eng 2f/2f mice; (2) preferential effects on certain cell types by somatic versus regional gene knockout; (3) potential dominant negative effect in Engϩ/-mice.

Author Disclosures: E. Choi: None. E. Walker: None. F. Shen: None. S. Oh: None. H. Arthur: None. H. Su: None. W. Young: None.

Background and Purpose: Brain arteriovenous malformations (BAVM) can rupture and cause serious morbidity and mortality. Hereditary Hemorrhagic Telangectasia-2 patients with mutations in activin receptor-like kinase 1 (ALK1) have a high frequency of BAVM. The arterial marker, Jagged-1, is increased in human BAVM. Mutations of the venous marker, EphB4, can cause AVMs in the mouse embryo; genetic variation in EphB4 is associated with human BAVM hemorrhage. We recently developed a phenotype in the adult mouse brain that resembles human BAVM by regional conditional Alk1 deletion and vascular endothelial growth factor (VEGF) stimulation. We hypothesized that deletion of the Alk1 gene disrupts arterial-venous specification of VEGF-induced neovasculature in the adult mouse. Methods: Adult Alk1-floxed mice with loxP sites flanking Exons 4-6 were injected into the basal ganglia with 2X10 7 PFU AdCre, an adenoviral vector expressing Cre recombinase, and 2X10 9 genome copies of AAV-VEGF, an adeno-associated viral vector (AAV) expressing VEGF. The brain, intestine, and jugular vein were collected 8 weeks after injection. Vessels were characterized with lectin and immunohistochemical stains. Results: Irregular dysplastic vessels with enlarged lumens were detected in the brain of Alk1-floxed mice treated with Ad-Cre and AAV-VEGF. Only 52% of vessels at the injection site with lumens larger than 15 ı `m were covered with smooth muscle. Jagged-1 staining was detected in the endothelial cells of 34% of the vessels, and EphB4 in 41% of the vessels, regardless of smooth muscle coverage. Interestingly, 22% of vessels expressed both Jagged-1 and EphB4, implicating an irregular phenotype. No abnormal vessels were detected in control vector injected brains, with 100% of vessels larger than 15 ı `m covered with smooth muscle. In the intestine, basilar artery, and jugular vein, there was Jagged-1 and EphB4 positive staining on arteries and veins, respectively. These results implicate that deletion of Alk1 resulted in disruption of arterial-venous determination after VEGF stimulation. Conclusions: We observed a loss of distinct arterial-venous identity in the dysplastic vessels induced by VEGF stimulation in adult mouse brain with regional Alk1 deletion, suggesting that disruption of arterial-venous determination leads to the formation of dysplastic vessels that are prone to rupture.

Author Disclosures: W. Chen: None. E. Walker: None. F. Shen: None. H. Su: None. W. Young: None.

W MP89 The use of Onyx in Different Types of Intracranial Dural Arteriovenous Fistula

Thiago G Abud, Jean-Pierre St.-Maurice, Daniel G Abud, Andrew Nguyen, Zolta ´n Szatma ´ry, Michael Mazighi, Annouk Bisdorff, Eugen Enesi, Luigi Chiumarulo, Damien Bresson, Armand Aymard, Emmanuel Houdart; Hosp Lariboisiere, Paris, France, Paris, France Purpose: Describe the treatment technique with injection of Onyx (ev3) by arterial approach of the different types of intracranial dural arteriovenous fistula (DAVF). Methods: Between January 2005 and January 2010 we treated at the Department of Interventional Neuroradiology, Hospital Lariboisie `re Paris, 44 DAVF in 42 patients. All patients were initially treated by arterial injection of Onyx. The average age was 56 years (27-86 years), 17 females and 28 males. The most frequent clinical presentation was pulsatile tinnitus ( 16), followed by intracranial hemorrhage (6) and headache (5). For the characterization of DAVF, we follow the classification of Hospital Lariboisie `re, Paris, France: 4 patients of Type I (direct drainage to the dural sinus and usual flow), 4 type IIa (with drainage to the sinus and sinus reflux), 11 type IIb (with drainage to the sinus and cortical vein reflux), 3 type IIa ϩ IIb, 15 type III (direct drainage into the cortical vein), 5 type IV (drainage to the cortical vein associated with venous aneurysmal dilatation) and a type V (medullar venous drainage). Results: A total of 58 arterial pedicles were catheterized, in most cases (38) were catheterized the middle meningeal. The average time of injection was 30 min (15-60 min) and average amount was 2.5 cc (0.6 to 6.5 cc). Regarding the 20 fistulas with venous drainage to dural sinus dural (Type I and II) achieved the preservation of the venous sinus in 7 of them. Of the 44 embolized fistulas, eight had a second time of embolization, 1 a third time; in 4 cases complementary treatment was performed by intravenous embolization and placement of coils and / or surgery. Complications were observed in six patients. 4 for nerve injury: two with facial palsy and two with neuralgia. The other two patients had complications in relation to extension of venous thrombosis due to embolization. All cases showed partial or complete regression of the clinical post-complication. Conclusion: The treatment of DAVF by intracranial arterial injection of Onyx is safe and allows, in most cases, occlusion of the arterial venous shunt. In the case of DAVF with direct sinus drainage, the sinus preservation is possible.

W MP90 Neurointerventional Approach for Arteriovenous Malformations and Aneurysms in the Pediatric Population.

Ana Delgado; JMH, Miami, FL Neuroendovascular interventions are now more common in children as an alternative for surgery in a diverse variety of vascular pathology, among these cerebral arteriovenous malformations (AVM) and aneurysms compromise children in approximately 12-18% and 1-5% respectively. Children with brain AVMs are prone to hemorrhages more frequently than adults with an associated high mortality. A retrospective review was performed in our institution regarding the efficacy of neuro-endovascular interventions in 53 patients under the age of 19 equally distributed by gender for ruptured and unruptured intracranial AVMs and aneurysms. Ninety seven AVM, 26 aneurysms and 5 AVF were encountered and 78 diagnostic angiograms, 42 embolizations (balloon assisted coil embolizations # 4, coil embolization #31 and embolization with onyx # 7) were performed. In 50 cases, follow up was completed and in 2 cases, recanalization was encountered for an AVM and one for an aneurysm. In both cases a second phase embolization was done. One asymptomatic complication occurred consisting in the rupture of an ultraflow microcatheter with extravasation of Onyx into the left vertebral artery treated with subsequent occlusion of the vertebral artery proximal to the embolic material. Advanced endovascular technologies implemented in neuroangiographic procedures in children seems to offer a feasible alternative to surgery for treatment of AVMs and aneurysms in the pediatric population.

Purpose: Recent studies suggest negative FLAIR can identify patients within the thrombolytic time window. However, CT is more commonly used than MRI as a pretreatment screening tool with frank hypodensity suggesting later stroke onset. Therefore, negative CT and negative FLAIR of unknown stroke onset has been proposed to represent patients with early stroke onset. Our aim is to find whether confirmed stroke patients with negative CT can be correctly identified to be within the thrombolytic time window. Methods: For CT reads, 4 expert readers blinded to time of stroke onset scored pretreatment CT and MRI scans from Sep 2000-Feb 2002. Eighty patients were included based on acute ischemic stroke and last seen normal (LSN) time ϭ time first seen with symptoms (FSS) Ϯ 30minutes. For FLAIR MRI reads, patients having pre-treatment MRI within 24 hours from witnessed stroke onset were selected from Apr 2005-Sec 2008. Eighty five patients were included based on left hemisphere acute ischemic stroke with LSN time ϭ FSS. Lacunar strokes and lesions with hemorrhagic transformation were excluded from both study sets. Two independent stroke neurologists blinded to time of MRI from LSN, scored FLAIR hyperintensity as present or not present corresponding to DWI-bright regions. The 3rd expert reader interpretation was used when there was a discrepancy between the first two readers. Logistic regression analysis was used to assess association between lesion visibility and time. Results: The sensitivity and specificity for negative CT to correctly identify early ischemic stroke onset Ͻ 6 hours is 80% and 46%, respectively. More than 40% of patients beyond 6 hours have a negative CT (Figure). Despite extended time range to 12 hours, negative CT specificity remained low at 45%. However, negative FLAIR specificity is 74% at 6 hours and 82% at 12 hours. The prevalence of lesion visibility increases with time on FLAIR (pϭ0.006), whereas CT lesion visibility is independent of stroke onset time (pϭ0.152). The average time for FLAIR to remain negative is 3.2h (SDϭ3.7h, Range 0.75-22.22; 95%CI 2.0-4.3) whereas average negative CT is at 8.9h (SDϭ14.5h, Range 0.60-69.9; 95%CI 5.0-12.8). Conclusion: Negative FLAIR is predictive of time but negative CT is independent of time and not a reliable indicator for estimating time range of early stroke onset. Because negative CT and negative FLAIR represent different time windows of stroke onset, it is not justified to combine them for the treatment of unwitnessed onset stroke patients. Negative FLAIR MRI is superior to negative CT in correctly identifying patients who are less than 6 hours of stroke onset.

Background: It has been reported that 25-40% of lacunar stroke patients show a progressive time course during the first several days of stroke and thus have poor functional outcome. We attempted to find 1) clinical and neuroimaging signs to predict neurological deterioration in the early phase, 2) whether to clarify the several antithrombotic drugs for preventing further progression and expecting a better functional outcome. Methods: We prospectively included 190 patients (mean age 67.9 yrs) admitted within 48 hrs after ischemic stroke between Jan 2007 and Dec 2009 in 7 stroke centers in Japan (Study for Treatment, Overt Signs and Pathophysiology of Branch Atheromatous Disease: STOP-BAD Group). Inclusion criteria were 1) 20-84 yrs of age, 2) pure motor hemiparesis, 3) acute ischemic lesion was identified only in the perforating artery territory on diffusion weighted MRI (DWI). Progressive-type stroke (PS) was defined as worsening by Ͼ or ϭ 1 point in the NIHSS for motor function within 7 days after onset. To identify predictors for PS, clinical characteristics including vascular risk factors, body temperature on admission, and initial DWI findings were evaluated. Antithrombotic agents of the first 7 days were recorded, such as heparin, argatroban hydrate, aspirin, cilostazol, clopidogrel sulfate, which were performed at each investigator's discretion. Functional outcome was assessed with the modified Rankin Scale (m-RS) at 3 months. Results: Fifty-two of 190 patients (27%) were classified into the PS group. In the PS group, 39 patients (75%) showed progression within the first 48 hrs after admission, while 13 patients (25%) deteriorated after 3 days of admission. Fluctuation of symptom before admission was more frequently observed in the PS group (28/52, 54%) than in the non-PS group (51/138, 37%) (pϽ0.05). Vascular risk factors, mean age, and laboratory tests were the same in two groups. Body temperature on admission was significantly higher in the PS group (36.9 degrees vs. 36.6 degrees, PϽ0.05). In the initial DWI, length and slice number of the lesion was larger in the PS group, while the width did not differ in the two groups. The unfavorable outcome (m-RS: 3-5) at 3 months was significantly higher in the PS group (31/52, 60%) than in the non-PS group (5/138, 4%) (pϽ0.001). In univariate analysis of each therapeutic agent, any treatment could not stop the progression. However, in a subanalysis of PS group, cilostazol (a phosphodiesterase 3 inhibitor) use within 7 days, especially in the early phase, were significantly correlated with good functional outcome (m-RS: 0-2) at 3 months (Day 1: pϭ0.0043, Day 2: pϭ0.0145, Day 7: pϭ0.0411). Conclusion: Fever on admission, initial DWI findings may allow us to predict PS. Early treatment using cilostazol, which protects the vessel endothelium in addition to antithrombotic function, resulted in good functional outcome in the chronic phase, even in the PS group.

Introduction:

The endovascular treatment of aneurysms is currently quantified by a global coil packing density measure. The local distribution of coils in the aneurysm can provide further insight into the physical mechanisms leading to coil-compaction but such distributions are yet unknown.

Here we quantify the local coil distribution by measuring the sizes of the aneurysmal voids left by the coil mass. Methods: Eight identical elastomer replicas of the rabbit elastase-induced aneurysm were embolized (Fig 1) by one interventional neurosurgeon; four models were coiled with balloon assistance and four with stent-support. The models were then embedded in epoxy blocks and the blocks sanded perpendicular to the aneurysm axis (height) at 100 micron intervals. A lightmicroscope image was acquired of the sanded surface at each interval (Fig 2). In each image, the space devoid of coils within the aneurysm lumen was optimally filled with circles of diameter not less than the coil diameter (Fig 3). The sizes of these circles over the entire sequence of images then represented the distribution of voids left by the coil mass. Results: The packing density of the stent-supported cases (mean Ϯ std.dev ϭ 40Ϯ7%) was significantly higher (t-test PϽ0.05) than the packing density of the balloon-assisted cases (31Ϯ2%). Figure 4 shows a histogram of the void sizes from one stent-support sample. Conclusion: Such quantifications of coil distribution can eventually be utilized in numerical simulations of intraneurysmal hemodynamics to estimate coil-compaction probabilities in the clinical setting.

Introduction:

The use of tPA is contraindicated in certain conditions where the risk of bleeding supersedes the benefits of use. A contraindication that can be overlooked in the work-up of an ischemic stroke patient, and lead to a hemorrhagic event, is the presence of an intracranial aneurysm or arteriovenous malformation. We assessed the intracranial hemorrhage (ICH) rate in ischemic stroke patients who had aneurysms and were treated with intravenous (IV) tPA. Methods: We retrospectively identified all patients from 2008 through May 2010 at our institution who 1) were treated with IV tPA for ischemic stroke, 2) were treated as a part of our stroke alert protocol, and 3) who were found to have an aneurysm. Hemorrhagic events were categorized as symptomatic or asymptomatic by a board certified vascular neurologist. Baseline demographic and clinical data were also retrieved. Results: Seven patients had aneurysms, the mean age was 70 years, 71% were female, 57% were transferred from another facility, the mean initial NIHSS score was 11 and mean time from symptom onset to IV tPA administration was 91 minutes. The 7 patients were only screened for the presence of ICH prior to IV tPA administration using a non-contrast head CT; vessel studies were not conducted prior to IV tPA treatment. All aneurysms were found incidentally after the administration of IV tPA, and had a mean size of 3.6 mm. CT angiograms (CTAs) visualized aneurysms in 4 patients (57%) with a mean size of 5 mm. CTAs were unable to visualize aneurysms in 3 patients; these were visualized with conventional angiograms and had a mean size of 2 mm. Only 3 patients (43%) with aneurysms developed ICHs, all were asymptomatic. All 7 patients survived to hospital discharge. Conclusions: The majority of patients with intracranial aneurysms did not hemorrhage after the administration of IV tPA. Administration of IV tPA in ischemic stroke patients with aneurysms did not result in any in-hospital deaths. Moreover, this case series suggests that CTA may be lacking in its ability to visualize small aneurysms. In conclusion, we believe aneurysm as a contraindication for IV tPA use in ischemic stroke patients requires further study. Institutions with larger databases are encouraged to compare the hemorrhage rate following IV tPA administration in those with and without aneurysms because the benefits of tPA treatment may outweigh the risks of hemorrhage.

Author Disclosures: C.V. Fanale: None. A. Orlando: None. K.A. Leonard: None. K.M. Salottolo: None. D. Bar-Or: None.

Th MP12 In Vitro Evaluation of a Novel Hyper-Elastic Thin Film Nitinol Covered Stent for the Treatment of Intracranial Aneurysms

Colin P Kealey, UCLA, Los Angeles, CA; Haithem H Babiker, Arizona State Univ, Tempe, AZ; Youngjae Chun, Steve Lin, K.P. Mohanchandra, David A Rigberg, Greg P Carman, Dan S Levi, UCLA, Los Angeles, CA; David H Frakes; Arizona State Univ, Tempe, AZ Background and Purpose: Endovascular coiling has revolutionized the treatment of intracranial aneurysms. Coiling is not, however, a panacea and studies have found significant rates of recanalization, as well as difficulties treating wide-neck and fusiform morphologies. The purpose of this study was to examine the flow limiting capabilities and early thrombotic response to a novel Hyper-Elastic Thin Film Nitinol (HE-TFN) covered stent for the treatment of intracranial aneurysms. Methods: Two types of covered stents (device I and II) with different porosities (75% and 80%, respectively) were constructed. A laser particle image velocimetry (PIV) system was used to quantify intra-aneurysmal flow under steady and pulsatile conditions in a model sidewall aneurysm. Parameters measured include cross neck flow, intra-aneurysmal kinetic energy, and root mean square (RMS) velocity. Values were compared to those obtained without a device in place. To examine the early thrombotic response, an in vitro circulation model was constructed. The system consisted of a glass aneurysm model connected to a continuous loop of silicone tubing placed within a 37 o waterbath. A peristaltic roller pump was used to propel fresh whole blood through the loop at a rate of 4 mL/sec. After 15 min., the devices were removed and analyzed with scanning electron microscopy (SEM). Results: PIV analysis under steady flow conditions (4 mL/sec) showed that device I reduced cross-neck flow by 54.1%, intra-aneurysmal kinetic energy by 98.4%, and intra-aneurysmal RMS velocity by 78.2% as compared to control. Device II reduced cross-neck flow by 23.5%, intra-aneurysmal kinetic energy by 85.9%, and intra-aneurysmal RMS velocity by 59.7%. A similar trend was observed at different flow rates and under pulsatile conditions. SEM of the devices following exposure to the circulation model showed accumulation of a dense fibrin network on the portion of HE-TFN covering the aneurysm's neck. The network was most dense at the corners of the pores, extending inwards towards the center and trapping both leukocytes and RBCs.

Conclusion:

The changes in intra-aneurysmal flow caused by, and the initial thrombotic response to, a novel HE-TFN covered stent for the treatment of intracranial aneurysms appear to be very favorable for aneurysm occlusion. PIV studies demonstrated dramatic reductions in cross-neck flow, kinetic energy, and RMS velocity. SEM analysis of the devices after exposure to blood showed a dense fibrinous network of blood products between the HE-TFN's pores, suggesting a possible mechanism for further flow reduction in vivo Although more extensive in vivo testing is needed, this device appears to represent a highly porous, flexible, and low profile novel flow diversion device.

Th MP13 Neurovascular Unit Remodeling During Recovery Involves Matrix Metalloproteinases In Ischemic Rat Brain

Yi Yang, Jeffrey F Thompson, Jeff W Hill, Thera A Mcavoy, Eduardo Y Estrada, Victor M Salayandia, Gary A Rosenberg; Univ of New Mexico, Albuquerque, NM We previously reported that matrix metalloproteinases (MMPs) increase the permeability of the blood-brain barrier (BBB) by degrading tight junction proteins (TJPs) and treatment with MMP inhibitors prevents BBB disruption. However, MMPs may have a beneficial role during recovery after stroke. Stroke recovery is associated with angiogenesis and BBB remodeling though the mechanisms of neurovascular remodeling during recovery are uncertain. We hypothesized that several studies have demonstrated that only activation of extrasynaptic (exSy) NMDAR produce cell death, whereas activation of synaptic (Sy) NMDAR prior to oxygen and glucose deprivation (OGD) induces survival through activation of the c-AMP response element binding protein (CREB). Objective: Our aim was to investigate whether activation of Sy NMDAR at post-ischemia also prevents OGD-induced neuronal death. Methods: Experiments were performed in cortical neurons treated with NMDA, bicuculline or Ro25-6981 for 10 min, either in control or OGD/reperfusion conditions. Bicuculline selectively activates Sy NMDAR by inhibiting gabaergic neurotransmission, and Ro25-6981 selectively inhibits exSy NMDAR. OGD was performed by incubating neurons in glucose-free DMEM in a 2% O2 atmosphere for 90 min. After this OGD period, normoglycemia and normoxia were restored and treatments were added. Phospho CREB (pCREB)immunocytochemistry was performed in neurons 15 min after treatments and cell death was determined 24 hours later. Results: Selective activation of Sy NMDAR provoked a 4-fold increase in pCREB in neurons whereas joint activation of both Sy and exSy NMDAR by addition of NMDA abolished this effect. Treatment with NMDA in the presence of Ro25-6981 induced a 4-fold increase of pCREB. We found that 30% of the OGD-treated neurons died 24 h after reperfusion, and that this effect was dramatically reduced by a short selective activation of Sy NMDAR following reperfusion, either using treatment with bicuculline or with Ro25-6981. Conclusion: Selective activation of Sy NMDAR at reperfusion was able to protect neurons from OGD-induced neuronal death by providing a necessary survival signal. These results offer an explanatory mechanism of the paradoxical failure of NMDAR antagonists to provide clinical benefit in acute stroke patients.

Author Disclosures: V. Guirao: None. A. Davalos: None. T. Gasull: None.

Th MP18 Therapeutic Benefit of Combination Simvastatin and Human Umbilical Cord Blood Cells Treatment of Stroke: Neurogenesis, Vascular and White Matter Remodeling

Xu Cui, Michael Chopp, Alex Zacharek, Henry Ford Hosp, Detroit, MI; Nicole Kuzmin-Nichols, Saneron CCEL Therapeutics, Inc., Tampa, FL; Chunling Zhang, Cynthia Roberts, Amjad Shehadah, Jieli Chen; Henry Ford Hosp, Detroit, MI Background & Objective: The therapeutic efficacy of cell-based therapy after stroke can be enhanced by making the host brain tissue more receptive to the administered cells and thereby facilitate brain plasticity. We hypothesized that Simvastatin increases human umbilical cord blood cell (HUCBC) migration into the ischemic brain and promotes brain plasticity and neurological functional outcome after stroke. Methods: Wistar rats were subjected to transient middle cerebral artery occlusion (MCAo) and administered PBS, Simvastatin (0.5mg/kg, gavaged daily for 7 days), HUCBCs (1ϫ10 6 , one time tail vein injection), combination Simvastatin and HUCBCs starting 24h after MCAo. Rats were sacrificed 14 days after MCAo. A battery of neurological functional outcome (mNSS, Foot-fault and Adhesive removal) tests, neurogenesis, vascular and white matter changes were measured. Subventricular zone (SVZ) explant, primary mouse brain endothelial cell (MBEC) and primary cortical neuron (PCN) cultures in vitro were also employed. Results: Combination treatment additively improved neurological outcome and significantly decreased lesion volume compared to MCAo control (pϽ0.05, nϭ8/group). Combination treatment significantly increased the engrafted-HUCBC numbers in the ischemic brain compared with HUCBC-monotherapy, and the number of engrafted-HUCBCs were significantly correlated with functional outcome (mNSS,rϭ0.751). Combination treatment significantly increased SVZ cell proliferation and neuroblast migration, upregulated angiogenesis and arteriogenesis measured by the vascular/arteriole density, perimeter/diameter as well as endothelial cell and smooth muscle cell proliferation in the cerebral vessels compared to MCAo control and monotherapy groups. In addition, combination treatment significantly increased Synaptophysin expression and brain-derived neurotrophic factor (BDNF), and the density of axons and myelin in the white-matter bundles in the ischemic brain compared to MCAo control (pϽ0.05, nϭ8/group). In vitro data show that neuroblast proliferation and migration significantly increased in the SVZ explant derived from combination treatment animals compared with MCAo or monotherapy alone animals. In addition, the capillary-like tube formation in MBECs and the neurite outgrowth in PCN cultures significantly increased in BDNF (50ng/ml) and Simvastatin combination with HUCBC conditioned medium compared with non-treatment controls, TrkB inhibitor (K252 200nM) significantly attenuated combination treatment-induced tube formation and neurite outgrowth (pϽ0.05, nϭ6/group). Conclusions: Combination treatment enhances HUCBC migration into the ischemic brain, increases BNDF expression and amplifies endogenous neurogenesis, synaptogenesis, and vascular and white matter remodeling, and improves functional outcome after stroke.

Background: Thrombocytopenia has been associated with increased mortality in conditions such as acute coronary syndrome, liver disease, and chronic HIV infection. Some case series have indicated that mortality rates are higher among ischemic stroke patients with thrombocytopenia, however these studies were limited by small sample size and did not adequately adjust for important potential covariates. Objective: We sought to examine whether thrombocytopenia present upon admission was associated with in-hospital mortality among patients with ischemic stroke. Methods: We used data from a retrospective cohort of ischemic stroke patients who were admitted to one of five hospitals (1998)(1999)(2000)(2001)(2002)(2003) within 48 hours of symptom onset excluding patients who received thrombolysis. Thrombocytopenia was defined as platelets less than 100,000/L. The outcome was in-hospital mortality. Factors considered for risk adjustment included: conditions that can lead to thrombocytopenia (e.g., liver disease); conditions that increase risk of bleeding (e.g., hemophilia); medications taken prior to admission that have an effect on platelets (e.g., aspirin); and predictors of in-hospital mortality (e.g., retrospective NIH Stroke Scale (NIHSS) and Charlson comorbidity score). Chi-square tests were used for unadjusted analysis, and logistic regression with backward stepwise elimination was used to obtain the most parsimonious adjusted model of the association between thrombocytopenia and mortality. Results: Among 1233 ischemic stroke patients, the rate of thrombocytopenia was 2.3% (Nϭ28), and overall 6.1% (Nϭ75) died in the hospital. In Background and Purpose: Awareness of stroke symptoms and the importance of rapid 911 activation is an important link in the chain of survival for stroke patients. Media campaigns to increase community awareness of stroke signs and symptoms and the importance of using 911 have shown short-term increases, but sustaining the increased levels of awareness has been a challenge. Methods: From October 2008 through October 2009, the Montana Stroke Initiative conducted a staged media campaign in a selected Montana county. Between October 2008 and May 2009, a 20-week high-intensity media campaign aired. The campaign included paid TV/radio ads, billboards, newspaper releases, and brochures. The high-intensity campaign was followed by a maintenance campaign which ran one week out of every three weeks (July-October 2009). The campaign was evaluated by 4 random digit dial telephone surveys (total of 1,600 people aged 45 and older). Two baseline telephone surveys, separated by 12 months, evaluated the variability of community responses without intervention. Surveys were also conducted after the high-intensity (June 2009) and maintenance campaigns (November 2009). Results: Between the 2 baseline surveys, there were no significant increases in awareness of stroke signs and symptoms or intent to call 911. After the high-intensity campaign, there were significant improvements in both awareness and intent to call 911, which were sustained after the maintenance phase. (Fig 1) Improvements were also noted in subgroups, including males, those aged 45-64 years and 65ϩ year olds. In addition, the percentage of respondents who would call 911 if they experienced numbness, speech difficulties, paralysis, or all 3 symptoms increased significantly from baseline. (Fig 2). Conclusion: Knowledge of stroke signs and symptoms and the intent to call 911 improved after a high-intensity media campaign, and the improvements remained after the maintenance phase. A staged media campaign was effective in increasing awareness and intent to call 911.

Th MP25 Brain Natriuretic Peptide Predicts Functional Outcome In Ischemic Stroke

Natalia S Rost, Alessandro Biffi, Lisa Cloonan, Massachusetts General Hosp, Boston, MA; Peter J Kelly, Mater Univ Hosp, Dublin, Ireland; David Greer, Yale-New Haven Med Cntr, New Haven, CT; Patrick T Ellinor, Karen L Furie; Massachusetts General Hosp, Boston, MA Background: Elevated plasma levels of brain natriuretic peptide (BNP) have been associated with cardioembolic (CE) stroke and higher post-stroke mortality. However, limited data are available on the value of BNP in determining functional outcome after stroke. We sought to determine whether plasma BNP levels were associated with long-term functional outcome in ischemic stroke patients. Methods: We conducted a cross-sectional study of the prospective cohort of consecutive patients aged Ն18 years admitted to our Stroke Unit through the Emergency Department between 2002 and 2005. All patients underwent clinical evaluation by a vascular neurologist, diagnostic neuroimaging, cardiac, and laboratory testing, including BNP collected during the index admission. Plasma BNP was measured using high-sensitivity immunoradiometric assay, and BNP level quintiles were used for analysis. Stroke subtypes were assigned using TOAST criteria. Outcomes were measured as 6-month modified Rankin Scale score ("good outcome" ϭ 0-2 vs. "poor") as well as mortality. Multivariate logistic regression was used to assess the association between the plasma levels of BNP and functional outcome in this cohort. Predictive performance of BNP for functional outcome was assessed by comparing ROC curves. Results: Of 514 ischemic stroke patients, 187 (32.9%) had CE, 130 (22.9%) had large artery, 54 (9.5%) had small vessel, 143 (25.1%) had undetermined, and 55 (9.7%) had other stroke subtypes. Mean age was 67.9 Ϯ 15 years; 46% were female. BNP levels were higher among the older subjects (pϽ0.0001) and women (pϽ0.0002). When adjusted for age and gender, elevated BNP levels were associated with lower ejection fraction (pϽ0.0001) and greater degree of left atrial dilatation (pϽ001). Furthermore, BNP was an independent predictor of atrial fibrillation (OR 2.0, 95%CI 1.6-2.5), and any CE mechanism (pϽ0.001). In multivariate analysis, elevated levels of BNP decreased the odds of good functional outcome (OR 0.2, 95%CI 0.1-0.6), as did female sex (OR 0.1, 95%CI 0.01-0.7) and coronary artery disease (OR 0.01, 95%CI 0.001-0.2). BNP was the only independent predictor of mortality in this cohort (OR 6.4,). The addition of BNP to models predicting functional outcome and mortality after CE stroke significantly increased their predictive performance (AUC estimate increase from 0.85 to 0.91, PϽ0.013 and 0.84 to 0.94, PϽ0.03, respectively). Conclusions: In this large, cross-sectional study of patients with ischemic stroke, plasma BNP levels were strongly associated with CE stroke and long-term functional outcome. Elevated BNP levels independently predicted poor functional outcome and mortality at 6 months. Inclusion of BNP levels significantly improved prediction of mortality, especially in patients with CE stroke. Further studies are warranted to establish the utility of plasma BNP as a predictor of stroke outcome.

Author Disclosures: N.S. Rost: None. A. Biffi: None. L. Cloonan: None. P.J. Kelly: None. D. Greer: None. P.T. Ellinor: None. K.L. Furie: None.

Th MP27 Cerebral Blood Volume Gradient Maps Depict Vulnerability to Hemodynamic Failure and Infarct Growth in Acute Ischemic Stroke

David S Liebeskind, Fabien Scalzo, Qing Hao, Jeffry R Alger, Xiao Hu, UCLA, Los Angeles, CA; for the UCLA Collateral Investigators Background: Cerebral blood volume (CBV) is an essential measure of perfusion in acute ischemic stroke. The biphasic nature of CBV, with peripheral hyperemia and central collapse towards the ischemic core tends to underestimate ultimate infarction if only low CBV thresholds are used. Detection of focal changes within the ischemic territory superimposed on global differences in CBV may also be difficult to measure. We developed CBV gradient images that illustrate propensity for hemodynamic failure to distinguish benign hyperemia from penumbra surrounding the ischemic core. Methods: Consecutive stroke cases with acute middle cerebral artery occlusion (MCAO) and serial MRI at baseline and day 5 were analyzed. CBV gradient maps were constructed using values from nearby regional voxels to estimate the local slope of CBV measures. Various radii extending to neighboring voxels were utilized to maximize the tissue fate predictive power of the gradient maps. Following co-registration with day 5 images, a nonlinear statistical model was used to quantify the predictive capacity of the CBV gradient images for infarction and accuracy was compared with Tmax prediction of tissue fate. Results: 42 cases (mean age 66.7Ϯ18.5 years; 26 women, 16 men) of acute MCAO with serial MRI were analyzed. CBV gradient maps were able to demonstrate a concentric region of abnormality around the ischemic core. Co-registered measures of the ischemic core with advanced hemodynamic collapse and uniformly low CBV were not apparent. Similarly, large areas of the surrounding territory with elevated CBV or hyperemia were not apparent on the CBV gradients maps. CBV gradient maps were able to accurately classify voxel outcome defined as infarction on day 5 fluid attenuation inversion recovery sequences, correctly predicting voxel-based hemodynamic failure. Voxel classification results revealed accuracies of 88.8Ϯ2.6% for CBV gradient maps compared with 90.2Ϯ2.4% using Tmax. Predictive capability was limited in a subset of cases with diffusely low CBV values. Cardioembolic stroke cases demonstrated more overt CBV gradient abnormalities compared with atherosclerotic etiologies. Conclusions: CBV gradient images can Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from Background: At present, the absence of a widely available diagnostic test for acute cerebral ischemia remains a limitation for improving the management of stroke. The triaging stage is likely to have the highest rate of stroke mimicking conditions and being the best scenario for a quick, accurate diagnostic assay to send to reference hospitals all true strokes that might get therapeutically benefit. Methods: In front of stroke suspicion (Ͻ3h from symptoms onset) blood samples were obtained at the Emergency Department to test selected biomarkers and later on a complete diagnostic protocol allowed to decide the diagnosis of "true stroke" (stroke) or a "stroke mimicking condition" (mimic). Finally, 230 cases were studied [146 strokes, 61 mimics (seizures, tumours, migraine, hypoglycemia, syncope…) and 23 healthy controls]. From a screening in a large (Ͼ150 biomarkers) protein-antibody library, in a sub-group of cases (discovery cohort), we identified 23 biomarkers useful to differentiate stroke from mimics (pϽ0.05). Those key biomarkers were combined in arrays and tested for validation in the whole study population by Search Light technology (Thermo Fisher Scientific). Results: The most relevant identified biomarkers were: Interleukin-17, basic Neurothrophic Growth Factor, Insulin Growth Factor Binding Protein 3 and Tumor Necrosis Factor Receptor 1. In fact, the multivariate analysis identified IL-17 OR 114.7; BNGF OR 9.2; IGFBP-3 OR 34.5; TNFR1 OR 8.7; Hypertension OR 3.5; Atrial Fibrillation OR 26.7 and Dyslipidemia OR 8.1 (all PϽ0.009), as independent parameters to differentiate stroke from stroke-mimicking conditions. That allowed building up a model with great predictive value (AUCϭ0.93) adding significant information to both clinical data alone and biomarkers alone (pϽ0.05). Negative predictive value for stroke obtained by combinations of 3 biomarkers was 100% and some combinations of only 2 biomarkers had 100% positive predictive value. The test allowed correctly allocating 46.9% of the mimics and 98.6% of the strokes. Conclusions: Results of this extensive study identified biomarkers able to differentiate stroke from mimics that will permit rapid referral of stroke patients to hospitals were acute treatments are available. Multicenter studies using point-of-care techniques to evaluate such a stroke diagnostic test in daily-practice conditions is now required.

Th MP30 Hyperacute Matrix Metalloproteinase-9 Levels Predicts Infarct Volume and Stroke Outcome

Svetlana Lorenzano, Natalia S Rost, Hua Li, Ken Arai, Sophia Hartdegen, Alona Muzikansky, Massachusetts General Hosp, Boston, MA; Michael K Parides, Mount Sinai Sch of Medicine, New York, NY; Rebecca Betensky, Harvard Sch of Public Health, Boston, MA; Ona Wu, Fabricio O Lima, Leonardo Batista, Ahmad Bayrlee, Lauren M Nentwich, Matthew B Maas, Aurauma Chutinet, Angel T Som, Loc-Duyen D Pham, Massachusetts General Hosp, Boston, MA; Danilo Toni, La Sapienza Univ, Rome, Italy; Gordon J Harris, Michael H Lev, Massachusetts General Hosp, Boston, MA; Steven K Feske, Brigham and Women's Hosp, Boston, MA; Peter J Kelly, Mater Hosp, Dublin, Ireland; Eng H Lo, Karen L Furie; Massachusetts General Hosp, Boston, MA Objectives: There are currently no validated acute stroke biomarkers to aid in risk stratification or selection of patients for acute therapeutic interventions. We previously reported a weak correlation between matrix metalloproteinase 9 (MMP-9) with NIHSS (rϭ0.33, pϭ0.05) and admission MRI ischemic infarct (DWI) volume (rϭ0.35, pϭ0.05) in a small sample of 52 hyperacute stroke subjects. We sought to replicate these findings in a larger sample in order to confirm and extend the validity of these relationships after adjustment for confounders. Methods: We prospectively measured MMP-9 on consecutive acute stroke patients (Ͻ 9 hours from symptom onset) in a multicenter acute ischemic stroke biomarker study. Clinical and demographic data including NIHSS scores at baseline, 48 hours, and discharge, stroke subtype, imaging, and 3 month mRS were collected. The outcome measure was the 90-day mRS, dichotomized as good (mRS 0-2) or poor (mRS 3-6). MMP-9 was analyzed using an ELISA assay. Patients with acute infection, active malignancy, or systemic inflammatory disorder were excluded. Pearson's correlation was used to quantify the association between continuous variables. Multivariate linear and logistic regression models were used to adjust for the effects Background: The ABCD2 score uses clinical criteria to stratify stroke risk after transient ischemic attack (TIA). The score has low specificity and a large proportion of individuals fall into the group in which guidelines recommend admission. The addition of brain imaging in the proposed ABCD2I score may reduce the number of unnecessary admissions. Objectives: 1) To validate the proposed ABCD2I score in TIA patients presenting to the emergency department (ED). 2) To evaluate the relative benefit of including only acute CT changes in the ABCD2I score.

3) To establish a low or high risk score with a similar risk to that proposed by the AHA guidelines. Methods: We prospectively identified and followed a cohort of patients receiving a final diagnosis of TIA in eight tertiary-care emergency departments and included all patients having a CT scan within 24 hrs. Primary outcome was stroke within 2, 7 and 90 days of index TIA. All CT scans were assessed by a neuroradiologist. The ABCD2I score (total 0 to 10) was calculated according to Giles et al. A modified ABCD2Ia score was calculated by assigning points only for evidence of acute infarction. An ABCD2 score of Ն 4 or an ABCD2I or ABCD2Ia score of Ն 5 separated low risk from medium-high risk patients. Discriminatory power was calculated from the area under the receiver operated characteristic curve (AUC) with 95% CIs. Results: 2046 patients met enrollment criteria and were included in the final analysis. The 90 day stroke rate was 3.4%. Ischemic changes were present in 565 (27.6%). The ABCD2Ia score had the greatest discriminatory power for stroke at 2, 7 and 90 days (Table ). ABCD2, ABCD2I, and ABCD2Ia identified 61.4%, 50.4% and 38.7% of patients as medium-high risk with an associated 2 day stroke rate of 1.9% (1.3-2.5%), 2.0% (1.3-3.1%) and 2.5% (1.6-3.9%), respectively. ACBD2, ABCD2I, and ABCD2Ia patients defined as low risk had a 0.9% (0.4-1.9%), 1.0% (0.5-1.8%), and 0.9% (0.5-1.6%) rate of stroke at 2 days, respectively. Conclusions: The ABCD2Ia score allows separation of patients into those needing urgent evaluation with more specificity than the ABCD2 or ABCD2I scores. Defining patients with a score of Ն 5 as medium-high risk would reduce hospital admissions while maintaining a low rate of the stroke in those not admitted.

Author Disclosures: J.K. Wasserman: None. J.J. Perry: None. D. Dowlatshahi: None. G. Stotts: None. M. Sivilotti: None. A. Worster: None. M. Emond: None. J. Sutherland: None. I. Stiell: None. M. Sharma: None.

Th MP33 Recruitment of Stroke Patients into Prehospital Research Before and After Implementation of a System-Wide Stroke Triage Policy

Nerses Sanossian, Marc Eckstein, Univ of Southern California, Los Angeles, CA; Samuel Stratton, Univ of California Los Angeles, Los Angeles, CA; Frank Pratt, Los Angeles County Fire Dept, Los Angeles, CA; William Koenig, Los Angeles County Emergency Med Services, Los Angeles, CA; Scott Hamilton, Stanford Univ, Palo Alto, CA; Robin Conwit, National Institutes of Health, Bethesda, MD; Randy Sanoff, Univ of California Los Angeles, Los Angeles, CA; Sidney Starkman, David S Liebeskind, Jeffrey L Saver, UCLA Stroke Cntr, Los Angeles, CA; FAST-MAG Investigators and Coordinators Background: Currently over half of all Americans live in region where acute stroke is routed preferentially to pre-specified stroke centers. Regionalized systems of stroke care are a means to improve care and may impact prehospital stroke research. Objective: To determine how implementation of a county-wide stroke diversion system affected patient recruitment and emergency medical services transport times in an ongoing prehospital stroke study. Methods: The Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial is a phase 3 NIH-funded study of magnesium sulfate or placebo initiated in the field throughout Los Angeles County within 2 hours of onset. FAST-MAG was ongoing and had recruited 876 subjects through 11/16/2009 when Los Angeles County implemented a county-wide stroke system of care. Patients suspected to have stroke using the Los Angeles Prehospital Stroke Screen with symptom onset 30 minutes. Since the implementation of this policy the number of PSCs has increased to 17. Monthly rates of enrollment were compared in the period prior to and following the date of implementation. The number of total enrollments, percentage of enrollments at PSC and field evaluation and transport times were compared. Results: FAST-MAG enrolled 1034 subjects as of June 25, 2010 for which data is available accounting for a period of 7 months and one week after the PSC diversion policy. There were 155 subject enrolled to 23 FM hospitals in the 31 weeks following regional stroke system implementation, compared to 134 patients brought to 41 FM hospitals in a similar period just prior to implementation. The monthly enrollment rates increased from 18.2 to 21.4, an 18% improvement. The percentage of subjects transported to PSCs increased from 21% in the period prior to implementation to 73% following PSC diversion (pϽ0.0001). The median prehospital evaluation and transport time increased by less than 3 minutes from 33.0 (SD 9.4) minutes before to 35.8 (SD 10.5) minutes after implementation of the PSC diversion. Mean transport time was not significantly different when comparing just patients taken to PSCs (33.8 Ϯ 8.5 before and 35.8 Ϯ 10.8 after implementation, pϭ0.37). Conclusions: Regionalized systems of stroke care can vastly increase the proportion of acute stroke patients cared for at stroke-capable hospitals and can improve recruitment of patients into prehospital stroke studies, with a small increase in prehospital evaluation and transport time. Implementation of a PSC system in Los Angeles County during the conduct of FAST-MAG provides a window into how regional policies can improve prehospital care and research yield.

Background: Past clinical scales differentiating likely intracerebral hemorrhage (ICH) from likely ischemic stroke (IS) have been developed based on symptoms and signs elicited 6 to 24 hours after stroke onset. There is a need to identify features that distinguish ICH from IS in the first minutes -2 hours after onset, to improve prehospital routing of patients (e.g. directing likely ICH patients to stroke centers with on site neurosurgery coverage), optimize prearrival notification of receiving hospitals, and permit field initiation of therapies tailored to likely stroke mechanism. Objective: To determine if a brief 3-question instrument can be administered in the field and whether responses may help differentiate ICH and IS in the first 1-2 hours after onset. Methods: The FAST-MAG Trial is a randomized placebo-control phase 3 study of magnesium sulfate vs. placebo initiated by paramedics in the field within 2 hours of stroke symptom onset. Physician-investigators elicit consent immediately from competent patients or on scene legally authorized representatives (LARs).Starting on 10/8/2008 investigators began to administer a 3-part stroke symptom questionnaire to all self-consenting patients: 1) do you have a headache (mild, moderate, severe), 2) do you have nausea, 3) have your symptoms worsened since onset. The questionnaire was administered to consecutive cases in parallel to paramedic field procedures. Results: From 10/8/2008 through 6/28/10 there were 391 subjects enrolled in FAST-MAG of whom 233 (60%) were competent and able to self consent. The questionnaire was successfully administered to 207 (89% of eligible). Among these 207 patients, average age was 70, 46% were female, median NIHSS on hospital arrival was 11, and time from last known well to field start of study drug was median 47 minutes. Of respondents, 99 (25%) had intracranial hemorrhage on the first imaging study after hospital arrival.

Frequency of positive responses on the questionnaire among the 233 patients was 21% (nϭ43) for headache, 12% (24) for nausea, and 9% (18) for worsening of symptoms from onset. In univariate analyses the presence of headache (OR 8.6,2), nausea (OR 5.2, 2.1-12.7), and progression (OR 7.4, were all significantly associated with hemorrhage on initial ED imaging. Having any positive responses on the screen was associated with ICH, while the number of positive responses and the intensity of symptoms (mild, moderate, severe) did not substantially increase predictive power. Conclusions: Self-reported headache, nausea, and early progression during the first 2 hours after stroke onset are powerful discriminators of likely ICH versus likely IS. A brief prehospital questionnaire is feasible to administer and identifies patients likely harboring ICH, potentially enabling enhanced neurosurgical response and tailored prehospital intervention.

Author Disclosures: N. Sanossian: None. S. Starkman: None. D.S. Liebeskind: None. L. Restrepo: None. L.K. Ali: None. R. Conwit: None. M. Eckstein: None. S. Stratton: None. F. Pratt: None. J.L. Saver: None.

Th MP36 Improvement in Emergency Physician Stroke Thrombolysis Knowledge: The Increasing tPA Stroke Treatment through Interventional behavior Change Tactics (INSTINCT) Trial

William J Meurer, Shirley M Frederiksen, Zhenzhen Xu, Allie M Kade, Lewis B Morgenstern, Univ Of Michigan, Ann Arbor, MI; Mary N Haan, Univ of California San Francisco, San Francisco, CA; John D Kalbfleisch, Phillip A Scott; Univ Of Michigan, Ann Arbor, MI Background: Barriers to the implementation of widespread stroke thrombolysis exist on multiple levels including the patient, provider and health system. We hypothesized that a multi-faceted interactive educational intervention would improve emergency physician (EP) stroke thrombolysis knowledge. Methods: Randomly selected Michigan community hospitals (nϭ24) were selected and matched into pairs as part of a cluster randomized controlled trial. Within each pair, one hospital was selected to receive an educational intervention that included CME lectures, mock stroke codes, and targeted email messaging. All emergency physicians in practice at each site were identified by a local stroke champion. A previously pilot tested, 15 item baseline knowledge survey was administered before and after the intervention. The interval between surveys was about 18 months. The survey was calibrated such that approximately 50% of the answers would be correct in a sample of practicing EPs. The knowledge score was the percentage of correct responses. A generalized estimating equation (GEE) was used to evaluate for change in knowledge score, while accounting for clustering within hospitals alone, and a GEE model with additional adjustment for the covariates: Emergency Medicine (EM) board certification, EM residency training, physician gender, emergency department volume, and hospital teaching status. Secondary models were constructed for two sub-domains of knowledge: treatment eligibility and treatment performance. Results: At baseline 278 EPs were identified within the 24 hospitals, of which 199 (72%) returned baseline survey. At 18 months 163 (59%) EPs completed the follow up survey. At baseline, the overall performance was similar between intervention and control groups (56.6% vs. 55%.) Post-intervention there was a significant increase in overall knowledge score in the treatment group (68.9%) versus control (52.8%). While accounting for clustering within hospitals, this was a 14.5% (95% CI: 8.4-20.6%) adjusted mean increase in the treatment versus control sites. Inclusion of the additional co-variates did not significantly change this estimate. In addition, the intervention group improved relative to the control group within the eligibility (15.4%; 95% CI: 12.5-18.6%), and performance sub-domains (19.9% 95% CI: 13.8-26%). Conclusions: The INSTINCT trial intervention was associated with improved EP physician stroke treatment knowledge. The lack of improvement seen in the control group suggests this was not the result of a test-retest phenomenon. The improvement of EP knowledge may be associated with more accurate and efficient thrombolytic decision making and delivery.

Author Disclosures: W.J. Meurer: Research Grant; Significant; Emergency Medicine Foundation. S.M. Frederiksen: Research Grant; Significant; NIH/ NINDS. Z. Xu: Research Grant; Significant; NIH/ NINDS. A.M. Kade: Research Grant; Significant; NIH/NINDS. L.B. Morgenstern: Research Grant; Significant; NIH/ NINDS. M.N. Haan: Research Grant; Significant; NIH/ NINDS. J.D. Kalbfleisch: Research Grant; Significant; NIH/ NINDS. P.A. Scott: Research Grant; Significant; NIH/ NINDS.

Th MP37 Effect Of Moderate And Excessive Alcohol Exposure On Female Versus Male Experimental Stroke Outcomes In Mice

Ling Zhang, Nicole L Libal, Patricia D Hurn, Stephanie J Murphy; Oregon Health & Science Univ, Portland, OR Stroke is a sexually dimorphic disease, with women being more protected from stroke relative to men. Heavy alcohol intake is a major stroke risk factor while moderate alcohol use (1 drink daily in women; 1-2 drinks daily in men) may offer neuroprotective benefits. However, little is known about the effects of varying levels of alcohol exposure on female outcomes as clinical and experimental research evaluating alcohol in stroke has focused mainly on males or did not stratify outcomes by sex. We evaluated the effects of acute moderate and excessive ethanol (EtOH) exposure on female vs. male mouse brain susceptibility to ischemic injury. We also explored the role of female sex steroids in the female response to EtOH exposure and experimental stroke. Female mice were ovariectomized (OVX) 7 to 8 days before EtOH exposure and experimental stroke to reduce endogenous levels of estrogen and progesterone. Intact and OVX females were given 0.2 g/kg (moderate dose, nϭ5-8/group) or 2 g/kg (excessive dose, nϭ7-8/group) EtOH i.p. while males were given 0.25 g/kg (moderate dose, nϭ8) or 2.5 g/kg (excessive dose, nϭ8) EtOH i.p. 1 h before 45 min of middle cerebral artery occlusion (MCAO). These EtOH doses mimic moderate or excessive alcohol in women and men based on blood Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation.

ethanol concentrations. Control female, OVX, and male mice (nϭ5-9/group) were given vehicle (saline, 0.015 mL/g) i.p. 1 h before MCAO. Brains were collected at 72 h reperfusion. Infarct volumes (% contralateral cortex) were determined by digital image analysis of 2 mm thick coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. In contrast to corresponding saline treated mice, acute moderate EtOH exposure (EtOH vs. saline) had no effect in females (40 Ϯ 4% vs. 48 Ϯ 4%) and OVX (58 Ϯ 8% vs. 42 Ϯ 9%) but decreased cortical infarct volumes in males (39 Ϯ 4%* vs. 53 Ϯ 2%) (*p Ϯ 1%* vs. 48 Ϯ 4%) and males (64 Ϯ 3%* vs. 53 Ϯ 2%) but were not significantly altered in OVX (49 Ϯ 4% vs. 42 Ϯ 9%) compared to corresponding saline treated mice (*pchemic injury in both sexes. However, the effect of excessive EtOH in female cortex is attenuated in OVX mice, suggesting female sex steroids may be involved. Further studies are needed to define the dose-response relationship and regional effects of EtOH in female ischemic brain and to assess the role of estrogen and/or progesterone in the female response to alcohol and stroke. Clinically, our observations suggest that excessive but not moderate alcohol consumption may alter stroke outcomes in women depending on hormonal status (pre-vs. post-menopause).

Author Disclosures: L. Zhang: None. N.L. Libal: None. P.D. Hurn: None. S.J. Murphy: Research Grant; Significant; R01 NS054684.

Th MP38 Neonatal Testosterone Administration Provides Neuroprotection After Stroke In Adult Male Rats

Rebecca W Persky, Fudong Liu, Gillian Weston, Stephanie Levy, Louise D McCullough; UCONN HEALTH CENTER, Farmington, CT Introduction: Stroke incidence and outcome differ between men and women; likely due to a combination of chromosomal sex and gonadal hormones not fully understood. In clinical populations, male sex is correlated with higher stroke risk until advanced age. Low circulating testosterone levels are associated with increased vascular risk in adult males; however high testosterone levels are associated with increased risk of thromboembolic events in boys. Emerging data suggest that cell death pathways are sexually dimorphic. Caspase-mediated cell death predominates in female brain, whereas poly (ADP) ribose polymerase (PARP) mediated cell death pathways are preferentially activated in the male brain. In this study we investigated the effect of exogenous neonatal testosterone on adult stroke outcomes. We also evaluated the potential of neonatal hormones to reorganize sex-specific ischemic cell death pathways after MCAO in adult rats. Hypothesis: We predicted that neonatal testosterone would enhance injury in adult rats of both sexes. Methods: Wistar rats were injected with 0.1mg testosterone proprionate in 0.05ml sesame oil or vehicle subcutaneously for 5 days following birth. On postnatal day 80, rats underwent 90 minute middle cerebral artery occlusion (MCAO) and were sacrificed 24 hours after stroke. Rats were perfused with PBS followed by 4% paraformaldehyde (for CV staining) or taken fresh and flash frozen (for Western). Western analysis was performed on subcellular fractions. Serum hormone levels were assessed by ELISA. Results: Infarct levels were significantly decreased in TP injected males compared with oil injected males in the striatum and hemisphere (36% vs. 79%, PϽ0.01, 15% vs. 33%, PϽ0.05, nϭ11). TP females had consistently lower infarct volumes than oil females. Serum testosterone levels were lower in TP males vs. oil males (pϽ0.01, nϭ10) and were low in both female groups. Estrogen levels were significantly increased in TP males compared to oil males and in tp females compared to oil females (pϽ0.05, nϭ10). TP male gonads were significantly larger than oil male gonads (pϽ0.01, nϭ7). An increase in cytosolic XIAP (X-linked inhibitor of apoptosis) cleavage was seen in TP males vs. oil males. Conclusions: Neonatal exogenous testosterone administration protected adult males from subsequent stroke. This was associated with lower adult testosterone levels, and higher adult estrogen levels. TP-treated males had increased activation of XIAP, a component of the cell death pathway conventionally seen in the female brain after stroke. Ongoing studies will examine the possibility that this effect is secondary to upregulation of aromatase.

Ischemic stroke is the one of leading causes of death and disability among adults in the U.S. Growing evidence suggests that there is a gender difference in stroke pathophysiology and outcomes. Recent experimental models of stroke and clinical trials showed that minocycline provides neurovascular protection reducing acute cerebral injury. Minocycline has multiple mechanisms of action including inhibition of MMP-9 and poly ADP ribose -1. However, it is unclear whether minocycline is effective in females. We tested minocycline in both genders using a novel embolic stroke model that closely mimics thromboembolic stroke in humans. Methods: Acute ischemic stroke was initiated by injection of an autologous fibrin-rich clot to the right middle cerebral artery (MCA) in wild type C57BL/BJ mice. Six groups of animals were used: a) young adult males (21Ϯ2 weeks old); b) young adult females (21Ϯ2 weeks old); and c) retired females (64Ϯ4 weeks old) with or without minocycline (6 mg/kg) given intravenously at stroke onset. At 24 hours after embolization, the neurological status of animals and their brains were analyzed. The infarct size of MCA territory was estimated by TTC as percentage of the contralateral hemisphere. The insertion of the clot into the distal internal carotid artery led to consistent reduction of CBF to about 21Ϯ4% of baseline. This highly reproducible reduction persisted for two hours (28Ϯ5% of baseline) and then we observed a slow spontaneous CBF restoration (ϳ50-65%) at 24 hours after stroke onset. Results: The model resulted in highly reproducible infarct in young males (37.0Ϯ2.3, nϭ6), young females (18.3Ϯ2.3, nϭ6) and retired females (38.1Ϯ3.6, nϭ6). As expected, young females were significantly more resistant to cerebral ischemic injury that was abolished by age in retired females. Overall neurologic deficits score was consistent with infarct volume for all groups and estimated as 3.3Ϯ0.2, 2.3Ϯ0.2 and 3.5Ϯ0.3 by Bederson Scale. Minocycline significantly reduced neurologic score (2.2Ϯ0.2, nϭ5, PϽ0.01) and infarct volume (16.8Ϯ1.5, PϽ0.001) in young males. Moreover, in our embolic model minocycline was neuroprotective for both females groups. The treatment with minocycline at stroke onset improved female behavioral deficits and significantly reduced infarct size (62-55% reduction). Conclusion: In a thromboembolic stroke model minocycline is an effective neuroprotector in both genders. This research has received full or partial funding support from the American Heart Association, National Center.

Background: Initial hematoma volume is one of the most powerful predictors of mortality after acute intracerebral hemorrhage (ICH). However, its impact on clinical course and outcome may vary widely depending on the time from symptom onset to baseline imaging (OIT). The speed of ultra-early hematoma growth (SuHG) may refine the predictive accuracy of initial hematoma volume and identify patients at risk of further ICH growth. We sought to explore the impact of SuHG on further ICH growth at 24h, clinical course and outcome in patients with acute ICH. Methods: We prospectively studied consecutive patients with acute primary supratentorial ICH evaluated Ͻ6 hours and with a known time from symptoms onset. Patients underwent baseline (Ͻ6h) and follow-up (24h) CT scans, and a CTA (Ͻ6h) for the blinded detection of spot sign (SS). ICH volumes were measured on baseline and 24h CT scans. SuHG was defined as the relation between baseline ICH volume/OIT. Hematoma growth (HG) was defined as ICH enlargement Ͼ30% or Ͼ6mL at 24h. Early neurological deterioration (END) was defined as increase Ն4 points in the NIHSS score or death at 24 hours. The mRS score was used to assess clinical outcome at 3 months. Results: A total of 123 acute primary supratentorial ICH were included in this study. Mean OIT was 165.2Ϯ84.6 min. Mean baseline ICH volume was 28.8Ϯ34 cc. Mean SuHG was 18.8Ϯ54.5 cc/h. SuHG was correlated with Glasgow Coma Scale (rϭ-0.525; PϽ0.001) and NIHSS (rϭ0.493; PϽ0.001) scores. CTA SS was seen in 19% of patients. SuHG was 3.5-fold faster in SS positive (33.2Ϯ43.2 cc/h) compared to SS negative (9.4Ϯ17.2 cc/h) patients (pϭ0.001). On 24h CT scan, HG was seen in 33.3% of patients. SuHG was significantly faster in patients who experienced further HG compared to those who did not (15Ϯ21.2 vs. 7.4Ϯ8.3 cc/h, pϭ0.049). SuHG markedly improved the accuracy of initial ICH volume and CTA SS in the prediction of END (Table ). A ROC curve identified a cut-off point value of SuHG of 9.2 cc/h (sensitivity 92.6%, specificity 80.9%) that independently predicted HG at 24h (OR 4.4, 95% CI 1.6 to 12.5, pϭ0.005), END (OR 27.5, 95% CI 5.5 to 136, PϽ0.001), and poor long-term outcome (OR 6.3, 95% CI 1.3 to 30.1, pϭ0.021) after adjusting for baseline NIHSS score, initial ICH volume and CTA SS. Conclusions: The speed of ultra-early hematoma growth represents a novel approach for improving the prediction of further HG, END and long-term outcome in patients with acute ICH. SuHG Ͼ9.2 cc/h emerged as the most powerful independent predictor of HG at 24h, END and long-term outcome.

intracerebral hemorrhage (ICH), can be used to calculate the rate of on-going hemorrhage. Methods: We retrospectively identified all primary ICH patients with spot signs who underwent both first-pass and delayed CTA acquisitions at our institution over a 10-year period. We then recorded the time interval between the 2 CTA acquisitions (T, in minutes) and utilized computer-assisted volumetric analysis to determine the volume of extravasated contrast material within the hematoma in each acquisition (Vspot1 for first-pass and Vspot2 for delayed, in mL). The rate of on-going hemorrhage was calculated as follows: (Vspot2-Vspot1)/T (in mL/min). If Vspot1ϾVspot2, the rate of on-going hemorrhage was designated as 0 mL/min. Medical records were reviewed for baseline clinical characteristics, in-hospital mortality and poor outcome among survivors (defined as a modified Rankin scale Ն4 at 3-month follow-up). Baseline and follow-up ICH volumes were calculated with computer-assisted volumetric analysis. Results: Sixty-nine patients were included in our study, with a mean age of 71.9 years (median 76 years, range 26-92 years). 42 patients were male (60.9%) and 27 female (39.1%). Mean initial ICH volume was 56.3mL (median 52.5mL, range 2-169.9mL). Mean time interval between first-pass and delayed CTA acquisitions was 2.24 minutes (median 1.87 minutes, range 0.13-9.58 minutes). 37 patients had a follow-up non-contrast CT examination performed (53.6%, mean time to follow-up 9.1 h, median 7.5 h, range 2.5-42.8 h). Mean volume of extravasated contrast material in the first-pass CTA was 0.16mL (median 0.04mL, range 0-2.32mL), and mean volume of extravasated contrast material in the delayed CTA was 1.15mL (median 0.35mL, range 0-11.6mL). The mean calculated rate of on-going hemorrhage was 0.48mL/min (median 0.13mL/min, range 0-3.53mL/min). Table 1 summarizes the risk of hematoma expansion and poor outcome for 3 patient groups with different rates of on-going hemorrhage. In multivariate logistic regression analysis, the rate of on-going hemorrhage was an independent predictor of hematoma expansion (OR 19.9, 95% CI 2.4-169.2, p-value 0.006) and in-hospital mortality (OR 3.6, 95%CI 1.1-12.2, p-value 0.036). Conclusion: Volumetric analysis of the CTA spot sign in primary ICH enables calculation of the rate of on-going hemorrhage, which, in turn, predicts the risk of hematoma expansion, in-hospital mortality and poor outcome among survivors.

Th MP45

The Impact of Blood Pressure Lowering on Perihematomal Edema Growth Measured by Serial Magnetic Resonance Imaging.

Chitra Venkatasubramanian, Michael Mlynash, Rashmi Narayana, Ryan W Snider, Demi Thai, Irina Eyngorn, Christine A Wijman, STANFORD UNIVERSITY, Palo Alto, CA; DASH investigators Background: Spontaneous intracerebral hemorrhage (ICH) causes progressive perihematomal edema (PHE) formation, worsening mass effect and tissue shifts. Whether blood pressure (BP) lowering attenuates PHE volume (Ev) growth is unclear. Objectives: In this prospective study, we aimed to evaluate the influence of BP reduction on Ev measured on serial MRIs by randomizing patients to two different levels of BP lowering. Methods: Consecutive patients with a primary supratentorial ICH of Ͼ/ϭ 5cc and GCS Ͼ/ϭ 6 were prospectively enrolled Ͻ 24 hours of symptom onset, and underwent MRIs at pre-specified intervals: 48Ϯ12 hours and thereafter, weekly for up to 3 weeks when possible. Patients were randomized to a mean arterial pressure (MAP) goal of 70-90 or 90-110 mmHg for at least 72 hours. Intravenous nicardipine or esmolol were primarily used for BP lowering. Hematoma volume (Hv) and Ev were determined on FLAIR of the baseline MRI. Baseline Hv was used for subsequent Ev calculations. Eleven additional patients with a MAP goal of 90-110 mmHg and Hv (Ϯ 5 cc) matching the 70-90 mmHg group were used as controls. Mann-Whitney U and Wilcoxon signed ranks tests were used to compare the two randomized and the control groups. Results: Twenty-seven patients with 77 MRIs were included. Sixteen patients (median age 52 years) were randomized, seven to the MAP of 70-90 mmHg group. Patients in the 70-90 mmHg group had a strong trend towards smaller baseline Hv (16 vs. 38 cc, pϭ0.06) and Ev (29 vs. 41cc, pϭ0.07), and higher baseline relative PHE (rPHEϭEv/Hv: 1.78 vs. 1.28, pϭ0.02) compared to the 90-110 mmHg group. Despite the imbalance in baseline Hv, absolute Ev growth from baseline to peak was identical (19 vs. 19 cc, pϭ0.8) in the two randomized groups, and rPHE growth was greater in the 70-90 mmHg group (1.64 vs. 0.52, pϭ0.04). The control group (with MAP 90-110 mmHg) was similar to the randomized 70-90 mmHg group with respect to baseline Hv (16 vs. 15 cc, pϭ1), Ev (29 vs. 28 cc, pϭ0.2) and rPHE (1.8 Vs 1.8, pϭ0.3). However, the 70-90 mmHg group had more absolute Ev growth (10 vs. 8 cc pϭ0.06) and rPHE growth (0.8 vs. 0.5, pϭ0.03) than the control group.. Conclusions: Aggressive BP reduction does not attenuate and may worsen perihematomal edema growth measured by MRI in patients with spontaneous ICH.

Introduction: Some studies suggest a protective role for statins following intracerebral hemorrhage (ICH). However, many failed to account for statin discontinuation following admission, did not include post-discharge outcomes, or were affected by loss to follow up. To address these limitations, we studied the relationship between pre-ICH statin use, in-hospital statin use, and 30-day mortality using a large stroke registry linked to population-based administrative data. Methods: Data were analyzed from 13 hospitals of the Registry of the Canadian Stroke Network. Primary outcomes were poor discharge mRS (defined as 4-6), and 30-day mortality. Continued statin use after admission was defined as any statin prescribed during the hospital stay. Multivariable logistic regression was used to determine the adjusted odds ratios (aOR) for statin use and outcomes, controlling for age, sex, stroke severity (measured by the Canadian Neurological Scale, CNS), elevated INR and other variables associated with the outcome in univariate analysis (pϽ0.10). Results: Data from 2466 consecutive ICH patients from 2003-2008 were analyzed: median age was 71 (IQR 58-80), 53.6% were male, and in-hospital mortality was 34.6%. Overall, 537 (21.7%) were taking statins prior to presentation: statin users were more likely to be older, to have medical comorbidities, and to be taking warfarin (pϽ0.05). Compared to non-users, statin users had similar rates of poor outcome (70% vs. 67%) and 30-day mortality (36% vs. 37%). Preadmission statin therapy was not associated with functional outcome (aOR for poor outcome 0.82, 95% CI 0.63-1.17, pϭ0.14) or increased mortality (aOR 0.88, 95% CI 0.68-1.15, pϭ0.36). Statins were discontinued on admission in 158/537 (29.4%); these patients were more likely to have severe stroke (CNS 0-4 in 65% vs. 27%, PϽ0.01), poor outcome by mRS (90% vs. 62%, PϽ0.01) and to have died by 30 days (71% vs. 21%, PϽ0.01). After adjusting for stroke severity, statin discontinuation was still associated with poor outcome (aOR 2.4, 95% CI 1.13-4.56, PϽ0.01) and higher mortality (aOR 2.0, 95% CI 1.30-3.04, PϽ0.01). These associations were also present after excluding palliative patients, and patients who died within 48 hours. Conclusions: We found no clear association between preadmission statin use and outcomes in ICH. However, statin discontinuation was independently associated with poor outcome and increased mortality. This may reflect a biological effect of statin withdrawal, although we cannot exclude the possibility of residual confounding by limitation of care, despite controlling for stroke severity, and excluding patients treated palliatively or who died early. A harmful effect of statin withdrawal has been reported from a randomized trial in ischemic stroke; our data suggest there may be a similar effect in ICH, and caution should be exercised when discontinuing statins soon after ICH.

Author Disclosures: D. Dowlatshahi: None. A.M. Demchuk: None. J. Fang: None. M. Sharma: None. E.E. Smith: None.

Th MP49 Stenting Or Angioplasty For Acute Stroke Due To Occlusion Or High Grade Stenosis Of The Extracranial Internal Carotid Artery Accompanying Intracranial Occlusions (tandem Lesions) In The Merci Registry: Incidence, Safety Profile And Clinical Outcomes

Tudor G Jovin, Univ. of Pittsburgh Med Ctr, Pittsburgh, PA; Thomas G Devlin, Erlanger Med Cntr, Chattanooga, TN; Marilyn M Rymer, St Luke's, Kansas City, MO; Ronald F Budzik, Riverside Methodist Hosp, Columbus, OH; Helmi L Lutsep, Oregon Stroke Ctr, OHSU, Portland, OR; Wade S Smith; Univ. of California, San Francisco, San Francisco, CA Background: Endovascular therapy for acute stroke due to tandem occlusive disease (TOD) of the extracranial internal carotid artery (ICA) and intracranial arteries with proximal revascularization (angioplasty with or without stenting), before or after distal revascularization is increasingly being utilized. However, data on incidence, safety & clinical outcomes of this approach are scarce. We aimed to evaluate procedural results with this distinct endovascular stroke population in the Merci registry. Methods: The Merci registry is a prospective multicenter registry with 1000 patients enrolled from 37 centers. The only required inclusion criteria was the use of any Merci Retriever in patients with acute stroke. Clinical outcomes at 90 days were obtained prospectively with good outcomes defined as modified Rankin Score Յ 2. Recanalization was reported using the TICI classification, with 2a, 2b & 3 considered as success. Patients with occlusion in the vertebrobasilar system were excluded. Results: A total of 746 patients were identified with completed 90d follow-up. Of those, 94 underwent proximal stenting with or without angioplasty and 37 underwent angioplasty alone. Table 1 outlines clinical, demographic & outcome data. Conclusions: With an incidence of 17.5% TOD is not uncommonly encountered during endovascular therapy for acute stroke in the anterior circulation. While patients with TOD tend to present later than those without TOD & are subjected to longer procedural times, a non significant trend towards higher recanalization rates, better clinical outcomes & lower incidence of sICH in TOD patients undergoing proximal stenting vs non TOD patients was observed. Proximal stenting is associated with better outcomes & lower incidence of sICH than angioplasty alone.

Introduction: Efficacy and safety of devices for the endovascular recanalization of acute ischemic stroke (AIS) are mostly validated in experimental vascular models and in-vivo animal models. Although critical for the evaluation, little is known about the mechanical similarities between these clot models and the human sources of embolic thrombi. The aim of this study is to explore the structure and mechanical properties of the cerebral emboli extracted from patients and model clots produced in-vitro. Methods: Nine thrombi were obtained from aspiration thrombectomy in AIS patients and 13 were collected during carotid endarterectomies (CEA). In-vitro embolus analogues (EAs) were prepared by simultaneously injecting whole blood/ACD mixture and CaCl 2 /thrombin solution into silicone tubing. Three variables of in-vitro clotting included species, thrombin concentration and addition of the radio-opaque component, barium sulfate. Dynamic mechanical analyzer was used to acquire the stress-strain behaviors of the clots in the controlled force mode, which gave an indication of clot hardness. Clot elasticity was analyzed from strain recovery experiments. Scanning electron microscopy (SEM) and Martius Scarlet Blue (MSB) stained sections were used to investigate the structure and composition of the specimens. Results: Two secant moduli that indicate clot hardness, designated as E1 and E2, are the slope of the stress-strain curve in the toe region (initial to 45% strain) and high strain (75%-95%), respectively. The softest clot material was obtained from AIS patients and was composed mainly of fibrin and erythrocytes (E 0-45% ϭ 0.026Ϯ0.0027MPa). Calcified thromboemboli showed the highest stiffness (E 0-45% ϭ 0.63Ϯ0.38MPa) followed by those that were cholesterol-rich (E 0-45% ϭ 0.17Ϯ0.039MPa). The histology and SEM results show that the EAs prepared in-vitro are mainly composed of homogeneously dispersed erythrocytes with several interspersed fibrin bands. Of the in vitro clots created in the lab, bovine EAs presented the highest stiffness and elasticity. The mechanical properties of the bovine EAs were not significantly altered by the addition of thrombin. Addition of thrombin at a concentration of 5 NIHU/ml blood resulted in increases in stiffness and elasticity of human and porcine EAs (pϽ0.05). The presence of barium sulfate significantly reduced the elasticity of all EAs (pϽ0.05). Conclusions: Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral emboli from AIS patients analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the CEA specimens was similar with that of the bovine EAs and thrombin induced porcine EAs.

patients with robust collateral circulation on admission CT angiography (CTA) have small (Ͻ one third MCA territory) admission infarct volumes, and are therefore not excluded from intra-arterial stroke therapy. Methods: Consecutive patients with new onset acute stroke symptoms, admitted between April 2003 and April 2008, were screened for presence of unilateral M1 MCA occlusion on CTA. Only cases with available acute diffusion images (DWI) (Ͻ9h, mean 5h), and MR-perfusion (MRP) were included. We dichotomized patients into two groups: those with none-or-diminished collaterals, and those with equal-to-increased collateral circulation. Student's t-test was used to compare admission imaging and clinical variables between study groups (i.e. DWI-lesion volumes on admission, MR perfusion mean transit time (MTT) volumes, NIHSS score, and systolic blood pressure). We also performed a multivariate logistic regression to determine which of these variables are associated with robust collateral circulation. Results: We included 63 patients in our study, 26 were classified as having good collaterals and 37 as having poor collateral circulation. In the univariate analysis, we found that admission DWI volumes (16Ϯ5.7 ml vs. 51Ϯ9.2 ml, pϭ 0.002), and MTT volumes (131Ϯ13.7 ml vs. 183.2Ϯ75.7 ml, pϭ 0.016) were lower in those with good collaterals. Patients with good collaterals also had lower admission NIHSS scores (13Ϯ7 vs. 16Ϯ7, pϭ0.048). In the multivariate analysis, we found admission DWI lesion volume to be the only independent variable associated with status of collateral circulation on admission (pϭ 0.028). Based on ROC curve analysis, good collateral status on admission CTA was highly specific for small admission DWI volume (volumeϽ 36 ml had 92% specificity and 43% sensitivity, area under the curveϭ 0.72; Figure ). Conclusion: Robust collateral circulation on CT angiography of acute stroke patients with proximal MCA occlusion strongly correlates with small admission MR diffusion/ MTT core infarct size. This may be of value in triage to intra-arterial therapy when MRI cannot be obtained.

Th MP55 Education Improves Use of Thrombolytics for Ischemic Stroke

Anne K Barton, Denise Kapnick, ProMedica North Region, Adrian, MI; Rebecca G Poetschke, Herrick Med Cntr, Tecumseh, MI; Steven A Sherman, Bixby Med Cntr, Adrian, MI; Greg Fuller, James Feeney; ProMedica North Region, Adrian, MI Background: Two community based, non-academic, rural, primary stroke certified hospitals that treat 70 strokes per year reviewed data in 2004 that indicated thrombolytic medication was not being administered to ischemic stroke patients despite a defined drug protocol. In addition, 61% of ischemic stroke patients arrived within 3 hours of stroke symptom onset. Possible reasons for under-utilization of t-PA include non-standard information related to risks/benefits of t-PA as well as delayed arrival. Purpose: This intervention seeks to provide standardized patient education to improve patient and family response to stroke symptoms with earlier hospital arrival, and for t-PA candidates/families to receive standardized information on t-PA risk/benefits. The overarching goal was to achieve increased thrombolytic administration rates. Method: To address the concern of non-uniform information being presented to patients, we developed an educational DVD, designed for viewing by the lay public and potential t-PA candidates. After reviewing possible sources for an educational video, one was created in two 4 minute sections: the first part described stroke risk factors, signs/symptoms, and the second part discussed thrombolytic treatment risk and benefits. Four groups have been exposed to the DVD starting in late 2006. First, medical staff education was initiated, including the ED physicians to raise awareness of the studies and information upon which the video was based. In 2008, it was mailed to 30,000 households in Lenawee County. The DVD continues to be used in community screenings and events, and the video is shown to potential t-PA candidates/ families in the ED. Results: The quality department tracks thrombolytic administration for all ischemic stroke patients as one measure of performance for primary stroke certification. Data demonstrates an increase in annual thrombolytic administration rate from 1.8% in 2004 to 6.5% of all ischemic stroke patients in 2009. Average arrival time from "last known well" has decreased from 327 minutes in 2007 to 259 minutes in 2009; in 2009 65% arrived within 3 hours. Conclusion: A standardized education tool (video) for medical staff, employees, patients and the community has been an important contributor to increased thrombolytic administration rate in this community hospital and a shortened time from stroke symptom onset to hospital presentation. More study is needed to demonstrate the relationship between the mailed DVDs and interval of symptom onset and ED presentation time. In conclusion, education and awareness has increased the use of thrombolytics in two community hospitals.

Author Disclosures: A.K. Barton: None. D. Kapnick: None. R.G. Poetschke: None. S.A. Sherman: None. G. Fuller: None. J. Feeney: None.

Th MP56 The Mann Assessment Of Swallowing Ability Predicts Dysphagia After Stroke With High Specificity Compared To Video-Fluoroscopy

Jeff M Edmiaston, Lisa T Connor, Andria L Ford; Washington Univ, Saint Louis, MO Background: Dysphagia is a common medical complication of stroke that leads to aspiration pneumonia if not identified early. The videofluoroscopic swallow study (VFSS, also known as the modified barium swallow study) is the gold-standard for identifying dysphagia. In some clinical settings, the VFSS is limited by radiation exposure, high expense, and is not always available at all hospitals or on weekends. At times it would be optimal to have a validated clinical bedside assessment that supplants the VFSS on a short-term basis. While the use of a clinical swallowing assessment is standard practice, prior studies have not validated a clinical assessment tool with high specificity for dysphagia prediction. We hypothesized that the Mann Assessment of Swallowing Ability (MASA) would identify dysphagia in the stroke population with high specificity compared to the gold-standard. We tested the MASA against the VFSS to determine its sensitivity and specificity in detecting dysphagia. Methods: Patients were recruited from an urban, tertiary care hospital. Inclusion criteria were: an admission diagnosis of acute stroke, ability to participate in VFSS (defined by MASA alertness score of Ͼ 5), and ageՆ18. The MASA was administered by study coordinator within 8 hours prior to the VFSS and then the VFSS was conducted by a speech language pathologist blinded to the MASA results. A patient was scored to have dysphagia present or absent using the MASA criteria. A score Ͻ 178 indicated at least mild dysphagia while a score Ն 178 was considered to reflect a normal swallow. The VFSS was scored utilizing the New Zealand Multidisciplinary Swallowing Index and a functional score was assigned using the Dysphagia Outcomes Severity Scale (DOSS). A DOSS score of Ͻ 5 was defined as "dysphagia", while a score of 6 or 7 was rated as "no dysphagia". Sensitivity, specificity, positive, and negative predictive values were calculated. Results: Our cohort included 216 subjects with suspected acute ischemic stroke. Mean age was 63 (22-97), 48% were female, 57% were Caucasian, and 42% were African-American. Mean NIHSS was 8.7. Sensitivity of MASA compared to VFSS DOSS was 90% and specificity was 87%. Positive and negative predictive values were 85% and 91%, respectively. Conclusion: The current state of practice in speech language pathology has the therapist conducting a clinical assessment of swallow function as an initial evaluation to determine the necessity for further evaluation or initiate oral intake. Previous studies have indicated that clinical assessments are not accurate when compared to the VFSS. This study, in addition to the initial study by Mann, provides evidence that the MASA has high specificity for dysphagia and should be considered the gold standard for clinical bedside assessments in the stroke population.

Author Disclosures: J.M. Edmiaston: None. L.T. Connor: None. A.L. Ford: None.

Th MP57 A Systems Approach to Stroke Care: Increased Access to Tissue Plasminogen Activator Therapies

Leigh Ann McCartney, Julie Fussner, Case Med Cntr, Cleveland, OH; Melissa Richardson, Geauga Med Cntr, Geauga, OH; Cathy Sila; Case Med Cntr, Cleveland, OH Background and Purpose: In 1993, University Hospitals Case Medical Center (UHCMC) began its expansion from a single tertiary academic medical center to its current 9 hospital health system. In 2006, the University Hospitals Neurological Institute (UHNI) was formed with the vision of system integration to deliver the highest quality of care throughout the health system. In July 2008 the UH Stroke and Cerebrovascular Center (UHSCC) launched its System Stroke Program (SSP). One vision of the program was to increase access to lifesaving treatment with tissue plasminogen activator (tPA) for acute ischemic stroke patients in the fifteen counties surrounding Cleveland. Methods: Through a hub and spoke model, patients that present to community hospitals in the University Hospitals (UH) health system as well as other communities surrounding Cleveland have access to the same treatment options as those that present to the tertiary care center. The community hospital staff in the UH health system are provided with standard education including an acute stroke clinical practice guideline, National Institutes of Health Stroke Scale (NIHSS) training, dysphagia assessment training, and stroke pathophysiology and treatment module. Community emergency medicine teams triage patients, perform an NIHSS assessment, obtain an emergency computed tomography (CT) of the head, complete a tPA eligibility checklist, and consult with a stroke service attending at UHCMC to determine a treatment plan. Patients that are eligible for treatment with tPA have intravenous treatment initiated at the community hospital and are transferred to UHCMC for further care by stroke experts including intra-arterial (IA) tPA and clot retrieval procedures. Results: Since the launch of the UHSSP, UHCMC has seen a 9.1% increase in the number of ischemic stroke patients treated with tPA therapy from 2.4% in 2008 to 11.5% in 2009. The use of IA tPA has increased 18% from 25% in quarter one of 2008 to 43% in quarter one of 2010. Conclusions:

The UHSCC has successfully increased access to life saving treatment with tPA for stroke patients in the fifteen counties surrounding Cleveland. Standardization of protocols, processes Unadjusted in-hospital mortality decreased (33.3% to 30.3%), but 30-day mortality increased (38.8% to 42.3%) over time with an 11% increase in risk-adjusted odds of 30-day mortality (ORϭ1.11, 95% CI 1.09 to 1.14). Within each subgroup, relative to 1993-1994, risk-adjusted 30-day mortality in 2005-2006 was increased for women (ORϭ1.21, 95% CI 1.17 to 1.25) and older patients (ORϭ1.14, 1.10-1.18 for 75-84 year olds and ORϭ1.37, 1.31-1.43 for Ͼ85 years). Mortality also increased for white patients, but decreased for blacks and other race-ethnic groups (Figure). Conclusions: There was an increase in risk-adjusted 30-day mortality rates for elderly patients hospitalized with ICH from 1993 to 2006 despite a decrease of in-hospital mortality. The increase was more marked for women, older age groups, and white patients. Understanding the reasons for the relative increases in post-ICH mortality may help to eliminate these differences.

Th MP62 Intracerebral Hemorrhage Specific Intensity of Care Quality Matrix

Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: Intracerebral hemorrhage (ICH) care can vary among centers and previous studies have demonstrated differences in ICH outcome based on variations in patient care in various settings. The purpose of this paper is to present the design of an evidence-based dataset of elements of a new ICH specific intensity of care quality matrix. Methods: The articles were identified based on personal knowledge of the subject supplemented by data derived from multi-center randomized trials, and selected non-randomized or observational clinical studies. The information was identified with multiple searches on MEDLINE from 1986 through 2009. The current guidelines from American Heart Association (AHA)/American Stroke Association (ASA) Stroke Council and The European Stroke Initiative (EUSI) Writing Committee for management of intracerebral hemorrhage were reviewed extensively for identifying quality indicators and available scientific evidence. For certain elements where stroke-specific data was not available, data derived from other disease process with direct relevance was used. Results: A total of 27 quality indicators related to 18 facets of care with thresholds for quality response were identified. A pilot study was performed to asses and score 1350 (27 indicator per patientX25 patientsX2 raters) quality indicators. The minimum proportion of patients meeting quality parameter ranged from 44% to 100% depending upon the variable. The lowest performance scores were observed in the early intubation and mechanical ventilation, treatment of significant intracranial mass effect or transtentorial herniation, and timely acquisition of computed tomographic scan of head. The highest performance scores were seen in treatment of any seizure within two weeks of admission, status epilepticus, and prevention of gastric ulcer. Conclusions: The next step in development of a new ICH specific intensity of care quality matrix is validation and refinement of the quality indicators and thresholds presented in the current report. Future activities may include selection and validation based on consensus of experts and/or application of the system to a large series of patients with ICH and assessment of relationship of components in isolation and as a group to outcome after severity adjustment.

Author Disclosures: A.I. Qureshi: None.

Th MP63 The Comparative Mortality of Ischemic Stroke vs. Intracranial Hemorrhage On and Off Warfarin: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study

Margaret C Fang, UCSF, San Francisco, CA; Alan S Go, Kaiser Permanente of Northern California Div of Rsch, Oakland, CA; Yuchiao Chang, Leila H Borowsky, Massachusetts General Hosp, Boston, MA; Niela K Pomernacki, Natalia Udaltsova, Kaiser Permanente Northern California Div of Rsch, Oakland, CA; Daniel E Singer; Massachusetts General Hosp, Boston, MA Background: When considering the net benefit of prescribing warfarin for atrial fibrillation, it is essential to compare the benefits associated with reducing ischemic stroke risk to the increase in intracranial hemorrhage (ICH) risk and severity. The impact of warfarin on stroke and ICH risk is relatively well studied, but the impact on event severity in atrial fibrillation is not. We compared 30-day mortality from ischemic stroke vs. ICH in a large community-based cohort of patients with atrial fibrillation. Methods: We followed a cohort of 13,559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system over a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. ICHs were categorized as intracerebral, subdural, or other ICH. Mortality was determined from healthplan databases and the State Death Index. We modeled the association of warfarin on 30-day mortality after ischemic stroke and ICH using multivariable logistic regression. Results: We identified 1025 ischemic strokes and 299 ICHs over ϳ65,000 person-years of follow-up. The annualized rate of ischemic stroke was 1.18% on warfarin and 1.97% off warfarin; the rate of ICH was 0.58% on warfarin and 0.32% off warfarin. Warfarin was associated with a substantially lower 30-day mortality rate after ischemic stroke, but higher mortality from ICH, particularly intracerebral hemorrhage (Table ). ICHs occurring on warfarin were 1.6 times more lethal than ischemic strokes occurring while off warfarin. Conclusions: Warfarin not only reduces the risk of ischemic stroke from atrial fibrillation, but also reduces 30-day mortality from ischemic stroke. However, warfarin conversely raises both the risk and mortality associated with ICH. Because ICH on warfarin is less common than ischemic stroke off warfarin, anticoagulation continues to be indicated for appropriate patients with atrial fibrillation. However, both the rates as well as severity of events need to be incorporated into rational decision-making when considering warfarin treatment.

Background:

The Early Use of Existing Preventive Strategies for Stroke (EXPRESS) trial demonstrated that urgent use of existing preventive medical treatment after a transient ischemic attack or minor stroke cut the 90 day risk of recurrent stroke by approximately 80%. While the ABCD 2 score can be used to stratify patients who are at high risk of recurrence of stroke or transient ischemic attack (TIA) following an initial TIA, it remains unknown whether hospital admission is required for all patients with TIA. Objective: To determine whether acute hospitalization following a TIA identifies any new clinical conditions that require immediate medical treatment. Methods: A review of 400 consecutive patients with a pre-admission diagnosis of TIA (ICD-9 435.9) admitted to two University affiliated comprehensive stroke centers was performed. Data relating to vascular risk factors, pre-hospitalization medical treatment, in-hospitalization medical treatment, and investigations performed (telemetric monitoring, brain imaging studies), and discharge medications were collected. The main outcome was defined as the in-hospital recurrence or worsening of neurological symptoms and the identification of any new medical conditions that led to the initiation of a new treatment. Results: The data regarding events recorded during hospitalization among 400 patients with TIA (mean age Ϯ standard deviation 67Ϯ15 years; 187 were men) is summarized in Table : 1. Table : 1 Conclusion: A reassessment of need for acute hospitalization of asymptomatic TIA patients must be considered given the low rates of newly identified medical conditions that require emergent treatment. New emphasis on the outpatient work up of TIA patients, with the initial evaluation and initiation of existing preventive medical treatments performed in the emergency department is required.

Th MP66 Impact of Stroke Clinical Prevention on Survival in Patients with Ischemic Stroke or Transient Ischemic Attack: A Propensity-Score Matching Approach

Jiming Fang, ICES, Toronto, Canada; Moira K Kapral, Gustavo Saposnik, Fiona Webster, Univ of Toronto, Toronto, Canada; Vladimir Hachinski; Univ of Western Ontario, London, Canada Background: Propensity score methods are increasingly being used to reduce the impact of treatment-selection bias in the estimation of casual treatment effects using observational data.

In the present study, we applied a propensity score matching approach to evaluate the impact of stroke clinical prevention (SPC) referral on survival in patients with ischemic strokes or transient ischemic attacks (TIA). Method: We analyzed data from 11 stroke centers in Ontario participating in the Registry of Canadian Stroke Network between July 2003 andMarch 2008, andlinked this to provincial administrative databases to capture physician visits, procedures including carotid revascularization, medication prescriptions and mortality within one year of the index stroke hospitalization. We compared care and outcomes in patients referred to SPCs compared to those without such a referral. Because of the substantial differences in baseline characteristics between patients with an SPC referral and those without, the propensity score greedy matching technique was applied to create 1:1 matched pairs. Standardized difference was used to compare balance in baseline variables between SPC and non-SPC patients. A Cox proportional hazards model with robust variance estimator to account for matching was used to discern the affect of SPC referral on survival. McNemar tests and paired t-tests were used to test the binary and continuous outcomes, respectively. Result: The original cohort included 16,468 patients with ischemic or TIA, 7,700 (47%) of whom were referred to a SPC at discharge. Over 70% of SPC patients were matched with non-SPC patients (5,575 matched pairs,total Nϭ11,150). In terms of standardized differences, the propensity-score matched cohorts were similar in demographic characteristics, stroke severity, medical history, inhospital acute treatment and modified Rankin scores at discharge. However, 1-year all-cause mortality of SPC patients was significantly lower than that of non-SPC patients (7% vs. 11%; Hazards Ratio 0.66; 95% CI: 0.58-0.74). Within 1 year of discharge, compared to those without SPC referral, patients referred to SPCs had more physician visits (14 vs. 12, PϽ0.0001), were more likely to undergo carotid imaging (47% vs. 39%, PϽ0.0001), and were more likely to be prescribed anti-hypertensive agents (87% vs. 84%, pϭ0.0003) and lipid lowering agents (76% vs. 69%, PϽ0.0001). Conclusion: In a propensity-score matched cohort, patients referred to SPCs had more physician visits, investigations and medications prescribed and has greater survival compared with those without a referral to a SPC.

Background: Intravenous tPA (IV tPA) improves outcomes in patients with acute ischemic stroke (AIS). We sought to determine if IV tPA use in AIS patients increased in Massachusetts in association with the Primary Stroke Service (PSS) program, a statewide stroke center designation and quality improvement (QI) initiative. Methods: We reviewed prospectively acquired data from the Massachusetts Department of Public Health (DPH) between October 2004 and June 2008. Data from 10,045 consecutive de-identified ED-based AIS encounters arriving Ͻ3 hrs after stroke onset at 68 participating Massachusetts PSS hospitals, representing 97% of all hospitals in the state, were analyzed. We evaluated the characteristics associated with IV tPA use over time among all AIS patients arriving within 2 hours of symptom onset. Results: In univariate analysis, IV tPA use among all patients arriving within 2 hours of symptom onset increased steadily from 2005 (the first full year of the program) to 2008 (18.4%, 21.9%, 22.6%, 25.5%, PϽ0.003). Patients treated with IV tPA were more likely to be younger (72.3Ϯ14.1 vs. 74.7Ϯ14.0, PϽ0.001), to have presented to a teaching hospital (41% vs. 34%, PϽ0.001), larger hospital (median 223 beds vs. 205 beds, pϭ0.002), or after EMS re-routing in July 2005 (96% vs. 94%, pϭ0.009). Factors independently associated with use of IV tPA in multivariable analysis were older age (OR 0.8, 95%CI 0.7-0.9 age 80-89; OR 0.6, 95%CI 0.4-0.8 age Ն90 vs. age Ͻ80) and increasing calendar year after 2004 (OR 1.1 per year, 95% CI 1.02-1.20) with a trend toward increased tPA use after EMS re-routing (OR 1.5, 95%CI 0.9-2.3). Twenty-eight hospitals participated in the AHA's Get With The Guidelines-Stroke (GWTG-S) program and received a performance achievement award during the study period. Patients arriving at those hospitals Յ2 hours after stroke onset were more likely to receive IV tPA after the hospital had received an award (32% vs. 20%, PϽ0.001). When award status was added to the multivariable model, it was independently associated with IV tPA use (adjusted OR developed model for accelerating enrollment in clinical trials. The model uses a highly-coordinated, geographically-localized, multi-institution strategy for participant identification, screening, and enrollment. Methods: Among 70 US investigators participating in an NIH-funded trial of stroke prevention, five were invited to develop Local Identification and Outreach Networks (LIONs). The networks were based on a recently described model. Each LION comprised a coordinating center servicing multiple hospitals. Hospitals provided the names of patients with stroke or TIA to researchers at the coordinating center who initiated contact; patients were offered home visits for consent and randomization. Outcomes of the validation study were feasibility, enrollment, data quality and cost. Results: Five LIONs varied in size from 2 to 8 hospitals. All 24 hospitals we approached in the five sites agreed to participate. The average monthly rate of enrollment at the five research sites increased from 1.4 participants to 3.5 after expanding from a single institution model to the LION format (mean changeϭ2.1, range 0.9-3.7). Monthly performance improved over time. Data quality was similar for LION and non-LION sites, except for drug adherence which was lower at LION sites. The average cost to randomize and follow one participant during the study interval was 2.5 times the cost under the per-patient, cost-reimbursement strategy at non-LION sites. The cost ratio declined from 3.4 in year one to 1.8 in year two. LIMITATIONS. The LION strategy requires unprecedented collaboration and trust among institutions. Applicability beyond stroke requires confirmation. Conclusion: LIONs are a practical, reproducible method to increase enrollment in stroke trial research. Twelve months were required for the average site to reach its potential. The per-participant cost at LION sites was higher than conventional sites, but declined over time.

Th MP75 Cilostazol Surpasses Aspirin in Secondary Stroke Prevention: Combined Analysis of Randomized Clinical Trials, CSPS II and CASISP

Yukito Shinohara for the CSPS II Group, Dept of Neurology, Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hosp, Tachikawa, Japan; Yining Huang for the CASISP cooperation investigators; Dept of Neurology, Peking Univ First Hosp, Beijing, China Objectives: The recent result of CSPS II showed superior efficacy of cilostazol versus aspirin in secondary stroke prevention. We performed a combined analysis of CSPS II conducted in Japan and CASISP in China, comparative trials of cilostazol and aspirin in secondary stroke prevention, to determine efficacy of cilostazol versus aspirin in a larger population with greater statistical power, and to examine differences in the main outcome and backgrounds of the two trials. Methods: Combined analysis of CASISP (nϭ719) and CSPS II (nϭ2672) data, involving 3391 patients (6907 person-years), was performed with the primary endpoint of first occurrence of stroke (cerebral infarction, cerebral hemorrhage, and subarachnoid hemorrhage) and secondary endpoints of: cerebral infarction; intracranial hemorrhage (cerebral hemorrhage, subarachnoid hemorrhage); and a cluster including stroke, TIA, MI and angina pectoris, both in the total population and in subgroups by stroke subtypes. Differences in the main outcome and patient characteristics between the two trials were also examined. Results: Primary endpoint rates were 2.82% per person/year in the cilostazol group and 3.89% in the aspirin group (pϭ0.0144). There were no significant differences for rates of cerebral infarction (pϭ0.3100) or cluster endpoint (pϭ0.0715) between cilostazol and aspirin. Cilostazol was significantly better than aspirin for preventing intracranial hemorrhage in the total population (pϭ0.0006), particularly in subgroup with lacunar infarction (pϭ0.0004). Examination of the patient backgrounds revealed that CSPS II included significantly higher rates of patients older than 65 years and patients with smoking/drinking habits, diabetes, hyperlipidemia, and hypertension, but not patients with BMI 25 or higher versus CASISP. As for outcome, rates of the primary endpoint tended to be higher in CASISP than CSPS II. Conclusions: Analyses of combined results confirmed that cilostazol is superior to aspirin in preventing stroke as well as intracranial hemorrhage especially in patients with lacunar infarction. CSPS II enrolled patients with higher risk versus CASISP, which might reflect more westernized life style in Japan versus China, however lower tendency of primary endpoint was seen, which might be attributable to more intensive control of risk factors in CSPS II versus CASISP. Background: Randomized clinical trials have shown that thiazide-based regimens reduce vascular risk in persons with known stroke. Although presumed efficacious, the impact of non-diuretic-based antihypertensives on vascular outcomes after stroke has been less well studied and is not convincingly proven. Specifically the totality of evidence regarding efficacy of renin angiotensin system (RAS) modulators in individuals with prior stroke is unclear. We assessed the efficacy of RAS modulators in persons with a history of stroke by conducting a systematic review and meta-analysis. Methods: Systematic literature search was performed. Inclusion criteria were 1) a randomized controlled trial; 2) participants with stroke history; 3) angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) as mandatory therapy in the active treatment group; 4) trials reporting cardiovascular events or just recurrent stroke as outcomes; 5) follow-up duration of at least 6 months. Studies were excluded if 1) mandatory ACE inhibitor or ARB used in control group; 2) additional treatment besides ACE inhibitor or ARB used in active group. Results: The search identified 7 randomized controlled trials comprising 28,805 participants with a history of stroke. Across all trials, RAS modulator therapy reduced cardiovascular events (relative risk 0.91, 95% confidence interval 0.86 to 0.96, PϽ0.001) (Fig 1). Across 6 trials with 25,791 participants with recurrent stroke reported as an endpoint, RAS modulator therapy marginally reduced stroke (relative risk 0.93, 95% CI confidence interval 0.86 to 1.00, Pϭ0.05) (Fig 2). Heterogeneity existed between estimates of cardiovascular events (pϽ0.01, I 2 ϭ65%) but not estimates of recurrent stroke (Pϭ0.46, I 2 ϭ0%). Conclusions: ACE inhibitor or ARB therapy modestly reduces the risk of future cardiovascular events in persons with a history of stroke. ACE inhibitor or ARB could be considered in patients with a history of stroke as add-on therapy, or in thiazide-intolerant patients.

Author Disclosures: M. Lee: None. J.L. Saver: None. K. Hong: None. Q. Hao: None. J. Chow: None. B. Ovbiagele: None.

Th MP77 Small Vessel Disease As A Multisystem Disorder: Association Of Cerebral Microbleeds With Renal Impairment In A Cross-sectional, Hospital-based Study

Simone M Gregoire, Kolawole W Wahab, UCL Institute of Neurology, London, United Kingdom; Khadija Rantell, UCL Div of Rsch and Strategy, London, United Kingdom; Hans R Ja ¨ger, David J Werring; UCL Institute of Neurology, London, United Kingdom Objectives: In view of the close similarity between the vasculature of the brain and the kidneys, microvascular pathological changes in one organ could reflect or predict similar changes in the other, with relevance for vascular prevention. Cerebral microbleeds (CMBs) are a new MRI marker for small vessel disease in the brain, with potentially important diagnostic and clinical implications. We investigated the relationship between CMBs and renal impairment in a cross-sectional, hospital-based, cohort study. Methods: We studied consecutive patients referred to our specialist stroke service (stroke unit and associated neurovascular clinics). Patients with complete medical records, a satisfactory MRI study including T 2 *-weighted sequence, and renal function tests (Ͻ4 weeks from the time of MRI) were included. We examined the MRI scans for the presence and number of CMBs and the presence of white matter changes (WMC) using validated scales, and estimated the glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. Predictors of microbleeds presence in the brain were tested using regression analyses. Findings: One hundred and ninety-six patients were included, with a median age of 68.0 years. The prevalence of CMBs in the cohort was 18.9%. In univariate analysis, the only factor associated with the presence of CMBs was mean total WMC score (OR 1.09, 95%CI 1.02-1.17, pϭ0.009). Multivariate logistic regression analysis showed that for every unit decrease in eGFR, the odds of having one or more CMBs increased by 3.1% (OR 0.97, 95% CIϭ0.94-0.99, pϭ0.017), and this was independent of the severity of WMC. Conclusions: In this stroke cohort, the presence of CMBs, a marker of small vessel disease, is associated with impaired renal function as measured by the glomerular filtration rate. Our findings provide further evidence that cerebral small vessel disease may be part of a systemic microangiopathic disorder. Optimal prevention Background and Purpose: Several studies have suggested that 25% human albumin (HA) confers neuroprotection. We investigated the safety and tolerability of this therapy in patients with aneurismal subarachnoid hemorrhage (aSAH). Methods: The ALISAH (Albumin in Subarachnoid Hemorrhage) Clinical Trial was a multi-center, prospective, open-label, doseescalation study. Subjects with aSAH (WFNS Scale I-III) received a 3-hour infusion of HA daily for 7 days beginning within 72 hours of symptom onset and after aneurysm treatment. Four successive HA dose tiers with 20 subjects each were planned ranging from 0.625 to 2.5 g/kg/day. Neurologic and cardiac function was sequentially monitored. The main safety outcome was severe or life-threatening heart failure up to 48 hours after treatment infusion. At 3 months the Glasgow Outcome Scale, Barthel Index, modified Rankin Scale, NIH Stroke Scale, and Stroke Impact Scale were measured. Results: Forty-seven subjects (mean age, 51 years) received HA at 2.2 ϩ/-0.7 days after aSAH onset (mean ϩ/standard deviation). Blood pressure increased after the first day of treatment and remained elevated thereafter. Serum osmolarity and creatinine were unaltered by HA treatment. Dose-related increases in plasma albumin and hemodilution were maximal at day 3 and were present 72 hours after termination of treatment. Heart failure to any degree requiring medical management was experienced by eleven patients (23%): 2 in dose tier 1 (0.625 g/kg); 3 in dose tier 2 (1.25 g/kg); and 6 in dose tier 3 (1.875 g/kg) with 2 severe or life-threatening events probably related to HA. Because of our pre-specified stopping rule the investigators and the DSMB agreed to terminate the study after 7 patients were enrolled in dosage tier 3. Conclusion: The ALISAH trial found that HA in doses ranging up to 1.25 g/kg/day x 7 days was tolerated by patients with aSAH without major dose-limiting complications. Because of the complexity and the amount of data a companion abstract presents neurologic outcome data and treatment effect analysis in these subjects.

Author Disclosures: J.I. Suarez: Research Grant; Significant; The ALISAH study was funded by NINDS: NS049135 (PI: JI Suarez). Other Research Support; Modest; GRIFOLS International supplied the 25% human albumin at no cost for the ALISAH study. R.L. Martin: None.

Th MP80 Elevated blood TNF-alpha and IL-6 are Associated with Poor 3-month Outcome following Subarachnoid Hemorrhage

Sherry H Chou, Brigham and Women's Hosp, Boston, MA; MingMing Ning, Massachusetts General Hosp, Boston, MA; Rachael G Konigsberg, Suzanne Simmons, David Bauer, Brigham and Women's Hosp, Boston, MA; Eric Loesch, Massachusetts General Hosp, Boston, MA; Steven K Feske, Brigham and Women's Hosp, Boston, MA; Eng H Lo; Massachusetts General Hosp, Boston, MA Background: Subarachnoid Hemorrhage (SAH) affects over 30,000 Americans per year and leaves over 50% of survivors with significant disability. Recent studies suggest SAH is associated with an inflammatory response which may mediate vasospasm and affect outcome. We hypothesize blood TNF-alpha and IL-6 levels are associated with vasospasm and SAH outcome, making them potential prognostic molecular biomarkers. Methods: We prospectively enroll consecutive SAH subjects, bank blood and CSF samples on post SAH days 0-3, 4-5, 6-7, and 10-14, and evaluate their 3-month modified Rankins score (mRS) via telephone follow-up. Angiographic vasospasm (VSP) is defined as Ͼ 50% reduction in vessel caliber on angiography. Poor outcome is defined as mRS Ͼ 2. We compared blood TNF-alpha and IL-6 levels by ELISA on post SAH days 0-3, 4-5, 6-7, and 10-14 in 32 SAH subjects with (nϭ17) and without (nϭ15) VSP and subjects with (nϭ22) and without (nϭ10) poor functional outcome at 3 months. Results: Poor outcome is associated with elevated mean TNF-alpha (pϭ0.0005) and IL-6 (pϭ0.01) averaged across all time points. Elevated TNF-alpha (pϽ0.0001) and IL-6 (pϭ0.004) on post SAH days 0-3 were most strongly associated with poor 3-month SAH outcome (Figure 1). After adjusting for SAH clinical severity (Hunt and Hess grade), elevated blood TNF-alpha (pϭ0.003) and IL-6 (pϭ0.02) remain independently associated with poor outcome at 3 months in a logistic regression model. Blood TNF-alpha and IL-6 levels are not associated with VSP at any time point. Conclusion: Elevated blood TNF-alpha and IL-6 levels on post SAH days 0-3, 4-5, 6-7, and 10-14 are strongly and independently associated with 3-month SAH outcome and may be potential predictive biomarkers for SAH outcome. Differential associations between TNF-alpha and IL-6 with respect to VSP and functional outcome suggest these inflammatory cytokines may play a divergent role in SAH-related pathogenesis. Further studies in larger cohorts are necessary to determine the role of TNF-alpha and IL-6 in SAH clinical outcome.

Th MP81 Plasma-type gelsolin (pGSN) is reduced in Human Blood and Cerebrospinal Fluid following Subarachnoid Hemorrhage

Sherry H Chou, Po-Shun Lee, Rachael G Konigsberg, Dana Gallachi, Brigham and Women's Hosp, Boston, MA; Ken Arai, Massachusetts General Hosp, Boston, MA; Suzanne Simmons, Brigham and Women's Hosp, Boston, MA; Eric Loesch, Massachusetts General Hosp, Boston, MA; David Bauer, Thomas P Stossel, Steven Feske, Brigham and Women's Hosp, Boston, MA; Eng H Lo, MingMing Ning; Massachusetts General Hosp, Boston, MA Background: Subarachnoid Hemorrhage (SAH) causes 27% of stroke-related potential life-years lost below age 65 and leaves over 50% of survivors with significant disability. Recent studies suggest SAH is associated with acute systemic inflammatory responses. A substrate of metalloproteinases (MMP), pGSN may play an important role in modulating actin-mediated inflammation and cell injury. Clinically, blood pGSN predicts mortality from critical illness. We previously found pGSN in plasma proteomic screening of patients with neurovascular injuries. In this study, we hypothesize pGSN is reduced in blood and CSF following SAH, and explore MMP activity as potential etiology for pGSN reduction. Methods: We prospectively enroll consecutive SAH subjects and bank blood and CSF samples on post SAH days 0-3, 4-5, 6-7, and 10-14. Controls subjects are consecutive non-vascular patients who undergo elective lumbar-drain trial. Blood and CSF in control subjects are banked on days 0-3 post lumbar drain placement. We compared blood and CSF pGSN levels in 30 SAH subjects with 20 controls and performed pGSN ELISA, pGSN Western blot, and MMP zymography. Results: Mean blood pGSN was higher in control subjects compared to SAH subjects at all time points (pϽ0.0001). Median CSF pGSN was lower in SAH compared with non-SAH controls (pϭ0.0009), and this effect was strongest on post SAH day 4-5 (pϭ0.02). Western blot on selected SAH and control subjects demonstrated that the SAH subjects had novel bands at 50 kD, which represents potentially cleaved pGSN fragments. Gelatin zymography in these subjects showed CSF MMP-9 activity was higher in SAH compared with controls (Figure 1), and a trend towards higher CSF MMP-9 activity with lower CSF pGSN (r2ϭ0.92;pϭ0.18). Conclusion: SAH is associated with reduced blood and CSF pGSN compared with normal control subjects. In SAH subjects, lower CSF pGSN levels correlate with higher MMP-9 activity, suggesting MMP-9 may cleave pGSN. Novel cleaved pGSN fragments are present in CSF of SAH subjects but not control subjects on Western blot. The molecular weight of these fragments corresponds to cleaved product we previously reported in the plasma of stroke patients. To our knowledge, this is the first report of pGSN fragments in CSF of SAH. From these preliminary findings, we hypothesize that pGSN reduction in SAH may be secondary to cleavage by MMP-9. Further studies of total pGSN, pGSN cleaved products, and MMP-9 activities in blood and CSF in larger patient cohorts with long-term outcome data are needed to understand the mechanism of pGSN in SAH.

This research has received full or partial funding support from the American Heart Association, National Center.

Introduction:

Cerebral vasospasm (VSP) is a leading factor for morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). Well-defined risk factors delineate the likelihood of VSP; however, there is a paucity of available prediction models, which, in contrast, allow cumulative integration of each individual SAH patient's clinical, laboratory, and imaging data to produce a "personalized" VSP risk profile. Method A retrospective analysis of a prospective aSAH database was performed (admission days 0-3).

Th MP83 Symptomatic Large Vessel Vasospasm after Aneurysmal Subarachnoid Hemorrhage is Associated with Low Pulsatility Index on Transcranial Doppler

Venkatakrishna Rajajee, Jeffrey J Fletcher, Aditya Pandey, Joseph J Gemmete, Neeraj Chaudhary, Teresa Jacobs, Byron G Thompson; Univ of Michigan, Ann Arbor, MI Background: Vasospasm occurs in 30-70% of patients with aneurysmal subarachnoid hemorrhage (aSAH) and can result in severe disability or death. Elevated mean flow velocity (MFV) on Transcranial Doppler (TCD) predicts vasospasm of the large intracranial arteries, although sensitivity and specificity are variable. The Pulsatility Index (PI), derived from the spectral doppler, is defined as-(Peak Systolic Velocity -End Diastolic Velocity) / MFV and is a measure of distal vascular resistance. Distal vascular resistance, and therefore the PI, may be low when there is compensatory distal vasodilatation following hypoperfusion caused by large vessel vasospasm. Low PI may predict critical lower limb ischemia in the setting of peripheral vascular disease. Objective: To study the predictive value of low Pulsatility Index for symptomatic large vessel vasospasm (SLVVS) after aSAH. Method: Medical records of patients admitted with aSAH between January 2007 and April 2009 were reviewed. Patients with poor acoustic windows and those who died within 72 hours were excluded. TCD was performed daily through transtemporal windows while the patient was in the ICU. Patients who suffered acute neurological decline underwent non-contrast CT followed by catheter angiography or CT angiography when no other cause was readily identified. Results: There were 79 patients with aSAH admitted in the study period. 21 of 79 (26.6%) had neurological decline associated with moderate or severe large vessel vasospasm on angiography. Median lowest recorded PI was 0.65 (95% CI 0.60-0.69), range 0.41-1.09. An ROC curve of lowest recorded PI in predicting SLVVS revealed an optimal PI of 0.58-sensitivity 66.67% (95% CI 43-85.4%); specificity 84.48% (72.6-92.7%), Area Under Curve 0.725; P(Areaϭ0.5)ϭ0.0045. Odds Ratio for PIϽ0.6 in predicting SLVVS was 8.54 (95% CI 2. 79-26.19, pϭ0.0002). All values of PIϽ0.6 in patients with SLVVS were recorded in vessels seen to be moderate or severe vasospasm on angiography. An ROC curve of highest recorded MFV in predicting SLVVS revealed optimal MFV of 139cm/s-sensitivity 85.71% (63.7-97.0%); specificity 70.69% (57.3-81.9%), Area Under Curve 0.774; p(Areaϭ0.5) Ͻ0.0001. Odds Ratio for MFVϾ 140cm/s in predicting SLVVS was pϭ0.0001). Regression analysis between PI and MFV revealed a coefficient of determination R 2 ϭ0.32, residual standard deviation 0.14. The equation was y ϭ 0.88 ϩ -0.0014 x; coefficient of the slope 0.0014 (95% CI 0.0018-0.0009), standard error 0.0002, PϽ0.0001. Conclusion: Pulsatility Index Ͻ0.6 on TCD, in addition to MFVϾ140cm/s, predicts symptomatic large vessel vasospasm after aneurysmal SAH. This may reflect compensatory distal vasodilatation in the setting of ischemia. The presence of low Pulsatility Index on Transcranial Doppler should increase the level of concern for impending symptomatic ischemia from vasospasm after aSAH.

Author Disclosures: V. Rajajee: None. J.J. Fletcher: None. A. Pandey: None. J.J. Gemmete: None. N. Chaudhary: None. T. Jacobs: None. B.G. Thompson: None. 72 patients had SAH by NCCT (94.7%) and 4 patients had CSF xanthochromia (5.3%). Among the former, 29 patients had perimesencephalic SAH (40.3%) and 43 had nonperimesencephalic SAH (59.7%, kappa 0.91, 95% CI 0.89-0.93). CTAs were performed in all patients and MRAs were performed in 71 patients (93.4%). Mean time interval between the initial catheter angiogram and the CTA was 1.05 days (median 1 day, range 0-7 days), and the MRA was 1.28 days (median 1 day, range 0-5 days). CT angiography demonstrated a causative cerebral aneurysm in 4 patients (yield of 5.3%, kappa statistic 0.88, 95% CI 0.86-0.9), all of which had non-perimesencephalic SAH (yield of 9.3%). Aneurysm locations were 1 anterior communicating artery (Figure 1), 1 posterior communicating artery, 1 right posterior inferior cerebellar artery, and 1 distal left posterior cerebral artery. Mean aneurysm size was 2.6mm (median 2.45mm, range 2.1-3.3mm). Two of the aneurysms underwent surgical clipping and two endovascular coil embolization. MR angiography only showed 1 of these aneurysms because 2 patients underwent treatment immediately after the CTA and in 1 patient the field of view did not include the aneurysm. No causative aneurysms were found in patients with perimesencephalic SAH or CSF xanthochromia. In 1 patient the CTA and MRA demonstrated a 2mm anterior communicating artery aneurysm that was found to be a fenestration in a repeat catheter angiogram. Conclusion: CT angiography is a valuable adjunct in the evaluation of patients with non-perimesencephalic SAH who have a negative initial catheter angiogram, demonstrating a causative cerebral aneurysm in 9.3% of patients.

Th MP84 Diagnostic Yield of CT and MR Angiography in Patients with Catheter Angiography Negative Subarachnoid Hemorrhage

Background: Dementia affects survivors of ischemic stroke at a greater rate than the general population, suggesting interaction between vascular lesions and neurodegenerative disease. If post-stroke dementia (PSD) reflects unmasking of preclinical Alzheimer's disease (AD), it might be predicted by increased binding of beta-amyloid (Abeta) in a typical AD pattern. Alternatively, other patterns of Abeta binding, reflecting cerebral amyloid angiopathy (CAA) or ischemiainduced Abeta deposits may be important determinants of PSD. Principal component analysis (PCA) is a multivariate technique that extracts patterns explaining the variance in data and is thus an ideal tool to explore the distribution of Abeta binding after acute ischemic stroke (AIS). Methods: We analyzed 11 C-PIB PET scans from 39 cognitively normal elderly individuals with hemispheric AIS enrolled in a longitudinal study investigating the use of PIB to predict PSD. PCA was performed on the voxels in non-infarcted hemisphere (to avoid effects of reduced blood flow on PIB uptake in infarcted hemisphere) from filtered, masked images normalized to cerebellar gray matter, aligned to MRI, and co-registered to Talairach atlas space using an affine transform. Mean cortical binding potential (MCBP) values for PIB were calculated as the average of binding potentials in regions of interest drawn in prefrontal cortex, precuneus, laterotemporal cortex, and gyrus rectus, excluding areas of infarct. Results: 11 C-PIB binding was elevated (MCBPϾ0.18) in 13 (33%) individuals with AIS (age 76Ϯ8 years) compared to 90% of 21 individuals with AD (age 77Ϯ7 years, CDR 1-2) and 31% of 76 healthy controls (age 75Ϯ6 years, CDR 0). PCA showed that the first 2 eigenvectors explained 70% of the variance among AIS participants; the subsequent 3 eigenvectors accounted for the bulk of the remaining variance. Eigenvector 2 was highly correlated with MCBP (rϭ0.85), reflecting the binding patterns characteristic of healthy controls and AD. A third eigenvector identified a pattern of posterior cerebral uptake particularly in lateral occipital lobe in 9 participants, 5 of whom had normal MCBP. Lobar microbleeds were seen in 2 of these participants (5 in 1; 1 in the other). Conclusion: 11 C-PIB binding followed an AD pattern in one-third of elderly individuals with hemispheric AIS, a similar rate as seen in normal controls. In addition, PCA identified at least 1 other pattern of uptake in a subset of participants. This pattern of prominent posterior binding suggests CAA, though only 2 of the participants with this pattern met MRI criteria for possible or probable CAA. Longitudinal data are needed to determine whether any PIB binding pattern is predictive of PSD.

Author Disclosures: A. Zazulia: None. J. Markham: None. T. Videen: None. T. Benzinger: None. M. Mintun: Employment; Significant; Avid Radiopharmaceuticals, Inc.. J. Morris: None.

Th MP86 Effect of Apixaban on Covert Stroke and Cognitive Function: AVERROES MRI-Brain Assessment Trial

Martin O'Donnell, John Eikelboom, Salim Yusuf, Stuart Connolly, McMaster Univ, Hamilton, Canada; On Behalf of the AVERROES Investigators Covert stroke is common in patients with atrial fibrillation, proposed to occur about five-times more often than clinical stroke. Cognitive impairment is a prominent consequence of covert stroke. However, it is not known whether anticoagulant therapy prevents covert stroke to a similar extent as clinical stroke. In the AVERROES trial, we evaluated the effect of apixaban on; 1) covert stroke (MRI of brain) and; 2) cognitive function. Methods: The AVERROES trial compared apixaban to antiplatelet therapy for prevention of stroke in patients with atrial fibrillation who failed or were considered unsuitable for warfarin, and was recently terminated early by the DSMB because of superiority of apixaban. In the MRI study, a baseline MRI of brain has been completed (FLAIR, DWI, T1, T2 and GRE sequences) in 1,184 participants, and we measured the prevalence of cerebral infarction, white matter hyperintensities (WMH) and microbleeds (MRI Lab, Essen, Germany). Follow-up MRI scans are expected to be complete by Nov 2010. Participants underwent cognitive assessment, with modified-Montreal Cognitive Assessment (m-MoCA), Digit Symbol Substitution test and Trails Making test-B. Results: In the 1,184 participants who completed baseline MRI (mean age 69 years), covert infarction was recorded in 25.6% of participants. In those without a history of clinical stroke (nϭ1,059), covert infarction was present in 20.1%. WMH were observed in most participants (84.6%), reported as mild in 45.3%, moderate in 29.3% and severe in 10.0%. Microbleeds were recorded in 9.9% of participants. Mean m-MoCA was 9.1 (SD 2.5) in patients with covert infarct, 8.9 (SD 2.7) in patients with severe WHD and 10.1 (SD 1.9) in those without covert infarction or WMH. In Feb 2011, we will present the effect of apixaban on rates of new covert stroke and cognitive decline (compared to antiplatelet therapy) and, the prognostic importance of baseline covert ischemia and microbleeds on clinical outcomes (ischemic and hemorrhagic stroke and cognitive decline).

Conclusion:

Covert stroke is common in patients with atrial fibrillation and associated with impaired cognitive testing. AVERROES-MRI will be the first large study to determine the effectiveness of anticoagulant therapy on the incidence of covert stroke.

Th MP87 Acute Ischemia in Left Angular Gyrus Impairs Comprehension of Syntax

Lydia A Trupe, George Washington Univ, Washington, DC, DC; Rebecca F Gottesman, Argye E Hillis; Johns Hopkins Univ SOM, Baltimore, MD Background: Studies from chronic stroke and fMRI have emphasized the role of Broca's area (left Brodmann's area 44 and 45) in syntax processing and working memory. However, conflicting results have been reported; many patients with lesions in Broca's area have no deficits in either syntax comprehension or working memory, perhaps because they have recovered through reorganization of structure-function relationships. Additionally, it is likely that both functions rely on more widespread cortical networks. We sought to identify other regions that when damaged acutely disrupt syntax comprehension and working memory, and investigated the relationship between them. Method: A series of 49 patients had tests of syntax processing and working memory and MRI within 24 hours of acute ischemic left hemisphere stroke, before extensive reorganization. Language tests included sentence-picture matching and enactment of sentences with both syntactically complex and simple sentence structures, and forward and backward digit span. MRI scans were analyzed by a technician masked to language results for ischemia on DWI and/or PWI in each of 11 Brodmann's areas (BA). We identified associations between dichotomous variables using chi square tests after Bonferroni correction, evaluated differences in means between groups using ANOVA, and identified correlations between tests using Spearman's rho. Results: There was a strong association between ischemia in BA 4, 6, 44, and 45 and impaired working memory defined by backward digit span Յ2 (X 2 ϭ 6.7 -19.9; pϽ 0.0001-0.009). Patients with acute ischemia in these posterior frontal regions had significantly reduced backward digit spans (e.g. mean 1.0 vs 4.0; PϽ0.002 for BA 6) compared to patients without ischemia in these regions, but did not have significantly impaired comprehension of syntactically complex sentences. In contrast, patients with acute ischemia in left BA 39 (angular gyrus) had significantly lower backward digit span (mean 1.6 vs 3.9; pϭ0.008) than those without acute ischemia in BA 39, but also had significantly impaired comprehension of only syntactically complex sentences. For example, they were impaired in sentence picture matching with semantically reversible object cleft sentences (eg. " It was the niece that the father kicked") compared to patients without ischemia in BA 39 (mean 77.6% correct vs 92.8% correct; PϽ0.04). Patients with acute ischemia in BA 20, 21, 22 were impaired in understanding all sentence types (syntactically simple and complex). Forward and backward digit span were correlated (r 2 ϭ.42; PϽ.0001), but there were no significant correlations between complex sentence comprehension tests and measures of working memory. Conclusion: Left angular gyrus has a critical role in comprehension of syntactically complex sentences that does not appear to be explained only by its role in working memory, and needs further investigation. This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: L.A. Trupe: None. R.F. Gottesman: None. A.E. Hillis: None.

Th MP88 White Matter Hyperintensity Burden is Associated with Cognitive Decline in a Stroke-free Cohort: the Northern Manhattan Study

Clinton B Wright, Chuanhui Dong, Tatjana Rundek, Univ of Miami, Miami, FL; Sandino Cespedes, Mitchell S Elkind, Columbia Univ, New York, NY; Charles DeCarli, Univ Of California, Davis, Sacramento, CA; Ralph L Sacco; Univ of Miami, Miami, FL Background: A heavy burden of white matter hyperintensities (WMH) is a risk factor for vascular cognitive disorders -cognitive impairment and dementia where vascular damage plays a role -but few large prospective population-based studies have used volumetric methods to examine the effect on cognitive decline. Also, many studies have been limited to non-Hispanic white participants, and the effect of WMH on cognitive decline among black and Hispanic people is not clear, even though they are at greater risk of stroke and dementia than whites. Methods: The Northern Manhattan Study (NOMAS) includes a stroke-free sample that underwent brain MRI. We used quantitative methods to assess WMH volume (WMHV) blind to participant characteristics and cognitive performance, and adjusted for intracranial volume (ICV) to correct for differences in head size. The modified Telephone Interview for Cognitive Status (TICS-m) has been collected annually in NOMAS. We examined cognitive change over time using mixed models, with an interaction term between quartiles of WMHV (Q4ϭhighest, Q1ϭlowest and reference) and time between baseline and each subsequent TICS-m, adjusting for relevant sociodemographic and vascular risk factors. Results: There were 1,099 NOMAS participants with both brain MRI measures of WMHV and subsequent TICS-m assessments available (mean (SD) age 71 (8.5), 61% women, 67% Hispanic, 18% black, 15% white). The mean WMHV was 0.67% of ICV (interquartile range 0.22-0.77% ICV). There was no significant difference in baseline TICS-m scores between those in different WMHV quartiles. Examining the dose effect of WMHV on cognitive decline with Q1 as the reference, scores on the TICS-m declined in a linear fashion for Q2 (-0.07 points/year) and Q3 (-0.11 points/year) but showed a steeper decline for Q4 (-0.33 points/year), and only Q4 had significantly lower TICS-m scores over time adjusting for age, sex, race-ethnicity, education, alcohol use, physical activity, peripheral vascular disease, and systolic blood pressure (Pϭ0.006). Examining the change in adjusted mean TICS-m scores across years of follow-up, scores of those with WMHV in Q4 declined steadily, and were significantly lower at five years (adjusted mean differenceϭ1.6 points, Pϭ0.0006). Conclusions: Despite similar baseline cognitive performance, we found that NOMAS participants with a WMH burden greater than 0.77% of ICV showed more cognitive decline than those in the lowest quartile in this multi-ethnic stroke-free community-based cohort. Prospective studies in diverse samples with more sensitive neuropsychological tests are needed to clarify the domains impacted by WMH in vascular cognitive disorders. Background: A composite measure of several chronic infections (infectious burden, or IB) is associated with risk of stroke and carotid atherosclerosis in our cohort. The association of IB with cognitive impairment and dementia remains mostly unexplored, however. We hypothesized that a measure of IB associated with vascular risk would also be associated with cognition and cognitive decline in a prospective cohort study. Methods: Crosssectional and prospective analyses among stroke-free community participants in the multi-ethnic Northern Manhattan Study were performed. Cognition was assessed using both the Mini Mental State Exam (MMSE) at enrolment and the modified Telephone Interview for Cognitive Status (TICS-m) during annual telephone follow up . IB was calculated based on a composite measure of serologies against microbial agents previously shown to be associated with risk of stroke and carotid plaque (i.e. Chlamydia pneumoniae, Helicobacter pylori, CMV, HSV1 and 2). Linear and logistic regression were used to measure the magnitude of association between IB and cognition after adjusting for other risk factors, and generalized estimating equation models were used to evaluate associations with TICS-m and its change over time. Results: Both serologies and cognitive assessments were available in 1623 participants (mean age 68.5ϩ/-10.1 yrs, 64.9% women). Median MMSE was 27 (interquartile range (IQR) 24-29) and median TICS-m 32 . In the unadjusted model IB index was associated with MMSE and TICS-m (both PϽ0.0001; see table). These effects were attenuated after adjusting for demographics, and there was little change after further adjusting for vascular risk factors. The effect of IB remained significant for TICS-m (pϽ0.0001; see table). IB was associated with MMSE ϭϽ24 (adjusted OR 1.22, 95% confidence interval 1.03-1.45). However, IB was not associated with cognitive decline over time (pϭ0.07). Conclusion: A measure of infectious burden that is associated with vascular disease risk was independently and inversely associated with cognitive performance in this multi-ethnic cohort, though it was not associated with further cognitive decline. Past infection and associated inflammationrelated vascular damage may contribute to cognitive impairment in the elderly.

Introduction:

The risk of symptomatic intracerebral hemorrhage (SICH) after intravenous thrombolysis (IVT) has been related to the persistence of arterial occlusion Ͼ2h as well as to delayed recanalization (Ͼ6h). It remains however unknown whether time to recanalization implies a progressive increase in the risk of SICH. Objetive: To study the relationship between the risk of SICH and time to recanalization evaluated by serial transcranial Dupplex monitoring within 24 hours of IVT (1, 2, 6, 12 and 24h), in a cohort of 151 patients with acute ischemic stroke due to large artery occlusion in the anterior circulation treated with i.v. alteplase. Methods: Patients were classified in 4 groups according to the time to complete recanalization (TIBI 4 or 5) as follows: Ͻ2h (nϭ58), 2-6h (nϭ10), 6-24h (nϭ33) and no recanalization (NR) at 24 hours (nϭ50). SICH was defined following the ECASS-2 criteria (any hemorrhagic transformation with NIHSS score worsening Ն4 points) and according to SITS-MOST criteria (parenchymal hematoma type 2 with neurologic worsening). Favorable outcome was considered when the modified Rankin score Յ2 at 3 months. Results: There were no differences among groups in localization of the occlusion (MCA/ICA 56/3, 10/0, 30/3, 44/6, pϭ0.37) or in stroke severity , 15 [8-19], 13 [9-17] y 16 [11][12][13][14][15][16][17][18][19][20], pϭ0.13), however, the patients from the NR group were significantly older than the other groups (68. 7Ϯ10.4, 65.2Ϯ14.5, 64.8Ϯ12.8, 72.2Ϯ11.3, pϭ0.039). SICH (ECASS/SITS-MOST) was observed in 6.9%/5.2% of the patients who recanalized Ͻ2h, in 0%/0% of the patients who recanalized between 2-6h, in 3%/3% of the patients who recanalized within 6-24h and in 4%/0% of those patients who did not recanalize at 24h. The rate of favorable outcome was 78%, 66%, 47% and 30% (pϽ0.001). Conclusions: Our findings are in line with the literature showing a relationship between time to recanalization and functional outcome. Based in the results of this study, a progressive increase in the rate of SICH with time to recanalization cannot be concluded.

W P2 Two Hour Improvement Of Patients In The NINDS t-PA Trials And Prediction Of Final Outcome

Thomas M Hemmen, Karin Ernstrom, Rema Raman; UCSD MEDICAL CENTER, San Diego, CA Background: Ongoing clinical trials are using the early response to intravenous t-PA (IV t-PA) to stratify patients into endovascular therapies. Little is known about the likelihood of ultra-early recovery after IV t-PA and its correlation with final stroke outcome. Using previously unpublished data points, we investigated the likelihood of neurological improvement 2 hours after IV t-PA compared to placebo in the NINDS IV t-PA studies. Methods: The two NINDS t-PA studies were randomized and placebo controlled; published in 1995 and proved that IV t-PA within 3 hours after stroke improved patient outcome at 3 months. Details regarding patient baseline demographics and study methods were published elsewhere. The NINDS t-PA dataset was obtained from a publicly accessible data repository. We analyzed patients by improvement of Ն4 points on the NIHSS at 2 hours after study drug or placebo bolus administration; and correlated this 2 hour improvement with the likelihood of good outcome (modified Rankin Scale 0 or 1) at 3 months. We adjusted for multiple confounders, including t-PA treatment. Results: Two hour improvement was seen in 112/312 (35.9%) of t-PA treated patients and 71/312 (22.7%) in the placebo groups (pϽ0.0001)). Smokers (pϭ0.012) and patients treated under 90 min (pϭ0.008) were more likely, diabetics (pϭ0.023) less likely to show improvement at 2 hours. The baseline NIHSS (meanϮSD) of patients with improvement was 16.1Ϯ6.5 versus 14.3Ϯ7.4 (pϭ0.001). Good outcome was achieved in 68/112 (60.7%) t-PA treated patient who had 2-hour improvement and 65/200 (32.5%) without (placebos groups 30/71 (42.3%) versus 53-241 (22.0%)). When adjusting for age, admission NIHSS, history of diabetes and t-PA treatment the odds for a good outcome in patients with 2 hours improvement was 7.69 (95% CI: 4.63, 12.76; PϽ0.0001). Conclusion: Early improvement was more common in t-PA treated patients compared to placebo, and was associated with good 90 day outcome. The use of early improvement after t-PA to predict final stroke outcome shows value.

Author Disclosures: T.M. Hemmen: None. K. Ernstrom: None. R. Raman: None. There is considerable interest in identifying differential subgroup effects of rt-PA, however often with discrepant results, especially regarding gender. Group imbalances in factors associated with outcome may contribute to discrepancies. Conventional statistical means by which imbalances are usually adjusted are based on assumptions of relationships between these factors that may not be valid. Subgroup analyses are especially vulnerable to imbalances as their numbers dwindle or issues such as recruitment bias emerge. We have developed new methods that accommodate imbalances and applied them to assess the influence of gender and race on rt-PA outcomes. Methods: pPREDICTS©(Mandava and Kent, Stroke 2009) is a method in which an outcome model based on placebo arms of multiple trials is generated with multi-dimensional statistical intervals to assess whether a population differs from expected outcome at similar baseline conditions (see figure; Ϯ pϭ.05 prediction intervals bound the outcome surface). pPAIRS© (Mandava et al Stroke 2010) is an algorithm by which subjects within groups are matched in Euclidean space for baseline factors and outliers eliminated. We applied both methods to the NINDS rt-PA dataset and examined outcomes based on gender and race. Results: There were major imbalances among the gender and race rt-PA and placebo groups at baseline, reinforcing the need for an assumption-neutral analysis method. Predicts©: The figure shows % achieving good outcome (mRSՅ2) compared to baseline NIHSS and age using the entire dataset. Placebo outcomes were close to the model for all groups. In Caucasians (C), significant improvement in functional outcome was seen for both genders (Fig 1a ; note both rt-PA outcomes are above the pϭ.05 interval). Overall, African Americans (AA) showed about half the degree of improvement, and this was explained by essentially no improvement for AA females, while AA males showed improvement that was only slightly below the pϭ.05 interval (Fig. 1b). Pairs©: Simultaneous matching for gender, race, baseline NIHSS, age, glucose and stroke subtype indicated that functional outcome after rt-PA in AA females was considerably worse than C females at similar baselines (e.g. median NIHSS 15.5 vs 15; mRS 0-1: 39% for AA vs 65% for C; pϭ.023) and mortality was 3X higher (27% vs 8%). Discussion: We were able to clarify the role of gender and race in treatment outcome that has been complicated by imbalances. We found good response to rt-PA regardless of gender in Caucasians, marginally less in AA males and poor in AA females. Factors that may explain this poor response are under investigation.

W P3 Gender and Race

Author Disclosures: P. Mandava: None. M. Munoz: None. K. Sarma: None. M.A. Brooks: None. W. Dalmeida: None. J. Anderson: None. R. Fabian: None. T.A. Kent: None.

W P4 Tissue Plasminogen Activator Use May be Associated with Increased Diffusion-Weighted Imaging Lesion Volume in Malignant Middle Cerebral Artery Syndrome

Tzu-Ching Wu, Mallik Kasam, Divya R Danda, Preeti Sahota, Renganayaki Pandurengan, William Hicks, Andrew D Barreto, Nicole R Gonzales, George A Lopez, James C Grotta, Sean I Savitz; UT Houston Med Sch, Houston, TX Objective: Tissue plasminogen activator (tPA) has been shown in animal and human studies to induce blood brain barrier opening and reperfusion injury. We hypothesized that in patients with malignant middle cerebral artery syndrome (MMCA), prior use of IV tPA may contributed to infarct expansion and cerebral edema increasing the need for hemicraniectomy (HC). We compared the MRI-DWI lesion volumes in patients with MMCA that necessitated (HC) who had received IV tPA (ϩ tPA) within 3 hours of symptom onset versus patients who did not receive IV tPA (-tPA). Methods: We retrospectively reviewed our registry from 07/03 to 02/10 and identified consecutive patients diagnosed with MMCA infarctions that underwent HC and had preoperative brain MRI performed within 24 hours of admission. The DWI volumes were calculated using a validated GUI (Graphical User Interface) tool developed in MATLAB R2010a software (by one of the author -MK). Relevant clinical data was gathered by chart review. Results: We identified 46 patients meeting our criteria (ϩ tPA ϭ 24 and -tPA ϭ 22). Demographics and risk factors are shown in the table. The mean MRI-DWI lesion volume in the ϩ tPA group was 213ml (SEϭ29) and mean MRI-DWI lesion volume in the -tPA group was 160ml (SEϭ29) with pϭ0.10. The ϩ tPA group also had 5 hemorrhagic transformations compared to 0 in the -tPA group (pϭ0.05). There was no statistical difference in clinical outcome defined by discharge mRS. The rates of patients that underwent intra-arterial therapy (ϩ tPA ϭ 29% vs -tPAϭ 27%, pϭ1.00) and recanalization (partial or complete) rates (ϩ tPA ϭ 41% vs -tPA ϭ20%, pϭ0.19) did not differ between the two groups. Conclusion: IV-tPA therapy may be associated with increased MRI-DWI infarct volumes in patients who develop MMCA and undergo HC. One possible reason may be that tPA increases the blood brain barrier permeability leading to increased edema formation and infarct expansion. Other potentially confounding variables such as baseline NIHSS, time to MRI and intra-arterial therapy were balanced between the two groups. However, our study is limited by its retrospective nature with a small sample number (nϭ46).

W P5 64 Slice Computed Tomography Perfusion (CTP) Imaging Predicts Outcome in Acute Ischemic Stroke Patients Who Receive IV Thrombolysis with rt-PA

Nobl Barazangi, Shirley Chen, Ann Bedenk, Jack Rose, David Grosvenor, David Tong; CPMC, San Francisco, CA Background: Some MRI based studies have suggested a role of perfusion imaging in identifying candidates for thrombolysis. However, CTP is far more accessible and new techniques allow whole-brain coverage using conventional 64 slice CT, potentially improving utility. We sought to determine the feasibility and utility of routine 64 slice CTP in rt-PA treated stroke patients, and to correlate the CTP results with follow-up MRI. Methods: Retrospective study of all consecutively treated IV rt-PA patients between 7/2006-6/2010 who received pretreatment 64 slice CTP. Pretreatment NCCT, CTA and CTP were compared with post treatment MRI including DWI and FLAIR. Outcome was determined by pretreatment and discharge NIHSS. Safety was evaluated by symptomatic ICH (sICH) rate and mortality. Results: 117 patients had a pre-treatment CTP. 50% demonstrated perfusion mismatch (pre-and postaverage NIHSS 10.3, 6.9); 42% no perfusion defect (NIHSS 7.5, 3.1); 8% matched defect (NIHSS 8.8, 9.9). 92 patients had a follow-up MRI; 37 (42%) patients had equal infarct size on CTP and MRI, 31 patients (34%) had smaller infarct size on MRI as compared to the area at Objective: Computerized Tomography Perfusion (CTP) is used to assess physiological brain tissue parameters in patients with acute ischemic stroke (AIS). Its utility for patients presenting within the 3 hrs time window is unknown and questionable given possible delay of thrombolytic administration and additional exposure to radiation. We addressed whether parameters on CTP for AIS patients treated with IV t-PA within 3 hrs of onset are predictive of good or bad outcome. Methods: We retrospectively identified patients from our stroke registry (7/07 to 2/10) who presented with AIS and underwent CTP and then received tPA within 3 hrs of symptom onset. Patients that underwent intra-arterial therapy were excluded. A neuroradiologist blinded to outcome performed CTP measurements on a commercially available Siemens Neuro PCT workstation. Total perfusion deficit was defined as the area of infarct territory with a relative time to peak greater than 4s compared to the contralateral side (TTP). Nonviable tissue (NVT) was defined as the area of infarct territory with absolute cerebral blood volume (CBV) less than 2ml/100g. Penumbra was defined as the area of TTP minus the area of CBV. Good clinical outcome (GCO) was defined as mRS 0-2, and poor clinical outcome (PCO) was defined as mRS 5-6 at hospital discharge. Clinical perfusion mismatch (CPM) was defined as admit NIHSS Ն 8 and NVT Յ25cm 2 . Results: We identified 44 patients with a mean age of 68 years , median NIHSS on admission of 13 and median discharge mRS of 4. NVT was statistically different in those with poor outcome (Table 1) and a strong predictor of poor outcome when NVT was greater than 50 cm 2 (ORϭ6 , 95%CI: 1.05-34, pϭ0.044). TTP was statistically different in patients that achieved and did not achieve GCO (Table 1;ORϭ0.97,pϭ0.037). There was no statistical correlation between penumbra area, percentage penumbra, and CPM with GCO in univariate analysis. Younger age and lower admission NIHSS were associated with GCO and higher NIHSS was associated with PCO. Using multivariate logistic regression controlling for age and admission NIHSS, none of the CTP parameters were statistically associated with outcome measures. Conclusion: CTP parameters derived from commercially available software and published thresholds do not provide useful value beyond the NIHSS for predicting good outcome for AIS patients treated with IV tPA within 3 hours of onset but may be useful in predicting poor outcome if the area of non-viable tissue is greater than 50 cm 2 . Our study is limited by its retrospective nature with a small sample and lack of standardization of CTP thresholds.

W P8 Is There An Association Between The First Moment Method MTT And Tmax Based Mismatch Estimates In Acute Ischemic Stroke?

Dattesh D Shanbhag, Rakesh Mullick, Sumit Nath, GE Global Rsch, Bangalore, India; Marie Luby, Lawrence L Latour, Steven Warach; NINDS, NIH, Bethesda, MD Background: In MRI of acute ischemic stroke (AIS), salvageable tissue is approximated as the diffusion (DWI) -perfusion (PWI) mismatch. The choice of PWI maps, such as first moment method MTT or deconvoluted Tmax, and segmentation approach can impact the estimated mismatch volume and thus the selection of patients for therapy. In this study, we compared the PWI lesion and mismatch volumes determined using MTT maps segmented manually, to those obtained using Tmax and an automated segmentation algorithm. The resulting binary classification of "presenceϭtrue" based on minimal cutoff volume was compared across methods. Methods: Twenty-seven IV-tPA treated patients having pre-and 2hr post-treatment MRI were included. A trained imaging scientist manually segmented lesions on DWI and MTT maps to form the gold standard (GS). An in-house tool, PANDA, was used to compute Tmax by AIF deconvolution and perform automated lesion segmentation and mismatch classification using: i) an automated algorithm (Auto-Tmax) based on lesion location knowledge, contralateral differences, and morphology and ii) basic thresholding Tmax maps at Ն4s, Ն6s, Ն8s and Ն10s, with no additional processing. For both approaches, CSF pixels were removed using the ADC maps generated from DWI images, to remove bias from elevated Tmax in ventricles. Patients were classified as "mismatchϭtrue" if mismatch volume exceeded a range of cutoff values of 25cc, 50cc, 75cc, or 100cc. Agreement with GS was compared across technique and cutoff value. Results: For both pre and post tPA treatment MRI, Auto-Tmax and basic thresholding Tmax Ն6s were found to provide similar volume estimates to those of GS. With Auto-Tmax, the mismatch agreement with GS was stable (ϳ83%), independent of cutoff value. For Tmax Ն6s, the best agreement was 81% at Ͼ25 cc and dropped off with increasing cutoff value. The error rates for mismatch agreement were higher with basic threshold segmentation compared to Auto-Tmax and worsened as the mismatch volume cutoff value was increased.

Conclusion:

We conclude that both Auto-Tmax and basic Tmax threshold of Ն6s provides a similar estimate of perfusion volume and mismatch detection to that of manual segmentation. However, Auto-Tmax resulted in a more robust classification independent of cutoff value, providing an automated method for mismatch detection that could eventually be used to select patients prior to therapy.

Background: Tissue plasminogen activator (t-PA) remains the only proven treatment for ischemic stroke but concurrent use of warfarin at the time of stroke poses a potential risk for symptomatic intracerebral hemorrhage (sICH). Few studies have addressed this risk. We studied all patients admitted to our service who were on warfarin at the time of their acute ischemic stroke and were treated with IV t-PA in order to define incidence and risk factors of sICH. Methods: Retrospective chart review of patients was conducted from our stroke registry from January 2003 to June 2010. We evaluated consecutive patients who received IV tPA within 0-3 hours while on warfarin. Patients who were off their warfarin were excluded. We collected demographics, National Institute of Health Stroke Scale (NIHSS) on admission, rates of symptomatic intracerebral hemorrhage (sICH), and discharge modified Rankin Scale (mRS) outcomes. Results: Among 61 patients, 13 patients (21%) had sICH. Comparing those patients who bled with those who did not have sICH, there were no significant INR level nor warfarin dose differences. There was no statistical difference in all BP parameters measured between the two groups. Four patients (31%) died in the hemorrhage group compared with 2 patients (5%) in the non-hemorrhage group. There was a statistical difference in mRS at discharge and mortality between the two groups. However, when corrected for baseline NIHSS and age, the ORs for either outcome were not statistically different (1.1, 95% CI: 0.2-7.3, pϭ0.9) and (0.2, 95%CI: 0.02-1.6, pϭ0.13), respectively. Although the percentage of hemorrhages decreased with lower INR levels, neither higher INR level nor warfarin dose predicted hemorrhage as the ORs were 0.2 (95%CI: 0.02-2.2, P-valueϭ0.6) and 0.9 (95%CI: 0.6-1.4, P-value: 0.2). No patients with INR less than 0.9 had hemorrhagic changes. Conclusion: Our data suggest that patients on warfarin have a higher risk of symptomatic hemorrhages after receiving IV-tPA compared to the overall known risk of 6% for sICH in patients who receive IV t-PA within 3 hrs. There was no correlation between INR level or the warfarin dose and the risk of sICH. There were worse outcomes and higher rates of death in the patients who had hemorrhages. However, worse outcomes in patients who bled could have been more related to the severity of the stroke at initial presentation. Further studies are therefore needed to evaluate the safety of IV-t-PA with concurrent warfarin use with respect to admission NIHSS score. Our study is limited by the small sample size.

Background and Purpose: Intravenous tissue plasminogen activator (IV t-PA) can improve clinical outcome in acute stroke patients. Early arterial recanalization has been recognized to salvage a vulnerable brain tissue in the diffusion-perfusion mismatch area, and thus believes as a predictor of good outcome. Indeed, and we are certain of the hyper-intense lesion on diffusion-weighted imaging (DWI) as brain tissue with irreversible damage. However, thrombolytic reversal or reduction of initial ischemic lesion on DWI has been reported in several recent studies. Thus, our aim is to investigate the frequency of stroke cases with DWI lesion decline after thrombolysis and to examine the association between clinical backgrounds including early recanalization and DWI lesion volume reduction. Methods: From January 2005 to June 2010, we prospectively enrolled patients with occluded artery of anterior circulation on initial magnetic resonance angiography (MRA) who were admitted to our stroke center within 3 hours of onset. All patients were treated with IV t-PA, and received magnetic resonance imaging study including DWI and MRA on admission and immediately (within 30 minutes) after IV t-PA. DWI lesion volume was measured manually using image analysis software (ImageJ 1.38, developed by the National Institutes of Health). Reduction of DWI lesion was defined more than 30% decrease of lesion volume from initial to follow-up MRI. Recanalization status was evaluated on follow-up MRA according to Thrombolysis In Myocardial Infarction (TIMI) flow grade. Complete recanalization was defined as TIMI grade 2 or 3. All patients were classified into two groups based on reduction of DWI lesion; reduction group (RD group) and no reduction group (non-RD group). We compared the clinical characteristics including complete recanalization between two groups. Results: Ninety-five patients (median age; 77, median initial National Institute of Health Stroke Scale; 16, 50 men) were included in this study. Reduction of DWI lesion was observed in 7 (7%) patients (RD group). In the RD group, initial glucose level (113mg/dl [interquatile range; 100-125mg/dl] vs. 139mg/dl [116-175mg/dl, pϭ0.009) was lower and complete recanalization was more frequently (86% vs. 10%, PϽ0.001) observed than non-RD group. There was no difference of other factors including age, sex, and interval from onset to initial MRI or IV t-PA between the groups. Conclusion: The frequency of early decrease of DWI lesion after IV t-PA therapy was 7%. Reduction of infarct volume should be associated with early complete recanalization after thrombolysis.

Author Disclosures: Y. Sakamoto: None. Y. Iguchi: None. M. Watanabe: None. T. Iwanaga: None. N. Matsumoto: None. K. Shibazaki: None. K. Kimura: None.

W P14 Presence of MRI 'Mismatch' and Infarct Growth in Different Time Windows After Stroke Onset: a cross-sectional study

Aneesh B Singhal, Ruijun Ji, Murat M Arsava, Mingwang Zhu, Hakan Ay, Ona Wu, Priya Garg, Vicky Tiglias, W. Taylor Kimberly, Lee H Schwamm, A. Gregory Sorensen; Massachusetts General Hosp, Boston, MA Background: The 'mismatch' between MTT and DWI lesion volumes (MTT-DWI) is believed to reflect salvageable tissue and is often used as a selection criterion in clinical trials. In patients serially imaged, 'mismatch' is known to reduce over time. The frequency of mismatch and the evolution of 'mismatch' tissue into infarction in different time windows, is not known. Methods:

The study cohort included 274 ischemic stroke patients who received DWI/PWI Ͻ12 hr after onset (i.e. last known well) and follow-up MRI on day 5 or later. Of these, nϭ230 had analyzable DWI and MTT lesion volumes; these patients were grouped by time from onset to [3][4][5][6][6][7][8][9][9][10][11][12]. Chi-square or ANOVA was used as appropriate. Results: Mean age, gender, vascular risk factors, mean admission BP, temperature, glucose, NIHSS score, and stroke etiology were not significantly different among time windows (ANOVA, pϾ0.05 for all). The groups showed no significant difference in mean admission DWI and MTT lesion volumes (Table ). The frequency of any mismatch and Ͼ30% mismatch was Ͼ75% in all groups, with substantial volumes of mismatch (Ͼ70 cc) in each group. There were no differences in mismatch frequency or mismatch volumes. The frequency of 90-day mRS 0-2 was highest (85%) in the 6-9 hr group and lowest (54%) in the 9-12 hr group. Infarct evolution as measured by absolute lesion growth, or penumbral salvage [(admission MTT-chronic FLAIR)/(admission MTT-admission DWI)], was similar among groups; percent lesion growth was significantly different, with decreasing growth in later time windows (pϭ0.04). Similar results were obtained when the analysis was restricted to patients with (a) onset witnessed or Ͻ1 hr since last seen well, (b) hemispheric lesions, (c) no thrombolysis. Conclusion: In patients undergoing DWI/PWI upto 12 hr after onset, we found a high frequency of patients with persistent mismatch. This may be explained by selection bias (e.g. clinical perfusion-MRI more likely to be performed if CTA shows arterial occlusion), and reflect limitations of MR techniques for estimating 'mismatch' during the earlier time frames of this study (e.g. no delay compensation). However, the similarities in ischemic lesion evolution in different time windows is notable. Multivariate analysis with potential confounders (e.g. thrombolysis, MRI technique) is needed to fully understand lesion growth in these cohorts. These data may impact clinical trials using MTT-DWI mismatch for patient selection, and call for an interrogation of techniques used for estimating mismatch.

Introduction:

In patients with suspected acute ischemic stroke, a head CT is most often the only neuroimaging necessary prior to treatment with IV t-PA. Occasionally, the history or clinical examination may raise the suspicion of an alternative diagnosis (stroke mimic). Hypothesis: We assessed the hypothesis that in some stroke code cases the use of rapid MRI might alter management by diagnosing stroke mimics in patients otherwise eligible for acute therapies such as IV t-PA. Methods: We retrospectively reviewed the charts of the 377 "stroke code" patients in 2008 at our comprehensive stroke center. Of those patients, 30 had "rapid MRI" (FLAIR, DWI, ADC, and GRE) to assist in the diagnosis. We further reviewed those 30 charts to determine if management was altered after the MRI. Results: Among 377 stroke codes in 2008, 30 (8%), underwent rapid MRI. The mean age and gender were similar between the patients who had emergent MRIs and those who did not (mean age 61.1 and 61.0 years, respectively; gender was 67% women and 56% men, respectively, p ϭ NS for both). All patients except one presented within the time period for acute treatment: 21 within 3 hrs, 5 within 4.5 hrs and 3 within 8 hrs. The most common presenting symptoms were: weakness (63%), aphasia (40%), dysarthria (17%), and altered mental status (13%). At the time of the stroke code, 17 of the patients were inpatients (11 of which were peri-procedural), and 13 were ED cases. Of the 30 patients, 19 had acute strokes on MRI and 11 were diagnosed as stroke mimics. Eight of the 19 acute stroke patients were treated (2 received IV t-PA, 6 underwent IA therapy). We refrained from acutely treating 22 of the 30 patients (11 mimics and 11 stroke patients in whom a contraindication was detected). Of the 11 mimics detected by MRI, 6 would have been eligible for t-PA within the 3 hr window and 1 patient was within 4.5 hrs. The reason for not using t-PA in 2 of the 11 stroke patients was directly due to MRI findings on the gradient echo sequence that were not detected on the non-contrast CT; 1 had multiple microhemorrhages and one had GREϩ metastases. Almost one-third of the patients (9 of 30) would have been potential candidates for IV t-PA but were excluded based on the MRI findings. Conclusions: In our series of "stroke code" patients who had rapid MRI out of concern for a possible stroke mimic, the majority did not receive thrombolytic therapy based on the MRI results. The test was useful in definitively selecting appropriate patients for acute intervention as well as in avoiding the unnecessary and potentially harmful treatment of patients with stroke Background and Purposes: Anti-coagulation therapy using warfarin is commonly done in patients with atrial fibrillation to prevent cardioembolic events. Intensity of anti-coagulation is recommended to be prothrombin time-international normalized ratio (PT-INR) 1.6-2.6 for elderly subjects with non-vulvular atrial fibrillation according to Japanese Guidelines, which is lower than that in Western countries (PT-INR 2-3), because the frequency of intracranial hemorrhage is significantly higher in Japanese. Here we examined the characteristics of patients developing ischemic stroke during oral anti-coagulant therapy. Methods: We designed Fukuoka Stroke Registry (FSR), a multi-centered prospective study for acute stroke, in Japan, which started registration at June 2007 (UMIN000000800). As of May 2010, 2,834 acute brain infarction (BI) have been enrolled. BI was classified into 4 subtypes according to the TOAST classification: atherothrombotic (AT), lacunar (Lac), cardioembolic (CE), and unclassified (Unc) infarction. Results: Two hundred and forty four BI patients (8.6%, mean 75 years) were taking warfarin at onset. CE (65.6%) was predominant, followed by AT (11.1%), Lac (10.2%), and Unc (13.1%), and 46.3 % patients had the history of BI. There were no differences in age and gender among the subtypes. Median PT-INR values were 1.28 (interquartile range (IQR) 1.09-1.59) in CE, in AT, in Unc. The PT-INR values in CE were significantly lower than those in other subtypes (pϽ 0.001). The median PT-INR was 1.50 (IQR 1.24-1.86) in recurrent BI patients, which was significantly higher than that in first-ever )) (pϽ0.01). Seventeen percent of CE had fair PT-INR values (1.6-2.0), and 7.6% had good PT-INR (Ն 2.0). In the good PT-INR group, the frequency of valvular heart disease (VHD) was significantly higher than that in other groups (pϽ 0.01). Systolic blood pressure on admission was significantly lower with the increase in the intensity of PT Stroke patients who presented to hospitals within 24 h of symptom onset were registered. The primary outcome was independent activity of daily living (ADL) corresponding to a modified Rankin Scale (mRS) score Յ1 at discharge. The outcome was compared between two periods in total and in three subgroups classified by the onset-to-arrival time (Յ2.5h, 2.5 -4.0h, 4.0 -24.0h). Results: 2663 patients (1596 men, 71.0Ϯ12.6 years old, 1783 ischemic stroke and 880 intracerebral hemorrhage [ICH]) from Period A and 3144 patients (1885 men, 72.0Ϯ12.4 years old, 2066 ischemic stroke and 1078 ICH) from Period B were enrolled into this study. The onset-to-arrival time of Period B was shorter than that of Period A (median 150 minutes vs. 180 minutes, PϽ0.001) and more patients arrived within 2.5 hours from the onset in Period B compared to Period A (50.5% vs. 39.9%, PϽ0.001). In overall patients, the initial NIHSS score and the mRS score at discharge were not different between 2 periods. In ischemic stroke patients of the earliest-arrival subgroups (Յ2.5h), the initial NIHSS score tended to be low vs. 9 [3-17], Pϭ0.063) and the mRS score at discharge was lower (median 2 [IQR 1-4] vs 3 [1-5], Pϭ0.024) in Period B than Period A. Independent ADL was 1.34 times (95% CI 1.01 -1.78, Pϭ0.044) more common in patients in Period B than Period A after adjustment for age, sex and the initial NIHSS score. In ischemic stroke patients of the other two subgroups and in ICH patients of any subgroups, no significant differences were observed in the initial NIHSS score and the mRS score at discharge between 2 periods. Conclusion: The onset-to-arrival time in stroke patients became shorter and the outcome of the ischemic stroke patients arriving within 2.5h of stroke onset improved in recent years in Japan. The 3-hour rt-PA rule may cause the limited improvement of outcomes only in the earliest-arrival subgroup of ischemic stroke patients.

Author Disclosures: F. Miyashita: None. T. Hagihara: None. H. Yokoyama: None. A. Okayama: None. C. Yokota: None. K. Minematsu: None. K. Toyoda: None.

W P21 Extending Therapeutic Window for Intravenous Thrombolysis to 4.5 hours Remains Safe and Effective in Asian Acute Ischemic Stroke Patients

Aftab Ahmad, Prakash R Paliwal, Shen Liang, Leonard L Yeo, Kay W Ng, Pei K Loh, Hock L Teoh, N Venketasubramanian, Benjamin K Ong, Vincent F Chong, Eric Tan, Mahendran Maliapen, Arvind K Sinha, Bernard P Chan, Vijay K Sharma; National Univ Hosp, Singapore, Singapore Background: Intravenously administered tissue plasminogen activator (IV-TPA) remains the only approved therapy for Asian acute ischemic stroke (AIS) patients within 3 hours of symptom-onset. The meta-analysis IV-TPA trials demonstrated that the therapeutic benefit could exist up to 270 minutes and this was confirmed recently in a randomized clinical trial (ECASS-III) as well as multicenter registry (SITS-MOST). Treatment rates for AIS remain low in Asian populations. Patients' late arrival and higher anticipated bleeding-risk are the major contributing factors. We aimed at evaluating the safety and efficacy of IV-TPA therapy in an extended therapeutic window among Asian patients in Singapore. Methods-Data from consecutive AIS patients treated with IV-TPA, in a standardized protocol, from Jan 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. All patients received standard-dose of IV-TPA (0.9mg/Kg body weight) Efficacy of IV-TPA was assessed with functional outcomes at 3-months (modified Rankin Scale (mRS) score, dichotomized as good outcome (mRS 0-1) and poor outcome (mRS 2-6). Safety of IV-TPA was assessed by rates of symptomatic intracranial hemorrhage (SICH). SPSS 16.0 was used for statistical analysis. Results: Of the total of 2271 AIS patients admitted to our center, 224 (9.9%) eligible cases were treated with IV-TPA during the study period. Baseline data included mean age 63Ϯ12 years; 131 (59%) males; mean onset-to-treatment time 157Ϯ38 minutes and median NIHSS 16 points. 190 ( ) patients were treated within 3 hours while 34 received IV-TPA in an extended therapeutic window. Hypertension was the commonest vascular risk factor in 170 (76%) while 73 (33%) patients suffered from atrial fibrillation (AF). Strokes involved anterior circulation in 189 (84%) as compared to 35 (16%) posterior circulation. Overall, 115 (51%) patients achieved good functional outcome (mRS 0-1 at 3 months). Female gender, AF, pre-TPA NIHSS score and HMCAS on follow-up CT scan were associated with poor functional outcome. Although, higher proportion of patients treated after 180 minutes had poor outcomes at 3 months (62% versus 46% in 0-180 minutes group), the difference was not statistically significant (OR 1.87;pϭ0.097). SICH occurred in a total of 9 (4.01%) patients. Although, higher proportion of patients treated in an extended window developed SICH (9.7% versus 3.3%), the difference was not significant (pϭ0.141). Conclusion: Intravenous thrombolysis in an extended therapeutic window is effective as well as safe in the treatment of acute ischemic stroke in our multiethnic Asian population in Singapore.

W P22 Long Term Follow-up Of Incidentally Found Intracranial Aneurysms In Patients With Acute Ischemic Stroke

Yoon-Sang Oh, Young-Min Shon, Beum Saeng Kim, Hae Kwan Park, A-hyun Cho; Catholic University, Seoul, Korea, Republic of Background: Sometimes intracranial aneurysms are incidentally found in patients with acute ischemic stroke, in whom long term anti-thrombotic therapy is essential for secondary stroke prevention. In these cases, natural history of intracranial aneurysms has not been well identified. Regarding this, we performed two years follow-up of clinical outcome and CT angiographic findings in acute ischemic stroke patients with incidentally found intracranial aneurysms. Methods: We consecutively included acute ischemic stroke patients within 7 days of onset. Demographics, risk factors, clinical outcome (modified Rankin Scale), aneurysm type, and maximum diameter of aneurysm were identified. Clinical characteristics of patients with aneurysm were compared to those without aneurysms. CT angiography was performed on admission and at least two years after the initial exam in order to evaluate the change of the aneurysms. The development of aneurysmal rupture and hemorrhagic complications directly due to intracranial aneurysm were checked. Results: Incidental intracranial aneurysms were found in 19 (6.1%) of the total 314 patients. The female sex and old age were associated with the presence of incidental intracranial aneurysms (patients with aneurysms vs. those without; 13/19,68.4% vs. 109/295,36.9%,pϭ0.006;72.2Ϯ13.1,65.5Ϯ13.4 years,mean,SD,pϭ0.043). The most common site of aneurysm was at the distal internal carotid artery (nϭ11), followed by the middle cerebral artery (nϭ6) and basilar artery (nϭ2). The diameters of the aneurysms ranged from 1.84 to 8.06 mm. All the patients except one who had cancer have been taking anti-thrombotics. No aneurysm rupture or subarachnoid hemorrhage has occurred during the two years of follow-up. In 7/19 patients, follow-up CT angiography could be performed. Six of them showed no change regarding aneurysm shape and size. In one, the aneurysm disappeared. Eight patients could not perform follow-up CT angiography because of death (5), refusal (1) and disability (2). The remaining four patients are supposed to perform follow-up CT angiography and the results are pending. Conclusions: There was no aneurysm rupture or subarachnoid hemorrhage during the two years of follow-up period even with the continuing long term anti-thrombotic treatment. On the follow-up CT angiography, the diameter and shape of aneurysms mostly did not change.

Introduction:

The endovascular treatment with detachable coils has become an established technique for the treatment of intracranial aneurysms. Despite all the advances in the techniques of embolization, it is known that 14.7% to 33.6% of aneurysms embolized are subjected to any type of recurrence. It is important the imaging surveillance of coiled aneurysms, to identify any recurrence of aneurysm reperfusion, to determine the need for retreatment. Traditionally, this control has consisted of repeated digital subtraction angiography (DSA). However, this method has a risk of neurological complications. Thus, many authors have advocated the use of noninvasive imaging methods, considering the magnetic resonance imaging (MRI) as a viable option in terms of safety and image quality. Material and Methods: This prospective study compared the magnetic resonance angiography (MRA), including time-of-flight (TOF) and contrast-enhanced (CE-MRA) techniques in relation to DSA in the evaluation of embolized cerebral aneurysms. We studied 30 patients, harboring a total of 43 embolized cerebral aneurysms. Thirty-four (79.1%) aneurysms were located in the internal carotid artery, 6 (13.9%) in vertebral-basilar system, two (4.7%) in middle cerebral artery and 1 (2.3%) in the anterior communicating artery. The size of the aneurysms was small in 15 cases (34.9%), medium in 12 (27.9%), large in 12 (27.9%) and giant in 4 (9.3%). The endovascular technique applied was: simple technique in 13 cases (30.2%), balloon remodeling in 21 cases (48.8%) and stent remodeling in 9 cases (20.9%). Two interventional neuroradiologists, with experience in both methods, interpreted the results independently. The status of aneurysm occlusion was assessed according to the Raymond scale. Results: There was full interobserver agreement in all evaluated methods. Intertechnical agreement, assessed by k statistics, was excellent, between 98). Disagreement occurred in only one case (2.3%), corresponding to a small aneurysm treated by balloon remodeling, located in the internal carotid artery, which was classified as Class I (Raymond scale) by TOF-MRA and class II by DSA and CE-MRA. Agreement between CE-MRA and DSA was perfect (k ϭ 1). In three aneurysms, treated by stent remodeling, parent-artery intraluminal stenosis was seen within the stent, which was not confirmed by DSA. Conclusions: Our study shows that DSA and both MRI techniques (TOF-MRA and CE-MRA) have excellent intertechnical and interobserver reproducibility for the assessment of aneurysm occlusion after embolization. However, in cases treated with stent remodeling, DSA may still be necessary to confirm an eventual parent artery stenosis identified by MRI.

W P24 Proteomic Analysis of Aneurysm Healing Mechanism after Coil Embolization: Comparison of Dense Packing with Loose Packing

Ramanathan Kadirvel, Yong-Hong Ding, Daying Dai, Debra A Lewis, David F Kallmes; Mayo Clinic College of Medicin, Rochester, MN Background and Purpose: In clinical practice, durability of occlusion following coil embolization is superior in densely packed as compared to loosely packed aneurysms. We probed, in a rabbit model, the biological mechanisms associated with densely packed, well healed, durably occluded aneurysms compared to loosely packed, poorly healed, imperfectly occluded aneurysms following embolization. Methods: Elastase-induced, saccular aneurysms were created in rabbits and were allowed to mature, after which aneurysms were either densely packed (Group 1, packing densityϾ30%) or loosely packed (Group 2, packing densityϽ20%) with platinum coils. After 2 weeks (nϭ6 for both groups) and 4 weeks (nϭ6 for both groups) of implantation, aneurysm samples harboring coils were harvested. Soluble proteins were extracted from the necks and domes of aneurysms and proteins were identified using mass The pathogenesis of cerebral aneurysms is multifactorial and obscure. As epidemiological data show a high incidence of cerebral aneursyms in postmenopausal women, we established a new cerebral aneurysm model in female rats subjected to estrogen deficiency, increased hemodynamic stress, and hypertension and studied the relationship between their aneurysms and endothelial tight junctions, oxidative stress and inflammation in the vascular wall. To examine the pathogenetic contribution of mineralocorticoid receptor (MR) we used the MR antagonist eplerenone and the MR agonist deoxycorticosterone acetate in saline (DOCA-salt). Compared to sham-operated rats, at the aneurysm site of experimental rats we observed a reduction in the tight-junction proteins occludin and ZO-1 and an increase in nicotinamide adenine dinucleotide phosphate-oxidase subunits, inflammatory-related molecules, and angiotensin II expression. In rats treated with eplerenone, opposite findings were made and the incidence of cerebral aneurysms was decreased; angiotesin II level in their vascular wall was decreased via the down-regulation of angiotnesin-converting enzyme (ACE) without affecting the blood pressure and their salt-intake was reduced. In contrast, the formation of cerebral aneurysms was increased in rats implanted with DOCA pellets as were their ACE levels in the vascular wall and their salt intake. Our results provide new insights into the formation of cerebral aneurysms in rats subjected to hypertension and hypoestrogenicity that the activation of MR combined with an increase in salt-intake is associated with the activation of the vascular renin-angiotensin system, thereby at least partly contributing to the formation of cerebral aneurysms independent of hypertension, and that eplerenone may represent an agent for the prevention and/or treatment of cerebral aneurysms.

Author Disclosures: K.T. Kitazato: None. Y. Tada: None. T. Tamura: None. K. Yagi: None. K. Shimada: None. T. Kinouchi: None. N. Matsushita: None. Y. Kanematsu: None. J. Satomi: None. T. Kageji: None. S. Nagahiro: None.

W P27 Quantitative Analysis Of Coil Embolization Of Brain Aneurysms: Multi-center Study Using Auto Measurement Software

Hidenori Oishi; Juntendo Univ Sch of Medicine, Tokyo, Japan Background and Purpose: Endovascular coil embolization has recognized as acceptable treatment for intracranial aneurysms. Despite of importance of precise morphological evaluation to anticipate stability of treated aneurysms and advancement of modern three dimensional imaging technology, no scientific evaluation method of morphological outcome has been established. Therefore, novel objective morphological evaluation system is mandatory. The aim of this study is to identify whether initial volume embolization rate (VER)correspond to long term stability of treated aneurysm measured by newly developed auto measurement software. Methods: This is a multi-center, prospective analysis for coil embolization using volume measurement software (NeuroVision, KGT, Tokyo, Japan). Between April 2009 and May 2010, 295 patients with unruptured aneurysms were enrolled in the study. Sixteen centers were participated. The aneurysms were treated predominantly using Matrix2 coils in combination with or without GDC bare platinum coil. Follow-up catheter 3D angiography at 12 months was performed. Pre, post embolization, and follow up 3D angiography DICOM data was recorded and evaluated at independent core lab using new measurement software. Special attention was paid for pre, post, and follow up embolization aneurysm volume and VER. Clinical outcomes were assessed using a modified Rankin scale. Factors related for aneurysm recurrence was statistically analyzed. Results: Two hundred fifty seven aneurysms were anterior circulation and 38 were posterior circulation. All aneurysm volume and VER were calculated automatically with NeuroVision. There was no morbidity and mortality after the treatment. Average volume (size) and VER were 165.2mm3 (6.1x5.8mm) and 25.5% respectively. Posterior circulation was better VER (29.8%) than anterior circulation (25.5%). Aneurysm location was not related to VER in the anterior circulation (ICA 25.3%; MCA 25.1%; ACA 25.2%) aneurysms also demonstrated equally good VER outcomes. The average VER of participated centers were range between 20 and 28%. Conclusions: This report is first multi center study using quantitative analysis after coil embolization of brain aneurysms without human bias. Using this software more scientific evaluation of coil embolization can be conducted. Mid term anatomical result will be reported.

Author Disclosures: H. Oishi: None.

W P28 Should We Treat Unruptured Intracranial Aneurysms? -Evaluation Of Clinical Outcome Between Conservative Management And Therapeutic Intervention

TOSHIHIRO ISHIBASHI, Yuichi Murayama, Satoshi Ikeuchi, The Jikei Univ, Tokyo, Japan; Takayuki Saguchi, Japanese Red Cross Med Cntr, Tokyo, Japan; Ebara Masaki, Hideki Arakawa, Koreaki Irie, Kato Masataka, Hiroyuki Takao, Norikata Kobayashi, Ikki Kajiwara, Hisashi Onoue, Takeki Ogawa, Toshiaki Abe; The Jikei Univ, Tokyo, Japan Background and Aim: management of unruptured aneurysm is controversial. We analyzed relationship between aneurysm size and clinical benefit of treatment in comparison to outcome of conservatively observed UIAs. Methods: Between March 2003 and April 2009, 876 patients with 1111 UIAs were referred to our institution. After informed consent, 326 patients with 370 aneurysm agreed either endovascular coiling or surgical clipping. 9 patients received both coiling and MC due to multiple aneurysms. The remaining 603 patients with 741 aneurysms were conservatively observed with 3D CTA evaluation. Results: In the treatment group, overall morbidity and mortality were 3.1% and 0.3%. In the observation group, 26 aneurysms ruptured (1.8%/year: 1405.7 person-year) during follow up. Of these, 10 patients were dead (38.5%) and 6 patients (23.8%) were disabled status (mRS 3-5). Treatment benefit was confirmed when aneurysm size was more than 6mm if morbidity was defined as modified Rankin scale 2(Pϭ0.0021). However, treatment benefit were only confirmed the aneurysms more than 8mm if morbidity was defined as mRS 1(Pϭ0.031). Conclusion: The patients with UIA need accurate and multi factorial information about therapeutic benefit before treatment.

Background and Purpose: Endovascular treatment of complex, wide-necked bifurcation cerebral aneurysms is challenging. A variety of techniques have been used to treat these aneurysms. Intra/ Extra-aneurysmal stent placement, the so-called "Waffle Cone" technique, has the advantage of using a single stent to prevent coil herniation and does not involve stent delivery to the efferent vessel. However, the published data on the use of waffle cone technique is limited. We present here our initial and followup experience with stent-assisted coiling of cerebral aneurysm to evaluate the durability of the waffle cone technique. Subjects and Methods: We retrospectively identified 10 consecutive patients who underwent stent-assisted coiling of an aneurysm using the waffle cone techniques from July 2009 to June 2010. Demographic, clinical, angiographic and procedural data were reviewed. Six month clinical and angiographic follow up were available in 6 cases. Results: Conventional stent assisted coiling was not performed in all cases because efferent artery anatomy precluded stent placement across the aneurysm neck. The Neuroform3® stent was used in 9 cases and the Enterprise stent was used in one. Complete or near complete occlusion of the aneurysm initially was achieved in all cases. No intraoperative aneurysm rupture occurred. No coil herniation was observed and the afferent and efferent vessels were patent at procedure completion. One patient developed thrombosis of an efferent artery 24 hours after treatment without permanent deficit. In one patient with Grade V subarachnoid hemorrhage, care was withdrawn after successful coiling of the aneurysm. Clinical and radiographic followup in the remaining 9 patients (mean 5.4 month) revealed no subsequent rebleeding or ischemic complications. Follow-up angiography performed six months after treatment demonstrated the aneurysm remained obliterated in 5 of 6 patients. The aneurysm recurred in one patient who had been treated using an Enterprise stent and received repeat coiling. All stents were patent without in-stent stenosis or thrombosis. The afferent and efferent vessels remained widely patent in all cases. Conclusion: Our preliminary experience suggests that stent-assisted coiling of aneurysm using the waffle cone technique is safe and effective. This stent placement strategy is a useful alternative for complex, wide-necked aneurysms when the anatomic configuration of efferent artery is unfavorable for conventional stent placement.

Author Disclosures: W. Liu: None. D.K. Kung: None. K.B. Mahaney: None. J. Rossen: None. D. Hasan: None.

W P31 Increased Packing Volumes of Endovacular-Treated Intracranial Aneurysms Correlates with Reduced Aneurysm Recurrence

Varun Bajaj, Katerina Dukleska, Jacqueline Kraus, Charles J Prestigiacomo, Chirag D Gandhi; UMDNJ-New Jersery Med Sch, Newark, NJ Background: Endovascular repair of intracranial aneurysms is a safe and effective treatment modality. However, concerns of endovascular treatment include durability of therapy and aneurysm recurrence. We hypothesized that increased packing volumes during coil embolization was associated with decreased aneurysm recurrence, and conversely, that lower packing volumes were associated with increased aneurysmal recurrence. Therefore, we correlated aneurysm packing volumes with aneurysm recurrence. Methods: The study population included 61 sequential aneurysm patients, (47 female, 14 male), admitted to a University Hospital from 2007-2010. Fifteen patients were excluded for incomplete data or pseudo-aneurysm. The remaining 46 patients, with 55 aneurysms, were placed into two groups. Group A, nϭ38, included those with a single coiling procedure and without recanalization (29 female, 9 male, median age 55 years, 40 procedures). Group B, nϭ8, included those with one or more coiling procedures and demonstration of aneurysm recanalization (6 female, 2 male, median age 51.5yrs, 18 procedures). Aneurysms were categorized according to presentation, location, shape, number of coils used, coil types, and immediate angiographic outcome. Using AngioCalc, an online program for cerebral aneurysm analysis, we determined aneurysm volumes, coil volumes, and total packing volume percentages for each aneurysm. Results: Aneurysm locations were: AcoA (nϭ18), ICA (nϭ1 right, nϭ3 left), Cavernous ICA, (nϭ1 right, nϭ2 left), Paraclinoid ICA (nϭ1 right), Ophthalmic ICA (nϭ3 right, nϭ3 left), Hypophyseal ICA (nϭ2 left), Supraclinoid ICA (nϭ2 right, nϭ2 left), PCoA (nϭ4 right, nϭ3 left), MCA (nϭ3 right), A1 ACA (nϭ1 right, nϭ1 left), Pericallosal ACA (nϭ1 left), P1 PCA (nϭ1 right), PICA (nϭ1 left), and Basilar Apex (nϭ2). AngioCalc analyses of these 55 aneurysms revealed similar average volumes between groups: Group A: 442.59mm3, (median 65.45mm3,849.05mm3),Group B: 428.65 mm3,(median 72.99 mm3,053.63 mm3). The average packing volume percentages were markedly different: Group A, 25.66%, Group B, 12.03%. Conclusion: Our data strongly indicates that for endovascular-treated intracranial aneurysms of similar volumes, packing volumes of ϳ25% are associated with reduced aneurysm recurrence rates compared to aneurysms with packing volumes of ϳ12%. This analysis is limited by AngioCalc's assumption of perfect shapes such as a sphere, cylinder, or ellipsoid. Future studies using CT angiography data will account for shape imperfections and may improve calculations of packing volume percentages.

Author Disclosures: V. Bajaj: None. K. Dukleska: None. J. Kraus: None. C.J. Prestigiacomo: None. C.D. Gandhi: None.

W P32 Derived Biomorphometric Criteria Can Predict Aneurysm Rupture Status: A CT Angiographic Analysis

Maulik Shah, Chirag D Gandhi, Charles J Prestigiacomo; UMDNJ-New Jersery Med Sch, Newark, NJ Introduction: Subarachnoid hemorrhages (SAH) occurring after rupture of an intracranial aneurysm has an overall morbidity and mortality rate of 50 to 60%. SAH affects young and healthy patients, creating economic and social effects. Determining variables to formulate an equation which can predict which aneurysms are more likely to rupture would allow better stratification of patients that may benefit from invasive procedures such as coil embolization and microsurgery. Prior studies have assessed several biomorphometric parameters which have variably correlated with rupture status. The objective of this study is to assess whether the ostium area and surface area of an aneurysm can potentially be used to predict the rupture status for intracranial aneurysms. Methods: Patients presenting to the University Hospital of UMDNJ with the diagnosis of ruptured or unruptured aneurysms were evaluated. CT angiography was performed according to standard protocol, which included 150 cc injection of contrast at 4cc per second. Images were obtained at 0.625mm thickness on the GE 16 slice scanner and processed with the GE Advantix Workstation. Biomorphometric variables such as aneurysm height, width and neck diameter were obtained in planes parallel and perpendicular to the flow of blood from 3-D reconstructions. The ostium area was calculated using the measured neck diameters in the formula to calculate area of an ellipse. Surface area calculations were obtained by isolating the region of interest, the aneurysm, in all axial sections, and importing these images into Adobe Photoshop for surface area calculations. Results were analyzed using Levene's Test for Equality of Variances. Results: Twenty consecutive patients with ruptured aneurysms and 20 patients with unruptured aneurysms were analyzed. Statistically significant differences were identified in ostium area, surface area to ostium area and volume to ostium area for the aneurysm. Neck diameter, parallel to flow, correlated positively with rupture status. Binary logistic regression of these individual parameters was then applied which demonstrated that the most significant predictors of rupture status were neck diameter in a plane parallel to flow and volume-to-ostium area with a predictive accuracy of 87.8 %. Conclusions: Although surface area assessment was statistically significant by the independent samples test, multi-variable regression suggests that volume-to-ostium area and neck size are more predictive of rupture status. Though no biophysical data is available with this mathematical study, these data strongly suggest that future studies are warranted in a larger population of patients.

Author Disclosures: M. Shah: None. C.D. Gandhi: None. C.J. Prestigiacomo: None.

W P33 Change of Hemodynamic Situations of Elastase Induced Aneurysms with Arterio-venous Fistula Creation in Rabbits

Yonghong Ding, Ramanathan Kadirval, Daying Dai, Debra A Lewis, David F Kallmes; Mayo Clinic, Rochester, MN Purpose: To explore if creation of arteriovenous fistula (AVF) can change the hemodynamic situations of elastase-induced aneurysms in rabbits. Materials and Methods: Right common carotid artery (RCCA) elastase-induced aneurysms were created in 10 rabbits (Group 1) 4 weeks after RCCA-REJV (right external jugular vein) fistula creation (Figure 1A), which involved end to side anastomosis of REJV to RCCA. Ten other aneurysms (Group 2) were created without AVF creation. Ultrasound examination and digital subtractive angiography (DSA) were performed 3 weeks after aneurysm creation. Doppler waveform features in the parent artery of aneurysms were evaluated. Occurrences of different features between two groups were compared using Fisher's Exact Test. Results: Persistent (through both systolic and diastolic) antegrade flow waveform in parent artery was shown in 7 (70%) of the aneurysms in group1 (Figure 1B), which was not shown in any aneurysms in Group 2. Systolic antegrade flow and diastolic reversal of flow were shown in all the aneurysms (100%) in Group 2 (Figure 1 C), which were shown in only 3 (30%) of the aneurysm in Group 1. Occurrence of persistent antegrade flow in Group 1 was significantly higher than that in Group 2 (p Ͻ .01). Conclusion: Persistent antegrade flow can be induced in the elastase-induced aneurysms with arteriovenous fistula creation, which is more close to the cerebral blood flow patterns in patients.

Background: Aneurysms of the middle cerebral artery (MCA) are frequently wide necked and incorporate important branches. These anatomical features have proved challenging for endovascular management, and have led many clinicians to favor neurosurgical clipping of aneurysms at this location. Stent-assisted embolization may increase the likelihood of successful endovascular treatment. Methods: We retrospectively reviewed all cases of stent-assisted coil embolization of unruptured MCA aneurysms performed at our institution and assessed procedural success, procedural complications, durability of treatment, and complications during follow-up. Results: Treatment was attempted in 23 patients and successful in 22/23 (96%). The median age was 61 years (mean 62). Aneurysm size was: Ͻ5 mm in 5/22 (23%); 5-9 mm in 14/22 (64%); and Ն10 in 3/22 (14%). There were 4 periprocedural complications, none of which resulted in either transient or permanent neurological morbidity or mortality. Angiographic follow-up was available in 18/22 (82%) and clinical follow-up in 19/22 (86%). On angiographic follow-up at a median of 1 year (mean 1.2 years), aneurysm occlusion was complete in 12/18 (67%). A neck remnant was present in 3/18 (17%). Persistent aneurysmal filling was present in 3/18 (17%) requiring retreatment in 1/18 (6%). In-stent stenosis of 50%, which was asymptomatic, occurred in 1/18 (6%). After a median clinical follow-up period of 1 year (median 1.2 years), no subarachnoid hemorrhage occurred. There were two ischemic events (one TIA and one lacunar stroke) both likely unrelated to the procedure. Conclusions: In this small series, the technical success rate was 96%, there were no transient or permanent neurological complications, and complete aneurysmal occlusion was achieved in two thirds of treated aneurysms on follow-up angiography. These results suggest that in selected patients, stent-assisted coil embolization of middle cerebral artery aneurysms can be performed with a high degree of technical success, a low procedural risk, and acceptable durability.

Author Disclosures: J.D. Fields: None. L. Brambrink: None. K.C. Liu: None. E. Helseth: None. G.N. Nesbit: None. S.L. Barnwell: None.

W P36 Stent-Assisted Coil Embolization of Brain Aneurysms Produces Safe and Durable Occlusion

Ajay K Wakhloo, Christine F Silva, Gabriela Spilberg, Univ of Massachusetts, Worcester, MA; Italo Linfante, Baptist Cardiac & Vascular Institute, Miami, FL; Eileen A Duhamel, Matthew J Gounis; Univ of Massachusetts, Worcester, MA Introduction: Stent-assisted coiling techniques have improved the endovascular treatment of wide-necked (neck Ն 4 mm or dome-to-neck ratio Ͻ 2) and fusiform intracranial aneurysms. We prospectively evaluated the safety and efficacy of a new generation neurovascular closed-cell stent (CCS) approved for the treatment of wide-necked intracranial aneurysms. We hypothesize that CCS-assisted coiling improves the durability of endovascular aneurysm treatment. Methods: Between June 2007 and March 2010, 107 wide-necked and fusiform/dissecting intracranial aneurysms were treated endovascularly in 99 patients using CCS. Fifteen (14%) aneurysms were located in the posterior circulation. The aneurysms were defined as wide-neck complex (81%), dissecting or fusiform (12%) or blister (7%). Ten (9%) were treated acutely following subarachnoid hemorrhage. Aneurysms that recanalized following primary coiling (21%) or clipping (2%) were also included. The mean aneurysm diameter and neck size was 5.9mm (2-25mm) and 4.8mm (2-15mm), respectively. Follow-up angiography was obtained for 67 patients (68%) at a mean of 10 months (5-21months). Immediate post-procedure control and follow-up angiograms were evaluated using the Raymond 1 scale by a core lab. Clinical evaluations were performed using a modified Rankin scale (mRS). Results: Immediate control angiography demonstrated total aneurysm occlusion in 39 (36%), neck filling was seen in 37 (34%), and dome filling was seen in 34 (32%) aneurysms. All serious adverse events occurring within 30 days were: 2 TIA, 4 minor strokes, 1 major stroke and 2 access site complications requiring surgical intervention. Permanent morbidity, defined as any increase from baseline mRS, and mortality during the follow-up period were 9% and 3%, respectively. Of the 2 patients that expired, one was due to rebleeding from a dissecting posterior-inferior cerebellar artery aneurysm 6 days after embolization, and the other due to an embolic stroke. In the small cohort of ruptured aneurysms, only 1 of 9 surviving patients has persistent neurological impairment. Procedure-related permanent morbidity and mortality during the follow-up period was 3% and 1.5%, respectively. Angiography at follow-up demonstrated total occlusion in 54 (77%), 14 neck remnants (20%), and 2 residual aneurysms (3%). The recanalization and retreatment rates in this series were 8.6% and 5.7%, respectively. Conclusion: Complex, wide-neck aneurysms may be successfully obliterated with CCS-assisted embolization. Recanalization rates for CCSassisted embolization compare favorably to historical controls (20% reported in the literature 2 and 13% from our own data 3 ). Caution should be exercised and further evaluation is required in using CCS-assisted coil embolization for acutely ruptured aneurysms. 1. Stroke 2001;32:199832: 2. Stroke 2009;;40:e523

W P37 The Incidence And Mechanisms Of Postoperative Cerebral Infarction After Clipping Surgery For Non-ruptured Intracranial Aneurysms -A Multivariate Analysis Study

Michiyuki Miyamoto, Satoshi Kuroda, Naoki Nakayama, Dept of Neurosurgery, Hokkaido Univ Graduate Sch of Medicine, Sapporo, Japan; Masaaki Hokari, Hiroshi Yasuda, Hisatoshi Saito, Dept of Neurosurgery, Sapporo Asabu Neurosurgical Hosp, Sapporo, Japan; Kiyohiro Houkin; Dept of Neurosurgery, Hokkaido Univ Graduate Sch of Medicine, Sapporo, Japan Background: There are few studies that denote the incidence and underlying mechanisms of cerebral infarction after clipping surgery for non-ruptured intracranial aneurysms. In this study, herefore, we evaluate the incidence and risk factors of silent or symptomatic cerebral infarction after clipping surgery. Subjects and Methods: This study included 198 patients who underwent clipping surgery for non-ruptured aneurysms in the anterior circulation for these three years. There were 52 males and 146 females. Their age ranged from 26 to 78 years. Newly developed cerebral infarction was identified using diffusion-weighted MRI or CT scan within two weeks after surgery. Multivariate analysis was employed to independent risk factors for postoperative cerebral infarction. Results: New cerebral infarction was found in 31 (15.7%) of 198 patients after surgery. Of these, 14 patients (7.1%) were asymptomatic. However, 15 (7.6%) and 2 (1.0%) patients developed transient and permanent neurological deficits, respectively. Cerebral infarction was located in the perforating artery territory in 24 patients and in the cortical branch territory in 7. The former was very small. The incidence of postoperative cerebral infarction was 47.1% in patients with anterior choroidal artery aneurysm, being significantly higher than those with other aneurysms. Multivariate analysis revealed that the location of aneurysm is an independent predictor for postoperative cerebral infarction (Pϭ0.0203). In addition, intracranial atherosclerosis on MR angiography may predict it, although its statistical significance was in a borderline (Pϭ0.0606). Conclusions: Cerebral infarction after clipping surgery for non-ruptured anterior circulation aneurysms is not rare. The location of aneurysm may be the most powerful predictor for it. Widespread application of intraoperaitve ICG videoangiography and motor evoked potential (MEP) may reduce its incidence in very near future.

Author Disclosures: M. Miyamoto: None. S. Kuroda: None. N. Nakayama: None. M. Hokari: None. H. Yasuda: None. H. Saito: None. K. Houkin: None.

W P38 Blister-Like Aneurysms: Single Center Experience and Literature Review

Ana Marcos Gonzalez, Ana P Narata, Hasan Yilmaz, Jilla Mazraeh, Philippe Bijlenga, Karl Schaller, Karl-Olof Lovblad, Vitor Mendes Pereira; Hopitaux Universitaires de Gene `ve, Geneva, Switzerland Introduction: Blood Blister-like aneurisms (BBAs) are still a controversial entity affecting intracranial vessels, a special type of aneurisms arising from the nonbranching sites of the supraclynoid Internal Carotid Artery (ICA), suspected to originate from a dissection and characterized by an extremely fragile wall, making its treatment very difficult. Hypothesis: Our aim is to describe the BBAs cases in our center, as well as review the literature about this subject, trying to establish a clearer and more practical concept of BBA, with a special focus on the treatment. Methods: We analyzed the 10 cases admitted to the University Hospital of Geneva, from 2004 to 2010, 9 of them presenting with Subarachnoid Hemorrhage in whom a BBA was considered to be the responsible of the bleeding, based on CT scan, arteriography or surgical findings. We assessed medical history, type of treatment (Neurointerventional ϩ/-Neurosurgery), complications and clinical outcome. Results: The mean age was 48y; 6 women and 4 men; 6 aneurysms on the right supraclynoid ICA, and 4 on the left one; 7 patients immediately complicated with hydrocephalus, 6 of them were treated with an external ventricular drainage, and 1 was treated with lumbar punctures; the treatment of the BBA consisted of stenting and coiling in 5 patients, only stenting in 1 patient, coiling and clipping in 1 patient, only clipping in 1 patient, and conservative treatment in 2 patients; among the complications of these treatment, we found 2 thromboembolic events after stenting in the acute phase; final outcome was good (modified Rankin scale at 3 months less or equal to 2) in 7 patients. Conclusions: BBAs should be considered as a segmental vascular disease, more than an aneurysm itself. Regarding our data, stenting and coiling seems to be a safe and effective treatment for BBAs, assuring a good long term follow-up, in spite of possible acute thrombotic complications.

W P39 Translational Stroke Research: Characterization of a New Embolism-Induced Intracerebral Hemorrhage Model to Assess Neuroprotection and Hemorrhage Reduction

Paul A Lapchak; Cedars-Sinai Med Cntr Dept. Neurology, Los Angeles, CA There has been some progress in the translational development of hemorrhage therapy that successfully reduces the escalating morbidity and mortality rate associated with brain bleeding. However, using an animal model representative of the human condition will be required for additional success. The rabbit large clot embolic stroke model (RLCEM) has previously been used to test drugs and devices for safety, because the model is particularly sensitive to embolism-induced intracerebral hemorrhage (ICH). This study refined the original embolization procedure using an automated, pump-assisted injection method to introduce large blood clots or macroscopic emboli into the middle cerebral artery (MCA) via an indwelling carotid artery catheter. ICH was classified into the following categories: (1) PH-parenchymal hemorrhage, (2) HIN-hemorrhagic infarction, (3) HPT-punctate hemorrhage and (4) SAH-subarachnoid hemorrhage. The study shows that rapid injection of blood clots (360ml/hr, 3 ml volume) produced a model where there is a high ICH incidence rate (79%) and a high stroke success rate (63%), compared to a low stroke success rate (19%) with no ICH when clots were injected at a slow rate (120ml/hr, 3 ml volume). Some of the animals had more than 1 type of ICH present in the brain. For quantitative purposes, we treated each individual hemorrhage observed as a separate entity. ICHs occurred throughout the brain and included the following structures: caudate putamen; thalamus; hippocampus; frontal, parietal, and occipital cortex; hypothalamus; suprachiasmatic area; cerebellum; pons; and midbrain. There were no apparent differences among the groups in the distribution of types or locations of hemorrhages. The rapid injection method, which produces a high ICH rate is particularly useful to study neuroprotective agents to attenuate embolism-induced ICH. In addition, we show that manual injection of blood clots, which produces a lower baseline ICH rate (41%) with a similar stroke success rate (65%), may allow investigators to study pharmacological agents to either up or down-regulate ICH incidence. Lastly, we show that in the rabbit embolic stroke model, hemorrhages are adjacent to areas of 2,3,5-triphenyltetrazolium (TTC)-negative tissue, normally associated with infarcted or ischemic tissue, suggesting that therapeutics that are neuroprotective may also be useful to limit the evolution of ischemic damage associated with a ICH, if not attenuate ICH itself. In conclusion, we have shown that we can modify ICH incidence in the RLCEM without directly affecting survival rate, by adjusting the rate at which an emboli is introduced into the brain vasculature, in particular the middle cerebral artery. In addition, we have provided evidence for distinct area of ischemic tissue (TTC-negative) adjacent to hemorrhages, areas that may be targets for neuroprotective agents to limit the extent of ICH damage.

Author Disclosures: P.A. Lapchak: None.

W P40 Translational Stroke Research I: Synthesis and In Vitro Optimization of a New Curcumin Hybrid Neurotrophic-Neuroprotective Compound

Paul A Lapchak, Cedars-Sinai Med Cntr Dept. Neurology, Los Angeles, CA; Pamela Maher, Dave Schubert; SALK Institute Neurobiology, La Jolla, CA

The plant polyphenolic curcumin is a multifunctional molecule with upwards of 10 separate activities. However, there are some properties of curcumin that could be improved, including bioavailability and its lack of neurotrophic activity and the ability to inhibit excitotoxicity. To circumvent some of these problems, we synthesized a library of hybrid molecules between cyclohexyl bisphenol A (CBA), a molecule with neurotrophic activity and curcumin. A simple pyrazole derivative, called CNB-001, that eliminates the labile dicarbonyl group of curcumin and stabilizes the molecule, was identified and further characterized as follows. For the in vitro studies, we used (1) an in vitro ischemia assay with HT22 cells treated with 20 M IAA iodoacetic acid (IAA), an irreversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase (G3PDH), (2) an oxidative stress (Oxytosis) assay with HT22 cells treated with the excitotoxic amino acid glutamate (5 mM), which induces cell death mediated by the depletion of intracellular glutathione and (3) a trophic factor withdrawal (TFW) assay with primary cortical neurons from 18-day-old rat embryos cultured at a low cell density in DMEM/F12 with N2 supplement. For the IAA and oxytosis assays, cell survival was measured using an MTT colorimetric assay. For the TFW assay, viability was determined after 2 days using a fluorescent live-dead assay (and the data presented as the percentage of input cells surviving. First, there was a dose-dependent effect of CNB-001 on the survival of HT22 cells using both the in vitro ischemia (EC 50 0.3 M) and oxidative stress (EC 50 0.7 M) assays. CNB-001 promoted the survival of freshly plated, low-density cultured rat cortical neurons in a dose-dependent manner with an EC 50 value of 0.7 M. Thus, CNB-001 has neurotrophic activity in addition to neuroprotective activity. Second, we used the IAA assay to elucidate mechanisms underlying the neuroprotective effects of CNB-001. After IAA treatment, there were decreases in both ERK and Akt phosphorylation that were prevented by treatment with CNB-001. We also found that KN62, a CaMKII inhibitor, reduce CNB-001 neuroprotection and blocked the effects of CNB-001 on both ERK and Akt phosphorylation suggesting that CaMKII regulates the ERK and Akt pathways and is a more proximal target of CNB-001. Since CNB-001 rescues HT-22 cells from ischemia, and both ERK and Akt activation and CaMKII expression are downstream pathways activated by neurotrophic molecules such as BDNF, we determined if BDNF could rescue HT-22 cells expressing the BDNF receptor, TrkA using the in vitro ischemia model. We found that BDNF rescues cells transfected with wild type TrkA (TK4), but not cells containing a mutated nonfunctional receptor (TK1) and this rescue is blocked by KN62. The rescue is not, however, as complete as with CNB-001, suggesting that CNB-001 also functions by other mechanisms that remain to be defined.

Author Disclosures: P.A. Lapchak: None. P. Maher: None. D. Schubert: None.

W P41 Translational Stroke Research II: In Vitro Cellular Toxicity Screening of an Optimized Curcumin Hybrid Neurotrophic-Neuroprotective Compound

Paul A Lapchak; Cedars-Sinai Med Cntr Dept. Neurology, Los Angeles, CA

In the present study, we used a comprehensive cellular toxicity (CeeTox) analysis panel to determine the toxicity profile for CNB-001 [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1phenyl-1H-pyrazoyl-3-yl)vinyl)-2-methoxy-phenol)], which is a hybrid molecule created by combining cyclohexyl bisphenol A, a molecule with neurotrophic activity and curcumin, a spice with neuroprotective activity. CNB-001 is a lead development compound, since we have recently shown that CNB-001 has significant preclinical efficacy in vitro in 3 separate assays. The industry standard CeeTox analysis assay allows investigators to determine the predicted C tox value (an estimated concentration where toxicity would be expected to occur in a rat 14-day in-vivo repeat dose study) for a drug. For this, rat hepatoma derived H4IIE cells were used as the test system. The CeeTox assay measures of cellular toxicity including mitochondrial function, apoptosis, oxidative stress, protein binding, solubility and microsomal metabolic stability. CNB-001 was soluble up to 100 M using the CeeTox assay system. The drug was not acutely toxic and no effect on membrane integrity or subcellular markers of acute toxicity, with the exception of a decrease in cell proliferation observed with a concentration that produced a half maximal response (TC 50 ) value of 88 M, suggesting a cytostatic effect. CNB-001 did not affect measures of oxidative stress or apoptosis (i.e. Caspase 3 activity). We found that CNB-001 resulted in an inhibition of Ethoxyresorufin-0-deethylase activity, indicating that the drug may affect cytochrome P4501A activity and that CNB-001 was metabolically unstable using a rat microsome preparation assay system. CNB-001 was metabolized via phase 1 metabolism, since only 42% of parent remained after a 30 minute incubation with rat microsomes. The only 'toxicity' of CNB-001 was a cytostatic effect effect was only observed at 183-643 fold the EC 50 for neuroprotective/neurotrophic activity using HT22 cell and primary cortical neuron in vitro assays. Based upon a proprietary CeeTox algorithm, the C tox Ranking (M) for CNB-001 was estimated to be 42 M which places it in the CeeTox Inc. category of moderate to low probability of in vivo effects. However, it is important to realize that the C tox ranking, a treatment regimen that may not be necessary for stroke patients. Taken together, the results indicate that there is a significant therapeutic safety window for CNB-001 and that it should be further developed as a novel neuroprotective agent to treat stroke.

Author Disclosures: P.A. Lapchak: None.

W P42 Translational Stroke Research III: In Vivo Activity and Mechanism of Action of a New Curcumin Hybrid Neurotrophic-Neuroprotective Compound

Paul A Lapchak, Cedars-Sinai Med Cntr Dept. Neurology, Los Angeles, CA; Dave Schubert, Pamela Maher; SALK Inst Neurobiology, La Jolla, CA

We have shown that the curcumin analog CNB-001 has neuroprotective and neurotrophic properties in vitro and has a large safety margin using comparison studies done using HT22 and H4IIE cells. For in vivo characterization of CNB-001, we used the rabbit small clot embolic stroke model (RSCEM), which is a useful translational stroke model and predictor of clinical efficacy (Lapchak, TSR 1(2), [96][97][98][99][100][101][102][103][104][105][106][107]2010). We tested the hypothesis that CNB-001 may be neuroprotective following cerebral ischemia using clinical rating scores as the endpoint. CNB-001 or DMSO were administered SC following the injection of small blood clots into the brain vasculature. Behavior was measured 24 hours following embolization in order to calculate the effective stroke dose (P50) that produces neurological deficits in 50% of the rabbits. A treatment is considered beneficial if it significantly increases the P50 compared to control. The initial study used a 5 min post-embolization treatment time, to ensure that the dose and route of administration of the drug can produce a neuroprotective or positive signal. There was a significant improvement in behavior and the P 50 value for the CNB-001-treated group was increased by 157% compared with control. At this dose there was no overt behavioral response or toxicity within the time frame of the study. In addition, when tested 1 hour post-embolization, CNB-001 significantly (PϽ0.05) reduced stroke-induced behavioral deficits and increased the P 50 value by 233% compared with the control group. To obtain insight into how CNB-001 functions in vivo, we examined a variety of signaling pathways previously implicated in stroke. Brain extracts were taken at 6 h post-embolism from control, stroked and CNB-001 embolized rabbits. Since the Ras-ERK cascade has been implicated in nerve cell survival in ischemia, we initially examined this pathway. A significant decrease in ERK phosphorylation in the stroked animals relative to control animals was observed, and this decrease was largely prevented in the presence of CNB-001 treatment. PI3K-Akt signaling, which is also implicated in neuronal cell survival following stroke was decreased in the stroked animals but was maintained in the presence of CNB-001. CNB-001 also has BDNF-like activity, and BDNF causes the activation of the ERK and Akt pathways. Since the expression of CaMKII is also increased by BDNF, we assayed CaMKII expression in CNB-001-treated animals. In this study, we found that CNB-001 increased CaMKII expression. Finally, the ER-associated chaperone ORP150 has been linked to the PI3K/Akt and BDNF signaling pathways. ORP150 expression was decreased in the stroked rabbit brains and this decrease was again prevented by CNB-001. In conclusion, CNB-001 promotes behavioral improvement following embolic strokes in rabbits, an effect that may be associated with the normalization of Ras-ERK and PI3K-Akt signaling pathways.

Author Disclosures: P.A. Lapchak: None. D. Schubert: None. P. Maher: None.

Background and Purpose: 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury following transient focal cerebral ischemia. ALOX15(-/-) mice in which the gene encoding 12/15-lipoxygenase has been knocked out, are protected against transient focal cerebral ischemia. But it is unknown whether similar protection occurs in global cerebral ischemia. In this study, we hypothesized that increased vascular and neuronal 12/15-LOX exacerbates brain damage by causing oxidative stress and the death of neurons in a transient global ischemia model, implying that neurovascular injury should be reduced in ALOX15(-/-) mice after transient global cerebral ischemia. Methods: Wild type and ALOX15(-/-) mice were subjected to 20 minutes of transient occlusion of the bilateral common carotid arteries. To test the first part of our hypothesis, immunostaining was used to study 12/15-LOX expression at different times following global ischemia. In addition, a mouse model of 8 minutes of cardiac arrest followed by resuscitation, was employed to confirm the validity of the staining data. 12/15-LOX activity was determined by measurement of 12-HETE (12hydroxyeicosatetraenoic acid), a 12/15-LOX metabolite in brain homogenates. Co-localization of 12/15-LOX with markers for oxidative stress and apoptosis was employed to study cell death processes. Results: 12/15-LOX was increased in a time-dependent manner in the vasculature and in neurons of cortex, striatum, and hippocampus following transient global ischemia. This was accompanied by a time-dependent increase in 12-HETE. Furthermore, 12/15-LOX co-localized with an oxidative stress marker, MDA2 (for proteins modified by oxidized lipids) and with FluoroJade-B (FJ-B), a marker for dying cells. 12/15-LOX expressing cells in the cortex also expressed high levels of apoptosis-inducing factor (AIF), a well-known mediator of non-caspase-related apoptosis. Very similar staining was found in the cardiac arrest model. Subjected to global ischemia, ALOX15(-/-) mice showed reduced FJ-B staining, compared to wild type mice. Likewise, ALOX15(-/-) mice showed reduced MDA2 and cleaved caspase-3 staining. Using a neurological severity score, ALOX15(-/-) mice were found to have less neurological impairment as compared to wild type. Conclusion: Taken together these data suggest that 12/15-LOX may contribute to neurovascular injury after global cerebral ischemia, in which activation of oxidative stress markers and both caspase-dependent and caspaseindependent apoptotic pathways are involved.

Author Disclosures: K. Yigitkanli: None. A. Pekcec: None. S. Minamishima: None. F. Ichinose: None. E.H. Lo: None. K. van Leyen: None.

W P44 Interferon Gamma Contributes to Increased Neural Injury Following Ischemic Stroke

Hilary Seifert, Christopher Leonardo, Aaron Hall, Lisa Collier, Alison Willing, Keith Pennypacker; University of South Florida, Tampa, FL Background: Immune cells enter the brain following ischemic stroke and initiate an inflammatory response resulting in delayed neural injury. Human umbilical cord blood (HUCB) cells administered 48 hrs following middle cerebral artery occlusion (MCAO) reduced inflammation resulting in decreased infarct volume. These cells migrate to the injured brain and spleen. The spleen contributes to increased neural injury following ischemia, as removal of the spleen prior to MCAO reduces infarct volume at 96 hrs. However, because labeled splenocytes were not found in the brain following MCAO the spleen likely contributes to increased injury through a humoral response. Hypothesis: Increases in splenic production of the proinflammatory cytokine interferon-gamma (IFN␥), which activates both microglia and peripheral macrophages in response to injury, is a mechanism by which the spleen contributes to increased neural injury following an ischemic stroke. Methods: Experiments were designed to establish a time course for IFNa ˜expression at 3, 24, 48, 72, and 96 hrs post-MCAO (nϭ3). Immunohistochemistry and ELISA were performed on brain and spleen samples, respectively, from rats which received MCAO and HUCB cell or vehicle treatment 48 hrs post-MCAO (nՆ3). To further examine whether IFNa ˜is a mechanism by which the spleen increases neural injury, experiments were performed in which rats received either splenectomy or sham-splenectomy surgeries 2 weeks prior to MCAO, and were then administered recombinant IFNa ˜or vehicle 48 and 72 hrs post-MCAO (nՆ4). Results: IFNa ˜was present in the brain and the spleen following MCAO and peaked 72 hrs post-MCAO (pϽ0.01). Systemic administration of HUCB cells reduced IFNa ˜levels in both the brain (pϽ0.01) and the spleen (pϽ0.01) at 72 hrs post-MCAO. Mostly T cells, but also B cells and NK cells, were producing IFNa ˜in the injured hemisphere. Splenectomized rats that received IFNa ˜had infarct volumes significantly greater than vehicle treated rats (pϽ0.001), demonstrating recombinant IFNa ˜abolishes the protective effect of splenectomy. Conclusion: These results indicate splenic derived IFNa ˜production is a mechanism by which the spleen increases neural injury following ischemic stroke.

Author Disclosures: H. Seifert: None. C. Leonardo: None. A. Hall: None. L. Collier: None. A. Willing: None. K. Pennypacker: None.

W P45 Neuroprotective Effect Of Agmatine After Focal Cerebral Ischemia In Diabetic Rats

Hui-Song Cui, Chin Hee Mun, Jong-Eun Lee, Won Taek Lee, Bon-Nyeo Koo, Kyung Ah Park; Yonsei Univ, College of Medicine, Seoul, Korea, Republic of Diabetes mellitus is a metabolic disorder associated with structural and functional alteration of various organ systems including the central nervous system. The aim of this present study was to investigate the progresses and pathogenesis of cerebral ischemia in diabetes. It is also aimed to determine the neuroprotective effect of agmatine administration during cerebral ischemic insult in diabetes. We established the streptozocine (STZ) induced diabetic model and middle cerebral artery occlusion (MCAO30) model in rat to demonstrate the difference in pathogenesis between simple cerebral ischemia and cerebral ischemia combined with diabetes. Diabetes was induced with streptozotocin (60 mg/kg, i.p.) in male adult rats. Diabetes rats underwent 30min suture-occlusion of the middle cerebral artery (MCAO30), and immediately injected with agmatine (100mg/kg, i.p.) following by reperfusion for 1 and 3 days. Moreover, different neurobehavioral tests were performed. The brain infarct volume was assessed with 2% solution of triphenyltetrazolium chloride (TTC). Western blot and immunohistochemical analysis were performed to determine neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) expression in ischemic brain tissues. Caspase-3 activity and TUNEL staining were used to evaluate cellular apoptosis. Agmatine treatment decreased blood glucose in STZ-induced rats mildly. Agmatine treatment significantly improved neurobehavioral activity, and reduced infarct size and edema volume in diabetic MCAO30 rats at 1, 3 day reperfusion period compared with no treatment group (pϽ0.01). Western blotting and immunohistochemistry results depicted that agmatine treatment significantly decreased nNOS and iNOS expression in diabetic MCAO30 rats at 1,3 day reperfusion period (pϽ0.01). Moreover, Immunohistochemisty and TUNEL staining results showed that agmatine treatment significantly decreased number of caspase-3-positive and TUNEL-positive cells in diabetic MCAO30 rats at 1 and 3 day reperfusion period, respectively (pϽ0.01). In conclusion, these results suggest that agmatine may protect brain from focal cerebral ischemic damage in diabetic rats.

Author Disclosures: H. Cui: None. C. Mun: None. J. Lee: None. W. Lee: None. B. Koo: None. K. Park: None. Background and Objective: Akt is implicated as a pro-survival signal in cerebral ischemic injury, as endogenous Akt phosphorylation transiently increases after cerebral ischemia and reperfusion, and PI3K/Akt inhibitors attenuate the effects of some neuroprotectants. Akt consists of 3 isoforms (Akt1, 2, 3), with predominance of Akt3 in the brain. How Akt isoforms affect stroke outcome, and whether exogenous Akt can protect neurons against ischemic injury is unclear. We examined whether Akt1 and Akt3 exert differential protective effects using in vivo focal ischemia and in vitro oxygen glucose deprivation (OGD) and serum deprivation (SD) models. Methods: We cloned constitutively active Akt1 and 3 (containing a src myristoylation signal and an HA-tag), and dominant negative Akt (AktDN) into a lentiviral vector that expresses eGFP via the IRES element, enabling co-expression of the Akt isoform and eGFP. To study exogenous Akt 1, Akt 3 and AktDN, we used an SD model in HT22 hippocampal neuronal cells, an OGD model in primary neuronal cultures, and a focal ischemia model in rats. Akt1, Akt3 and AktDN were expressed in HT22 cells by lipofectamine transfection, and lentivirus-expressing Akt1, Akt3 and AktDN were used to infect primary cortical cultures or stereotaxically injected into the brain cortex to be subjected to focal ischemia. We evaluated neuronal survival using a CCK8 kit in vitro, and measured brain infarction using TTC staining in vivo. Results: Western blot analysis showed that lentiviral expression of Akt1 and 3 increased Akt phosphorylation, and microscopy examination showed corresponding GFP expression and HA staining. Both Akt1 and 3 overexpression increased cell viability and decreased ROS production in HT22 cells induced by SD (PϽ0.01). However, Akt3, but not Akt1, increased the cell viability in primary cortical cultures after OGD (PϽ0.01). AktDN had no effect on cell survival in both HT22 cells and primary cortical cultures. Although gene transfer of both Akt1 and 3 reduced infarction size after stroke compared with the control group injected with lentiviral GFP vectors (nϭ6/group, PϽ0.01), Akt3 overexpression resulted in a smaller infarction than that of Akt1 (nϭ6, PϽ0.05), whereas AktDN overexpression had no effect. Conclusion: Both in vitro and in vivo studies showed that lentiviral-mediated overexpression of active Akt3 confers stronger protection than that of Akt1, suggesting that Akt isoforms have differential effects on neuronal survival after stroke. Key Words: cerebral ischemia, Akt1, Akt3, stroke Author Disclosures: M. Li: None. R. Xie: None. M. Cheng: None. R. Giffard: None. R. Roth: None. R. Sapolsky: None. H. Zhao: None.

W P46 Akt Isoforms Differentially Protect Against Stroke-induced Neuronal Injury in Vitro and in Vivo

W P47 Activation Of Phosphorylation Of The Signal Transducer And Activator Of Transcription-3 By Peroxisome Proliferator-activated Receptor Gamma Agonist Contributes To Neuroprotection In The Peri-infarct Region After Ischemia

Tomoya Kinouchi, keiko Kitazato, Kenji Shimada, Nobuhisa Matsushita, Shinji Nagahiro; Institute of Health Biosciences, The Univ of Tokushima Graduate Sch, 3-18-15 Kuramoto-cho,, Tokushima, Japan A previous study reported that the peroxisome proliferator-activated receptor gamma (PPAR␥) agonist pioglitazone (PGZ) reduced cerebral ischemic damage by inhibiting phosphorylation of the signal transducer and activator of transcription-3 (p-STAT3). However, another study suggested that estradiol was neuroprotective after cerebral ischemia via an increase in p-STAT3 mediated by estrogen receptor ␣ (ER␣). Thus, the role of p-STAT3 after cerebral ischemia remains controversial. To verify the role of p-STAT3 and PPAR␥ in neuroprotection, we did or did not subject 10-week-old female Wistar rats to bilateral oophorectomy (OVX ϩ , OVX -). After 4 weeks we administered 1.0 or 2.5 mg/kg PGZ for 3 days and then performed 90-min middle cerebral artery occlusion-reperfusion (MCAO-R). We subsequently compared OVX ϩ and OVX -rats. Cortical-but not basal ganglia infarcts were significantly larger in OVX ϩ than OVX -rats; they were smaller in PGZ-treated rats. There was an inverse correlation between the infarct size and the expression of PPAR␥ and p-STAT in the peri-infarct region; PGZ increased their expression independent of estrogen and ER␣. Each inhibitor of PPAR␥ and STAT3 abolished the induction of p-STAT3 and neuroprotection in PGZ-treated rats. Notably, p-STAT3 heterodimerized with PPAR␥ translocated to the nucleus to bind to specific DNA regions although PPAR␥ did not bind to DNA directly. The increase in p-STAT3 was associated with the transcriptional activation of anti-apoptotic-and survival genes and the reduction in caspase-3. Our findings suggest that the activation of p-STAT3 by PGZ is essential for penumbral neuroprotection and may be beneficial in elderly men and postmenopausal women with ischemia.

Author Disclosures: T. Kinouchi: Research Grant; Modest; Takeda Pharmaceutical Company Limited. K. Kitazato: None. K. Shimada: None. N. Matsushita: None. S. Nagahiro: None.

W P48 Potential for Intravenous Oxygen-Carriers to Improve Oxygenation of Penumbra and Prolong its Lifespan

I Mhairi Macrae, Graeme Deuchar, William Holmes, Univ of Glasgow, Glasgow, United Kingdom; Celestine G Santosh; NHS Greater Glasgow & Clyde, Glasgow, United Kingdom Background: Potentially salvageable penumbral tissue has a limited lifespan and, without intervention, becomes incorporated into irreversibly damaged ischaemic core in the first hours post-stroke. Perfluorocarbon molecules (PFCs, particle size ϳ0.2m) are very efficient, non-toxic oxygen carriers that, when combined with oxygen ventilation, could improve oxygenation of penumbra and support its survival. Using a rodent stroke model and magnetic resonance imaging (MRI) we tested the hypothesis that increasing oxygen delivery to penumbra (100% oxygen ventilation with i.v. perfluorocarbon emulsion) would maintain aerobic metabolism and slow penumbral loss, thereby extending time available for therapeutic intervention. Methods: Following permanent middle cerebral artery occlusion in rats serial scanning (Bruker 7T Biospin ) produced maps of ischaemic injury (from apparent diffusion coefficient, ADC maps) and cerebral blood flow (arterial spin labelling) to define penumbra from perfusion diffusion mismatch. Lactate data in penumbra were generated from MR spectroscopy. Intravenous perfluorocarbon (1.5mls) with 30mins 100% O 2 (nϭ6) was compared to saline with 100% O 2 (nϭ4). Results: In the control saline group (Figure ), penumbra lactate increased by 15% during 30mins hyperoxia and by a further 36% following return to air (30mins). In the PFC group, penumbral lactate decreased by 21% during hyperoxia with a 17% increase on returning to air, thereby maintaining levels below the pre-hyperoxia baseline. ADC lesion expansion during 30mins O 2 ϩ 30mins air, was 69Ϯ7mm 3 in the saline group and 37Ϯ10 mm 3 in the PFC group (meanϮSEM, PϽ0.05). Conclusions: Over the study time course, PFC with 100%O 2 inhibited the temporal increase in lactate levels and loss of penumbral tissue suggesting the potential to prolong penumbra survival and extend the time window for intervention and improved outcome.

Author Disclosures: I. Macrae: None. G. Deuchar: None. W. Holmes: None. C.G. Santosh: None.

W P49 Xenon Echogenic Liposome's Neuroprotection Dose Response During Transient Middle Cerebral Artery Occlusion

George L Britton, Jr., Davide Cattano, Hyunggun Kim, David D McPherson, Shaoling Huang; The Univ of Texas Health Science Cntr in Houston, Houston, TX

Dose Response of Xenon-Containing Liposomes on Neuroprotective Effects During

Transient Middle Cerebral Artery Occlusion Background: Neurologic impairment following ischemic injury continues to complicate the quality of life for stroke survivors. Xenon (Xe) has favorable neuroprotective properties. We have developed a novel methodology for ultrasoundcontrolled Xe delivery using Xe-containing echogenic liposomes (ELIP), and demonstrated their neuroprotective effects. This study aims to evaluate the dose response of Xe-ELIP to improve neuroprotection at 3 hours after stroke onset. Methods: Xe-ELIP were created by a previously developed freeze-under-pressure method. Male Sprague-Dawley rats (nϭ14 total) underwent right middle cerebral artery occlusion for 2 hours. Rats were evenly divided into treatment groups received 100 ı `l , 200 ı `l and 400 ı `l of Xe-ELIP through the ascending right common carotid artery 60 minutes after reperfusion. Ultrasound (0.26 MPa) was applied over the right internal carotid artery to trigger Xe release from the Xe-ELIP. Infarction size and behavioral outcomes were determined 3 days after intervention. Results: The freeze-under-pressure method encapsulated 10 ı `l of Xe in 1 mg of ELIP. Treatment groups that received 200 l or 400 l of Xe-ELIP 3 hours after stroke onset (60 minutes after reperfusion) reduced the infarction size by 68% and 83%, respectively (pϽ0.001 vs. control). There was no improvement for animals with 100 l Xe-ELIP treatment (pϭ0.14) compared to the control group. All behavioral tests mirrored neurological results. Conclusion: This study demonstrates the dosage range of Xe-ELIP to provide best neuroprotection when administered within 3 hours, most effectively at 4 mg without toxic effect. This novel strategy for targeted therapeutic gas delivery may facilitate neuroprotection after cerebral ischemia-related injury with the potential to improve stroke treatment.

W P50 Tissue Plasminogen Activator/Xenon Co-Encapsulation Provides Thrombolysis with Neuroprotection for Thrombotic Stroke Treatment

Tao Peng, Susan T Laing, Hyunggun Kim, David D McPherson, Shao-Ling Huang; Univ of Texas Health Science Cntr at Houston, Hosuton, TX Background: Xenon (Xe) is a nontoxic neuroprotective gas, however its clinical application is limited by delivery methods issues. We have previously demonstrated tissue-plasminogen activator (tPA) encapsulation into echogenic liposomes (ELIP) for targeted ultrasound highlighting and lysis of thrombus. Co-delivery of Xe and tPA to the thrombus with ultrasound-triggered release of Xe and tPA into the cerebral circulation is an attractive strategy for stroke treatment. This study evaluates co-encapsulation of Xe into tPA-ELIP, with ultrasound-controlled site-specific Xe release. Materials and Methods: Xe-tPA-ELIP composed of phospholipids and cholesterol were prepared by the pressurized-freeze method. Whole porcine clots were treated with plasma, free tPA, free tPA with Xe saturated solution, tPA-ELIP, tPA-ELIP with Xe saturated solution, and Xe-tPA-ELIP. Clots were weighed before and after 30 minutes of treatment, and percent clot mass loss was reported. Ultrasound (1 MHz, continuous wave, 2 W/cm 2 , for 10 sec) was used to trigger the release of Xe from Xe-tPA-ELIP. Xe release from Xe-tPA-ELIP was evaluated by comparing the total Xe amount encapsulated before and after ultrasound application. Results: Ten ı `l of Xe was entrapped into 1 mg of tPA-ELIP with retention of ultrasound reflectivity. Xe release of Xe-tPA-ELIP was enhanced with ultrasound activation (62Ϯ19% increase; PϽ0.05 vs. No ultrasound). Xe-tPA-ELIP (40Ϯ3%) and tPA-ELIP (36Ϯ6%) resulted in effective clot lysis (both PϽ0.001 vs. control) with an effect similar to treatment with free tPA (pϭ0.67 and pϭ0.96 vs. free tPA). Xe saturated solution inhibited free tPA activity (14Ϯ8%). This inhibitory effect by Xe was negated by encapsulation of tPA into ELIP (38Ϯ3%; pϭ0.01 vs. Xe saturated solution), suggesting a protective effect of the liposomes for tPA activity when delivered together with Xe. Conclusions: We have demonstrated coencapsulation of a neuroprotective agent, Xe, and a thrombolytic agent, tPA, into ELIP with effective clot lysis and drug release using ultrasound. Xe-tPA-ELIP has an exciting potential with targeted thrombolytic delivery and ultrasound-facilitated neuroprotective agent release into the brain for thrombotic stroke treatment.

W P51 Neuroprotection of VELCADE is associated with Downregulation of Toll-like Receptor Signaling Pathway in Aged Rats after Stroke

Li Zhang, Michael Chopp, Yuji Ueno, Xianshuang Liu, Yisheng Cui, Zheng Gang Zhang; Henry Ford Hosp, Detroit, MI Background and Purpose: Activation of toll-like receptor (TLR) signaling pathway exacerbates ischemic neuronal damage. The present study tests the hypothesis that treatment of VELCADE, a selective proteasome inhibitor, modulates the TLR signaling pathway leading to neuroprotection in aged rats after stroke. Methods: Male Wistar rats at the age of 18 months were subjected to embolic middle cerebral artery occlusion (MCAo). VELCADE at a dose of 0.2mg/kg was intravenously administered 2h after stroke onset (nϭ12). Ischemic rats receiving the same volume of saline were used as a control group (nϭ15). Neurological functional outcome and infarct volume were measured. TLR2 and TLR4, and NF-e ˆB expression were measured immunohistologically on brain tissue 6h and 24h after stroke onset. To examine the effects of VELCADE on neuronal TLRs and their downstream target gene expression, primary rat cortical neuronal cultures were challenged by oxygen and glucose deprivation (OGD) in the absence or presence different concentrations of VELCADE (0.1, 1, or10ng/ml). Results: In the normal brain, the immunoexpression of TLR 2 and TLR 4 was not detectable. Occlusion of the MCA for 6h substantially increased the density of TLR2 (137.2Ϯ27.2/mm 2 , nϭ3) and TLR4 immunoreactive vessels (130Ϯ30.9/mm 2 , nϭ3), which was co-localized to increased NF-kB positive vessels. However, 24 after MCAo, in addition to vessels, TLR2 and TLR4 immunoreactive neurons were also detected in the ischemic boundary region. Treatment with VELCADE significantly reduced density of vessels with TLR2 (44.4Ϯ4.2/mm 2 vs 73.4Ϯ4.3/mm 2 ), TLR4 (39.9Ϯ3.4/mm 2 vs 64.8 Ϯ3.9mm 2 ), and NF-e ˆB expression (16.9Ϯ2.2/mm 2 vs 29.2Ϯ3.1mm 2 ) compared with saline treated rats. Moreover, VELCADE significantly reduced infarct volume (20.9Ϯ2.0% vs 31.2Ϯ3.4%) and modified neurological severity score (7.3Ϯ0.3 vs 9.0Ϯ0.4) 7 days after stroke compared with saline treated rats. In vitro, Western blot analysis revealed that OGD for 3h robustly upregulated TLR2, TLR4, MyD88, an essential adaptor for TLR signaling, NF-e ˆB, and Caspase 3 protein levels in neurons. VELCADE at doses of 1 and 10ng/ml led to a 50-100% reduction in OGD upregulated TLR2, TLR4, MyD88, NF-e ˆB, and Caspase 3. Conclusions: The present study provides a novel mechanism by which VELCADE suppresses ischemia-activated TLR signaling pathway in cerebral endothelial and neuronal cells, leading to reduction of ischemic cell damage and improvement of neurological outcome.

Author Disclosures: L. Zhang: None. M. Chopp: None. Y. Ueno: None. X. Liu: None. Y. Cui: None. Z. Zhang: None.

W P52 VELCADE Suppresses Tissue Plasminogen Activator-induced Genes That Promote Coagulation And Vascular Permeability In Cerebral Endothelial Cells Of Aged Rats After Stroke

Tao Tang1, Xian Shuang Liu1, Li Zhang1, Charles Chen1, Haifa Kassis1, Lindsey Karp1, Dept of Neurology, Henry Ford Hosp, Detroit, MI; Michael Chopp1,2, 1Dept of Neurology, Henry Ford Hosp, Detroit, MI 48202; 2Dept of Physics, Oakland Univ, Rochester, MI 48309, Detroit, MI; Zheng Gang Zhang1; Dept of Neurology, Henry Ford Hosp, Detroit, MI Background and Purpose: Treatment of experimental stroke with a proteasome inhibitor, VELCADE, neutralizes tissue plasminogen activator (tPA) aggravated BBB disruption, amplifies the thrombolytic effects of tPA, and exerts potent neuroprotection. The present study investigated the effect of VELCADE on expression of genes mediating coagulation and vascular permeability in single cerebral endothelial cells of the aged rat after stroke. Methods: Male Wistar rats at the age of 18-20 months were treated with VELCADE (0.2 mg/kg, nϭ4) alone, tPA (5 mg/kg, nϭ4) alone, VELCADE in combination with tPA (nϭ4), or saline (nϭ5) 2h after embolic middle cerebral artery occlusion (MCAo). All rats were sacrificed 24h after MCAo. Single cerebral endothelial cells were isolated by laser-capture microdissection from brain tissue immunostained with an antibody against von Willibrand factor (vWF), a marker of endothelial cells, and expression of matrix metaloproteinase 9 (MMP-9) intracellular adhesion molecule-1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1) was assayed by real time RT-PCR. Results: Stroke significantly (P Ϯ 1.3), ICAM-1 (2.4 Ϯ 0.3), and PAI-1 (1.5 Ϯ 0.8) of single endothelial cells in the ischemic boundary regions compared with the levels in homologous areas of the contralateral hemisphere. Treatment with tPA alone further increased MMP-9 (75 Ϯ 2.2), ICAM-1 (133 Ϯ 2.1), and PAI-1 (257 Ϯ 22.7) in the ischemic boundary regions compared with levels in rats treated with saline. However, VELCADE monotherapy significantly (PϽ0.05) reduced mRNA levels of MMP-9 (7.9 Ϯ 1.2), ICAM-1 (1.4 Ϯ 0.1), and PAI-1 (1.1 Ϯ 0.2) compared with saline treated rats. Moreover, in rats treated with VELCADE in combination with rtPA, VELCADE significantly reduced tPA-upregulated MMP-9 (8.0 Ϯ 1.2), ICAM-1(1.4 Ϯ 0.2) and PAI-1(2.2 Ϯ 0.2) expression compared with levels in rats treated with saline. Conclusion: The present study suggests that downregulation of ischemia-and tPA-induced MMP9, ICAM-1 and PAI-1 in cerebral endothelial cells by VELCADE could contribute to beneficial effects of VELCADE on the neurovascular unit in the aged rat.

W P53 Caspase Activation and MAPK Pathways are Important for Endogenous Neuroprotection in Suprachiasmatic Nucleus Neurons

Sumedha W Karmarkar, Stacey L Krager, Jared A Cohen, Jamie T Stark, Shelley A Tischkau, Kathy Bottum; Southern Illinois Univ, Springfield, IL Background: Currently few strategies exist to protect brain cells from stroke. Suprachiasmatic nucleus (SCN) neurons are naturally resistant to excitotoxic challenges that are lethal for other brain regions. We are trying to understand the mechanisms behind this endogenous neuroprotection in order to exploit these processes to defend against stroke. Methods: Immortalized cultures derived from the SCN (SCN2.2) and from the neighboring hypothalamus (GT1-7) were treated with 10 mM glutamate (Glu) or media in the presence or absence of inhibitors to caspase 3,8, and 9 and ERK. Cell death was assessed by the live dead assay and TUNEL. Caspase activity was quantified with an activity assay. Members of the MAPK pathway were evaluated by immunoblot. A cardiac arrest model of global ischemia was also used to compare levels of activated caspases after ischemia or sham surgery. Results: In both our cell culture model and our in vivo global ischemia model, caspases 3, 8 and 9 were higher in the Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from SCN than in other neurons. Surprisingly, following either Glu or global ischemic insult, activity of all 3 caspases failed to increase in SCN, but did increase in other neurons. Inhibition of ERK allowed caspase activity levels to increase in the SCN following Glu challenge, and resulted in cell death in the previously resistant SCN. Exposure to Glu in the SCN2.2 cells caused a decrease in p38 levels and an increase in pERK levels. Just the opposite was seen in the GT1-7 cells, in which Glu exposure caused an increase in p38 and a decrease in pERK. Conclusions: SCN neurons are resistant to both Glu excitotoxicity and global ischemia through inhibition of caspase activation (associated with higher baseline levels) and facilitation of ERK activation. Further investigation into these endogenous pathways of neuroprotection is needed. This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Author Disclosures: S.W. Karmarkar: None. S.L. Krager: None. J.A. Cohen: None. J.T. Stark: None. S.A. Tischkau: None. K. Bottum: Research Grant; Modest; SIU CRC Grant.

W P55 Recombinant Expression Of Arginine Decarboxylase Rescues Mouse Cortical Neural Stem Cells From Oxidative Burden

Kiran Kumar Bokara, Sung Ung Moon, Yong Heui Jeon, Won Taek Lee, Kyung Ah Park, Jong Eun Lee; Yonsei Univ, College of Medicine, Seoul, Korea, Republic of Ischemia/reperfusion injury ends up in the cascade of generating peroxinitrite and hydroxyl radical, which are capable of damaging lipids, proteins and DNA. Neural stem cells (NSCs) have attracted enormous attention for their potential applications in ischemic injury, but little is known about how the unique properties of NSCs are affected by oxidative stress prevails at the injury site. We have investigated the effects of stress induced by H 2 O 2 on mouse NSCs. Agmatine, an endogenous primary amine and a novel neuromodulator synthesized from the decarboxylation of L-arginine catalysed by arginine decarboxylase (ADC) reported to possess neuroprotective properties. In this present study we determined whether the expression of ADC in NSCs can prevent the cells from stress injury. Retrovirus expressing human ADC (vhADC) was generated using a pLXSN vector. Cortical NSCs were infected with vhADC and subjected to H 2 O 2 injury (200 M for 15 hrs). Immunocytochemical staining results showed high expression of hADC protein in the vhADC infected NSCs (ADC-NSCs). HPLC analysis revealed high concentration of agmatine in the ADC-NSCs. H 2 O 2 induced increase in lactate dehydrogenase leakage and intracellular ROS formation in NC and LXSN-NSCs but were prevented in ADC-NSCs (p Ͻ 0.05). DNA fragmentation and chromatin condensation following H 2 O 2 injury was effectively abolished in ADC-NSCs. Apoptotic proteins p53, bax and caspase-3 cleavage showed significant (p Ͻ 0.05) decreased expression in ADC NSCs compared with contol and LXSN-NSCs suggesting the prevention from apoptotic cell death. The results of this study for the first time demonstrated that retroviral delivered hADC genes in NSCs synthesized agmatine endogenously and the ADC-NSCs were protected from oxidative injury which were evidenced by decrease in the LDH leakage by free radical scavenging, reduced chromatin and DNA fragmentation, prevented the apoptotic cell death. Our findings have opened up new avenues and more effective therapeutic approaches for improving the microenvironment/niche to which the stem cells homes and must resides during transplantation in ischemic and neurodegenerative diseases.

Author Disclosures: K. Bokara: None. S. Moon: None. Y. Jeon: None. W. Lee: None. K. Park: None. J. Lee: None.

W P56 Partial Ablation of Neuroprogenitor Cells in the Nestin-␦-HSV-TK-eGFP Transgenic Mice Did Not Affect Stroke Size

Hui Sun, Steven Wu, Dept of Neurological Surgery, UCSF and SFVAMC, San Francisco, CA; Steven G. Kernie, Univ of Texas Southwestern Med Cntr, Dallas, TX; Jialing Liu; Dept of Neurological Surgery, UCSF and SFVAMC, San Francisco, CA Backgrounds: Emerging data suggests that there is a strong association between post-stroke functional recovery and neural regeneration. In order to assess the contribution of neurogenesis to post-stroke outcome, we adapted a causal approach to specifically ablate neuroprogenitors by gene targeting. In nestin-␦-HSV-TK-eGFP transgenic mice, the expression of a truncated viral thymidine kinase gene and an EGFP gene under the control of a nestin promoter is restricted to neural progenitor cells, enabling the conditional attenuation of neurogenesis by ganciclovir (gcv) and tagging of neural stem cells. The current study sought to investigate the degree to which ischemia-induced regeneration is dependent on the survival and differentiation of early progenitor cells and to determine whether ablation of neuroprogenitor cells affects stroke outcome. Methods: Gcv (200 mg/kg/day) or vehicle (saline) was administered via osmotic pumps in nestin-␦-HSV-TK-eGFP transgenic mice for 4 weeks beginning at six weeks of age. Stroke was induced by the distal MCAO method. In the gcv-treated group, both sham and stroke mice continued to receive gcv until 8 days following MCAO. All mice were euthanized at 8 days after MCAO or sham surgery and processed for immunohistochemistry. Double immunofluorescence staining for GFP/DCX was performed to quantify the type-1 (GFP immunoreactive) and the more differentiated type-2 progenitor cells (DCX immunoreactive) in the subventricular zone (SVZ) and the dentate gyrus (DG). Infarct volume was determined by unbiased stereology. Results: Following 4 weeks of gcv treatment, both type-1 and type-2 progenitor cells were reduced by 90% in the DG of the sham. Although MCAO increased the number of type-1 and type-2 progenitor cells, even in the continued presence of gcv, there was still a 60% reduction of dentate progenitor cells among the gcv-treated mice, compared to those treated with vehicle. The magnitudes of ablation by gcv and increase by MCAO were similar for both types of progenitor cells in the SVZ. Four weeks of gcv treatment did not impair stroke-induced gliogenesis. However, gcv reduced the dendritic arborization of DCX cells in the DG and SVZ. Although mice with conditional ablation of neuroprogentior cells had a tendency to have a larger infarct volume (gcv: 5.4Ϯ1.6 mm 3 ; vehicle: 3.5Ϯ1.8 mm 3 ; pϾ0.5), the difference was not statistically significant. Conclusions: Conditional partial attenuation of neuroprogenitor cells can be successfully achieved in nestin-␦-HSV-TK-eGFP transgenic mice with stroke, without affecting stroke-induced gliogenesis. The partial ablation of neuroprogenitor cells by 60% prior to stroke did not significantly worsen the stroke size. Ongoing investigation will determine whether the reduction in neurogenesis impairs post-stroke functional recovery and to what extent neurogenesis is restored following the removal of gcv. This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: H. Sun: None. S. Wu: None. S. Kernie: None. J. Liu: None.

W P57 Therapeutic Time Window, Dose Response, and Biodistribution of Autologous Bone Marrow Mononuclear Cells for Ischemic Stroke

Bing Yang, Roger Strong, Sushil Sharma, Xiaopei Xi, James C. Grotta, Jaroslaw Aronowsk, Sean I. Savitz; UT medical school at Houston, Houston, TX Background: Mononuclear cells (MNCs) from the bone marrow are being investigated in phase I clinical trials in stroke patients. However, dose response, therapeutic time window and biodistribution have not been well-characterized in animal stroke models. Methods: 32 Long Evans male rats (3 months old) underwent common carotid artery/middle cerebral artery occlusion (CCA/MCAo) for 3 hrs and then 24 hrs later were randomized to receive saline IV or a bone marrow aspiration followed by an IV infusion of separated autologous MNCs. Animals that were assigned to MNCs received 1 million/kg, 10 million/kg or 30 million cells/kg and were evaluated on the cylinder and corner tests up to 28 days after stroke. In a separate experiment, 26 Long Evans rats underwent CCAo/MCAo, were randomized at 72 hrs or 7 days after stroke to receive a saline injection or autologous bone marrow MNCs (10 million/kg), and evaluated on the cylinder and corner tests up to 28 days after stroke. MNCs were tracked using Q-dot nanocrystals to monitor their migration and survival. Results: Animals treated with 10 million or 30 million cells/kg had significant reductions in neurological deficits compared to saline controls on both tests (pϽ0.05). There were no significant differences between 10 and 30 million cells/kg at 28 days. Animals treated with 1 million cells/kg had no significant differences in deficits on either test compared with saline treated controls. Animals treated with MNCs up to 72 hrs after stroke showed a significant reduction in neurological deficits by 28 days (pϽ0.05). Animals treated at 7 days did not show a difference in behavior on either test compared to saline controls throughout the study period. Labeled MNCs were found in the brain, spleen, lung, liver, and kidney at 1 hr and exponentially decreased to near undetectable levels over the ensuing week after injection. Conclusion: In the CCA/MCA model, we found a maximum reduction in neurological deficits at 10 and 30 million cells/kg and a therapeutic time window up to 72 hrs after stroke.

Author Disclosures: B. Yang: None. R. Strong: None. S. Sharma: None. X. Xi: None. J. Grotta: None. J. Aronowsk: None. S. Savitz: Research Grant; Significant; NIH R21 and HHMI.

W P58 Superiority Of Intra-arterial Delivery Of Auotologous Mononuclear Cells Compared With Intravenous Delivery In Ischemic Stroke

Ramy El Khoury, Sushil Sharma, Bing Yang, Vivek Misra, Roger Strong, James Grotta, Jarek Aronowski, Sean Savitz; UNIVERSITY OF TEXAS IN HOUSTON, Houston, TX Background: Bone marrow mononuclear cells (MNCs) is an investigational autologous cellular therapy for ischemic stroke. Both IV and intra-arterial (IA) routes of delivery are currently being explored in clinical trials but the optimal model of delivery is debatable. Recent studies from our laboratory suggest that rats treated with IA delivery of MNCs have better outcomes after stroke compared with rats treated with intravenously administered MNCs. One of the principal mechanisms of MNC-induced stroke recovery is immune-modulation and trophic factor up-regulation. Purpose: To investigate mechanisms that might partially explain the differences in outcome between IV and IA delivery of MNCs, we measured cytokines and cell death of peri-infarcted tissue as well as infarct size of rats treated either with IA or IV MNCs after stroke. Methods: Stroke was induced in middle-aged Long Evans rats by middle cerebral artery occlusion (MCAO). At 24 hrs after stroke, rats were randomized to receive an IV saline injection or an IV or IA (internal carotid artery) administration of 10 million autologous MNCs. Brain tissue from the ipsilateral cortex at 48 hrs after stroke was homogenized and the supernatant was analyzed for IL-1a ˆusing ELISA. In separate experiments, animals underwent the same protocol but brains were perfusion fixed and analyzed by TUNEL for cell death. In a third set of experiments, animals underwent the same protocol and at 7 days were sacrificed for infarct size analysis. Data are Mean Ϯ SE of 5-7 animals in each experimental group and analyzed by ANOVA. Results: IL-1 a ˆwas significantly (pϽ0.05) decreased in the brains of IV or IA treated groups compared with saline controls (see table 1). There was significantly more reduction in IL-1a ˆin the IA group as compared with the IV MNC group (pϽ0.05). TUNEL-positive cells were significantly reduced in the peri-infarcted regions of IV or IA-MNC-injected rats, respectively, compared with saline treated animals (pϽ0.05). IV and IA MNC-treated rats exhibited significantly reduced infarct size as compared with saline-treated rats. Greater protection was observed in the IA compared with the IV MNC administered groups (pϽ0.05). Conclusion: These findings suggest that MNCs promote cytoprotection in peri-infarct areas and reduce infarct size maturation after ischemic stroke. Intra-arterially administered MNCs led to better cytoprotection and decreased inflammatory cytokines at the site of ischemic injury as compared with intravenously delivered MNCs. The delivery approach might therefore influence the extent to which MNCs may promote recovery after stroke.

Background:

The main treatment for ischemic stroke -intravenous administration of tissue plasminogen activator -is only efficacious within 4.5 hours of the ischemic event. There is therefore a significant medical need to develop novel technologies for stroke patients. Human umbilical tissue-derived cells (hUTC) are currently evaluated. In this study, the optimal route of administration was analyzed, using a rodent transient middle cerebral artery occlusion (MCAo) model. Method: 120 male Wistar rats underwent transient middle cerebral artery occlusion (MCAo). All animal were then randomly assigned to one of 10 groups, for a total of 12 animals per group (8 animals for behavioral testing and 4 animals for serum evaluation and hUTC detection at 60 days), as defined below. Group 1: 3 million (MM) hUTC administered intravenously (IV); Group 2: 2 MM hUTC administered intraarterially (IA); Group 3: 1 MM hUTC administered via intracisterna magna (ICM); Group 4: 1 MM hUTC administered intrathecally (IT); Group 5: 1 MM hUTC administered intracerebrally (IC). Groups 6 to 10 were control groups treated with vehicle only (Group 6: IV; Group 7: IA; Group 8: ICM: Group 9: IT; Group 10: IC). Behavioral tests were performed at day 1 post-stroke and weekly thereafter. These tests included the modified neurological severity score (mNSS), the foot-fault test and the adhesive test. All animals were sacrificed at day 60. Histological assessments included infarct area measurement, immunohistochemical analyses to evaluate cell proliferation, cell death, and new vessels and synaptogenesis. Results: Significant functional improvements in behavioral test scores in hUTC-treated groups were observed as early as Day 14 post stroke. The IV route of administration exhibited the most consistent functional recovery across all 3 behavioral tests as compared to controls treated with vehicle only. The IC route was the second-most consistent. IA, ICM and IT routes of administration also demonstrated significant points of functional recovery but not with the consistency demonstrated with IV or IC administration. Histological evaluation showed that hUTC treatment increased cell proliferation, vessel number and microvessel diameters in the ipsilateral ischemic hemisphere. Apoptosis was decreased in animals receiving IC and IV delivery of hUTCs while synaptophysin expression was increased in all hUTC treatment groups except those receiving IT delivery. Antibodies generated against hUTC were detected in all cell treatment cohorts as was expected in this xenogenic model this however did not negatively impact the significant behavioral recovery that was observed. Efforts to detect hUTC via human genomic DNA detection methods proved inconclusive. Conclusion: Significant reduction in behavioral deficits was observed in all cell treatment cohorts with intravenous administration demonstrating the most robust effects.

Author Disclosures: K. Hong: Employment; Significant; Klaudyne Hong is an employee of ATRM. M. Romanko: Employment; Significant; Michael Romanko is an employee of ATRM. A. Gosiewska: Employment; Significant; Anna Gosiewska is an employee of ATRM. Y. Li: None. M. Chopp: None.

W P60 Bone Marrow Stromal Cells Promote Skilled Motor Functional Recovery and Enhance Contralesional Axonal Connections after Ischemic Stroke in Adult Mice

zhongwu liu, Yi Li, Rui Lan Zhang, Li Zhang, Yisheng Cui, Xia Shang, Michael Chopp; Henry Ford Health System, Detroit, MI To elucidate the neuroanatomical mechanisms underlying motor functional recovery after stroke treated with bone marrow stromal cells (BMSCs), we investigated axonal connections of the corticospinal tract (CST) between the contralesional cerebral cortex and the stroke-impaired side of the spinal cord in adult mice. Adult male mice, in which the CST was transgenicly labeled with yellow fluorescent protein (YFP), were subjected to right hemispheric pyramidotomy (PT) and right permanent middle cerebral artery occlusion (MCAo) or sham surgery. One day later, the mice were randomly selected to receive 0.4 ml of phosphate-buffered saline (PBS) or 1 x 10 6 BMSCs in PBS injected into a tail vein. Foot-fault test and single pellet reaching test were performed 3 days after MCAo and weekly thereafter to monitor skilled motor functional deficit and recovery. To retrogradely label axonal pathways between the impaired left forelimb and the cerebral cortices, 10 l of trans-synaptic tracer pseudorabies virus (PRV)-614-m red fluorescent protein (RFP) were injected into the left forelimb flexor muscles 4 weeks after stroke (4 days before sacrifice). The brain and cervical cord were processed for vibratome sectioning to detect the RFP labeling in the cortical pyramidal neurons and the YFP labeling in the denervated side of the spinal cord with a confocal imaging system. Significant functional improvements were evident at 4 weeks compared with 3 days after PT and MCAo in mice treated with PBS (nϭ8, PϽ0.01) or BMSCs (nϭ10, PϽ0.01), but not in mice suffering PT and sham MCAo treated with either PBS (nϭ8) or BMSCs (nϭ10), while BMSC treatment significantly increased functional recovery compared with PBS treatment in the PT-MCAo mice (pϽ0.05). Furthermore, in the PT-MCAo mice, both CST axonal density in the denervated side Introduction: Niaspan, an extended-release formulation of Niacin (vitamin B3), has been widely used to increase high density lipoprotein (HDL) cholesterol and to prevent cardiovascular diseases and stroke. We have previously demonstrated that Niaspan (40mg/kg) administered at 2 hours after stroke induces neuroprotection. Tissue plasminogen activator (tPA) is an effective therapy for acute stroke, but its use remains limited by narrow therapeutic window. In this study, we tested whether combination treatment with low-dose Niaspan (20mg/kg) and tPA administered 4 hours after embolic stroke in a rat model provides neuroprotection. Methods: Adult male Wistar rats (nϭ8/group) were subjected to embolic middle cerebral artery occlusion (MCAo) and treated with low-dose Niaspan (20mg/kg) alone, tPA (10mg/kg) alone, combination of low-dose Niaspan and tPA, or Saline (control) 4 hours after stroke. A battery of functional outcome tests was performed. Rats were sacrificed at 7 days after MCAo and lesion volumes were measured. To investigate the underlying mechanism of combination treatment neuroprotective effect, deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), cleaved caspase-3, tumor necrosis factor alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9) and toll-like receptor 4 (TLR-4) immunostaining were performed. Results: Combination treatment with low-dose Niaspan and tPA decreased mortality rate and significantly improved functional outcome compared to saline control group (pϽ0.05), while treatment with Niaspan or tPA alone did not significantly decrease mortality or improve functional outcome compared to saline control group. Additionally, combination treatment significantly reduced infarct volume compared to saline control group (pϭ0.006) and infarct volume was significantly correlated with functional outcome (pϭ0.0008; rϭ0.63). Monotherapy with Niaspan or tPA did not significantly decrease infarct volume compared to saline control group. Combination treatment reduced apoptosis as measured by significant reduction in the number of TUNEL-positive cells and cleaved caspase-3 expression in the ischemic brain compared to saline control group (pϽ0.05). Combination treatment also significantly reduced the expression of TNF-alpha, MMP-9 and TLR-4 in the ischemic brain compared to Niaspan, tPA and saline treatment groups (pϽ0.05). Conclusion: Treatment of stroke with combination of low-dose Niaspan and tPA at 4 hours after embolic stroke reduces infarct volume, improves neurological outcome and provides neuroprotection. The neuroprotective effects of combination treatment were associated with reduction of apoptosis and attenuation of TNF-alpha, MMP-9 and TLR-4 expression.

Author Disclosures: A. Shehadah: None. J. Chen: None. Y. Cui: None. L. Zhang: None. C. Roberts: None. M. Lu: None. M. Chopp: None.

W P62 Niaspan Treatment Promotes Vascular Remodeling And Improves Functional Outcome After Stroke In Type 1 Diabetes Rats

Xinchun Ye, Dept of Neurology, Jinling Hosp, Nanjing Univ Sch of Medicine, Nanjing, China; Michael Chopp, Alex Zacharek, Yisheng Cui, Amjad Shehadah, Xu Cui, Cynthia Roberts, Dept of Neurology, Henry Ford Hosp, Detroit, MI; Xinfeng Liu, Dept of Neurology, Jinling Hosp, Nanjing Univ Sch of Medicine, Nanjing, China; Jieli Chen; Dept of Neurology, Henry Ford Hosp, Detroit, MI Diabetes mellitus is a risk factor for stroke. Niaspan (a prolonged release formulation of niacin) treatment of stroke increases vascular stabilization and improves functional outcome after stroke in wild type (WT) rats. In this study, we investigated the changes and the molecular mechanisms of cerebral vascular damage after stroke in type-1 diabetic (T1DM) and tested the therapeutic effect of Niaspan in T1DM-rats. T1DM was induced in adult male Wistar rats via injection of streptozotocin. At 14 days after induction of diabetes, rats were subjected to 2h transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan 40mg/kg starting 24h after MCAo daily for 14 days (nϭ17/group). WT-rats were also subjected to 2h MCAo. Compared to WT-MCAo rats, the ischemic lesion volume was not increased in T1DM-rats, however, T1DM-rats exhibited significantly increased brain hemorrhage and decreased functional outcome after stroke compared to WT-MCAo rats (pϽ0.05). T1DM-rats had significantly increased blood glucose level and blood-brain barrier (BBB) damage measured by endothelial barrier antigen (EBA), ZO1 (a tight junction protein), and desmine (a pericyte marker) compared to WT-MCAo rats. Niaspan treatment of stroke in T1DM-rats significantly decreased brain hemorrhage and BBB damage as well as promoted vascular remodeling measured by vWF, desmine and a-SMA immunostaining and improved functional outcome after stroke compared to non-treatment T1DM-control rats (pϽ0.05). To further investigate the mechanisms of Niaspan-induced vascular remodeling, Angiopoietin-1(Ang1), Ang2, matrix metaloproteinase-9(MMP9) and toll-like receptor-4 (TLR4) expression were measured in the ischemic border zone (IBZ). T1DM-rats exhibited significantly increased Ang2, MMP9 and TLR4 expression, but decreased Ang1 expression in the IBZ compared to WT-MCAo rats (pϽ0.05).

Niaspan treatment significantly decreased Ang2, MMP9 and TLR4 expression and increased Ang1 expression in the IBZ compared to T1DM-control rats. In vitro data show that arterial explant cell migration significantly decreased in arteries derived from T1DM compared to WT-rats. Niacin and Ang1 treatment increased artery cell migration compared to non-treatment T1DM-control (pϽ0.05). Anti-Ang1 significantly decreased Niacin-induced arterial cell migration. These data indicate that T1DM-increases brain hemorrhage and vascular damage as well as decreases functional outcome after stroke compared to WT-MCAo animals. Niaspan treatment attenuates the increased brain hemorrhage, vascular damage and improves functional outcome after stroke in T1DM animals. Niaspan may provide novel therapeutic effects for the treatment of T1DM-stroke and Ang1 contributes to Niaspan-induced vascular remodeling.

Author Disclosures: X. Ye: None. M. Chopp: None. A. Zacharek: None. Y. Cui: None. A. Shehadah: None. X. Cui: None. C. Roberts: None. X. Liu: None. J. Chen: None. The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for several ischemic models including stroke. However, transplanted NPCs have some limitations -low viability by deterioration of microenvironment, mal-differentiation and inflammation in ischemic region. Therefore, approaches towards enhancing NPCs therapeutic modality remain as an elusive goal. Here, we suggested that NPCs infected with retrovirus containing human arginine decarboxylase genes (hADC) which can synthesize agmatine endogenously ameliorated ischemic injury, regulated proliferation and differentiation of NPCs in vivo. Male Sprague-Dawely rats (280Ϯ15g) were subjected to 60min MCAO by well established method. Animals were divided into 4 different group; experimental control group, agmatine treatment group, mock vector (LXSN) infected-NPCs transplantation group, hADC infected-NPCs transplantation group. Animals were transplanted with BrdU-labeled NPCs (1*10 6 cells/10ı `l, single dose) 7days after injury. To determine the functional recovery, rota-rod and limb placing test were excuted after MCAO. Immunohistochemistry was performed with anti-Ki67, anti-BrdU, anti-doublecortin (DCX), anti-nestin, anti-Tuj1, anti-GFAP and anti-Olig2 antibodies to verify whether hADC-NPCs transplantation could induce proliferation and differentiation at the injury site. Behavior experiments showed that rats transplanted with transgenic NPCs and agmatine treatment improved the score of both rota rod and limb placing tests depicting the neurological motor functional recovery compared with experimental control and LXSN-NPCs transplantation group. Reflex response was regained to 70% in hADC-NPCs transplantation and agmatine treatment group, but experimental control group recorded 50% reflex response for 4weeks after MCAO. Immunohistochemistry results showed numerous Ki67, BrdU and DCX-positive cells in hADC-NPCs transplantation and agmatine treatment group at 14days after MCAO representing the activation of proliferation at the injured site. Moreover, the hADC-NPCs transplanted group expressed more of nestin, Tuj-1, GFAP and Olig2 immunopositive cells compared with experimental control and LXSN-NPCs transplantation group showing that the transplanted NPCs were differentiated to mature neural cells at 28days after injury. Overall results demonstrate that combined treatment improves the microenvironment at the injury site and has a therapeutic clue for functional repair against CNS injuries.

W P63

Author Disclosures: J. Kim: None. Y. Park: None. K. Park: None. W. Lee: None. J. Lee: None.

W P64 Essential Role Of Interleukin-6 For Post-stroke Angiogenesis

Karen Gertz, Golo Kronenberg, Tina Baldinger, Mustafa Balkaya, Charite ´, Berlin, Germany; Christian Werner, Ulrich Laufs, Saarland Univ, Homburg, Germany; Matthias Endres; Charite

´,

Berlin, Germany

Abstract Rationale: There is still a paucity of studies investigating longer-term endpoints after ischemic stroke. The pleiotropic cytokine interleukin (IL)-6 mediates multiple effects which may be both beneficial and detrimental to the injured brain but its impact on regeneration and chronic outcome after cerebral ischemia is not known. Objective -Here, we tested the hypothesis that IL-6 is an integral part of the regenerative long-term response of the brain to cerebral ischemia and is required for post-stroke angiogenesis. Methods and Results: We investigated the influence of IL-6 on long-term outcome in a well-characterized model of mild ischemic stroke. To do so, IL-6 knockout (IL6-/-) vs. wildtype littermate mice were subjected to 30 minutes of middle cerebral artery occlusion (MCAo) and reperfusion. As assessed by microarray analysis, there was a significant up regulation of angiogenesis-associated gene transcription at 2 but not at 10 days after MCAo in wildtype mice which was largely blunted in IL-6-/-mice. Similarly, circulating VEGF levels were elevated early after insult in wildtype, but not in IL-6-/-mice. Also, ischemia-induced STAT3 phosphorylation observed in wildtype mice was completely absent in IL-6 deficient mice. A 7-day series of daily bromodesocyuridine injections was begun on the day of MCAo. Histologic outcome at 28 days after MCAo/ reperfusion revealed higher numbers of newly generated endothelial along with macrophage/ microglial cells in wildtype compared to IL-6-/-mice. The density of perfused microvessels which was quantified using endovascular, auto-fluorescent Evans blue staining and tiled-field imaging was increased density of perfused microvessels in ischemic striatum of wild-type mice which was blunted in IL-6-/-mice. Moreover, while ischemic lesion sizes did not differ at early time points after MCAo, IL-6-/-mice showed increased lesion volumes and worse functional outcome at 4 weeks. Conclusion: These results identify IL-6 as an essential factor for post-stroke angiogenesis affording long-term histologic and functional protection.

W P65 Roles of PDGF-PDGF-R␤ Signaling in Brain Pericytes in Ischemic Stroke

Koichi Arimura, Dept of Medicine and Clinical Science and Dept of Neurosurgery, Graduate Sch of Med Sciences, Kyushu Univ, Fukuoka, Japan; Tetsuro Ago, Masahiro Kamouchi, Hiroshi Sugimori, Kuniyuki Nakamura, Koji Ishitsuka, Dept of Medicine and Clinical Science, Graduate Sch of Med Sciences, Kyushu Univ, Fukuoka, Japan; Tomio Sasaki, Dept of Neurosurgery, Graduate Sch of Med Sciences, Kyushu Univ, Fukuoka, Japan; Takanari Kitazono; Dept of Medicine and Clinical Science, Graduate Sch of Med Sciences, Kyushu Univ, Fukuoka, Japan Growing bodies of evidence suggest that brain pericytes play various important roles in brain functions, such as regulation of capillary blood flow, maintenance of blood-brain barrier, and angiogenesis. The platelet-derived growth factor (PDGF)-B and its receptor PDGF-R␤ signaling are requisite for recruitment of pericytes to capillary vessels and subsequent maturation and stabilization of the vessels during embryonic development. It has been reported that PDGF-B prevents neuronal cell death from ischemic insults in adult rodent models. However, the detailed mechanisms as to how the PDGF-PDGF-R␤ signaling protects neurons from ischemic damage are still unknown. In the present study, we investigated the mechanisms for protective roles of PDGF-PDGF-R␤ signaling in brain ischemia using a rodent middle cerebral artery occlusion model (MCAo) and cultured brain pericytes. Immunohistochemistry (IHC) demonstrated that PDGF-R␤ was upregulated gradually (peak at day 5) and specifically in capillary vessels of peri-infarct area, and was co-stained with NG-2 and Desmin, markers for pericytes, in MCAo. We confirmed that PDGF-R␤ was expressed highly in cultured brain pericytes, but not in cultured endothelial cells. Among various stimuli tested, basic fibroblast growth factor (bFGF) increased the expression of PDGF-R␤ significantly at both mRNA (3.5-fold at 6 hr, PϽ0.01) and protein (2-fold at 24 hr, PϽ0.01) levels in the cultured pericytes where FGF receptor 1 is specifically expressed. IHC demonstrated that bFGF was expressed in MAP2ϩ neurons and NG-2ϩ pericytes, but not in GFAPϩ astrocytes, in peri-infarct area, suggesting that bFGF produced by neurons and pericytes in response to ischemia accounted for the upregulation of PDGF-R␤. Immunoblot analyses demonstrated that PDGF-B activated markedly the Akt signaling in the pericytes, which was consistent with the finding that Akt was phosphorylated in the microvascular cells of peri-infarct area. PDGF-B attenuated the cell death induced by serum-depletion in the cultured pericytes, which was prevented by LY294002, an inhibitor of PI3K. PDGF-B significantly phosphorylated the pro-apoptotic factor Bad. Finally, we found that the brain pericytes produced potently a variety of neurotrophins, such as nerve growth factor and neurotrophin-3, at mRNA levels. In conclusion, the PDGF-PDGF-Ra ˆsignaling plays important roles not only in recruitment of pericytes into peri-infarct area during ischemic insults but also in mediating their survival in the pro-apoptotic environments, where the pericytes appear to play a protective role probably through the production of various neurotrophic factors.

Introduction: Pharmacological agents that mimic trophic factors might promote one or more repair mechanisms following ischemic stroke. Animal experimental data have demonstrated that CDP-choline (Cit) administration is effective in recovery. Aims: To analyze the possible repair mechamism of CDP-choline through the functional evaluation in a model of focal cerebral ischemia in rats. Material and Methods: 28 Sprague Dawley male rats distribuited in 4 groups: 1-Healthy with ip CDP-choline (500 mg/kg); 2-Sham (surgery without infarct); 3-Control (surgery ϩinfarct); 4-CDP-choline (surgeryϩinfarctϩ ip CDP-choline (500 mg/kg). We analyzed: Functional evaluation score (Rogers) and lesion volumen by Magnetic Resonance Imaging (MRI) at 24h and 14 days. At 14 days: Neuronal death by TUNEL and Endogenous Cellular Proliferation (BrdU) by inmunohistochemistry. In peri-infarct zone LRP, synaptophysin, GFAP and VEGF by Western Blot and inmunofluorescence. Rats were sacrificed at 14 days. Results: All treatment groups treated with CDP-choline showed less functional deficit (1.57Ϯ1.51; 0.71Ϯ0.75) than control group (3.4Ϯ0.89; 2.6Ϯ0.89) with significant differences at 24h and 14 days, respectively (pϽ0,05). CDP-choline group not decreased infarct size, but reduced significantly the number of TUNELϩ cells (Cit: 20.85Ϯ3.93; Control: 40.6Ϯ6.46), increase synaptophysin (Cit: 0.58Ϯ0.25; Control: 0.28Ϯ0.14) and VEGF (Cit: 1.06Ϯ0.14; Control: 0.41Ϯ0.1) and decrease LRP (Cit: 0.73Ϯ0.75; Control: 1.03Ϯ0.91) and GFAP (Cit: 0.79Ϯ0.29; Control: 1,12Ϯ0.3) respect to control group (pϽ0,05). Conclusions: CDP-choline trophic effect reduce cerebral damage (protective mechanism) and also by increase endogenous celular proliferation (repair mechanism), this might explain the observed benefit of CDPcholine on functional recovery.

W P67 Concurrent Use of Granulocyte Colony-Stimulating Factor and Magnetic Stimulation Inhibits Angiogenesis and Functional Recovery in Stroke Rats

Byung-Mo Oh, Jaewon Beom, Tai R Han, Seoul Nat'l Univ. Hosp, Seoul, Korea, Republic of; Dae-Yul Kim, Asan Med Cntr, Univ of Ulsan College of Medicine, Seoul, Korea, Republic of; Nam-Jong Paik; Seoul National Univ Bundang Hosp, Seongnam, Korea, Republic of Objective: To evaluate the effect of concurrent use of granulocyte colony-stimulating factor (G-CSF) and repetitive transcranial magnetic stimulation (rTMS) on the angiogenic mechanism and functional recovery after stroke. Methods: Seven-week-old male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion and allocated into four groups (nϭ11 in each group): Saline with sham rTMS (group 1), G-CSF with sham rTMS (group 2), G-CSF with 1 Hz rTMS (group 3), and G-CSF with 20 Hz rTMS (group 4). Animals were received G-CSF or saline for 5 days and treated with 20-minute rTMS on their lesioned hemisphere for 2 weeks starting on the first day. Neurological function was evaluated on days 1, 7, 15, and 25. Western blot of Akt, phospho-Akt, endothelial nitric oxide synthase (eNOS) and phospho-eNOS (nϭ6 in each group) as well as immunofluorescence of BrdU/NeuN, BrdU/PECAM-1 and Iba-1 were conducted. Results: Group 4 showed worse function in the modified foot fault test than group 2 on day 7 (pϭ.009). Neurological functional score was poorer in group 3 and 4 than in group 2 on day 25 (pϭ.015). The level of Akt (pϭ.003) and phosphor-Akt (pϭ.047) in the ischemic core was lower in group 4 than in group 2. The level of phospho-Akt in ischemic border zone was lower in group 2, 3 and 4 than in group 1 (pϭ.043). Expression of eNOS in ischemic core was lower in group 3 than in group 2 (pϭ.047). In addition, expression of phospho-eNOS in ischemic core was lower in group 4 than in group 1 and 2 (pϭ.015), whereas lower in group 3 and 4 than in group 1 in ischemic border zone (pϭ.010). Iba-1 expression was greater in the G-CSF and rTMS-treated group than in the saline group. Conclusion: The concurrent G-CSF and rTMS, administered in the early subacute phase of ischemic stroke, may exert a hazardous effect on angiogeneic mechanism and functional recovery.

W P68 A Role for Semaphorin 3A in Stroke Recovery

Kazim Yigitkanli, Anton Pekcec, Stefanie Pallast, MASSACHUSETTS GENERAL HOSP, Charlestown, MA; Alexander Antipenko, Dimitar Nikolov, Sloan-Kettering Institute, New York, NY; Eng H Lo, Klaus Van Leyen; MASSACHUSETTS GENERAL HOSP, Charlestown, MA Background and Purpose: Semaphorin 3A (Sema3A) is known for its role in axon guidance in the developing brain, but may also have detrimental effects after neural injury in the adult. We hypothesized that Sema3A may contribute to an inhibitory environment for neural regeneration after stroke by preventing axon extension and re-establishment of the neural network. Methods: We used immunohistochemistry to detect the expression of Sema3A and its receptor neuropilin-1 (NRP-1), in the post-ischemic cortex. To study the effect of increased levels of Sema3A in the recovery period following transient focal ischemia, we injected recombinant Sema3A into the striatum. To investigate the mechanisms of signalling through Sema3A, we treated cultured primary cortical neurons from either wild-type mice, or mice in which the downstream mediator 12/15-lipoxygenase had been knocked out, with recombinant Sema3A. Alternatively, Sema3A signaling was blocked by an inhibitory peptide, or by inhibition of 12/15-lipoxygenase. Results: Both Sema3A, and its receptor NRP-1 were increased in a time-dependent manner following transient focal ischemia. Injected recombinant Sema3A led to massive cortical damage, and this was prevented by co-administration of LOXBlock-1, a specific inhibitor of 12/15-lipoxygenase. Sema3A inhibited axon growth in wild-type neurons, but not in neurons derived from 12/15-lipoxygenase knockout mice. Similarly, Sema3A effects on axon extension were diminished in wild-type neurons in the presence of the inhibitory peptide, or an inhibitor of 12/15-lipoxygenase. The 12/15-lipoxygenase metabolites 12-HETE and 12-HPETE were able to replicate the effects of Sema3A, suggesting they may be downstream mediators of Sema3A signaling. Conclusion: Taken together, our results demonstrate Sema3A signalling through its receptor NRP-1 and 12/15-lipoxygenase contributes to a prohibitive environment for recovery after experimental stroke. Disruption of the Sema3A pathway may provide a therapeutic benefit during stroke recovery.

W P69 Comparison Of Different Motor Behavioral Tests On Different Brain Injury In Rats

Jian Shi, Dongmin Wang, Tina I Lam, Raymond A Swanson, Stephen M Massa; Neurology of VA Med Cntr and Univ of California, San Francisco, CA Background and Purpose: Motor dysfunction, apart from cognitive impairment, is a common sequela in patients with moderate to severe brain injury, including stroke and traumatic brain injury. Currently there are a number of behavioral tests available for measuring motor dysfunction in rodents, such as Rotor-Rod, CatWalk, etc. However, it is still unclear which test best identifies motor impairment after different degrees of brain injury over time. The purpose of this study was to compare functional impairment after two levels of TBI in rat by two methods of automated test, CatWalk and Rotor-Rod. Methods: A linear motor impactor was used to generate the severe traumatic brain injury (sTBI) with 5.0 mm diameter tip, with 5mm depth, 1.5m/sec velocity and 120 ms contact time left of the mid-sagittal suture centering at (AP: 0.0 mm; ML: 3.0mm); while moderate traumatic brain injury (mTBI) was generated with 2.5 mm tip, with 2.5 mm depth, 1.5 m/sec velocity and 120 ms contact time at (AP: 0.0 mm; ML: 2.0mm). 18 rats were randomly divided into three groups: mTBI, sTBI and sham. Before TBI, rats were trained for two days on the Rotor-Rod and CatWalk equipments. Results: 1) Bederson's score was used to verify the motor deficits of injured rats, and sTBI and mTBI were significant different (2.83Ϯ0.1 vs 1.83Ϯ0.1, pϽ 0.01). 2) In Fig, Rotor-Rod analysis revealed a significant decrease in latency to fall of sTBI rats compared to sham in the 1st week after TBI; however, there was no significant change in mTBI rats. In the 2 nd week, latencies were decreased to about 70% in sTBI and mTBI. From 3 week on, there was no significant decrease in injured animals relative to sham. 3) Quantitative CatWalk analysis at one week showed that sTBI caused significant decreases in Intensity in the contraleteral forepaw and both hind paws; while mTBI resulted in only contralateral hind paw deficit. Moreover, CatWalk analysis showed significant decreases in Intensity, Maxium areas, and Phase dispersion of contralateral right front and hind paws of mTBI rats 10 weeks after injury. Conclusions: For sTBI, CatWalk showed significant motor impairment in the first week after TBI as well as the differences between sTBI and mTBI; importantly, the CatWalk also showed significant motor abnormalities in mTBI rats 10 weeks after injury, while the Rotor-Rod was insensitive. Our data suggest that the CatWalk may be more sensitive to different degrees of brain injury over time. This is important for studies that employ pharmacological, physical or gene therapeutic interventions to improve regeneration and functional recovery after brain injury.

W P70 Social Isolation Worsens Stroke Outcome, Role of Nuclear Factor KappaB and Sex

Louise D McCullough, Jun Li, Fudong Liu, Venugopal Reddy Venna; Univ of Connecticut health center, Farmington, CT Background: Social isolation (SI) is associated with dramatic long-term physiological and psychological consequences in both clinical and experimental studies. SI prior to an induced stroke increases injury, secondary to an enhanced inflammatory milieu. However, how SI worsens stroke outcome implied mechanisms and role of sex remains unknown. Identifying the involved mechanisms could dramatically change the treatment conditions for stroke patients and offer new therapeutic strategies. Nuclear Factor KappaB (NFkB) is an important transcription factor activated in stroke, and plays a critical role in initiating several inflammatory mechanisms. The aim of this study is to determine if SI activates NFkB translocation and leads to worsened stroke outcome. The role of sex in SI mediated NFkB translocation is also investigated. Methods: Stroke was induced by reversible middle cerebral artery occlusion (MCAO-60 minute) in mice (20-25g; C57BL/6N). Different group of animals for infarct analysis (nϭ8/group) and molecular analysis (nϭ4/group). Infarcts are analyzed by TTC at 24hrs after stroke and expressed as percentage of contralateral structure. Adrenal weights (mg/100g) and brains for protein analysis obtained from non-stroked mice cohorts. NFkB translocation was assessed using western blot analysis on fractionated nuclear samples from brain homogenates and levels were expressed as the ratio to the control band with densitometry analysis. Data expressed as meanϮsem except for deficits (NDS), presented as Median (Interquartile-range). Results: SI for two weeks increased body-weights compared to pair-housed (PH) cohorts in both male (26.06Ϯ0.52 vs 23.02Ϯ0.71; PϽ0.05) and females (24.88Ϯ1.01 vs 19.06Ϯ1.26; PϽ0.05. nϭ8/group). SI has significantly worsened outcome in males (Total infarct: Males: 56.10Ϯ3.52; Females 59.05Ϯ4.31) compared to PH, NDS (Males: SI 3.0(1) vs. PH 2.0(0), PϽ0.05, nϭ8; Females SI 3.5(1) vs. PH 1.5(0.5) PϽ0.01). SI males had significant decrease in adrenal-weights compared to PH (14.21Ϯ0.38 vs 17.62Ϯ0.44; PϽ0.05), such changes were not significant in SI and PH females (21.4Ϯ0.27 vs 19.61Ϯ0.79). Interestingly striking sex differences in NFkB levels were observed with highest in SI males and PH females.

Conclusions: In this study, SI not only worsens stroke outcome in both sexes but also worsens NDS, this effect was more pronounced in females. We found that SI inversely influenced body and adrenal weights in males while increased body-weights in females without changes in adrenal weights. Western blot analysis indicates Isolation differentially influences NFkB translocation in males and females. Thus for the first time, our results highlights that NFkB could be an important mechanism involved in gender specific deleterious effects of SI.

Author Disclosures: L.D. McCullough: None. J. Li: None. F. Liu: None. V. Venna: None.

W P71

The Vermicelli Pasta Handling Task Reveals Different Patterns Of Adaptive Versus Maladaptive Forepaw Use Depending On Stroke Model Miranda Brenneman, Krystal Schaar, Roger Strong, Bing Yang, Sean Savitz; Univ of Texas Med Sch, Houston, TX Background: A novel measure of dexterous forepaw function has recently been described that is quantitative, easy to administer, and sensitive to the effects of damage to sensory and motor systems in the CNS of rats. We investigated differences in forepaw function following acute ischemic stroke caused by two different stroke models: reversible common carotid artery/ middle cerebral artery occlusion (CCA/MCAo) and middle cerebral artery occlusion (MCAo). The CCA/MCAo is a model of selective cortical infarction whereas the MCAo produces cortical and subcortical damage. Methods: In this study, 17 Long Evans rats at 3mo of age underwent CCA/MCAo for 2hrs (nϭ9) or MCAo for 90min (nϭ8). Rats were given 7cm lengths of vermicelli pasta and the number of forepaw adjustments were counted as rats manipulated the pasta. Animals were fasted 18hrs prior to testing. Atypical movements, indicative of impaired forepaw use, were also quantified. Testing was administered pre-operatively and once a week for 4 weeks after stroke. Results: Rats with MCAo made significantly more adjustments (overall group meanϭ14.6, pϭ0.013) with the impaired limb compared to CCA/MCAo rats (overall group mean ϭ7.11). Rats with MCAo also took on average nearly 3 times as long to eat the pasta at Weeks 1-4 compared to the CCA/MCAo group (all p's Ͻ0.010). In addition, atypical movements were significantly increased at Weeks 1-4 (pϭ0.007) compared to pre-stroke baseline but did not differ between the groups. Conclusions: Previous work from our lab has shown a persistent decrease in impaired limb forepaw adjustments and time to eat after CCA/MCAo, suggesting greater efficiency in pasta handling that does not rely on the unimpaired limb. Conversely, the present data suggest that while the MCAo group is making more adjustments than the CCA/MCAo group, these adjustments are ineffective in eating the pasta efficiently and may actually hinder the animals, causing them to eat more slowly. The MCAo model shows a different profile of more pronounced forepaw impairment compared with the CCA/MCAo model and may be more useful in evaluating whether new therapies can enhance hand function after stroke.

Author Disclosures: M. Brenneman: None. K. Schaar: None. R. Strong: None. B. Yang: None. S. Savitz: None.

W P72 A Selective TrkB Agonist, 7,8-dihydroxyflavone, Enhances Motor Performance and Promotes Motor Map Integrity Following Cortical Stroke

Zuha Warraich, Jeffrey Kleim; Univ of Florida, Gainesville, FL Brain Derived Neurotrophic Factor (BDNF) has been associated with reducing infarct volume and enhancing cortical plasticity post stroke through activation of the Tyrosine Kinase Receptor (TrkB). Recent work has identified 7,8 Dihydroxyflavone (DHF) as a potent TrkB agonist and a potential therapeutic agent for treating several neurological disorders including stroke. We investigated the behavioral and neurophysiological effects of DHF treatment in a rodent model of cortical ischemia. DHF (5mg/kg, i.p.) was administered two hours prior to and once daily for three weeks post stroke. Stroke was induced by application of the vasoconstricting peptide ET 1 directly onto the distal branches of the middle cerebral artery. Animals were assessed on battery of forelimb motor tests including cylinder paw placement, sunflower seed opening, and pasta handling during a three week period post stroke. Intracortical microstimulation (ICMS) was then used to derive motor maps of forelimb movement representations in motor cortex three to four weeks post stroke. Results showed that rats receiving DHF had significantly reduced motor impairments and larger forelimb motor maps than vehicle treated animals. Histological analysis also revealed reduced infarct volume in DHF treated animals. These results suggest that DHF may be a viable compound for reducing loss of neural tissue and promoting physiological and behavioral improvement post stroke. This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).

Author Disclosures: Z. Warraich: None. J. Kleim: None.

W P73

The Practice of Carotid Endarterectomy in a Large Metropolitan Population Matthew L Flaherty, Brett M Kissela, Univ of Cincinnati, Cincinnati, OH; Heidi Sucharew, Cincinnati Children's Hosp Med Cntr, Cincinnati, OH; Kathleen Alwell, Charles J Moomaw, Daniel Woo, Pooja Khatri, Adeoye Opeolu, Simona Ferioli, Joseph P Broderick, Dawn Kleindorfer; Univ of Cincinnati, Cincinnati, OH Introduction: Carotid endarterectomy (CEA) reduces stroke risk when performed for appropriate indications and with an acceptable perioperative rate of morbidity and mortality. Studies from the 1980s in our population demonstrated that perioperative risk exceeded the recommended boundaries of 3.0% for asymptomatic stenosis and 6.0% for symptomatic stenosis. We investigated indications and outcomes for CEA in our population during 2005. Methods: We ascertained all CEAs performed at 16 hospitals within the Greater Cincinnati/ Northern Kentucky (GCNK) region during 2005 as part of the GCNK Stroke Study. To allow 30-day follow-up, only CEAs performed before 12/01/05 were included in this analysis. Only residents of the core five-county GCNK region were included. Study nurses used an ICD-9 code of 433.1x with a DRG of 533 or 534 to identify cases. Patients were also included if they were identified as part of routine study surveillance for stroke and TIA. All identified TIAs or strokes which occurred before or after the CEA (during 2005) were abstracted by study nurses and reviewed by a study physician. The indication for CEA was categorized as asymptomatic or symptomatic stenosis. Stroke after CEA was ascertained if it occurred during the index hospitalization or if the patient returned to an emergency room or hospital after discharge with stroke symptoms. Death following CEA was tracked using study records, the Ohio and Kentucky Death Indices, and the Social Security Death Index. Events were analyzed using Kaplan-Meier statistics with censoring at the outcome of interest and the end of the study period. Perioperative complications other than stroke or death (such as myocardial infarction) were not routinely tracked. Results: Among approximately 1.3 million GCNK residents, 482 CEAs were performed between 1/1/05 and 12/1/05. There were 318 CEAs for asymptomatic stenosis (mean age 71, 56% male) and 164 CEAs for symptomatic stenosis (mean age 70, 59% male). For asymptomatic stenosis, 30-day perioperative risk of stroke or death was 3.5% (95% CI: 1.4-5.4%). For symptomatic stenosis, 30-day risk was 5.5% (1.9-8.9%). Conclusions: Carotid endarterectomy remains a common procedure in our population, with the majority of CEAs performed for asymptomatic stenosis. The point estimate for perioperative CEA risk for asymptomatic stenosis remains above the recommended benchmark and may reduce or eliminate benefit from this procedure. Population-based surveillance of outcomes following carotid revascularization remains important in the era of both carotid endarterectomy and carotid artery stenting.

W P74 Collaterals and Venous Outflow Determine Outcome in Acute Internal Carotid Artery Occlusion

David S Liebeskind, Meng Lee, UCLA, Los Angeles, CA; Nerses Sanossian, USC, Los Angeles, CA; Qing Hao, Rana Fiaz, Latisha K Ali, Doojin Kim, Bruce Ovbiagele, Sidney Starkman, Paul M Vespa, Sarah Song, Radoslav Raychev, Hermelinda G Abcede, Nestor Gonzalez, Satoshi Tateshima, Reza Jahan, Gary R Duckwiler, Fernando Vin ˜uela, Jeffrey L Saver, UCLA, Los Angeles, CA; for the UCLA Collateral Investigators Background: Acute internal carotid artery occlusion (ICAO) frequently causes devastating stroke. Arterial revascularization is often considered, yet hemodynamics may be important. Ipsilateral venous outflow has also recently been implicated in malignant middle cerebral artery infarct growth. We tested the hypothesis that hemodynamic features noted at angiography, including collateral circulation and the venous outflow pathways, may influence tissue fate and the clinical outcome in acute ICAO. Methods: Consecutive cases of acute ICAO evaluated with concurrent MRI and digital subtraction angiography (DSA) were studied. Serial diffusionweighted imaging (DWI) was acquired immediately prior to angiography and at day 5, chronicling the evolution of infarct volume. DSA collaterals (ASITN/SIR), ipsilateral transverse sinus hypoplasia (TSH) and early venous drainage (EVD) were graded. These features were analyzed with respect to clinical variables, arterial revascularization and infarct growth. Results: 51 cases (mean age 66Ϯ16 years; 26 men, 25 women) of acute ICAO with DSA and DWI were analyzed. Initial NIHSS (median 19) was associated with baseline DWI lesions of mean 54Ϯ47 cc. Collateral grade was evenly distributed from 0-4 (median 2). Ipsilateral TSH was noted in 35% with no difference based on side of stroke (pϭ0.58) and EVD was seen in 22%. Collaterals and venous findings were unrelated to age or gender. More extensive collaterals were associated with smaller baseline DWI lesions (pϽ0.01) but not with initial NIHSS. With increasing collateral grade there was diminished infarct growth (pϭ0.02), less mass effect (pϽ0.01), and less frequent hemicraniectomy (pϭ0.02). Collaterals strongly influenced discharge mRS (pϽ0.01). TSH was associated with increased infarct growth (pϭ0.04) and hemicraniectomy (pϭ0.09). EVD, however, was unrelated to infarct evolution. Baseline hemodynamic status or higher collateral grade was associated with successful reperfusion after intervention (pϭ0.01) measured by thrombolysis in cerebral infarction (TICI) scoring. Arterial revascularization alone was not a predictor of infarct evolution or clinical outcome without consideration of collaterals. Conclusions: Collateral circulation is a strong determinant of infarct volume, lesion evolution and discharge clinical outcome in acute ICAO. Venous outflow features are also influential on infarct growth in this type of stroke. Arterial revascularization alone may be insufficient to offset the hemodynamic aspects of this condition that warrant further investigation.

W P75 Carotid Atherosclerotic Plaque Neovascularization Identified by Contrast-Enhanced Magnetic Resonance Imaging

Zhong-Song Shi, Xiao-bing Jiang, Wei-si Yuan, Dong-hong Liu; Dept of Neurosurgery, First Affiliated Hosp of Sun Yat-sen Univ, Guangzhou, China Background: A large animal model of carotid atherosclerosis may greatly facilitate the identification of imaging characteristics of vulnerable plaques and the selection of patients for intervention. In this study, we assess the histological features associated with vulnerable plaques in a swine model of carotid atherosclerosis and evaluate the MRI patterns of neovascularity, which is a feature of vulnerable plaque. Methods: Carotid atherosclerosis models were created in the miniswines using the combination of partial ligation and high cholesterol diet as previously published, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. All animals were imaged in a 1.5 Tesla MR scanner at three months, and carotid arteries were obtained and sectioned at 4 mm intervals for histopathological examination. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabilis. The atherosclerotic changes of these carotid artery segments were classified as AHA/Stary type I to VI, and the instability feartures of carotid plaque were assessed. Neovascularity was assessed histologically and using immunohistochemisty with anti-matrix metalloproteinases-9 and vascular endothelium growth factor antibodies. TIWI pre-and post-contrast were used to match the histology findings. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the plaques were measured in the matching pre-and post-contrast T1WI. Result: 191 carotid segments from ten carotid atherosclerotic artery models were assessed histologically. 139 segments showed atherosclerotic changes, and 102 segments had the advanced plaque (Stary IV to VI). Advanced atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal (pϽ0.0001). Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. A large lipid core, an abundance of foam cells, intra-plaque hemorrhage, any thrombus, marked plaque and cap inflammation, a thin fibrous cap, cap rupture and AHA/Stary VI were associated with vulnerable plaque (all PϽ0.0001). The matched contrast-enhanced MR imaging and histology slices showed moderate to good correlation for ratio of plaque size to lumen diameter (rϭ0.80, PϽ0.001). CNR was significantly higher in the group of plaques with marked neovascularization than in those without (pϽ0.05). Conclusion: Carotid atherosclerosis model with vulnerable plaque and distal embolism can be created by the combination of partial ligation and high cholesterol diet in the miniswines. Vulnerable plaques were associated with distinct markers. Increased plaque CNR is associated with neovasculization in the plaques and may be used to identify vulnerable plaques.

Author Disclosures: Z. Shi: None. X. Jiang: None. W. Yuan: None. D. Liu: None.

W P76 Effects Of Carotid Endarterectomy On Brain Cognition, Metabolism And Perfusion

M.Angels Font, Imma Rico, Fundacio IDIBELL, Barcelona, Spain; Alex Fernandez, IDI-Hosp St.Pau, Barcelona, Spain; Jaime Mora, Hosp Universitari de Bellvitge, Barcelona, Spain; Ana Carvajal, Fundacio IDIBELL, Barcelona, Spain; Laura Rodriguez, Cristina Gamez, IDI-Hosp Universitari de Bellvitge, Barcelona, Spain; Ana Luque, Hosp Universitari Mutua Terrassa, Terrassa, Spain; Lina Badimon, ICCC, Barcelona, Spain; Jerzy Krupinski; Hosp Universitari Mutua Terrassa, Terrassa, Spain Introduction: Carotid endarterectomy artery (CEA) decreases the risk of suffering a stroke. However, the effects of CEA on cognition, brain methabolism and perfussion continues to be controversial. Hypothesis: CEA may improve brain cognition and metabolism as measured by advanced neuroimaging and neuropsychology. Methods: We included 17 patients, 10 men and 7 women, mean age of 65 with severe unilateral carotid stenosis asymptomatic, or symptomatic which present with no acute lesion in MRI (TIA, amaurosis fugax) schedulded for CEA. We excluded patients with recent stroke or postoperative complications. We performed regular neurological studies, including 18-FDG PET, a HMPAO-SEPCT and neuropsychological studies before and three months after surgery. We performed a voxel-by-voxel analysis using SPM5 to analyse image studies. A comparison of the brain PET and SPECT images between basals and post-CEA images was performed using a paired t-test analysis. The SPM maps were obtained using a cluster and voxel level threshold of PϽ0.05 corrected by False Discovery Rate (FDR). Regions of interest (ROI) analysis were applied in cerebral lobes and subcortical structures regions using WFU-Pickatlas toolbox software for SPM version. We analysed neuropsychological studies by t-paired test (pϽ0.05, SPSS v.15.0). Results: 10 patients were operated on severe left carotid stenosis and 7, on right carotid stenosis. All patients presented with several vascular risk factors. A statisticallly significant improvement in 18FDG uptake was found on voxel-by-voxel and ROI analysis in occipital lobes, left cerebellum and right inferior temporal lobe of patients scheduled for left CEA in PET studies. A statistically significant improvement in cerebral perfussion was found on voxel-by-voxel and ROI analysis in contralateral occipital lobe in the same group. Neuropsychological studies show a significant improvement in verbal domains caused by the interference between newly learned tasks with old material, anatomically dependent on prefrontal cortex, so called proactive interference, in patients undergoing left CEA. Differences were maintained after excluding patients with recent TIA.

Conclusion:

There was an improvement in metabolism and perfusion in posterior regions, and in verbal domains after CEA.

Introduction: Assessment of embolization risk from carotid plaques and subsequent indication to revascularization is usually based on grade of stenosis; other morphological and serological determinants of plaque vulnerability are not broadly considered. Hypothesis. Plaque vulnerability may be associated with specific serological parameters. Methods: High sensitivity C-Reactive Protein (hsCRP) and Vascular Endothelial Growth Factor (VEGF) were assessed preoperatively in a group of consecutive patients with either symptomatic or asymptomatic carotid stenosis undergoing carotid revascularization procedures (endarterectomy -CEA, or stenting -CAS). Plaques from CEA were histologically divided into vulnerable and non-vulnerable (evaluating: microvessel density, fibrous cap thickness, inflammatory infiltrate and lipid core) in a blinded manner. In CAS, vulnerable plaques were defined by analyzing microscopically and ultrastructurally embolic debris captured by distal filters (filter surface involvement and occluded pores percentage). Results were correlated by Fisher's test, Student's t test and regression analysis. Results: A total of 48 patients were included in the study (22 CEA,26 CAS). Mean hsCRP was 9.9Ϯ17.1 mg/l, mean VEGF was 489.8Ϯ248.6 pg/l; in symptomatic patients hsCRP levels were significantly higher compared to the asymptomatic ones (14.9Ϯ22.3 vs. 4.7Ϯ3.5 mg/l, PϽ0.05). In the CEA group, a vulnerable plaque was present in 9/19 samples (47%) and was significantly correlated with higher hsCRP levels (Ͼ5mg/l, OR 3; CI 95%1.2-7.5, PϽ0.05) and with VEGF levels (636.8Ϯ304.7 vs. 356.0Ϯ216.8 PϽ0.05; OR 3.6 when VEGFϾ500 pg/l CI 95%1.02-12.7, PϽ0.05). In CAS, all filters had microscopic debris (mean occluded pore percentage 29.2%Ϯ10.3, surface involvement 28.8%Ϯ 8.1); the presence of more than 25% of occluded pore and surface involvement were correlated with higher hsCRP (Ͼ5mg/l) levels (OR 2.5 CI 95% 1.2-5.3 and OR 3.0 CI 95%1.2-7.5 respectively) and with a trend toward higher VEGF levels (775Ϯ200 vs. 486Ϯ17.6 pg/ml, pϭ0.07). Conclusion: High levels of hsCRP and VEGF are associated with plaque vulnerability. Although these data need to be confirmed by wider studies, this study suggests that serological determinants are useful in recognition of vulnerable plaques with higher risk of embolization.

Author Disclosures: G. Faggioli: None. R. Pini: None. G. Pasquinelli: None. R. Mauro: None. S. Fittipaldi: None. E. Beltrandi: None. A. Freyrie: None. C. Rapezzi: None. A. Stella: None.

W P78 Predictors of One-Year Outcomes of Carotid Artery Stenting in Medicare Patients with Symptomatic and Asymptomatic Carotid Artery Stenosis

Fen Wei Wang, Creighton Univ, Omaha, NE; Barry Uretsky, Univ Arkansas for Med Science, Little Rock, AR; Yong-Fang Kuo, Univ of Texas Med Branch, Galveston, TX; Dennis Esterbrooks, Aryan Mooss, Syed Mohiuddin; Creighton Univ, Omaha, NE Background: Carotid artery stenting (CAS) has been suggested as an alternative to surgical carotid endarterectomy (CEA) for patients with carotid stenosis, a major risk factor for stroke. We identified predictors of one-year outcomes after CAS in both symptomatic (S) and asymptomatic (A) patients using the Medicare database. Methods: All patients age Ն 66 years with a discharge diagnosis of carotid revascularization for the years 2004-2006 were identified in a 5% nationwide random sample of Medicare patients based on ICD 9-CM codes. Outcome measures included in-hospital stroke and all-cause death rates in years 2004-2006 (CASϭ1323) (CASϭ1323) and one-year outcomes for 2004 and2005 (CASϭ737). Results: S Patients (nϭ168) comprised 12.7 % of CAS patients and did not differ from A group (nϭ1155) for age, gender, race and comorbidities except that S group had a lower prevalence of coronary artery, chronic obstructive pulmonary and peripheral vascular disease. In-hospital all-cause mortality (2.98% vs 0.61%, pϭ0.0025) and stroke rates (6.55% vs 1.2%, PϽ0.0001) were higher in the S group compared with the A group. By 1 year, significant differences persisted for stroke (18.3%, S vs 3.4%, A; PϽ0.0001) and stroke/death/MI (31.2%, S vs 14.6%, A; PϽ0.0001). Using multivariate Cox models, independent predictors of 1 -year stroke/death/MI after CAS in S patients were limited to age Ն 80 years old (HR 2.87, 95% CI 1.15-7.12; pϭ0.023). In A patients only, predictors of 1-year stroke/death/MI after CAS were renal failure (HR 2.0, 95% CI 1.08-3.71; pϭ0.028), heart failure (HR 1.69, 1.01-2.80; pϭ0.044) and age Ն 80 years old (HR 1.59,pϭ0.031). Conclusions: Patients with symptomatic status have increased risk of adverse clinical outcomes compared with asymptomatic patients. Age Ն 80 years is associated with increased risk of an adverse outcome within both S and A groups. In A patients, adverse outcomes relate to other serious comorbidities.

W P79 Are Distal Protection Device 'Protective' during Carotid Angioplasty and Stenting?

Tiziano Tallarita, Alejandro A Rabinstein, Harry Cloft, David Kallmes, Gustavo S Oderich, Robert D Brown, Jr, Giuseppe Lanzino; Mayo Clinic, Rochester, MN Purpose: To evaluate the peri-procedural outcome after carotid artery stenting (CAS) with embolic brain protection (EBPϩ) versus without embolic brain protection (EBP-). Methods: We retrospectively reviewed data from a prospective non-randomized database of 357 patients who underwent CAS in the Neuroradiology Division of our Institution from 1999 -2009. One hundred five patients underwent angioplasty and stenting without distal protection while 252 were treated with distal protection. Patients were analyzed according to their EBP status (ϩ or -) for the primary endpoints of perioperative stroke, death or myocardial infarction (MI). Secondary endpoints included postoperative serum creatinine increase, acute carotid artery thrombosis/restenosis, intensive care unit (ICU) stay and length of in-hospital stay, as well as other minor adverse events. Results: Unprotected stenting was mostly performed in the early years of this study and this is reflected in significant baseline differences between the two groups as in our earlier experience CAS was utilized in patients with more significant co-morbidities. Diabetes mellitus (pϭ0.04), previous myocardial infarction (MI) (pϭ0.037), and symptomatic lesion (pϭ0.013) were significantly more common in the EBP-cohort. Despite these baseline differences, there were no significant differences in the primary endpoints (2% in the EBPϩ group and 4.8% in the EBP-, pϭ0.15). The incidence of ipsilateral stroke in the EBP-and in the EBPϩ group was 2.8% vs 1.2%, respectively (pϭ0.27). There were two perioperative deaths (one in each group) and four MIs (three in EBPϩ arm and one in EBP-arm, all non-Q infarcts) (pϭ NS) and the ICU stay was longer in the EBP-(1.6 Ϯ 1.6 days) than in the EBPϩ (1.3 Ϯ 1.0 days) (pϭ.051). There were no differences in occurrence of serum creatinine elevation after procedure or in early in-stent occlusion between the two groups. Conclusion: Although the difference in occurrence of perioperative complications was not statistically significant between the two groups, the slightly higher incidence of ipsilateral stroke in unprotected CAS may be explained by the different distribution of risk factors, symptomatic status and experience of operator, unfavorable for the EBP-arm. In accordance with recent literature, this series cast doubts as to the real effectiveness of distal embolic protection devices in reducing peri-procedural complications.

Author Disclosures: T. Tallarita: None. A.A. Rabinstein: None. H. Cloft: None. D. Kallmes: None. G.S. Oderich: None. R.D. Brown: None. G. Lanzino: None.

W P80 Angioplasty and Stenting in Common Carotid Artery Origin Stenosis: A Review of 16 Patients

Armen Choulakian, Abhineet Chowdhary, Michael J Alexander; Cedars-Sinai Med Cntr, Los Angeles, CA Introduction: Angioplasty and stenting of the common carotid artery (CCA) origin may be technically challenging due to the typical heavy calcification of these lesions, and the significant transition in vessel size necessitating precise placement of these stents. For these reasons, these lesions are excluded from analysis in most carotid stenting trials and registries. Methods: This was a retrospective study of a consecutive series of 16 patients with symptomatic CCA origin stenosis treated by angioplasty and stenting between July 2000 and July 2010. There were 9 males and 7 females in the series, with a mean age of 59 (range 14 to 88). Two of the patients had concomitant CCA bifurcation stenosis of 50% or greater which was treated with stenting at the time of the CCA angioplasty and stenting. All cases were performed with the use of a distal protection device, and all patients were pre-medicated with aspirin and clopidogrel prior to the procedure. The etiology of the CCA origin stenosis was primarily atherosclerotic disease in 11 patients, radiation therapy for malignancy related in 2 patients, William's disease in 1 patient, Takayasu's arteritis in 1 patient, and post vein bypass in 1 patient. Clinical follow up in 14 patients averaged 25 months, with 2 patient lost to follow up, and imaging follow up averaged 18 months. Results: The baseline stenosis in this series was 78% (range 50% to 95%), and the post angioplasty and stenting residual stenosis was 21%. There were no peri-procedural thromboembolic complications and one peri-procedure myocardial infarction, which was non-disabling. One patient died 5 months post-procedure from underlying malignancy, and one other patient was lost to follow up. With an average clinical follow up of 25 months in the remaining patients, two patients (14%) developed recurrent stenosis with ischemic symptoms that required repeat angioplasty and stenting. Both patients had isolated circulations. Two other patients (14%) have asymptomatic recurrent stenosis greater than 50% that is being managed with medical therapy. Conclusions: Angioplasty and stenting at the CCA origin can be performed with low morbidity. However, with an average imaging follow up of 18 months, there was a 28% re-stenosis rate of greater than 50%, with half of those presenting with recurrent symptoms.

Author Disclosures: A. Choulakian: None. A. Chowdhary: None. M.J. Alexander: None.

W P81 Validity of 18 F-fluorodeoxyglucose PET in Identifying Inflamed and Vulnerable Carotid Plaque -A Radiological and Pathological Study

Satoshi Kuroda, Katsuhiko Maruichi, Naoki Nakayama, Kiyohiro Houkin, Kenji Hirata, Tohru Shiga, Nagara Tamaki; Hokkaido Univ Hosp, Sapporo, Japan Objective: In this report, we assessed whether 18 F-fluorodeoxyglucose (FDG) PET can identify inflamed and vulnerable plaque at higher risk for subsequent ischemic stroke in patients with internal carotid artery (ICA) stenosis. Methods: This prospective study included 23 patients with ICA stenosis of more than 70%, including 18 males and 5 females. Their age ranged from 48 to 85 years. All 23 patients underwent 18 F-FDG PET, CT, MRI, and ultrasound to evaluate the plaque morphology and composition prior to carotid endarterectomy (CEA). Following surgery, the specimens were examined, using HE staining and immunohistochemistry. Results: Carotid plaque had a high uptake of 18 F-FDG in 9 (39%) of 23 patients. Intraoperative observations revealed that their carotid plaques were lipid-rich and vulnerable. Histological analysis detected a dense accumulation of lipid and activated macrophages in these plaques. On the other hands, such high uptake of 18 F-FDG was not observed in other 14 patients (61%). Of these, 12 were fibrous and were considered as "stable" plaques. Other two lesions had large subintimal hemorrhage associated with ulcer formation. Conclusion: The present results suggest that 18 F-FDG PET would be valuable to identify the inflamed, vulnerable plaque and predict the risk for subsequent ischemic stroke in patients with severe ICA stenosis.

Author Disclosures: S. Kuroda: None. K. Maruichi: None. N. Nakayama: None. K. Houkin: None. K. Hirata: None. T. Shiga: None. N. Tamaki: None.

W P82 Pathology of Symptomatic and Asymptomatic Carotid Plaques. Are There Really Any Differences?

Patricia M Riccio, Francisco R Klein, Carlos Vigliano, Pedro Gonza ´lez, He ´ctor Raffaelli, Luciano A Sposato; Favaloro Foundation, Buenos Aires, Argentina Background and Purpose: Numerous authors have raised that, besides the degree of stenosis of the internal carotid artery, it is also important to identify the structural components of the atherosclerotic plaque. Moreover, the presence of markers of plaque vulnerability has been associated with an increased risk of ischemic stroke (IS) and transient ischemic attack (TIA). Our objective was to compare the histological features of atherosclerotic plaques of symptomatic and asymptomatic patients undergoing carotid endarterectomy (CEA). Methods: We assessed every patients undergoing CEA at our institution between 01/01/2006 and 12/31/2009. We analyzed the presence of the following pathologic findings in symptomatic and asymptomatic carotid plaques: 1) fibrosis, 2) myofibroblastic hyperplasia, 3) lipidic-necrotic core, 4) calcification, 5) hemorrhage, 6) inflammatory infiltrate, 7) mural thrombus, and 8) ulceration. We compared the frequency of these items between symptomatic and asymptomatic plaques. Finally we stratified each item into a 4-point semiquantitative severity scale (0 to 3) and we generated a score for every case by adding the value of each item. We compared the mean and median scores for symptomatic and asymptomatic cases. Results We assessed 203 carotid plaques/patients: 164 (74.2%) males, aged 68Ϯ9 years. Twenty-eight (14.8%) were performed in symptomatic patients and 175 (86.2%) in asymptomatic individuals. The frequency of the presentation of the 8 carotid pathology items in symptomatic and asymptomatic patients was (values expressed in %): 1) fibrosis: 100.0 vs. 100.0, P ϭ 1.00; 2) myofibroblastic hyperplasia 96.4 vs. 94.3, P ϭ 0.64; 3) lipidic-necrotic core: 100.0 vs. 99.4, P ϭ 0.69; 4) calcification: 89.3 vs. 92.6, P ϭ 0.55; 5) hemorrhage: 50.0 vs. 40.0, P ϭ 0.32; 6) inflammatory infiltrate: 42.9 vs. 56.0, P ϭ 0.19; 7) mural thrombus 21.4 vs. 17.7, P ϭ 0.64; 8) ulceration: 17.9 vs. 9.1, P ϭ 0.16, respectively. The mean pathology score for symptomatic and asymptomatic cases was 4.5Ϯ2.0 vs. 4.4Ϯ2.1, P ϭ 0.81. Conclusions: We found no differences in the carotid pathology of symptomatic and asymptomatic patients. Introduction: Acute ischemic stroke resulting from cardioembolic or atherothrombotic occlusion of the internal carotid artery (ICA) results in high rates of morbidity and mortality. Endovascular therapy is traditionally not recommended; however some retrospective studies have shown endovascular therapy to be feasible and beneficial in select patients. We report our experience in endovascular recanalization of acute stroke patients with ICA occlusion. Methods: We performed a retrospective analysis of all ischemic strokes with ICA occlusion diagnosed by digital subtraction angiography (thrombolysis in cerebral ischemia (TICI) -0) who underwent angioplasty, stenting, or mechanical embolectomy (Merci retrieval or penumbra) from February 2002 to April 2010. Adjunctive therapy with IV rt-PA within 4.5 hours and/or IA rt-PA within 8 hours of onset was used in appropriately selected patients. Post intervention outcome was assessed by TICI scores, head CT (secondary hemorrhages, classified using ECASS I criteria) and National Institutes of Health Stroke Scale (NIHSS) score at 24 hours. Good recannalization was defined as TICI score IIb-III. Clinical outcome was measured by discharge disposition. Discharge to home and in-patient rehabilitation was considered good outcome and nursing homes, hospice homes or death were considered poor outcome. Univariate analysis was done using t-test, Chi-square and Fisher exact test when appropriate. Results: 82 patients with internal carotid occlusion were identified out of 2976 ischemic strokes. Male to female ratio was 1.6:1. Mean age was 68.3Ϯ15 yrs (range 28-95 yrs). Left to right ICA occlusion ratio was 1.22:1. Mean baseline NIHSS was 19Ϯ7.3 (medianϭ18; rangeϭ 1-41). Mean time to ET was 261Ϯ154 minutes (medianϭ 230 minutes; rangeϭ 45-955 minutes). Mean duration of procedure was 138Ϯ59 minutes (rangeϭ 38-357 minutes). 79% patients had tandem MCA1 occlusion. Recanalization, outcome, and hemorrhage rates are shown in Table . Good outcome was achieved in 50% of cases. Conclusion: Revascularization of acute carotid occlusions in the stroke setting is technically feasible and potentially of great benefit. It may help to reduce stroke volume and increase good outcome in selected patients.

Author Disclosures: M. Mittal: None. N. Akhtar: None. C. Martin: None. W. Holloway: None. M. Rymer: Speakers; Modest; Genentech, Inc.. R. Sugg: None.

W P84

The Risk of Carotid Endarterectomy in Patients with > 120 days since Qualifying Cerebrovascular Event Patricia M Riccio, Francisco R Klein, He ´ctor Raffaelli, Luciano A Sposato; FAVALORO FOUNDATION, Buenos Aires, Argentina Background and Purpose: The North American Symptomatic Carotid Endarterectomy Trial (NASCET) published in 1991 prompted the resurgence of endarterectomy for the treatment of symptomatic patients with severe stenosis (70-99%) of extracranial internal carotid artery. The concept of 'symptomatic stenosis' has led to misinterpretations, resulting in the prescription of carotid endarterectomy (CEA) in patients with dizziness, syncope, carotid bruits, etc. Another common misunderstanding is to consider patients as symptomatic when their qualifying cerebrovascular event did not occur within 120 days before surgery. Our objectives were: a) to evaluate the frequency of the diagnoses that prompt to CEA in asymptomatic patients, b) to determine how often CEA is prescribed in patients with cerebrovascular events not occurring within 120 days before surgery and c) to compare the outcome of this latter group with that of asymptomatic patients. The frequencies of diagnosis leading to CEA were: D1: 62 (32.6%), D2: 37 (19.5%), D3: 17 (8.9%), D4: 13 (6.8%), D5: 16 (8.4%), D6: 11 (5.8%), D7: 9 (4.7%) D8: 9 (4.7%), D9: 9 (4.7%), D10: 4 (2.1%) and D11: 3 (1.6%). The D4 group showed significant differences regarding the combined outcome of SI, MI and/or death when compared with the rest of the cohort: OR 5.8, 95%CI 1.3-25.1, P ϭ 0.02. Conclusions: In our cohort, CEA performed in patients with cerebrovascular events not occurring within 120 days before surgery was associated with a fivefold risk of SI, MI and/or death.

Author Disclosures: P.M. Riccio: None. F.R. Klein: None. H. Raffaelli: None. L.A. Sposato: None.

W P85 Correlation of Local Hemodynamics and Morphologic Changes in the Carotid Sinus

Woowon Jeong, Jaehoon Seong; Univ of Central Oklahoma, Edmond, OK Background: The morphology of adult carotid sinus and atherosclerosis are major risk factors for ischemic stroke. It has been investigated that the function of carotid sinus is pressure sensing and the regulation of heart rate, however, the development of the carotid sinus are not clearly understood yet. A recent study reported lifelong development of carotid sinus morphology from infancy to maturity. The most significant finding was the substantial development of the carotid sinus during late adolescence. For further investigation to understand correlation between hemodynamics and morphology in the sinus, a computational study was initiated using a finite-element-based Navier-Stokes equation solver. Methods: Three dimensional virtual models of the carotid bifurcations were created in four postnatal stages, infancy, childhood, adolescence, and young adulthood using 3D CAD design software (SolidWorks). The geometry of four age representative models was obtained from the previous investigation. A finite-element analysis computational fluid dynamics tool (ANSYS CFX) was employed to perform blood flow simulation. Physiological flow, time-averaged flow rate of 4.3 mL/s, was applied to common carotid artery in all models. The peak systolic Reynolds number and the Womersley number were set to 848 and 2.1. A constant viscosity and density of blood were assumed 3.5 cp and 1060 kg/m 3 . Results: Velocity profiles at the mid-sinus area showed similar flow pattern during a cardiac cycle in all models. Mean and peak flow rates in the cross sectional area at mid-sinus did not show difference among all models. However, maximum values of wall shear stress at peak systole showed that infant model had the lowest value, which is 10 percent lower than those of other models. Kinetic energy (KE) was also measured at the mid-sinus and adjacent external carotid artery locations. When compared mean KE between two locations in each model, infant and pediatric models showed about 30 percent higher KE level at the sinus, however adolescence and young adult models did not show much difference. Conclusions: It is of both fundamental and clinical interest to understand the hemodynamics and developmental forces that play a role in maturation of the sinus. This understanding may lead to better prognostication and therapy of carotid disease.

Author Disclosures: W. Jeong: None. J. Seong: None. Background and Purpose: Psychomotor agitation has been described in up to 22% of patients undergoing vascular surgery. Its detection is important because it may be one of the first neurological manifestations of periprocedural stroke. Some authors have suggested that statins administered within the week before surgery reduces the risk of psychomotor agitation. Our goal was to conduct an exploratory analysis to assess the frequency of psychomotor agitation after carotid endarterectomy (CEA) and to evaluate the relationship between psychomotor agitation and atorvastatin administered before the procedure. Methods: We assessed the frequency of psychomotor agitation among every patient undergoing CEA at our institution between 01/01/2006 and 12/31/2009. We performed a univariate analysis to assess the association between atorvastatin and psychomotor agitation within the first 48 hours after CEA. An association was deemed significant if a two-tailed P value of Յ 0.05 was reached (2, t-test and Mann Whitney). We compared age, gender, frequency of vascular risk factors, degree of stenosis of the operated and contralateral artery, history of dementia or depression, chronic obstructive pulmonary disease, chronic renal failure, and postoperative complications between patients treated and not treated with atorvastatin. Results Overall, 221 CEA were performed during the study period. We excluded 22 cases with simultaneous CEA a coronary artery bypass graft surgery, leaving 199 patients for the analysis: 145 (72.9%) were male, with a mean age of 69Ϯ8 years. Forty-four (22.1%, 95%CI 16.9-28.4) patients were previously treated with atorvastatin. We detected psychomotor agitation in 17 cases (8.5%, 95%CI 5.4-13.2). The proportion of patients who developed psychomotor agitation among patients previously treated with atorvastatin and among those not receiving this drug was (0.0 vs. 11.1%, P ϭ 0.015). We found no differences regarding age, gender, frequency of vascular risk factors, degree of stenosis of the operated and contralateral artery, history of dementia or depression, chronic obstructive pulmonary disease, chronic renal failure, and postoperative complications between patients treated and not treated with atorvastatin. Conclusions: In our exploratory analysis of patients undergoing CEA, atorvastatin administered in the week before surgery was associated with a lower frequency of psychomotor agitation. Larger cohorts are needed to assess the relation between atorvastatin and psychomotor agitation.

W P87 Variants at APOE Influence Risk of Deep and Lobar Intracerebral Hemorrhage

Alessandro Biffi, Akshata Sonni, Christopher D Anderson, Massachusetts General Hosp, Boston, MA; Brett Kissela, Univ of Cincinnati, Cincinnati, OH; Jeremiasz M Jagiella, Jagiellonian Univ, Krakow, Poland; Helena Schmidt, Med Univ Gratz, Grazt, Austria; Jordi Jimenez-Conde, Hosp del Mar, Barcelona, Spain; Björn M Hansen, Lund Univ, Lund, Sweden; Israel Fernandez-Cadenas, Vall d'Hebron Hosp, Barcelona, Spain; Devin L Brown, Univ of Michigan, Ann Harbor, MI; Scott L Silliman, Univ of Florida, Jacksonville, FL; Magdy B Selim, Beth Israel Deaconess Med Cntr, Boston, MA; Bradford B Worrall, Univ of Virginisa, Charlottesville, VA; James F Meschia, Mayo Clinic Jacksonville, Jacksonville, FL; Joan Montaner, Vall d'Hebron Hosp, Barcelona, Spain; Arne Lindgren, Lund Univ, Lund, Sweden; Jaume Roquer, Hosp del Mar, Barcelona, Spain; Reinhold Schmidt, Med Univ Gratz, Gratz, Austria; Steven M Greenberg, Massachusetts General Hosp, Boston, MA; Agnieszka Slowik, Jagiellonian Univ, Krakow, Poland; Joseph P Broderick, Daniel Woo, Univ of Cincinnati, Cincinnati, OH; Jonathan Rosand, Massachusetts General Hosp, Boston, MA; International Stroke Genetics Consortium Introduction: Prior studies investigating the association between APOE alleles ⑀2 / ⑀4 and risk of Intracerebral Hemorrhage (ICH) have been inconsistent, limited to small sample sizes and did not account for confounding by population stratification or determine which genetic risk model was best applied. Hypothesis: we sought to determine whether APOE alleles ⑀2 / ⑀4 influence risk of ICH, whether confounding by population stratification might explain any observed association, and which genetic risk model best describes the effect of these alleles on disease risk. Methods: We performed a large-scale genetic association study of 2,189 ICH cases (1104 lobar and 1085 deep) and 4,041 controls from seven cohorts, which were analyzed using additive models for ⑀2 and ⑀4. Results were subsequently meta-analyzed using a random effects model. A proportion of the individuals (322 cases and 357 controls) had available genome-wide data to adjust for population stratification. We used the Likelihood Ratio (RT) test and Receiver Operator Characteristics (ROC) curves to determine which genetic model (dominant, recessive or additive) best predicts ICH presence in our large sample. Results: ⑀2 and ⑀4 were associated with lobar ICH (Figure) at genome-wide significance levels (Odds Ratio (OR) ϭ 1.82, 95% Confidence Interval (CI) 1.50 -2.23, p ϭ 6.6 x 10 -10 and OR ϭ 2.20, 95%CI 1.85 -2.63, p ϭ 2.4 x 10 -11 respectively). Restriction of analysis to definite / probable CAA ICH uncovered a stronger effect. ⑀4 was also associated with increased risk for deep ICH (OR ϭ 1.21, 95% CI 1.08 -1.36, p ϭ 2.6 x 10 -4 ). Risk prediction evaluation identified the additive model as best describing the effect of APOE genotypes on risk of both lobar and deep ICH (all p-values Ͻ 0.01). No evidence of confounding due to population stratification was identified. Conclusion: APOE ⑀2 and ⑀4 are independent risk factors for lobar ICH, consistent with their known associations with amyloid biology. In addition, we present preliminary findings on a novel association between APOE ⑀4 and deep ICH. Finally, we demonstrate that an additive model for these APOE variants is superior to other forms of genetic risk modeling previously applied.

Introduction: Atrial fibrillation (AF) is a most common arrhythmia and an independent risk factor of ischemic stroke. Recently, advancing genome-wide association studies has showed that risk variants for AF are related to ischemic stroke in Caucasian patients. However, the association has not been replicated in Asian patients. The aim of this study is to demonstrate the association in Japanese stroke patients. Method: We enrolled consecutive ischemic stroke patients who admitted to Nagasaki university hospital within seven days of onset. Three single nucleotide polymorphisms (SNPs) of risk variants for AF, rs2200733 and rs10033464 on chromosome 4q25, and rs7193343 on chromosome 16q22 were tested using direct sequencing. The patients with acute ischemic stroke were classified into five subtypes according to the Trial Org 10172 in Acute Stroke Treatment classification, such as cardioembolism (CE), large-artery atherosclerosis, small-vessel disease, other determined etiology and stroke of undetermined etiology. We investigated the prevalence of three SNPs in the five groups. Furthermore, we divided patients into two groups, CE with AF and non-CE without AF, to determine odds ratios (ORs) with 95 % confidence intervals (CIs) for both dominant and recessive genetic models. Result: We included 60 patients of CE, 21 of large-artery atherosclerosis, 11 of small-vessel disease, 20 of other determined etiology and 37 of stroke of undetermined etiology. The prevalence of two copies of rs2200733T was significantly higher in CE than the other stroke groups (p ϭ 0.012). The other SNPs had no association with any stroke subtypes. The ORs for the dominant rs2200733 model, TT and CT vs CC, and recessive model, TT vs CT and CC, were 3.72 (95 % CI 1.24 -11.13; p ϭ 0.0145) and 6.05 (95 % CI 2.28 -16.05; p ϭ 0.0001), respectively. Conclusion: Our result suggested that a variant SNP for AF, rs2200733 on chromosome 4q25, was associated with CE in Japanese stroke patients. The investigation of rs2200733 in acute stroke patients may be useful for diagnosis and treatment of CE.

Author Disclosures: Y. Tateishi: None. A. Tsujino: None. A. Nagatani: None. H. Nakajima: None. R. Nakata: None. T. Masuda: None. M. Tokuda: None. T. Fukuda: None. M. Motomura: None. K. Sumikawa: None.

W P89 The Contribution of Cystatin C Gene Polymorphisms on Cerebral Ischemic White Matter Lesions

Shingo Mitaki, Dept of Neurology, Shimane Univ Sch of Medicine, izumo, Japan; Atsushi Nagai, Sheikh Abdullah, Dept of Laboratory Medicine, Shimane Univ Sch of Medicine, izumo, Japan; Toru Nabika, Dept of Functional Pathology, Shimane Univ Sch of Medicine, izumo, Japan; Shuhei Yamaguchi; Dept of Neurology, Shimane Univ Sch of Medicine, izumo, Japan Background and Purpose: Cystatin C (CSTC) is a 13k Da protein consisting of 120 amino acids, encoded by a 7.3-kb gene located on chromosome 20. CSTC functions as a major, general extracellular cysteine protease inhibitor in mammals. In vitro experiments have indicated that it can inhibit several cysteine proteases, such as cathepsins B, H, K, L and S. The promoter polymorphism, -82G/C, and signal peptide polymorphism, ϩ148G/A, were reported to account for reduced promoter activity and reduced CSTS secretion, respectively. The haplotype containing these SNPs was reported to be associated with low level of serum CSTS and coronary artery disease. These observations suggest that exaggerated protease activity due to the reduced production of an endogenous inhibitor, CSTC, could contribute to vascular remodeling. In healthy adults, the concentration of CSTC is 5 times higher in CSF than in plasma. Given the physiological function of CSTC described above, it might play an important role in cerebrovascular pathological changes. Accordingly, the effects of CSTC polymorphisms on ischemic white matter lesions were investigated under the case-control study design. Methods: Three CSTC polymorphisms were genotyped in 100 cases, identified by magnetic resonance imaging as having periventricular hyperintensity (PVH), grade 3 on Fazekas scale, and 200 controls with no PVH. Plasma CSTC levels in these subjects were also measured. Expression vectors containing wild type or ϩ148A mutant type CSTC cDNAs were transfected into astrocytoma cells. Expression of CTSC mRNA was analyzed by quantitative RT-PCR. Intracellular and the secreted CSTC protein levels were determined by Western blot and ELISA, respectively. Results: A significant association was found between the CSTC haplotype and the ischemic white matter lesions (odds ratioϭ1.86; Pϭ0.04). In a logistic regression model, the mutant haplotype was also associated with low plasma CSTC levels (odds ratioϭ0.38; Pϭ0.02). The in vitro transfection study revealed that, in spite of no effects observed on the CSTC mRNA level, the ϩ148A allele significantly increased intracellular but decreased the levels of secreted CSTC protein. Conclusions: Our study demonstrates the significance of CSTC polymorphisms in the generation of white matter lesions. The ϩ148A allele of the CSTC decreased the extracellular level of CSTC protein probably by attenuating its secretion.

Author Disclosures: S. Mitaki: None. A. Nagai: None. S. Abdullah: None. T. Nabika: None. S. Yamaguchi: None.

W P90 Cumulative Association of Six Variants in the KCNK17, LRP, NOS3, SCNN1A and MMP12 Genes with Ischemic Stroke

Sophie Domingues-Montanari, Israel Ferna ´ndez-Cadenas, Alberto del Rio-Espinola, Maite Mendioroz, Pilar Delgado, Anna Penalba, Marta Rubiera, Marc Ribo ´, Anna Rosell, Jose Álvarez-Sabı ´n, Joan Montaner; Institut de Recerca -Hosp Vall d'Hebron, Barcelona, Spain Background: We previously reported the association of single nucleotide polymorphisms (SNPs) in five chromosomal regions with ischemic stroke (IS). Each SNP alone showed a moderate association, with odds ratios (OR) ranging from 1.35 to 3.05, so we hypothesized that their combination could reveal a stronger association with IS. Methods: We evaluated the combined association with IS of 6 SNPs around the KCNK17 (rs10947803), LRP1 (rs7956957), MMP12 (rs2276109), NOS3 (rs10275136 and rs310585) and SCNN1A (rs5742912) genes in a Spanish population comprising 540 IS subjects and 540 control subjects. IS subjects were divided in cardioembolic (44.8%), atherothrombotic (20.9%) and undetermined (34.3%) etiologies. Statistical analysis and logistic regression were performed under an additive model. Predicted probabilities were calculated with receiver operating characteristic (ROC) curves and compared using the MedCalc software. Results: Each SNP was significantly associated with IS after adjustment for the other SNPs and established risk factors, including male gender, age over 55, diabetes mellitus, dislipidemia, hypertension and cigarette smoking. IS risk increased depending on the number of risk alleles carried. Additionally, the combination of 6 SNPs showed clear contribution to risk in comparison with conventional clinical stroke risk factors only, with predictive probabilities of 69.1% vs. 63.4% (pϽ0.001). In subjects who had any five or more of these SNPs, the predictive probability for IS was significantly higher compared with subjects carrying none or only one SNP (ORϭ26.06, PϽ0.001). Moreover the risk increased with the number of genetic plus clinical risk variable carried, although no subject in our population carried more than 9 markers. Finally, a risk score was assigned to each variable depending on the a ˆvalue from the logistic regression and a risk scale from 1 to 45 was then used to classify subjects into three categories. 51.0% of IS cases were in the low risk category (score Ͻ 18) compared to 72.4% in the moderate (19 Ͻ score Ͻ 26, PϽ0.001 vs. low) and 92.3% in the high risk (35 Ͻ score, PϽ0.001 vs. low). This model permitted to reclassify 10% of the subjects with a moderate risk determined by classical risk factors into the high risk category considering both genetic and clinical data. Conclusions: Six SNPs plus classical stroke risk factors showed a cumulative and significant association with IS. These results open diagnostic and therapeutic expectations in stroke. Background and Purpose: The thrombomodulinϪprotein C system located on the endothelial surface plays a key role in both thrombosis regulation and inflammatory response. Thrombomodulin acts to decrease thrombin's pro-coagulant activity and to increase activated protein C, a natural anti-coagulant. The activation of protein C by the thrombin-thrombomodulin complex is enhanced when the substrate protein C is presented by the endothelial cell protein C receptor. These functions make the thrombomodulin (THBD) and endothelial cell protein C receptor (PROCR) genes promising candidate genes for stroke susceptibility and were predefined hypotheses for the Genetics of Early-Onset Stroke Study. Methods: Study subjects were drawn from a population-based case-control study of ischemic stroke among men (57%) and women (43%) aged 15-49 and included 832 cases of first ischemic stroke (41.4% African-American) and 883 age-comparable control subjects (49% African-American). Controls were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Analyses were performed on 17 single nucleotide polymorphisms (SNPs) in THBD and 19 SNPs in PROCR, which included the combined SNPs available from Illumina's Omni-1 QUAD GWAS and CVD SNP panels, providing thorough gene-specific coverage. Among Caucasians, SNPs in PROCR were among the top 5 risk-associated polymorphisms in our ongoing CVD and GWAS analyses. Results: Of the 17 THBD SNPs analyzed, 2 SNPs (rs1042579, rs3179123) were associated with stroke (ORϳ0.6, pϭ0.03) among African-Americans using an additive vascular model (adjusting for age, sex, race, hypertension, diabetes, smoking, MI). No THBD associations were found in Caucasians. Of the 19 PROCR SNPs analyzed, 10 SNPs were significant (ORϳ1.4 pϭ0.0008-0.02) among Caucasians using the same model; 9 of these SNPs were in strong linkage disequilibrium. No PROCR associations were found in African-Americans. Stroke subtype models showed no significant associations in either gene. Conclusions: THBD and PROCR polymorphisms may have race-specific associations with early-onset ischemic stroke. Replication studies are in progress to confirm these findings.

W P92 The Effect of Survivorship Bias on Cross-Sectional Case-Control Genetic Studies of Highly Lethal Diseases

Christopher D Anderson, Massachusetts General Hosp, Boston, MA; Michael A Nalls, National Institutes of Health, Bethesda, MD; Alessandro Biffi, Natalia S Rost, Steven M Greenberg, Massachusetts General Hosp, Boston, MA; Andrew B Singleton, National Institutes of Health, Bethesda, MD; James F Meschia, Mayo Clinic, Jacksonville, FL; Jonathan Rosand; Massachusetts General Hosp, Boston, MA Background: Survivorship bias is the phenomenon by which individuals are excluded from analysis of a trait because of mortality related to the expression of that trait. In genetic association studies, variants increasing risk for disease onset as well as risk of disease-related mortality (lethality) could be difficult to detect in cross-sectional casecontrol designs, possibly leading to underestimation of a variant's effect on disease risk. Hypothesis: We hypothesized that a simulation of longitudinal and case-control genetic association studies would allow quantification of the erosion in effect size estimates attributable to survivorship bias. Methods: We modeled cohorts for three diseases of high lethality (intracerebral hemorrhage, ischemic stroke, and myocardial infarction) using existing longitudinal data. Based on these models, we constructed an iterative simulation of case-control genetic association studies for genetic risk factors of varying effect sizes, lethality, and minor allele frequencies (MAF). Results: For each disease, erosion of detected effect size was larger for case-control studies of individuals of advanced age (age Ͼ75 years) and/or variants with very high event-associated lethality (Genetic-conferred Relative Risk for event-related death Ͼ2.0). We found that survivorship bias results in no more than 20% effect size erosion for cohorts with mean age Ͻ75 years, even for variants that double lethality risk. Ascertainment of at least 40% of lethal cases reduces this phenomenon, resulting in Ͻ20% effect size erosion even for cohorts of advanced age with extremely lethal phenotypes. Furthermore, we found that increasing effect size erosion was accompanied by depletion of MAF in the case population, yielding a "signature" of the presence of survivorship bias. Once again, ascertainment of 40% of lethal cases mitigated this MAF depletion. Conclusion: Our results demonstrate that failure to enroll lethal cases can distort the measured effect sizes for genetic variants affecting both disease incidence and lethality. However, this bias results in Ͻ20% erosion in effect size for commonlyencountered cohort conditions. Our simulation provides formulae to allow estimation of effect size erosion given a variant's odds-ratio (OR) of disease, OR of lethality, and MAF. These formulae will add precision to power calculation and replication efforts for case-control genetic studies. Our approach requires validation using prospective data. This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont). Introduction: Elevated homocysteine (Hcy) is an independent risk factor for stroke and vascular disease. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with Hcy levels and related diseases. For specific associated SNPs, the associations differed by sex. We sought to investigate the relationship of five previously associated SNPs in participants of VISP including potential sex differences. Methods: VISP was a double-blind, randomized clinical trial comparing low vs. high dose folic acid, vitamin B6, and vitamin B12 in patients with a non-disabling cerebral infarction and Hcy levels above the 25th percentile. Data were drawn from a genetic substudy including 2164 participants. Genotypic data were available for rs1801133, rs2274976, rs526934, and rs6586282 from an Ilumina GoldenGate assay. The fifth SNP, rs1047891, was genotyped using a Taqman assay. We studied the SNPs and log transformed plasma Hcy levels using unadjusted, minimally adjusted (sex, race, age), and fully adjusted (sex, race, age, body mass index, smoking status) linear regression models. We also used sex and race stratified analyses. RESULT: SNP rs1047891 in the carbamoyl phosphate synthase 1 (CPS1) gene was associated with Hcy in women (minimally adjusted, P ϭ 0.03) (Table ). For rs1801133 in the methylenetetrahydrofolate reductase (MTHFR) gene, the SNP was associated with Hcy in white men and women (minimally adjusted, P ϭ 0.05) and white men (minimally adjusted, P ϭ 0.05). None of the other three SNPs investigated were associated with Hcy. Conclusion: SNPs rs1047891 and rs1801133 demonstrate a sex effect regarding an association with plasma Hcy levels consistent with those reported in the literature; an effect in women for rs1047891 and an effect in men for rs1801133. Further studies should examine these SNPs in a larger, more diverse cohort and consider sex differences.

W P94 Gender Differences In Long-term Mortality After Ischemic Stroke

Marı ´a C Zurru ´, Claudia Alonzo, Laura Brescacı ´n, Fabiana Ortega, Silvina Brienza, Daniela Gil, Julieta Montecchia, Marcelina Carretero, Luis Ca ´mera, Gabriel Waisman, Edgardo Cristiano, Hosp Italiano de Buenos Aires, Buenos Aires, Argentina; Bruce Ovbiagele; UCLA Stroke Cntr, Los Angeles, CA Background: Women generally have worse stroke outcomes than men. Older age at stroke onset could be a determinant of this fact, but also differences in vascular anatomy, vascular risk factor control or hormonal profile could be implied in stroke outcome. We aimed to assess short-term outcomes and long-term mortality and recurrence by sex in patients hospitalized with ischemic stroke within a Latin American Healthcare system. Methods: Between 12/06 -05/10, consecutive acute ischemic stroke patients admitted within a Buenos Aires healthcare system were prospectively enrolled in a secondary prevention program. We compared vascular risk factor prevalence and control between sexes, the independent effect of sex on functionality, cognitive status and depression one month post-discharge, as well as on long-term mortality. Results: Among 413 stroke patients, mean age 74.2Ϯ10 years (women 76Ϯ9; men 72Ϯ11; pϭ0.0005), 52% females. Large artery stroke subtype was more frequent in men (15% vs 10%) and cardioembolic events in women (20% vs 14%). Differences between both sexes are shown in the table below. After two years of follow-up Kaplan-Meier analysis shows higher all-cause mortality in women (82 % vs 89 % ). Logrank test 0.01. Conclusions: women had worse short-term outcomes on functionality and cognition, as well as higher long-term mortality, despite vascular risk factor control at target levels in both sexes. These sex disparities were not explained only by age differences. Consecutive patients with the diagnoses of transient ischemic attack (TIA), acute ischemic stroke (AIS), and intracerebral hemorrhage (ICH) were identified and a retrospective chart review was performed to obtain demographics, history of HTN, home antihypertensive medication use, admission BP, discharge BP, LOS, and antihypertensive medications at discharge. Results: A total of 393 consecutive patients admitted to a single tertiary care center from November 2008 thru June 2010 were included (Whites: TIA 31,AIS 93,and ICH 17;Blacks: TIA 38,AIS 176,ICH 38). Demographics and data elements are shown in the Table. Blacks were more likely to have a history of HTN (range 80%-90% vs. 63%-65% across all three diagnoses), to take antihypertensives at home, have higher BP values on admission respectively), and required twice as many medications at discharge to treat HTN in patients with AIS and ICH. Blacks were more likely to receive calcium channel blockers (all diagnoses) as well as ACE-inhibitors (TIA). Median LOS tended to be longer for Blacks in AIS patients (7d vs. 5d, pϭ0.053). Conclusions: Black patients with TIA, AIS and ICH had greater prevalence of pre-existing HTN and the use of antihypertensives prior to the event. Despite this, they had higher admission BP and required more vigorous antihypertensive treatment by discharge. Refractory hypertension may be one of the factors affecting the stroke rate as well as the increased LOS seen in our Black patients with AIS.

Background: Dolichoectasia (DE) of cerebral vessels has been associated with adverse neurological outcomes, including stroke, but few population-based studies exist and normative data on vessel size are lacking. In addition, data are limited in Hispanic and black people who are at greater risk of stroke than whites. We investigated the prevalence of basilar artery (BA) DE and intracranial artery characteristics in a diverse urban community to establish population-based norms. Methods: The Northern Manhattan Study (NOMAS) is communitybased and includes stroke-free participants who underwent head MRA. We used visual assessment and Smoker's criteria to assess basilar DE based on diameter (Ͼ2 SD cutoff of 4.6 mm in Smoker's clinical sample with mean age 48 years), transverse position compared to midline, and height of BA bifurcation. Using a semi-automated 3D tool, with automated tracking of vessel centerlines, we estimated anterior and posterior circulation artery diameters and BA length and volume. We used t or Chi Square tests, and multivariable linear regression to compare arterial measurements and participant characteristics. Results: There were 402 NOMAS participants with MRA data available (mean age 72Ϯ8, 62% women, 56% Hispanic, 23% black, 18% white). The meanϮSD, IQR of vessel diameters were: BAϭ3.8Ϯ0.6 mm, 3.4-4.2 mm; left ICAϭ5.0Ϯ0.7 mm, 4.6-5.4 mm; right ICAϭ5.0Ϯ0.6 mm, 4.6-5.3 mm. The prevalence of BA DE was 20%. Eleven percent of our sample met Smoker's BA diameter cutoff of 4.6 mm (Ͼ2SD), but only 2% met our Ͼ2 SD cutoff of 5.1 mm, in this older population-based cohort. Transverse position was lateral to midline in 63%, and the BA bifurcated at or above the third ventricle floor in 48%. Adjusting for age and sex, DE prevalence was greater in blacks (22%) and Hispanics (23%), compared to whites (12%; black vs white Pϭ0.04, Hispanic vs white Pϭ0.03). In models adjusting for age and race/ethnicity, a larger BA volume/length ratio existed in men than women (Pϭ0.002). Examining age, sex, and race/ethnicity, men had larger BA diameters (Pϭ0.01), and both left and right ICA diameters (pϽ0.001), but correcting for total cranial volume (TCV) reversed the association (women greater than men; PϽ0.001 for all diameters). Adjusting for sex and race/ethnicity, ICA diameters were greater among those over 75 years (Pϭ0.04), and correcting for TCV strengthened the association (compared to age Ͻ65: PϽ0.05 for age 65-74, PϽ0.01 for age 75ϩ). Conclusions: Basilar DE was common in our stroke-free sample. Blacks and Hispanics were more affected than whites. Larger arterial diameters were seen in older participants, and sex differences were observed. Correction for head size appeared to be important and has generally not been done in prior studies. Our findings differ somewhat from the patient sample on which Smoker's criteria are based, and suggest brain artery architecture varies with age, sex and race.

W P97 The Presence of Intracranial Artery Calcification is Associated with Mortality and Vascular Events in Ischemic Stroke Patients

Jean-Marc Bugnicourt, Hopital Universitaire d'Amiens, Amiens, France; Claire Leclercq, Hopital universitaire d'Amiens, Amiens, France; Jean-Marc Chillon, Universite ´de Picardie Jules Verne, Amiens, France; Ziad A Massy, Sandrine Canaple, Chantal Lamy, Olivier Godefroy; Hopital Universitaire d'Amiens, Amiens, France Introduction: Although intracranial artery calcification (IAC) is a known risk factor for ischemic stroke, its association with stroke outcome has not been assessed. The present study sought to evaluate the occurrence of all-cause death and vascular events in ischemic stroke patients with IAC. Methods: Three hundred and twelve patients with ischemic stroke were included by a single center. The seven main cerebral arteries were screened for IAC (defined as hyperdense foci with a peak density of more than 130 Hounsfield units). Complete follow-up datasets were available for 302 of the 312 patients. Major vascular events (included ischemic stroke, myocardial infarction, peripheral arterial disease (i.e. limb-threatening ischemia)) and all-cause deaths were noted. Results: IAC was present in 260 patients (83%). Over a median follow-up period of 26.8 months, 67 (22%) deaths or ischemic events occurred. Kaplan Meier analysis showed that the occurrence of all-cause mortality and cardiovascular events was significantly greater in patients with IAC than in IAC-free patients (pϭ 0.0012, log-rank test). A multivariate Cox proportional hazards analysis established that the IAC score (hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.01-1.55; pϭ0.04) and glomerular filtration rate (HR: 0.89 for each increment of 10 ml/min/1.73m2; 95%CI: 0.98-1.0; pϭ0.045) were significantly associated with both all-cause mortality and vascular events. Conclusions: In ischemic stroke patients, the presence of IAC is significantly associated with both all-cause mortality and vascular events, suggesting that careful attention should be given to the presence of IAC as a prognostic indicator in a simple head CT scan. (Oxford Vascular Observational Study: OXVASC) the presence of vertebro-basilar (VB) stenosis identified a group of patients with posterior circulation stroke who have a high early recurrent stroke risk. Pooled individual patient data from these two studies were analysed in order to confirm whether VB stenosis is a predictor of early stroke recurrence independently of other risk factors, and whether intracranial or extracranial stenosis confers a higher risk. Methods -208 consecutive patients from the SGH study and 151 patients from the OXVASC study presenting with posterior circulation TIA or stroke were recruited and prospectively followed for 90 days. CE-MRA or CTA at presentation and 90 day follow up was available in 327. Any recorded posterior circulation TIA/stroke in the month prior to the presenting episode was referred as first event. Results: Taking the first event as the index case, the risk of recurrent stroke at 90 days was 24.6% in patients with any VB stenosis (Ͼ50%), compared to 8.9% in those without stenosis (OR ϭ 4.2; P Ͻ 0.0001). The risk of stroke was higher in patients with intracranial stenosis 33.3% (OR ϭ 6.5; P Ͻ 0.0001) and lower 16.2% in patients with extracranial stenosis (OR ϭ 2.5; P ϭ 0.06). Taking the presenting episode as the index event the risk of recurrent stroke was 9.6% in patients with stenosis compared with 2.8% in those without stenosis (OR ϭ 3.7; Pϭ0.012). The risk of recurrent stroke was higher in those with intracranial stenosis 13.8% (OR ϭ 5.6; P Ͻ 0.0001); the risk was non significant in those with extracranial stenosis 5.4% (OR ϭ 2.0; Pϭ0.39). Cox regression analysis showed that VB stenosis confers a higher risk of early stroke recurrence independently of hypertension, hypercholesterolaemia, diabetes, smoking, previous stroke and gender. RRϭ3.5; P Ͻ 0.001 and RRϭ2.96; P ϭ 0.05, taking the first and the presenting event as the index case respectively. Conclusions: VB stenosis is an independent predictor of stroke recurrence in patients presenting with posterior circulation stroke and TIA. Intracranial stenosis confers a higher risk. The high early recurrent risk provides a strong rationale for randomised trials, such as VIST, determining whether stenting can reduce recurrent stroke risk.

Author Disclosures: G. Gulli: None. L. Marquardt: None. P.M. Rothwell: None. H.S. Markus: None.

W P99 Chlamydia Pneumoniae In Early Lesions Of Patients With Carotid Atherosclerosis

Ana Luque, Hosp Universitari Mutua Terrassa, Terrassa, Spain; Marta M.Turu, ICCC, Barcelona, Spain; Mark Slevin, MMU, Manchester, United Kingdom; JO Juan-Babot, Norma Rovira, ICCC, Barcelona, Spain; Ana Carvajal, M.Angels Font, Fundacio IDIBELL, Barcelona, Spain; Jerzy Krupinski; Hosp Universitari Mutua Terrassa, Terrassa, Spain Background and Purpose: Infectious agents, like Chlamydia pneumoniae, could play an important role in the development of atherosclerosis. Recent studies reported that C. pneumoniae directly interferes with infected host cells hypoxia-inducible factor-1a ´regulation during intracellular replication in hypoxia. Objectives were to study at what level of the lesion the infection appears and how this affects the development of the lesion. Furthermore, we studied a relationship between the presence of C. pneumoniae and an over-expression of the hypoxia-inducible factor-1a ´in carotid lesions. The study was performed in 38 carotids with stenosis Ͻ50%, 25 carotids with stenosis Ͼ70% and 10 middle cerebral arteries. Results: The presence of C. pneumoniae was detected with PCR. Sera from 22 patients who underwent carotid endarterectomy were subjected to a commercial micro-immunofluorescence test for measuring antibodies to C. pneumoniae. Immuno-histological analysis of carotid arteries was used to detect the presence of hypoxia-inducible factor-1a ´. 42.1% of carotids with stenosis Ͻ50% were negative whereas 57.9% were positive. 90.9% of the positive results came from preatheroma lesions whereas only 9.1% came from atheroma lesions. 32% of carotids with stenosis Ͼ70% were positive. All of the 10 middle cerebral arteries were negative. Of the 22 serum samples studied, 91% were positive and 9% were negative. There was a significant correlation between the over-expression of HIF-1a ´in the plaque area with the presence of C. pneumoniae in some parts of the artery (pϽ0.05). Conclusions: C pneumoniae might play an important role in activation and development of the initial stages of the carotid atherosclerotic lesions.

Author Disclosures: A. Luque: None. M. M.Turu: None. M. Slevin: None. J. Juan-Babot: None. N. Rovira: None. A. Carvajal: None. M. Font: None. J. Krupinski: None.

W P100 Cervical Carotid Artery Dissection is Associated with Styloid Process Length

Jonathan M Raser, Michael T Mullen, Brett L Cucchiara, Scott E Kasner, Steven R Messe; Hosp of the Univ of Pennsylvania, Philadelphia, PA Background: Cervical carotid artery dissection is a common cause of stroke in the young. The styloid process varies in length, angulation and proximity to the carotid artery, and there are rare reports of cervical carotid dissection in the presence of an elongated styloid. We hypothesized that styloid process anatomy may be a risk factor for dissection. Methods: We performed a retrospective case-control study comparing patients with carotid artery dissection to control patients without dissection. Cases were identified by searching our hospital radiology database from 2001-2009 for all patients with unilateral cervical carotid artery dissection on CT angiography (CTA). Controls were selected from patients who underwent CTA and were explicitly noted to lack carotid dissection, and were matched by sex and age. Two observers blinded to radiology reports measured bilateral styloid length, angulation relative to midline structures, and proximity to the carotid artery lumen by review of axial CTA images. The length of the styloid was calculated by three-dimensional linear approximation, and values were averaged between observers. Results: Fifty-one cases of dissection were identified and matched with 51 controls (53% male, mean age 55.2 Ϯ 14.7 years for both). Interobserver correlation was high (rϾ0.86) for all measurements. In cases and controls combined, there was substantial variability in styloid process length (range 4.6 to 58.5 mm) and angulation relative to midline (range 14°to 104°), but styloid length (rϭ0.83) and angulation (rϭ0.77) were highly correlated when comparing the left and right sides. In cases, there was no difference comparing length ipsilateral to dissection to the contralateral side (mean length 30.1 vs. 29.1 mm, pϭ0.49) or angulation relative to midline between ipsilateral and contralateral processes (45°vs. 43°, pϭ0.57). The styloid process ipsilateral to the dissection was longer in cases than controls (mean length 30.1 vs. 27.0 mm, pϭ0.03). For every mm increased styloid length, there was an OR for dissection of 1.07 (95% CI 1.003 -1.13, pϭ0.04). In the top quartile of styloid length (Ͼ30.7 mm) compared to the bottom three quartiles, the OR for dissection was 2.9 (95% CI 1.1 -7.6, pϭ0.02). There was no difference in styloid angulation relative to midline between cases and controls (45°vs. 40°, pϭ0.21). In many cases, measurement of proximity of the styloid to the carotid artery ipsilateral to dissection was limited by pseudoaneurysm, stenosis, or occlusion. There was moderate correlation (rϭ0.33) in proximity measurements in controls between sides, allowing consideration of the contralateral side as a proxy for ipsilateral anatomy. The contralateral styloid of cases was not significantly closer to the artery than controls (4.4 vs. 5.2 mm, pϭ0.12). Conclusion: This study suggests that elongation of the styloid process is a risk factor for carotid dissection.

Author Disclosures: J.M. Raser: None. M.T. Mullen: None. B.L. Cucchiara: None. S.E. Kasner: None. S.R. Messe: None.

W P101 Differential Association of Lipid Index in Extracranial and Intracranial Atherosclerosis

Mi-Young Oh, Beom Joon Kim, Wi-Sun Ryu, Seung-Hoon Lee, Byung-Woo Yoon; Seoul National Univ Hosp, Seoul, Korea, Democratic People's Republic of Background: Intracranial and extracranial vascular beds had dissimilar histological characteristics. Atherosclerotic change would involve each of them in a different manner. Several studies to investigate the risk factors of intracranial large artery atherosclerosis(IC-LAA) revealed that hyperlipidemia did not have significant correlation with IC-LAA, in contrast to extracranial large artery Atherosclerosis (EC-LAA). The distinct effect of serum lipids on atherogenesis in the intracranial vascular bed from that in the extracranial vascular beds remained unclear. We assessed the hypothesis that serum lipid indices would be associated with the occurrence of EC-LAA but not with IC-LAA. Methods: We retrospectively analyzed 414 patients admitted with acute ischemic stroke from January, 2009 through November, 2009 to Seoul National University Hospital. Patient with incomplete workup or poorly qualified imaging were excluded (nϭ5). Baseline demographic and clinical information collected at admission. All patients had fasting lipid panels drawn the day after hospital admission. Low density lipoprotein (LDL) cholesterol was calculated. Non-high density lipoprotein (HDL) cholesterol, LDL:HDL,Total cholesterol (TC):HDL, Triglyceride(TG):HDL ratios were also investigated. Based on the clinical syndromes, the results of vascular studies, we divided patients into three groups: 1) those with occlusive lesion (Ն50% stenosis or occlusion) of extracranial portion of carotid artery and vertebral artery (EC-LAA group, nϭ115). 2) Those with occlusive lesion of proximal portion of middle cerebral artery, basilar artery, intracranial portion of internal carotid artery and VA (IC-LAA group, nϭ127). 3) Those without significant occlusive lesion (non-LAA group, nϭ167). Results: The level of TC, LDL-cholesterol, non-HDL cholesterol, LDL/HDL ratio was higher in the EC-LAA group than IC-LAA and non-LAA group. Multi nominal logistic regression analysis was used to assess the association between the lipid indices and the EC-LAA, IC-LAA groups. Non-LAA group was as a reference. EC-LAA group was associated with TC (ORϭ1.434 per 1mmol/L increase, 95% CI 1.081-1.904), LDL-cholesterol (ORϭ 1.464 per 1mmol/L increase, 95% CI 1.074-1.996) and non-HDL cholesterol (ORϭ1.434 per 1mmol/L increase, 95% CI 1.072-1.918). IC-LAA group did not achieve significant association with lipid indices.

Conclusion:

The results of our study may be regarded as an evidence of differential effect of cholesterol in the pathophysiology of atherosclerosis of extracranial and intracranial vasculature.

Author Disclosures: M. Oh: None. B. Kim: None. W. Ryu: None. S. Lee: None. B. Yoon: None.

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W P102 PFO Risk Factors and Onset Age of First-Ever Stroke in Young Adults

Ruijun Ji, Lee H Schwamm, M. Ahsan Pervez, Aneesh B Singhal; Massachusetts General Hosp, Boston, MA Background: Several studies have documented the association between patent foramen ovale (PFO) and cryptogenic stroke, particularly in young adults. Certain anatomic features or coagulation profiles are believed to increase stroke risk. We investigated the relationship between PFO and the age at onset of first-ever PFO-associated stroke in consecutive young adult stroke patients. Methods: We reviewed our Get with the Guidelines-Stroke database from 2005-2010 (nϭ2643 cases) to identify 215 consecutive inpatients, age 18-45y. Additional clinical details were abstracted from the medical records by a stroke neurologist. The following characteristics of the PFO (diagnosed by trans-esophageal or trans-thoracic echo with contrast) were recorded: degree of right-to-left (R-L) shunt (small vs. large), presence of R-L shunt at rest, and presence of an ASA. We also recorded the presence of deep vein thrombus (DVT) and abnormal hypercoagulable panel results (protein C, protein S, or anti-thrombin III deficiency; factor V Leiden mutation; prothrombin gene mutation; elevated antiphospholipid IgG antibody level). The mean onset age of first-ever stroke was compared between patients with and without these factors, and between patients with different numbers of risk factors. Results: A total of 199 patients (93%) underwent echo evaluation; R-L shunt was detected in 97 (49%). Of these, 82 were considered to have a 'PFO-associated' stroke; the rest were excluded due to established etiologies such as cerebral artery dissection. The mean onset age of first-ever stroke was significantly lower in patients with large R-L shunts, R-L shunts at rest, with DVT, or abnormal hypercoagulable panel, as compared to patients with small R-L shunts, R-L shunt only with Valsalva, absence of DVT, or negative hypercoagulable lab abnormalities, respectively (Fig. 1). Patients with or without concomitant ASA had no significant difference in the mean age at onset (pϭ0.53). Patients with Ͼ2 risk factors had an earlier onset age as compared to patients with 0-1 risk factors (35Ϯ8 vs. 39Ϯ7 yr, pϭ0.02, Fig. 2). Conclusion: These data suggest that stroke risk in patients with PFO, as measured by onset age, may be increased in the presence of certain anatomic and lab profiles. Our results may have therapeutic implications. Further research is warranted.

W P103 Trends In Pregnancy Hospitalizations That Included A Stroke In The United States From 1994 To 2007: Reasons For Concerns?

Elena Kuklina, Xin Tong, Pooja Bansil, Mary G George, William M Callaghan; Cntr for Disease Prevention and Control, Atlanta, GA Background and Purpose: Despite the encouraging decline in overall stroke incidence and mortality among adults in the developed countries, recently concern that trends in young adults may be less favorable. Given a well documented increase on the prevalence of risk factors for stroke among pregnant women in the United States, we investigated the hypothesis of increasing trends among this group in a large nationwide dataset. Methods: Hospital discharge data were obtained from the Nationwide Inpatient Sample developed as part of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. Pregnancy-related hospitalizations with stroke were identified using the International Classification of Diseases, Ninth Revision (ICD-9-CM). All statistical analyses accounted for the complex sampling design of the data source. Results: Between 1994Between -1995Between and 2006Between -2007, the rate (per 1,000 deliveries) of any stroke (hemorrhagic, ischemic, transient ischemic attack, cerebral venous thrombosis, or unspecified) among antenatal hospitalizations increased by 47% (from 0.15 to 0.22 per 1000 deliveries) and by 83% (from 0.12 to 0.22 per 1000 deliveries) among postpartum hospitalizations while remaining steady at 0.27 for delivery hospitalizations. In 2006-2007, about 32% and 53% of antenatal and postpartum hospitalizations with stroke, respectively, had indications for hypertensive disorders or chronic heart disease or heart disease. Changes in the prevalence of these problems from 1994-1995 to 2006-2007 explained almost all of the increase in postpartum hospitalizations with stroke during the same period. Conclusions: Our results have demonstrated an increasing trend in the rate of pregnancy-related hospitalizations with stroke in the United States, especially during the postpartum period, from 1994-1995 to 2006-2007. Author Disclosures: E. Kuklina: None. X. Tong: None. P. Bansil: None. M.G. George: None. W.M. Callaghan: None.

W P104 Stroke and Major Adverse Cardiac Events and Mortality in Peripartum Lupus Patients: A Population-Based Study

Pao Hsien Chu, Chang Gung Memorial Hospital, Taipei, Taiwan; Chao-Hsiun Tang; Taipei Med Univ, Sch of Health Care Administration, Taipei, Taiwan Objectives: To determine the incidence of stroke and the other major adverse cardiac events (MACE) and mortality in peripartum systemic lupus erythematosus (SLE) patients in Taiwan. Methods_ A population-based cohort study was performed on 1,132,089 parturients from 1999 to 2003 using a dataset linking birth. The Kaplan-Meier method was used to estimate the cumulated MACE-free rates and survival rates, and the log-rank test was used to examine the effect of SLE on the incidence of MACE and mortality. Cox-proportional hazard regression modeling incorporating sociodemographic factors and obstetric complications was used to determine the adjusted hazard ratios (HR) of SLE on the risk of MACE and mortality among peripartum women. Results: The incidence rate of any MACE and mortality among the peripartum women in the lupus group was 194.67 and 438.82 per 100,000 patient years respectively. Compared to women without SLE, peripartum women with SLE had higher MACE, including stroke (HR 8.02, CI 3.79-16.99, PϽ0.0001), myocardial infarction, (HR, 54.43, CI 16.04-184.78, PϽ0.0001), heart failure (HR 11.10, CI 2.71-45.52, PϽ0.0001), percutaneous coronary intervention (HR 228.32, CI 43.34-1203.00, PϽ0.0001), thrombolysis therapy (HR 110.88,PϽ0.0001), any MACE (HR 9.95, CI 5.60-17.67, PϽ0.0001), and maternal death (HR 11.68,PϽ0.0001). Their greater risk remained significant at least 12 months postpartum. Conclusions: Although stroke, MACE and mortality are rare events in women of reproductive age, they are increased about ten-fold among peripartum women with lupus. Clinicians would be well advised to pay attention to the possibility of MACE in lupus patients even after successful delivery.

Author Disclosures: P. Chu: None. C. Tang: None.

W P105 Trends in Substance Abuse and Stroke: A Population-Based Study

Felipe De Los Rios La Rosa, Univ of Cincinnati, Cincinnati, OH; Jane Khoury, Cincinnati Children's Hosp, Cincinnati, OH; Kathleen Alwell, Charles J Moomaw, Dawn Kleindorfer, Joseph P Broderick, Daniel Woo, Matthew L Flaherty, Pooja Khatri, Opeolu Adeoye, Simona Ferioli, Jane Eilerman, Brett M Kissela; Univ of Cincinnati, Cincinnati, OH Introduction: Currently, the literature suggest that adults aged less than 45 years old represent about 5% of the stroke population. This figure has been rising over time in our region, where we have reported an increase from 4.5% in 1993-94 to 7.3% in 2005. Reasons for this increase are unclear, however increased use of recreational substances that have the potential to cause stroke is one possibility. We attempt to describe substance abuse trends in stroke patients within the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS), a populationbased study of stroke incidence. Methods: We used ICD-9 discharge codes 430-436 to ascertain potential stroke events during three one-year study periods (7/93-6/94, 1999, 2005) among residents of 5 counties that comprise the largely biracial study population of 1.3 million. All potential cases underwent medical record abstraction, and then physician review to determine case vs. not a case, and to further classify stroke subtype. Research nurses abstracted data from the medical record; substance abuse items included street drug, smoking, and alcohol use. Smoking was defined as current if present within the last 3 months. Alcohol abuse was present if there was consumption of 3 or more servings per day, or if heavy use was documented in the chart. Street drug use was defined as use of a substance reported in the chart or positive urine/blood test. Results: Over the 3 periods, there was a slight increase in current smoking (21%, 21%, and 24%, respectively), no change in alcohol abuse (5%-6% for all 3 periods), and an increase in street drug abuse (0.5% to 1.5% to 4.6%). In 2005, among 170 subjects with street drug abuse, 47% used marijuana, 35% used cocaine/crack, and 18% other; 76% had positive urine/blood testing. Smoking and alcohol consumption at time of stroke peaked in the 35-65 year range, while street drug abuse was clearly more prevalent at youngest ages, falling off precipitously after age 55 (Table ). Ischemic strokes (IS) accounted for 61% of events where substance abuse was reported. Current smoking was reported in 18-25% in subjects with intracerebral hemorrhage (ICH) and (IS), but in 40% of subarachnoid hemorrhages (SAH). Alcohol abuse was reported in 6-8% of all stroke types. Street drug abuse was reported in 10% of ICH, 5% of IS, and 14% of SAH. Conclusions: We found that even though smoking and alcohol use have remained relatively stable, street drug use showed an increase across study periods. The number of stroke subjects with street drug abuse is not trivial and this may contribute to the increased stroke incidence in younger age groups over time seen within our region.

W P106 Effect of Caffeine Consumption on Carotid Intimal Media Thickness and Risk of Stroke: The Framingham Offspring Study

Hebah M Hefzy, Lonnie Schultz, Henry Ford Hosp, Detroit, MI; Joseph F Polak, Tufts Univ Sch of Medicine, Boston, MA; Andrew N Russman; Henry Ford Hosp, Detroit, MI Background/Purpose: Recent studies support the hypothesis that caffeinated coffee consumption may reduce the risk of stroke. The association between caffeinated coffee consumption and reduction in cerebrovascular events remains unclear. Carotid intima media thickness (IMT) is a validated measure of atherosclerosis that predicts incident stroke and myocardial infarction. We sought to explore the association between caffeinated beverage use and carotid IMT with a goal of investigating one possible mechanism by which caffeinated beverages reduce the risk of stroke. Methods: We studied members of the Framingham Offspring Cohort (examination 6) who had carotid ultrasonography performed. Data regarding caffeine use, comorbidities predisposing to stroke and atherosclerotic disease, and factors influencing carotid IMT were obtained. Statistical analyses were done to evaluate the cross sectional relationship of caffeinated beverage use and carotid IMT and time to event analyses assessing the relationship of caffeinated beverage use and carotid IMT with the outcomes of death, stroke, and myocardial infarction (MI). Results: 3,380 patients were included. On multivariate analysis, after correcting for age, sex, body mass index, diabetes mellitus, hypertension, and smoking, higher mean of the maximum common carotid IMT values during diastole were noted among caffeine and coffee drinkers (p ϭ 0.037 and 0.0088 respectively). The mean of the maximum common carotid IMT was significantly associated with a higher risk of MI (adjusted HR ϭ 1.10, 95% CI 1.03-1.18, pϭ0.0032), stroke (adjusted HR ϭ 1.12, 95% CI 1.02-1.24, pϭ0.0234) and death (adjusted HR ϭ1.09, 95% CI 1.03-1.16, pϭ0.0050). Hazard ratios correspond to a 0.2 mm increase in carotid IMT. Increasing mean of the maximum internal carotid IMT measurements were also significantly associated with a greater risk for MI and death, but not stroke. Conclusions: Our results confirm previous findings that increasing carotid IMT is associated with stroke, death, and MI. These preliminary findings suggest that the mechanism by which caffeine and coffee consumption reduce the risk of stroke is not related to a beneficial effect on carotid IMT. Further investigations into the relationship between caffeine consumption and its role in the reduction of cerebrovascular events are necessary.

Author Disclosures: H.M. Hefzy: None. L. Schultz: None. J.F. Polak: None. A.N. Russman: Research Grant; Modest; Harris Stroke Fund, NINDS NETT program. Speakers; Significant; Pfizer, Boehringer Ingelheim Pharmaceuticals. Consultant/Advisory Board; Significant; Abbott Vascular.

W P107 Cerebral Venous Thrombosis in a Mexican Multicenter Registry of Cerebrovascular Disease: The RENAMEVASC Study

Jose ´Ruiz-Sandoval, Erwin Chiquete, L. Jacqueline Ban ˜uelos-Becerra, Carolina Torres-Anguiano, Christian Gonza ´lez-Padilla, Hosp Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Mexico; Antonio Arauz, Instituto Nacional de Neurologı ´a y Neurocirugı ´a, Mexico City, Mexico; Carlos Cantu ´, Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n, Me ´xico, City, Mexico; Luis M Murillo-Bonilla, Instituto Panvascular de Occidente, Guadalajara, Mexico; Jorge Villarreal-Careaga, Hosp General de Culiaca ´n, Culiaca ´n, Sinaloa, Mexico; Fernando Barinagarrementeria, Hosp Angeles de Quere ´taro, Quere ´taro, Mexico; RENAMEVASC investigators Background: Cerebral venous thrombosis (CVT) is the rarest form of cerebrovascular disease. Few studies exist on all-type acute stroke addressing the relative frequency, characteristics and outcome of hospitalized patients with CVT. We aimed to describe a first-step stroke surveillance system on CVT. Methods: CVT cases were selected from the RENAMEVASC register, conducted during two years in 25 centers. Risk factors, neuroimaging and 30-day outcome as assessed by the modified Rankin scale (mRS) were analyzed. Results: From 2000 all-type acute cerebrovascular disease patients, 59 (3%; 95% CI: 2.3-3.8%) had CVT (50 women, female-to-men ratio 5.5/1, mean age 33 years). Puerperium (42%), contraceptive use (18%) and pregnancy (12%) were the main risk factors in women. In 67% men CVT was registered as idiopathic. No thrombophilia assessment was practiced. Longitudinal superior sinus was the most frequent CVT location (78%). Extensive (Ͼ5 cm) venous infarction occurred in 36% cases. Most patients (64%) were treated with heparin or heparinoids. Decompressive craniectomy occurred in 3%. Thrombolysis was not performed. Systemic venous thromboembolism (14%), endotracheal intubation (14%) and pneumonia (8%) were the main in-hospital complications. Thirty-day case fatality rate was 3% (95% CI: 0.23%-12.2%), inversely associated with Glasgow coma scale (GCS). Functional independency (mRS 0-2) was attained in 73%, being positively associated with increasing GCS, and negatively associated with age. Conclusions: Relative frequency of CVT in hospitalized Mexican patients is higher than in other registries. Thrombophilia assessment was suboptimal. In this primarily young cohort, acute case fatality rate is low, but at expense of more neurologic impairments.

W P108 Insufficient Platelet Inhibition Is Related With Acute Cerebral Infarction After Coronary Artery Angiography.

Bum Joon Kim, Eun-Jae Lee, YoungRok Do, Dept of Neurology. Asan Med Cntr, Seoul, Korea, Republic of; Seong Hwan Lee, Dept of Cardiology. Asan Med Cntr, Seoul, Korea, Republic of; Dong-Wha Kang, Sun Uk Kwon; Dept of Neurology. Asan Med Cntr, Seoul, Korea, Republic of Coronary artery angiography (CAG) occasionally causes cerebral infarction. The dislodgement of atheroma form the aortic arch during CAG has been raised as the most plausible mechanism, but the exact mechanisms of the infarction have not been clearly verified yet. We hypothesized that platelet aggregation would be one of the most important mechanisms of CAG related cerebral infarction. In phase 1 study, among the patients who were admitted to Asan Medical Center (AMC) due to acute coronary syndrome between Jan 2006 and July 2006, we retrospectively reviewed DWI and MR angiography, which was performed within 7 days after CAG, as a presurgical evaluation of coronary artery bypass graft (CABG) surgery. We analyzed the incidence and lesion patterns of acute ischemic lesions (AILs) defined by high signal intensity lesions on DWI, which represents acute cerebral infarction. In phase 2 study, we have prospectively recruited 102 patients who were scheduled for CABG after diagnostic CAG in AMC between July 2007 and June 2009. The extent of platelet inhibition by anti-platelet agents was measured using aspirin reaction unit (ARU), P 2 Y 12 reaction unit (PRU) and % inhibition within 6 hours after CAG. DWI and MR angiography were performed within 7 days after CAG. These parameters were compared between the two groups divided by the occurrence of AILs after CAG. AILs were observed in 45 patients (15.6%) in phase 1 study and 17 patients (16.7%) from phase 2 study. Majority of the AILs were located at the cortex (88.9%), and slightly more frequently observed in right carotid circulation (55.6%) than in left carotid (30.8%) or in vertebra-basilar circulation (13.7%). ARU and PRU were significantly higher in the patients with post-CAG acute cerebral infarction than those without (ARU: 489.5Ϯ71.5 vs 446.3Ϯ53.5; pϭ0.02, PRU: 351.7Ϯ65.2 vs 330.7Ϯ77.0; pϭ0.002). % inhibition, which represents the portion of inhibited platelets, was lower in the patients with post-CAG acute cerebral infarction (6.1Ϯ10.7 vs 15.3Ϯ17.8; pϭ0.02). WBC count (OR 1.354 95% CI 1.072-1.711; pϭ0.01) and ARU (OR 1.014 95% CI 1.004-1.024; pϭ0.006) were independently related to the occurrence of post-CAG acute cerebral infarction from the result of multivariate analysis. This study reveals that insufficient platelet inhibition by anti-platelet agents can cause acute cerebral infarction after CAG.

W P109 The Unchanging Risk of Stroke Following Cardiac Valve Replacement

Colleen G Lechtenberg, Richard M Dubinsky; Univ of Kansas, Kansas City, KS Objective: To determine if the incidence of stroke following cardiac valve replacement has changed over 20 years. Background: Heart valve replacement surgeries account for 20% of all cardiac procedures and the number is expected to rise as the population ages. (Birkmeyer, NEJM 2002) Our previous work showed the rate of stroke after CABG was 1.4% (Dubinsky, Neurology 2007). Methods: Retrospective cohort analysis of the Nationwide Inpatient Sample (NIS, HCUP, AGRQ.gov), a 20% stratified sample of US hospital admissions, from 1988 -2007. All adult admission records for cardiac valve surgery were analyzed. Records were divided into five-year cohorts to examine for trends over time. Logistic regression was used to control for confounders and the Charlson score for comorbidities. Because of multiple comparisons and the large number of records, p was set a priori at Ͻ .0001. Results: Of 311,945 records, 47.22% were women. The rate of post-operative stroke changed over time : 1988-92: 3.47%, 1993-7: 4.50%, 1998-02: 4.20%, 2003-7: 3.45%.; while the median age and comorbidities increased, length of stay and mortality decreased, and the proportion discharged to nursing homes increased. The rate of post-operative stroke was higher for women, those with Ͼ median age, more comorbidities, and for the middle two cohorts. Logistic regression for post-operative stroke: male vs. female 0.94 (95% CI 0.90-0.97); age Ͼ median 1.27 (1.22-1.32); Charlson score Ͼ 4 compared to 0: 11.41 (10.56-12.3), 3 vs 0: 7.59(7.00-8.20), 2 vs 0: 5.08 (4.70-5.47), 1 vs 0: 3.22(3.00-3.47); 2003-7 vs 1988-1992:0.61(0.57-0.66), 1998-02:0.87(0.82-0.93), 1993-7: 1.01(0.95-1.08). Conclusion: Over the last 20 years, the incidence of stroke following valvular surgery has changed little and remains three times that seen after CABG. Advances in cardiac surgical techniques have resulted in older patients with more comorbidities undergoing valve replacement surgery.

Author Disclosures: C.G. Lechtenberg: None. R.M. Dubinsky: None.

W P110 Impact Of CHADS 2 Score On Severity And Outcome Of Ischemic Stroke

Dohoung Kim, Jong-Won Chung, Chi Kyung Kim, Wi-Sun Ryu, Eun-Sun Park, Seung-Hoon Lee; Seoul National Univ Hosp, Seoul, Korea, Republic of Background: CHADS 2 is a widely used system for estimating risks of incident stroke in patients with atrial fibrillation (AF). However, effects of CHADS 2 score on stroke severity and outcome in patients with stroke due to AF has not been elucidated yet. Method: We enrolled acute ischemic stroke patients with AF who visited the stroke unit within 7 days after onset between October 2002 and September 2008. The CHADS 2 scores were categorized into three groups: 0 point, low risk; 1-2, intermediate risk; 3-6 high risk. Poor neurological state was defined using the established systems: the National Institute of Health Stroke Scale (NIHSS) scoreϾ3 and the modified Rankin Scale (mRS) scoreϾ2 at discharge. Mortality information was obtained until the end of 2008. Results: A total of 298 patients with AF-related stroke were included in this study. The high risk CHADS 2 scores at admission were a powerful predictor of poor neurological outcome [for NIHSS: odds ratio (OR) 2.68, 95% confidence interval (CI) 1.11-6.44; for mRS: OR 2.97, 95% CI 1.23-7.16] after control of all possible confounders. In addition, the high risk CHADS 2 scores were an independent predictor of all-cause death during the follow-up (hazard ratio (HR) 3.01, 95% CI 1.18-7.65) and vascular death (HR, 12.25, 95% CI, 1.50-99.90). Conclusion: Although the CHADS 2 was originally designed in order to find patients with future risk of stroke, our study shows that this system may be used to predict poor neurological outcome after AF-related stroke.

Author Disclosures: D. Kim: None. J. Chung: None. C. Kim: None. W. Ryu: None. E. Park: None. S. Lee: None.

W P111 Predictive Value of The Essen Stroke Risk Score for the recurrence of non-cardioembolic stroke in Japanese patients. The Results from the EVEREST (Effective Vascular Event REduction after STroke) registry

Yasushi Okada, Clinical Rsch Institute and Cerebrovascular Medicine, Kyushu Med Cntr, Fukuoka, Japan; the EVEREST Steering Committee Background/Aim: The Essen Stroke Risk Score (ESRS) was derived from cerebrovascular patients in the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events) trial. It was proved to be useful for secondary prevention strategies using the REACH (REduction of Atherothrombosis for Continued Health) registry data. However, it was still unknown whether the score is applicable in Japanese patients. We aimed to confirm clinical predictability of the ESRS in the EVEREST (Effective Vascular Event REduction after STroke) cohort that involved 3,452 Japanese outpatients with non-cardioembolic stroke (Ischemic Stroke; IS) of low to moderate disability from 2006 to 2008. Recurrent IS at one year follow-up was used as a primary outcome. Methods: To calculate annualized event rate, the total number of events was divided by total number of patient-year in each category of ESRS points. Cummulative event rate in each category of ESRS was compared by log-rank test. Results: Of the 3,452 the patients initially recruited, one year outcome data was available in 3,411 patients (follow-up rate 98.8%) Patient characteristics at baseline were as follows: mean age of 69 years, 67% of men, 75% of hypertension, 26% of diabetes mellitus, 2.2% of atrial fibrillation, and 23% of current smokers. ESRS distributed from 1 to 7 points, while 59% of them were with point 3 or less. There were 10 fatal strokes (5 from ischemic, 5 from hemorrhagic) and 5 cases of cardiovascular deaths, but no deaths from myocardial infarction. IS recurrence occurred in 157 cases (4.5%) and hemorrhagic stroke occurred in 15 (0.4%) during one-year follow-up. Annualized event rates were 3.27%, 3.15%, 3.85%, 5.49%, 6.14%, 5.28% for ESRSϭ1, 2, 3, 4, 5, 6/7, respectively (Pϭ0.0051, for the difference among ESRS groups). Patients with ESRS of 4 or more exhibited significantly higher events rate of IS recurrence than others (Pϭ0.0007). Conclusions: Similar to the result from the REACH registry, the ESRS may be used as a useful predictor for IS recurrence in Japanese stroke patients of the EVEREST registry.

Author Disclosures: Y. Okada: Research Grant; Significant; sanofi-aventis KK.

W P112 Albuminuria, Kidney Function and Risk of Stroke in the REGARDS Cohort

Suzanne E Judd, David G Warnock, Paul Muntner, UAB, Birmingham, AL; William M McClellan, Emory Univ, Atlanta, GA; Dana Rizk, UAB, Birmingham, AL; Mary Cushman, Univ of Vermont, Burlington, VT; Virginia Howard, George Howard; UAB, Birmingham, AL Background: Chronic kidney disease has been associated with increased stroke risk but previous studies have not evaluated the independent contributions of urinary albumin/creatinine ratio (ACR: mg/gm) and reduced estimated glomerular filtration rate (eGFR: ml/min/1.73 m 2 ) in the same cohort. Methods: The association between ACR and eGFR with incident stroke was evaluated among participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS), a national population-based longitudinal cohort of 30,239 blacks and whites, aged Ͼϭ45, enrolled 2003-2007. After excluding those with a history of stroke or end stage renal disease, the analysis population included 24636 participants. Blood, a spot morning urine, and physical measurements were collected during an in-home visit. Participants are followed every 6 months to identify incident strokes which were physician verified. The hazard ratio for incident stroke was calculated for eGFR and log-transformed ACR modeled as continuous variables normalized by standard deviation (SD). Adjustment was made for baseline age, sex, race, age-race interaction, anti-hypertensive medication use, systolic blood pressure, smoking, diabetes, history of heart disease, and body mass index. Results: Among REGARDS participants with eGFR Ͼϭ90, higher ACR was associated with an increased multivariable adjusted hazard ratio for stroke (HRϭ1.67 (95% CI 1.33, 2.08) for each SD increase in log transformed ACR. This association was weaker for individuals with lower eGFR levels (p for interaction 0.02). In contrast, there was no association of eGFR and stroke across all strata of ACR (figure). Each SD change in eGFR was associated with stroke only in univariate models (HRϭ1.35, 95% CI 1.23, 1.47). After adjustment for age, race, and sex this association was no longer present (HRϭ1.08, 95% CI 0.97, 1.20). Conslusions: Among REGARDS participants ACR was associated with risk of incident stroke, independent of other factors, and only in those with normal eGFR. eGFR was not associated with stroke risk after accounting for ACR and other risk factors, in particular age, race and sex. Lack of association of ACR with stroke among those with eGFR Ͻ60 ml/min/1.73 m 2 may be due to competing risks of mortality, coronary events or incident ESRD. These findings suggest that measurement of ACR might be helpful to assess stroke risk in adults with normal kidney function.

Diabetes is a risk factor for both first and recurrent stroke. We previously showed that particularly type 1 diabetes (T1DM) is independently associated with 5-year risk of death and recurrent vascular events in young adults after ischemic stroke, while T2DM is not. We compared demographics and stroke type (TOAST) with outcome clinical features and prognosis between T1DM-, T2DM-, and nondiabetic patients using data of 1008 consecutive patients (age 15-49) with first-ever ischemic stroke (Helsinki Young Stroke Registry). Kaplan Meier statistics allowed risk estimations of (1) nonfatal or fatal recurrent ischemic stroke; (2) nonfatal or fatal myocardial infarction (MI), other arterial thrombotic event or revascularization procedure; (3) composite vascular endpoint (MI, any stroke, revascularization, or vascular death); and (4) death of any cause. Multivariate Cox proportional hazards function was used to investigate independent association of demographics and stroke type with outcomes 1 and 3 in T1DM-patients. Patients with T1DM (nϭ44) had more frequently hypertension and cardiovascular disease at baseline and their index stroke was more often related to small-vessel disease compared with nondiabetic patients (nϭ904). Compared with T2DM-patients (nϭ60), T1DMpatients were younger, less obese, but had more frequently cardiovascular disease and their index stroke was small-vessel stroke. After a mean follow-up of 9.0 (Ϯ3.8) years in survivors, patients with T1DM were at considerably higher risk of all studied outcomes (PϽ0.001 for all endpoints) compared with nondiabetic subjects, and at higher risk of MI/other arterial events and particularly composite vascular events (65.6% at 10 years) compared with T2DM-patients (46.9% at 10 years). In univariate comparison, female gender, longer diabetes duration, and retinopathy were associated with recurrent ischemic stroke. Female gender, dyslipidemia, hypertension, retinopathy, longer diabetes duration, and worse renal function were related to higher risk of a composite vascular event. In multivariate analysis, female gender (odds ratio 4.32; 95% confidence interval 1.48-12.58) and baseline retinopathy (6.33; 1.40-28.58) were associated with recurrent nonfatal or fatal ischemic stroke while dyslipidemia was associated with the composite vascular endpoint (3.28; 1.28-8.41). We conclude that young adults with first-ever ischemic stroke and T1DM had a distinct risk factor and etiologic profile compared with nondiabetic subjects and with T2DM-patients_and had strikingly high long-term risk of vascular events. Retinopathy had the strongest association with recurrent ischemic stroke and may reflect a generalized and active form of small-vessel disease.

Author Disclosures: R. Liebkind: None. J. Putaala: None. D. Gordin: None. L.M. Thorn: None. E. Haapaniemi: None. C. Forsblom: None. P. Groop: None. M. Kaste: None. T. Tatlisumak: None.

W P115 Effects Of Obesity On Clinical Outcome In Patients With Brain Infarction Fukuoka Stroke Registry

Tsuyoshi Omae, Imazu Red Cross Hosp, Fukuoka, Japan; Masahiro Kamouchi, Takanari Kitazono; Medicine and Clinical Science, Graduate Sch of Med Sciencies, Kyushu Univ, Fukuoka, Japan Background: Although obesity is recognized as a cardiovascular risk factor, it is not fully understood whether obesity is associated with a worse clinical outcome. An obesity paradox, a decrease in mortality with increasing BMI, has been shown in patients with cardiovascular diseases; however, it is not reported in patients with cerebrovascular disease. The aim of this study is to determine if BMI influences the clinical outcome of the patients with acute brain infarction. Methods: The Fukuoka Stroke Registry is a multicenter epidemiological and observational study of acute stroke involved seven stroke centers in Fukuoka in south part of Japan, established on 2007. This study was approved of the local ethic committee of Kyushu University and each hospital. FSR is consisted of two database systems, i.e. prospective and retrospective databases. Prospective database recruited consecutive patients with acute stroke within seven days from the onset. At the hospitalization, written informed consent was obtained. The database collected data on patient demographics, medical history and outcomes. Moreover, long-term prognosis was collected. We analyzed the prospective data of these patients with first-ever brain infarction. BMI, subtype of brain infarction (athelotholombotic (ATBI), lacunar (Lac), cardioembolic (CE) and others), age and presence of risk factors (hypertension, diabetes mellitus and hyperlipidemia) were compared scores of modified Rankin scale (mRankin) at 1 year after onset. We defined good prognosis as mRankin 0 and 1 and poor prognosis as 2 to 6. Results: 1,432 patients with first-ever brain infarction were registered to FSR (from June 2007 to June 2009). BMI was significantly higher in the patients with good prognosis than those with poor prognosis (23.7Ϯ3.6 kg/m2 vs 22.2Ϯ4.0, PϽ0.01). Both younger age (66.9 yearsϮ11.5 vs. 76.0Ϯ11.2, PϽ0.01) and presence of hyperlipidemia (53.3% vs. 39.8%, PϽ0.01) were related with good prognosis. Neither hypertension nor diabetes influenced the prognosis. Distribution of the stroke subtype was significantly difference between good (18.6% in ATBI, 36.0% in Lac, 15.6% in CE and 29.9% in other) and poor prognosis (28.6%, 17.3%, 30.3%, 23.9%, respectively). Multivariable analysis showed that BMI, age, stroke subtype and presence of hyperlipidemia were independent predictors of one-year prognosis. Conclusions: In our stroke registry, high BMI is associated with good prognosis at one year after onset in patients with first-ever brain infarction. The relationship between BMI and outcome in patients with cerebrovascular disease is complex, and further study is important to elucidate the precise relationship.

Author Disclosures: T. Omae: None. M. Kamouchi: None. T. Kitazono: None.

W P116 Influence of Body Mass Index (BMI) on Arterial Stiffness

Sandra Morovic, Zlatko Trkanjec, Vida Demarin; Univ Hosp Sestre milosrdnice, Zagreb, Croatia Hypothesis: Increased body weight (BMI) is an independent risk factor for stroke. We believe that BMI is associated with arterial stiffness. The aim of this study was to assess influence of growing BMI on arterial stiffness. Patients and Methods: Subjects were grouped into four BMI categories; normal weight (29 subjects, BMIϭ18.5-24.9), overweight (43 subjects, BMIϭ25.0-29.9), obese class I (23 subjects, BMIϭ30.0-34.9), and obese class II (10 subjects, BMIϭ35.0-39.9). There were no subjects in severely underweight (BMI40) categories. Arterial stiffness was measured in all subjects by Duplex sonography, e-Tracking mode on Aloka prosound a ´7, in both common carotid arteries, 3 cm proximal to carotid bifurcation. Logistic regression analysis was performed, adjusting for blood pressure, diabetes and age. Adjustment for cholesterol levels was not possible due to insufficient data. Level of significance in logistic regression for right ACC was PϽ0.028, and for left ACC was PϽ0.206. Results: There were 105 subjects, 54 females, and 51 males. Mean age was 58.4 years. Average BMI in four BMI categories was 22.6 in normal weight (BMIϭ18.5-24.9), 27.3 in overweight (BMIϭ25.0-29.9), 32.7 in obese class I (BMIϭ30.0-34.9), and 36.9 in obese class II (BMIϭ35.0-39.9). Average beta-stiffness measurements on common carotid arteries were for BMI normal weight group 7. 96 (right ACC 7.81,left ACC 8.11),overweight group 8.77 (right ACC 8.85,left ACC 8.69), obese class I group 9.26 (right ACC 8.98, left ACC 9.47), and obese class II group 13.05 (right ACC 12.31,left ACC 13.5). In the regression analysis adjusted for confounding factors, the association of BMI and arterial stiffness remained significant (right ACC PϽ0.0055; left ACC PϽ0.0007). Conclusion: There is significant association of BMI with arterial stiffness. We speculate that arterial stiffness is a marker of stroke risk and that a decrease in stiffness may precede a decrease in stroke risk.

Author Disclosures: S. Morovic: None. Z. Trkanjec: None. V. Demarin: None.

Background: Initial NIHSSS is highly predictive of outcome after ischemic stroke (IS). However after mild IS inconsistent prediction exists as well as some bias towards language symptoms. Objective Using latent profile analysis, we examined if grouping strokes by presence of individual NIHSSS symptoms could provide additional prognostic information beyond the total NIHSSS. Methods We identified all cases of clinically defined IS in 1999 and 2005 within a biracial population of 1.3 million. Research nurses extracted information from medical charts including retrospective NIHSSS. Latent profile analysis was used to form groups of 2005 IS patients with similar NIHSSS item responses; heterogeneity of NIHSSS responses is minimized within and maximized across profiles. Profile group was used as an independent predictor of patient outcome, 90 day and overall mortality and modified Rankin (mRS) at discharge Յ1, using Kaplan-Meier and logistic regression. IS cases occurring during 1999 were used for validation of the profiles. Results: A total of 2,251 clinically defined IS cases were identified in 2005, 2,468 in 1999. Fifteen cases in 2005 and 40 in 1999 were excluded due to missing NIHSSS. For patients with more than one IS occurrence during the year, the NIHSSS from the first IS was used. The 2005 IS patients had median age 72 years, and were 22% black, 56% female; 1999 patients were similar. Median NIHSSS for both study periods was 4 (IQR 2, 7). Six distinct profiles (A -F) were identified within the 2005 IS cases (Figure 1). Between the two most extreme profiles, 90 day mortality ranged from 55% in profile A to 5% in F, mRS at discharge Յ 1 was 0% for A vs. 34% for F. Profiles falling between these two extremes, C and D, both had median NIHSSS of 5, but different outcome rates for 90 day survival (C 23% vs. D 11%, p Ͻ 0.01) and discharge mRS Յ1 (C 5% vs. D 10%, pϭ0.04). Difference in 90 day survival remained significant after adjusting for age, race, and gender. C patients were more likely to have decreased level of consciousness and abnormal language, whereas D were more likely to have abnormal right arm and right leg motor function. Characterization of 1999 cases using the profiles yielded similar associations with outcome. Conclusions: We describe a novel profile method of analyzing baseline symptoms and severity of IS patients that provides additional information regarding outcome beyond the baseline NIHSSS. In particular, we found two symptom profiles with identical median NIHSSS but with widely disparate outcomes. Such profiles might be clinically useful for prognosis, and could conceivably be used in future clinical trial design.

Background: Death due to ischemic stroke has declined in the US over the past 50 years, although to varying degrees in different regions of the country. Because there is no national surveillance system, less is known about patterns of stroke incidence. Purpose: To estimate national and regional ischemic stroke incidence rates among the elderly in the US in 1996 and 2006 using administrative data. Methods: The study cohort included all fee-for-service Medicare beneficiaries Ͼϭage 68 years discharged with an incident ischemic stroke (ICD-9 primary codes 433, 434, 436, without a discharge diagnosis of ischemic stroke for 3 years prior to index event). A hierarchical Poisson model was constructed to estimate age-, sex-, and race-adjusted incidence rates nationally for the country's 306 hospital referral regions (HRRs) in 1996 and 2006. National maps were created to show HRR-specific rates categorized as being higher, no different, or lower than the national average using a significance level of 0.05. Results: We identified 244,232 incident ischemic stroke cases in 1996 and 245,882 in 2006. The mean age, sex-, and race-adjusted ischemic stroke incidence rates declined from 90.8Ϯ14.4 cases per 10,000 person-years in 1996 to 79. 3Ϯ19.2 in 2006 (Figure). Incidence varied by HRR during both periods, with higher rates in the Southeastern US. More HRRs had incidence rates higher than the national average in 2006 as compared with 1996 (44.1% in 2006, 34.6% in 1996). Similar proportions of HRRs had lower than average rates during each period (27.5% in 2006, 28.4% in 1996). Conclusions: Ischemic stroke incidence among the elderly declined in the US over the past decade suggesting improvements in primordial and primary prevention. Rates were not geographically uniform and were consistently higher in the Southeast. Understanding the reasons for this geographic disparity in stroke incidence might help to better target preventive interventions.

W P122 Risk Of Stroke Following Self-report Of Stroke, Tia Or Stroke Symptoms In The Regards Study

Suzanne E Judd, Univ of Alabama Birmingham, Birmingham, AL; Dawn O Kleindorfer, Univ of Cincinnati, Cincinnati, OH; Leslie A McClure, J D Rhodes, Univ of Alabama Birmingham, Birmingham, AL; Mary Cushman, Univ of Vermont, Burlington, VT; Virginia Howard, George Howard; Univ of Alabama Birmingham, Birmingham, AL Introduction: It is well known stroke and TIA are risk factors for subsequent stroke. However, no population studies have compared stroke risk in persons with previous stroke vs TIA, vs presence of stroke symptoms not diagnosed by a physician. We studied the risk of future stroke with increasing progression of symptom/diagnosis status: 1) asymptomatic (Asx), 2) those reporting stroke symptoms only (SS), 3) TIA, 4) stroke in the distant past (DS), and 5) recent stroke (RS). Methods: In 2003-2007 the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort enrolled 30,239 black and white Americans age 45 and older. Stroke status groups were self-reported during the baseline interview; DS and RS were defined as strokes occurring Ͼ5 or Ͻ5 years before baseline, respectively. SS were a history any of six sudden onset stroke symptoms. Stroke status categories were mutually exclusive using the hierarchy of Asx, SS, TIA, DS, RS (e.g. a participant reporting RS and TIA was classified as RS). Incident stroke was ascertained and validated during follow up. We derived Kaplan-Meier estimates of stroke risk, and used Cox proportional hazards models to obtain hazard ratios. Additional data were collected using a combination of in home assessment with a health professional and telephone interview. Results: With 4.4 Ϯ 1.6 years follow up and including 557 validated strokes, compared to Asx persons, SS, TIA, DS and RS all had increased risk of future stroke, with increasing magnitude of risk in each hierarchical group (see figure). Adjusting for age, race, sex, region, income, education, hypertension, diabetes, smoking status, dyslipidemia, atrial fibrillation, and history of cardiovascular disease, stroke risk was 1.3-fold increased for SS (95% CI 1.0, 1.7), 1.7-fold for TIA (95% CI 1.2, 2.5), 2.2-fold for DS (95% CI 1.5, 3.2) and3.0-fold for RS (95% CI 2.2, 4.1). Discussion: Results suggest a spectrum of risk from stroke symptoms to TIA, distant stroke, and recent strokes, and imply a need for establishing these categories in patients in order to prevent stroke. This paradigm could be tested in controlled clinical trials.

W P123 Mitral-Doppler Measurements are Weakly Correlated with the Risk of New-Onset Atrial Fibrillation in Patients with Cryptogenic Stroke

Luc Cormier, Cntr Hospier Universitaire de Sherbrooke, Sherbrooke, Canada; Nathalie Carrier, Serge Lepage, Jean-Franc ¸ois Roux, Felix Ayala-Paredes, Andreanne Jean, Hoa Do, Btissama Essadiqi, Paul Farand; CHUS, Sherbrooke, Canada Introduction: Paroxysmal atrial fibrillation is a frequent under-diagnosed etiology for cryptogenic stroke. While electrical manifestations of atrial fibrillation (AF) can easily be missed given the transient nature of this arrhythmia, recovery of the mechanical function of the atria has been shown to be a slower phenomenon. We hypothesized that, in patients in sinus rhythm following cryptogenic stroke, abnormal mitral-Doppler findings, such as small A-wave velocity and large E/A ratio, could predict the risk for stroke recurrence and new-onset AF. Method: A retrospective analysis of all subjects admitted at the Centre Hospitalier Universitaire de Sherbrooke with a diagnosis of cryptogenic ischemic stroke from January 1993 to August 2009 was conducted using the hospital database. Data from early echocardiography performed during initial stroke workup were recorded. Data collected included mitral-Doppler A-wave velocity, E-wave velocity and E/A ratio, and were correlated with the incidence of recurrent stroke and new-onset AF in the study population. Results: Out of 698 subjects meeting the inclusion criteria, 68 (9.7 %) had recurrent stroke and 98 (14 %) had new-onset AF detected after the index hospitalization. No statistically significant correlation was found between the risk of stroke recurrence and A-wave velocity (pϭ0.859) or E/A ratio (pϭ0.880). Moreover, new-onset AF did not correlate with either A-wave velocity (pϭ0.143) or E/A ratio (pϭ0.368). However, a multivariate logistic regression model showed that E/A ratio (ORϭ2.4), presence of high blood pressure (ORϭ1.7) and age over 60 years old (ORϭ1.1) were independent predictors of a new onset AF in the study population. Meanwhile, A-wave and E-wave velocity were not predictors of stroke recurrence. Conclusions: Mitral-Doppler E/A ratio is a weak clinical predictor of new-onset AF among patients with cryptogenic ischemic stroke. This observation suggests that unrecognized paroxysmal AF may be a less common cause of cryptogenic stroke than we think. It is also possible that atrial mechanical dysfunction is a poor indicator of recently converted AF. Also, the time to recovery of effective atrial mechanical after a newly converted AF may be shorter than that required to obtain the echocardiography. Finally, many of new onset AF episodes could be silent and were not recorded. However, Mitral-Doppler E/A ratio could be used in more complex models for predicting new onset AF and stroke recurrence.

W P124 Iphone and iPad Display of Acute Stroke CT Scans: Discrimination of Hemorrhage and Early Ischemic Changes

Xingzhi Guan, Jeffrey L Saver, Noriko Salamon, UCLA Stroke Cntr, Los Angeles,, CA; Farzad Buxey, UCLA Stroke Cntr, Los Angeles,, CA; Newsha Poursohi, UCLA Sch of Public Health, Los Angeles,, CA; Qing Hao, UCLA Stroke Cntr, Los Angeles,, CA; Nerses Sanossian, Univ of Southern California, Los Angeles,, CA; David S Liebeskind; UCLA Stroke Cntr, Los Angeles,, CA Background: Telestroke systems have recently expanded potential access to subspecialty stroke expertise around the clock at remote locations. Advances in technology now permit rapid transfer of medical images to portable devices for critical decisions about emergent stroke therapies, yet the quality of such interpretations remains unaddressed. We tested the diagnostic accuracy of remote image interpretation via two distinct handheld devices compared with in-hospital readings in a setting that simulated routine clinical practice. Methods: Noncontrast CT scans obtained on hospital arrival in 60 consecutive acute stroke patients within 3 hours of stroke symptom onset were analyzed. Scans were divided into 3 groups and loaded on different interpretation platforms: iPhone, iPad, and desktop computer. Three readers, including a neuroradiologist, a stroke neurologist imaging expert, and a general neurologist, separately rated the CT scans without knowledge of clinical history. Every reader utilized each of the interpretation platforms for 20 cases, limited to a duration of 5 minutes per scan. Images were evaluated for early ischemic changes (EIC) and hemorrhagic findings, including ASPECTS rating and detection of potential contraindications to thrombolysis. Results: 60 noncontrast CT scans were rated by 3 readers across 3 interpretation platforms. The average patient age was 69.4 years. The cross-platform accordance rates for diagnoses were: iPad vs desktop PC, SAH -100%, ICH -96.7%, EIC -88.3%; iPhone vs desktop PC, SAH -100%, ICH -95%, EIC -90; iPad vs iPhone, SAH -100%, ICH -98.3%, EIC -86.7%. Conclusion: Subarachnoid and intracerebral hemorrhages on noncontrast CT are sensitively detected when imaging interpretation is performed by readers with various skill levels on portable devices such as the iPhone or iPad. Early ischemic changes are also detected well, considering the subtle nature of these findings in hyper-early images. Further studies should prospectively test the performance of remote image interpretation in thrombolytic decisions. Objectives: Subacute levels of high sensitivity CRP (hsCRP) after stroke have previously been associated with poor outcome, however earlier studies were confounded by stroke severity, and their impact diminished by the extended window for blood draws. This study was designed to determine if hsCRP measured in the hyperacute phase of stroke could predict outcome, particularly in mild strokes where outcome is difficult to predict. Methods: We prospectively measured hsCRP and NIHSS scores on consecutive acute stroke patients (Ͻ 9 hours from symptom onset) in a multicenter acute ischemic stroke biomarker study. Patients with acute infection, active malignancy, or systemic inflammatory disorder were excluded. Pearson's correlation was used to quantify the association between continuous variables. Multivariate linear and logistic regression models were used to adjust for the effects of potential confounding variables. Continuous NIHSS scores were dichotomized at the median (NIHSS score 5) as "mild" (1-5) and "moderate-severe" (6-33). The outcome measure was the 90-day mRS, dichotomized as good (mRS 0-2) or poor (mRS 3-6). Results: We included 309 patients, 44% female, mean age 69.2 (range 23-97 years), with baseline NIHSS, baseline hsCRP and 3 month mRS in this analysis. There were 167 (54%) mild strokes and 142 (46%) moderate-severe strokes. Thirty seven percent (114 patients) had a poor outcome. The mean hsCRP was 6.4 mg/L (s.d. 9.6 mg/L) in mild strokes, compared to 14.0 mg/L (s.d. 37.1 mg/L) in moderate-severe stroke. In univariate analyses, hsCRP correlated with NIHSS (r ϭ0.24, PϽ0.01), systolic and diastolic BP (rϭ-0.17 and -0.16, respectively, PϽ0.01), and WBC (rϭ0.16, PϽ0.01), but was not associated with demographic characteristics, medical conditions, or medications. In unadjusted univariate models, poor outcome was correlated with baseline NIHSS, age, and level of hsCRP. However, in a multivariate model, the effect of hsCRP was attenuated after adjustment for baseline NIHSS score. In a stratified analysis, after adjustment for age, sex, and tPA use, hsCRP predicted poor outcome in mild stroke (OR1.05, 95% CI 1.01-1.10, pϭ0.03) but not moderate-severe stroke (OR1.0, 95% CI 0.99-1.01, pϭ0.43). The logistic regression models yielded an AUC of 0.84 for mild stroke and 0.69 for moderate-severe stroke. Conclusions: hsCRP is a better predictor of outcome in patients with mild, rather than moderate-severe, stroke. In mild strokes, each 1 mg/L increase in hsCRP, increases the risk of poor outcome by 5%.

W P126 Effect of Age and Circle of Willis Anatomy on Blood Flow in Major Cerebral Vessels

Sepideh Amin-Hanjani, Xinjian Du, Nada Mlinarevich, Sean Ruland, Meide Zhao, Fady T Charbel; Univ of Illinois at Chicago, Chicago, IL Objective: We sought to examine the effect of age and anatomic variations in the Circle of Willis on flow rates in individual major cerebral vessels, using quantitative magnetic resonance angiography (QMRA) to assess both vascular anatomy and flow. Methods: 326 healthy adult volunteers with no history of cerebrovascular disease underwent QMRA of head and neck vessels using commercially available software, NOVA (Vasol, Inc.). Individual vessel and combined territory flows were reviewed in relationship to patient variables and Circle of Willis anatomy. Results: The volunteers ranged from 18 to 84 (mean 48) years old, with 58 (48%) females. Mean blood pressure (MBP) ranged from 66-127 mmHg (mean 93). Total cerebral blood flow (CBF), defined as the sum of bilateral internal carotid artery (ICA) flows and vertebral artery flows, was not altered through the MBP range (pϭ0.20) when adjusting for age, consistent with cerebral autoregulation. Total CBF declined with age (pϽ0.001), from 768 Ϯ 115 ml/min in the youngest decades (age 18-35), to 645 Ϯ 103 ml/min in the oldest decades (age 65-84). This represents a 2.7 ml/min/year drop in a linear regression model, although a local regression model suggests a relative plateau in flows in the mid-decades (age 40-60) (see Figure ). In paired intracranial vessels, the left middle cerebral artery and left posterior cerebral artery demonstrated higher flows (pϽ0.01) than the right. Vessels proximal to the circle of Willis, the ICA and basilar artery (BA), were examined relative to cerebrovascular anatomic variants. The BA flow in the overall cohort averaged 138 Ϯ 40 ml/min, but was significantly lower in individuals with one or both fetal PCAs (84 Ϯ 28 ml/min, nϭ39) compared to those with no posterior communicating arteries (PcoAs) (155 Ϯ 31 ml/min, nϭ115) (pϽ0.001). Similarly ICA flows were affected by PcoA and PCA anatomy, but also by the anterior cerebral artery (ACA) A1 segment anatomy. ICA flows were significantly higher on the side of a fetal PCA (277 Ϯ 55 ml/min) compared to those with absent PcoAs (250 Ϯ 56 ml/min) (pϽ0.01). Furthermore, flow was significantly lower in the setting of absent or hypoplastic A1 segment (defined as flow Ͻ 15 ml/min) at 194 Ϯ 49 cc/min compared to 259 Ϯ 54 ml/min (pϽ0.01). Conclusions: Cerebral vessel flows are affected predominantaly by age and, for proximal intracranial vessels, also by the patient's specific cerebrovascular anatomy. Understanding of these variations carry important implications for interpretation of vessel flows in the setting of cerebrovascular disease.

W P130 Ultrasonography and Pathology in Symptomatic and Asymptomatic Carotid Plaques

Virginia A Pujol Lereis, Gustavo E Sevlever, Roberto Lagos, Claudia P Cejas, Eugenia Arias, Lucia Fernandez Cisneros, Sergio Garrido, Sebastian Ameriso, Guillermo P Povedano, Sebastia ´n F Ameriso; Institute for Neurological Rsch, FLENI, Buenos Aires, Argentina Background: Atherosclerotic disease is a process in which stability conditions may change to produce an ischemic event. Carotid plaques provide a unique opportunity for the study of atherosclerosis in living subjects. Differences in the characteristics of carotid plaques between symptomatic and asymptomatic patients would identify genuinely unstable plaques. We analyzed ultrasound and pathology findings of carotid plaques obtained during surgery. Methods: Data was obtained from the FLENI Stroke Data Bank. We analyzed demographics, clinical features, and ultrasonography and pathology findings in carotid plaques of patients who had carotid endarterectomy (CEA) between July 2005 and June 2010. We used standardized criteria for ultrasonographic and pathological classifications. The ultrasonographist and the pathologist provided a "stable/unstable" assessment for each plaque. We considered symptomatic those patients who met NASCET criteria. We excluded patients who were not studied within the one week prior to surgery in the institutional Doppler laboratory and those in whom substantial fragmentation of the plate occurred during surgery. Results: We evaluated 164 carotid plaques (54% asymptomatic, 46% symptomatic) from 161 patients undergoing CEA. There were no differences in age, gender distribution, vascular risk factors, degree of carotid stenosis, and statin use between symptomatic and asymptomatic sunjects. Use of aspirin and antihypertensive drugs were more frequent in asymptomatic patients (pϽ0.02). Prevalence of ultrasonography findings consistent with unstability was similar in symptomatic and asymptomatic plaques. Pathology findings determined unstability in 61 of 75 (81%) symptomatic plaques and in 32 of 89 (36%) asymptomatic plaques (pϽ0.001). Conclusions: Presence of symptoms prior to CEA and pathology findings are reliable methods for identifying unstable plaques. A potential role of aspirin and antihypertensive drugs in plaque stabilization deserves further study. Non invasive diagnostic methods that identify unstability are needed during the presymptomatic and preoperative periods.

Author Disclosures: V.A. Pujol Lereis: None. G.E. Sevlever: None. R. Lagos: None. C.P. Cejas: None. E. Arias: None. L. Fernandez Cisneros: None. S. Garrido: None. S. Ameriso: None. G.P. Povedano: None. S.F. Ameriso: None.

W P131 Can iPhones Be Used For The Evaluation Of Acute Stroke?

May A Kim, Monique Mogensen, Benjamin Emanuel, Nerses Sanossian, Meng Law, Gene Y Sung; Univ of Southern California/Keck Sch of Medicine, Los Angeles, CA Objectives: Recent technological advances allow for rapid transfer of medical images to portable viewing devices for critical decisions about acute stroke management, yet the diagnostic utility of interpretations needs to be systematically evaluated. We tested the intra-observer accuracy (IOA) and confidence of a stroke diagnosis on non-contrast head CT scan at presentation utilizing a portable viewing device (iPhone, by Apple). Methods: Three neurologists (R1, R2, R3) retrospectively reviewed 33 non-contrast head CT scans of patients presenting to the emergency department with symptoms of acute stroke. CT scans selected for inclusion into the study had a range of findings including hemorrhage (8), subtle infarct (9), obvious infarct (8), and normal (8). Cases were initially reviewed using the mobile hand-held device utilizing a mobile display technology with a web-based thin client application system followed by review on a standard PC display system. Data on the presence of infarct and/or hemorrhage and level of confidence 1 (lowest) to 4 (highest) was collected using a standardized form. Simple IOA between the iPhone and standard PC workstation interpretations, as well as average confidence levels was calculated. Results: Simple IOA for acute ischemic infarcts between the portable viewing device and standard PC was good for all readers (R1ϭ82%, R2ϭ 79%, R3ϭ79%). Differences in simple agreement were primarily secondary to chronic infarcts being mistaken for subtle infarcts on the iPhone. IOA for hemorrhages between the iPhone and PC were 100% for all 3 readers. Average confidence levels of interpretations on the iPhone vs. the PC were as follows: R1ϭ3.63 vs. 3.72 (pϭ0.41), R2ϭ3.93 vs. 3.90 (pϭ0.32), R3ϭ3.33 vs. 3.27 (pϭ0.70), respectively. None were statistically significant. Conclusions: Overall confidence when interpreting acute stroke imaging on a portable viewing device was good. The simple IOA of acute stroke imaging interpretation using an iPhone compared to a PC workstation was good. Chronic infarcts being mistaken for subtle infarcts on the iPhone accounted for the small percentage of intra-observer discordance. With the continued development of mobile technology, it is very likely that mobile devices will play a significant role in patient care in the future.

Author Disclosures: M.A. Kim: None. M. Mogensen: None. B. Emanuel: None. N. Sanossian: None. M. Law: None. G.Y. Sung: None.

W P132 A Tissue-Based Definition of Transient Ischemic Attack: a Lose-Lose Situation for US Healthcare Dollars

Laura Heitsch, Jane Khoury, Heidi Sucharew, Kathleen Alwell, Charles J Moomaw, Opeolu Adeoye, Daniel Woo, Matthew L Flaherty, Pooja Khatri, Simona Ferioli, Joseph P Broderick, Brett M Kissela, Dawn O Kleindorfer; UNIVERSITY OF CINCINNATI, Cincinnati, OH Objectives: The AHA/ASA recently endorsed a tissue-based definition of transient ischemic attack (TIA), requiring absence of infarction on imaging. MRI/DWI was recommended as the preferred imaging modality. In a bi-racial population of 1.3 million, we determined the proportion of TIA patients who would be reclassified as ischemic stroke (IS) by the new definition and estimated the impact of changing discharge diagnosis from TIA to IS on Medicare expenditure and hospital reimbursement. Methods: All clinical TIA cases (focal neurologic symptoms lasting Ͻ 24 hours) that presented to every local emergency department in our region in 2005 were identified by screening ICD-9 codes 430-436. Medical records were reviewed by study physicians who adjudicated TIA cases. Ischemic lesions on MRI/DWI were redefined as IS. A model, incorporating risk factors previously identified for a ϩ DWI, was built to determine how many additional TIAs from 2005 would be reclassified as IS if all had received MRI/DWI. Medicare reimbursement rates for DRG code 69 ($4618, uncomplicated TIA), for DRG code 66 ($5421, uncomplicated IS), and for a brain MRI/DWI ($544) were used to estimate Medicare expenditures and net hospital reimbursement, ie the sum of DRG payment minus the cost of MRI. Incremental changes in Medicare expenditure and net hospital reimbursement were estimated and then extrapolated to US healthcare expenditures. Results: In 2005, 834 clinically defined TIA patients were identified in the Cincinnati region. In total, 323 had MRI/DWI, of which 51 with ϩDWI were redefined as IS. Our model estimated that if all subjects had received MRI, 175 (21%) of the TIA cases would have a ϩDWI, resulting in an additional 124 cases reclassified as IS. The incremental DRG payments for the 124 reclassified DWIϩ strokes would result in increased Medicare expenditures of $99,572 for 2005. However, this would require an additional 511 MRIs to be performed, at a cost of $277,984. Subtracting this cost from DRG payments would result in a decreased net hospital reimbursement of $178,412. Extrapolating these results to the entire US population with 200,000 clinically defined TIA cases/year presenting to emergency departments, we estimated 40,600 cases would be reclassified as IS, with increased Medicare expenditures of $21 million while net hospital reimbursements would decrease by $41 million. Conclusions: While performing MRI/DWI on all clinically defined TIA cases in our population would identify additional cases of infarction, it would result in increased overall healthcare expenditures and decreased hospital reimbursements. Given the current economic environment and given the fact that a DWIϩ MRI may not change the clinical management of these patients, further research is warranted to determine which TIA patients would benefit from an MRI/DWI. The combination of PC-VIPR and automated spline interpolation allows calculation of velocity, volume flow rate, and WSS in vessels of interest with total processing time of 15 minutes per vessel. We anticipate that by combining WSS, velocity measurements, and morphology acquired using PC HYPRFlow, we can better evaluate patients at risk of atherosclerosis, aneurysms, transient ischemic attacks, and hemorrhagic or ischemic stroke due to pathology in the carotid siphon.

Background:

We have recently presented pilot results for the Oxygen Challenge MRI Technique in acute ischemic stroke (Santosh et al, JCBFM, 2008;Dani et al, Annals of Neurology, 2010). This deoxyhaemoglobin sensitive technique involves the transient application of hyperoxia during continuous T2*-weighted MRI. We have demonstrated that in 'healthy' tissue, T2*-weighted signal increases after hyperoxia. In operationally defined infarct core such increases are attenuated, and signal increases in regions likely to be penumbra are generally exaggerated. These findings support the concept that this technique is sensitive to underlying metabolic activity. In this study we investigated if Crossed Cerebellar Diaschisis (CCD; hypometabolism in the contra-lesional cerebellar hemisphere following stroke) could be detected by Oxygen Challenge MRI. Methods: Inclusion criteria were 1) ischemic anterior circulation stroke, 2) scanned Ͻ24h, and 3) DWI lesion Ͼ 50ml. Regions of interest were manually delineated in the ipsi-and contra-lesional cerebellar hemisphere and the magnitude of T2*-weighted signal increases was measured by 'percentage signal change' and the 'area under the T2*-weighted signal intensity-time curve'. Results were compared between hemispheres using the Wilcoxon signed ranks test. Results: The magnitude of signal change was greater in the ipsilateral cerebellar hemisphere compared to the contralateral cerebellar hemisphere in 6/12 (50%) of subjects (Figure 1). In no case was the change greater in the contra-lateral hemisphere compared to the ipsilateral hemisphere. For the 12 subjects, the mean percentage signal change in the ipsilateral cerebellar hemisphere (5.1%, standard deviation ϭ 2.7%) was significantly greater (pϭ0.03) than the corresponding value in the contralateral cerebellar hemisphere (3.8%, standard deviation ϭ 3.1%). Analyses of 'area under the curve' also showed this difference (pϭ0.002). No difference between hemispheres was detected using standard perfusion MRI 'time to peak ' maps. Conclusion: Oxygen Challenge showed an attenuated response in the contra-lesional cerebellar hemisphere, consistent with CCD. The failure to observe changes on perfusion maps is consistent with the observation that metabolic changes are significantly more pronounced than perfusion changes in CCD (Gold and Lauritzen, PNAS, 2002). These results further validate the Oxygen Challenge technique, and further evaluation is warranted. Background: Developing countries are currently experiencing a health transition from infectious to chronic conditions in which cardiovascular diseases are having a devastating impact on the population. Data on stroke subtypes in Vietnam are not available in the literature. Objectives: We sought to learn more about patient characteristics of hospitalized stroke by developing a stroke registry in Da Nang, Vietnam. Methods: Data on all potential strokes admitted to Da Nang Hospital for three months (April-June 2010) were entered into a system based on the WHO Stroke STEPS instrument. Data were collected by physicians and nurses in the Ministry of Health who treated these patients. Results: During these three months, a total of 212 strokes presented to the Emergency room and were treated in the intensive care unit (33%), cardiology (51%) or general internal medicine (16%) wards. Of these, 205 were classified as definite strokes in adults 18 years of age or older. This was a first (incident) stroke for 86% of the patients. Age ranged from 18 to 90 years with a mean of 49.5 (SD 16.1) years. Over 40% of the strokes occurred in women. Utilizing CT scans to classify subtype, 94 (46%) were diagnosed as ischemic, 88 (43%) were hemorrhagic, and 23 (11%) were unspecified. There were no differences in age or gender by stroke subtype. Neurological signs present at admission differed significantly by stroke subtype (p Ͻ .001): 65% of patients with hemorrhagic strokes were found to have disturbed consciousness compared to 28% of those with ischemic stroke; 75% with haemorrhages had speech disturbances compared to 60% with ischemic stroke and 95% of patients with ischemic stroke presented with weakness compared to 76% of those with hemorrhagic stroke. While a high rate of hypertension was identified at admission (84%), there was no difference by stroke subtype. Eleven patients (5.6%) died while in hospital after an average length of stay of 17 days, 5 with ischemic and 6 with hemorrhagic subtype. Of those discharged from the hospital alive, many were seriously disabled: 18% were discharged with severe disability as assessed by the modified Rankin scale, 30% had moderate disability/were unable to walk, 18% had moderate disability but were able to walk, and 35% had no or slight disability. Conclusions: Stroke in Vietnam is a serious cause of morbidity presumably due to untreated hypertension occurring at relatively young ages and presenting in a much higher percentage of women than in developed countries. Specific risk factors for this population need to be investigated and verified. Culturally appropriate interventions for treatment and prevention will be critical to help ease the burden of this disease.

W P138 Proposed Angiographic Criteria for Measurement of Vertebral Artery Origin Stenosis, the Vertebral Origin Treatment with Endovascular therapy (VOTE) method

Marc A Lazzaro, Aamir Badruddin, Michael Abraham, Osama O Zaidat; Med College of Wisconsin, Wauwatosa, WI Introduction: Vertebral artery origin (VAO) stenosis is a treatable cause of stroke, however no standard measurement criteria have been established. The tortuous VAO anatomy presents challenge in interpretation of stenosis severity. We assessed the hypothesis that inter-rater agreement of VAO stenosis measurement could be improved with exclusion of the tortuous V1 segment in measuring normal artery diameter. Methods: A retrospective database of patients referred for endovascular therapy of VAO stenosis was accessed and a consecutive series of ten patients was identified. Magnified cerebral angiograms were reviewed independently by three experienced angiography raters on a picture archiving and communications system and stenosis was measured using a submillimeter digital caliper. Two measurement methods were compared differing only by the location used for measurement of the normal diameter: 1. within the V1 segment, or 2. at the beginning of the V2 segment. The equation for measurement of VAO stenosis was [1 -(Dstenosis/Dnormal)] x 100, where Dstenosis was the diameter of the most stenotic portion of the lesion. The first method used the V1 segment for measurement of Dnormal. In the second method, Dnormal was the diameter of the first disease-free portion of the V2 segment with exclusion of any region of post-stenotic dilatation. Average interobserver agreement for stenosis variance of 10% and 5%, intraclass correlation coefficient (ICC), and kappa were calculated for each of the two measurement methods. Results: Ten consecutive patients with VAO stenosis were reviewed. No tandem lesions were present. All stenoses were greater than 50%, and mean stenosis was 71.9% (SD 10.7) with the first method and 66.9% (SD 10.6) with the second method. Average interobserver agreements were 80% with the first method and 87% with the second method. Intraclass correlation coefficient showed higher inter-rater agreement when the V2 segment was used to measure normal diameter (ICC ϭ 0.7750), when compared to the use of the V1 segment for measurement of normal diameter (ICC ϭ 0.7256). Kappa statistics were the best between the 3 raters with 10% variance with the use of the V2 segment at 0.73 (overall agreement 87%). Conclusions: Exclusion of the tortuous V1 portion in measurement of the normal diameter shows improved inter-rater agreement and allows a simple method for measurement of high-grade vertebral artery origin stenosis. If validated in larger series, these criteria can be a consistent method of vertebral artery origin stenosis measurement in future studies.

Author Disclosures: M.A. Lazzaro: None. A. Badruddin: None. M. Abraham: None. O.O. Zaidat: None.

W P139 NIHSS Thresholds for Prediction of Perfusion Deficits in Acute Cerebrovascular Syndromes

Trevor A Steve, Michael E Knash, Negar Asdaghi, Thomas Jeerakathil, Ashfaq Shuaib, Derek Emery, Christian Beaulieu, Kenneth S Butcher; Univ of Alberta, Edmonton, Canada Background and Purpose: Perfusion-weighted imaging (PWI) in acute ischemic stroke patients provides useful diagnostic and prognostic information. Due to increased costs and resource allocation, PWI is not routine in many centers and is used on an ad hoc basis, without clear selection criteria. The severity of clinical deficits is often part of the decision making process in selecting patients for PWI. We aimed to identify a threshold for clinical severity, based on the National Institutes of Health Stroke Scale (NIHSS) score, that would predict perfusion deficits as well as PWI-diffusion-weighted imaging (DWI) mismatch in patients presenting with acute focal neurological symptoms. Methods: Patients with acute ischemic cerebrovascular syndromes were imaged with PWI-DWI acutely and an NIHSS score was assessed prior to MRI. An arterial input function selected from the contralateral middle cerebral artery and deconvolution algorithm were used to generate Tmax maps from raw PWI data. Tmax maps were thresholded to a 4 second delay (Tmaxϩ4s) and manual planimetric measurements of Tmaxϩ4s and DWI lesion volume were made. Patients were considered to have significant PWI deficits if the Tmaxϩ4s volume was Ͼ10 ml. A PWI-DWI mismatch was considered to be Tmaxϩ4svol/ DWIvolϾ1.2. We conducted an ROC analysis of the sensitivity and specificity of the NIHSS for prediction of PWI deficits and mismatch paterns. Results: A total of 76 patients were included; 33 (43.4%) of whom had no perfusion deficits and 43 (56.6%) of whom had perfusion deficits. The median time from onset to MRI was 7.50 hours (IQRϭ4.00,15.48) in patients with PWI deficits and 13.00 hours (IQRϭ6.48,19.67) in those without PWI changes (pϭ0.091). The median NIHSS of patients with PWI deficits (13, IQRϭ7,18) was higher than that of patients without PWI deficits (4, IQRϭ3,5); (pϽ0.001). Patients with perfusion deficits had minimum and maximum NIHSS scores of 1 and 23 respectively. Patients without perfusion deficits had minimum and maximum NIHSS scores of 0 and 18 respectively. Logistic regression indicated that NIHSS score was a significant predictor of perfusion deficits (ORϭ1.4 per 1 NIHSS point, PϽ0.001). ROC analyses indicated good to moderate sensitivity and specificity of NIHSS score as a predictor of PWI deficits (AUCϭ0.86) and mismatch (AUCϭ0.68). An NIHSS Ն10 had a PPV and specificity for PWI deficits of 92.6% and 93.9% respectively but only 58.1% sensitivity. In our study, an NIHSS cutpoint of Ͼϭ1 would have been required to capture all patients with significant PWI deficits. Conclusions: Higher NIHSS scores do predict the presence of focal hypoperfusion, but even patients with mild clinical deficits often have blood flow changes. Penumbral imaging should be considered in all patients with neurological deficits, even when NIHSS scores suggest a mild clinical syndrome.

W P140 Temporal Evolution of Imaging Findings of Extracranial CranioCervical Arterial Dissection with Clinical Correlation: Mid-term Follow-Up

Mona M Mohsen, Lahey Clinic Med Cntr, Burlington, MA; Fawaz Al-Mufti, MetroWest Med Cntr / Framingham Union Hosp, Framingham, MA; Barbara Hum, Kinan Hreib, Mathew E Tilem, Edward Jewell, Nicholas Tsapatsaris, Seon Kyu Lee; Lahey Clinic Med Cntr, Burlington, MA Background and Objective: Extracranial craniocervical arterial dissection is believed to have a relatively benign natural history and generally is managed with anticoagulation or antiplatelet therapy. The clinical decision on the duration of anticoagulation is often based on follow up imaging findings. The purpose of this study is to analyze the temporal evolution of vascular imaging findings in extracranial craniocervical arterial dissection patients. Methods: Thirty two patients (M:Fϭ23:9, mean ageϭ49) with clinical evidence of craniocervical arterial dissection and at least one of the following suggestive imaging findings on either CT Angiography or MR angiography were included. Suggestive imaging findings include: 1) arterial stenosis, 2) arterial occlusion, 3) ectatic change of lumen, 4) pseudoaneurysm, and 5) dissection flap. The temporal evolution of imaging findings were analyzed by 2 neuroradiologists. Results: Twenty five patients had spontaneous dissection (25/32, 78%), and 7 patients had a history of trauma (21.8%). Fourteen patients presented with TIA/stroke (14/32, 43.7%), 9 patients had neck pain (28.1%), and 5 patients presented with Horner's syndrome (15.6%). There were 19 internal carotid artery dissections (59.3%), 9 vertebral artery dissections (28.1%), 2 common carotid artery dissections (6.3%) and 2 bilateral carotid dissections (6.3%). In 27 patients (84%), at least one follow up vascular imaging study was available (meanϭ1.5 years). On presentation, arterial stenosis, arterial occlusion, ectatic change of the lumen, pseudoaneurysm, and dissection flap were identified in 29 (91%), 6 (19%), 6 (19%), 12 (38%) and 16 (50%) respectively. On follow up, arterial stenosis improved in 58% (14/24), worse in 8.3% (2/24) and showed no interval change in 33.3% (8/24). The mean follow up period which demonstrated luminal narrowing improvement was 77 days (medianϭ87.5 days). Regarding pseudoaneurysms, there was no change in shape and size of the lesion in 58% (7/12), larger in size in 25% (3/12), smaller in size in 8% (1/12). Two patients developed a new pseudoaneurysm at the dissection site on follow up imaging. All patients were managed with anticoagulation or antiplatelet therapy since the diagnosis. During the follow up period, all patients were stable, without any additional neurological episode except one patient who developed a TIA (3.7%, nϭ1/27). Conclusion: Post-dissection vascular imaging findings are dynamic. With medical management, more than half of the arterial stenoses after craniocervical dissection improved within a relatively short period of time (about 2.5 months) and the risk of repeated neurological event appears to be very low.

Author Disclosures: M.M. Mohsen: None. F. Al-Mufti: None. B. Hum: None. K. Hreib: None. M.E. Tilem: None. E. Jewell: None. N. Tsapatsaris: None. S. Lee: None.

W P141 New Auto-Freeze, Operator-Independent, Carotid Intima-Media Thickness Measurement for Atherosclerosis Screening

Takenori Fukumoto, Steven Lynum, Makiko Urabe, Akihiro Kawabata, Yushi Nishimura, Takao Suzuki, Makoto Kato, Ichiro Okabayashi, Panasonic Healthcare Co., Ltd., Yokohama, Japan; Ram Bedi, Puget Ultrasound, Inc., Issaquah, WA; Kiyoko Ishikawa, Yokohama Stroke & Brain Cntr, Yokohama, Japan; Albert Yen, Haider Hassan, David Panthagani, Alok Bandekar, CardioNexus Corp, Houston, TX; Craig Hartley; Baylor College of Medicine, Houston, TX Most current methods for measuring carotid intima-media thickness (CIMT) require the user to manually identify a region of interest (ROI) and obtain the CIMT measurement offline from an ECG R-wave triggered image frame. We developed a new ultrasound instrument dedicated to carotid screening which combines real-time, automated R-wave triggered border detection and an auto-freeze function to capture the CIMT measurement, obviating the need for external ECG and offline reading.

We tested the inter-observer variability of our automated border detection program in a study in which 5 sonographers (4 experienced and 1 "beginner" with Ͻ2 months experience; S.G.1-5) each obtained a mean-CIMT measurement (single angle, far wall, distal common carotid artery-CCA) from 30 healthy individuals . Maximum difference from manual reading of ECG R-wave triggered images obtained with commercially available ultrasound systems was Ͻ 0.02mm. Intra-observer variability was very good (all coefficients of variation, or CV, were Ͻ6.8%, even for the "beginner").

To test the intra-observer variability of this device, we conducted a separate study in which a non-sonographer (Ͻ1 month training) obtained mean-CIMT (single angle, far wall, distal CCA) measurements in triplicate from 21 healthy individuals. Intra-operator variability was excellent (mean CV Ͻ5.0%). Coefficient of repeatability was 0.088mm. Of note, average time to obtain each auto-freeze measurement was 33 sec.

In summary, acquisition of CIMT measurements using our new ultrasound instrument with automated border detection, automated R-wave trigger, and auto-freeze features demonstrated very good reproducibility and excellent repeatability, even when used by a novice operator. Moreover, the capability to quickly obtain CIMT measurements in real-time and without a need to perform manual, offline measurement may be a desirable feature in the clinical setting.

Author Disclosures: T. Fukumoto: Employment; Significant; Panasonic Healthcare Co., Ltd. S. Lynum: Employment; Significant; Panasonic Healthcare Co., Ltd. M. Urabe: Employment; Significant; Panasonic Healthcare Co., Ltd. A. Kawabata: Employment; Significant; Panasonic Healthcare Co., Ltd. Y. Nishimura: Employment; Significant; Panasonic Healthcare Co., Ltd. T. Suzuki: Employment; Significant; Panasonic Healthcare Co., Ltd. M. Kato: Employment; Significant; Panasonic Healthcare Co., Ltd. I. Okabayashi: Employment; Significant; Panasonic Healthcare Co., Ltd. R.

W P143 Primary Central Nervous System Vasculitis: Circulating Endothelial Cells as Potential Diagnostic Biomarkers

Milani Deb, Stefan Gerdes, Meike Heeren, Juergen Lambrecht, Hans Worthmann, Annemarie Goldbecker, Anita Blanka Tryc, Hannover Med Sch, Hannover, Germany; Walter Schulz-Schaeffer, Univ Med Cntr Goettingen, Goettingen, Germany; Almuth Brandis, Karin Weissenborn, Marion Haubitz; Hannover Med Sch, Hannover, Germany Background: Histological evidence of vasculitis is the only proof of primary central nervous system vasculitis (PCNSV) at present. But, a biopsy is often omitted due to the invasive character and possible complications of the procedure. The number of circulating endothelial cells (CEC) has been shown to be elevated in patients with ANCA-associated vasculitis. We hypothesize that the CEC value is also elevated in patients with PCNSV and may contribute to the diagnosis of PCNSV. Methods: CEC were assessed in 19 patients in the age of 30-84 years (13 male) with clinical and additional examination findings suspicious of PCNSV. In 11 of them a brain biopsy was performed. Three patients were under immunosuppressive treatment. The patients' data were compared to those of 16 healthy controls (age range: 42-58 years, 8 male), 74 controls with cerebrovascular risk factors (age range: 54-60 years, 41 male) and 49 patients with ischemic stroke (age range: 61-79 years, 24 males) as disease controls. CEC's were measured by immunomagnetic isolation from peripheral blood. Patients with infectious diseases, malignoma and systemic vasculitis etc. were excluded. Results: Three brain biopsies showed a vasculitis. Interestingly, in these patients CEC values outranged 400 cells/ml. In the patients under successful immunosuppressive treatment the CEC value was significantly lower (range 0-52 cells/ml; p Ͻ0.05). The CEC values in the control groups were also significant lower (healthy controls: range 0-16 cells/ml, PϽ0.01; patients with cerebrovascular risk factors: 0-20 cells/ml, PϽ0.01; patients with stroke: 8-144 cells/ml, PϽ0.01). In the remaining 13 patients with clinical and additional findings highly suspicious for PCNSV the median CEC value was 220 cells/ml, and thus significantly higher than in the immunosuppressive treated patients (pϽ0.01) and the healthy and disease control groups (pϽ0,001 for each group). Discussion: However, our data are not sufficient to finally describe the sensitivity or specificity of CEC for the diagnosis of PCNSV. But, for the first time we could show that CEC are significantly elevated in patients with active biopsy proven PCNSV. Thus, CEC may well be a potential biomarker for PCNSV, expecially in not performed or biopsy negative settings. Continuous analysis of CEC in patients who undergo brain biopsy for the diagnosis of PCNSV and the monitoring of CEC numbers in patients treated for PCNSV shall provide data for a final judgement about the diagnostic use of CEC in this pathology.

Author Disclosures: M. Deb: None. S. Gerdes: None. M. Heeren: None. J. Lambrecht: None. H. Worthmann: None. A. Goldbecker: None. A. Tryc: None. W. Schulz-Schaeffer: None. A. Brandis: None. K. Weissenborn: None. M. Haubitz: None.

W P144 Validation Of New Ultrasound Parameters For Assessment Of The Collateral Pathway Through The Ophthalmic Artery In Internal Carotid Artery Occlusion

Tomotaka Tanaka, Hideaki Kanki, Akihiro Watanabe, Ryosuke Doijiri, Mutsuko Sawada, Mariko Yasui, Masahiro Uemura, Kazuyuki Nagatsuka; National Cerebral and Cardiovascular Cntr, Suita, Osaka, Japan Background and Purpose: The external carotid artery (ECA) may function as a collateral pathway through the ophthalmic artery in internal carotid artery (ICA) occlusion. The conversion to low resistance doppler sonography waveform in the ECA has been termed 'internalization' because the abnormal tracings in the ECA mimic the ICA, however, the criterial indicator of the internalization has not been reported. We determined the criterion for judgment of internalization by neck ultrasonography (US). Methods: We retrospectively analyzed the patients with unilateral ICA occlusion that were able to undergo digital subtraction angiography (DSA) and neck US. The clinical features, each parameter of the neck US, the DSA data and 15 O-labeled positron emission tomography (PET) data were evaluated. Furthermore, the degree of collateral flow via the ophthalmic artery observed in DSA was graded into three groups (grade 0: no filling of ophthalmic artery; grade 1: retrograde flow in the ophthalmic artery with filling of the carotid siphon; grade2: to MCA and/or ACA). We used ANOVA to analyze the relationships of the ECA collateral flow Grade and the parameters of the neck US. Results: 45 patients who underwent both DSA and US (43 men; mean age 68.1Ϯ7.9 years; 23 patients occluded on the right side) were analyzed. PET data were obtained for 32 patients (71.1%). Retrograde flow via the ophthalmic artery was detected in 27 cases (60.0%). The patients were divided into two groups those with (grade 1 or 2) and those without (garade 0) retrograde flow via the ophthalmic artery. Patient characteristics were no statistically different in age, sex, obstruction side and risk factors between the two groups. History of cerebral infarction and elevated oxygen extraction fraction (OEF) measured with PET were significantly higher in the patients with retrograde flow (pϽ0.05). Compared to each parameter of the neck US the optimal cut-off value of the ratio of the pulsatility transmission index (PTI: the ratio of pulsatility index (PI) of the occluded side ECA to PI of the ipsilateral common carotid artery) for detecting internalization was 0.94 with a sensitivity of 92.6%, and a specificity of 94.5%, respectively. The relationship between the ECA collateral flow grade and the PTI was statistically significant ( PϽ0.01; one way ANOVA). Conclusion: PTI is the optimal parameter to determine the internalization of ECA as a collateral pathway through the ophthalmic artery as well as providing a platform for the easy detection of elevated OEF indicating misery perfusion in ICA occlusion.

Introduction and Hypothesis:

Causal relationship between patent foramen ovale (PFO) and stroke is still controversial. We hypothesized that PFO characteristics (i.e., size or shunt amount) and ischemic lesion burden (i.e., infarct volume or number) might be correlated, if PFO plays a role as embolic source. Methods: Of ischemic stroke patients admitted to Asan Medical Center between January 2000 and April 2007, we identified patients who had (1) acute ischemic lesion on diffusion-weighted imaging (DWI) within 5 days of symptom onset, (2) undetermined cause of stroke according to TOAST classification and (3) only PFO detected by extensive cardiac work-up including transthoracic, transesophageal echocardiography and Holter monitoring. Volume, pattern and number of acute ischemic lesions on baseline DWI were obtained. Arterial occlusion relevant to index stroke was evaluated with MR angiography. Lesion patterns were classified as large territorial, perforator artery (large Ͼ or ϭ2cm, small Ͻ2cm), pial artery, or border zone infarcts. PFO characteristics on echocardiographic studies included size, shunt degree (minimal versus moderate versus severe, according to number of bubbles), shunt pattern (left-to-right versus right-to-left versus bi-directional) and presence of atrial septal aneurysm (ASA). The PFO size was measured as the maximum separation of the septum primum from the septum secundum in digitally, stored transesophageal echocardiographic images. Initial stroke severity was examined according to National Institutes of Health Stroke Scale (NIHSS) Scores. Results: 75 patients (male 56% and mean age 45.3Ϯ13.9) were included for this study. 10 patients (13.3%) had ASA. Median DWI lesion volume was 7.0 cm 3 (range; 0.1-196.6 cm 3 ). In univariate analysis, PFO size was positively correlated with log-transformed infarct volume (LIV) (regression coefficientϭ0.469, pϭ0.009). After adjusting hypertension, previous stroke history and migraine (all PϽ0.2 by univariate analysis), PFO size remained independently associated with LIV (regression coefficientϭ0.481, pϭ0.007). Larger PFO size was associated with large territorial infarct (odds ratio [OR]ϭ2.077, 95% confidence interval [CI] 1.119-3.858, pϭ0.021) and occlusion of relevant artery (ORϭ1.467, 95% CI 0.969-2.222, pϭ0.07). The initial NIHSS scores tended to be positively correlated with PFO size (Spearman's coefficient rhoϭ0.223, pϭ0.054). Lesion number was negatively correlated with PFO size (Spearman's coefficient rhoϭ-0.251, pϭ0.03). Conclusions: PFO size and ischemic lesion burden was positively correlated in cryptogenic stroke with PFO. These results support the idea that PFO may be an embolic source of stroke in patients with cryptogenic stroke.

Author Disclosures: J. Jung: None. Y. Do: None. J. Song: None. J. Lee: None. D. Kang: None.

W P146 Impaired Cerebrovascular Reactivity Assessed By Transcranial Doppler In Hepatic Cirrhosis

Carlos Cantu, Marina Green-Go ´mez, Ricardo Macı ´as-Rodrı ´guez, Jorge Baruch, Aldo Torre; Instituto Nacional de Ciencias Me ´dicas y, Mexico City, Mexico Background: In patients with hepatic cirrhosis systemic vasodilatation secondary to portal hypertension induces a continuous activation of two vascular regulatory systems, the renin-angiotensin-aldosterone and the sympathetic nervous, which stimulate a dysfunctional circulatory vasoconstriction involving kidneys, muscles, skin, and brain. This provides a substrate for damage to cerebral microvessels and probably, it may constitute a physiopathologic pathway of development and progression of hepatic encephalopathy (HE). The primary aim of this study was to evaluate the cerebrovascular reactivity (CVR) assessed by transcranial Doppler in patients with hepatic cirrhosis with and without HE. Material and Patients: Sixty cirrhotic patients were studied and severity was classified according with Child score. Also, HE was determined by West Haven evaluation. The proximal segments of the middle cerebral artery were examined on each side and the following parameters were evaluated: peak systolic blood flow velocity, end-diastolic blood flow velocity, mean flow velocity, and pulsatility index (PI). CVR was examined using the breath-holding index (BHI). The BHI values included in the analysis were the means of the 2 tests and of right and left values. CVR reflects the compensatory dilatory ability to maintain constant cerebral blood flow. Results: There were 62% women; mean age was 49 years. According with Child score 33 patients (55%) had severe hepatic damage (Child score Ͼ8) and 45% mild to moderate disease (Childe Ͻ8). Fifty percent (30 patients) had HE. Classification of HE correlated with anemia (pϽ0.000), hyponatremia (pϽ0.008), and severity of disease (Child Ͼ7, Pϭ0.049). Patients with severe hepatic damage (Child Ͼ8) showed lower CVR with BHI (0.83; 95%CI 0.45-1.12) as compared with patients with mild to moderate hepatic damage (1.25; 95%CI 0.86-1.53; Pϭ0.006) and higher PI (1.07, 95%CI 0.95-1.21 versus 0.87, 95%CI 0.83-1.05; Pϭ0.002). Similar results were obtained when PI and CVR were compared between patients with and without HE. Conclusions: This study provides evidence of significant vasoreactivity reduction and increased PI in patients with severe hepatic damage and HE, as indicators of impairment of cerebral microvasculature circulation. This suggests that overactivation of systemic vascular mechanisms have an effect on cerebrovascular regulation, first, with functional damage, and, with progression of the disease, structural damage.

Author Disclosures: C. Cantu: None. M. Green-Go ´mez: None. R. Macı ´as-Rodrı ´guez: None. J. Baruch: None. A. Torre: None.

W P147 Predictive Factors For A Neurological Deterioration In The Acute Phase Of Ischemic Stroke -Fukuoka Stroke Registry

Shigeru Fujimoto, NIPPON STEEL YAWATA MEMORIAL HOSPITAL, Kitayushu, Japan; Hiroshi Sugimori, Dept of Medicine and Clinical Science, Graduate Sch of Med Sciences, Kyushu Univ, Fukuoka, Japan; Juro Jinnouchi, Takayuki Matsuki, Seizo Sadoshima, NIPPON STEEL YAWATA MEMORIAL HOSPITAL, Kitayushu, Japan; Takanari Kitazono; Dept of Medicine and Clinical Science, Graduate Sch of Med Sciences, Kyushu Univ, Fukuoka, Japan Background & Purpose: A neurological deterioration in the acute phase can be associated with a bad outcome in stroke patients. We investigated the predictors for a neurological deterioration in the acute phase of ischemic stroke. Subjects & Methods: Consecutive 1732 ischemic stroke patients who were admitted to the 7 stroke centers in Fukuoka, Japan within 24 hours after the onset were included in the present study. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification: Large-artery atherosclerosis, Cardioembolism, Small-vessel occlusion, and Others. We observed a neurological deterioration (a NIHSS score worsening of Ն1-point), stroke recurrence, or any death in the acute phase (the first 21 days) and also evaluated the outcome 3 months after admission. Modified Rankin Scale of 0 or 1 was defined as a good outcome. Results: A neurological deterioration was observed in 233 (13.5%) patients. A stroke recurrence or any death was observed in 76 (4.4%) patients. A neurological deterioration was significantly associated with a good outcome (OR; 0.17; 95%CI, 0.06ϳ0.50). With regard to the TOAST classification, a neurological deterioration was most frequent in Large-artery atherosclerosis (21.1%) and was less frequent in Small-vessel occlusion (7.1%). The site of ischemic lesions on the magnetic resonance imaging (MRI) or computed tomography on admission was significantly associated with a neurological deterioration (pϽ0.0001): both cortex or cerebellar lesions and brain stem or subcortex lesions (18.0%), only brain stem or subcortex lesions (15.1%), only cortex or cerebellar lesions (9.6%), and no ischemic lesions on MRI (7.3%). A stenosis of Ն50% or a total occlusion of the major brain artery, diabetes mellitus, a motor hemiparesis, NIH stroke scale score, systolic blood pressure (SBP), white blood cell, low density lipoprotein cholesterol, blood sugar, and HbA1c values on admission showed an association with a neurological deterioration on univariate analysis. On multivariate analysis, a major brain artery stenotic lesion (OR, 1.99; 95%CI 1.44ϳ2.75), ischemic lesions including both cortex and subcortex (OR, 1.99; 95%CI, 1.26ϳ3.16), motor hemiparesis (OR, 2.62; 95%CI, 1.69ϳ4.05), and SBP Ն162mmHg (OR, 1.79; 95%CI, 1.32ϳ2.42) were significantly associated with a neurological deterioration in the acute phase. In comparison with patients without any those 4 independent predictive factors, patients with 1, 2, 3, andall 4 factors have 5.1, 12.3, 18.4, and22.4-fold risk for a neurological deterioration. Conclusions: A major brain artery stenotic lesion, the site of ischemic lesions, a motor hemiparesis, and SBP value on admission were significant predictors for a neurological deterioration in the acute phase of ischemic stroke.

Author Disclosures: S. Fujimoto: None. H. Sugimori: None. J. Jinnouchi: None. T. Matsuki: None. S. Sadoshima: None. T. Kitazono: None.

W P148 Significance of VEGF in Ischemic Stroke -Research for Biomarkers in Ischemic Stroke (REBIOS)

Ryu Matsuo, Tetsuro Ago, Masahiro Kamouchi, Jun Hata, Kyushu Univ, Fukuoka, Japan; Tetsu Isomura, Wakako Watabe, Hideto Awano, Kazuo Suzuki, MOLECUENCE Corp, Yokohama, Japan; Kenji Fukuda, St-Mary's Hosp, Kurume, Japan; Yasushi Okada, Kyushu Med Cntr, Fukuoka, Japan; Yutaka Kiyohara, Takanari Kitazono; Kyushu Univ, Fukuoka, Japan Background and Purposes: Blood biomarkers for stroke diagnosis would be helpful, especially under the situations without imaging modalities. However, there is no biomarker clinically available for diagnosis of ischemic stroke so far. Heterogeneous mechanisms of ischemic stroke hampers the identification of biomarkers associated with ischemic stroke. In the present study, we aimed to discover blood biomarkers for diagnosis of ischemic stroke and to evaluate its predictive capability for prognosis. Methods: We designed Research for Biomarkers in Ischemic Stroke (REBIOS) study, and 132 patients with brain infarction (atherothrombotic (AT) 27, cardioembolic (CE) 39, lacunar (Lac) 39, and unclassified 27 cases) were recruited from the Fukuoka Stroke Registry, a prospective multi-centered study for acute stroke in Japan. Blood samples as well as clinical information were obtained from the patients at 5 points after the stroke onset, day 0 (within 24 hours after the onset), 3, 7, 14, and 90. Ninety molecules were measured by HumanMAP® v 1.6 (Rules-Based Medicine, Inc.). Age and sex -matched healthy subjects from the Hisayama study in Japan were enrolled as the control group (nϭ110). Results: Among the molecules we tested, we identified vascular endothelial growth factor (VEGF) as one of the biomarkers that increased significantly and immediately after the stroke onset in all subtypes (AT 581 Ͻ27Ͻ 154, CE 563 Ϯ 204, Lac 595 Ϯ 243 pg/ml at day 0), compared with controls (435 Ϯ 130 pg/ml, PϽ0.0001). A receiver operating characteristic analysis demonstrated that ischemic stroke was differentiated from the healthy subjects with sensitivity 62% and specificity 82% (cut-off value: 480 pg/ml). VEGF values at day 90 remained significantly high in all stroke subtypes (AT 612 Ϯ 176, CE 599 Ϯ 204, Lac 651 Ϯ 268 pg/ml), and were correlated strongly with those at day 0 (pϽ0.0001, rϭ0.79). In CE, VEGF values at day 0 were significantly higher in the group with poor prognosis (modified Rankin Scale 3 to 6) at day 90 than in the group with good one (640 Ϯ 200 pg/ml vs 488 Ϯ 154 pg/ml, PϽ0.05). Conversely, VEGF values at day 0 tended to be higher in the group with good prognosis in AT. Conclusion: Plasma VEGF levels could be a biomarker useful for diagnosis of ischemic stroke regardless of its subtype. The significance of VEGF in ischemic stroke may be different among its subtype, especially in terms of prediction of prognosis.

Author Disclosures: R. Matsuo: None. T. Ago: None. M. Kamouchi: None. J. Hata: None. T. Isomura: None. W. Watabe: None. H. Awano: None. K. Suzuki: None. K. Fukuda: None. Y. Okada: None. Y. Kiyohara: None. T. Kitazono: None.

W P149 Visinin-like Protein-1 (VILIP-1): A Novel Plasma Biomarker For The Detection Of Acute Cortical Ischemic Stroke

Rawan Tarawneh, Andria L Ford, Matt Ohlendorf, Elizabeth Macy, Jay McQuillan, Rosana Ponisio, Jack H Ladenson, Jin-Moo Lee; Washington Univ Sch of Medicine, St Louis, MO Background: The diagnosis of acute ischemic stroke is largely based on clinical evaluation and the absence of hemorrhage on head CT. It has been estimated that up to 7-15% of acute strokes are clinically misdiagnosed. Therefore, biomarkers that can reliably detect acute neuronal injury may have great utility in improving diagnostic accuracy and clinical decisionmaking. Visinin-like protein-1 (VILIP-1), a calcium sensor protein expressed exclusively in neurons, has demonstrated utility as a neuronal injury marker in Alzheimer disease patients. Here, we examined the utility of plasma VILIP-1 in the detection of acute ischemic stroke. Methods: Suspected acute ischemic stroke patients were enrolled within 12 hrs of symptom onset after obtaining informed consent. NIHSS and plasma samples were obtained on presentation (Ͻ12), 24, and 72 hrs after symptom onset. Ischemic stroke patients were classified into cortical and subcortical localization based on clinical signs and symptoms as well as magnetic resonance imaging (MRI) when available (nϭ39). Plasma was assayed for VILIP-1 using a commercial chemiluminescence assay (Singulex, USA). In the subset of patients with cortical ischemic stroke who had MRI (nϭ 22), DWI (diffusion-weighted imaging) lesions were manually delineated by a board-certified neuroradiologist (RP) who was blinded to all clinical and VILIP-1 results. Infarct volumes were measured using Image-J v.1.43. Unpaired t-tests and Spearman correlations evaluated group comparisons and relationships between VILIP-1 levels and NIHSS or infarct volumes. Results: Seventy patients with discharge diagnosis of brain ischemia were enrolled, including 48 cortical strokes, 15 subcortical strokes, and 7 TIAs. Eleven patients were diagnosed as stroke mimics, including stroke recrudescence (5), post-ictal paralysis (4), diabetic cranial nerve palsy (1), and conversion disorder (1). In addition, 36 healthy age-matched controls were enrolled. Plasma VILIP-1 levels were higher in ischemic stroke compared to controls at 12 hrs (83.6 and 58.2 pg/ml, respectively, pϭ0.003), 24 hrs (94.3 pg/ml, pϭ0.048), and 72 hrs (118.8 pg/ml, PϽ0.0001). Moreover, plasma VILIP-1 levels were higher in cortical strokes compared to stroke mimics at 12 hrs (90.8 and 36.3 pg/ml, respectively, pϭ0.03). While cortical strokes had higher VILIP-1 levels compared to subcortical strokes (90.8 and 61.1 pg/ml, respectively, pϭ0.034), subcortical strokes were not different from controls (pϭ0.64) within 12 hrs of onset. Peak VILIP-1 levels values were at 72 hrs, at Background and Purpose: Cardiac sources can be identified as etiology for ischemic stroke in up to one third of the cases. Thereby, early detection of potentially life-threatening courses due to severe cardiac insufficiency, arrhythmia and thrombus formation -as frequently found in endocarditis (EC) or myocarditis (MC) -is of great importance for planning diagnostic and therapeutic procedures. The present study aims to identify screening parameters that may help to detect stroke patients suffering from MC and EC at hospital admission. Methods: A hospital-based database with 950 cases of ischemic stroke was retrospectively screened for the occurrence of MC and EC, detected by echocardiography. Patients with EC (nϭ12) or MC (nϭ3) were compared to those devoid of EC/MC concerning age, clinical parameters (Glasgow Coma Scale [GCS], National Institute of Health Stroke Scale [NIHSS]), inflammatory (C-reactive protein [CRP], leukocyte count) and cardiac (troponin T, myoglobin, creatine kinase [CK], creatine kinase isoenzyme [CK-MB]) serum markers. Furthermore, MRI/CT-based differences in type of infarction (lacunar, territorial, border zone stroke) and lesion pattern (single territory vs. multiple territories) were analyzed. Results: Patients with EC/MC were significantly younger than non-affected patients (means, 61.1 years vs. 68.7 years; PϽ0.05). NIHSS and GCS did not differ significantly between the groups. Leukocyte count and CRP were significantly increased in patients with EC/MC (means, 11.4 exp9/l vs. 9.0 exp9/l; 74.0 mg/l vs. 15.3 mg/l; PϽ0.05 for each). Identifying patients with EC/MC, a receiver operating characteristics (ROC) analysis revealed superiority for CRP (area under curve [AUC], 0.832; PϽ0.001). Troponin T, myoglobin, CK and CK-MB tended to increased values in patients with EC/MC, which failed statistical significance. Surprisingly, percentage rates for type of infarction and lesion pattern did not differ significantly between patients with EC/MC and non-affected patients. Conclusions: CRP and leukocyte count were identified as helpful parameters for the detection of EC and MC in ischemic stroke patients at hospital admission. Significantly increased values should accelerate further diagnostic procedures -especially echocardiography -with the objective of EC/MC exclusion.

Author Disclosures: D. Michalski: None. D. Schneider: None. S. Budig: None. W. Ha ¨rtig: None. A. Hagendorff: None. C. Hobohm: None.

W P151 Elevated Plasma Levels of Soluble Form of RAGE and High Mobility Group Box 1 in Patients with Acute Stroke

Sung-Chun Tang, Dept of Neurology, Stroke Cntr, National Taiwan Univ Hosp, Taipei, Taiwan; Chaur-Jong Hu, Dept of Neurology, Taipei Med Univ-Shuang Ho Hosp, Taipei, Taiwan; Hung-Yi Chiou, Dept of public health, Taipei Med Univ, Taipei, Taiwan; Jiann-Shing Jeng; Dept of Neurology, Stroke Cntr, National Taiwan Univ Hosp, Taipei, Taiwan Background and purposes: The receptor for advanced glycation end products (RAGE) and high mobility group box 1 (HMGB1) have been shown to mediate ischemic brain damage in experimental stroke model, but little is known about its clinical implication. Here we reported the plasma levels of HMGB1 and soluble form of RAGE (sRAGE) in patients with acute stroke. Methods: We prospectively recruited patients with acute ischemic and hemorrhagic stroke and age-and sex-matched healthy controls. Plasmas were collected from patients at 3 time points after stroke: within 48 hours, 3 days and 7 days. The plasma levels of HMGB1 and sRAGE were determined by the ELISA. Results: There were 118 patients (male, 62.7%; mean age, 64.8Ϯ15.5 years; ischemic stroke, 65.3%) with acute stroke and 110 controls. The NIH stroke scale (NIHSS) score at admission was 11.6Ϯ7.4. After acute stroke, plasma HMGB1 levels were significantly elevated in all 3 time points and kept increasing with time course (controls 6.4Ϯ2.9 ng/mL, vs. stroke, 15.8Ϯ31.1, 19.4Ϯ37.1, and 20.7Ϯ44.0 ng/mL, respectively; all PϽ0.001). By contrast, sRAGE levels were significantly elevated in samples collected within 48 hours but decreased gradually with time course (control 751.2Ϯ322.4 ng/mL, vs. stroke, 996.1Ϯ1073.4, 834.3Ϯ790.9, and 721.9Ϯ823.0 ng/ml, respectively, Pϭ0.019, 0.152, and

Introduction And Objectives:

The current classifications of stroke are based on identifying their most likely cause. A new classification capable to describe a complete "stroke phenotyping" has been recently proposed, the ASCO scale: A, atherosclerosis; S, small vessel disease; C, cardiac source; O, other cause. Each of the 4 phenotypes is graded 1, 2, or 3. One for 'definitely a potential cause of the index stroke', 2 for 'causality uncertain', 3 for 'unlikely a direct cause of the index stroke (but disease is present)'. When the disease is absent, the grade is 0; when grading is not possible due to insufficient workup, the grade is 9. The main objective is to analyze the presence of "mixed" cerebrovascular disease in the stroke etiological classification, using the TOAST and ASCO classifications. Materials And Methods: Observational study of the first 30 ischemic stroke patients admitted to our Stroke Unit in 2010. The clinical records were given to two stroke expert neurologists, two general neurologists and two resident neurologists, who were blinded to the final etiological stroke classification. The physicians classified each stroke patient twice, according to TOAST and ASCO classifications. Results: ASCO scale showed more than one possible stroke profiles in 66-83% (minimum and maximum percentage between the six observers) of strokes. There was not a strong concordance between the TOAST and ASCO scales in the atherothrombotic and small vessel disease group. ASCO scale revealed atherothrombotic disease in 40%-65% of stroke not so classified by TOAST, and small vessel disease in 42% to 57% of the strokes that had not been diagnosed as lacunar strokes by TOAST. However, a cardiac source by ASCO was identified in all patients with cardioembolic stroke by TOAST. Up to 94% of patients with cardiac source as definitively cause of stroke (C1) by ASCO presented scores of 1-3 in the other items (A, S, O). This kind of "mixed" vascular disease is observed in 63%-80% of strokes caused by cardioembolism according to TOAST (pϽ0,001). ASCO revealed evidence for other stroke etiologies in most of strokes of undetermined origin by TOAST (50%-80%, 40%-75%, and 40%-99%, for atherosclerosis, cardioembolism and small vessel disease, respectively).

Conclusion:

The ASCO scale shows more than one stroke profile in most of patients. The concordance between ASCO and TOAST is strong in cardioembolism but poor in large and small vessel disease. ASCO shows other stroke profiles in most of strokes of undetermined origin by TOAST.

Author Disclosures: P. Alonso-Singer: None. R. Cazorla-Garcia: None. G. Ruiz-Ares: None. I. Sanz-Gallego: None. M. Aguilar-Amat: None. P. Martinez Sanchez: None. B. Fuentes: None. E. Diez-Tejedor: None.

W P154 Pelvic Magnetic Resonance Venography For Detection Of Deep Vein Thrombosis In Young Patients With Cryptogenic Ischemic Stroke And Patent Foramen Ovale

Feliks Koyfman, Helena Lau, Matthew Ogrodnik, Jose R Romero, Carlos S Kase, Aleksandra Pikula; Boston Univ Med Cntr, Boston, MA Background: Despite comprehensive evaluation the cause of stroke remains unidentified in as many as 64% of young adults (Ͻ55 years old). Patent foramen ovale (PFO) has been related to ischemic stroke, particularly in patients with cryptogenic stroke. Paradoxical embolism has been suggested as one of the mechanisms for stroke in these patients, leading to the search for deep vein thrombosis (DVT). Prior studies demonstrated presence of pelvic DVT on pelvic Magnetic Resonance Venography (MRV) in 20% of young adults with cryptogenic stroke and known PFO. However, the sensitivity of pelvic MRV remains low and its utility in routine evaluation of patients with cryptogenic stroke and PFO is still unclear. Methods: Medical records of patients 15-49 years old admitted to Boston Medical Center between January, 2005 and February, 2010 with diagnosis of ischemic stroke were retrospectively reviewed. Patients diagnosed with PFO on Transthoracic (TTE) or Transesophageal echocardiogram (TEE) were selected and their lower extremities Duplex scan (LE Duplex) and pelvic MRV were reviewed. Both venous studies were performed following standard procedures, and MRV was obtained within 3Ϯ2 days of admission. Descriptive statistics are presented. Results: A total of 114 patients with ischemic stroke (62.3% men) were identified (mean age: 41; range: 19-49 years), representing 11.4% of all patients admitted with a diagnosis of ischemic stroke during the same period. TTE or TEE was done in 111 (97.4%) patients, including TTE in 110 (96.5%) and TEE in 58 (50.9%) patients. PFO was detected in 20 (17.5%) patients. Pelvic MRV and LE Duplex were available in 12 (60%) and 18 (90%) of these patients, respectively. One patient with PFO was found to have LE thrombosis confirmed by LE Duplex, but none of the pelvic MRV detected a DVT. Conclusion: While prior studies revealed high prevalence of pelvic DVT among young patients with cryptogenic stroke and PFO using pelvic MRV, we were unable to corroborate this observation in our sample. Our study is limited by its sample size and design. Given that pelvic MRV is a costly test, further studies are required to assess its role in the routine evaluation of patients with cryptogenic stroke and PFO.

Author Disclosures: F. Koyfman: None. H. Lau: None. M. Ogrodnik: None. J.R. Romero: None. C.S. Kase: None. A. Pikula: None.

W P155 A New Contrast Agent Of A Drop Of Diazepam Added To Saline To Detect PFO With Transesophageal Echocardiography

Noriko Matsumoto, Kazumi Kimura, Yuki Sakamoto, Nobuyuki Kaneko, Shuichi Fujii, Takashi Shiromoto, Kenichirou Sakai, Junichi Uemura, Shinji Yamashita, Takeshi Iwanaga, Masao Watanabe, Kensaku Shibasaki, Yasuyuki Iguchi; Dept of Stroke Medicine, Okayama, Japan Background and Purpose: Patent foramen ovale (PFO) has been known as one of potential embolic sources for ischemic stroke, especially in cryptogenic stroke. Contrast transesophageal echocardiography (c-TEE) has been a sensitive technique to diagnose PFO. Usually, agitated saline (air bubble) is used as contrast agents, but air bubble is easy to be broken and it is frequently difficult to diagnose PFO. Therefore, stable contrast agent is expected. Diazepam is a benzodiazepine with water solubility non-water-soluble powders. Therefore, Diazepam seems to be better as contrast agents than saline. The aim of this study was to investigate whether use of a drop of Diazepam added to saline can improve the detection rate of PFO with c-TEE. Methods: We prospectively studied consecutive ischemic stroke patients admitted to our hospital. To detect PFO, c-TEE was performed 2 times using 2 kind of contrast agents as follow; saline only, and saline with a drop of Diazepam. We compared the detection rate of PFO between the 2 conditions. Next, we divided patients into 4 grade on the basis of the number of micro-bubble in left atrium within 3 cardiac cycles after opacification of the right atrium; non-PFO, small PFO; Ͻ10 micro-bubbles, moderate PFO; 10 to 50 micro-bubbles; large PFO; Ͼ50 micro-bubbles. We investigate the change of detection rate for PFO and PFO grade using a drop of Diazepam. Results: 559 patients (male 400, age 69.6Ϯ11.7 years) were enrolled in the present study. Detection rate of PFO was higher in cooled saline with a drop of Diazepam than saline only (36.9% vs. 20.4%, PϽ0.0001, Figure 1). For PFO grade for saline only and saline with a drop of Diazepam, non-PFO was 77.6% and 56.2%, small PFO was 14.2% and 26.0%, moderate PFO was 6.0% and 9.8%, and large PFO was 2.2% and 8.0%, respectively (pϽ0.0001, Figure 2). Therefore, using saline with a drop of Diazepam, the amount of stable micro-bubble increased and detection rate of PFO improved, in particular small and moderate PFO. Conclusion: Using of one drop of Diazepam can improve the detection rate of PFO with c-TEE, especially in small and moderate PFO.

Introduction: Intravenous thrombolysis is used infrequently for stroke. Estimation of nationwide changes in utilization over time can help inform the design and interpretation of interventions to improve tPA use. Our primary objective was to estimate the change in tPA use over time using a nationally representative sample. We also estimated the proportion of stroke patients who presented to hospitals that used tPA for stroke. Methods: The Nationwide Inpatient Sample is the largest all-payer database of U.S. acute care hospitalizations; it is designed to capture 20% of all inpatient stays. Ischemic stroke cases were identified using ICD-9 codes from the principal diagnosis. Use of tPA was identified using procedure code 99.10. The analysis was limited to cases admitted from the ED and to hospitals which any reported procedure codes (Ͼ90%). While accounting for the complex survey design, we estimated the national proportion of ischemic stroke patients receiving tPA for each month from 2000 to 2007. A model was constructed to fit the rates using multivariate adaptive regression splines (MARS) to evaluate for non-linear trends. Finally, hospitals were categorized as either treating any stroke patients with tPA for a year versus not. We used logistic regression to compare the odds of a stroke case being admitted to a non-treating hospital over the years queried. Results: The NIS contained 470842 stroke cases from 2000-2007 meeting the inclusion criteria corresponding to a population estimate of 2.3 million stroke hospitalizations. The monthly rate of tPA treatment ranged from 0.8% to 4.3%. The monthly rates along with 95% CI are presented in the figure. The best fitting MARS model provided slope transition points of Aug-02, Feb-05, and Aug-06 (R squared using cross validation 0.93). The annualized rates of increase for each period are depicted in the figure. The total proportion of stroke cases presenting to hospitals using stroke tPA was 59.7% in 2000 versus 75.4% 2007 (OR: 2.1 [95% CI 1.6-2.7]). Conclusions: The use of tPA has increased substantially from 2000 to 2007 in U.S. hospitals. The rate of increase in tPA use has not been stable over time, with several apparent transitions within the upward trend. While some of this increase may be attributable to improved coding, the inclusion of a broad cross section of hospitals strongly suggests nationwide improvement in use.

W P159 Post-Graduate Academic Neurovascular Fellowship for Advanced Practice Nurses and Physician Assistants Significantly Increases tPA Treatment Rates: Results from the First Graduating Class of the NET SMART Program

Anne W Alexandrov, Univ of Alabama at Birmingham, Birmingham, AL; Tenisha Baca, Arizona State Univ, Phoenix, AZ; Karen C Albright, Univ of Alabama at Birmingham, Birmingham, AL; Stephen DiBiase, Arizona State Univ, Phoenix, AZ; Andrei V Alexandrov, Univ of Alabama at Birmingham, Birmingham, AL; NET SMART Faculty and Fellows Background: Standard academic training for acute care advanced practice nurses (APNs) and physician assistants (PAs) has evolved into a "generalist-hospitalist" model that includes less than 30 minutes didactic content on stroke, while APNs credentialed in primary care receive no content on stroke diagnosis and treatment. Methods: We developed and implemented a first-of-its-kind, post-graduate, federally-funded neurovascular fellowship program for APNs and PAs that utilizes a hybrid internet-based didactic/clinical training approach in partnership with vascular neurologists across the U.S. All program content is evidence-based, updated regularly, and externally vetted by expert vascular neurologists to ensure accuracy and relevancy; learning materials are accessible via the internet 24/7/365. Fellows must pass written exams, and vascular neurologist overseen clinical skills testing to complete each section of the program, as well as a final on-site clinical validation session to ensure mastery of program content and skills prior to graduation. The primary aim of the NET SMART program is to increase the early identification and treatment of acute stroke patients, with outcomes measured during and after program completion. Results: The first graduating class consisted of 18 (17 APNs; 1 PA) fellows, representing 12 US states. Employing practice sites were 28% university-affiliated comprehensive stroke centers (CSC); 5% university-affiliated primary stroke centers (PSC), 39% community hospital CSC, and 28% community hospital PSC; 94% of graduates worked at a certified or state-designated stroke center with 17% of these programs receiving their designation while the graduate was enrolled. Baseline tPA treatment rates on entry into the fellowship averaged 3.3%, and increased over a period of 1.4 years on average to 11.6% at the time of program completion (paired tϭ9.34; mean differenceϭ8.3, 95%CIϭ6.4-10.2; PϽ.001) without a significant increase in acute stroke patient admissions and an average sICH rate of 4.4% (range 2%-6.25%). 100% of sponsoring vascular neurologists rated themselves as confident in their graduates' ability to appropriately select candidates for reperfusion therapy. Conclusions: APN/PA completion of the NET SMART fellowship is associated with a safe and significant increase in tPA treatment across a variety of stroke center settings. Use of this peer-reviewed educational model builds confidence in the use of mid-level providers to deliver safe reperfusion therapy, while providing standardized, accessible evidence-based education that retains APN/PA resources within their original practice settings.

W P160 Engaging Clinicians, Patients and Family Members in the Development of Decision Support for Hyperacute Stroke

Darren Flynn, Lynne Stobbart, Madeleine J Murtagh, Institute of Health and Society, Newcastle Univ, Newcastle Upon Tyne, United Kingdom; Christopher Price, Northumbria Healthcare NHS Trust, Ashington, United Kingdom; Helen Rodgers, Gary A Ford, Institute for Ageing and Health (Stroke Rsch Group), Newcastle Univ, Newcastle Upon Tyne, United Kingdom; Richard G Thomson; Institute of Health and Society, Newcastle Univ, Newcastle Upon Tyne, United Kingdom Background: Decision support tools (DSTs) are warranted to expedite assessment of eligibility for thrombolysis and (where appropriate) communication of risks/benefits to patients/families.

Based on findings of an interview study, relevant research literature, an international survey of available examples and a locally designed decision analytic model we designed draft paper-based DSTs that expressed short-term outcomes (symptomatic intracerebral haemorrhage, death, independence/dependence at 6-months) and long-term outcomes (QALYs; life expectancy -overall and expected time in an independent and dependent state; and 5-year survival), with and without thrombolysis, as a function of patient characteristics (age, stroke severity, onset to treatment time, systolic BP). Objectives: To obtain feedback from (i) clinicians on DSTs to expedite eligibility decision making for thrombolytic treatment (structured look-up tables and tables of decisions rules for different levels of benefit from thrombolysis), risk presentation (bar graphs, pictograms and flowchart diagrams), and communication of risks/benefits to patients/families; and (ii) patients/families on risk communication tools (bar graphs, pictograms and flowchart diagrams). Methods: DSTs were presented to 12 stroke clinicians (7 stroke physicians, 5 stroke nurses) and 15 patients/families (8 patients, 7 family members) within interactive group workshops. We elicited their views and preferences on the form and content of draft DSTs, including their perceived value during the hyperacute stroke phase. Results: Clinicians were generally supportive of presenting short-term outcomes to patients/families, although views on the most effective format to achieve this did not reach consensus. Mixed views were reported on the utility of long-term outcomes for supporting eligibility decisions. The volume of material prompted clinicians to suggest the development of a computerised version of the DSTs. The challenge of integrating the DSTs within existing care pathways was also highlighted by clinicians. Patients/families expressed negative reactions to the presentation of information on average life expectancy, and preferred the balanced presentation of 'short-term' risks and benefits using pictograms or clustered bar graphs (used within verbal presentation by trusted clinicians). Conclusions: Computerised DSTs are likely to be the most efficacious format for supporting clinical decision-making within the hyperacute period of stroke. Short-term outcomes using pictograms or clustered bar graphs (showing natural frequencies) are feasible options for the balanced presentation of risks/benefits of thrombolytic treatment to patients and families.

Introduction: Participation by emergency medical services (EMS) plays a crucial role in achieving excellent acute stroke care. In order to raise the level of acute stroke recognition, we have moved from the concept of a simple scale to something more complex, incorporating education and participation in our hospital's stroke program. Methods: For this study we have worked with a single EMS group over a 12 month period, providing them with a stroke assessment tool containing an abbreviated National Institute of Health Stroke Scale (NIHSS), time of onset and assessment, glucose, Coumadin use, epilepsy and surgical and trauma history. EMS obtained NIHSS certification, attended scheduled educational programs, stroke committee and Joint Commission meetings, community presentations, and helped develop the hospital's stroke DVD. The Emergency Trauma Center (ETC) was included in this program and asked to respond positively to calls from EMS reporting their assessment tool results. We tracked: 1. Percentage of patients with acute stroke who received intravenous (IV) or intrarterial (IA) recombinant tissue plasminogen activator (rt-PA) 2. Symptom to drug time 3. Door to CT time 4. Door to drug time. NIHSS results presented by EMS were compared to results obtained by the neurologist seeing the patient acutely. Results: 101 patients reported to the ETC with possible acute stroke. 50% of these patients were determined to be mimics, a higher figure than usually reported, suggesting that EMS "erred" on the side of inclusion. 1. 20% of eligible patients were treated with IV or IA rt-PA, nearly double the year before and among the highest figure in the country. 2. Symptom to drug time was 150 minutes. 3. Door to CT time averaged 15.5 minutes 4. Door to drug time was 67.6 minutes. The abbreviated NIHSS was very close to the full NIHSS obtained by the neurologist, though some patients improved or worsened once they arrived in the ETC. Conclusion: We have demonstrated that alliance with EMS, through the use of a stroke assessment tool, recognized by the ETC, educational programs explaining the tool and stroke care standards and participation by EMS in all aspects of our Stroke Center programs can increase rt-PA administration and improve time to evaluation and treatment. Other benefits such as improved communication and respect between EMS and ETC cannot be easily measured, but certainly occurred to the delight of all who participated. . Methods: We used the Robert Wood Johnson University Hospital (RWJUH) Brain Attack Database, which includes demographic and clinical data on all emergency department (ED) patients alerted to the stroke team as a Brain Attack between January 1, 2009 and June 30, 2010. Outcome variables included the time from door to stroke team arrival, CT completion, CT interpretation, EKG, laboratory results, treatment decision, and intravenous (IV) rt-PA administration. The primary independent variable was Brain Attack activation before ED arrival (pre-hospital) versus on or after ED arrival (no pre-hospital). Analysis of covariance was used with patient predictors (age, sex, initial NIHSS) as covariates in addition to the one of interest (pre-notification vs. no pre-notification). Statistical significance was defined as a p-value Յ 0.05. Results: There were 231 patients (116 pre-notification, 115 no pre-notification) alerted as a Brain Attack from the RWJUH ED within the study period. Patients with pre-hospital notification were older, had more severe strokes, and were treated with IV rt-PA twice as often (Table 1). Pre-notification of a Brain Attack resulted in a significant reduction in all studied stroke time targets, except the door to treatment decision time and rt-PA administration (Table 2). Conclusions: Pre-hospital notification of suspected stroke patients reduces time to stroke team arrival, CT scan completion, and CT scan interpretation. IV thrombolysis occurred twice as often in the pre-notification group, however, there was no difference in door to rt-PA administration time. Background: In clinical trials, initiation of experimental therapies for time urgent neuroemergency conditions like stroke is increasingly occuring in the prehospital EMS system, allowing delivery within the first minutes after onset. However, paramedic exposure to conducting research has been limited. In the Field Administration of Sroke Therapy -Magnesium (FAST-MAG) study, the first phase 3 clinical trial of prehospital neuroprotective therapy for stroke, strategies have been devised to address paramedic perceptions of barriers. Methods: A survey was performed of 61 paramedics in Los Angeles County by nurse coordinators and research assistants from the FAST-MAG study, complemented by direct observations and interactions with medics by 12 FAST-MAG nurse-coordinators responsible for 228 fire stations. Results: Leading paramedic concerns include 1) avoiding delay in transport times, 2) cell phone connection difficulties, 3) calls to enrolling lines that do not result in patient enrollments (screen failures), and 4) need for explicit informed research consent, rather than implied consent. To minimize potential delays, FAST-MAG procedures were designed to occur simultaneously with routine care, such that the paramedics call an enrolling line and an on-call physician elicits the consent. By tracking the times from paramedic arrival on scene to ED arrival, study staff demonstrated that study procedures are not increasing time spent in the field over historical norms or national averages. Establishing a proper phone connection can be hampered by variable cell phone reception and unanswered calls. We have iteratively improved our response system, including implementing a simultaneous ring, voice over internet phone system. In addition, improved cell tower coverage has reduced dropped calls. Paramedic expectations are now framed by educating that 50-60% of patients meeting paramedic screening criteria will not meet the complete study entry criteria. Additionally, several exclusion criteria have been migrated to the paramedic stage from the MD stage, reducing screen failures and increasing paramedic autonomy. Federal regulations require explicit informed consent and determination of the competency of the patient to provide consent, or if appropriate, the availability of a proper legally authorized representative. Repeated education has highlighted these concepts but paramedics continue to have questions regarding the consent process.

W P164 The Impact of Ambulance "Ramp Time" Delays on Acute Stroke Pathways

Ian T Mosley, Monash Univ, Melbourne, Australia; Janet E Bray, Eastern Health, Melbourne, Australia; Caroline Nicolas, George Braitberg; Monash Univ, Melbourne, Australia Background: Over recent years rapid care pathways implemented in the pre-hospital and Emergency Department (ED) settings have been successful in reducing times to evaluation and treatment for acute stroke patients. However, over a similar period of time hospitals in Australia have experienced increased ED overcrowding and increased patient presentations by ambulance. This has resulted in delays transferring the patient after triage from an ambulance stretcher to an ED cubicle ("Ramp Time"). Patients remaining on ambulance stretchers in the ED (including stroke patients) cannot be appropriately assessed or investigated. Little is known about the impact of "Ramp Time" delays on rapid care pathways for stroke patients. We hypothesised that among stroke patients presenting by ambulance: • Stroke patients experiencing "Ramp Time" delays could be identified, • Demographic and clinical factors associated with prolonged "Ramp Times" (triage to ED cubicle time Ͼ15 minutes) could be identified. Methods From January to June in 2010, all ambulance-transported patients presenting to one of three hospital emergency departments with a final ED diagnosis of stroke or TIA were assessed. Hospital medical records were retrospectively analysed. Results 527 patients were included in the study. (351 Stroke and 176 TIA). Around half of patients (46%, nϭ243) experienced some "Ramp Time" delays with the majority of delayed cases (nϭ172) remaining on the ambulance stretcher. Median Ramp Time delay was: 17 minutes (IQ range 6 -46); maximum delay was 241 minutes. An unexpected finding was that a number of ambulance transported stroke patients (nϭ 76) were off-loaded after triage into a waiting room normally occupied by walk in patients. These patients experienced longer median delay times of 37 minutes (IQ range 13-102). No demographic or clinical variables were associated with prolonged "Ramp Time" delays. Patients with a triage assessed urgent priority code (1 or 2) were associated with shorter delay times (pϭϽ0.001). Conclusions: "Ramp Time" delays were experienced by half of stroke patients including those who presented rapidly following symptom onset and those recognized as stroke at triage. No clinical variables other than an urgent triage code reduced the likelihood of prolonged delays. Other factors like ED overcrowding may contribute to delays. Ambulance "Ramp Time" delays in the ED may restrict the timely application of rapid care pathways for many stroke patients and requires further investigation.

Author Disclosures: I.T. Mosley: None. J.E. Bray: None. C. Nicolas: None. G. Braitberg: None.

W P165 The Analysis Of The Influence Of Demographic And Logistic Factors On Effectiveness And Safety Of Treatment With Rt-pa The Patients With Acute Ischemic Stroke In Agricultural Region In South-east Poland.

Piotr Sobolewski, Monika Sledzin ˜ska, Wiktor Szczuchniak, Marcin Grzesik, Renata Hatalska Żerebiec, Anna Sobota; SPZZOZ Sandomierz, Sandomierz, Poland Material and Methods: Between September 2006 and December 2009 in the stroke center in Sandomierz 1034 patients with acute ischemic stroke (ais) was treated, including 143 patients (14,31% of all patients with ais) treated i.v. rt-PA and 5 patients treated with combined therapy i.v. and i.a. (aged 42-88, mean 69,14Ϯ9,73 ; 83 men (56,08%) , 65 women (43,92%); time window 0-6 hours for the i.v. and combined therapy). We analysed status of the patients in the moment of admission, after 1 and 3 months after symptoms onset according to National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Score (mRS). We analysed also the influence of demographic and logistic factors on effectiveness and safety of treatment. Results: The average time from the onset of the disease to the beginning of the treatment was 150,13Ϯ46,06 (42,5-interquartile range) minutes. In the moment of admission the average NIHSS was 12,20Ϯ4,86 (8,0) and average mRS was -4,15Ϯ0,81 (2,0). After 1 month mean NIHSS and mRS were respectively: 4,40Ϯ5,12 (5,0); and 2,46Ϯ1,98 (3,00); and after 3 months: 4,00Ϯ9,46 (5,00); 2, 25Ϯ2,11 (3,5). No correlation between onset-to -needle time, and patients' status at 30 th and 90 th day was found. We stated statistically significant correlation between distance from place of onset to our center and patients status at 30 th day (pϽ0,017). Also there were statistically significant difference between clinical status of patients (using mRS) from urban and country populations (pϽ0,013). Conclusions: Place of living(town and country) and distance from place of symptoms onset to hospital determines effectiveness of treatment, evaluated after 30 days using mRS. There is still requirement for improving organisation of prehospital procedures in agricultural regions.

Author Disclosures: P. Sobolewski: None. M. Sledzin ˜ska: None. W. Szczuchniak: None. M. Grzesik: None. R. Hatalska -ʲerebiec: None. A. Sobota: None.

W P166 Extension Of The IV tPA Window Does Not Impact Performance Of A Resident-Based Acute Stroke Protocol

Andria L Ford, Jennifer A Williams, David K Tan, Jin-Moo Lee, Colin P Derdeyn, Peter Panagos; Washington Univ, Saint Louis, MO Background: Extending the IV tPA window to 4.5 hours might lead to a lack of urgency in the treatment of patients with acute ischemic stroke, particularly using a resident-based acute stroke protocol. In November 2008, we instituted an extended 3-4.5 hour IV tPA stroke protocol. We hypothesized that door-to-needle (DTN) times might be longer: (1) in the 0-3 hr window and (2) within the extended window owing to newer exclusion criteria and the reduction of time pressure after the change in our protocol. Methods: Since 2004, we have utilized a resident-based stroke protocol placing neurology residents in decision-making roles for tPA administration. Patient demographics, NIHSS, and quality control metrics including DTN times, symptomatic intracerebral hemorrhage (sICH) rate, and discharge locations were prospectively collected. In November 2008, we adopted the ECASS III trial-based IV tPA extended treatment protocol. To test how the extended window may affect safety and efficiency, we assessed DTN times, sICH, and discharge outcomes in two comparisons: (1) 0-3 hr metrics pre-extended window (2004)(2005)(2006)(2007) vs. 0-3 hr metrics post-extended window (2008)(2009)(2010) ; and (2) 0-3 hr metrics vs. 3-4.5 hr metrics since initiation of extended tPA window. T-or Wilcoxon Rank Sum Tests were used for parametric and non-parametric continuous data, respectively. Chi-squared or Fisher's Exact Tests were used for parametric and non-parametric binary data, respectively. Results: From 2004-2007, 113 patients were treated with IV tPA. Since initiation of the extended tPA window (11/08 to 7/10), 94 patients were treated with IV tPA: 78 patients Ͻ 3 hours, 16 patients between 3-4.5 hours. Comparing the pre-extended window metrics (2004)(2005)(2006)(2007) to post-extended window metrics (2008)(2009)(2010), there was no significant difference between mean DTN times (60 vs. 61 minutes, pϭ0.78) or rate of sICH (3.5% vs. 2.6%, pϭ0.70). "Favorable" discharge location (home or inpatient rehabilitation) was 76% pre-extended window vs. 77% post-extended window, pϭ0.90; "unfavorable" discharge (nursing home or death prior to discharge) and 24% pre vs. 23% post, pϭ0.90. Since initiation of the extended window in 2008, there was no difference in median DTN times between the 0-3 and 3-4.5 hr windows (60 vs. 66 minutes, pϭ0.15), nor did rates of sICH differ (2.6% vs. 0%, pϭ1.0). Furthermore, discharge outcomes were similar: 77% for 0-3 hrs vs. 69% for 3-4.5 hours (pϭ0.53) for favorable discharge location and 23% vs. 31% (pϭ0.53) for unfavorable discharge location. Conclusions: Our resident-based stroke protocol provided efficient and safe delivery of IV tPA to acute stroke patients up to 4.5 hours. The protocol did not demonstrate "relaxed" DTN times due to a longer window in either the 0-3 or the 3-4.5 hour cohorts.

Author Disclosures: A.L. Ford: None. J.A. Williams: None. D.K. Tan: None. J. Lee: None. C.P. Derdeyn: Research Grant; Modest; Genentch, Inc; provided alteplase for an NIH-funded study. Consultant/Advisory Board; Modest; W.L Gore and Associates. P. Panagos: Speakers; Modest; Genentech Speakers Bureau.

W P167 CT Angiography Based Protocol Does Not Delay Thrombolysis In Acute Ischemic Stroke

Simerpreet Bal, Bijoy Menon, Nandavar Shobha, Andrew M Demchuk, Michael D Hill; Foothills Med Cntr,Univ of Calgary, Calgary, Canada Introduction: Despite information provided by CT Angiography regarding site of occlusion, extent of at risk tissue, thrombus burden and collateral status, its use is not uniformly accepted. Lack of additional utility over NCCT in decision making and delay in door to needle time are arguments used against the use of a CTA based protocol in acute ischemic stroke management. We compare interval times during a CTA based acute ischemic stroke protocol with an earlier non-CTA based protocol at our center. Methods: We reviewed our experience with stroke thrombolysis in a university hospital in Calgary, Canada from April 1996 to December 2009. 850 patients treated with thrombolytic therapy (IV and IV/ IA TPA) during this period with complete data were included in the analysis. Time to treatment was divided into the following interval times: onset to door, door to needle and onset to needle.Patients were categorised into three groups: Group 1(April 1996 -Dec 2002) (Noncontrast CT Scan based thrombolysis ) nϭ297, Group 2 (Jan 2004-Dec 2009) (CT Angiography based thrombolysis).The period from Jan to Dec 2003 (nϭ49) was considered a washout period and not included in the analysis as we gradually integrated the CTA protocol into standard care that year.Interval times were compared between the 2 groups using non-parametric test of medians and by multiple linear regression. Results: 801 patients were included in the final analyses. Median onset to door times in group 1 and Group 2 were 55 minutes (IQR 48)

W P168 A Four-Year Retrospective Evaluation of Blood Pressure Management Before IV Thrombolysis

Marc Lapointe, M. J Glace; Med Univ of South Carolina, Charleston, SC Delays in intravenous (IV) t-PA administration can prolong ischemia and worsen outcomes during stroke. Severe uncontrolled hypertension is a contraindication to tPA and adequate blood pressure (BP) reduction is necessary. Stroke guidelines offer limited therapeutic strategies. Hypothesis: During the acute treatment of ischemic stroke: 1) severe hypertension can significantly contribute to delays in the initiation of IV t-PA administration, and 2) the repetitive and/or aggressive administration of IV antihypertensive agents can cause potentially significant hypotensive excursions during or immediately after the IV t-PA infusion. Methods: Electronic medical records from the Medical University of South Carolina were retrospectively examined to identify ischemic stroke patients presenting from May 2006 to May 2010. The records of patients with a diagnosis of ischemic stroke were used to determine the incidence of severe hypertension requiring acute BP reduction before IV t-PA administration. BP reduction practices were described and evaluated in terms of therapy used, efficacy (time to achieve targeted BP) and safety (hypotensive excursions). Results: During the evaluation period, 93 patients received IV t-PA and 17 (18%) of them required acute BP reduction. Of these patients, 11 (65%) received IV bolus labetalol first line. Eight patients (47%) required the continuous infusion of nicardipine. Patients required a median number of either 3 separate doses or titration adjustments [range: 1-9] of any IV antihypertensive agents to achieve and/or maintain the targeted BP. Seven (47%) patients required more than one antihypertensive agent. Following the initial CT scan, the average time delay between the first IV antihypertensive agent given and the administration of IV t-PA after achieving the targeted BP was 27 minutes [range: 5-55]. Although no patient experienced clinically significant hypotension requiring treatment, potentially significant hypotensive excursions (i.e. systolic BP Ͻ 130 mm Hg) were identified in 3 (18%) patients during the first 3 hours following the initial IV tPA bolus. Patients who received the continuous administration of nicardipine often required a dose reduction during the acute management. Conclusions: The incidence of acute BP reduction prior to IV t-PA administration is relatively low. However, severe hypertension often requires polypharmacy and can significantly contribute to delays in the initiation of IV t-PA administration. We propose that specific antihypertensive regimens should be studied in the setting of acute ischemic stroke to optimize rapid BP reduction prior to IV t-PA administration while preventing potentially significant hypotensive excursions.

Author Disclosures: M. Lapointe: Research Grant; Significant; The Medicines Company. Speakers; Modest; Boehringer Ingelheim. Speakers; Significant; The Medicines Company. Consultant/Advisory Board; Significant; The Medicines Company. M.J. Glace: None. Background: Sex differences in the effect of intravenous (IV) rt-PA therapy for ischemic stroke are controversial. The aim of this study was to elucidate the sex differences in the stroke outcome after low-dose IV rt-PA (0.6mg/kg alteplase) therapy. Methods: A retrospective, multicenter, observational study was conducted to clarify the practical conditions of low-dose IV rt-PA therapy in 10 stroke centers in Japan (SAMURAI rt-PA Registry: Stroke 2009;40:3591-3595). Studied were consecutive patients with a premorbid modified Rankin Scale (mRS) Յ 2 who were treated with IV rt-PA from October 2005 through July 2008. We assessed baseline data, including sex, age, comorbidities (hypertension, diabetes, hyperlipidemia, and atrial fibrillation), time from onset to treatment, NIH stroke scale (NIHSS) score, Alberta Stroke Programme Early CT score (ASPECTS), and presence of internal carotid artery (ICA) occlusion identified on MR angiography or carotid ultrasound. Outcomes were a favorable outcome defined as an mRS score 0-2 and death at 3 months, as well as symptomatic intracerebral hemorrhage (sICH) within 36 hours: i.e. a parenchymal ICH associated with neurological deterioration corresponding to an increase of Ն4 point from the baseline NIHSS score. Results: Of 554 patients (358 men, 71Ϯ11 years) who were studied, 282 (50.9%) had a favorable outcome and 35 (6.3%) died at 3 months. Symptomatic ICH was identified in 16 patients (2.9%). Women were older (mean age 75Ϯ11 vs. 69Ϯ12 years, PϽ0.001), more frequently had atrial fibrillation (50.8 vs. 37.5%, pϭ0.004), and had higher median initial NIH Stroke Scale score (13 vs. 12, pϭ0.009) than men. There were no significant sex differences in hypertension, diabetes, hyperlipidemia, time from onset to treatment, ASPECTS, and ICA occlusion. Women had less favorable outcome (41.3% vs. 56.2%, pϭ0.001) than men. There Background and Purpose: Information about cerebral artery occlusive lesions is not taken into account for the CT-based patient selection of intravenous rt-PA therapy. The safety and efficacy of intravenous rt-PA for patients without cerebral artery occlusion (CAO) have not been elucidated. This study was aimed to clarify characteristics and outcomes in stroke patients without CAO who were treated with 0.6 mg/kg alteplase from the SAMURAI rt-PA registry, a retrospective, multicenter, observational study. Methods: Studied were 416 patients with premorbid modified Rankin Scale (mRS) of 0-1 who underwent MRA to identify CAO before rt-PA therapy. Endpoint events were intracranial hemorrhage (ICH) within the initial 36 hours, and favorable (modified Rankin Scale [mRS] 0-1) and unfavorable (mRS 4-6) outcomes, and mortality at 3 months. Results: CAO was documented in 327 patients (78.6%, 211 men, 71.9Ϯ11.3 years old), but not in 89 patients (21.4%, 65 men, 67.0Ϯ11.5 years old). As compared to patients with CAO, those without CAO were younger (pϽ0.001) and more frequently diabetic (27.0% vs. 16.8%, pϭ0.031), and had less commonly atrial fibrillation (13.5% vs. 48.3%, PϽ0.001), higher initial systolic (154.2Ϯ15.4 mmHg vs. 149.4Ϯ19.4 mmHg, pϭ0.030) and diastolic blood pressure values (85.7Ϯ13.4 mmHg vs. 81.0Ϯ14.7 mmHg, pϭ0.006), higher ASPECTS on DWI (median 9 vs. 8, PϽ0.001), lower initial NIHSS score (median 7 vs. 14, PϽ0.001), more commonly lacunar infarction (19.1% vs. 1.5%, PϽ0.001) but less frequently cardioembolic stroke (30.3% vs. 68.5%, pϭ0.007). With regards to endpoint events, patients without CAO had less frequently ICH within the initial 36 hours (11.2% vs. 22.9%, pϭ0.015), more frequently favorable outcome (56.2% vs. 33.6%, PϽ0.001), less commonly unfavorable outcome (16.9% vs. 43.3%, PϽ0.001), and no mortality at 3 months (vs. 7.7%, PϽ0.001) than those without CAO. After adjustment with various baseline features, absence of CAO was no longer associated with favorable outcome(OR 1.37, 95% CI 0.77-2.41), unfavorable outcome (0.58, 0.28-1.12), and ICH within the initial 36 hours (0.67, 0.30-1.37). Among patients without CAO, higher initial NIHSS score (OR 1.08, 95% CI 1.00-1.17 per 1-score increase, pϭ0.048) were associated with 3-month unfavorable outcome after multivariate adjustment with underlying features. Conclusions: Although 3-month outcomes of stroke patients without CAO after rt-PA were better than those of patients with, these associations became insignificant after adjustment with baseline features. The initial neurological severity was associated with 3-months outcome in patients without CAO.

W P169 Female Sex Is Associated With Unfavorable Outcomes Following Low-dose Intravenous Rt-pa Therapy: The Samurai Rt-pa Registry

W P171 Re-exacerbation Within 24 Hours After T-pa Infusion Was Associated With Small-vessel Disease

Jyunichi Uemura; Kawasaki Med Sch, Kurashiki, Japan Background and Purpose: We sometimes experience re-exacerbation within 24 hours after IV t-PA. The purpose of this study was to examine the characteristics of re-exacerbation patients within 24 hours after t-PA infusion. Methods: Consecutive stroke patients with t-PA within 3 hours of onset between October 2005 and March 2010 were studied. After t-PA infusion, we evaluated NIHSS in every 15 minutes for first one hour, every 30 minutes until six hours, and every one hour until 24 hours. We divided the patients into four groups, Improvement(Im) group; improved in NIHSSՆ4 points, Unchanged(Un) group; exacerbated or improved in NIHSSϽ4 points, Exacerbation(Ex) group; exacerbated in NIHSSՆ4 points, and, Re-exacerbation(Re-Ex) group; after t-PA infusion improvement of NIHSSՆ4 points, however, the neurological symptom was re-exacerbated in NIHSSՆ4 points. We compared age, sex, stroke subtype, risk factors, right to left shunt (RLS), use of antiplatelet and anticoagulant medication, BMI, initial NIHSS, time from onset to t-PA infusion, laboratory data on admission, and hemorrhagic infarction on MRI T2* amng four groups. Results: 222 patients (male 135 patients, median 76 years old) were enrolled into the present study. Re-Ex group had 16(7%) patients, Ex group had 23(10%) patients, Im group had 99(45%) patients, and Un group had 84(38%) patients. There was no difference in age, male, risk factor, RLS, initial NIHSS, antiplatelet and anticoagulant drug use, BMI, initial NIHSS, and time to t-PA, and laboratory data on admission among four groups. However, Re-Ex group most frequently had small-vessel disease and hemorrhagic cerebral infarction among 4 groups (44% and 25% for Re-Ex group, 9% and 22% for Ex group, 5% and 6% for Im group, and 17% and 14% for Un group, PϽ0.001 and Pϭ0.041). Multivariate logistic regression analysis identified small-vessel disease was an only independent factor associated with re-exacerbation within 24 hours after t-PA infusion (OR 12.5, 95% CI 2.57-61.14, Pϭ0.018). Conclusion: Re-exacerbation within 24 hours after t-PA infusion was associated with small-vessel disease.

Author Disclosures: J. Uemura: None.

W P172 Safety of a 'Drip and Ship' Intravenous Thrombolysis Protocol for Patients with Acute Ischemic Stroke

Simin Mansoor, Ramin Zand, Mervat Wahba, Univ of Tennessee Health Science Cntr, Memphis, TN; Elias A Giraldo; Mayo Clinic, Rochester, MN Introduction: The 'drip and ship' approach for intravenous thrombolysis (IVT) is becoming the standard of care for patients with acute ischemic stroke (AIS) in communities without direct access to a stroke specialist. We aimed to demonstrate the safety of our "drip and ship' IVT protocol in terms of symptomatic intracerebral hemorrhage (sICH). Methods: Retrospective study of consecutive patients with AIS treated with IVT from January 2003 to June 2010. Information on patients' demographics, clinical characteristics, neuroimaging, sICH, and outcome was obtained from our stroke registry. A group of patients were treated with IVT by an emergency physician in phone consultation with a board-certified vascular neurologist (BCVN) at one of our three stroke network affiliated hospitals (SNAH). These patients were subsequently transferred to our JCAHO-certified primary stroke center (CPSC) after completion of IVT ('drip and ship' protocol). The other patients were treated directly by a BCVN at CPSC. The study received IRB approval. Results: We studied 147 patients treated with IVT. Of them, 21 patients received IVT at SNAH and 126 patients were treated at CPSC. There were no significant differences between the two groups in mean age (57 versus 60 years) and mean stroke symptom onset-to-needle time (159 versus 144 minutes). The patients who received IVT at SNAH had a lower median NIHSS score on admission compared to the patients treated at CPSC (4.5 versus 11, p Ͻ 0.001). Among patients treated at SNAH, two patients had sICH. This number was not significantly higher among patients treated at CPSC (6 out of 126). Conclusions: This study suggests that our 'drip and ship' protocol for IVT is safe. The patients treated with the 'drip and ship' approach had lower NIHSS scores on admission as compared to the patients treated at CPSC. Further research is warranted.

Author Disclosures: S. Mansoor: None. R. Zand: None. M. Wahba: None. E.A. Giraldo: None.

W P173 IV rt-PA Administration in the Expanded Time Window (3-4.5 hours) in Practice: Utilization and Outcomes

Wondwossen G Tekle, Ameer E Hassan, Gustavo J Rodriguez, Saqib A Chaudhry, Gabriela Vazquez, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Introduction: A randomized double-blind trial (ECASS III) demonstrated that intravenous recombinant tissue plasminogen activator (rt-PA) administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke. In May 2009, the American Stroke Association guidelines recommended the use of IV rt-PA for patients presenting within 3 and 4.5 hours after symptom onset. Objective: To determine the rate of patients treated with IV rt-PA within the 3 and 4.5 hour time window and associated outcomes in general practice. Methods: We retrospectively reviewed all patients who were treated with IV rt-PA at two comprehensive stroke centers from September 2008 to July 2010 and identified a total of 98 patients. In addition, we identified patients who arrived to the ED of those centers within 2.5 to 4 hrs of symptom onset between January 2007 and June 2010 and received only endovascular treatment. We compared the rates of favorable outcome (determined by using modified Rankin scale 0-2 at discharge and 3-month follow up), and NIHSS score improvement by Ն 4 points or 0 at discharge among patients treated with IV rt-PA within 3-4.5 hrs with those who received IV rt-PA within 0-3 hrs, and subsequently with patients presenting at similar time window treated only with endovascular treatment. Result: The 98 IV rt-PA treated patients had mean admission NIHSS score ϩSD: 11.4Ϯ6.6, mean ageϩSD: 66Ϯ17 and 47 (48%) were women. 14% of patients received IV rt-PA within 3-4.5 hours. Baseline characteristics were not different between both comparison groups. Favorable clinical outcome at discharge (50% vs. 56%, pϭ0.77), 3 months (64% vs. 64%, pϭ1.0), and NIHSS score improvement (43% vs. 58%, pϭ0.38) were not different between those treated within 3-4.5 and 0-3 hrs time windows. There appeared to be a non-significantly higher rate of favorable outcomes at discharge (25% vs. 50%, pϭ0.24), and at 3 months (42% vs. 64%, pϭ0.43) among patients treated with IV rt-PA within 3-4.5 hrs compared with those treated with primary endovascular treatment. Conclusion: An additional 14% of patients received IV rt-PA because of treatment window expansion from 3 to 4.5 hours with comparable outcomes to those treated within 3 hours after symptom onset. The shift of those patients from primary endovascular treatment does not appear to adversely affect patient outcome. Background: Many patients found to have stroke signs during paramedic evaluation in the field will have complete and rapid resolution of those signs. There may be clinical factors which identify whether a patient is more likely to have clinical resolution (CR) on subsequent examination. Previous studies have evaluated the proportion of patients with cerebral ischemia and hemorrhage with complete resolution of signs but have not focused on patients evaluated in the field in the first hours after symptom onset. Objective: To determine the frequency and predictors of rapid CR of motor signs of unilateral weakness among stroke patients evaluated in the field using the Los Angeles Prehospital Stroke Screen (LAPSS) which incorporates the Los Angeles Motor Score (LAMS), a 0-5 scale quantifying unilateral weakness of the face, arm, and hand. Methods: The study population is comprised of consecutive subjects enrolled in the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) clinical trial were evaluated in the field using the LAPSS within 2 hours of their last-known-well-time (LKWT) and randomized to receive intravenous Magnesium Sulfate or placebo. A second evaluation was performed by the FAST-MAG study nurse coordinator in the emergency department (ED). CR was defined using the definition of a follow-up ED evaluation LAMS score of 0 indicating no weakness. Clinical, demographic, and enrollment-related factors were compared in those with CR and those without. Results: A total of 1029 subjects were evaluated in the field using the LAMS an average of 45 minutes after LKWT. Median (range) of field LAMS 4 (1-5), and 131 (13%) experienced CR of motor weakness (LAMSϭ0) on the follow-up evaluation performed a median of 108 minutes following the field LAMS. A host of clinical factors were evaluated for an association with CR including age, gender, ethnicity, time to evaluation, blood pressure, medical history (hypertension, diabetes, dyslipidemia, atrial fibrillation, coronary artery disease, valvular heart disease) and results of initial imaging. The only variable which significantly predicted complete clinical resolution was absence of intracerebral hemorrhage on initial imaging. There were 240 cases (23%) with ICH on initial ED imaging of which only 2 (Ͻ1%) experienced CR, compared to 15% of the 789 with no evidence of ICH on initial imaging. Conclusions: Among patients with motor stroke signs Ͻ2 hours in duration from symptom onset evaluated in the field, approximately 13% will have complete resolution of motor weakness on subsequent evaluation in the ED. We were not able to find any predictors of CR which would be beneficial in the field. Those patients with resolution of motor symptoms in the first few hours are highly unlikely to have intracerebral hemorrhage. The FAST-MAG study will be able to evaluate whether treatment with Magnesium Sulfate affected rates of CR.

W P175 Mri Based Tia Triage Study

Connie Wolford, Michael Mlynash, Neil E Schwartz, Archana Purushotham, Maarten Lansberg, Stephanie Kemp, Gregory W Albers, Jean-Marc Olivot; STANFORD STROKE CENTER, Palo Alto, CA Rapid Diagnostic Evaluation of TIA Using a Clinical Decision Area Triage Approach Background The AHA scientific statement on the evaluation of TIA recommends an urgent evaluation including a brain MRI and neck vessel imaging within 24 hours after symptom onset. The purpose of this ongoing prospective study is to determine whether an ER-based triage system that performs acute evaluation, including brain MRI and neck vessel imaging within less than 24 hours, is feasible and associated with a low rate of early stroke. Methods In January 2010 we initiated a new triage protocol for suspected TIA patients at the Stanford Emergency Department (ED). Patients considered likely to have suffered a TIA are transferred to the Clinical Decision Area (CDA) which is a short term (Ͻ24 hours) observation unit where patients undergo brain MRI and neck vessel imaging, close cardiac and neurological monitoring and a consult from a stroke neurologist. If the CDA evaluation reveals an acute ischemic lesion on DWI, a symptomatic intracranial or extracranial stenosis or other unstable condition, the patient is admitted to the Stanford Stroke Service. Patients with a negative evaluation in the CDA are discharged and followed up in the outpatient TIA clinic. Patients are assessed for outcome events at 7, 30 and 90 days. Results Sixty seven suspected TIA patients were enrolled over 6 months. Sixty four (96%) arrived at the ED within 24 hrs of symptom onset. Sixty-two underwent DWI and 65 had neck vessel imaging. MRI was performed within 24 hrs of symptom onset in 48 patients (77%), and within 24 hrs of ED arrival in 55 patients (89%). Thirty seven patients had a final diagnosis of stroke (nϭ11) or TIA (nϭ26). In addition, 11 patients had a diagnosis of a possible TIA. Median ABCD2 score was 4 (IQRϭ3-4). An acute ischemic lesion on DWI was detected in 16 patients (24%) and a symptomatic vessel stenosis was present in 6%. Forty-six patients were transferred from the ER to the CDA. Nineteen patients (28%) were admitted to the Stroke Service (8 directly from the ED and 11 from the CDA). Forty eight patients were discharged home (35 from the CDA and 13 from the ED). Only one patient suffered a subsequent stroke; 30 day stroke rate was 0.014 (95% CI: 0.002-0.08). The patient with a subsequent stroke was discharged from CDA after normal initial evaluation [MRI, MRA, EKG] then experienced a minor stroke, NIHSSϭ1, seven days after discharge. Conclusion: Urgent TIA evaluation, including obtaining an MRI and vessel imaging within 24 hours, is feasible using an ED-based clinical observation unit. Preliminary data suggest this approach is associated with low stroke rates.

Author Disclosures: C. Wolford: None. M. Mlynash: None. N.E. Schwartz: None. A. Purushotham: None. M. Lansberg: None. S. Kemp: None. G.W. Albers: None. J. Olivot: None.

W P176 TIA Patients' Arrival Time To The Emergency Department Within A Population: No Association With Symptom Severity, Duration, Or ABCDD Score

Shannon Kohake, Heidi Sucharew, Kathleen A Alwell, Charles J Moomaw, Brett M Kissela, Daniel Woo, Opelu Adeoye, Matthew Flaherty, Pooja Khatri, Simona Ferioli, Dawn Kleindorfer; Univ of Cincinnati, Cincinnati, OH Background: Ongoing trials are investigating the efficacy of early intervention after TIA in preventing subsequent ischemic events. Arrival patterns among TIA patients are of interest from both a public health and clinical trial perspective. Previously we reported that over time TIA patients within our population are arriving more quickly for emergency care. We sought to describe specific factors that impact emergency department (ED) arrival times in TIA. We hypothesized that greater symptom severity, longer symptom duration, and higher ABCDD score (a score used to predict risk of future stroke in TIA) would shorten arrival times in TIA patients within our large biracial population. Methods: Using ICD-9 codes 430-436, we ascertained and physician-verified all TIA events (symptom duration Ͻ24 hours) presenting to a local ED within our population of 1.3 million in 2005. Time of symptom onset and ED presentation, symptom duration, initial retrospective NIHSS score, description of clinical deficits, patient demographics, and medical history were recorded as documented in the medical record. The relationships between ED arrival time and symptom severity, symptom duration, and ABCDD score were analyzed with generalized estimating equations. Results: The total number of TIA events presenting to an ED in 2005 was 834. The mean age was 69, 42% were male, and 12% were black. Overall, 56% resolved prior to arrival. The percent with exact/estimated/unknown onset and arrival times was 57%, 32%, and 11%, respectively. Symptom duration was known or estimated in 829 events; duration was Ͻ10 minutes in 10%, 10-59 minutes in 30%, and at least 60 minutes in 61%. Initial NIHSS score was available for 704 events, with a median score of 1 (interquartile range: 0, 2). ABCDD score was known for 818 events; 22% had a score of 0-3, 50% had a score of 4-5, and 29% had a score of 6-7. There was no association between symptom severity, symptom duration, or ABCDD score and time to ED arrival. Conclusion: Contrary to our hypothesis, we found that within our population the time from symptom onset to ED arrival for TIA patients was not associated with duration or severity of symptoms, or with ABCDD score. As with ischemic stroke patients, documentation of symptom onset times remains problematic, with only half of the TIA events having exact times documented. Patients at highest risk for subsequent ischemic stroke do not appear to seek emergency care more quickly than patients at lower risk. Continued public health campaigns are needed to emphasize stroke risk factors and encourage quick action even if symptoms resolve.

Introduction: Clinical scores to predict the stroke risk in patients with TIA do not incorporate imaging data, which could improve the prognostic accuracy. Evidence for the incidence of intracranial CT angiography (CTA) abnormalities and their prognostic significance in patients presenting with TIA are scant. Methods: We retrospectively indentified all patients with an emergency department (ED) discharge diagnosis of TIA by ICD-9 code (435) between 1/2009 -3/3010, and who underwent CT angiography at time of evaluation. ED diagnosis of TIA was validated, and clinical and demographic data were abstracted from electronic medical records by a neurologist blinded to radiographic findings. Follow-up was evaluated up to 1 year after index event. Two neurointerventionalists, blinded to clinical data, reviewed and scored each CTA independently. Each reader located and viewed 10 pre-specified extracranial and 13 intracranial arterial segments per study. Degree of stenosis was categorized into none, mild (1-49%), severe (50-99%), or occluded. A third neuroradiologist adjudicated any differences. Dichotomous variables were compared using Chi squared test or Fisher's exact if appropriate. Multivariate logistic regression was used to identify predictors of CTA abnormalities, and to evaluate the association of CTA abnormalities with stroke outcome. Results: Of 99 patients with an ED discharge of TIA, 57 had undergone CTA and had validated TIAs. The mean age was 72 Ϯ12 years, and 54% were women. Mean ABCD2 score was 4.5 Ϯ1.6, with 60% having an ABCD2Ն4. Seven patients (12%) had at least one intracranial vessel segment with severe stenosis, and 2 (4%) patients had intracranial occlusions. Seven patients (12%) had at least one extracranial vessel segment with severe stenosis. No extracranial occlusion was seen in this cohort. In 9 patients (16%), their severe stenoses or occlusions could account for their presenting symptoms. Three subjects (8%) had strokes within 1 year of the index TIA, and 6 (16%) had recurrent TIA. There were no significant differences in follow-up stroke (7% vs. 11%, pϭ0.7), TIA (11% vs. 33%, pϭ0.11), or combined vascular event (4% vs. 11%, pϭ0.38) between subjects with no severe stenoses, and those with at least one severe intra or extracranial stenosis or occlusion. Among the 3 patients with stroke during the follow-up period, one had severe stenoses in both the anterior and posterior intracranial circulations, and 2 had no severe stenosis. Conclusions: Severe intra-or extracranial vascular stenoses or occlusions are relatively common among patients presenting to the ED with TIA. The

Introduction:

We have previously shown within a population that 18% of acute ischemic stroke (AIS) events were not given a diagnosis consistent with stroke in the Emergency Department (ED). These missed diagnoses were more likely in patients who presented with altered mental status or nonfocal weakness. Here, we further characterize the subtypes of AIS that were missed in the ED, and we evaluate the impact of a missed diagnosis on hospital length of stay (LOS). We hypothesized that patients with large vessel disease or embolic stroke would be less likely to be missed and patients with a missed diagnosis would have an increased LOS. Methods: ICD-9 codes 430-436 were screened to identify all stroke cases that presented to EDs of all 16 adult hospitals in the Greater Cincinnati/Northern Kentucky region in 2005. Cases were abstracted by research nurses and confirmed by study physicians. For this analysis, transient ischemic attacks, hemorrhagic strokes, and in-hospital strokes were excluded. An ED diagnosis of AIS was defined as a neurologic diagnosis indicative of stroke, including "rule-out stroke" and/or focal neurologic deficit description (ie. "left sided weakness" or "aphasia"). AIS subtypes were categorized by study physicians into large vessel, small vessel, cardioembolic, other identified cause, or an undetermined etiology. "Other" causes of stroke included cocaine use, dissection, surgery (peri-or immediate post-op), angio/cath/PTCA, cancer, hypercoagulable states, or venous thrombosis. Stroke subtypes and LOS were compared between patients with and without an ED diagnosis of AIS using Pearson's chi-squared test or the Mann-Whitney U-test, as appropriate. Results: Of 1498 confirmed AIS cases presenting to an ED, 275 (18.4%) had an ED diagnosis that was inconsistent with AIS. Sex, age, race, and medical history were similar between those with and without a missed diagnosis. Missed diagnosis of AIS was associated with stroke subtype (pϭ0.039); large vessel, 14.7% (35/238) missed, small vessel 17.0% (53/312), cardioembolic 17.8% (58/326), other causes 33.3% (15/45), and undetermined 19.8% (114/577). Patients with a missed diagnosis of stroke were more likely to have an increased LOS (5 days vs. 4 days, PϽ0.001). Conclusion: In our region, nearly 1 out of 5 cases of AIS were not given an ED diagnosis of AIS. The probability of a missed ED diagnosis was higher among cases with an "other" subtypes of stroke, and patients with a missed diagnosis also had a longer hospital LOS. A missed diagnosis could lead to missed opportunities for early treatment, therefore, a heightened awareness of atypical causes of ischemic stroke is necessary in patients presenting to the ED with atypical symptoms. The sole FDA approved treatment for acute stroke is tissue type plasminogen activator (tPA). However, tPA potentiates impairment of pial artery dilation (PAD) in response to hypotension after photothrombosis in pigs. ATP and Ca sensitive K channels (Katp and Kca) are important regulators of cerebrovascular tone and mediate PAD in response to hypotension. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and JNK, is upregulated after photothrombosis, with JNK contributing to vasodilator impairment. This study examined the effect of photothrombosis on Katp and Kca-mediated cerebrovasodilation and the roles of tPA and MAPK in this effect. Methods: Photothrombotic injury (PTI) was produced by directing a laser (532 nm) onto piglet pial arteries after injection of erythrosine B. Drugs were given 30 min before or 2h after PTI. Phosphorylated and total ERK, p38, and JNK MAPK were measured by ELISA in the CSF of piglets equipped with a closed cranial window. Data (nϭ5) were analyzed by ANOVA, with significance at p less than 0.05. Results: PTI blunted PAD induced by the Katp agonists cromakalim, calcitonin gene related peptide (CGRP) and the Kca agonist NS 1619, which was exacerbated by tPA given before or after injury. JNK and p38 were upregulated after PTI, which was potentiated by tPA while ERK was unchanged. The JNK antagonist SP600125, given before or after PTI, prevented impairment of PAD in response to cromakalim and CGRP, but did not effect the response to NS 1619. The p38 antagonist SB203580 potentiated impairment of PAD by cromakalim, CGRP, and NS 1619 after injury, while the ERK antagonist U 0126 had no effect. Discussion: These data indicate that photothrombosis impairs K channel mediated cerebrovasodilation. tPA augments loss of K channel function after injury by upregulating JNK, while p38 may serve in a protective role. These data suggest that photothrombosis produces cerebrohemodynamic dysregulation during hypotension by impairing Katp and Kca mediated cerebrovasodilation via upregulation of JNK. These data suggest that thrombolytic therapy for treatment of CNS ischemic disorders can produce cerebrohemodynamic dysregulation through impairment of ionic controls of cerebrovascular tone.

Author Disclosures: W. Armstead: Research Grant; Significant; NIH RO1 NS53410. J. Riley: None. D. Cines: None. V. Muzykantov: None. A. Higazi: None.

W P181 MicroRNA 17-92 Cluster Mediates Erythropoietin-induced Cerebral Angiogenesis

Hua Teng, Henry Ford Hosp, Detroit, MI; Michael Chopp, 1Henry Ford Hosp, 2Dept of Physics, Oakland Univ, 1Detroit, 2Rochester, MI; Xianshuang Liu, Lei Wang, Yisheng Cui, Zheng Gang Zhang; Henry Ford Hosp, Detroit, MI Introduction: MicroRNAs, a class of non-coding small RNAs, regulate angiogenesis. Erythropoietin (EPO) enhances angiogenesis in the ischemic brain. However, the role of microRNAs in EPO induced angiogenesis has not been elucidated. In the present study, we tested the hypothesis that miR17-92 cluster mediates EPO-induced angiogenesis. Methods and Results: Cerebral endothelial cells (CECs) were isolated from microvessels of adult non-ischemic rats (nϭ10) or rats subjected to 7 days of the right middle cerebral artery occlusion (MCAo, nϭ6). MicroRNA microarray analysis of CECs revealed that ischemia downregulated and upregulated many miRNAs including miR-19a, a member of miR17-92 cluster. Real-time RT-PCR shows an increase in miR-19a in ischemic CECs (1.6Ϯ0.1 vs 1.1Ϯ0.04 in non-ischemia, nϭ3, PϽ0.05), which confirms microarray finding. Incubation of CECs with EPO (10 U/ml) significantly (pϽ0.05) upregulated miR-19a (7.2Ϯ0.6 vs 1.0Ϯ0.03, nϭ3), which was associated with substantial increases in capillary tube formation (3.5Ϯ0.9 vs 2.1Ϯ0.5 mm/mm 2 ), an in vitro angiogenesis assay. Western blots show that EPO significantly reduced thrombospondin 1 (TSP1, 0.7Ϯ0.2 vs 1.0Ϯ0.003, nϭ3) and connective tissue growth factor (CTGF) by 25% compared with the control. Transfection of CECs with miR17-92 cluster decreased TSP1 and CTGF protein levels to 79% and 72% of scrambled control, respectively, leading to significantly increased tube formation (8.2Ϯ0.5 vs 4.9Ϯ1.4 mm/mm 2 , nϭ5) compared with levels in CECs transfected with scramble, which is consistent with fact that the miR17-92 cluster targets the TSP1 and CTGF in endothelial cells and downregulation of TSP1 promotes angiogenesis. In addition, EPO increased c-Myc protein levels in CECs (2.1Ϯ0.1 vs 1.0Ϯ0.001, nϭ3, PϽ0.05). Conclusions: The c-Myc has been shown to upregulate expression of the miR17-92 cluster. Thus, the present study indicates that EPO triggers c-Myc which upregulates miR17-92 cluster, leading to enhancement of angiogenesis by targeting anti-angiogenic genes TSP1 and CTGF.

Author Disclosures: H. Teng: None. M. Chopp: Research Grant; Significant; PO1 NS23393. X. Liu: None. L. Wang: None. Y. Cui: None. Z. Zhang: Research Grant; Significant; RO1 HL64766.

W P182 Infarct Size Prediction Using A Combined Technique Of Laser Doppler Flowmetry And Near-infrared Fluorescent Thrombi Imaging In A Mouse Model Of Embolic Stroke

Dong-Eog Kim, Jeong-Yeon Kim, Byeong-Teck Kang, Jin-Ok Choi, Dong Kun Lee, Won Jun Choi, Sang-Wuk Jeong, Molecular Imaging & Neurovascular Rsch Lab, Dongguk Univ. Ilsan Hosp., Goyang, Korea, Republic of; Kwangmeyung Kim, Ick Chan Kwon; Biomedical Rsch Cntr, Korea Institute of Science and Technology, Seoul, Korea, Republic of Background: There is a notion that failure of bench-to-clinic translation is partly due to the fact that experimental studies vary considerably in quality and reliability. Embolic stroke models have been great assets to stroke researchers, however they provide less control over the location and extent of the thrombi. Objectives: 1) To describe a near-infrared fluorescent (NIRF) imaging technique to measure the distribution and extent of the cerebral thrombi on ex vivo mouse brain and 2) to show how the technique, in combination with laser Doppler flowmetry (LDF) monitoring in vivo, could be helpful in predicting infarct size variability. •Methods: Autologous blood clots were labeled with a Cy5.5 NIRF imaging agent that can detect activity of the factor XIII coagulation enzyme. In 10-week-old mice (nϭ45), the NIRF labeled clot emboli (3.70mm 3 ) were injected into the proximal portion of the left middle cerebral artery (MCA), while monitoring the cerebral blood flow (CBF) for 30 minutes using a LDF machine. Twenty-four hours later, the animals were euthanized, and the brains were removed and imaged ex vivo using a NIRF imaging machine. The brains were then used for immediate TTC staining to delineate the infarct area. After normalization, pixel counts of Cy5.5 NIRF signal in the left MCA and adjacent arteries, which represent thrombi extent, were calculated. The left hemisphere infarct volumes were measured and expressed as a percentage of the intact right hemisphere volume. Results: We confirmed that molecular optical labeling of thrombi and NIRF imaging allowed clear visualization of cerebral thrombi ex vivo. Representative brain sections showed corresponding thrombus filling the vessels. Next we observed that the decrease of CBF on LDF following placement of thrombi was rather variable (44.9Ϯ16.1% of the baseline, range 17ϳ78%). Moreover, we could demonstrate that substantial heterogeneity existed in the distribution and extent (150.6Ϯ121.4 pixels, range 0ϳ557) of remaining thrombi at 24h. Accordingly, infarct size was quite variable (30.6Ϯ10.1%, range 9.9ϳ52.8%). The CBF decrease was positively correlated with the infarct size (rϭ0.41, PϽ0.05). The thrombi extent was also positively correlated with the infarct size (rϭ0.40, PϽ0.05). A multiple regression analysis revealed that both CBF decrease and thrombi extent could independently (and when combined, better) predict the infarct size (r ϭ0.53, PϽ0.

W P183 Neuroprotective Effect of TAK-937, a Novel Cannabinoid Receptor Agonist, in Rat Permanent and Thrombotic Middle Cerebral Artery Occlusion Models

Koji Murakami, Motohisa Suzuki, Noriko Suzuki, Kazuhiro Hamajo, Tetsuya Tsukamoto, Masato Shimojo; Takeda Pharmaceutical Company Limited, Osaka, Japan Introduction: TAK-937 is a novel, highly potent and selective cannabinoid (CB1/CB2) receptor agonist. We examined the effect of TAK-937 in a permanent middle cerebral artery occlusion (MCAO) model in rats. In addition, the effect of TAK-937 in combination with tissue-type plasmsminogen activator (t-PA) was examined in a rat thrombotic MCAO model. Methods: Thrombotic MCAO was induced by photo-irradiation of MCA with rose bengal administration. Permanent MCAO was induced by coagulation of MCA electrically in male young-adult and aged rats. TAK-937 across a dose range between 10 to 100 ı `g/kg/hr or vehicle was intravenously infused starting 1, 3, 5 or 8 hr to 24 hr after MCAO (nϭ7ϳ18 for each group). t-PA at 3 mg/kg was intravenously administered as a bolus injection in 20% of total volume, followed by an infusion of the remainder over a period of 30 min 1, 1.5 or 2 hr after MCAO (nϭ5ϳ7 for each group). Infarct volume was determined by 2, 3, 5-triphenyltetrazolium chloride staining method 24 or 48 hr after MCAO. In combination studies, t-PA was administered at 3 mg/kg together with TAK-937 at either 30 or 100 g/kg/hr. These were compared with the results of single administration of t-PA at 3 mg/kg, and TAK-937 at 10 and 30 g/kg/hr (nϭ5ϳ8 for each group) and their infarct volume was determined 24 hr after MCAO. Results: TAK-937 significantly reduced infarct volume in a dose dependent manner when administered up to 5 hr after in young-adult rats with permanent MCAO (pϽ0.025). No such effect was observed when TAK-937 was administered 8 hr after MCAO. Moreover, TAK-937 at 100 g/kg/hr showed significant reduction of infarct volume in aged rats with permanent MCAO (pϽ0.05). t-PA administered 1 hr after MCAO significantly reduced the infarct volume in rats with a thrombotic MCAO (pϽ0.05) but such effect was not observed when t-PA was administered later than 1 hr. Combined treatment of t-PA with 30 or 100 g/kg/hr of TAK-937 1 hr after MCAO showed further reduction in infarct volume compared to t-PA alone (pϽ0.025). Conclusion: TAK-937 exerted neuroprotective effects in both young adult and aged rats with a wide therapeutic time window in a rat permanent MCAO model. Furthermore, TAK-937 produced an enhanced therapeutic effect when given in combination with t-PA in a rat thrombotic MCAO model.

W P184 Visualization of Clot Lysis in a Rat Embolic Stroke Model

Bernt Tore Bratane, Ronn P Walvick, Nils Henninger, Kenneth M Sicard, James Bouley, Univ of Massachusetts Med, Worcester, MA; Zhanyang Yu, Eng Lo, Xiaoying Wang, Harvard Med Sch, Charlestown, MA; Marc Fisher; Univ of Massachusetts Med, Worcester, MA Objectives: The purpose of this study was to develop a novel MRI method for imaging clot lysis in a rat embolic stroke model, and to compare tissue plasminogen activator (tPA) based clot lysis with and without recombinant Annexin-2 (rA2). Methods: Experiment 1: In vitro optimization of clot visualization using multiple MRI contrast agents in concentrations ranging from 5 to 50L in 250L blood. Experiment 2: In vivo characterization of the time course of clot lysis using the clot developed in the previous experiment. Diffusion, perfusion, angiography, and T1-weighted MRI for clot imaging were conducted prior to and during treatment with vehicle (n ϭ 6), tPA (n ϭ 8) or rA2ϩtPA (n ϭ 8) at multiple time-points. Brains were removed for ex vivo clot localization facilitated by Evans Blue (EB) staining of the clot developed in experiment 1. The T1 and EB clot visualization is displayed in Figure 1.

Results: Clots created with 25L Magnevist© were the most stable and provided the highest contrast-to-noise ratio. In the vehicle group, clot length as assessed by T1-weighted imaging correlated with histology (r ϭ 0.93). Clot length and CBF-derived ischemic lesion volume were significantly smaller than vehicle at 15 minutes post-treatment initiation in the rA2ϩtPA group, while in the tPA group no significant reduction from vehicle was observed until 30 minutes post-treatment initiation. The rA2ϩtPA group had a significantly shorter clot length than the tPA group at 60 and 90 minutes post-treatment initiation, and significantly smaller CBF deficit than the tPA group at 90 minutes post-treatment initiation (see Figure 2).

Conclusion:

We introduce a novel MRI based clot imaging method for in vivo monitoring of clot lysis. Lytic efficacy of tPA was enhanced by rA2. demonstrated that inhibition of CaMKK is detrimental in stroke. CaMKK directly activates CaMK IV (Calcium/Calmodulin Dependent Protein Kinase IV). Although CaMK IV is a known cellular survival factor, its role in stroke remained unknown. In this study, we assessed the hypothesis that inhibiting CaMK IV is detrimental in experimental stroke. Methods: Stroke was induced by reversible middle cerebral artery occlusion (MCAO-90 minutes) in male CaMKK IV knockout (KO) mice and littermate (WT) mice. The matrix metalloproteinases (MMP) inhibitor SB-3CT or vehicle was injected at the onset of stroke to CAMK IV KO mice. Stroke outcome was determined with TTC-staining at 24 hrs. Neurological scoring was done prior to sacrifice. Immunohistochemistry was used to assess blood brain barrier protein collagen IV loss. Gel zymography was used to measure the activity of MMP 9. Data are presented as meanϮsem. Results: CaMK IV KO mice had significantly increased cortical (KO 64.9 Ϯ 4.9% vs. WT 48.9Ϯ4.1%, PϽ0.05), striatal (KO 77.8Ϯ5.8% vs. WT 62.2Ϯ2.5%, PϽ0.05) and total (KO 61.0Ϯ5.1% vs. WT 43.4Ϯ3.7%, PϽ0.05) (nϭ7/pg) infarct volumes compared to WT littermates. This was reflected in exacerbated neurological deficits (KO 3.1Ϯ0.3 vs. WT 2.3Ϯ0.2, PϽ0.05) in KO mice. Stroke-induced mortality was seen in 6 out of 13 in CaMK IV KO mice with increased intracerebral hemorrhagic transformation rate whereas no WT control mice died. A dramatic loss of collagen IV (55%) was seen in CaMK IV KO mice 4 hours after stroke, an effect not seen in WT controls. The exacerbated blood brain barrier disruption in KO was associated with enhanced MMP 9 activity after stroke. Treatment of MMP 9 inhibitor SB-3CT reversed the detrimental phenotype of CaMK IV KO mice and reduced mortality rate and decreased infarct size. There were no differences in physiological parameters between CaMK IV KO and WT groups. In addition, local cerebral blood flow measured by Laser Doppler Flow was equivalently reduced during ischemia (KO 11.2Ϯ1.1% versus WT 12.3Ϯ1.1%, nϭ4/pg) and was restored equally in early reperfusion. Conclusion: Our data demonstrated that genetic deletion of CaMK IV is detrimental after experimental stroke and this effect was secondary to BBB disruption and activation of MMP9 activation. This suggests that CaMK IV may represent a novel therapeutic target for stroke treatment and to restore BBB dysfunction. This research has received full or partial funding support from the American Heart Association, National Center.

W P186 Anesthesia Confounds in Experimental Stroke and Preconditioning

Liang Zhao, Thaddeus S Nowak, Jr.; Univ of Tennessee Health Science Cntr, Memphis, TN Prolonged anesthesia is often required in the application of imaging and recording modalities to experimental stroke, but its potential impact on the parameters under study is not always considered. A specific confound was identified in the course of monitoring CBF transients as an index of peri-infarct depolarizations (PIDs) using speckle contrast perfusion imaging, in a model of lesion-induced preconditioning in Spontaneously Hypertensive Rats. Animals (5-12 per group) experienced initial surgery under brief isoflurane anesthesia to produce small cortical freeze lesions (cold lesions, CL), or a sham procedure. The following day rats were subjected to permanent tandem MCA/CCA occlusion, again under isoflurane anesthesia. CL rats allowed to recover from anesthesia exhibited significantly smaller 24 h edema-corrected infarct volumes than a Naı ¨ve group, with no effect of the Sham procedure, demonstrating a robust preconditioning phenomenon (Naı ¨ve 116 Ϯ 14, Sham 113 Ϯ 11, CL 85 Ϯ 14 cubic mm; P Ͻ 0.05 CL vs. Naive). However, animals maintained under isoflurane anesthesia for perfusion imaging exhibited comparably reduced PID incidence in Sham and CL groups (both 3 Ϯ 1 vs. 7 Ϯ 2 in Naı ¨ve), and no differences in infarct volume after the acute 4 h monitoring interval (Naı ¨ve 99 Ϯ 20, Sham 85 Ϯ 11, CL 94 Ϯ 9 cubic mm). In contrast, transition to a ´-chloralose immediately after occlusion increased overall PID incidence and eliminated the Sham effect, but maintained reduced PID number in the CL group (Naive 17 Ϯ 5, Sham 15 Ϯ 6, CL 6 Ϯ 2; P Ͻ 0.05 CL vs. Naive). Furthermore, 4 h infarct volumes in these groups faithfully replicated the initial preconditioning study (Naive 112 Ϯ 13, Sham 111 Ϯ 16, CL 90 Ϯ 18 cubic mm; P Ͻ 0.05 CL vs. Naive). These results identify a subtle influence of prior isoflurane exposure on acute stroke pathophysiology when under anesthesia with the same agent. Replacement of isoflurane with a ´-chloralose accelerates infarct progression, acutely replicates subsequent histopathological outcome in the model under study, and reveals a specific impact of cold lesion preconditioning on the incidence of PIDs, considered to be of direct mechanistic relevance to infarct evolution. Although a ´-chloralose itself markedly attenuates absolute brain blood flow and metabolism it has been widely used in studies of neurovascular coupling. It now appears to be of specific utility in avoiding confounding effects of repeated isoflurane anesthesia in experimental stroke.

Author Disclosures: L. Zhao: None. T.S. Nowak: None.

W P187 Neuroprotective Effect of TAK-937, a Novel Cannabinoid Receptor Agonist, in a Rat Transient Middle Cerebral Artery Occlusion Model

Noriko Suzuki, Motohisa Suzuki, Kazuhiro Hamajo, Koji Murakami, Tetsuya Tsukamoto, Masato Shimojo; Takeda Pharmaceutical Company Limited, Osaka, Japan Introduction: TAK-937 is a novel, highly potent and selective cannabinoid (CB 1 /CB 2 ) receptor agonist. This study examined the effects and explored the mechanism of actions of TAK-937 in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: Male Sprague-Dawley (SD) rats were subjected to 2 hr transient MCAO by inserting an intraluminal suture. TAK-937 at 3, 10, 30 and 100 g/kg/hr or vehicle was intravenously administered for 22 hr from 2hr after MCAO and their infarct volume was determined in a dose-response study (nϭ16ϳ20 for each group). Functional outcomes (neurological symptom and foot-fault test) and brain atrophy were also evaluated 4 weeks after 2 hr transient MCAO and TAK-937 at 30 and 100 g/kg/hr or vehicle treatment (infusion for 22 hr) (nϭ23ϳ27 for each group). Effects of TAK-937 at 30 g/kg/hr (infusion for 22 hr) on infarct volume were also examined in 2 hr transient MCAO in female and ovariectomized (OVX) SD rats (nϭ10ϳ15 for each group). In a study to assess contribution of hypothermia to the neuroprotective effects of TAK-937, brain temperature of freely moving male SD rats was telemetrically monitored and maintained between 37 and 38 °C during intravenous infusion of TAK-937 at 100 g/kg/hr for 24 hr after MCAO using a multi-channel brain temperature controlling system (nϭ10ϳ11 for each group). Subsequently, infarct volume was determined. Results: In the dose response study, infarct volumes at 3, 10, 30 and 100 g/kg/hr of TAK-937 were reduced in a dose-dependent manner compared with infarct volume in the vehicle treated animals by 3.5 (pϾ0.025), 23.5 (pϽ0.025), 48.9 (pϽ0.025) and 66.3% (pϽ0.025), respectively. TAK-937 at 30 and 100 g/kg/hr significantly ameliorated neurological symptom, motor impairment and brain atrophy until 4 weeks after MCAO (pϽ0.025). TAK-937 at 30 g/kg/hr also reduced infarct volume in female and OVX rats (pϽ0.05). When the hypothermic effect of TAK-937 at 100 g/kg/hr (about 4 degree Celsius) was completely reversed to the same level of brain temperature in the vehicle group by warming, the neuroprotective effect of TAK-937 was partially attenuated (pϽ0.01) although significant reduction in cerebral infarct volume was still observed (pϽ0.05). Conclusion: TAK-937 exerts neuroprotective effects in a transient MCAO model in male, female and OVX rats. This neuroprotective effect may be mediated in part by the induction of hypothermia. TAK-937 also brings long-term improvement in functional outcomes and brain atrophy at 4 weeks.

Author Disclosures: N. Suzuki: Employment; Significant; Takeda Pharmaceutical Company Limited. M. Suzuki: Employment; Significant; Takeda Pharmaceutical Company Limited. K. Hamajo: Employment; Significant; Takeda Pharmaceutical Company Limited. K. Murakami: Employment; Significant; Takeda Pharmaceutical Company Limited. T. Tsukamoto: Employment; Significant; Takeda Pharmaceutical Company Limited. M. Shimojo: Employment; Significant; Takeda Pharmaceutical Company Limited.

W P188 Very Brief Focal Cerebral Ischemia Induces A Delayed Immune Response In Peripheral Blood Of Rats

Xinhua Zhan, Bradley P Ander, Frank R Sharp; MIND Institute, Univ of California at Davis, Sacramento, CA Background: Inflammation is a common event observed in both acute and chronic neurological conditions including stroke, Alzheimer's disease, and multiple sclerosis. Currently, inflammation is considered a critical determinant outcome following acute brain injury. A prominent inflammatory response occurs following both ischemic stroke and hemorrhagic stroke. Although one third of patients with transient ischemic attack (TIA) go on to have ischemic strokes, the link between TIA and subsequent ischemic stroke has not been identified. Related to this issue, we have shown that inflammatory response occurs in the brain 1 and the peripheral blood 2 in rats at 24h postischemia in both animal models of TIA and stroke. However, the delayed inflammatory response has not been identified in TIA patients or animal models. In the current study we investigate whether brief focal ischemia in rats, simulating TIA in humans, produces delayed inflammatory response in peripheral blood. Method: Adult rats (nϭ3 in each group) were subjected to 10 minutes of middle cerebral artery occlusion followed by 48h or 72h of reperfusion and compared to 24h of reperfusion. Whole blood was obtained and RNA expression assessed on whole genome Affymetrix microarrays. Results: Compared to 24h, 48h and 72h reperfusion resulted in significantly altered expression of 90 and 428 genes, respectively (absolute fold change Ն 1.5 and false discovery rate Յ 0.05). Among these genes, 3 and 25 genes were involved in inflammatory response at 48h and 72h postischemia, respectively. Most of these inflammatory related genes (24 out of 25) were not regulated at 24h postischemia compared to naı ¨ve controls as we previously demonstrated 2 , which suggested a delayed inflammatory response. The inflammatory related genes were mainly involved in the pathways of 'T cell receptor signaling', 'CTLA4 signaling in cytotoxic T lymphocytes', 'calcium-induced T lymphocyte apoptosis', and 'cytotoxic T lymphocyte-mediated apoptosis of target cells'. These results provide evidence that delayed adaptive immune responses occur at 72h postischemia in the peripheral blood of rats. We postulate that this will also occur in humans. Conclusion: Very brief focal ischemia induces a delayed immune response in peripheral blood of rats. The data supports the possibility that human patients with TIAs may have similar changes in blood gene expression, and that some of these changes may depend on the duration of post cerebral ischemia.

W P189 TLR3 Ligand Attenuates Cerebral Ischemia/Reperfusion Injury

Xia Zhang, Tuanzhu Ha, Jim Kelley, Race Kao, David Williams, Chuanfu Li; EAST TENNESSEE STATE UNIVERSITY, Johnson City, TN Introduction: Innate immune and inflammatory responses have been implicated in cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLR) play a critical role in the induction innate immunity and inflammatory response. However, it is unclear whether modulation of TLR will induce protection against cerebral I/R injury. The TLR3 mediated signaling pathway directly stimulates production of interferon-a ˆand local injection of interferon-a ˆhas been shown to decrease cerebral I/R injury. We hypothesized that modulation of TLR3, with Poly I:C ligand, will induce protection against cerebral I/R injury. Methods: To evaluate our hypothesis, we treated male C57BL/6 mice with the TLR3 ligand, Poly I:C (nϭ8, 75 g/25 g body weight) or placebo (nϭ8) by i.p injection one hr before the brains were subjected to cerebral ischemia (60 min) followed by reperfusion (24 hrs). Untreated mice (nϭ8) were subjected to cerebral I/R. We also treated TLR3 knockout mice with Poly I:C one hr prior to cerebral I/R. Infarct size was examined by TTC staining. Morphology of neurons in brain sections was examined by Nissl staining. Cellular proteins were isolated for Western blot analysis. Results: Poly I:C treatment significantly decreased infarct size by 55.9% compared with untreated I/R mice (10.0Ϯ1.72 vs. 22.7Ϯ2.73). Morphologic examination showed that there was less neuronal damage in the hippocampus of Poly I:C treated mice compared with untreated I/R mice. Poly I:C induced protection was abolished in TLR3 knockout mice. Western blot analysis showed that cerebral I/R increased the levels of Fas by 28.2%, FasL by 54.1%, phospho-ASK-1 by 52.0%, phospho-JNK by 64.3%, and NF-e ˆB binding activity by 32.1%, respectively, in untreated mice compared with sham control (nϭ5/group). In contrast, Poly I:C administration significantly attenuated I/R-increased the levels of FasL, Fas and phospho-ASK1, phospho-JNK, and NF-e ˆB binding activity. Conclusion: Poly I:C treatment induces protection against cerebral I/R injury through a TLR3 dependent mechanism. TLR3 ligand-induced protection involves a decrease in the I/R-activated Fas-mediated apoptotic signaling pathway. Modulation of TLR3 could be a potential approach for protection against stroke.

Author Disclosures: X. Zhang: None. T. Ha: None. J. Kelley: None. R. Kao: None. D. Williams: None. C. Li: None.

W P190 Activation of AMP-activated Protein Kinase Differs in Young and Aging Mice after Stroke

Fudong Liu, Sharon Benashski, Persky Rebecca, Yan Xu, Jun Li, Louise McCullough; University Conn Health Center, Farmington, CT Introduction: Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved energy sensor that regulates cellular metabolism and is activated via phosphorylation (pAMPK). Numerous stimuli can increase the activation of AMPK, including increasing AMP/ATP ratio. Acute activation of AMPK is detrimental in models of focal stroke as both pharmacological inhibitors and genetic deletion of the catalytic isoform of AMPK are neuroprotective. The AMP/ATP ratio increases with age and chronic exposure to metabolic stress may accelerate the aging process. However, AMPK activity decreases in peripheral tissues with age. Whether this also occurs in the aging brain, and how this contributes to the ability of the aging brain to cope with an acute stressor such as stroke is not known. This study investigated the activation of AMPK and the response to AMPK inhibition after induced stroke in both young and aging mice. Hypothesis: Stroke induced pAMPK expression will be higher in young than in aging mice. The AMPK inhibitor, Compound C administration will protect young, but not aging, mice from stroke. Methods: Focal stroke was induced by middle cerebral artery occlusion (MCAO) in young (8-10 weeks old) and aging (16-18 months old) C57BL6 male mice. Compound C was intraperitoneally administered at the onset of MCAO. Behavioral deficits and infarct volumes were assessed 4 or 24 hours after MCAO. Separate cohorts were utilized for Western blotting for pAMPK. Results: Levels of pAMPK were higher in aging brain compared to young mice at baseline. Stroke induced robust activation of AMPK as measured by phosphorylation in young mice, yet this response was muted in the aging brain. Male mice had a reduction in infarct volume with age, with smaller infarcts in aging animals but more severe behavioral deficits. Inhibition of pAMPK reduced infarct volumes in young animals (Total infarct, vehicle vs. drug: 55.9Ϯ2.4 vs. 32.8Ϯ4.0 %, nϭ6 animals/gp, PϽ0.05), but had no effect in aging mice. Compound C administration led to significant hypothermia in both age groups, which contributed to an additive neuroprotective action in young mice, but not in aging. Conclusions: Aging increases baseline pAMPK levels, but aging mice have an ameliorated stroke-induced pAMPK response. Neuroprotective agents that are efficacious in young animals may be ineffective in aging.

Author Disclosures: F. Liu: None. S. Benashski: None. P. Rebecca: None. Y. Xu: None. J. Li: None. L. McCullough: None.

W P191 Angiogenic Factor Expression And Vascular Damage After Stroke In Type 2 Diabetic Mice

Alex Zacharek, Michael Chopp, Xu Cui, Cynthia Roberts, Jieli Chen; Henry Ford Hosp, Detroit, MI Diabetes mellitus is a major health problem associated with both microvascular and macrovascular disease. Disequilibrium of angiogenesis promoters and inhibitors in Diabetes may lead to exuberant but dysfunctional neovascularization. In this study, we investigated the changes and the molecular mechanisms of cerebral vascular damage after ischemic stroke in type-2 diabetic (T2DM) mice. Adult male db/db T2DM and non-diabetic wild-type (WT) mice were subjected to sham and transient middle cerebral artery occlusion (MCAo) and sacrificed 24 h after surgery. The angiogenic factors were measured by angiogenic protein array. In the blood serum, Endothelial Growth Factor (EGF), platelet-derived growth factor (PGDF)-AA and angiopoietin-1(Ang1) level were decreased, while Plasminogen Activator Inhibitor-1(PAI-1), Monocyte Chemotactic Protein-1 (MCP-1), Macrophage Inflammatory Protein-1 (MIP-1), Matrix Metalloproteinase-8 (MMP8) and Matrix Metalloproteinase-9 (MMP9) were increased in sham T2DM-mice compared to WT-mice. We compared the difference of angiogenic factors between WT-MCAo and DM-MCAo mice in the ischemic brain. Angiogenin, PAI-1, MCP-1, MMP9 and endothelin-1 were increased, while TIMP-4 and Ang1 were decreased in the ipsilateral hemisphere of T2DM-MCAo mice. Using immunostaining, T2DM significantly increased brain hemorrhage and vascular density, but decreased vascular perimeter and arterial diameter in the ischemic border compared to WT-MCAo mice (pϽ0.05). T2DM also exhibited decreased BBB function as measured by tight junction protein (occludin) and a-SMA expression in the ischemic brain compared to WT-mice (pϽ0.05). T2DM had significantly decreased Ang1, Tie2 and PDGF expression and increased MMP9 and Ang2 expression in the ischemic brain compared to WT-mice. To investigate the mechanism underlying T2DM induced vascular damage, mouse brain endothelial cell (MBEC) primary culture, MBEC capillary tube formation and arterial explant cell migration assays were employed. MBEC capillary tube formation was significantly increased, but arterial cell migration significantly decreased in artery extracted from T2DM-mice compared to WT-mice. Ang1, Tie2 and PDGF gene expression significantly decreased, while Ang2 and MMP9 gene expression was significantly increased in culture with MBECs derived from T2DM mice compared to MBECs from WT mice (pϽ0.05). High glucose also significantly decreased vascular stabilization using an in vitro co-culture MBEC and smooth muscle cell (SMC) model compared to normal glucose control. Ang1 treatment attenuated the decreased arterial cell migration and increased capillary tube formation stabilization in T2DM-MBECs (pϽ0.05). Our data indicate that, T2DM disequilibrium regulates angiogenic promoters and inhibitors and plays an important role in T2DM-induced vascular damage after stroke.

Author Disclosures: A. Zacharek: None. M. Chopp: None. X. Cui: None. C. Roberts: None. J. Chen: None.

W P192 The RXR Agonist, Bexarotene Reduces Infarction Volume in Transient Cerebral Ischemia

Sophia Sundararajan, Jon Niemi, D'Arbra Blankenship, Molly Karl, Elizabeth Hilow, Gary Landreth; CASE WESTERN RESERVE UNIV, Cleveland, OH Activation of several nuclear transcription factors, including peroxisome proliferator-activated receptor ␣ and ␥, and liver X receptors (LXR) is neuroprotective in animal models of ischemic stroke. These receptors form heterodimers with the nuclear receptor, retinoid X receptor (RXR). This complex can be activated by agonists to either receptor. Activation modulates gene transcription either by binding to target gene promoters or through transrepression of other transcription factors. Mechanisms of transrepression include competing for coactivators, direct binding to transcription factors, and inhibiting corepressor clearance. We hypothesize that RXR agonists, which activate heterodimers containing PPAR␣, PPAR␥ and LXR simultaneously may be a more potent neuroprotective stimulus than agonists for either factor alone. The RXR agonist, bexarotene, is FDA approved to treat cutaneous manifestations of T-cell lymphomas and acute myeloid leukemia. The primary toxicity with chronic treatment is hypertriglyciderimia and hypercholesterolemia. We tested the neuroprotective actions of bexarotene, an RXR agonist, in the suture model of transient focal ischemia. Male Wistar rats were treated with IV bexarotene dissolved in saline or saline at the time of two hour middle cerebral artery occlusion (MCAO). All animals underwent physiologic monitoring including cerebral blood flow (CBF), arterial blood pressure and arterial blood gases. There was no difference in the physiologic parameters of any group of animals. Reperfusion was confirmed by CBF at the time of suture removal. Rats were euthanized 24 hours later and infarct volume calculated. Treatment with either 5 or 10 mg/kg bexarotene resulted in reduced infarction volumes relative to that in saline treated rats (p0.5) in both experiments. Activation of PPARs and LXR are anti-inflammatory and this is felt to contribute to their neuroprotection. We find that the inflammatory infiltrate in brains from bexarotene treated animals is significantly reduced following MCAO (pϽ0.001; Mann Whitney U test. Saline treated: nϭ 318 hpf/4 rats; Bexarotene 5mg/kg: nϭ530 hpf/6 rats; Bexarotene 10mg/kg: 448 hpf/5 rats. These data demonstrate that bexarotene is neuroprotective in an animal model of cerebral ischemia even when administered 3 hours after ischemic onset. Administration of bexarotene is associated with a reduced inflammatory infiltrate and this may be the mechanism of neuroprotection.

Introduction:

The purpose of this study was to determine, in a rodent model of cerebral ischemia, whether a molecular cascade involving HIF-1␣, AQP-4 and AQP-9 is causally related to the regulation of glycerol in brain tissues and the formation of brain edema. Methods: Middle cerebral artery occlusion (MCAO) followed by 2 hour reperfusion were performed in male Sprague-Dawley rats (250-280g). The anti-AQP-4, anti-AQP-9 antibody, or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1␣) were given at the time of MCAO. The rats were sacrificed at 1 and 24 hours after reperfusion and their brains were examined for protein expression, glycerol concentration and brain edema. Extracellular and intracellular glycerol concentration of brain tissue was calculated with enzymatic glycerol assay. The protein expressions of HIF-1␣, AQP-4 and AQP-9 were determined by Western blotting. Brain edema was measured by brain water content. Results: Compared to control, significant edema (p Ͻ 0.01) and significantly increased glycerol (p Ͻ 0.05) was observed after stroke. Stroke also significantly (p Ͻ 0.05) enhanced expression of HIF-1␣, AQP-4, and AQP-9. Edema was significantly (p Ͻ 0.01) decreased after inhibition of AQP-4, AQP-9 or HIF-1␣, respectively. Extracellular glycerol was also significantly (p Ͻ 0.01) decreased after inhibition of AQP-4, AQP-9 or HIF-1␣ while intracellular glycerol was not, even increased (p Ͻ 0.01) 1 hour after stroke. Inhibition of HIF-1␣ significantly (p Ͻ 0.01) suppressed the expression of AQP-4 and AQP-9. Conclusion: HIF-1␣ plays a role in regulating cerebral glycerol and brain edema formation via a molecular pathway involving AQP-4 and AQP-9. Pharmacological blockade of this pathway in stroke patients may provide novel therapeutic strategy.

Author Disclosures: T. Higashida: None. Y. Ding: None. C. Peng: None. M. Guthikonda: None.

W P195 Hypothermia Identifies Extracellular Calcium-sensing Receptor (CaSR) As A Potential Therapeutic Target

Jong Youl Kim, UCSF, San Francisco, CA; Nuri Kim, Univ of California, Berkeley, Berkeley, CA; Midori A Yenari, Wenhan Chang; UCSF, San Francisco, CA Background: Hypothermia has been shown to be effective in improving neurological outcome from cardiac arrest. The mechanisms of protection are multifold, but may be useful in identifying appropriate therapeutic targets. The extracellular calcium-sensing receptor (CaSR), originally found in parathyroid cells, senses minute changes in extracellular [Ca 2ϩ ] and promotes intracellular Ca 2ϩ release. It is also expressed in the brain where calcium overload worsens ischemic brain injury, but the role of CaSR in brain ischemia is completely unknown. Methods: To study the role of CaSR in brain ischemia, we subjected male mice (C57/BL6) to global cerebral ischemia (a model that results in brain injury much like that seen following cardiac arrest) by subjecting them to 10 min bilateral carotid artery occlusion followed by reperfusion for 3d. We then assayed CaSR expression in mice exposed to therapeutic hypothermia (33C for 3h starting at the onset of reperfusion) and in mice with selective hippocampal CaSR deficiency by immunohistochemistry and immunoblots. Results: Forebrain ischemia led to increased expression of CaSR, especially within neurons of the susceptible hippocampus but not in astrocytes. Mild hypothermia protected CA1 neurons from ischemic damage and inhibited CaSR induction. Mice deficient in hippocampal CaSR were protected compared to wildtype (nϭ7/group, PϽ0.05). Since GABA-B receptor-1s (GABA-B-R1) can heterodimerize with CaSR and suppress its expression, and GABA-B-R1 is involved in inhibitory neurotransmission, we studied GABA-B-R1 deficient cultured hippocampal neurons. CaSR was increased in neurons lacking GABA-B-R1, suggesting a new role of CaSR in potentiating ischemic neuronal death, and may be inversely linked to GABA-B-R1. Conclusion: CaSR may be a new therapeutic target for treatment of ischemic brain injury. This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: J. Kim: None. N. Kim: None. M.A. Yenari: None. W. Chang: None.

W P196 Three Variations of an Angiographic Rabbit Model of Acute Embolic Stroke

William C Culp, Rene Flores, Aliza T Brown, Leah J Hennings, Paula K Roberson, Sean D Woods, Jeff H Hatton, Robert D Skinner, Michael J Borrelli; Univ of Arkansas for Med Sciences, Little Rock, AR Background: Models of stroke in rabbits have successfully mimicked stroke volumes, hemorrhage, and recanalization rates. Techniques developed in rabbits have successfully transitioned into human therapies. Smaller models are more popular but often fail in translation to humans. To refine the rabbit model, three modified angiographic techniques were used to mimic different types of clinically relevant embolic stroke. Hypothesis: Delicate angiographic techniques can produce different types of infarct depending on embolic agent. Methods: We report control rabbits with embolization but no therapy, Nϭ76, from a total of 640 test animals. New Zealand White rabbits (5.2 Ϯ 0.07 kg) received subselective internal carotid angiography from a femoral artery approach using a 3 F catheter and magnification angiography techniques. Internal carotid artery (ICA) injection of emboli occluded the branches. Fresh clot was prepared by clotting fresh rabbit blood in 1.0 mm diameter plastic tubes for 3 to 6 hours at 37°C and cutting to 1 mm length. Aged clot used 1.5 mm plain glass tubes with clotting for 6 hours at 37°C, then cooling to 4°C for 72 hours and cutting to 4 mm length. Groups included 1) fresh clot (Nϭ50), 2) aged clot (Nϭ13), and 3) insoluble embolic spheres 700-900 microns in diameter for modeling atheroma (Nϭ13). Follow up angiograms identified occluded vessels. Vital stains on 4 mm sections were used to measure infarcts and histology measured hemorrhage. Results: Fresh clot animals resulted in very small infarcts averaging 0.45% of total brain volume. These were sometimes difficult to see on angiography and a high proportion, 60%, cleared completely with autolysis and recanalization within 24 hours. These small strokes often resembled transient ischemic attacks but were too mild to compare stroke therapies. Aged clot animals produced moderate anterior infarcts averaging 4.5%, a volume with clinical relevance. These were well tolerated in all but one with stray clot to the brain stem. Autolysis cleared 23%. Sphere animals produced similar moderate anterior infarcts averaging 4.3% in size that were well tolerated. The aged clot and spheres were well seen on angiograms, usually involving the middle cerebral artery or a combination of the middle and anterior cerebral arteries. There was no autolysis with spheres. Rabbits survived long term, up to 90 days, unless emboli reached the posterior cerebral artery or superior cerebellar artery. This occurred in about 4% of all cases and most of these required early euthanasia due to the severity of the stroke. Stroke volumes achieved using aged clot and spheres were useful in separating results of therapies. Conclusion: Angiographic models using small fresh clots, larger aged clots, and insoluble spheres are reliable and useful models of transient ischemic attack, strokes from large embolic thrombus, and strokes from insoluble atheroma, respectively.

Author

W P197 Perfusion-diffusion Mri Of Non-human Primate Stroke

Hsiao-Ying Wey, Ghazwan M Kroma, James T Scribner, Jinqi Li, Mary M Leland, Lisa Jones, Timothy Q Duong; UTHSC at San Antonio, San Antonio, TX Background: Numerous interventions have been developed and shown effective in rodent models; however, none of these has been proven effective in human besides rtPA. The rodent stroke model simply does not adequately reflect the complexity and dynamics of human stroke. It is the Stroke Therapy Academic Industry Roundtable (STAIR) recommendation that NHP stroke models need to be established for assessing novel interventions before clinical trials. Non-human primate (NHP) stroke model and non-invasive imaging technologies, such as MRI, are of significant importance albeit challenging. This study described the development of a baboon stroke model and the spatiotemporal evolution of the ischemic lesion by perfusion and diffusion MRI on a clinical scanner. Methods: Three normal female baboons (15-20kg) were subjected to permanent (nϭ1) or 90-min (nϭ2) MCAO using an endovascular approach (balloon occlusion at M1). Animals were anesthetized with ϳ2% isoflurane during stroke surgery and 0.8ϳ1.0% isoflurane with vecuronium (0.1mg/kg) during MRI. Multimodal MRI including anatomical, perfusion (arterial spin labeling), diffusion, and MRA were performed on a clinical Siemens 3T scanner. Images were acquired every 30 min from 1 hour postreperfusion up to 6 hours (permanent) or 4 hours (transient). Data were processed using custom-codes written in Matlab. Quantitative cerebral blood flow (mL/100g/min) and apparent diffusion coefficient (mm2/s) maps were calculated. Lesion volume was derived with thresholding (CBFϾ70mL/100g/min and ADCϽ0.53x10-3 mm2/s). Final infarct was determined with T2 images. Results: Perfusion-diffusion mismatch was robustly detected in the one animal underwent permanent stroke. In the transient ischemia group, hyperperfusion were detected repeatedly. The percent ipsi-lesional to contra-lesional CBF and ADC were ϳ149.6% and ϳ72.5% respectively at one-hour post-reperfusion. The percent ipsi-to contra-lesional ADC ratios degraded (ϳ63.8%) overtime indicating the tissue progress to infarct. The percent ipsi-to contra-lesional CBF ratios remain relatively constant (ϳ136.8%) up to four hours after reperfusion, and the defined lesion volume approximates the final infarct. Conclusions: This study described for the first time of monitoring both the spatial and temporal evolution of perfusion and diffusion characteristics on NHP stroke model using a clinical MRI scanner. Repeated perfusion measurements on large NHP were not feasible previously with DSC-MRI. The perfusion-diffusion mismatch approximates the penumbra was shown. An interesting hyperperfusion was observed within the diffusion lesion in transient stroke. Future studies will utilizes this multimodal MRI protocol to evaluate the spatiotemporal changes of baboon stroke, which provides a potential platform for developing novel interventions.

This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: H. Wey: None. G.M. Kroma: None. J.T. Scribner: None. J. Li: None. M.M. Leland: None. L. Jones: None. T.Q. Duong: Research Grant; Significant; AHA EIA 0940104N.

Introduction and Purpose:

Epidemiologic studies report cardio-vascular protection conferred by omega-3 fatty acids, in particular docosahexaenoic acid (DHA). Few experimental studies have addressed the neuroprotective potential of DHA in acute stroke treatment. DHA accumulation in brain has been evidenced through a specific uptake of DHAcontaining lysophosphatidylcholine (lysoPC). Our aim was to use multimodal MRI to assess in vivo neuroprotection conferred by DHA and by a stabilized biomimetic form of LysoPC-DHA (AceDoPC) in an animal model of acute stroke. Methods Rats underwent a one-hour proximal MCA occlusion with the intraluminal thread model. Immediately following reperfusion, animals were randomly and blindly treated by i.v. injection of i) saline (nϭ8), or ii) plasma from donor rats (nϭ10), or iii) DHA (nϭ10) or iv) AceDoPC (nϭ10), both solubilised in plasma. Twenty-four hours after reperfusion, animals were submitted to behavioral tests and sacrificed. MRI was performed on a 7T Bruker magnet at H0 during occlusion and at H24 before sacrifice. The MR exam covered the entire MCA territory and included a 2D angiography, DWI, DSC-PWI, and T2w imaging. Initial and final lesions were defined respectively as hypointense signal on H0 apparent diffusion coefficient (ADC) maps and hyperintense signal on H24 T2w images (Fig. 1). After sacrifice, brain tissue was used to measure F2-isoprostane content. Results Median neuroscores exhibited a non significant trend to decrease in treatment groups (6.5, 6 and 4 in plasma, DHA and AceDoPC groups respectively) compared to the saline group (8), reflecting fewer deficits in treated animals. Mean initial lesion size was comparable in the four groups, as well as PWI/DWI mismatch. Between H0 and H24, lesion size increased in the saline group (meanϮSD: ϩ18%Ϯ20%), was stable in the plasma group (-3%Ϯ29%), decreased in the DHA group (-17%Ϯ15%, PϽ0.05), and further decreased in the AceDoPC group (-34%Ϯ27%, PϽ0.05). Lipid peroxidation was decreased in the AceDoPC group compared to the other groups.

W P199 ADAMTS13 Is Neuroprotective Against Brain Ischemia-Reperfusion Injury By Improving Post-ischemic Microcirculation And Inflammation

Masayuki Fujioka, NEUROSURGERY, NEUROSCIENCE CTR, Osaka Saiseikai Ibraki General Hosp, Nara Med Univ, Osaka, Japan; Kazuhide Hayakawa, Kenichi Mishima, Takafumi Nakano, Dept of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka Univ, Fukuoka, Japan; Carl Muroi, NEUROSURGERY, Zurich Univ, Zurich, Switzerland; Toshiyuki Miyata, Rsch Institute, National Cardiovascular Cntr, Osaka, Japan; Kazuo Okuchi, Emergency CTR, Nara Med Univ, Nara, Japan; Michihiro Fujiwara, Dept of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka Univ, Fukuoka, Japan; Bo K Siesjo; Laboratory for Experimental Brain Rsch, Lund Univ, Lund, Sweden ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type-1 motifs 13) specifically cleaves the bond between tyrosine-1605 and methionine-1606 in the A2 domain of von Willebrand factor (VWF) multimer and thus reduces its prothrombotic and proinflammatory activities. VWF can activate platelets and leukocytes on the stimulated vascular endothelial cells. These activated platelets and leukocytes together contribute to both microcirculation impairment and inflammatory reactions after reperfusion in the ischemic brain. Therefore, ADAMTS13 may ameliorate the ischemia-reperfusion injury of the brain by cleaving the VWF. We investigated the role of ADAMTS13 in the ischemia-reperfusion pathology in the brain with using middle cerebral arterial occlusion (MCAO) model of ADAMTS13-gene-knockout mice. The ADAMTS13-deficient (ADAMTS13 KO) and wild-type (WT) mice were subjected to 30 minutes' MCAO followed by 23.5-hour reperfusion. The infarct volume was estimated on the brain tissue stained with TTC 23.5 hours after reperfusion. Plasma HMGB1 (high-mobility group box1) level was analyzed by Westernblot 24 hours after MCAO. The immunoreactivity of the ischemic brain tissue against HMGB1/NeuN or HMGB1/MPO (double immunofluorescent labeling) was also analyzed. The regional cerebral blood flow (rCBF) of the ischemic cortical tissue was measured by laser Doppler flowmetry during the period between 30 minutes before and 24 hours after MCAO. We also investigated if infarct volume after MCAO was reduced by intravenous infusion of ADAMTS13 protein in mice stroke model. ADAMTS13 KO mice had increased volume of brain infarction compared with WT. The plasma HMGB1 increased more in ADAMTS13 KO mice than in WT after MCAO. Ischemia induced more remarkable neuronal death and more inflammatory cells expressing HMGB1 in ADAMTS13 KO-mice cortical tissue compared to WT. The rCBF in ADAMTS13 KO mice progressively decreased more remarkably than that in WT during reperfusion phase after ischemia. In addition, extrinsic ADAMTS13 reduced infarct volume in mice after MCAO. ADAMTS13-gene-deletion aggravates brain damage, systemic and local inflammatory responses, and rCBF after ischemia-reperfusion. ADAMTS13 administration improves ischemic brain injury. This suggests that ADAMTS13 plays a possible neuroprotective role against brain ischemia by regulating the VWF-dependent thrombosis and inflammation in the reperfusion injury. To better understand the downstream TLR signaling events, we determined downstream effector cytokine/chemokine expression in mice with deletions or mutations of the two major adaptors of the TLR signaling pathway using a model of focal ischemia. Methods: We examined the cytokine expression profile in the brains and serum of MyD88 -/-, TRIF mutant and wild type (WT) mice at baseline, 3 and 24 h following permanent Middle Cerebral Artery Occlusion (pMCAO) using the 25-plex mouse cytokine/chemokine bead array. We also evaluated neutrophil infiltration in the brains of MyD88-/-and TRIF mutant mice and WT mice 24h after pMCAO. Results: The most striking differences were in serum IL-6 levels 3h after pMCAO; MyD88-/-, 14.7 Ϯ 3.4 pg/ml, TRIF mutant; 88.3 Ϯ 54.7 pg/ml and WT mice;172.6Ϯ 23.6 pg/ml; (pϭ0.027). Similar differences, with lower serum IL-6 levels, were detected 24h after pMCAO; MyD88-/-, ϳ 2.5Ϯ 3.7 pg/ml, TRIF mutant; ϳ19.0Ϯ 16.2 pg/ml and WT mice; 44.7 Ϯ12.6 pg/ml ;( pϭ0.05). In addition, brain and serum Interferon-inducible Protein 10 (IP-10) expression, which occurs primarily via the TRIF pathway, were significantly lower in TRIF mutant mice compared to MyD88-/-and WT mice. Brain IP-10 at 3h: TRIF mutant mice; 710.5 Ϯ 223.0 pg/ml/g, MyD88-/-mice; 1087.5Ϯ 190.4 pg/ml/g and WT mice; 2077.2 Ϯ 803.6 pg/ml/g; (pϭ 0.049). Serum IP-10 at 24h: TRIF mutant, 94.2 Ϯ 19.9 pg/ml, MyD88-/-, 120.8 Ϯ 26.6 pg/ml and WT, 156.1 Ϯ 11.2 pg/ml; (pϭ0.049). Neutrophil chemoattractants, Keratinocyte Chemoatracttant (KC) and Granulocyte Colony Stimulating Factor (G-CSF) were also markedly lower in the serum and brains of MyD88-/-mice following pMCAO compared to WT and TRIF mutant mice and corresponded with a strong trend towards fewer neutrophils/field in the brains of MyD88-/-mice; 8.3Ϯ9.3 compared to WT, 17.3Ϯ8.0, and TRIF mutant, 35.2Ϯ 24.3 following pMCAO. Conclusions: The pattern of inflammatory chemokine/cytokine expression in MyD88-/-and TRIF mutant mice, following focal cerebral ischemia, is consistent with the phenotypes expected following disruption of either pathway. In addition, neutrophil chemoattractants, KC and G-CSF are produced in a MyD88-dependent manner and may direct neutrophil migration to the site of ischemia after pMCAO. Nevertheless, the less pronounced inflammatory environment in MyD88-/-mice does not confer protection in cerebral ischemia. Therefore these results suggest the possibility of another, yet-to-be determined, TLR signaling pathway involved in production of damaging mediators during cerebral ischemia.

W P201 Rapamycin Enhances Autophagic Mediated Protection in a Permanent Middle Cerebral Artery Ligation Stroke Model

Samuel Herberg, Nasrul Hoda, MEDICAL COLLEGE GEORGIA/Georgia Health Sciences Univ/Charlie Norwood VAMC, Augusta, GA; John R Barrett, S Periyasamy-Thandavan, William H Jackson, Daniel L Hess, David C Hess, Patricia V Schoenlein, MEDICAL COLLEGE GEORGIA/Georgia Health Sciences Univ, Augusta, GA; William Hill; MEDICAL COLLEGE GEORGIA/Georgia Health Sciences Univ/Charlie Norwood VAMC, Augusta, GA Background: Under stress conditions, including nutrient depravation and ischemia, autophagy promotes cell survival by recycling proteins and organelles through lysosomes. Excessive autophagy, however, can lead to cell death, including apoptotic (PCD type I) and autophagic cell death (PCD Type II). During stroke, it is unclear whether autophagy promotes neurovascular unit cell survival or death. We hypothesized that increased autophagy after stroke is "protective" and that inducing autophagy by pharmacologic agents would reduce infarct size. Methods: We induced ischemia in C57BL/6J mice using a permanent MCA ligation model, with sacrifice 48 hours or 7 days after stroke. Mice were treated i.p. with chloroquine (30, 60, or 90 mg/K/d for 2 days), an autophagy inhibitor, rapamycin (1.25 or 2.5 mg/K/d for 2 days), an autophagy activator via inhibition of mTOR, or treated with vehicle (saline or 10% DMSO in 100 ul). The autophagy markers LC3 p62 and Beclin-1 were analyzed by Western blot and immunohistochemistry, additional Markers included Bcl2, and infarct size was measured by TTC staining.

Results: Chloroquine at 30, 60 and 120 mg/kg reduces lesion size in a U shaped function between 28 & 34% (pϾ0.01). Rapamycin reduced lesion size 64.0% at 1.25 mg/kg and 62.5% at 2.5 mg/kg. The reduction in lesion size for chloroquine and the 10 mg/kg rapamycin was statistically significant (Kruskal-Wallis One Way ANOVA pϭ0.016). LC3 is decreased in the infarct side, suggesting turnover of LC3 by the fusion of autophagosomes and lysosomes. P62 increased, suggeating increased chaparone mediated clearance of damaged protein aggregates. Chloroquine increased LC3 by preventing its turnover and had no significant change on p62 levels. Rapamycin led to increased LC3 and p62, consistent with increased induction of autophagy. Summary: 1) Stroke increases autophagy and Bcl2 levels. 2) Since chloroquine and rapamycin both decreased lesion size, this suggests cross-talk between autophagy and other programmed cell death pathways and/or direct effects of the drugs on such pathways.

W P202 Preconditioning Induces Sustained Neuroprotection by Inhibition of AMPK

Venugopal Reddy Venna, Jun Li, Louise D McCullough; Univ of Connecticut health center, Farmington, CT Background: Brief non-injurious cerebral ischemia (Ischemic preconditioning) induces neuroprotection and protects the brain from subsequent injury, a process also known as ischemic tolerance. We have previously shown that Adenosine monophosphate-activated protein kinase (AMPK), a key regulator of energy balance, is increased following stroke. This enhanced AMPK activity is detrimental in stroke as AMPK inhibition or genetic deletion of AMPK is neuroprotective. The objective of this study was to determine if ischemic preconditioning alters AMPK activity and thus induces sustained neuroprotection. Methods: Focal ischemia was induced by reversible middle cerebral artery occlusion (MCAO-non-injurious-3min (IPC); injurious-90 minute (referred as stroke hereafter)) in mice (male, 20 to 25 g; C57BL/6N, Charles River Laboratories). Stroke was performed 72 hours after IPC or sham surgery. Compound C (i.p 5mg/kg), an AMPK inhibitor (Calbiochem, San Diego, CA) was given at the onset of stroke. Different cohorts were used for infarct analysis (nϭ8/group) or molecular studies (nϭ4/group). Infarct volume was analyzed by TTC at 24hrs post-stroke. Protein levels were expressed as a ratio to a control actin band after densitometry analysis. Results: Three minutes of MCAO caused no visible injury; IPC 72 hrs before stroke induced significant neuroprotection (Total infarct: 33.1Ϯ3.9; nϭ7) compared to stroke (Total Infarct: 45.01Ϯ3.4; nϭ8) PϽ0.05. In addition, these improvements were correlated with changes in AMPK activity in WT mice. Preconditioning activated AMPK at 4 hrs (Sham-operated 4hrs 0.43Ϯ0.22; IPC 4hrs 0.71Ϯ0.13), but decreased AMPK activity at 72 hrs (Sham 72hrs 0.45Ϯ0.18, IPC 72 hrs 0.32Ϯ0.13; stroke 0.83Ϯ0.11; IPCϩ stroke 0.52Ϯ0.16). Interestingly, Compound C treatment abolished the beneficial effects of IPC, Compound C (35.71Ϯ4.11; nϭ6/gp) IPCϩ compound C (33.28Ϯ4.74; nϭ6/gp. pϾ0.05). Conclusions: Preconditioning is neuroprotective. IPC activated AMPK at early time points; however it reduced AMPK activation at 72 hours compared to sham IPC mice. Mice subjected to IPC had reduced AMPK activation after stroke. The effect of IPC is abolished in compound C treated mice. In conclusion, these studies suggest that AMPK plays an important role in mediating the beneficial effects of ischemic preconditioning. AMPK inhibition ameliorates ischemic tolerance.

Author Disclosures: V. Venna: None. J. Li: None. L.D. McCullough: None.

W P203 A Role For Spleen CCR2؉ Monocytes In Stroke-Induced Injury In Hyperlipidemia

Eunhee Kim, Yi Bao, Luye Qin, Sunghee Cho; Burke/Cornell Med Rsch Inst, White Plains, NY Infiltration of peripheral monocytes/macrophages is implicated in stroke pathology. However, in vivo evidence regarding monocyte deployment and mobilization to the infarct area is scarce.

Recent studies indicate that hyperlipidemia, a prevalent co-morbid condition, increases the number of pro-inflammatory (CCR2ϩ/LY6C hi ), but not anti-inflammatory (CCR2-/ LY6C low ) monocytes. In addition, we have previously reported that hyperlipidemia increases infarct size and pro-inflammatory inflammatory markers in the brain and peripheral macrophages. The present study investigates whether CCR2ϩ/LY6C hi monocytes in the spleen, an important reservoir for monocytes deployment upon injury, contribute to stroke pathology. Male wild type mice fed normal chow (WT) and ApoE KO mice fed a high fat diet (AKO) for 8 weeks were subjected to 30 min transient middle cerebral arterial (MCA) occlusion and subsequent infarct size and CCR2 expression in the brain and spleen were determined. FACS analysis prior to ischemia showed an increased number of CCR2ϩ monocytes in the spleen from AKO mice compared to WT (22.4 vs 11.9%). Three days after ischemia, both mice exhibited a significant reduction in spleen size (pϽ0.001) with a greater reduction in AKO mice relative to WT (30.7 vs.14.3%). Correlation among infarct volume, spleen weight, and brain CCR expression revealed that the larger the injury induced in AKO mice, the greater the reduction in spleen size (pϽ0.001 nϭ9), and the higher the expression of CCR2 in the post-ischemic brain (pϽ0.001, nϭ13). No such correlations were observed in WT mice. In AKO mice, stroke increased CCRϩ/LY6Cϩ monocytes (yellow indicated by arrowheads, upper right panel) in the infarct territory at 3 days whereas the number of cells were reduced in the subcapsular red pulp (SCRP) of spleen, a region where monocytes are clustered (lower panel). This study indicates that CCR2ϩ monocytes are deployed from the spleen following focal cerebral ischemia and contribute to stroke-induced inflammation and injury. The previously unrecognized role of spleen monocytes in cerebral ischemia suggests a novel strategy to limit ischemic brain injury by targeting CCR2 in peripheral monocytes.

Author Disclosures: E. Kim: None. Y. Bao: None. L. Qin: None. S. Cho: None.

W P204 MSCs Decrease TGF ␤1 Expression In Microglia Which Downregulate Astrocytic PAI-1 Expression After Stroke

hongqi xin, Yi Li, Li H Shen, Ruilan Zhang, Li Zhang, Zheng G Zhang, Michael Chopp; Henry Ford Health System, Detroit, MI Introduction: Endogenous tissue plasminogen activator (tPA) activity promotes neurite remodeling after stroke. Astrocyte-derived plasminogen activator inhibitor-1 (PAI-1) modulates tPA activity in brain. We have previously shown MSCs decrease astrocytic transforming growth factor beta1 (TGF ␤1) expression which subsequently decreases the PAI-1 level in an autocrine manner in the ischemic brain; however, the role microglia as a source of TGF ␤1 and PAI-1 regulation has not been investigated. Materials and Methods: Adult C57BL/6 mice were subjected to permanent middle cerebral artery occlusion (MCAo) followed by injection of 1ϫ10 6 MSCs (nϭ6) or phosphate-buffered saline (nϭ6) into the tail vein 24 hrs later. Animals were sacrificed at 14 days after stroke and paraffin slides were used for immunostaining. In vitro coculture systems with MSCs, astrocytes and microglia were also employed, and were subjected to oxygen and glucose deprivation (OGD) to mimic the ischemic condition. Western blot and RT-PCR were employed to detect the gene expression in protein and mRNA level. Results: At day 14 after stroke, activated microglia aggregated in the IBZ and highly expressed TGF ␤1, and MSC treatment significantly decreased TGF ␤1 expression in microglia (32.0Ϯ4.3%, PϽ0.05). In vitro, RT-PCR results showed TGF ␤1 mRNA level in both astrocytes (C8-D1A, ATCC, CRL-2541) and microglia (EOC 20, ATCC, CRL-2469) were increased after OGD (97.2Ϯ14.1% and 162.3Ϯ24.5%, respectively, PϽ0.01) compared to normoxic conditions, and coculture of astrocytes and microglia significantly increased TGF ␤1 levels under normal (27.2Ϯ11.2% and 62.5Ϯ14.3%, in astrocytes and microglial cells, respectively, PϽ0.05) and OGD conditions (87.1Ϯ24.3% and 131.7Ϯ34.8%, in astrocytes and microglial cells respectively, PϽ0.01). Addition of MSCs into the astrocyte and microglial coculture system significantly decreased the TGF ␤1 mRNA level in normal (47.3Ϯ17.2% and 43.7Ϯ14.1%, in astrocytes and microglial cells, respectively, PϽ0.01) and OGD conditions (73.7Ϯ24.8% and 77.3Ϯ14.3%, in astrocytes and microglial cells, respectively, PϽ0.01). PAI-1 mRNA was below the threshold of detection in microglia. OGD or coculture of astrocytes with microglia increased the PAI-1 mRNA in astrocytes, and addition of MSC to the coculture significantly decreased PAI-1 level in microglia cocultured astrocytes under OGD conditions (52.5Ϯ13.3%, PϽ0.01). Western blot results also confirmed the similar protein level changes in astrocytes and microglia. Conclusions: MSCs decrease TGF a ˆ1 expression in IBZ microglia which contribute to the downregulation of PAI-1 level in astrocytes. Introduction: Clevidipine, a rapidly-acting, vascular-selective, L-type dihydropyridine calcium channel blocker, lowers blood pressure (BP) by reducing systemic vascular resistance and has a pharmacokinetic half-life of approximately 1 minute. The ACCELERATE trial evaluated blood pressure (BP) reduction with IV clevidipine in patients with acute intracerebral hemorrhage (ICH). Methods: Patients presenting with symptoms of ICH within 12 hours and systolic BP (SBP) Ͼ160 mmHg were enrolled and treated with open-label IV clevidipine. Clevidipine was started at 2.0 mg/h and titrated every 90 seconds until SBP Յ160 mmHg was achieved, then titrated to keep SBP between 140 to 160 mmHg. Glasgow Coma Scale (GCS) score, NIH Stroke Scale (NIHSS) score, and hematoma volume were measured. Results: Thirty-five patients (27 men, mean age 64 years) were enrolled and received clevidipine. Prior to treatment, median GCS score ϭ 14, median NIHSS score ϭ 13, mean hematoma volume ϭ 29 mL, mean SBP ϭ 186 mmHg and mean diastolic BP ϭ 85 mmHg. Mean time to infusion from symptom onset was 5.5 hours. Mean on-drug infusion duration from initiation to end of treatment was 28 hours. For patients who met study criteria (nϭ33), median time to achieving target SBP (Ͻϭ160 mmHg to Ͼϭ140 mmHg) was 5.5 min (95% CI 3,10). All patients achieved SBP Յ160 mmHg within 30 min, and 97% did so without additional or alternative antihypertensives. At 6 hours after termination of infusion, mean change in NIHSS score was 1.6 (mean baseline 13.7, post-baseline 15.3); and mean change in GCS score was -1.4 (mean baseline 12.9, post-baseline 11.5). Minimal intracerebral hematoma volume change was observed after SBP reduction with clevidipine. In patients requiring intracranial pressure (ICP) monitoring, cerebral perfusion pressure was maintained in an optimal range and no meaningful increases or other changes in ICP were observed. No patients had SBP Ͻ90 mmHg within 30 min after clevidipine initiation. Adverse events (AEs) were consistent with previous clinical experience; the most common was pyrexia (7 patients). Hypotension was reported as an AE for 3 patients; BP increased with resolution of AE after clevidipine dose was reduced or the infusion stopped. Conclusions: Clevidipine rapidly and effectively reduces BP in patients with acute ICH and was well tolerated in ACCELERATE patients (nϭ35), with evidence of a good safety profile consistent with previous experience in other clinical settings. Minimal changes were observed in GCS and NIHSS at 6 hours post-discontinuation and in hematoma volume on 24-hour CT scans.

W P207 A Low Proportion of Patients with Intracerebral Hemorrhage Meet the Eligibility Criteria of the Surgical Trial in Intracerebral Hemorrhage II Study

Matthew A Kirkman, Naomi Greenwood, Navneet Singh, Pippa J Tyrrell, Andrew T King, Hiren C Patel; Greater Manchester Neurosciences Cntr, Manchester, United Kingdom Background: Spontaneous supratentorial intracerebral hemorrhage (ICH) is a devastating condition with a high morbidity and mortality, and optimal management of the condition remains controversial. The Surgical Trial in IntraCerebral Hemorrhage II (STICH II) study was initiated to look at the role of early surgery versus conservative management for individuals with superficial lobar ICH, as the initial STICH trial showed the greatest benefit from early surgery in this subgroup. STICH II commenced in November 2006 with the aim of recruiting 600 patients, but as of June 2010 only 329 have been recruited worldwide. Even at the co-ordinating centre, Newcastle upon Tyne, where recruitment is highest, only 29 have been recruited. Despite our best efforts we have failed to recruit to STICH II. The aim of this study was to assess the reasons for poor recruitment overall and, in particular, at our centre. To do this, we estimated how many patients with ICH referred to the Greater Manchester Neurosciences Centre (GMNC) met the inclusion and exclusion criteria of the STICH II trial. Methods: The number of patients eligible for STICH II was determined from the GMNC neurosurgical referral database and from admissions to the local Stroke Unit over one year (January 1st to December 31st 2008). The referral database is a prospectively recorded database of all patients referred to the on-call neurosurgery service (catchment area 3.2 million). Eligibility was determined by the predefined STICH II inclusion and exclusion criteria, and equipoise was agreed by two neurosurgeons. Results: Of the 434 ICH referrals in 2008, 168 (38.7%) were lobar ICH; 53 (31.5% of lobar ICH) of these met the radiological and GCS criteria for STICH II, but only 16 (9.5% of lobar ICH; 3.7% of all ICH) had equipoise agreed on by two neurosurgeons. Thirty-five ICH patients were admitted to the Stroke Unit, and twelve (34.3%) of these had lobar ICH; none were eligible for STICH II when accounting for the radiological and GCS criteria. These figures suggest that only 360 of the almost 10,000 patients who suffer an ICH each year in the UK would be eligible for recruitment into STICH II.

Conclusions:

The number of patients meeting the eligibility criteria for recruitment into STICH II is small, in part because of the difficulty in establishing equipoise -a well-recognized problem in neurosurgical clinical trials. Time constraints in a busy neurosurgical emergency referral system undoubtedly exacerbate recruitment problems. Overall, this necessitates an aggressive recruitment approach for STICH II, focusing on neuroscience centers with neurosurgical units.

W P210 The Effect Of Leukoaraiosis Burden On Admission Hematoma Volume And Hematoma Growth In Patients With Spontaneous Intracerebral Hemorrhage

Ethem Murat Arsava, Ozlem Kayim Yildiz, Hacettepe Univ, Faculty of Medicine, Dept of Neurology, Ankara, Turkey; Erhan Akpinar, Hacettepe Univ, Faculty of Medicine, Dept of Radiology, Ankara, Turkey; Mehmet Akif Topcuoglu; Hacettepe Univ, Faculty of Medicine, Dept of Neurology, Ankara, Turkey Background: Hematoma expansion occurs in approximately one-third of patients presenting with intracerebral hemorrhage (ICH). The disruption of the neighboring secondary vessels around the primary vascular rupture site has been implicated as one of the contributing factors to hematoma expansion. Leukoaraiosis (LA), an established risk factor for ICH, is pathologically characterized by arteriosclerotic changes in cerebral vessels, enhanced capillary permeability and impaired blood brain barrier functions, all of which in theory might favor secondary vascular rupture and therefore increase the risk for hematoma expansion. On the other hand, the lower capillary density and increased gliosis observed in brains with LA might prevent this domino effect. In this study our aim was to assess the effect of LA burden on admission hematoma volume and hematoma expansion in patients with spontaneous ICH. Methods: A consecutive series of patients with a diagnosis of ICH and admission computed tomography (CT) imaging within 24 hours of symptom onset and a follow-up CT imaging within 72 hours symptom onset were included into the study. LA burden was determined by using the Fazekas scale on admission CT images. Hematoma volume was calculated by using the ABC/2 method. Significant hematoma growth was defined as an increase of Ն33% or 12.5 mL with respect to baseline volume. Spearman's correlation and chi-square tests were used to assess the bivariate relationships between LA burden and outcome variables (admission hematoma volume and hematoma expansion). Multivariable models were developed to analyze the independent effect of LA burden on outcome variables. Results: The study population comprised of 116 patients (70 male, 46 female). Neither the periventricular LA burden (pϭ0.50), nor the subcortical LA burden (pϭ0.66) showed any correlation with admission hematoma volume. A total of 26 patients (22%) had significant hematoma expansion on follow-up. Periventricular and subcortical LA burden was similar between patients with and without significant hematoma expansion (pϭ0.52 and pϭ0.87, respectively). A relationship between LA volume and admission hematoma volume or hematoma expansion was also not evident in multivariable models. Conclusion: We were unable to show any association between the amount of LA and hematoma volume or expansion. Further studies with larger number of patients and volumetric LA measurements are needed to totally negate the role of LA as a determinant of admission hematoma volume or hematoma expansion in the setting of ICH.

Author Disclosures: E. Arsava: None. O. Kayim Yildiz: None. E. Akpinar: None. M. Topcuoglu: None.

W P211 Charlson Comorbidity Index Independently Predicts Long-term Functional Outcome in Patients after Intracerebral Hemorrhage

Barak Bar, J C Hemphill, III; UCSF, San Francisco, CA Objective: Medical comorbidities are common in patients with intracerebral hemorrhage (ICH). While it seems reasonable that comorbid conditions influence recovery from ICH, studies of early mortality and long-term outcome have not systematically included adjustment for comorbid conditions. In fact, there is currently no standard method of assessing patient comorbidities for ICH studies. The Charlson Comorbidity Index (CCI) is a tool commonly used in outcome studies for other diseases and has been validated across many conditions, including ischemic stroke. The CCI is determined as the sum of point values ascribed for various patient comorbid conditions. The purpose of this current study was to assess whether the CCI could be determined in a cohort of ICH patients and whether it was associated with long-term outcome independent of other commonly assessed predictors. Methods: We performed a prospective observational cohort study of all patients with ICH admitted through the emergency departments at two UCSF hospitals from 6/1/2001-5/31/2004. Components of the ICH Score (admission Glasgow Coma Scale score, initial hematoma volume, presence of intraventricular hemorrhage, infratentorial ICH origin, and age) were recorded along with other clinical, neuroimaging, and in-patient care parameters. Outcome was assessed using the modified Rankin Scale (mRS) at multiple time points post-ICH out to 12 months. The CCI was derived by using information from hospital discharge ICD-9 CM codes as well as patient history obtained during the acute ICH hospital admission. CCI scores were categorized as 0, 1, 2, and 3 or greater. In order to assess whether the CCI was independently predictive of long-term outcome, multivariable ordinal logistic regression was performed adjusting for components of the ICH Score as well as the use of early DNR orders (within the first hospital day). Results: A total of 243 patients were included in the study with CCI scores of 0 (36.2%), 1 (25.5%), 2 (16.1%), and 3 or greater (22.2%). Only twenty eight percent of patients with high CCI scores (Ն3) achieved a 12-month mRS of 3 or better (disabled but ambulatory) compared with 49% of patients with CCI scores of 0 (pϭ0.011). High CCI (Ն3) was independently predictive of 30-day mortality (OR 8.8, pϭ0.026) even after adjustment for the above described predictors and withdrawal of medical support. CCI was also independently predictive of worsened 12-month functional outcome, with higher CCI having a greater impact (CCIϭ2, ORϭ2.3, pϭ0.062; CCI Ն3, ORϭ3.5, pϭ0.001). Conclusion: The Charlson Comorbidity Index can be determined in patients with ICH and is independently associated with early mortality and long-term functional outcome. This effect is independent of the use of early DNR orders or withdrawal of support and therefore is unlikely to be principally due to physician use of early care limitations.

Author Disclosures: B. Bar: None. J.C. Hemphill: Other Research Support; Significant; Novo Nordisk. Ownership Interest; Significant; Ornim.

W P213

Objectives:

The ICH score was developed to predict 30-day mortality after intracerebral hemorrhage (ICH). We aimed to design a model to predict 1 year functional outcome after ICH and compare its performance with the ICH score (acknowledging that the latter was not designed for this purpose). We hypothesized that admission NIH Stroke Scale (NIHSS) is a more powerful outcome predictor than admission Glasgow Coma Scale (GCS). Methods: The DASH study is a prospective NIH funded study assessing the diagnostic utility of brain MRI in spontaneous ICH or intraventricular hemorrhage (IVH). We evaluated the association of baseline variables with 12-month poor outcome (i.e. modified Rankin scale (mRS) Ն4) and with mortality using logistic regression. Variables significant in the univariate analysis at ␣Ͻ0.2 were entered in the multivariate analysis and kept in the model at ␣Ͻ0.01. Results: Of 166 prospectively enrolled patients, 138 had a 1 year mRS score and were included in the analysis. Baseline characteristics were: age 63Ϯ17 years, 49% females, IVH in 44%, median (IQR) hematoma volume (HV) 15 (6-38) mL, admission GCS 14 (9-15), and admission NIHSS 8 (2-17). Overall mortality rate was 27%, and 46% of patients had a poor outcome at 1 year. In the univariate analysis, history of hypertension, age, HV, IVH, GCS, NIHSS and history of coagulopathy/thrombocytopenia predicted poor outcome and mortality, while hemorrhage location (deep versus other) and diabetes predicted only poor outcome. In the multivariate analysis, age and NIHSS were the strongest independent predictors of poor outcome and mortality: OR ϭ 2.2 and 1.7 (pϽ0.001) with increase of NIHSS by 5 points; and ORϭ2.6 and 1.8 (pϽ0.001) for 10 years of age increase, respectively. In addition, IVH (ORϭ3.8, pϭ0.01), deep location (ORϭ9.5, PϽ0.001), and coagulopathy/thrombocytopenia (ORϭ2.8, pϭ0.089) independently predicted poor outcome. The sum-score points of a 6 point "functional ICH score" were: NIHSS (0-8ϭ0, 9-19ϭ1, Ն20ϭ2), age (Ͻ70 ϭ 0, Ն70 ϭ 1), IVH (noϭ0, yesϭ1), hemorrhage location (deepϭ1, otherϭ0) and coagulopathy/thrombocytopenia (noϭ0, yesϭ1). The "functional ICH score" predicted poor outcome at 1 year better than the ICH score: area under ROC curve 0.85 and 0.73, respectively (pϭ0.044). No patient with a "functional ICH score" ϭ0 had poor outcome and no patient with a score of 4 or 5 had good outcome compared to 22% poor outcome in patients with an ICH score ϭ0 and 25% good outcome with a score ϭ4. Both scores performed similarly in predicting mortality. Conclusions: The "functional ICH score" may be a useful tool to help predict 1 year functional outcome after ICH. Age and admission NIHSS (rather than GCS) are strong predictors of outcome at this time point. Future studies are needed to validate these findings.

Author Disclosures: M. Mlynash: None. C.A.C. Wijman: Research Grant; Significant; NIH.

W P214 Hematoma Expansion in Anticoagulant Associated Intracerebral hemorrhage Despite Prothrombin Complex Concentrate Treatment

Negar Asdaghi, Candice C Poon, Thomas Jeerakathil, Ken Butcher; Univ of Alberta, Edmonton, Canada Background: Anticoagulant associated intracerebral hemorrhage (AAICH) has high mortality rate and poor neurological outcome. Rapid reversal of anticoagulation remains the cornerstone of medical therapy. Prothrombin complex concentrate has been shown to rapidly reverse coagulopathy. We aim to determine whether rapid INR reversal with PCC decreases the rate of hematoma growth in patients with AAICH. Methods: We conducted a prospective study in patients presenting with acute AAICH who received PCC. All patients had standardized CT assessment 24 hours after treatment. Hematoma volume was planimetrically measured on serial scans. Rates of hematoma expansion were compared to control patients with acute AAICH presenting in the two year period prior to approval of PCC for treatment of AAICH. Patients in the control group received fresh frozen plasma (FFP) and/or vitamin K and also underwent follow-up CT scan. The goal of therapy was an INR1/3 from baseline. Results: A total of 16 patients received PCC and 19 were treated with FFP/vitamin K. The median GCS in the PCC 15 (IQRϭ 2) and control 14 (IQRϭ4) groups was comparable (pϭ0.31). Baseline International Normalized Ratio (INR) was also similar in the PCC (3.7, IQRϭ2) and control groups (3, IQRϭ2, p-0.47). The PCC and control groups were balanced with respect to time from onset to baseline scan (236min, IQRϭ 355min vs 325 min, IQRϭ744 min, pϭ0.15) and baseline hematoma volume (medianϭ21.2 ml, IQRϭ 43.6 vs medianϭ25.9, IQRϭ74.2,pϭ0.64). Treatment with PCC resulted in a more rapid INR correction (128.5 min, IQRϭ617) than FFP/vitamin K (540min, IQRϭ730, pϭ0.005). Hematoma expansion rates were not different in PCC treated (4/16, 25%) and FFP/vitamin K treated patients (2/19, 10.5 %, 2 ϭ0.46, pϭ 0.50). There was a trend towards higher absolute hematoma expansion volumes in PCC treated patients (meanϭ 8.3Ϯ13.0 ml) relative to the FFP/vitamin K group (-3.28 mlϮ13.9 ml, pϭ0.07). Multivariate regression analysis did not reveal a relationship between baseline INR (Rϭ 0.4, pϭ0.43), GCS (Rϭ0.1,pϭ0.65,systolic

W P215 Dynamic Cerebral Autoregulation Is Impaired After Acute Intracerebral Hemorrhage

Kazuma Nakagawa, The Queen's Med Cntr, Honolulu, HI; Jorge M Serrador, Harvard Med Sch, Boston, MA; Sarah L LaRose, Farzaneh A Sorond; Brigham and Women's Hosp, Boston, MA Introduction: The understanding of cerebral autoregulation status after intracerebral hemorrhage (ICH) is important in maintaining optimal cerebral blood flow to the perihematoma penumbra. However, there are limited and conflicting data available on dynamic cerebral autoregulation after ICH. Hypothesis: We assessed the hypothesis that dynamic autoregulation is less effective in patients with acute ICH compared to community-dwelling healthy subjects by performing a case-control study. Methods: Twenty-one patients (66Ϯ15 years) with acute (Ͻ72 hours) lobar or basal ganglia ICH were prospectively studied and compared to twenty-three age-matched controls (65Ϯ9 years). Continuous measures of mean flow velocity (MFV) in the middle cerebral artery (MCA) and mean arterial blood pressure (MAP) were obtained over 5 min. Cerebrovascular resistance index (CVR i ) was calculated as the ratio of MAP to MFV. Dynamic autoregulation was assessed using transfer function analysis of spontaneous MAP and MFV oscillations in the very low (0.03-0.07 Hz) and low (0.07-0.15 Hz) frequency ranges. Inter-group differences in cerebrovascular hemodynamics were tested using t-test. Within the ICH group, intra-individual differences in MFV, transfer function coherence, gains, and phases between the ipsilateral and contralateral sides were tested using a repeated measures two-way ANOVA. An interaction between hemispheric differences and hematoma size was ascertained by using hematoma size as a covariate. Results: The ICH group demonstrated higher CVR i compared to controls (ipsilateral: 1.91Ϯ1.01 mmHg⅐s⅐cm -1 , pϭ0.04; contralateral: 2.01Ϯ1.24 mmHg⅐s⅐cm -1 , pϭ0.04; vs. control: 1.42Ϯ0.45 mmHg⅐s⅐cm -1 ). The ICH group had higher gains than controls in the very low (ipsilateral: 1.10Ϯ0.35 % 2 /mmHg 2 , pϭ0.03; contralateral: 1.20Ϯ0.85 % 2 /mmHg 2 , pϭ0.08; vs. control: 0.84Ϯ0.40 % 2 /mmHg 2 ) and low (ipsilateral: 1.51Ϯ0.76 % 2 /mmHg 2 , pϭ0.0001; contralateral: 1.61Ϯ1.03 % 2 /mmHg 2 , pϭ0.001; vs. control: 0.78Ϯ0.32 % 2 /mmHg 2 ) frequency ranges. The ICH group also demonstrated lower phases than controls in the low frequency range (ipsilateral: 20.0Ϯ35.5 degrees, pϭ0.03; contralateral: 24.4Ϯ32.8 degrees, pϭ0.07; control: 41.8Ϯ29.6 degrees). Within the ICH group, an interaction between inter-hemispheric differences in the very low frequency phase and hematoma size was observed (PϽ0.05). Conclusions: Dynamic cerebral autoregulation on both hemispheres are less effective in patients with acute ICH compared to healthy controls. Our findings also suggest that dynamic autoregulation may be further impaired in patients with larger hematomas.

Author Disclosures: K. Nakagawa: Research Grant; Significant; Hawaii Community Foundation Medical Research Program. Other Research Support; Significant; Queen Emma Research Fund. J.M. Serrador: None. S.L. LaRose: None. F.A. Sorond: None.

W P216 Hemicraniectomy And Craniotomy Have Similar Early Outcomes In Patients With Intracerebral Hemorrhage

Ramy El Khoury, Yoshua Esquenazi, Meghan McIntosh, Renganayaki Pandurengan, Jeanie Choi, Amrou Sarraj, M. Rick Sline, Nicole Gonzales, Andrew Barreto, James Grotta, Nitin Tandon, Sean Savitz; UNIVERSITY OF TEXAS AT HOUSTON, Houston, TX Background: Spontaneous intracerebral hemorrhage (ICH) accounts for 20% of all strokes and carries the highest morbidity and mortality. The role of surgery for ICH remains controversial. Craniotomy (C) with clot evacuation is the main reported surgical modality. There is little published data on decompressive hemicraniectomy (HC). We compared all cases of hemicraniectomy with craniotomy at our center for ICH patients. Methods: From our prospectively collected database from August 2004 until April 2010 we identified all patients with spontaneous ICH, excluding aneurysms, AVMs, and tumors. We compared two groups: patients with HC (ϩ/-clot evacuation) versus craniotomy. We collected age, ethnicity, admission NIHSS and GCS, location of hemorrhage and volume of ICH (calculated using the AxBxC/2 formula). Primary outcome was (modified Rankin Scale) mRSՅ4 at discharge. Secondary outcomes included intensive care unit length of stay (LOS), total hospital length of stay, and in-hospital mortality. Results: We identified a total of 1330 spontaneous ICH. Less than 10% underwent surgical procedure. There were 64 HC patients (of which 8 had no clot evacuation), and 23 patients with craniotomy (Table 1). There was a trend to perform HC vs C on younger patients (52.5 years vs. 59 years; pϭ 0.055). Median NIHSS (19.5 vs. 19) and GCS (11 vs.7) at presentation were similar. The majority of patients were taken within 24hrs of symptom onset. The locations of the hemorrhages, whether lobar or basal ganglia were not significantly different. There was no significant difference in mRS Յ4 at discharge, intensive care LOS, or total hospital LOS. There was no significant difference in mRS scores, or mortality after adjustment for age and ICH volume. Conclusion: In our limited retrospective study, hemicraniectomy and craniotomy had similar hospital length of stay, mortality, and early clinical outcomes. We are now determining the 90 day outcome of survivors to further assess for possible differences between the surgical groups.

W P217 Clinical Characteristics Stratify the Utility of Magnetic Resonance Imaging in Patients With Spontaneous Intracerebral Hemorrhage

Hooman Kamel, Babak B Navi, J. Claude Hemphill, III; UCSF, San Francisco, CA Background: The prevalence and predictors of underlying lesions on MRI in patients with spontaneous ICH are not well characterized. A prior study reported a low prevalence of structural lesions on conventional angiography in hypertensive patients older than 45 years of age with non-lobar ICH. We therefore investigated the performance of this clinical prediction model in a consecutive series of patients who underwent MRI for unexplained ICH. Methods: Using an administrative database, we identified all adults hospitalized at our institution with a diagnosis of ICH between January 1, 2006 and September 30, 2009. We included only patients with a head CT at baseline and a brain MRI within the following 6 months. We excluded patients with a clear cause of ICH, such as trauma, coagulopathy, or hemorrhagic infarction. Electronic medical records were used to collect information on demographic characteristics, medical history, blood pressure, and location of ICH. Hypertension was defined as a reported history of hypertension or blood pressure Ͼ 140/90 mm Hg on admission. Non-lobar ICH included hemorrhage in the basal ganglia, thalami, or posterior fossa. Our primary outcome was a finding on MRI that changed the treating physicians' diagnosis of the cause of ICH. We applied Fisher's exact test to determine whether the yield of MRI was significantly lower in hypertensive patients older than 45 years of age with non-lobar ICH compared to the other patients. Results: Our cohort comprised 123 patients (mean age 64 Ϯ 17 years, 55% male), of whom 109 (89%) had hypertension. In addition to non-contrast CT and MRI, 91 patients (74%) underwent CT angiography and 92 (75%) MRI with gadolinium. Findings on MRI changed the treating physicians' diagnosis of the cause of ICH in 30 cases (24%, 95% CI 17-32%); 10 of these patients (8% of the total cohort) were found to have vascular malformations, 10 (8%) amyloid angiopathy, 9 (7%) infarcts with hemorrhagic transformation, and 1 (1%) posterior reversible encephalopathy syndrome. None had a brain tumor. MRI findings that changed diagnosis were significantly less common in hypertensive patients older than 45 years of age who had non-lobar ICH (2 of 42 cases; 5%, 95% CI 0-11%) than in the rest of the cohort (28 of 81 cases; 35%, 95% 24-45%) (p Ͻ 0.001). Discussion: Our findings suggest that the diagnostic yield of MRI in the evaluation of spontaneous ICH varies significantly according to patient characteristics. We have validated a prior study's finding that hypertensive patients older than 45 years of age with non-lobar ICH seldom have clinically significant underlying lesions. On the other hand, MRI frequently changed the diagnosis in patients not meeting this profile. These results may help with determining appropriate indications for MRI in patients with spontaneous ICH.

Author Disclosures: H. Kamel: None. B.B. Navi: None. J. Hemphill: None.

W P218 Thrombin Triggers Angiogenesis In Rat Brains Following Intracerebral Hemorrhage

Hua-Jun Zhou, Institute of Neurology, Xiangya Hosp, Central South UnivCentral South Univ, Changhsa, China; Tao Tang, Institute of Integrative Chinese Med., Xiangya Hosp, Central South Univ, Changhsa, China; Qi-Dong YANG; Institute of Neurology, Xiangya Hosp, Central South UnivCentral South Univ, Changhsa, China Background and Purposes: Our recent studies have demonstrated that angiogenesis occurs in rat brains with intracerebral hemorrhage (ICH). Thrombin, a serine protease, is activated at the site of cellular injury, and experiments have confirmed that thrombin mediates mitogenesis and induce tumor angiogenesis. Accordingly, the purpose of the present study is to assess the hypothesis that thrombin triggers ICH-related angiogenesis. Methods: This study was divided into 2 parts. In the first part, rats (nϭ5 in each group at each time point) received 100 L 0.9% sterile saline (sham) or 100 uL autologous blood with or without a thrombin inhibitor, hirudin (5 U) into right globus pallidus, and then received intraperitoneal injections of BrdU (50 mg/kg) at day 3, day 7 and day 14. In the second part, The rats (nϭ5 in each group at each time point) received either 1 U(50L)thrombin or 50L 0.9% sterile saline (sham) by direct infusion into the right globus pallidus, and then received intraperitoneal injections of 5-bromo-2deoxyuridine (BrdU) (50 mg/kg) at day 1, day 3 and day 7. Brains were perfused to identify BrdU ϩ /vWF ϩ cells and the expression of HIF-1a ´, VEGF, Ang-1 and Ang-2 was evaluated by immunohistochemistry or quantitative real time reverse transcription-polymerase chain reaction (Real time PCR). Results: In the sham-control group, little BrdU ϩ /vWF ϩ cells or immunopositive vessels could be observed. After ICH induction, BrdU-labeled nuclei in cerebral endothelial cells (ECs) resided around the hematoma, and immunoreactivity of VEGF, Ang-1, HIF-1a ´and Ang-2 increased notably (PϽ0.01) compared with that of sham-operated animals. Real time PCR demonstrated that notable up-regulation of VEGF, Ang-1 and Ang-2 mRNA could be detected in the ipsilateral hemisphere (PϽ0.01) compared with that of sham-operated animals. However, after infusion of hirudin, the BrdU-labeled nuclei in ECs decreased significantly (PϽ0.01), and the HIF-1a ´, VEGF, Ang-1 and Ang-2 positive vessels reduced dramatically around the hematoma (PϽ0.01). Furthermore, the up-regulation of HIF-1a ´at protein level, VEGF, Ang-1 and Ang-2 at protein and mRNA level was inhibited (PϽ0.05). After infusion of thrombin, a few BrdU ϩ nuclei in ECs were found in the affected globus pallidus, and VEGF, Ang-1, HIF-1a ´and Ang-2 immunoreactivity increased (PϽ0.05) compared with that of saline-infused animals. Conclusions: Our results demonstrated that thrombin could induce angiogenesis in rat brains and may be an important trigger for ICH-induced angiogenesis.

Author Disclosures: H. Zhou: Research Grant; Significant; Graduate degree thesis Innovation Foundation CSU 2008yb048. T. Tang: Research Grant; Significant; HNNSF10JJ2023. Q. Yang: None.

W P219 The Role Of Iron In Brain Injury After Intraventricular Hemorrhage

Zhi Chen, Ya Hua, Richard F Keep, Karin Muraszko, Guohua Xi; Univ of Michigan, Ann Arbor, MI Background: Intraventricular extension of hemorrhage is a predictor of poor outcome in intracerebral hemorrhage (ICH) and iron overload contributes to brain injury after ICH. The current study investigated the role of iron in ventricular dilatation and neuronal death in a rat model of intraventricular hemorrhage (IVH). Methods: There were three parts in this study. First, male Sprague-Dawley rats had a 200-l injection of either autologous blood or saline into the right lateral ventricle and were euthanized at day 1, 3, 7 and 28. Second, rats received intraventricular injection of iron or saline and were euthanized one day later. Third, rats had IVH and were treated with deferoxamine (DFX, 100 mg/kg, i.m. at 2 and 6 hours after IVH and then every 12 h for 7 days) or vehicle, and rats were euthanized 4 weeks later. All rats had magnetic resonance imaging (MRI) and brains were used for histology. Results: Intraventricular injection of autologous arterial blood resulted in marked enlargement of cerebral lateral ventricles. Lateral ventricular volumes in IVH rats were much larger than in rats receiving saline injection at 24 hours (61.7 Ϯ 5.7 vs. 8.4 Ϯ 1.3 mm3 in saline group, PϽ0.01) through 4 weeks (40.4Ϯ6.8 vs. 10.1Ϯ8.0 mm3, PϽ0.01). T2* lesions were mainly located in the lateral ventricle of the injection side at 1 day after blood injection. Thereafter, the T2* lesion volume progressively declined but lesions were still observable at day 28, when they were mainly at the edge of the lateral. Four weeks after IVH, hippocampal volumes were smaller in IVH rats compared to saline injected controls (87.0Ϯ2.6 vs. 102.2Ϯ5.1mm3 in the saline group, PϽ0.01). To examine the effect of iron on ventricular dilation, rats were injected with iron or saline into the right ventricle. At 24 hours, lateral ventricular volumes were significantly larger in rats injected with iron (25.7Ϯ7.7 vs. 9.0Ϯ1.4 mm3 in the saline group, PϽ0.01). DFX was used as an iron chelator. DFX treatment reduced lateral ventricular volume significantly at 2 weeks (34.0 Ϯ8.9 vs. 44.0Ϯ10.2 mm3 in vehicle-treated group, PϽ0.05) and 4 weeks (32.7Ϯ10.6 vs. 43.8 Ϯ9.7 mm3 in vehicle-treated group, PϽ0.05) after IVH. There was a trend of decreasing of intraventricular T2* lesion volume in DFX-compared to vehicle-treated rats from the first week, but the difference only reached significance at 4 weeks after IVH (7.8Ϯ1.9 vs. 10.1Ϯ2.4 mm3, PϽ0.05). In addition, DFX reduced IVH-induced hippocampal tissue loss (89.0 Ϯ2.7 vs. 85.2Ϯ 4.1 mm3 in the vehicle-treated group, PϽ0.05) and CA-1 neuronal loss (148 Ϯ 23 vs. 120Ϯ29 cells/mm in the vehicle-treated group, PϽ0.05) at 4 weeks after IVH. Conclusions: Iron has a role in brain injury following IVH. DFX may be a therapy for patients with IVH or intraventricular extension after ICH.

Background and Purpose: Method for evaluating intraventricular extension of intracerebral hemorrhage (IVH) is not well established. We sought to prospectively evaluate IVH, LeRoux and Graeb Scores with regard to their abilities to predict outcome. Subacute IVH dynamics as well as the impact of EVD on IVH and outcome were also investigated. Methods: Sixty-five consecutive primary ICH patients were admitted to Columbia University Medical Center between February 2009 and March 2010. Baseline demographics, clinical characteristics, and EVD status were prospectively recorded. Admission CT scans performed within 24 hours of onset were reviewed for ICH location, hematoma volume, and presence of IVH. Scans with IVH were assigned IVH, Graeb, and LeRoux Scores. For each patient, the last scan performed within 6 days of ictus was similarly evaluated. Outcomes at discharge and 3-months were assessed using modified Rankin Scale (mRS). Receiver operating characteristic (ROC) analysis was used to determine the accuracies of the grading scales in predicting poor outcome (mRS Ն 3). Results: Forty-two patients had evidence of IVH on admission. Mean ICH and IVH volumes were 25 Ϯ 24 ml and 17 Ϯ 22 ml, respectively. Poor outcome was seen in 81% and 67% of patients at discharge and 3-month, respectively. Within 6 days, 20 (47.6%), 2 (4.8%) and 20 (47.6%) patients had either increase, decrease, or no change in their IVH volume, respectively. Direction of volume change was not associated with outcome (p ϭ 0.502). Areas under the ROC curve were similar among the IVH, Graeb, and LeRoux Scores when assessed at admission (0.809, 0.744, and 0.781, respectively) and within 6 days post-ictus (0.831, 0.774, 0.787, respectively). The IVH Score was associated with higher Youden Index than the Graeb and LeRoux Scores both at admission (0.522 vs. 0.412 vs. 0.515, respectively) and within 6 days post-ictus (0.559 vs. 0.522 vs. 0.493, respectively). Patients who received EVD had higher mean IVH volumes (28 Ϯ 26 ml vs. 5.7 Ϯ 6.9 ml, p ϭ 0.001) and increased incidence of hydrocephalus (91% vs. 24%, p Ͻ 0.0001) at admission but had similar outcome at discharge and 3-month as those with no EVD. Conclusions: The IVH Score predicts outcome with good accuracy in ICH patients with IVH both at admission and within 6 days post-ictus. It may perform better than the Graeb and LeRoux Scores in this high-risk population. IVH growth is common even after the first 24 hours but its impact on clinical outcome remains to be elucidated. EVD improves outcome in patients with severe IVH with particularly poor prognosis at admission. During the first session of ECP, cerebral blood flow velocity (CBFV) of middle cerebral artery (MCA) and mean blood pressure (BP) during ECP were recorded in 19 patients with good temporal window (Figure 1). Results: Mean NIHSS on admission was 8.7 for ECP group and 9.0 for the control group. Nine patients in the ECP group and 4 in the control group had a posterior circulation infarct. The proportion of patients with good outcome at 6 months (modified Rankin Scale dichotomized at 0-2) was 69.0% in the ECP group and 17.2% in the control group (ORϭ10.7, 95% CIϭ3.1 to 37.0; adjusted ORϭ15.6 for hypertension, diabetes and ischemic heart disease, 95% CIϭ3.4-66.8). Mean BP increased by 8.0% during ECP. Among 14 patients with MCA territory infarct, there was a 16.5% and 9.8% increase in mean CBFV in the relevant and irrelevant MCA, respectively (pϾ0.05). Although not statistically significant, the average increase in mean CBFV of bilateral MCAs was greater in patients with good functional outcome when compared with those with poor outcome (13.0% vs 11.1%). Conclusions: This study shows that ECP therapy increases mean CBFV in bilateral MCAs and might improve functional outcome of patients with progressing ischemic stroke. Further randomized studies are needed to demonstrate whether or not ECP may serve as an adjunctive therapy for patients with progressive ischemic stroke.

Author Disclosures: J. Han: None. L. Xiong: None. W. Lin: None. Y. Soo: None. T. Leung: None. K. Wong: None.

W P224 Intracranial Stenosis in the Young Patients May Represent a Distinct Syndrome

Farhan Siddiq, Gabriela Vazquez, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: Intracranial stenosis in the young patients from anecdotal experience appears to have different characteristics from that observed in the older population. Objective: To demonstrate that risk factor profile of young patients with intracranial stenosis is different when compared with older patients with intracranial stenosis using a case-control study. Methods: We reviewed data pertaining to clinical and angiographic characteristics of patients with intracranial stenosis (ICS) treated at three university affiliated tertiary care hospitals and identified their stroke risk factors. ICS patients were matched to a healthy population (without any history of stroke) using the National Health and Nutrition Examination Study (NHANES; 2003-04) by age, sex, and race/ethnicity. We stratified the population in two age groups (Ͻ45 and Ͼ45 years) and estimated the the relative risk (odds ratios) and attributable risk of known cardiovascular risk factors on the occurrence of angiographically confirmed intracranial stenosis. Results: A total of 17 (11%) patients from 153 patients with intracranial stenosis were aged 45 years or less in the study population. These patients were more likely to be women (53% versus 28%, PϽ0.05). The location of the lesion in the young patients was more likely to be in the internal carotid artery (65% versus 29%, PϽ0.05) and less likely to be in the vertebral or basilar artery (12% versus 45%, PϽ0.05). When compared with the control population from NHANES study group, it appears that the attributable risk of hypertension, diabetes mellitus, and coronary artery disease for intracranial stenosis was lower among patients Յ 45 years than that for intracranial stenosis in patients Ͼ 45 years of age (6.4% versus 13.1%, 19.9% versus 33.0% and 1.0% versus 10.8%, respectively). Attributable risk of cigarette smoking on intracranial stenosis did not differ between patients aged Յ 45 and those Ͼ 45 years old (11.9% versus 11.0%, respectively). Hyperlipidemia had a greater attributable risk of intracranial stenosis in patient Յ45 year old than those Ͼ 45 year old (23.3% versus 9.3%). Conclusions: Intracranial stenosis in the young patients appears to be different when compared to older patients because of prominently lower contribution of known cardiovascular risk factors and different location of atherosclerosis.

Author Disclosures: F. Siddiq: None. G. Vazquez: None. A.I. Qureshi: None.

W P225 Delayed Absorption Of The Contrast Media In CT Angiography Indicates Plaque Stability In Carotid Stenosis

Nobutaka Horie, Dept of Neurosurgery, Nagasaki Univ Sch of Medicine, Nagasaki, Japan; Minoru Morikawa, Dept of Radiology, Nagasaki Univ Sch of Medicine, Nagasaki, Japan; Shunsuke Ishizaka, Kentaro Hayashi, Kazuhiko Suyama, Izumi Nagata; Dept of Neurosurgery, Nagasaki Univ Sch of Medicine, Nagasaki, Japan Background and Purpose: Plaque vulnerability is an important factor in the symptomatic carotid stenosis, and recent study focuses on the plaque morphology with some imaging modalities. Here, we prospectively evaluated plaque stability with subtraction method in CT angiography, and compared with MR imaging and histological findings. Methods: Fifty lesions in forty four patients (38 male, ages 71.7Ϯ1.8) showing moderate to severe carotid stenosis (Ͼ50% in NASCET) were consecutively included in this study. Dynamic study with CT angiography (Aquilion Tsx-101A, TOSHIBA) was performed and images were obtained twice in the early and delayed phase with an interval of 2 minutes. Three equivalent axial slices were selected (thickest plaque and distal/proximal plaque with an interval of 3mm) in both phases and subtracted Hounsfield unit (HU) value in the plaque. The data was analyzed in association with plaque MR imaging (Black Blood method; Signa, GE Medical Systems) and pathological findings with surgical specimens. The reading of the images was analyzed by 2 experienced readers who were blinded. Results: Subtracted HU value was significantly associated with symptomatic presentation compared with the HU value in early phase (pϽ0.01), and negatively correlated with signal intensity on MRI T1WI and TOF. In terms of the histology, the plaques with fibrous tissue had higher subtracted HU value suggesting delayed absorption of the contrast media in the fibrous tissue. Conclusions: This study first shows functional plaque evaluation using new method in CT angiography. With this method, blooming effect due to calcification could be figured out and gives us more accurate information regarding plaque morphology. Delayed absorption of the contrast media could suggest plaque stability.

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International Stroke Conference and Nursing Symposium Poster Presentations e223

by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from Background and Purpose: Although digital subtraction angiography (DSA) provides excellent and accurate visualization of the intracranial artery stenosis(ICAS), it has several limitations. Purfusion images are known to show the hypoperfused and critical brain areas in the hyperacute ischemic stroke patients. However, it remains unclear whether perfusion images can give additional information for ICAS in subacute or chronic stroke patients. Our purpose was to evaluate the ability of MR perfusion images to help detect and quantify intracranial stenosis and occlusion compared with DSA and MR angiography (MRA). Methods: From 2008, 83 patients underwent 3D time-of-flight (TOF) MRA, MR perfusion images and DSA for suspected cerebrovascular lesions like ICAS and intracranial aneurysm. All three studies were performed within a 14-day period. Four readers blinded to prior estimated or calculated stenoses, patient history and clinical information, examined 1079 vessel segments including basilar artery, PCA, M1,M2, A1,A2 and distal ICA. Lesions were categorized as normal (0-49%), moderate (50-69%), and severe (70-100%). DSA was the reference standard. Unblinded consensus readings were obtained for all discrepancies. First, we compared the only MRA with MRA combined with perfusion images(MRA/P). Results: A total of 73 diseased vessel segments were identified on DSA. After consensus interpretation, MRA/P revealed higher sensitivity and specificity than that of only MRA for intracranial stenosis (sensitivity, 68% versus 55%, P ϭ 0.02;specificity, 85% versus 35%, P Ͻ0.01). MRA/P had a higher positive predictive value than only MRA(88% versus 51%, P Ͻ 0.01) and a high interoperator reliability. All of five patients with false positive lesions on MRA/P had the large territorial infarction. Three false negative lesions on MRA/P were caused by the well developed collateral flows from ECA. Conclusion: Perfusion MR images enhanced the accuracy of diagnosis for ICAS, compared with only MRA and were recommended during evaluation of TOF MRA for detection of intracranial stenosis and occlusion. Perfusion images combined with MRA might reduce the frequency of unessential DSA in the patients without significant ICAS.

Author Disclosures: H. Park: None. C. Hong: None. I. Han: None. J. Rha: None.

W P227 Burden Of Symptomatic Steno-occlusion In Patients With Acute Cerebral Ischemia In Korea: Prevalence, Distribution And Functional Outcome

Jihoon Kang, Hee-Joon Bae, Moon-Ku Han, Myung Suk Jang, Seoul National Univ Bundang Hosp, Seongnam, Korea, Republic of; Jong-Moo Park, Nowon Eulji General Hosp, Eulji Univ, Seoul, Korea, Republic of; Tai Hwan Park, Seoul Med Cntr, Seoul, Korea, Republic of; Kyung Bok Lee, Soonchunhyang Univ College of Medicine, Seoul, Korea, Republic of; Youngchai Ko, Soo Joo Lee, Eulji Univ Hosp, Eulji Univ, Dae-jeon, Korea, Republic of; Keun Hwa Jung, Seoul National Univ College of Univ, Seoul, Korea, Republic of; Yong-Jin Cho, Ilsan Paik Hosp, Inje Univ, Ilsan, Korea, Republic of; Kyung-Ho Yu, College of Medicine, Hallym Univ, Anyang, Korea, Republic of; Byung-Chul Lee, College of Medicine, Hallym Univ,, Anyang, Korea, Republic of; Jungyoung Lee, Dept of Biostatistics, Korea Univ College of Medicine, Seoul, Korea, Republic of; Jae-Kwan Cha, College of Medicine, Dong-A Unversity, Busan, Korea, Republic of; Jun Lee; Yeungnam Universty Med Cntr, Dae-gu, Korea, Republic of Background: Symptomatic steno-occlusion (SSO) of cerebral arteries in patients with acute ischemic stroke has a great impact on their treatment options and prognosis. However, we do not know well about how prevalent it is, how it is treated, and what its outcome is, especially in the Korean stroke population, where intracranial cerebral atherosclerosis is a major cause of stroke and the fraction of cardioembolic stroke is increasing with rapid aging of society.

Method: Between September, 2008 and March, 2010, a consecutive series of 5395 patients, who were hospitalized due to acute ischemic stroke to 9 centers that were scattered nationwide and participating in the 'Clinical Research Center for Stroke' program funded by the Korean government, were collected prospectively. 3181 patients were presented within 24 hours from symptom onset and had relevant lesions on diffusion weighted image (DWI). Among them, 3080 patients who underwent MR angiography (MRA) to evaluate cerebral vascular status were enrolled in this study. Demographics, clinical profiles, treatments, clinical outcomes, and imaging characteristics including vascular status on MRA were gathered prospectively. SSO was defined by stenosis or occlusion of cerebral arteries with relevant ischemic lesions on the corresponding arterial territory on DWI. Result: A total 1951 (63.3%) patients (mean age: 68.7 Ϯ 12.0 years old, male 57.8%) of study subjects had SSO. Compared to those without SSO, they were older age, high glycosylated hemoglobin level and high cardioembolic sources (CE) with statistical significance. The median NIHSS score of patients with SSO was 6 (interquartile range: 2-14); those without SSO was 3 (1-6). Proportion of thrombolysis was 18.5% with SSO and 9.3% without SSO. The most affecting vessel was middle cerebral artery (34.6%), and followed by extracranial internal carotid artery (14%), vertebral artery (12.4%), basilar artery (8.7%) and intracranial internal carotid artery (8.7%). SSO were independent risk factor of poor functional outcome (mRSϾ2) at discharge adjusted by age, initial stroke severity,CE, thrombolysis and initial BP status (odds ratio: 1.72, 95% confidence interval: 1.42-2.09). Of patients with SSO, 559 (18.1%) presented multiple vessel involvement. Proportion of poor functional outcome of patient with multiple SSO (67.6%) was higher than those with single SSO (49.9%) and without SSO (29.6%). Patterns of multiple SSO were both anterior and posterior circulation (8.6%), unilateral anterior circulation (6.8%), posterior circulation only (2.7%) and bilateral anterior circulation (1.4%). Positioning of SSO in terms of anterior or posterior circulation was associated with age, hypertension history and CE. Discussion: About 63% of patients with acute ischemic stroke had SSO and 1/3 of them had multiple involvements. Distribution and patterns of SSO were associated with functional outcome.

W P228 Prevalence Of Intracranial Atherosclerotic Disease Coexisting With Extracranial Atherosclerosis In The North Indian Population

Dheeraj Khurana, Jomal Mathews, Vivek Gupta, S Prabhakar; PGIMER, Chandigarh, India Background: Coexistent intracranial and extracranial atherosclerotic disease holds a worse prognosis than either disease alone. Data on this atherosclerotic burden is not available from India. Objectives: 1. To determine the prevalence of intracranial atherosclerotic disease(IAD) in patients with extracranial atherosclerotic disease(EAD)2. To study the association of risk factors with the intracranial and extracranial atherosclerosis. Methods: Patients 18 years and above with ischemic stroke or TIA in the anterior or posterior circulation were prospectively recruited.On confirming presence of extracranial atherosclerotic disease by ultrasound duplex,CT angiography (CTA)of the carotid and cerebral arteries was carried out within 3 months of the stroke.Risk factor assessment included hypertension, diabetes mellitus, hyperlipidemia, and cigarette smoking. Results: 60 patients were studies. Mean age was 64.65 years (45 -82 years). 78.33% were males.80% had anterior circulation symptoms,20% had posterior circulation. 13(21.67%) patients presented with TIAs. 78.33% were hypertensive,40% were diabetics,58.3% were dyslipidemic and 21.67% were smokers. Mean time period between stroke onset to CT angiography was 32 days (range:1 -86 days). Duplex ultrasound revealed significant extracranial disease( Ն50% stenosis or occlusion)in 41.67% patients. Prevalence of IAD on CTA was 88.33%. Males constituted 75.47 %.46.67% had anterior circulation disease alone, 5%posterior circulation and 36.6% had combined anterior and posterior circulation disease. 46.67% had significant IAD (Ն50% stenosis). 20% had significant disease in anterior circulation, 20 % in posterior circulation and 6.66% combined disease.Among the diseased segments, IAD was commonest in the carotid siphon (71.42%) followed by the intracranial portion of the vertebral artery (14.91%) and PCA (5.56%).Anterior and middle cerebral artery IAD was found in 2.5 and 3.1% segments, basilar in 2.5%. Significant combined EAD and IAD was present in 21.67% patients.15 patients had significant IAD without coexisting significant EAD. 30.78% patients of significant EAD had accompanying ipsilateral significant IAD in the carotid siphon or vertebral artery. 18.33% had extracranial disease alone corresponding to the involved side of stroke, 8.3% had significant IAD and combined significant IAD and EAD was present in 11.67%.None of the risk factors reached significance on comparing EAD with combined IAD and EAD. Conclusion: 1. IAD has a high prevalence in the north Indian ischemic stroke population.2. IAD is an important contributor to ischemic stroke etiology in this population accounting for ϳ20% of ischemic strokes.3.IAD may be independent of EAD as a risk factor for ischemic stroke in this population.4.No specific risk factor is significantly associated with either coexistent disease or IAD alone in our study.

Author Disclosures: D. Khurana: None. J. Mathews: None. V. Gupta: None. S. Prabhakar: None.

W P229 High Levels of Apolipoprotein B/AI Ratio in Ischemic Stroke Patients with Intracranial Atherosclerosis

Jong-Ho Park, Stroke Cntr, Kwandong Univ. Myongji Hosp, Goyang, Korea, Republic of; Eun-Ja Lee, Dept of Diagnostic Radiology, Kwandong Univ. Myongji Hosp, Goyang, Korea, Republic of; Hyun Jeong Han; Dept of Neurology, Kwandong Univ. Myongji Hosp, Goyang, Korea, Republic of Background & Objectives: Apolipoprotein B (apoB) level represents the small dense oxidized low-density lipoprotein (ox-LDL) particles and apolipoprotein AI (apoAI) level represents the number of antiatherogenic [(high density lipoprotein (HDL)] particles. ApoB/apoAI ratio is a valid risk indicator of ischemic stroke. Insulin resistance, a basis of metabolic syndrome (MetS) is associated with small dense ox-LDL particles. Because intracranial large artery atherosclerosis (IC-LAA) is associated with the MetS and oxidation injury, we hypothesized that IC-LAA could be more associated with serum level of apoB/apoAI ratio than extracranial (EC)-LAA. Methods: We prospectively investigated demographic features and risk factors in ischemic stroke patients (Յ7 days of onset) who underwent brain MRI/MRA from March 2008 through June 2010. Stenosis was diagnosed in cases showing a degree of luminal narrowing of Ն50%. The stroke subtypes were categorized as IC-LAA, EC-LAA, small artery occlusion (SAO), cardioembolism (CE), and stroke of undetermined etiology (SUE). MetS was diagnosed following the AHA/NHLBI criteria. We defined a high apoB/apoAI ratio as the highest gender-specific quartile (Ͼ75 th percentile; Ͼ0.91 in male, Ͼ0.87 in female). We performed comparative studies of apoB/apoAI ratio based on angiographic findings and examined associations between quartiles of apoB/apoAI ratio and IC-LAA by controlling possible confounders. Results: We finally included a total of 388 patients (mean age 68.1Ϯ12.8; 210 males). One hundred and ninty-six patients (50.5%) were in the IC-LAA group, 34 patients (8.8%) were in the EC-LAA group, 77 patients (19.8%) were in the SAO group, 62 patients (16.0%) were in the CE group, and 19 patients (4.9%) were in the SUE group. The serum levels of apoB/apoAI ratio were higher in the IC-LAA than the other subtypes (Pϭ0.014). Patients with a higher quartile of apoB/apoAI ratio showed increasing tendency to have higher MetS and its 5 components, stenosis, and apoB level, and lower level of apoAI (all PϽ0.05). The number of IC-LAA showed a tendency to increase in proportion to the quartile of apoB/apoAI ratio (PϽ0.0001) while the EC-LAA demonstrated no association. ApoB/apoAI ratio showed an independent predictor for IC-LAA, and a higher risk of IC-LAA in individuals with highest quartile of apoB/apoAI levels (OR 2.57; Pϭ0.009) vs. patients with low apoB/apoAI levels. In terms of multiple(Ն3) IC-LAAs, as compared with patients with 1 st quartile, the adjusted ORs for IC-LAA increased from 3.90 for the 2 nd quartile (Pϭ0.025) to 4.94 for the 3 rd quartile (Pϭ0.009) and as high as 8.54 for the highest quartile (PϽ0.0001). Conclusions: High level of apoB with ox-LDL particle might be causal factor for IC-LAA. We suggest that apoB/apoAI ratio might be a useful biological marker for identifying patients likely to be harboring IC-LAA.

Author Disclosures: J. Park: None. E. Lee: None. H. Han: None.

W P230 Predictors of Neurologic Deterioriation in Large Vessel Strokes Presenting Outside the Traditional Treatment Window

Johanna L Morton, Muhammad S Hussain, Ken Uchino, Ferdinand K Hui, Irene L Katzan; Cleveland Clinic, Cleveland, OH Background: Patients presenting with ischemic stroke in the setting of large vessel occlusions outside the established treatment time window for endovascular intervention present a therapeutic challenge. In this subacute stroke population, there is a lack of evidence to support which patients benefit from endovascular intervention to salvage remaining reversible ischemic tissue (penumbra) and which subgroups are at risk for further neurological deterioration from infarct progression. Methods: Retrospective cohort study of patients presenting with large vessel occlusion Ͼ 6 hours from symptom onset to Cleveland Clinic between 5/09 and 6/10. Results: 43 patients (mean age 63.5 Ϯ 14.0, 41.9% female) met inclusion criteria. Mean NIHSS on admission was 13.7Ϯ8.3, median time from last known well to imaging was 21.0 hours. The majority (72.1%) had intracranial occlusions; these patients had higher NIHSS scores than those with extracranial occlusions only (mean NIHSS 16.5 vs 6.4, PϽ0.001). Neurological worsening or death during hospitalization occurred in 51.2% of patients overall, and was significantly more frequent in patients with intracranial occlusions (61.3%) than in those with extracranial occlusions (25%, pϭ0.03) and in patients with cardiac embolism (76.9%) compared to those with large vessel disease (40%, pϭ0.03). Patients who worsened had higher initial NIHSS (15.9 vs 11.4, pϭ0.08), were older (68 vs 59 years, pϭ0.03), had shorter times from last known well to imaging (21.6 vs 29.9 hours, pϭ0.11). 16 of 43 patients (37.2%) received endovascular therapy. Intervention was not associated with reduced rates of neurological worsening overall (62.5% intervention vs 44.4% no intervention, pϭ0.14) or within the following subgroups: intracranial occlusions [66.7% (8/12) intervention vs 57.9% (11/19) no intervention, pϭ0.62], NIHSS Ͻ 10 [75% (3/4) intervention vs 12.5% (1/8) no intervention, pϭ0.07], ASPECTS scores Ն 8 (80% vs 20%, pϭ0.21), good collateral vessel grading score [20% (1/5) vs 12.5% (1/8), pϭ0.71]. Conclusions: Patients presenting with ischemic stroke and large vessel occlusions outside the traditional treatment time window for endovascular therapy represent a high risk population for neurological deterioration. In this analysis, patients with intracranial occlusions, higher initial NIHSS, cardioembolic disease, and older age had higher rates of neurological worsening. Although subject to selection bias, endovascular therapy in this patient population was not associated with reduced rates of neurological deterioration. Further study of this population is required to identify the predictors of neurological deterioration, and to determine the best medical or endovascular interventional strategies to salvage remaining ischemic penumbra and prevent infarct extension.

Author Disclosures: J.L. Morton: None. M.S. Hussain: None. K. Uchino: None. F.K. Hui: None. I.L. Katzan: None.

W P231 Optimal Pressure of External Counterpulsation for Cerebral Blood Flow augmentation in Ischemic Stroke Patients

Wen Hua Lin, Li Xiong, Jing Hao Han, Thomas Leung, Yannie Soo, Vincent Mok, Xiang Yan Chen, Lawrence K.S. Wong; The Chinese Univ of Hong Kong, Hong Kong, Hong Kong Background: External counterpulsation (ECP) is a non-invasive method used to augment cerebral perfusion but the optimal pressure used has not been well documented. We aim to find the optimal pressure of ECP treatment in relation to the cerebral blood flow. Methods: We recruited 30 ischemic stroke patients with large artery occlusive disease. The mean time after symptom onset was 6.41 days. We monitored the blood flow velocities of bilateral MCAs before and during ECP therapy using TCD. We started ECP treatment pressure on the lower body from 0.02MPa (150mmHg), then gradually increased to 0.025MPa (187.5mmHg), 0.03MPa (225mmHg), 0.035MPa (262.5mmHg). TCD parameters, including peak systolic velocity PSV, end-diastolic velocity EDV, peak diastolic augmentation velocity PDAV and mean flow velocity MV were recorded for 3 minutes before and during each pressure increment. Monitoring data on MCA was analyzed based on whether it was ipsilateral or contralateral to the infarct. Results: The mean flow velocities on the symptomatic side under different ECP pressures, increased 18.49% (0.02MPa), 19.33% (0.025MPa), 19.16% (0.03MPa) and 18.46% (0.035MPa). All were significantly higher than baseline but did not differ among different pressures. Under increasing pressures, PDAV gradually increased (78.70%, 88.24%, 96.66%, 103.02% respectively compared with baseline EDV, PϽ0.001) while PSV decreased (3.60%, 2.64%, 1.02%, -1.88% compared with baseline PSV, pϭ0.001) and EDV decreased (-1.35%, -4.18%, -9.28%, -11.87% compared with baseline EDV, pϭ0.002). Contralateral MCA velocity change tendency showed similar picture. Conclusion: 150mmHg appears to be the optimal pressure to be used to increase cerebral blood flow. Further increase in pressure does not increase cerebral blood flow velocity.

Author Disclosures: W. Lin: None. L. Xiong: None. J. Han: None. T. Leung: None. Y. Soo: None. V. Mok: None. X. Chen: None. L. Wong: None.

W P232 Predictors Of Outcome In Conservatively Treated Patients With Symptomatic Basilar Artery Occlusive Disease

Angelos M Katramados, Andrew Russman, Brian Silver, Lonni Schultz, Panayiotis D Mitsias; Henry Ford Hosp, Detroit, MI Purpose: To identify clinical and radiological predictors of outcome in patients with cerebral ischemia attributed to basilar artery occlusion that were treated conservatively with antiplatelets or anticoagulation. Methods: We retrospectively identified patients who were treated in the Acute Stroke Unit of Henry Ford Hospital with clinical and radiological evidence of cerebral ischemia attributed to basilar occlusive disease, and did not receive endovascular treatment because of delayed presentation or other contraindications. 18 patients were identified. Demographics, patterns of clinical presentation, parenchymal and vascular involvement as well as stroke etiology were reviewed and correlated with functional outcome at discharge. Results: Hypertension was the most prominent risk factor, with many patients sharing multiple vascular risk factors. Of the 18 patients included in this analysis, 11 had a modified Rankin Score (mRS) equal to or less than 3, and 7 had an mRS equal to or more than 4 upon discharge. Decreased level of consciousness upon presentation, tetraparesis/tetraplegia, bulbar/pseudobulbar manifestations, oculomotor findings, occlusion of the proximal 1/3 of the basilar artery, radiological evidence of brainstem ischemia and an acute pattern of onset (without preceding transient attacks) were associated with a poorer outcome. Patients with recurrent transient symptoms tended to do well, although some of them would progress to deteriorate clinically. Age, gender, presence of specific vascular risk factors, headache, demonstration of hyperdense vascular signs, and treatment with antiplatelets versus anticoagulation did not have a significant correlation with mRS upon discharge. Discussion: Basilar artery occlusive disease has a grave prognosis in the absence of endovascular intervention. No difference in outcomes with antiplatelets or anticoagulation treatment is observed in this study. Certain clinical and radiological parameters are noted to be significantly associated with functional outcome and can be used to guide management decisions. These parameters signify extensive brainstem ischemia that cannot be reversed with conservative measures.

Author Disclosures: A.M. Katramados: None. A. Russman: None. B. Silver: None. L. Schultz: None. P.D. Mitsias: None.

W P233 Prediction Of Asymptomatic Cerebrovascular Diseases Before Bypass Surgery For Peripheral Artery Disease

Shigeru Fujimoto, Satoshi Suzuki, Shinji Yamamura, Juro Jinnouchi, Takayuki Matsuki, Takuya Inoue, Takeo Amemiya, Seizo Sadoshima; NIPPON STEEL YAWATA MEMORIAL HOSPITAL, Kitayushu, Japan Background & Purpose: Both cerebrovascular disease (CVD) and peripheral artery disease (PAD) are atherothrombotic disease and sometimes coexist with each other. We investigated predictive factors for CVD before bypass surgery for PAD. Subjects & Methods: For the present study, 102 consecutive PAD patients without a history of any stroke who were planned to undergo a bypass surgery were included. Before the surgery, all patients were studied by ankle brachial index (ABI), duplex carotid ultrasonography, magnetic resonance imaging (MRI) including diffusion weighted imaging (DWI), and MR angiography. A stenosis of Ն70% or occlusion of the major intracranial or extracranial cerebral arteries was defined as a severe vascular lesion. We also investigated the predictive factors for severe cerebrovascular lesions. Results: A severe vascular lesion of the intracranial and extracranial cerebral arteries was observed in 15 (15%) and 19 (19%) patients respectively. There were asymptomatic ischemic lesions on MRI in 62 (61%) patients. Among them, 9 (9%) patients had asymptomatic high-intense lesions on DWI. Severe carotid stenosis (44% vs 16%, pϭ0.0372), low echoic plaques (89% vs 30%, PϽ0.0001), or ulcerative plaques (44% vs 7%, pϭ0.0003) were more frequent in patients with than without high-intense lesions on DWI. Eight patients were diagnosed as having an indication for cerebral revascularization before the bypass surgery for PAD: carotid endarterectomy in 7 and extracranial-intracranial bypass in 1. In patients with severe vascular lesions of the intracranial cerebral arteries, female was more frequent (53% vs 24%, pϭ0.0138) and ABI value was relatively lower (0.29Ϯ0.22 vs 0.42Ϯ0.28, pϭ0.0772) in comparison to patients without severe vascular lesions. ABI value was relatively lower in patients with than without severe vascular lesions of the extracranial cerebral arteries (0.26Ϯ0.21 vs 0.42Ϯ0.27, pϭ0.0667). Female was more frequent (43% vs 24%, pϭ0.0464), ABI value was lower (0.29Ϯ0.28 vs 0.44Ϯ0.28, pϭ0.0199), and hypercholesterolemia and ischemic heart disease were relatively more frequent in patients with than without severe vascular lesions of the intracranial or extracranial cerebral arteries. On multivariate analysis, ABI was a significant predictor for a severe vascular lesion of any cerebral arteries. With regard to the sensitivity-specificity curve analysis, the ABI cut-off value of 0.40 or less yielded the highest diagnostic accuracy (sensitivity, 68%; specificity, 66%) for severe cerebrovascular lesions. The ABI cut-off value of 0.67 or less yielded a complete sensitivity. Conclusions: ABI value was a significant predictor for severe cerebrovascular lesions before the bypass surgery for PAD. Asymptomatic high-intense lesions on DWI could be observed in PAD patients with severe carotid stenosis, low echoic plaques, or ulcerative plaques.

Author Disclosures: S. Fujimoto: None. S. Suzuki: None. S. Yamamura: None. J. Jinnouchi: None. T. Matsuki: None. T. Inoue: None. T. Amemiya: None. S. Sadoshima: None. The extent of carotid artery atherosclerosis correlates with increased plasma concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and with a decreased plasma concentration of high-density lipoprotein cholesterol (HDL). Emerging data suggest that a triglyceride (TG):HDL ratio may be a better predictor of vascular risk than the traditional lipid measures such as TC and LDL. However, there have been few reports on the association between serum lipid indices and steno-occlusive disease of the intracranial arteries. Objective: The purpose of this study was to directly compare the clinical utility of TC, LDL, TG, HDL, and the TG:HDL ratio as predictors of intracranial arterial stenosis in stroke-free Korean adults using brain magnetic resonance angiography (MRA). Methods: We retrospectively analyzed the records of 361 stroke-free subjects who consecutively visited a general health promotion center in a university-affiliated hospital from February 2006 through April 2009. Included subjects underwent brain 3D time of flight MRA as part of their voluntary health checks. The presence of stenosis (Ն25%) in the basilar artery (BA) and in the horizontal portion of the middle cerebral artery (MCA) was assessed using brain MRA. All patients had fasting lipid panels drawn. We categorized serum lipid indices into quartiles and logistic regression analyses were performed. Results: The subjects were 183 men and 178 women, and their mean age was 52 Ϯ 10 years. Eight subjects were using lipid-lowering medication. One hundred thirty-seven subjects (38%) had MCA stenosis, and 105 subjects (29%) had BA stenosis. Univariate analyses of the correlations between clinical parameters and BA stenosis and between clinical parameters and MCA stenosis were performed. Patients with MCA stenosis were older and more likely to be on antihypertensive medication than patients without MCA stenosis. Systolic blood pressures were significantly higher in patients with BA stenosis than in patients without BA stenosis. None of the serum lipid indices was associated with prevalence of MCA stenosis. None of the traditional lipid measures was associated with prevalence of BA stenosis. However, the TG:HDL ratios in the upper three quartiles compared with the lowest quartile were associated with increased prevalence of BA stenosis with odds ratios of 2.4 (95% CI 1.2-5.0), 3.3 (95% CI 1.6-6.8), and 2.5 (95% CI 1.2-5.2), respectively. Adjustment for age, systolic and diastolic blood pressure, and the prior use of antihypertensive medication did not substantially change the associations. Conclusion: The TG:HDL ratio is a better predictor of the intracranial stenosis, especially BA stenosis than any standard lipid measure in stroke-free Korean adults.

W P234

Author Disclosures: J. Park: None. J. Koo: None. Y.A. Kim: None. K. Kang: None.

W P235 Collaterals Determine the Hemodynamic Impact of Atherosclerotic Intracranial Stenosis

David S Liebeskind, UCLA, Los Angeles, CA; Nerses Sanossian, USC, Los Angeles, CA; Qing Hao, Rana Fiaz, Noriko Salamon, Jeffry R Alger, Jeffrey L Saver, UCLA, Los Angeles, CA; for the UCLA Collateral Investigators Background: Degree of luminal stenosis is the principal variable used to guide potential therapeutic strategies for symptomatic intracranial atherosclerosis (SIA) but the role of hypoperfusion remains unclear. Collaterals have recently been shown to dramatically alter risk of recurrent stroke in intracranial stenosis. Our aim was to characterize the association of delay and dispersion on CT/MR perfusion (CTP/MRP) imaging with type of perfusion (antegrade versus collateral) on digital subtraction angiography (DSA) in patients with SIA. Methods: Consecutive cases of SIA with concurrent CTP/MRP and DSA were analyzed. CTP/MRP measures of cerebral blood volume (CBV) and TmaxϾ4s were calculated. DSA features including degree of luminal stenosis, length and irregularity were assessed in blinded fashion. Antegrade perfusion on DSA was measured by Thrombolysis in Cerebral Infarction (TICI) grade and collaterals were scored by ASITN/SIR grade. CTP/MRP lesion volumes were analyzed with respect to all DSA parameters. Results: 28 cases (mean age 62.8Ϯ14.1 years; 16 men, 12 women) of recent SIA and concurrent CTP/MRP and DSA were analyzed. Stenoses ranged from 50-99%, with lesion length ranging from 1.0-12.9 mm and irregularity noted in 10/28 (36%). CBV lesion volumes included ischemia (mean 0.9%Ϯ0.9), penumbra (mean 3.4%Ϯ2.6), and hyperemia (mean 20.3%Ϯ5.3). TmaxϾ4s lesions indicative of abnormal delay included mean 17.3%Ϯ8.8. DSA measures were evenly distributed across the full range of scores for antegrade perfusion (TICI) and collaterals. Extensive variability was also noted between the extent of delay on TmaxϾ4s and dispersion of hyperemia on CBV across the full range in degree of luminal stenosis. Antegrade perfusion measured on DSA (TICI) was inversely correlated with compensatory collateral grade (pϽ0.01). Such DSA measures of antegrade flow beyond the lesion and downstream collaterals provided distinct information from CTP/MRP measures of delay and dispersion. Conclusions: The hemodynamic impact of intracranial atherosclerosis on antegrade flow reflects collateral perfusion, not just degree of stenosis. Downstream hyperemia or elevated CBV may balance delayed perfusion yet these parameters appear distinct from DSA measures. Noninvasive imaging may therefore complement conventional angiographic characterization of SIA.

Author Disclosures: D.S. Liebeskind: Research Grant; Significant; K23NS054084. Consultant/ Advisory Board; Modest; CoAxia, Inc.. N. Sanossian: None. Q. Hao: None. R. Fiaz: None. N. Salamon: None. J.R. Alger: None. J.L. Saver: None.

W P236

Individual Vessel and Regional Blood Flow Measurements: Implications for Flow and Collateral Assessment in Cerebrovascular Occlusive Disease Sepideh Amin-Hanjani, Xinjian Du, Meide Zhao, Sean Ruland, Nada Mlinarevich, Fady T Charbel; Univ of Illinois at Chicago, Chicago, IL

Objective: We sought to analyze blood flow rates in individual major cerebral arteries and vessel territories, using quantitative magnetic resonance angiography (QMRA). Methods: 326 healthy adult volunteers with no history of cerebrovascular disease underwent QMRA of head and neck vessels using commercially available software, NOVA (Vasol, Inc.). Individual vessel flows were measured in the internal carotid artery (ICA), middle cerebral artery (MCA), anterior cerebral artery (ACA) A1 and A2 segments, posterior cerebral artery (PCA), basilar artery (BA), and vertebral artery (VA). In a subset (nϭ192) with a full complement of vessel flows (including A2s), regional distal territory flows, incorporating primary (Willisian) and secondary (leptomeningeal) collaterals were calculated (see figure). Specifically, for MCA or ICA territory we examined flows for the anterior circulation left region (LR) and right region (RR) ϭ MCA ϩ A2 ϩ PCA; for VA or BA territory, we looked at the posterior region (PR) ϭ BA ϩ PCAs. Results: In the full cohort, mean age was 48 (18-84) years old, with 48% females; the subset cohort was not demographically different. For individual vessels, the range of blood flows, as reflected by the coefficient of variation (CV) was larger for paired vessels with potential for anatomic variability* (hypoplasia or dominance), such as VAs or A1 segments compared to MCA and PCAs. The BA flows also showed larger variability **, likely reflecting the wider range of flows given distal anatomic variants such as fetal PCA, and posterior communicating artery (PcoA) anatomy. For regional territory flows, LR and RR have a lower CV, than their individual vessel counterparts, ICA and MCA. Similarly the PR has a lower CV than its individual vessel counterparts, the BAs and VAs. Conclusions: In evaluating the flow effects of cerebrovascular occlusive disease, comparison to normative distal territory flows, rather than individual vessel normative flows, may provide a more robust measure of flow compromise, as the former is less susceptible to anatomic variants. Furthermore, territorial flows provide a more global measure of hemodynamic status, incorporating both primary and secondary collaterals.

Background: Intracranial stenosis is the commonest causes of stroke among Asian patients. An association exists between the degree of stenosis and stroke recurrence. In severe intracranial steno-occlusive disease, perfusion is maintained by collateral pathways and cerebral autoregulation (CA). CA may be impaired due to inadequate cerebral vasodilatory reserve (CVR) & intracranial steal phenomenon, so-called the 'reversed-Robin Hood (RRH) syndrome'. Identification of patients with inadequate CVR may help in selecting high-risk patients who could benefit from various revascularization procedures. Methods: We prospectively included patients with symptomatic and severe intracranial steno-occlusive disease (intracranial carotid artery and middle cerebral artery). Severe intracranial stenosis was defined according to validated transcranial Doppler (TCD) velocity criteria and blunted flow in distal segments. CVR was evaluated with TCD and breath-holding index (BHI) Ͻ0.69 determined inadequate reserve. RRH was detected as transient velocity reduction in affected artery at the time of velocity increase in the reference normal artery. Intracranial steal magnitude was calculated in these cases. Patients with RRH were further evaluated with acetazolamidechallenged HMPAO-SPECT and net deficit in metabolic perfusion was calculated. Results: 101 patients (73 males, mean age 56yrs; range 23-78yrs) with severe intracranial stenosis fulfilled our TCD criteria of inadequate CVR on TCD. RRH phenomenon was observed in 33 (33%) patients with a median steal magnitude of 17% (inter-quartile range, IQR 10). Acetazolamidechallenged HMPAO-SPECT demonstrated significant metabolic perfusion deficit (median 8%; IQR 13%) in 31 out of these 33 cases (sensitivity 77%, specificity 97% with positive predictive value 97%). A strong relationship between RRH on TCD and acetazolamide-challenged HMPAO-SPECT was noted on ROC curve analysis (area under curve 0.93; 95% confidence interval 0.88-0.98;petazolamide-challenged HMPAO-SPECT (Pearson correlation coefficient, rϭ0.643;pchemia (pϭ0.04; RR 1.7, 95%CI 1.2-3.6). Conclusions: Reversed Robin Hood syndrome in patients with severe intracranial stenosis is associated with very high risk of cerebral ischemic events. Acetazolamide-challenged HMPAO-SPECT is reliable in the diagnosis of reversed Robin Hood syndrome in patients with severe steno-occlusive disease of intracranial carotid and middle cerebral artery. Identification and quantification of intracranial steal magnitude helps in identifying a target group of patients for possible revascularization procedures.

W P238 Increased Hemorrhagic Risk of Thrombolysis in Acute Ischemic Stroke Patient with Malignancy

Kyung-Yul Lee, Young D Kim, Yonsei Univ College of Medicine, Seoul, Korea, Republic of; Seung H Oh, CHA Univ Sch of Medicine, Seongnam, Korea, Republic of; Sung H Ahn, Chosun Univ College of Medicine, Gwangju, Korea, Republic of; Seo H Kim, Yonsei Univ Wonju College of Medicine, Wonju, Korea, Republic of; Sang W Han; Sanggye Paik Hosp, Seoul, Korea, Republic of Background and Purpose: As the prevalence of malignancy increased, there is increased chance of thrombolysis in ischemic stroke patient with malignancy. However, it is not well known about the hemorrhagic risk of thrombolysis in these patients. We evaluated the risk of symptomatic and asymptomatic hemorrhage after thrombolysis in acute ischemic stroke with current or remote malignancy. Methods: We retrospectively reviewed stroke database from five university hospitals and selected patient who received thrombolytic treatment with current or remote malignancy. Symptomatic and asymptomatic intracranial hemorrhage was evaluated by the 24 hour brain CT after thrombolysis and clinical symptom. Risk of hemorrhage according to the malignancy status and type of thrombolysis was also analyzed. Results: Of 843 patient who treated by thrombolytic therapy, 40 (4.7%) patients had a malignancy. Twenty patients had current malignancy and remaining had remote malignancy. Twenty-four patients received intravenous (IV) tPA only, 3 received IV tPA plus intra-arterial urokinase (IAU), 8 received IAU only, 2 received stent insertion, and 3 received IV tPA plus IAU plus stent insertion. Intracranial hemorrhage occurred in 19 (47.5%) patients (symptomatic 6, asymptomatic 13). Nine hemorrhages (symptomatic 3, asymptomatic 6) occurred in current malignancy and 10 hemorrhages (symptomatic 3, asymptomatic 7) occurred in remote malignancy. Intracranial hemorrhage occurred 37.5% in IV tPA, 62.5% in IAU, 66.7% in IV tPA plus IAU, 0% in stent insertion, and 100% in IV tPA plus IAU plus stent insertion. Conclusions: Intracranial hemorrhagic risk after thrombolysis is high in patient with malignancy when we consider reported risk of hemorrhage of the previous clinical trials. Status of malignancy does not affect the risk of intracranial hemorrhage. Further study is needed to verify this finding.

W P239 C-Arm CT Cerebral Blood Volume, MR Diffusion-Weighted Imaging, and Histology in a Canine Model of Acute Ischemic Stroke

Martijn J van der Bom, Univ Med Cntr Utrecht, Utrecht, Netherlands; Manik Mehra, Ronn P Walvick, Ajay K Wakhloo, Matthew J Gounis; Univ of Massachusetts, Worcester, MA Although MR perfusion-diffusion mismatch is well validated, emergency MR imaging is not widely available. Increasingly, CT based perfusion-cerebral blood volume mismatch is employed to triage patients. We hypothesize that C-arm CT cerebral blood volume (CBV) will correlate well with MR diffusion weighted imaging (DWI) and histopathology in an experimental model of acute ischemic stroke. Methods: Seven purpose-bred dogs were anesthetized as per the procedures approved by our IACUC. Autologous blood clot was prepared by mixing whole blood with thrombin and barium, and allowed to age for 24 hours. Following baseline MR imaging, a 5F catheter was placed in either internal carotid artery and a 1cm clot fragment was delivered. MRI was performed on a 3.0 Tesla system using an 8 channel receive only knee coil and serial diffusion and perfusion sequences were acquired. Within 10 minutes following the last diffusion scan (at 4 hours post stroke), the animals were transferred to the angiography suite, where non-contrast and contrast enhanced flat-panel cone-beam CT sequences were acquired. Animals were then euthanized and the coronal brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride (TTC). Apparent Diffusion Coefficient (ADC) maps were generated and imported into Matlab for image processing. ADC values below 0.53 *10 -3 mm 2 /s were identified and segmented. The CBV was determined by dividing the difference of the change in HU of the brain by that of the in-flowing blood between the contrast enhanced and non-contrast CT. A brain mask was generated from T2 weighted MRI and registered to the CT data for analysis. For all subjects mean CBV values and standard deviation (SD) were determined in a volume of interest (5ϫ5ϫ5 voxels, 0.12 ml) in healthy and ischemic tissue. CBV lesion volumes were calculated using various thresholds based on the SD measured in healthy brain and resulting volumes were compared to infarct volumes measured with histology by a linear regression analysis. Time-to-peak perfusion images were analyzed using commercial software. Results: Complete occlusion was successfully induced with an embolus lodged in the middle cerebral artery in all animals. The perfusion imaging revealed hypoperfused brain with heterogeneous severity due to the variability of collateral circulation. The final ADC lesion volume was 4,385Ϯ1,930mm 3 (meanϮ standard error of the mean) and the mean perfusion lesion was 6,483 Ϯ 1,515mm 3 . The TTC infarct volume was 4,408 Ϯ 1,805mm 3 . The mean CBV lesion with an optimized threshold of 2.5xSD was 3,567Ϯ1,010 mm 3 . As compared with the correlation between DWI and TTC (R 2 ϭ0.99), the correlation between the CBV lesion volume and TTC was not as strong (R 2 ϭ0.84). Conclusion: Our preliminary results indicate that there a fair correlation between histologically defined infarct and optimized C-arm CT CBV volumes.

Author Disclosures: M.J. van der Bom: None. M. Mehra: None. R.P. Walvick: None. A.K. Wakhloo: None. M.J. Gounis: None.

W P240 Variability in the Relationship Between Diffusion and Perfusion Volumes in Acute Stroke Patients

Richard Leigh, Argye E Hillis, Peter B Barker; Johns Hopkins Univerisity, Baltimore, MD Background: Multimodal MRI is often used to triage acute ischemic stroke (AIS) patients for intervention. Perfusion weighted imaging (PWI) is thought to identify deficits in blood flow. Reduced apparent diffusion coefficients (ADC) on diffusion weighted imaging (DWI) is thought to reflect densely ischemic tissue which in most cases of human stroke will progress to infarction. Areas of reduced cerebral blood volume (CBV) (derived from PWI) are sometimes also used as a surrogate for DWI while Time-to-peak (TTP) is a PWI measure sometimes used to identify non-infarcted at-risk tissue. Hypothesis: The tissue damage characterized by DWI is directly related to the CBV in a relationship that is similar between patients. Conversely TTP maps should be less likely to reflect ischemia. Methods: Twenty AIS patients with a diffusion-perfusion mismatch were retrospectively identified from our stroke database. Lesion volumes over a range of thresholds were calculated from DWI using ADC maps and from PWI using CBV maps and TTP maps. Varying the threshold which defines the lesion determines its volume. For a given volume, the ADC threshold was plotted against the corresponding PWI threshold. Results: Figure 1 shows the relationships between ADC value and CBV expressed

W P242 Effect of Transcranial Doppler Ultrasound on Combined rt-PA and Eptifibatide Thrombolysis in an in-vitro Human Clot Model

Wan-Tsu W Chang, Jason M Meunier, George J Shaw; Univ of Cincinnati, Cincinnati, OH Background: Recombinant tissue plasminogen activator (rt-PA) is the only FDA approved thrombolytic therapy for acute ischemic stroke. Interest in improving the lytic efficacy and reducing the bleeding complication of rt-PA thrombolysis has led to the study of adjunctive therapies such as GP IIb-IIIa inhibitors and ultrasound enhanced thrombolysis (UET). The ideal acoustic parameters for UET are unknown at this time. Previous studies looking at low frequency ultrasound ( ϳ kHz) showed increased initial lytic rates with ultrasound exposure. However, while ultrasound increased the overall lytic efficacy of single agent thrombolytic therapy, it did not increase the efficacy of combined rt-PA and eptifibatide thrombolysis. Objective: We determined the effects of high frequency 2 MHz transcranial Doppler ultrasound (TCD) on the thrombolytic efficacy of combined rt-PA and eptifibatide thrombolysis in an in-vitro human clot model. Methods: Human whole blood clots were made from blood obtained from volunteers, after appropriate institutional approval. Clots were incubated at 37°C for 3 hours and aged for 3 days at 4°C to maximize lytic resistance. Sample clots were exposed to human fresh-frozen plasma (hFFP) alone (control), and rt-PA and eptifibatide (rt-PAϩEpf) in hFFP at a concentration of 0.5 and 0.63 ı `g/ml respectively. Exposures were for 30 minutes at 37°with (ϩUS) and without ultrasound (-US) with a 2 MHz TCD. Clot width was measured using a microscopic imaging technique and mean percent fractional clot loss (FCL) at 30 minutes was used to determine thrombolytic efficacy. Data were analyzed using Matlab (Version 6.5R13, Natick, MA). Results: Each of 4 treatment groups had a minimum of 8 clots (range: 8-181) from 3 different donors (range: 3-23), for a total of 218 clots. In control groups, FCL was 14.7 Ϯ 3.7% (mean Ϯ standard deviation; -US) and 12.5 Ϯ 3.4% (ϩUS). FCLs for the rt-PAϩEpf groups were 66.6 Ϯ 21.2% (-US) and 59.9 Ϯ 18.0% (ϩUS) (Figure 1). Conclusion: Unlike low frequency ultrasound enhanced single agent thrombolytic therapy, the use of high frequency 2 MHz transcranial Doppler does not affect thrombolytic efficacy of combination therapy with rt-PA and eptifibatide in an in-vitro human clot model.

Background: Computed tomography (CT) is the current gold standard in evaluation of stroke patients for acute thrombolysis. The relative mismatch between regional cerebral perfusion and blood volume on computed tomography perfusion (CT-P) scan in acute ischemic stroke patients has been used to identify presence of salvageable tissue. However, insecurity and conflicting data exist over the ability of clinicians to correctly recognize and interpret these changes. Objective: To evaluate the agreement and variability in interpreting CT and CT-P imaging between stroke specialists in stroke patients qualifying for endovascular treatment. Methods: All endovascular treated acute ischemic stroke patients were identified through a prospective database maintained from two comprehensive stroke centers. 25 consecutively treated patients were used for this analysis. Their emergency department presentation, initial CT images, and CT-P data were independently read and classified by 5 board eligible/certified vascular neurologists with additional subspecialty training to decide whether or not to select for endovascular treatment. The CT images and CT-P images were evaluated separately and used as the sole decision making criteria, two weeks apart from each other (memory wash-out period). For each set of imaging, inter-rater and intra-rater reliability scores were obtained using Coneh's Kappa statistic to assess the proportion of agreement beyond chance. Results: Kappa-values for the CT images was 0.43 (ranged from 0.14, 0.8) (moderate agreement), and for the CTP images was 0.29 (ranged from 0.07, 0.67) (fair agreement) among the 5 reviewers. There was substantial variability within the group and between images. Observed agreement was found to be 75% with CT images and 59% with CTP images (with no adjustment for chance). Kappa-Values for intra-rater reliability was -0.14 (ranged from -0.27, 0.27) (poor agreement). Conclusion: There is considerable lack of agreement, even among stroke specialists, in recognizing and quantifying early CT changes and CTP identified salvageable tissue. This mandates a careful evaluation of CT and CT-P methods of recognizing and quantifying early ischemic changes prior to widespread adoption as an exclusion or inclusion criteria.

W P244 Head-to-Head Comparison of Combination tPA Thrombolysis in an in-vitro Human Clot Model

Jason M Meunier, Christy K Holland, Tyrone M Porter, Christopher J Lindsell, George J Shaw; The Univ of Cincinnati, Cincinnati, OH Introduction: Incidence of hemorrhage linked to treatment of ischemic stroke with tissue plasminogen activator (tPA) has led to interest in combination therapies such as ultrasound (US) enhanced thrombolysis (UET) or plasminogen (Plg), with the goal of decreasing the administered volume of tPA. High-frequency US (ϳMHz) such as 2 MHz transcranial Doppler (TCD) has demonstrated increased recanalization in-situ, but long-term benefits may not be significant. Low-frequency US (ϳkHz) has demonstrated higher lysis capabilities but has been associated with a high incidence of hemorrhage. In-vitro studies using plasminogen have shown enhancement of lysis while minimizing bleed-outs. This study compared the enhancement of tPA-induced lysis using combination therapy, with US at low or high frequency, or with Plg, in an in-vitro clot model. Methods: Blood was drawn from 30 subjects after local Institutional Review Board approval. Clots were made in 20-L pipettes and placed in a water tank for microscopic visualization during treatment. Sample clots were exposed to tPA in human fresh-frozen plasma (hFFP) at concentrations of 0, 0.5, 1.00, and 3.15 ı `g/ml. Clots were exposed to tPA alone, tPA and Plg (ϩPlg), tPA and 120 kHz US (ϩUS), or tPA and 2 MHz TCD (ϩTCD) for 30 minutes. The extent of thrombolysis was determined by assessing clot width as a function of time, using a time-lapse microscopic imaging technique; the fractional clot loss (FCL) at 30 minutes was used to determine thrombolytic efficacy. Results: Each of 16 treatment groups had a minimum of 8 clots (range: 8-158) from 3 different donors (range: 3-24). There was no enhancement of lysis for any combination therapy with a tPA concentration of 0 ı `g/ml; lysis for all groups increased when tPA (0.50 ı `g/ml) is added. As tPA concentration increased from 0.50 to 3.15 ı `g/ml, lysis increased for the ϩUS and ϩPlg groups (increasing the FCL from 50.3% to 70.2%, ϩUS; 65.2% to 82.5%, ϩPlg) but remained constant for the ϩTCD group (57.6% to 54.6%). Thrombolytic efficacy was similar for ϩUS and ϩPlg groups at all concentrations. Conclusions: Improvement of lytic efficacy in combination therapy is dependent on tPA concentration. Background: General anesthesia (GA) use is correlated with worse clinical outcomes and increased mortality in retrospective studies of patients undergoing endovascular therapy for acute ischemic stroke. We sought to quantify sedation practice patterns and better characterize the decision to use GA versus conscious sedation (CS) among sites in the ongoing Interventional Management of Stroke (IMS) III trial. Methods: The IMS III trial is a randomized study of IV rtPA versus combined IV/intra-arterial (IA) therapy for ischemic strokes (NIHSSϾ/ϭ8). Specific sedation practices are not mandated. To capture sedation practice patterns, we surveyed stroke (neurology/emergency medicine) and neurointerventional local principal investigators at the 55 IMS III sites in the United States, Canada, and Australia using a multiple-choice questionnaire. Questions pertained to use of GA, CS, and sedation logistics. For the summary statistics, data are provided based on site except when local clinical and neurointerventional PIs gave discordant answers, in which case both answers are included. Results: Respondents included neurointerventionalists (53.7%), stroke clinicians (39.0%), and emergency physicians (7.3%). Among 33 sites (60% response rate) and 41 surveys, 40.5% electively sedate (GA or CS) most patients prior to IA treatment, 8.1% sedate only cases planned for mechanical thrombectomy, 37.8% electively sedate cases based on individual clinical factors, and 13.5% do not electively sedate patients. Among those who perform elective sedation for any reason, approximately half start with GA and half start with CS, and the majority sedate patients prior to performing the diagnostic angiogram. Among those who electively sedate with GA first, 46.7% extubate immediately after the procedure while 26.7% typically extubate between 12-24 hours. Elective GA use is driven primarily by personal experience with unsedated patients (73.3%), but institutional standards guide the decision for some (20.0%). Although 52.9% reported that GA contributed to Ͻ15-minute delay in initiating IA therapy, 29.4% reported a 30-45 minute delay. Among those who use GA routinely, 28.6% reported not treating brief decreases in blood pressure during GA induction. Among those that electively sedate and use CS first, most noted that switching to GA due to respiratory depression (84.2%) or inadequate pain control (68.4%) was rarely or never needed. Among those that do not electively sedate patients by any method, 71.4% use CS as their initial method when it becomes clinically necessary. Conclusions: Sedation practices are highly variable among clinical sites in the IMS III trial. Half of sites electively sedate most patients, and half of those who sedate use GA as the standard approach. Whether the risks of GA (intubation, induction-related hypotension, and treatment delay) are justified requires further study.

Author Disclosures: J.A. Sohn: None. J.

W P247 Manual Aspiration Thrombectomy, A Novel Approach To Endovascular Therapy For Acute Stroke

Oana V Spataru, Tudor Jovin, Lawrence Wechsler, Michael Horowitz, Amer Malik, Lin Ridwan, Mouhammad Jumaa, Zaidi Syed, UPMC, Pittsburgh, PA; Aitziber Aleu; Univ Hosp Germans Trias I Pujol, Barcelona, Spain Introduction: Manual aspiration thrombectomy (MAT) is an endovascular recanalization modality that is frequently used in acute coronary artery syndromes. In intracranial vessels however, there is little experience to date with this method . We aimed to evaluate recanalization rates, clinical outcomes and safety with this method in a consecutive case series treated at our center. Methods: Retrospective review of a prospectively acquired acute endovascular stroke database comprising 560 patients to date, from which patients treated with MAT were identified.MAT was carried out with the Distal Access Catheter (DAC) 0.54 and 0.43 French and Penumbra Reperfusion Catheter 0.52 and 0.41 French placved in the thrombus and attached to a syringe. Collected data include baseline demographics, risk factors, clinical and imaging characteristics. Successfully recanalization was defined as TIMI 2 and 3, Outcome (available in all patients analyzed) was considered favorable if mRS at 90 days was Յ 2. Results: Between 11/2008 (date of first use of MAT) and 07/ 2010, 186 patients were treated. Of those, 126 patients underwent MAT and were included in the analysis. Median age: 65, median NIHSS: 16, occlusion location M1 MCA 67-53 %, ICA terminus 36-28%, M2 MCA 4-3.2%, vertebrobasilar 19-15%, tandem extracranial carotid-intracranial carotid occlusion 23-18.5%. Median ASPECTS score 8. tPA administered in 44-35% (iv) and 50-40.6% (ia). MERCI device used in 115-92%, Penumbra device used in 51-41%.Median time from stroke onset to procedure start -390 minutes. Median treatment duration-118 minutes, TIMI 2 and 3 recanalization was achieved in 114/90.5% of patients, with TIMI 3 recanalization noted in 31/24.6%, Parenchymal hematoma was noted in 16-15.5% of patients. Favorable outcome was achieved in 53-42.% of patients. When compared to all patients in our data base (nϭ560), MAT was associated with higher recanalization rates then patients treated without MAT, 90% vs 71%, p tivariate logistic regression analyses, admission NIHSS (OR 0.85, 95%CI 0.75-0.97, pϭ0.018), age (OR 0.88, 95% CI 0.82-0.94 PϽ 0.0001), intubation (OR 0.12, 95% CI 0.02-0.63, Pϭ0.012) and baseline ASPECT scores (OR 2.45, 95% CI 1.36-4.41, Pϭ 0.003), but not TIMI 2-3 recanalization were found to be significant predictors of outcome. The latter was attributed to the high overall recanalization rate observed. Conclusion: MAT is a useful addition to the armamentarium of endovascular treatment modalities for acute stroke. When used as part of multimodal recanalization strategies it appears to enhance the recanalization rate and possibly to improve outcome. In addition, when used in substitution to other treatment modalites it may significantly reduce procedural cost. Elad I Levy, Univ at Buffalo, State Univ of New York, Buffalo, NY; Maryam Rahman, Univ of Florida, Gainesville, FL; Alexander A Khalessi, Patrick T Beyer, Sabareesh K Natarajan, Mary L Hartney, Univ at Buffalo, State Univ of New York, Buffalo, NY; David J Fiorella, Stony Brook Univ Med Cntr, Stony Brook, NY; L. N Hopkins, Adnan H Siddiqui, Univ at Buffalo, State Univ of New York, Buffalo, NY; J Mocco; Univ of Florida, Gainesville, FL Background and Purpose: Although early data demonstrate encouraging angiographic results following intracranial stent deployment for acute ischemic stroke, longer-term follow-up is necessary to evaluate clinical outcomes, as well as durability of angiographic results. We report 6-month clinical and radiologic follow-up data of the 20 patients prospectively enrolled in the Stent-Assisted Recanalization in acute Ischemic Stroke (SARIS) trial. Methods: Twenty patients were prospectively enrolled to receive self-expanding intra-arterial stents as first-line therapy for acute ischemic stroke treatment. Patients were scheduled for follow-up 6-months after treatment for clinical evaluation (modified Rankin Scale [mRS] score obtained by a trained certified research nurse/nurse practitioner) and repeat cerebral angiography. Angiographic interpretation was performed by an independent adjudicator. Results: At 6 months, mRS score was Յ3 in 60% of patients (nϭ12) and was Յ2 in 55% of patients (nϭ11). Mortality at 6-month follow-up was 35% (nϭ7). Follow-up angiography was performed for 85% (11 of 13) of surviving patients. All patients undergoing angiographic follow-up demonstrated Thrombolysis in Myocardial Infarction 3 flow on digital subtraction angiography or stent patency on computed tomographic angiography. None of the patients demonstrated evidence of in-stent stenosis (Ն50% vessel narrowing). Conclusion: The midterm angiographic and clinical results following intracranial stent deployment for acute ischemic stroke are encouraging. Further study of primary stent-for-stroke treatment is warranted.

W P249 Solitaire Device for Immediate Flow Restoration and Revascularization in Acute Stroke. Geneva experience

Vitor M Pereira, Ana Paula Narata, Hasan Yilmaz, Ana Marcos Gonzalez, Isabelle Momjian-Mayor, Roman Sztajzel, Karl-olof Lovblad; Univ Hosp of Geneva, Geneva, Switzerland Introduction: Acute revascularization improves outcomes after large vessel acute ischemic strokes (AIS). We now describe the angiographic and clinical results of the use of a novel mechanical clot retriever (Solitaire device). Methods: Patients presenting with AIS were treated at the Geneva University Hospital. We work under a bridging stroke protocol where patients arriving until 4h30min start IV thrombolysis and, at 30 minutes, if no clinical improvement or transcranial Doppler initial recanalization (TIBI 3), a bridge to IA therapy is performed. Patients with any contraindication to IV rtPA or arriving later than 4h30min are treated direct with IA therapy. Results: From March to December 2009, twenty-five cases of acute stroke due to occlusion of the intracranial internal carotid (nϭ5) or middle cerebral (nϭ20) arteries were treated using the Solitaire AB or FR device as the first line treatment modality. Fifteen patients were men (60%). The mean age was 66,3 years (range, 20-85) and the mean baseline NIHSS score was 18,7 (range, 8-30). Twelve (48%) patients had IV treatment before endovascular procedure and thirteen (52%) patients went directly to intra-arterial mechanical therapy. The mean time from the onset of symptoms to treatment was 250 minutes. The mean time from first angiogram to reperfusion (TICI Ն2) was 42 minutes. A final satisfactory angiographic result (TICI 2b and 3) was obtained in all patients. In twenty-two patients, the device was used exclusively with a mean of 2,3 attempts to get final result. The overall hemorrhagic complication rate was 20% but only 12% symptomatic. One subarachnoid hemorrhage with no clinical significance was also observed. One patient developed malignant edema in spite of an angiographic result of TICI 2b. Good outcomes at 90 days (mRS Յ2) were achieved in 16/25 (64%) patients. The group with previous IV treatment had 66% favorable outcome (8/12) and group direct mechanical IA had 61% favorable outcome (8/13) there were no statistical difference between these two groups. The best predictor of a favorable outcome at 3 months (mRS 0-2) was time to recanalization. Logistic regression model and comparison with age, NIH at admission, final TICI and time to recanalization (OR 0.94 95% CI 0.9 to 0.99) demonstrated a statistical significance (pϾ0.036). Conclusion: Mechanical thrombectomy with the Solitaire device appears to be safe and effective and may result in faster recanalization.

Author Disclosures: V.M. Pereira: Consultant/Advisory Board; Modest; ev3. A. Narata: None. H. Yilmaz: None. A. Marcos Gonzalez: None. I. Momjian-Mayor: None. R. Sztajzel: None. K. Lovblad: None.

Background & Purpose: Prior safety analyses focused on symptomatic intracerebral hemorrhage (sICH) rates comparing intravenous (IV) tPA, primary intra-arterial (IA), and IV-IA bridging procedures while data are generally lacking comparing medical complications of these treatment strategies. Subjects&Methods: Consecutive patients with acute ischemic stroke and a proximal intracranial arterial occlusion undergoing IV tPA, primary IA or IV-IA bridging treatment at a tertiary care center were analyzed. Neurological deficits were scored with the NIH Stroke Scale. Identified medical complications were classified as serious adverse events (SAEs) and adverse events (AEs). sICH was defined as parenchymal ICH (PH1 and 2 types) that was temporarily and causatively associated with an NIHSS increase of 4ϩ points. Outcome variables also included mortality, length of hospital stay (LOS), and modified Rankin scores at 3 months. Results: A total of 213 acute stroke patients received reperfusion treatment for a proximal intracranial occlusion (104 IV tPA, 73 primary IA, and 36 IV-IA). Apart from symptom onset-to-treatment time differences and median pre-treatment NIHSS scores (12, 15, 17 respectively, pϭ0.01), all groups were similar with respect to average age (63, 60, 60 yrs, pϭ0.28). Captured in-hospital SAEs included pulmonary embolism, MI, cardiac arrest, respiratory failure, sepsis, and sICH (Figure). AEs included seizures, pneumonia, DVT, pulmonary edema, UTI, and asymptomatic ICH (Figure). After adjustment for baseline stroke severity, age, and sICH, SAEs decreased the chance of recovery to mRS 0-2 at 3 month with IA or IV-IA (OR 4.0, 95%CI 1.2-13.2, pϭ0.025) but not with IV (OR 2.7, 95%CI 0.5-13, pϭ0.24). SAEs increased the risk of poor outcomes (mRS 4-6 at 3 month) after IA or IV-IA (OR 3.5, 95%CI 1.2-10.2, pϭ0.02), but not with IV alone (OR 3.1, 95%CI 0.8-12, pϭ0.11). Despite SAEs, mRS 0-2 at 3 month was achieved by 35% IV, 34% IA and 44% IV-IA patients, pϭ0.52. Conclusions: SAEs frequently occur frequently after reperfusion (in 1/5 patients with IV, 1/3 with primary IA and 1/2 with IV-IA). These events, independent of sICH, lead to a 3.5-fold increased risk of poor outcomes after IA or IV-IA procedures. More vigilant medical management may be preventative against SAEs, thus resulting in more patients achieving good functional outcomes after reperfusion treatment.

W P252 M5, a Thrombolytic Which Induced Significant Functional Recovery and Less ICH than tPA in Rat Stroke Models

Simone Tomasi, Neuroscience Institute of Turin, Univ of Turin, Turin, Italy; Paolo Sarmientos, Primm s.r.l., Milan, Italy; Giada Giorda, Alessandro Vercelli, Neuroscience Institute of Turin, Univ of Turin, Turin, Italy; Victor Gurewich; Vascular Rsch Laboratory, BI Deaconess Med Cntr, Harvard Med Sch, Cambridge, MA M5 is a mutant of the fibrin-specific proenzyme, single-chain urokinase-type plasminogen activator. M5 has the unusual property that its non-specific two-chain enzymatic form (tcM5) is inhibited rapidly by plasma C1-inhibitor (C1I). As a result, non-specific plasminogen activation, responsible for the hemorrhagic complications of plasminogen activators, can be prevented by C1I. Exceptionally, the rat endogenous C1I does not significantly inhibit tcM5, making rats unusually sensitive both to the side effects of M5 and to the salutary effects of added C1I. Two stroke models were used in a proof of concept study: (I) irreversible ischemia by ligation of the ICA and cauterization of the MCA in order to evaluate ICH. Thrombolytic infusions (30 min) were administered 4h later ; (II) reversible ischemia by thromboembolic occlusion of the MCA and infusions 2h later. Rats were given either tPA (10mg/Kg) or M5 (15mg/Kg) ϩ/an adjunctive bolus of C1I or saline ϩ/-C1I. In model I, ICH mortality was high with both tPA (57%) and M5 (75%) but was reduced significantly by C1I to 25% and 17% respectively. In model II, M5ϩC1I induced the lowest infarct volume and caused the least non-lethal ICH (17%) and was the only group among the six to achieve significant reduction in functional neuroscore between pretreatment (3.30.2) and 24h later (2.00.4). The infarct volumes of tPA alone and M5ϩC1 were comparable (9221 and 8815 mm 3 respectively), indicating a comparable fibrinolytic effect. However, tPA alone caused much more ICH and was accompanied by the greatest edema volume (64mm 3 or 70% of the infarct volume), consistent with tPA's known disruption of the blood brain barrier. Adjunctive C1I increased the tPA infarct volume to 14215 mm 3 , making it no longer significantly less than controls (21328 and 22713). However, C1I also reduced the tPA edema volume significantly to 24% of infarct volume. Activation of the complement pathway by tPA has been previously described by others, which may explain this C1I effect. In conclusion, the combination M5ϩC1I was as effective as tPA alone and more effective than tPAϩC1I, causing significantly less ICH, edema volume, and the most functional improvement. These in vivo findings with M5 validate the in vitro data with C1I and provide a promising development for a new, effective and safer treatment of ischemic stroke.

Author Disclosures: S. Tomasi: None. P. Sarmientos: None. G. Giorda: None. A. Vercelli: None. V. Gurewich: None.

W P253 Comparison of Acute Medical Treatments in Ischemic Stroke Patients Aged 80 Years or Older

Haralabos Zacharatos, Ameer E Hassan, Gabriela Vazquez, Haitham H Hussein, Gustavo J Rodriguez, M. Fareed K Suri, Kamakshi Lakshminarayan, Mustapha A Ezzeddine, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, Minnesota, Minneapolis, MN Objectives: To compare the clinical outcomes of acute ischemic stroke patients aged Ն80 years treated with either intravenous recombinant tissue plasminogen activator (IV rt-PA), endovascular intervention with or without IV rt-PA, and non-thrombolytic medical treatment. Methods: A retrospective, non-randomized, observational study of patients, admitted within 9 hours of symptom onset, at three academic, University affiliated hospitals. The main outcome measures were neurological improvement, defined by improvement in National Institute of Health Stroke scale (NIHSS) score at 7 days or discharge of Ͼϭ4 or achieving a score of 0, symptomatic and asymptomatic intracerebral hemorrhage, favorable outcome (discharge modified Rankin score 0-2), and in-hospital mortality. Results: A total of 44 patients received IV rt-PA, 46 received endovascular intervention with or without IV rt-PA, and 66 received non-thrombolytic medical treatment. IV rt-PA treated patients had a significantly clinically higher chance of favorable outcome [OR (odds ratio) 5.6; 95% CI (confidence interval) (1.8-17.5)], when compared with non-thrombolytic medical treatment. A significantly higher rate of neurological improvement was observed among the IV rt-PA [OR 7.2; 95% CI (2.7-19.5)] and endovascularly treated patients [OR 5.8; 95% CI (2-16.8)] when compared with non-thrombolytic medical treatment. Conclusions: A prominently higher rate of neurological improvement and favorable clinical outcome was observed among acute ischemic stroke patients Ն80 years treated with IV rt-PA or endovascular intervention when compared with non-thrombolytic medical treatment; supporting the use of acute thrombolytic therapies in this patient population when contraindications are not present.

Author Disclosures: H. Zacharatos: None. A.E. Hassan: None. G. Vazquez: None. H.H. Hussein: None. G.J. Rodriguez: None. M.K. Suri: None. K. Lakshminarayan: None. M.A. Ezzeddine: None. A.I. Qureshi: None.

W P254 In Vivo Thrombolytic Efficacy of Tissue Plasminogen Activator-Loaded Echogenic Liposomes

Melvin E Klegerman, Melanie R Moody, Hyunggun Kim, Beverly Smulevitz, Shao-Ling Huang, Univ of Texas Health Science Cntr, Houston, TX; Christy K Holland, Univ of Cincinnati, Cincinnati, OH; David D McPherson, Susan T Laing; Univ of Texas Health Science Cntr, Houston, TX Background: Clinical studies have shown that pulsed Doppler ultrasound (US) can enhance the thrombolytic efficacy of tissue plasminogen activator (tPA) administered to acute ischemic stroke patients. We previously demonstrated that tPA-loaded echogenic liposomes (ELIP) enhanced thrombolysis in a rabbit aorta thrombus model in the presence of color Doppler US. We also demonstrated that tPA-loaded ELIP retain their acoustic reflectivity and tPA affinity for fibrin. This study aimed to compare tPA-loaded ELIP to other US-enhanced thrombolytic protocols. Methods: Clots were induced in the abdominal aortas of male New Zealand white rabbits (2-3 kg) using thrombin and a sclerosing agent (sodium ricinoleate) after aortic denudation with a balloon catheter. Treatment (200 g of tPA alone, tPA mixed with 50 l Definity, or tPA-loaded ELIP) was given proximal to the clot through a catheter introduced into the abdominal aorta from the carotid artery. The clot within the aorta was visualized and color Doppler US (6 MHz) was applied externally over the clot for 30 minutes at low MI (0.2) to induce acoustically-driven diffusion or for 2 minutes at high MI (0.4) to cause fragmentation of microbubbles and ELIP. Degree of recanalization was determined by Doppler flow measurements distal to the clots. Results: All treatments showed thrombolysis, measured as % recanalization at 2-minute intervals, maximum % recanalization in a 30 minute period (Fig. 1), and rate of total recanalization within 30 minutes. However, tPA-loaded ELIP appeared to be the most efficacious regimen. Enhancement of the thrombolytic effect by the addition of US at these settings was not observed for any of the treatments, but we confirmed that high MI color Doppler US increased tPA exposure at the liposomal surface. Conclusions: We have demonstrated that tPA-loaded ELIP thrombolytic efficacy is comparable to other previously described effective treatment protocols, while offering the advantage of US monitoring. Future studies will focus on optimization of US-induced thrombolytic efficacy. A synthetic PAI-1-derived 18-mer peptide, consisting of an amino acid structure of Ac-MAPEEIIMDRPFLYVVR-amide, was shown to be a modulator of tPA activity in two rat stroke models. In one model, embolic stroke was induced by intra-carotid injection of micro-clots to rats, while in the other model, mechanical stroke was induced by transient occlusion of the middle cerebral artery (tMCAO). tPA (6 mg/kg) was administered IV with or without THR-18 (1 mg/kg) at 2 or 4h post occlusion. In the embolic stroke model, addition of THR-18 to tPA led to an improvement in vessel patency post reperfusion. In both the embolic and mechanical models, the combination of tPA and THR-18 resulted in reduced mortality and a lower frequency (10% versus 30-45%) of tPA-induced intracranial hemorrhage, as well as dramatic reductions of infarct size and brain edema as compared to the control and tPA-treated rats. THR-18 alone was without effect. Comprehensive toxicological studies were performed in rats and dogs, utilizing doses of 5 to 50 mg/kg of THR-18. At doses of 15 mg/kg or higher, some insoluble test material was deposited in the lungs of rats, but not in the dogs. In dogs, a significant decrease in blood pressure, which persisted for 30 -60 min, was seen following administration of 10 and 30 mg/kg of THR-18, but not following the 5 mg/kg dose. No other drug-related adverse effects were found. A First-In-Human Phase 1 dose-escalation study was conducted in healthy volunteers. THR-18 was administered intravenously at doses of 0.25 -1 mg/kg during 15min. No adverse effects were found noted following administration of the 0.25 and 0.5 mg/kg doses. At higher doses (0.75 and 1 mg/kg), several instances of orthostatic hypotension were noted during the first 1.5 hours post drug administration. No clinically significant changes in blood pressure were noted at any dose in the supine position. No serious or severe adverse events were reported throughout the study. Following these encouraging phase I safety data , we plan to further evaluate THR-18 in stroke patients receiving tPA in a multinational Phase IIa clinical study. This study is expected to commence in 2011.

W P257 Intra-arterial Thrombolysis Initiated Greater than 24 Hours after Stroke Onset

Brian Jankowitz, Ridwan Lin, Syed F Zaidi, Mouhammad A Jumma, Maxim Hammer, Lawrence R Wechsler, Michael Horowitz, Tudor Jovin; UNIVERSITY OF PITTSBURGH, Pittsburgh, PA There is growing evidence to support the hypothesis that vessel recanalization is the strongest determinant of outcome in patients with acute ischemic stroke due to large vessel occlusion.

Current selection criteria for recanalization therapy utilizes rigid time windows. However the evolution from ischemia to infarction occurs at variable rates. We assessed the hypothesis that it is safe to treat patients by endovascular means beyond the 24 hour time window in highly selected patients based on the presence of a small ischemic core and large ischemic penumbra (substantial mismatch-SM). Methods: Retrospective review of a prospectively acquired clinical database of all patients treated at the University of Pittsburgh Medical Center between 2004 and 2009. Patients were included if they presented with a symptomatic intracranial large vessel occlusion that was treated by intra-arterial thrombolysis greater than 24 hours after stroke onset. Wake-up strokes were included if above criteria were met. Presence of SM was determined by MRI or CT perfusion. Results: We identified 34 patients out of a total of 385 patients (8.8%). Mean and median times from symptoms onset to groin puncture were 63 and 48 hours respectively. Median age: 67. Median presenting NIHSS was 13. Distribution of vessel occlusion: vertebrobasilar 16/47%, internal carotid terminus 5/14%, M1 MCA 9/26.47%, M2 MCA 4/12.12% Recanalization rates: 24/70.5% TIMI score of 2 or 3, and 10/29.4% TIMI 3. PH1/PH2 parenchymal hematoma occurred in 3% and HT1/HT2 hemorrhagic transformation occurred in 21%. Follow-up was available in all patients. Mortality rate was 9/27.7%. A good outcome (mRS of 0,1,2) was achieved in 16/47.6% of patients. Conclusions: Our results indicate that intra-arterial therapy initiated beyond 24 hours after ictus can be performed with a safety profile that is no different compared to treatment within conventional time windows. Due to lack of a control group clinical efficacy of this approach cannot be evaluated. Prospective randomized controlled are needed to adequately answer this question.

Author Disclosures: B. Jankowitz: None. R. Lin: None. S.F. Zaidi: None. M.A. Jumma: None. M. Hammer: None. L.R. Wechsler: None. M. Horowitz: None. T. Jovin: None.

W P258 General Anesthesia during Mechanical Thrombectomy Negatively Impacts Functional Independence and Mortality in Only Less Severe Ischemic Stroke

Christine Wong, Nancy Hills, UCSF, San Francisco, CA; Gary Walker, Concentric Med, Inc, Mountain View, CA; Wade Smith; UCSF, San Francisco, CA Background: Use of general anesthesia (GA) during mechanical thrombectomy for acute ischemic stroke has been correlated with worsened outcomes. In this prospective, multicenter registry, we evaluated use of GA during thrombectomy as a predictor of 90-day morbidity and mortality and examined whether this effect was dependent on stroke severity at onset. Methods: Prospectively collected data including demographics, baseline clinical variables, and procedural characteristics were obtained from the Merci Registry. Univariate and multivariable analyses were performed to assess the relationship between these variables and primary outcome measures of morbidity (mRS 0-2) and mortality at 90 days. Mixed logistic models with facility as random effect were used to adjust for variance between study centers. Using ROC curves to determine the appropriate cutoffs for NIHSS, regression analyses were again performed for dichotomized strata of NIHSS to elucidate a differential effect of GA depending on stroke severity. Results: Data for 761 patients from 34 centers were included in the analyses. Median age was 69.4 years, and median initial NIHSS was 18. Sixty-three percent of all patients were intubated and placed under GA for thrombectomy with wide variability in the proportion of intubated patients by center (5.9-100%). GA status, recanalization, age, history of congestive heart failure, procedure duration, and baseline NIHSS were all independent determinants of morbidity and mortality in univariate analyses. In addition, prior TIA and IA thrombolysis were determinants of morbidity, while diabetes was predictive of mortality in univariate analyses. In a multivariable model, GA remained significantly associated with lower likelihood of good outcome (OR 0.51; pϭ0.003) and higher risk of mortality (1.84; pϭ0.008). Use of GA in patients with more severe stroke (NIHSSϾϭ20) was not associated with good outcome (OR 0.73; pϭ0.43) or mortality (OR 1.38;pϭ0.27). However, for those with less severe stroke (NIHSSϽ20), the effect of GA remained independently associated with poor outcome (OR 0.40 for mRS 0-2; PϽ0.001) and mortality (OR 2.40; pϭ0.005). Conclusion: Use of GA during mechanical thrombectomy for ischemic stroke correlates with mortality and worsened functional outcomes in those with less severe stroke (NIHSSϽ20) but not in those with more severe stroke (NIHSSϾϭ20). Treating physicians should consider using alternative sedation modalities for patients with less severe stroke, but need not avoid tracheal intubation in patients with more severe stroke.

Author Disclosures: C. Wong: None. N. Hills: None. G. Walker: Employment; Significant; Clinical Research Senior Director. W. Smith: Ownership Interest; Significant; Stock Ownership. Consultant/Advisory Board; Significant; Consultant.

W P259 Intra-Arterial Thrombolysis Demonstrates Better Clinical Outcome than Intra-Arterial Thrombectomy

Nicole R Gonzales, Andrew D Barreto, Nusrat Harun, Tzu-Ching Wu, Preethi Sahota, Amrou Sarraj, Ramy El Khoury, William Hicks, Navdeep S Sangha, Vivek Misra, George A Lopez, Sean I Savitz, James C Grotta; Univ of Texas Med Sch, Houston, TX Background: A recent meta-analysis suggested that intra-arterial (IA) thrombolysis substantially improves clinical outcomes in acute ischemic stroke. Due to lack of concurrent controls in study design, similar data is not available for IA thrombectomy. We hypothesized that IA thrombolysis would demonstrate improved clinical outcomes compared with IA thrombectomy. Methods: From our prospectively collected stroke registry, we identified all patients who underwent IA therapy from November 1996 to January 2010. Patients were divided into two treatment groups: IA thrombolysis only (Group A, with/without mechanical clot disruption with the guidewire) or IA thrombectomy (Group B, MERCI or PENUMBRA with/without thrombolysis). The primary outcome measure was good clinical outcome at discharge defined as modified Rankin Scale (mRS) 0-2. Secondary outcome measures included recanalization (TICI Ն2b), need for hemicraniectomy, symptomatic intracranial hemorrhage (sICH), and length of stay (LOS). Statistical analysis for treatment effect included chi square, fisher's exact and multivariate logistic regression. Results: A total of 257 patients underwent IA therapy (147 Group A, 110 Group B). The two groups were similar in age (63 yrs. vs. 61 yrs., pϭ0.26), gender (55% male vs. 50% male, pϭ0.45) and median NIHSS (17 vs. 19, pϭ0.17). Despite lower rates of recanalization in Group A (51.4% vs. 74.0%, pϭ0.0003), a higher proportion of patients in Group A had a good outcome (21.7% vs. 12.7%, pϭ0.07). There was no difference between groups in the occurrence of sICH (4.8% Group A vs. 7.3% Group B, pϭ0.43) or any other secondary outcome measure. Our multivariate model adjusted for baseline NIHSS, age, and recanalization demonstrated that patients in Group A were more likely to have a good outcome (OR 2.24, 95% CI 1.002-5.000, pϭ0.0496). Conclusions: In our population, IA thrombolysis was associated with better clinical outcomes despite lower recanalization rates when compared with IA thrombectomy. This analysis is limited by its retrospective nature, but suggests the possibility that a group of patients less likely to benefit may be driving the results or, more concerning, the possibility of harm (not related to sICH) with IA thrombectomy. Given the cost associated with thrombectomy and lack of data supporting its clinical efficacy, current and future randomized controlled trials evaluating IA thrombectomy are imperative to clarify these issues since IA thrombectomy is quickly becoming 'usual care' for acute ischemic stroke. 1 and2)

Conclusions: There is a minimal rate of conscious sedation failure among patients undergoing neuro-endovascular procedures with minimal rates of adverse outcomes. Such observations support broader use of local anesthesia in neuro-endovascular practice.

Introduction:

The physical characteristics of the occlusive thrombus in acute stroke may have therapeutic implications. Specifically, clot with high fibrin content may be more adhesive and difficult to retrieve by endovascular techniques. Ideally, the interventional strategy should be based on information about the physical characteristics of the clot that could be ascertained during non-invasive imaging before treatment. Thrombus with a high erythrocyte content is hyperdense on CT, whereas fibrin-rich clot may be isodense. We hypothesized that the physical clot characteristics that determine CT density may also determine likelihood of retrieval with the Merci device. Methods: We reviewed all acute stroke cases treated with the Merci device at UCLA between 2006 and 2007 that underwent pretreatment non-contrast CT. Each CT was assessed for the presence or absence of the hyperdense vessel sign (HVS) by a neuroradiologist (PV) who was blinded to treatment outcome. Angiographic outcome after treatment with the Merci device was assessed using the Thrombolysis in Cerebral Infarction scale (TICI) by a neuro-interventionalist (MTF) who was blinded to CT findings. Results: We identified 22 patients that had a non-contrast CT before attempted Merci thrombectomy (mean age 69; median NIHSS 18), 20 of whom had MCA occlusion, 5 also involved the ICA, and 2 presented with basilar occlusion. Fifteen patients exhibited the HVS, of whom 13 had successful revascularization (TICI 2a or better) after Merci thrombectomy. In contrast, 7 patients did not exhibit the HVS, of whom only 1 experienced successful revascularization with the Merci device. This difference was highly significant (pϭ0.0023; Fisher's exact test). Conclusion: The absence of the HVS on non-contrast CT in acute ischemic stroke was strongly predictive of failure of revascularization using the Merci device. In contrast to the erythrocyte-rich thrombi that are associated with the HVS, the occlusive thrombus in these cases may have a higher proportion of platelets and fibrin, which may create a more resistant clot. The absence of HVS on pre-treatment CT may serve as an indicator of adhesive clot which may require a more aggressive or alternative therapeutic approach.

Author Disclosures: M.T. Froehler: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. S. Tateshima: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. R. Jahan: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. G. Duckwiler: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. Ownership Interest; Modest; minor stockholder in Concentric Medical. Consultant/Advisory Board; Modest; scientfic advisor for Concentric Medical. F. Vinuela: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. L.K. Ali: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. S. Starkman: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. D. Liebeskind: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. J. Saver: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke. P. Villablanca: Employment; Modest; Employee of the University of California, which holds patent rights in retrieval devices for stroke.

W P262 Gasometric Analysis Of Blood Samples Directly Obtained Beyond Arterial Mca Occlusion During Endovascular Procedures Predicts Response To Revascularization

Alan Flores, Hosp Vall D' Hebron, Barcelona, Spain; Joao Sargento-Freitas, Hosp Universitario Coimbra, Coimbra, Portugal; Marta Rubiera, Jorge Pagola, David Rodriguez-Luna, Socorro Pin ˜eiro, Olga Maisterra, Joan Montaner, Jose Alvarez-Sabin, Carlos Molina, Marc Ribo; Hosp Vall D' Hebron, Barcelona, Spain Background: Endovasclar procedures for acute stroke may last several hours until final recanalization is achieved. During this time, measures offering information about the degree of ischemic damage of the affected brain tissue may help the physician taking decisions about whether to pursue or not efforts to achieve recanalization. We studied gasometric parameters of blood samples drawn through the microcatheter. Methods: Acute stroke patients undergoing endovascular procedures were studied. After clot was crossed with the 2.3 French microcatheter a 3-4 ml. blood sample was obtained from the arterial segment distal to the occlusion (Post). Simultaneously another sample was obtained from femoral artery (Pre). A gasometric study was immediately performed. We defined clinical improvement as NIHSS decrease Ն4 points at discharge or 7 days. Infarct volumes were measured on 24 hour CT scan. Results: Post-occlusion blood sampling was performed in 12 patients with an acute middle cerebral artery occlusion. No complications related to the procedure were observed. The gasometric analysis showed differences between Pre and Post blood samples in mean oxygen partial pressure (Post-paO2 73.2 Vs Pre-paO2 79.3; pϭ0.007), mean oxygen saturation (Post-Sat O2 93.08% Vs Pre-Sat O2 94.4%: pϭ0.006) and mean anion GAP (Post-Gap 12.00 Vs Pre-Gap 13.02: pϭ 0.04). Despite that neither Post-paO2 (rϭ0.07;pϭ0.8) nor Post-SatO2 (rϭ0.1; pϭ0.8) were correlated with time from symptom onset to gasometry, the final infarct volume was inversely correlated with Post-paO2 (rϭ-0.722, pϭ0.018) and Post-SatO2 (rϭ-0.664, pϭ0.036). We identified a cut point value of Post-paO2Ͼ70 mmHg that better predicted differences in final infarct volume (386 Vs 69 cc; pϭ0.032) and discharge NIHSS (27 Vs 12; pϭ0.011). The only variables associated with clinical improvement were Post-paO2Ͼ70 (pϭ0.014) and dyastolic blood pressure (pϭ0.03). In the logistic regression model adjusted for time to recanalization Post-paO2Ͼ70 emerged as the only independent predictor of clinical improvement (OR:27 95%CI:1,043-689,790; pϭ0.047). Conclusion: Direct local blood sampling from the ischemic brain is feasible during endovascular procedures in acute stroke patients. A gradient in oxygenation parameters was demonstrated between Pre and Post occlusion blood samples. This information may be used to predict clinical outcome and help in decision making in the angio-suite. Background: Occlusion of cerebral vessels which leads to stroke may also induce significant hypoxia in regions adjacent to infarction, penumbra. The duration and extent of penumbra is clinically important, as it determines the window and brain volume in which interventions may save hypoxic but viable tissue. Understanding the development and duration of the penumbra in animal models is necessary in order to design meaningful models that translate to effective clinical therapies. In this study, we demonstrate incidence and characteristics of penumbra at 24 hours post infarction in a rabbit thromboembolic model with and without thrombolytic therapy. Methods: New Zealand White rabbits (5.2 Ϯ 0.03 kg, nϭ51) were assigned to one of three groups: stroke induced by aged autologous clot (nϭ23), stroke induced by insoluble microspheres (nϭ14), and sphere-stroked animals treated with 3m microbubbles plus ultrasound (nϭ14). Stroke rabbits were embolized with 3 to 5 hr autologous cylindrical blood clots or 700-900m diameter insoluble microspheres using selection of the internal carotid artery. Rabbits were euthanized at 24 hr and infarct volume was measured following triphenyltetrazolium chloride (TTC) staining of brain sections. Penumbra was visualized using immunostaining of pimonidazole injected fifteen minutes prior to euthanasia. Penumbra was defined as strong staining adjacent to and contiguous with infarcted regions. Morphometric analysis of the stained slides was used to measure infarct area and penumbra area in each brain section. Brain sections from unstroked animals were used as a negative staining control. Results: Penumbra was present in 8/51 (15.7%) stroked rabbits. Penumbra incidence did not vary by model (p ϭ0.62) or with treatment (pϭ0.65). There was no relationship of penumbra size to stroke volume (pϭ0.64). Average size of penumbra as a percentage of total lesion (infarct plus penumbra) was 14% Ϯ4% (range 0.96% to 35%). Conclusions: Potentially reversible penumbra is present in 15.7% of rabbits at 24 hours after embolic stroke. At this time point, penumbra can represent as much as 35% of the total lost brain tissue. Intervention at this time point may be of benefit to a significant patient population, and could potentially result in significant clinical improvement.

Author Disclosures: L. Hennings: Research Grant; Significant; NIH R011R01HL082481. R. Flores: Research Grant; Significant; 1R01HL082481. P. Roberson: Research Grant; Significant; 1R01HL082481. A. Brown: Research Grant; Significant; 1R01HL082481. J. Lowery: Research Grant; Significant; 1R01HL082481. M. Borrelli: None. W.C. Culp: Research Grant; Significant; 1R01HL082481.

W P264 A Novel Dimension Changing Distal Access Aspiration Catheter For Acute Stroke Treatment

Satoshi Tateshima; UCLA Med Cntr, Interventional Neuroradiology, Los Angeles, CA Objective: To test the feasibility use of a novel dimension changing distal access aspiration guide catheter in an in vivo vasculature setting. Methods: Two Swine were utilized to assess intracranial access, thrombus aspiration ability, and safety of a novel dimension changing distal access aspiration guide catheter compared to another commercially available neuro guide catheter. In this study, thrombi were prepared in such a way to represent characteristics of those found in acute stroke patients. The thrombi were injected into target maxillary arteries, via a 6Fr guiding catheter. The thrombi were allowed to set up in situ for at least 15 minutes until complete localized occlusion of the target vessels were confirmed by angiography. Once the occlusion was confirmed, the novel guide would be positioned adjacent to the target occlusion, then expanded to a larger ID and used to aspirate thrombus focally with or without the aid of a mechanical thrombectomy device positioned through the lumen in a coaxial fashion; additionally a histological safety study was conducted in the renal arteries to assess vasculature damage when this novel device is positioned and expanded. Parameters collected for this assessment study were navigational assessment, vessel straightening, clot aspiration, and vessel trauma. A commercially available neuro vasculature indicated guide catheter was used as a control. Results: Deeper, more distal access was achieved with the novel dimension changing aspiration guide catheter, which conformed much better to the vessel tortousity, and with much less vessel straightening than the commercially available control. Insofar as the renal artery safety study, histopathology revealed no differences in vascular damage between the novel guide and the control. Distal clot was aspirated with the novel guide, whereas the commercially available guide catheter could not reach the target occlusions. Conclusions: The novel dimension changing distal access aspiration guide catheter appears feasible for distal access and thrombus aspiration in the swine neurovascular model with much less vessel straightening when compared to a guide catheter control.

Background and Purpose:

Previous studies have suggested that the Perfusion-Diffusion Mismatch (PDM) model is more accurate than the Clinical-Diffusion Mismatch (CDM) model for selecting patients who are likely to benefit from reperfusion therapy. However, these studies have not accounted for site of occlusion. Our purpose is to compare CDM and MTT-DWI mismatch in patients with proximal MCA occlusion and small infarct core on presentation. Methods: Single institution, retrospective study of consecutive AIS patients admitted between 01/05-03/08 fulfilling the following criteria: (1) MCA-M1 Occlusion on admission CTA; (2) MRI performed Յ10 hours from stroke onset; (3) Stroke Volume Յ25cc on admission MRI-DWI. CDM was defined as baseline NIHSS Ն8 and DWI volume Յ25cc (as proposed by Davalos et al). MTT-DWI mismatch was defined as a MTT lesion ([MTT-DWI])/DWI) volume Ն 20% and Ն10cc larger than the DWI lesion volume. Significant infarct growth was defined as Ͼ5cc (at least 20%) increase in infarct volume on follow-up imaging. Univariate and multivariate analysis were performed to define the predictors of significant infarct growth. Results: A total of 43 patients were identified (mean age, 75.8Ϯ16.4 years; 62% females; median/IQR baseline NIHSS 13/8-17; median/IQR time from symptoms to DWI, 5/3-6 hours; median/IQR glucose: 125/111-153 mg/dL; 65% right-sided lesions; median/IQR baseline DWI volume, 6.5/1.8-12.5). Nine patients underwent IV thrombolysis, six endovascular treatment, and six combined therapy. On univariate analysis, larger admission DWI volume (pϽ0.0001), baseline NIHSS Ն8 (pϭ0.001), lack of IV and/or endovascular treatment (pϭ0.021), glucose levels Ͼ125mg/dL (pϭ0.024), CTA-collaterals equal or less than contralateral hemisphere (pϭ0.046), and lower admission ASPECTS (pϭ0.049) predicted infarct growth. Baseline NIHSS Ն8 was the only independent predictor of stroke growth in the multivariate analysis (pϭ0.001). All patients had MTT-DWI mismatch greater than 20%. There was no significant association between the amount of MTT-DWI mismatch and infarct growth (pϭ0.33). Conclusions: CDM is the most powerful predictor of infarct growth in patients with MCA-M1 occlusion and small infarct core. All M1-occlusion patients with a small stroke on presentation will have a significant oligemic MTT lesion regardless of NIHSS on presentation and the intensity of the mismatch does not necessarily predicts infarct growth. Therefore, MTT-DWI oligemic mismatch is patients with proximal MCA occlusions is not an accurate measurement of clinical meaningful penumbra. The degree to which these results may be generalizable to other, more strictly defined surrogates of penumbra, including thresholded transit time and CBF measures, is currently under investigation.

Author Disclosures: R.G. Nogueira: Consultant/Advisory Board; Modest; Rapid Medical Inc.. Consultant/Advisory Board; Significant; Concentric Medical Inc.. A. Kemmling: None. L.M. Souza: None. S. Payabvash: None. A.J. Yoo: None. M.H. Lev: None.

W P266 Collateral Circulation as a Prognostic Factor in the Selection of Patients for Endovascular Treatment of Acute Ischemic Stroke

Salvatore Mangiafico, Valentina Saia, Ilaria Romani, Vanessa Palumbo, Giovanni Pracucci, Sergio Nappini, Patrizia Nencini, Fabrizio Ricciardi, Mascia Nesi, Domenico Inzitari, Careggi Hosp, Florence, Italy; for the Florence Stroke Team Background: Endovascular treatment (ET) showed to be safe for acute ischemic stroke (AIS), but uncertainty remains about which patients mainly benefit from this treatment. Preclinical and neuroimaging studies suggest that collateral circulation (CC) could preserve ischemic penumbra, reducing infarct size and improving clinical outcome. We aim to evaluate the role of CC on functional outcome in patients treated with ET. Methods: We analyzed consecutive patients treated with ET for AIS due to proximal middle cerebral artery (M1) and internal carotid artery (ICA) occlusion from 2004 to 2009. We prospectively collected clinical data and retrospectively reviewed neuroimaging data. Early ischemic changes and extension of infarction were evaluated with ASPECTS on baseline and 24h CT scans. Collaterals were scored on pretreatment coronal section angiograms using the Collateral Circulation Score (CCS). Based on extent of collaterals in Anterior (ACA) and Middle (MCA) Cerebral Artery territory, this score identifies 5 grades of collateralization: 0ϭno flow in both ACA and MCA; 1ϭflow in ACA; 2ϭflow in MCA above insular region; 3ϭflow in MCA including insular region; 4ϭflow in MCA-M1. We dichotomized CCS in good (2-4) and poor CC (0-1). We defined good outcome in the presence of mRSՅ 2 at 90 days. Hemorrhage was considered symptomatic in the presence of Ͼ1 point increase on NIHSS. Results: Out of 67 patients with anterior circulation AIS, we identified 44 patients with proximal occlusion (29 ICA, 15 M1); 23 patients were excluded from analysis (17 with distal occlusion and 6 for low quality imaging). There were 29/44 (66%) patients with good (mean age 67.5ϩ/-14.3; M 69%) and 15/44 (34%) patients with poor CC (mean age 67.9ϩ/-12.4, M 33%). Poor CC patients had larger size lesions (24h ASPECTS meanϩ/-DSϭ2.9ϩ/-2.9 vs 4.8ϩ/-2.1; pϭ0.037) and higher rate of symptomatic hemorrhage (27% vs 10%, pϭ0.161) compared to good CC patients. Good outcome was observed in no patients with CCS 0, 10% with CCS 1, 50% with CCS 2 and 40% with CCSϾ 3 (pϭ0.048 Ϭ2 for trend). A synergic effect between recanalization and collaterals was also observed, with good outcome in 10% of patients with recanalization/CCS 0-1 and 80% of patients with recanalization/CCS 2-4 (OR 0.090, CI 0.016-0.506; pϭ0.006) Discussion: In our series the absence of CC is associated with increased size lesion and worse outcome. We suggest the evaluation of CC could be used as a tool for the selection of patients for ET.

W P267 Facing The Clot: Angiographic Appearance Predicts Recanalization And Clinical Outcome In Acute Ischemic Stroke

Peter Adamczyk, Jeffrey L Saver, Qing Hao, UCLA Med Cntr, Los Angeles, CA; Nerses Sanossian, Univ of Southern California, Los Angeles, CA; Rana Fiaz, Latisha K Ali, Doojin Kim, Bruce Ovbiagele, Sidney Starkman, Paul Vespa, Sarah Song, Radoslav Raychev, Hermelinda G Abcede, Nestor Gonzalez, Satoshi Tateshima, Reza Jahan, Gary R Duckwiler, Fernando Vinuela, David S Liebeskind, UCLA Med Cntr, Los Angeles, CA; UCLA Stroke Investigators Background: Previous studies have suggested that the angiographic appearance of an occlusion during acute stroke may offer some predictive value of endovascular thrombolysis outcomes. Various methods of describing such occlusions have been utilized. We evaluated different methods of grading angiographic clot margins to assess thrombolytic outcomes in patients with acute cerebral ischemia undergoing endovascular recanalization. Methods: We identified a cohort of consecutive patients admitted between January 1, 2007 and July 31, 2010 who presented with acute stroke symptoms from internal carotid artery (ICA) or middle cerebral artery (MCA) occlusions and underwent endovascular recanalization therapy (ERT) with intra-arterial tissue plasminogen activator (IA-tPA) or mechanical thrombectomy. Patients were included regardless of whether intravenous tissue plasminogen activator (IV-tPA) was infused before ERT. Contrast opacification proximal to the angiographic occlusion was categorized as blurred or sharp. The target lesion was also described as tram track if any flow was observed around the clot, complete cutoff if no contrast flow was present around the clot, and tandem if multiple occlusions were identified along the vessel. Assignments were based on consensus opinion by two investigators. Analyzed outcomes included revascularization graded on the Acute Occlusive Lesion (AOL) and Thrombolysis in Cerebral Infarction (TICI) scales and global disability at discharge (modified Rankin Scale -mRS). Results: Among the 65 patients, median age was 73 (range 22 -95) and 65% were female. Occlusion sites were: ICA -19; M1 MCA -40; distal MCA -6. The average time to endovascular recanalization was 390 Ϯ 154 minutes and 10 patients (15.4%) received IV-tPA prior to angiography. ERT techniques included IA-tPA in 7 and mechanical thrombectomy in 58. Sharp vs blurred clot margins did not predict recanalization, with median AOL of 3 vs 2, p ϭ 0.121, and median TICI of 2b vs 2a, p ϭ 0.118. Patients with sharp clot margins had better discharge functional outcome, median mRS 3 vs 5, pϭ 0.001. Patients with a tram track morphology clot appearance had better recanalization outcomes than those with complete clot cutoffs: median AOL 2 vs 3, PϽ0.05, and median TICI 2a vs 2b, pϭ0.057. Only two patients demonstrated tandem lesions. Differences in discharge disability score for clot morphology groups did not reach significance: mRS median 4 vs 5, p ϭ 0.151. Conclusions: The initial angiographic appearance of the clot face predicts recanalization and clinical outcomes after endovascular therapy. These features may guide future revascularization approaches.

predictors of clinical outcomes. However these studies did not take final infarct volume into consideration. We aimed to analyze predictors of clinical outcomes considering final infarct burden assessed by magnetic resonant diffusion weighted imaging (MR DWI) following endovascular treatment for patients with acute ischemic stroke with similar territory at risk (M1 MCA occlusion). Methods: Retrospective review of a prospectively acquired database of endovascular acute stroke therapy at University of Pittsburgh Medical Center was performed. Patients with M1 MCA occlusion and available DWI MRI on follow-up were selected. Data abstracted included baseline risk factors, national institute of health stroke scale (NIHSS) and Alberta Stroke Program Early CT (ASPECT) scores, time to treatment and type of endovasuclar treatment (mechanical and/or pharmacologic). Patient outcome data including Thrombolysis in Myocardial Infarction (TIMI) recanalization grade, post treatment DWI volumes obtained by a blinded investigator using a semiautomated method, and 90 day modified Rankin scores (mRS) were reviewed. Successful recanalization was defined as TIMI grade 2 & 3. Clinical outcome was considered favorable if 90 day mRS was Յ 2. Results: Between November 2002 and April 2010, we identified 178 patients. Ninety day functional outcomes were available in 168 patients. TIMI grade 2 & 3 recanalization was achieved in 144 (80.9%) patients. Overall 76 (45.8%) patients had favorable outcomes. Patients with favorable outcomes had lower final infarct burden as compared to the unfavorable outcome cohort (55.2 ml versus 127.8 ml, PϽ0.01). Also patients achieving successful TIMI 2 & 3 recanalization had lower final infarct volumes than patients who failed recanalization attempt (77.1 ml versus 152.9 ml, p Ͻ 0.01). While in univariate analysis baseline NIHSS (OR 0.91, CI 0.85-0.97, PϽ0.01) and successful recanalization (OR 2.75, CI 1.14-6.6, pϭ0.02) along with higher pretreatment ASPECT scores (OR 1.34, CI 1.03-1.73, pϭ0.02) were found to be significantly associated with favorable outcomes, multivariate analysis identified only age (OR 0.88, CI 0.83-0.93, PϽ0.01), and post treatment DWI infarct volume (OR 0.98, CI 0.97-0.99, PϽ0.01) as significant predictors of favorable outcome. Conclusion: Our study findings indicate that amongst a homogenous patient population with intracranial MCA M1 occlusion, age and final infarct volume rather than recanalization or baseline stroke severity appear to be the only predictors of clinical outcome following endovascular therapy for acute ischemic stroke.

W P273 Stenting Angioplasty In The Treatment Of Venous Sinus Stenoses:clinical And Angiographic Outcome In 34 Patients

Xunming JI Y Jian CHEN; Xuanwu Hosp, Capital Med Univ, Beijing, China Object: Cerebral venous sinus stenoses have been considered as a mechanism responsible for raised intracranial pressure without a mass lesion or cerebral edema. Very few studies have been carried out on venous sinus stenosis treatment with stenting . As an invasive treatment, the safety and efficacy has been controversial. The purpose of present study was to evaluate the clinical and neuroimaging-based results in 34 venous sinus stenosis patients treated with stent angioplasty. Methods: 34 consecutive patients (twenty-three women and eleven men, age range 18 to 56 years) who had presented with isolated intracranial hypertension with venous sinus stenoses underwent examination with magnetic resonance venography (MRV), digital subtraction angiography (DSA), direct retrograde cerebral venography and manometry to confirm morphologic features and venous pressures. All patients demonstrated irregular filling defect in venous sinuses and the pressure gradients across stenoses over 15cmH 2 O were treated with intrasinus stenting placement with or without auxiliary balloon angioplasty and intrasinus pressures and correlated with clinical outcome were recorded before and after the procedure. During the follow-up period of more than 6 months, symptoms, fundus examination, intracranial pressures, stent patency rates and complications were assessed. Results: All 34 patients were treated with sinus stenting angioplasty. In the 33 patients stenotic cerebral sinus were improved by stenting and a reduction in intrasinus pressure was achieved (the pressure gradient Ͻ3.5cmH 2 O). During the mean follow-up 22.5months (range 6ϳ84months), 31 patients (91.2%) were improved or asymptomatic and the follow-up DSA or MRV demonstrated absence of stent thrombosis and restenosis. Out of 34, only one patient had been confirmed intraparenchymal hematoma after procedure and died of brain hernia. In 2 patients, the intracranial hypertension did not improved after procedure. During follow-up period, DSA showed dural arteriovenous fistula (DAVF) involving the transverse sinus in these two patients, thus embolism treatment were performed. Conclusions: Our result indicates that Stenting angioplasty is a save and effective treatment in Venous sinus stenosis, suggesting that endoluminal stenotic lesions with a distinct pressure gradients across the stenoses lead to raised intracranial pressure and that endovascular treatment in this type of stenoses is a promising treatment.

Author Disclosures: X.Y.Y.Y. Jian CHEN: None.

W P274 Usability Testing the Self-Management TO Prevent Stroke Tool

Jane Anderson, Kimmel Barbara, Michael E. DeBakey VA Med Cntr, Houston, TX; Scott Russell, Adam Neddo, Josh Robinson, Roudebush VA Med Cntr, Indianapolis, IN; Mahesh Merchant; Roudebush, VA Med Cntr, Indianapolis, IN Background: Paper-based clinical practice guidelines are difficult to integrate with clinicians' real time workflow and documentation needs. Decision support tools incorporated into the electronic medical record may enhance implementation of best practices for secondary stroke prevention. The STOP Stroke Tool is a clinical decision support application that prompts clinicians on guidelines for secondary stroke prevention, and provides simultaneously access to patient education materials and self-management plans for stroke risk factors. Methods: Usability-engineering methods were applied to develop and test the STOP Stroke Tool. Iterative prototype testing sessions with end-users were completed to evaluate the functionality and usability of multiple renditions of a STOP Stroke Tool prototype. End-users included physicians and nurses involved in the follow-up care of Veterans with ischemic stroke or transient ischemic attack. During each testing session, clinicians provided feedback to guide design strategies and to identify usability barriers and facilitators. Multiple testing methods were applied. Documentation of guidelines was compared among multidisciplinary clinicians (Nϭ15) using test case scenarios. Usability was evaluated with Think-Aloud protocols, questionnaires and open-ended survey questions. Most recently, (Nϭ12) clinicians viewed a demonstration video of a newer web-based prototype and provided feedback on barriers and facilitators to implementing the tool in practice. Nonparametric, descriptive statistics and direct content analysis were applied to analyze the data. Results The initial template-based prototype prompted a significant increase (p Ͻ .05) in provider documentation for 6 of 11 guidelines as compared to baseline documentation while using the standard system. Out of a possible 56 points, usability was scored high (M ϭ 48.9, SD ϭ 6.8). Themes around implementation barriers were related to 'time constraints', 'lack of interoperability with the current system', 'learning how to use the tool', and 'access to the tool'. Themes around implementation facilitators were focused on the tool providing 'reminders for best practices' 'automated documentation', 'systematic care processes' and 'comprehensive stroke follow-up'. Conclusions: Results support that usability-engineering strategies can be successfully applied to produce guideline prompting and clinical decision support for secondary stroke prevention in the electronic medical record. Current testing is focused on describing provider and patient collaborative management of stroke risk factors while using the STOP Stroke Tool.

Author Disclosures: J. Anderson: None. K. Barbara: None. S. Russell: None. A. Neddo: None. J. Robinson: None. M. Merchant: None.

W P275 Stroke Patient Education Tools Increase Nursing Compliance and Documentation of Stroke Patient Education

Kathleen Furlong, Deborah M Mastrolia; Hoag Hosp, Newport Beach, CA Background: Annually 795,000 people experience a new or recurrent stroke. Approximately 185,000 are recurrent strokes. The incidence of Transient Ischemic Attack (TIA) in the United States is estimated to be 200,000 to 500,000 per year. After TIA, the 90 day risk factor of stroke is 3.0% to 17.3% and is highest within the first 30 days. Several studies revealed a lack of knowledge regarding stroke/TIA risk factors and symptoms. Purpose: The purpose was to increase patient, family and caregiver awareness to the signs and symptoms of stroke/TIA and secondary stroke prevention, while giving nurses the tools for complete and consistent education according to the Stroke Get With The Guidelines (GWTG) recommendations. Methods: A 97 page comprehensive stroke patient education workbook was given to each stroke and TIA patient to review their personal risk factors and stroke etiology. In 9/2008, a stroke patient education form was implemented. This form addresses stroke signs, symptoms, 911, stroke risk factors, cholesterol levels, secondary stroke prevention medications, healthy lifestyle modifications, neurology and rehab follow-up. The nurse uses the tool each shift upon admission and requires patient/caregiver initials for each topic discussed. Stroke GWTG core measures are documented in the electronic charting. Patient educational videos and Stroke Smart magazines are also provided. Results: Analysis of stroke patient education for 956 patients from 1/1/2008 through 6/30/2010 with ischemic, TIA, or hemorrhagic stroke revealed a significant improvement. The quarter prior to implementation of our tool results were 90.6% (96/106).The quarter after increased to 98% (96/98). We have maintained at least 97% each quarter since then. Conclusions: The combination of these tools ensures that all required stroke education is completed. As a result of the multiple educational interactions, tools and documentation, there is increased awareness by nurses of the need for patient stroke education. Starting education upon admission has eased the discharge process. Further follow-up is warranted to validate increased awareness of stroke symptoms and secondary stroke prevention by the patient and caregiver.

Author Disclosures: K. Furlong: None. D.M. Mastrolia: None.

W P276 Cerebrovascular Risk Factors are Different in Patients with Ischemic and Hemorrhagic Stroke in Northeastern Brazil

Monique B Alves, Jr., Hosp Israelita Albert Einstein, Sa ˜o Paulo, Brazil; Joa ˜o J Carvalho, Hosp Geral de Fortaleza, Fortaleza, Brazil; Gisele S Silva, Hosp Israelita Albert Einstein, Sa ˜o Paulo, Brazil; Cı ´cera B Machado, Secretaria da Sau ´de do Estado do Ceara ´, Fortaleza, Brazil; Georgiana A Viana, Bento F Santos; Hosp Israelita Albert Einstein, Sa ˜o Paulo, Brazil Introduction: Risk factors for ischemic and hemorrhagic strokes are similar but not exactly the same. Our objective was to compare the prevalence of classic stroke risk factors of patients admitted with stroke or transient ischemic attack (TIA) in Fortaleza, Ceara ´, Brazil. Fortaleza is the state capital of Ceara ´(Northeastern Brazil), has a population of over 2.5 million, and is the 5th largest city in Brazil. Hypothesis: We hypothesized that patients admitted with hemorrhagic and ischemic stroke in Fortaleza have similar but not identical risk factors. Methods: Data were prospectively collected from patients admitted to the EDs of 19 hospitals in Fortaleza with a diagnosis of stroke or TIA by trained research coordinators from June-2009 to May-2010. In 2008, 90% of the patients admitted with stroke in Fortaleza were evaluated in either one of the 19 hospitals studied. Daily visits to EDs of the selected hospital were performed and all patients admitted with a diagnosis of stroke or TIA were prospectively evaluated. A dedicated nurse coordinator reviewed all the patients. Controversies were discussed with two stroke neurologists. Results: We evaluated 1510 patients: 1084 had ischemic stroke (IS) (71,8%), 303 hemorrhagic strokes (ICH) (20%), 82 subarachnoid hemorrhage (SAH) (5,4%) and 41 TIA (2,7%). Mean age was 67.9 Ϯ 14.5 yo (50.2% males). Patients with ICH (including SAH) were younger (61 Ϯ 15.2 years-versus 69 Ϯ 13.6 years-IS patients, PϽ0.01). The two groups were similar in gender, prevalence of hypertension, hyperlipidemia, smoking and previous myocardial infarction. Patients with ICH had more frequently a history of alcohol abuse (IS 24.2% versus ICH 31.5%, pϭ0.03), and patients with IS had a higher frequency history of previous stroke (IS 46.1% versus ICH 26.4%, PϽ0.01) and diabetes (IS 46,5% versus ICH 37. 4%, pϭ0.01). Conclusion: Although risk factors for IS and ICH are similar, diabetes and previous stroke seem to be more frequent in patients with IS; conversely, alcohol abuse is more frequent in patients with ICH. A more focused approach for primary and secondary prophylaxis in patients with IS and ICH should be based in the knowledge of the differential risk factors for distinct stroke subtypes.

W P277 Stroke: Bridging the Gap Between Knowledge and Practice

Katie M Wright, Judy Werstler; Aultman Hosp, Canton, OH Background and Issues: The implementation of evidence-based treatment guidelines into clinical practice has been shown to improve stroke outcomes. Although evidenced-based guidelines have been developed along with improved treatment and diagnostic capabilities, there are many inconsistencies with how these guidelines are applied in clinical practice. Bedside nurses were left trying to recall the ten stroke performance measures while caring for multiple patients with varying diagnoses and co-morbidities. As a result, there were repetitive oversights which created a gap between recommendations and actual clinical practice. This became a pattern, continued from shift to shift and resulted in inconsistencies in care provided. Internal observations revealed that the utilization of interdisciplinary resources, such as dietitians and diabetic educators, were being underutilized. Purpose: A tool was developed to assist the nursing staff in tracking compliance with each of the ten Performance Measures. The tool also promoted an organized approach to the interdisciplinary management of each stroke patient. The goal of the implementation of the tool was to increase the compliance with each performance measure to levels above the national benchmark as well as increased utilization of dietitians and diabetic educators within the organization. Methods: The tool is initiated upon admission and is used throughout the hospital stay. The charge nurse oversees the completion of the tool by obtaining updates from the interdisciplinary team each shift. Data entered onto the tool guides the charge nurse to obtain appropriate medical orders to ensure compliance with each performance measure. In addition, consults are generated to the diabetic educator and dietitian based upon lab results and basic admission data. Results: Since implementation of the tool in early 2008, we have seen great improvement with adherence to the Performance Measures. Of the ten Performance Measures, seven have shown a consistent increase and three have remained within statistical control and are significantly higher than the national benchmark. Based upon recommendations from the nursing staff, changes were made to the tool to include spaces for actual lab results (LDL and A1C). In addition, critical elements specific to required discharge medications along with contraindications were added to the tool. The tool is continuously reviewed and recommendations for changes and additions are closely evaluated. As a result of the increased compliance with the Performance Measures, Aultman Hospital was recently awarded the Gold Plus award for exemplary stroke care from the American Heart Association and received the Gold award in both 2008 and 2009.

Author Disclosures: K.M. Wright: None. J. Werstler: None.

W P278 System Standardization of Dysphagia Assessment Education Increases Compliance with Acute Stroke Patients

Julie Fussner, Erin Supan, Leigh Ann McCartney, Univ Hosps Case Med Cntr, Cleveland, OH; Melissa Richardson, Univ Hosps Geauga Med Cntr, Chardon, OH; Christine Garrett, Univ Hosps Bedford Med Cntr, Bedford, OH; Cathy Sila; Univ Hosps Case Med Cntr, Cleveland, OH Introduction: Dysphagia may occur in up to 65% of stroke patients per the American Stroke Association. One of the most common complications of a stroke is aspiration pneumonia caused by dysphagia. The University Hospitals Stroke and Cerebrovascular Center (UHSCC) developed an educational module to teach nurses caring for stroke patients how to assess for dysphagia. Methods: The UHSCC developed a bedside dysphagia protocol to standardize dysphagia assessments across the health system. Nurses caring for stroke patients were educated on the protocol requirement. The director of the UHSCC and a speech therapist created a DVD that demonstrated dysphagia assessments performed on real patients to aid in the education of the nurses. In the initial pilot, 100 nurses viewed the video and were given a pre and post test to assess the effectiveness of the teaching mechanism. The DVD is now available to all nurses on an electronic learning management system. Compliance with dysphagia assessments for stroke patients is monitored using the Get With the Guidelines program. Results: Of the 100 nurses who viewed the DVD in the pilot, 67 had no prior dysphagia assessment education. The average pre test score of these nurses was 80% and the average post test score was 90% (p value Ͻ 0.0001). Forty three nurses in the pilot had prior dysphagia education. This group's average pre test score was 87% and the average post test score was 96% (p value ϭ 0.0003). The DVD competency requirement for the system was rolled out in 2009 and 96% of the nurses caring for stroke patients throughout the UH health system have been educated using the video presentation. Compliance with dysphagia assessments for stroke patients across the UH health system has increased from 40% in Q1 2009 to 82% in Q1 2010. Conclusions: Standardization of dysphagia education across the UH Health system through the use of this educational tool has resulted in a significant increase in dysphagia assessment compliance for stroke patients. This DVD is now used as an annual competency throughout the health system for nurses caring for stroke patients with plans for all medical-surgical nurses to complete in 2011.

W P279 Initial NIHSS and Timely t-PA Predicts 3 Month Disability

Linda Catalli, Regional Med Cntr San Jose, San Jose, CA; David Pickham, Regional Med Cntr San Jose; Univ of California, San Francisco, San Jose, CA; Raul Guisado; Regional Med Cntr San Jose, San Jose, CA The effectiveness of intravenous alteplase (IV t-PA) in the treatment of acute ischemic stroke has been proven in multiple trials. The long term outcome of treatment however, depends on multiple factors that can influence clinical decision making. The purpose of this study was to explore the effect of initial stroke severity and initial response to treatment on the 90-day outcome of patients with acute ischemic stroke (IS) treated with IV t-PA. Methods: As part of an on-going study 38 consecutive patients treated with IV t-PA for acute IS at four community Primary Stroke Centers were followed prospectively for 3 months. Demographics, initial and post-procedure NIHSS score and post-hospital disposition were abstracted from the ASA Get With The Guidelines Database. A 90-day modified Rankin Scale (mRS) score was obtained by phone interview by a trained stroke coordinator. Results: Thirty-eight patients received IV t-PA and a mRS at 90 days. Mean age was 72 yrsϮ15. Mean NIHSS on admission was 10Ϯ7 and post-procedure NIHSS was 4Ϯ7, for a net treatment effect (NIHSS delta) of -5Ϯ7. NIHSS on admission and discharge correlated positively with patients mRS (rho ϭ .741 & rho ϭ .583, PϽ.0005, respectively). In-hospital NIHSS delta did not correlate with mRS (pϭ.286). Timely IV t-PA treatment was associated with greater in-hospital NIHSS delta (rho ϭ -.349, pϭ.047), but timely IV t-PA did not show significant association to mRS (pϭ.378). Conclusion: We demonstrate that 90-day outcome post IS is predicted by stroke severity, measured by the NIHSS on admission and discharge. Timely administration of IV t-PA was not directly correlated with 90-day outcome, but is associated with improved in-hospital NIHSS score and therefore functioning on discharge, which is correlated with 90-day outcome. These findings lend empirical support to public health initiatives to increase early presentation and shorten door to needle times in patients with acute IS.

Author Disclosures: L. Catalli: None. D. Pickham: None. R. Guisado: None.

W P280 Community-acquired Pneumonia In Acute Ischemic Stroke

Debora C Mariano-Gambaro, Daniela Morales, Aline M Franco, Larissa A Silva, Taiza E Santos-Pontelli, Ilana V Werneck, Daniel G Abud, Joa ˜o P Leite, Octavio M Pontes-Neto; Stroke Service, Univ of Sao Paulo, Ribeira ˜o Preto, SP, Brazil Background and Purpose: Pneumonia is an important complication of ischemic stroke and increases mortality 3-fold. We aimed to determine key characteristics associated with communityacquired pneumonia in admission of acute ischemic stroke patients. Methods: We studied a series of consecutive patients with acute ischemic stroke who were admitted to hospital from January 2006 to June 2008. The evaluation included patients's clinical status, NIHSS and Glasgow Coma Scale, laboratory and radiological data. The diagnosis of pneumonia was defined if the patient had an infiltrate on chest radiograph that was new or progressive, along with clinical findings suggesting infection, which include the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation in the first 48 hours of admission (according American Thoracic Society 2005 consensus). Results: We studied 554 patients with acute ischemic stroke; 52 (9.38%) met the study criteria for community-acquired pneumonia. Subjects who developed pneumonia were older (69.4Ϯ15.22 vs 64.3 Ϯ 14.3 years); had higher modified NIHSS scores: 17 (IR 10-24) vs 9 (IR 4-17); lower Glasgow Coma Scale scores 12 (IR 9-14) vs 14 (IR 12-15); higher level of glycemia (141Ϯ53.7 vs 131Ϯ59.2mg/dL) and lower mean arterial blood pressure (102.5Ϯ23 vs 113.24 Ϯ 21.6mmHg) on admission. These patients had higher mean length of hospital stay (22.3Ϯ29 vs 13.47Ϯ20 days) and higher mean of in-hospital mortality (50% vs 14.9%). In logistic-regression analysis, independent predictors (P Ͻ 0.05) associated with pneumonia were age (ORϭ1.04;ICϭ1.02-1.05); NIHSS (ORϭ1.06; IC1.03-1.09) and glycemia at admission(ORϭ 1.01;ICϭ1.01-1.02). Conclusions: Community-acquired pneumonia after acute ischemic stroke is frequent and is associated with older age, severity of stroke deficits (NIHSS) and glycemia at hospital admission. Patients who developed community-acquired pneumonia had higher length of hospital stay and higher in-hospital mortality. controlled trial designed to assess the safety of pioglitazone (PIO) in patients with intracerebral hemorrhage (ICH). Objectives are to determine the maximal tolerated dose of PIO and to evaluate the rate of ICH and edema resolution with MRI. Patients are seen every 2 weeks for 8 weeks, day 90 and 6 months for FUVs. FUVs evaluate safety and functional measures, glucose logs, drug accountability, and MRI. Initially, our primary study coordinator (PSC) conducted data collection during the acute hospitalization and subsequent outpatient FUVs were to occur in a Clinical Research Unit (CRU) which provided different coordinator support. We determined the number of missed FUVs that occurred when our PSC was not involved in the FUV process. We considered a FUV 'missed' by the CRU if the patient did not show or if our PSC had to collect the data by means other than a CRU visit (e.g. site visit or phone follow-up). Results: A total of 36 patients have been enrolled. Four patients have died and their data are not included. FUVs for the first 21 subjects were conducted by the CRU. FUVs for subjects 22-34 were conducted by the PSC. The proportion of FUVs missed by the CRU was 33% (39/120 possible FUVs) compared with only 2% (1/60 possible FUVs, PϽ0.0001) when the PSC communicated directly with patients. A total of 45% of patients followed by the CRU had more than 1 missed FUV compared to 0% when followed by the PSC (pϽ0.01). Conclusion: In our cohort of patients with ICH, protocol compliance with FUVs was better with one primary contact than when multiple people were involved in FUVs. Possible reasons include non-familiarity with the study population and their needs, lack of flexibility in scheduling in a busy CRU and no other method for data collection if the patient no-shows. As a result of our findings, data collection has significantly improved thus ensuring internal validity of the study.

W P282 The Effectiveness of Four Translation Strategies on Nurses' Adoption of an Evidence-Based Bladder Protocol

Jamey S Frasure; Univ of Cincinnati, Cincinnati, OH The Effectiveness of Four Translation Strategies on Nurses' Adoption of an Evidence-Based Bladder Protocol Background: Mixed evidence exists regarding the effective use of the four translation strategies of educational materials, educational meetings, reminders, and audit and feedback on the adoption and implementation of interventions by nurses. Many clinical practice guidelines for the care of the stroke patient advocate for bladder training, but evidence-based bladder protocols for the stroke patient are not available. The best available bladder protocol identified was a prompted voiding algorithm from the Registered NursesЈ Association of Ontario. Review of the literature reported 32-79% of hospitalized stroke patients suffer from urinary incontinence. Strong support for prompted voiding demonstrated reduction of urinary incontinence in patients with cognitive deficits. Purpose: The primary purpose of this study was to examine the effects of an intervention consisting of four translation strategies: educational materials (clinical practice guideline), educational meetings, reminders, and audit and feedback on nursesЈ adoption of an evidence-based bladder program for stroke patients in an acute care setting. The second purpose was to evaluate the difference in incontinence episodes of patients before and after nurses received the intervention. The third purpose of the protocol was to evaluate the influence of nursesЈ attitudes on adoption and use of the evidence-based bladder program after receiving the intervention. Methods: A time-series design, using 8 one-week time points before the intervention and 16 one-week time points after the intervention, was used to obtain the required sample, n ϭ 29. The nurse and medical record samples were convenience samples from a 40-bed neuroscience acute care unit affiliated with a 695-bed academic medical center. The purpose of the intervention was to teach and encourage nurses to adopt a prompted voiding algorithm for stroke patients. The Research Utilization Survey was used to evaluate the influence of nursesЈ attitudes on the adoption and the use of the evidence-based bladder program after receiving the intervention. Results: Data supported the degree of change as a two-fold increase in the nurses' adoption of an evidence-based bladder protocol, but there was no statistical difference in the incontinence episodes pre-and post-intervention. The increased research utilization and attitude scores were not statistically significant. Nurses' level of basic nursing education was positively associated with the adoption and the use of the evidence-based bladder protocol. Conclusions: This study was the first to provide empirical support for the influence of the combination of these four translation strategies and nurses' attitudes toward research on adoption of evidence-based practice in a time-series design study.

Author Disclosures: J.S. Frasure: None.

W P283 Preserving Patient Safety During Handoffs for Acute Stroke Patients that Receive Alteplase.

Kimberly Gray, Susan Hickenbottom; St. Joseph Mercy Hosp, Ypsilanti, MI Background and issues: Patients receiving IV tissue plasminogen activator (tPA) for acute ischemic stroke (AIS) are at risk for bleeding and other complications. Recommendations for vital signs and neurological checks during and after administration are very strict and must be retrievable in the medical record, with accurate nursing documentation. Transportation from the location where tPA was administered to an ICU creates opportunities for delay in or missed documentation as a result of handoffs between care providers. Purpose: To improve documentation and safety measures for tPA patients in a new electronic medical record (EMR). Methods: With a change to a new EMR in 10/09, our Stroke Collaborative Practice Team created a new order set and visible reminders to enhance safety for tPA patients. Retrospective chart review noted vitals and neurochecks were not consistently documented in the medical record according to treatment guidelines. Emergency Department and inpatient acute stroke admission packets were updated with a paper tPA flowsheet. The flowsheet outlines the 24-hour requirements for vital signs and neurochecks, and contains several patient precautions and monitoring requirements. Additionally, a 'head of the bed' tPA precaution sign was also placed in the ED and ICU admission packets to become a visible in-room reminder that the patient is at risk for post-tPA complications. Both items were placed on our hospital's intranet to allow printing from any patient care area. Education of nursing staff on use of the flowsheet, a review of the expectations for vitals and neuro checks in tPA patients, and the head of the bed sign was completed by 100% of ED staff in 9/09. The ICU nursing staff was also educated on these changes. An order to place the head of the bed sign was revised in the AIS departmental order set. Results: All tPA patient charts were reviewed from 10/09 to 2/10. Six patients received IV tPA for AIS during the review period; in all instances the patients had appropriate, consistent documentation using the flowsheet. Spot checks were completed to ensure the head of the bed sign was posted in the patients' rooms (100% compliance). Conclusion: A formalized documentation tool specifically for AIS patients receiving tPA, as well as a precaution sign with visible reminders for caregivers, has helped to ensure that patients are monitored according to evidence-based guidelines and protected from potential complications after receiving a high risk, but infrequently used, medication.

Author Disclosures: K. Gray: None. S. Hickenbottom: None.

W P284 Implementation of the American Stroke Association Sharegiver Program (Peer Support)

Teresa M Damush, Indiana Univ Sch of Medicine/VA Stroke QUERI, Indianapolis, IN; Jane Anderson, Houston VAMC, Houston, TX; Gloria Nicholas, Indiana Univ Sch of Medicine/VA Stroke QUERI, Indianapolis, IN; Barbara Kimmel, Houston VAMC, Houston, TX; Thomas Kent, Baylor College of Medicine/Houston VAMC, Houston, TX; Linda S Williams; VA Stroke QUERI, Indianapolis, IN As part of a post stroke intervention study, we have locally adapted the American Stroke Association Sharegiver program and implemented at two Veteran Administration Medical Centers located in Indianapolis and Houston. The program entails training stroke survivors to serve as peer support for current hospitalized patients with stroke and supervising the peers as they deliver the support. We describe the program contents and administration. We recruited and trained 13 stroke peer sharegivers over 18 months across 2 sites. A coordinator at each facility assigned new patients to each stroke peer based upon availability. The stroke peers reported their frequency of interactions with their assigned patients to the coordinator. The supportive interactions were made in person at the medical center or by telephone. To understand the motivation behind the stroke peer volunteerism and to understand the barriers that arose and how they were resolved, we conducted focus groups of the stroke peers at both medical centers and are analyzing the transcripts for common themes. Our data demonstrates the feasibility of implementing a stroke peer support program for stroke survivors alongside traditional care. We plan to create an implementation toolkit to disseminate to clinical programs. This project was supported by a grant from the Veterans Health Administration IAB 05-297.

Author Disclosures: T.M. Damush: None. J. Anderson: None. G. Nicholas: None. B. Kimmel: None. T. Kent: None. L.S. Williams: None.

W P285 Early Mobilization of Ischemic Stroke Patients post-Intravenous TPA Infusion

Lesia Mooney, Scott Arnold, Olivia Chavez, William David Freeman, James Meschia; Mayo Clinic Florida, Jacksonville, FL Background and Purpose: To examine safety of early mobilization of IV tissue plasminogen activator (TPA) treated acute ischemic stroke patients by Physical Therapy (PT) and Occupational Therapy (OT) before 24hours. Methods: We conducted a prospective study between February to June 2010 of early mobilization (i.e., PT/OT initiated between 12 and 24 hrs post TPA) of all IV TPA-treated patients at a single, academic medical center, Mayo Clinic, Jacksonville, FL. A safety screen was performed before mobilization occurred in acute stroke patients who received IV TPA. Safety screen included hemodynamic and neurologic stability including orthostatic blood pressure, absence of adverse symptoms, and no active bleeding. If safety screen failed, the patient mobilization was postponed and rescreened later by nursing until stable for subsequent PT/OT. Secondary analysis was review of hospital length of stay (LOS) by two-tailed unpaired t-test for the prospective group of patients compared to a control group, which was mobilized per standard 24 hrs post TPA infusion (AHA guidelines). Results: 12 patients were identified in the study period (6 female, 4 males, mean age, 66, range 52-91 years). Mean admission NIHSS was 12 (range 2-29). One patient was not screened before mobilization, and another screened after 24hrs, both being excluded from analysis. Of the remaining 10 patients screened, 90% (9/10) of screened patients met safety screen criteria. One patient failed orthostatic blood pressure screening on two occasions by 24hrs. Compared to the historical controls, the average LOS (ALOS) for the prospective group which passed safety screen (nϭ9) was 3.1 days (range 1 -9, SD ϭ 2.4), compared to the control group (nϭ9) ALOS was 3.6 days (range; 2-9, SDϭ 2.9), which did not meet statistical significance (pϭ0.7). Conclusions: Early mobilization of ischemic stroke patients between 12 and 24 hours after IV-TPA infusion appears safe for 90% of patients, whereas but one patient failed due to orthostatic hypotension but was of advanced age (91 years). There was no difference in average length of stay compared to the control population which is mobilized patients 24hrs after TPA infusion. Further, larger powered studies are needed to provide guidelines about safety and factors which shorten length of stay for stroke patients and provide best outcomes Author Disclosures: L. Mooney: None. S. Arnold: None. O. Chavez: None. W. Freeman: None. J. Meschia: None.

W P286 Efficacy of Health Education

Estela Sanjuan, Eva M Garcia-Vega, Pilar Sanchez-Camacho, Rosa Sun ˜er; Hospital Universitario Dr. Josep Trueta De Girona, Girona, Spain Background & Purpose: Stroke knowledge in general population is very poor in all countries around the world. It is necessary to provide health education with information about the risk factors to prevent it, and its warning signs to reach an early recognition and treatment. The aim of this study is to evaluate the increase of knowledge about stroke warning signs and risk factors, after an educative intervention addressed to hospitalized stroke patients and their relatives. Methods: pre-post prospective study by interviewing patients and their relatives with close-ended questions about their knowledge of stroke, before and after an educative intervention. The study was conducted from the 1st of March 2010 to the 1st of June 2010 in the University Hospital of Girona (Spain). Pre-post comparisons were made using parametric T student analysis. Results: We interviewed a total of 50 people (8 stroke patients and 42 relatives) with a mean age of 47.12 Ϯ 16.6 years old. 62 % were women. Differences between pre and post scores were statistically significant when comparing the number of stroke symptoms and risk factors known before and after the educative intervention, with a p-value of 0.01 and 0.00 respectively. Pre-test interview showed that subgroups like: patients, women, higher level of studies and younger people had a higher previous knowledge of stroke than the rest. Otherwise the post test scores were very similar in all groups. Hypertension, identified previously by a 90% of the participants, was the most known risk factor, followed by Hypercholesterolemia (78%) and Smoking (72%). Warning signs most commonly recognized were weakness and (96%) slurred speech (88%). After receiving the information, 92% of the participants considered changing their life habits into a healthier lifestyle, and more than an 80% could identify the key-factors to recover and prevent new events. The educational program was very well appreciated by the participants with an overall score of 9.96 out of 10. Conclusion: An educational intervention can improve people's knowledge of stroke which is necessary to prevent it, helps to recover from it, and to seek urgent medical attention in case of recurrences. Nurses have a key role doing these educational programs due to being an important part of the patient's treatment, and changing patient's and family's lifestyles. The effects of the intervention are temporary so it is necessary to reevaluate it in a mid-long period.

Author Disclosures: E. Sanjuan: None. E.M. Garcia-Vega: None. P. Sanchez-Camacho: None. R. Sun ˜er: None.

W P287 Can Clinical Presentation Provide Clues to Conversion Disorder in Code Stroke Patients? A Descriptive Analysis of Clinical Findings

Mary K Brethour, Huntsville Hosp and UAB, Huntsville, AL; Anne V Alexandrov; UAB, Birmingham, AL Background: Stroke mimics are well described in the literature, and include seizure with Todd's paralysis, complicated migraine, hypertensive encephalopathy, hypoglycemia, and conversion disorder. While conversion disorder is often described as inconsistent clinical findings, few papers detail conversion disorder presentations mimicking acute stroke. We aimed to describe common features of conversion disorder to enable improved detection of this disorder. Methods: Presenting clinical findings in consecutive code stroke patients that ultimately were diagnosed with conversion disorder were analyzed to determine if trends in clinical presentation could be identified. Results: During a 12 month period, 23 code stroke patients were assigned a diagnosis of conversion disorder at discharge. Mean age was 45 (range 15 to 63); 78% were women. Admission NIHSS scores ranged from 0-18, with a median of 8; only 5 patients presented with an NIHSS Ͻ 5 points. Distribution of NIHSS findings demonstrated a higher prevalence of motor findings affecting the non-dominant left arm (57%), and the left leg (61%), as compared to the right arm (22%) and right leg (30%). In patients presenting with left hemiparesis, 46% exhibited aphasia (mild-moderate) as well as dysarthria (mild-moderate). Left arm and bilateral lower extremity weakness was found in 3 (13%) patients, with 2 of these also presenting with aphasia and dysarthria. Of patients presenting with right motor weakness, only 9% were scored as aphasic (mild-moderate), while 80% were dysarthric (mild-moderate). No patients presented as mute or demonstrated a receptive component to their aphasia. One patient in the series was treated with IV tPA on 2 separate admissions with resolution of symptoms; 2 patients were discharged home from the ED and the remaining 21 were admitted to the hospital for a complete stroke work-up. Conclusion: Conversion disorder patients may exhibit a higher prevalence of motor findings affecting the non-dominant side, with a disproportionate increase in lower extremity weakness and preservation of language fluency and reception. These findings may indicate a subconscious need to maintain control despite significant underlying stress and anxiety.

Author Disclosures: M.K. Brethour: None. A.V. Alexandrov: None.

W P288 Reducing Urinary Tract Infections in Stroke Patients Using Bladder Scanning technology and Nurse Managed Algorithms

Millie Hepburn, Sara Andrew, Sherin Joseph, Karen Mansfield, Suzanna Horvath; Columbia Univ Med Cntr, New York, NY Effective measures to prevent urinary infection are generally lacking in stroke patient populations. Our research team developed innovative strategies to reduce urinary tract infections (UTIs) in our ischemic and hemorrhagic stroke patients. Routine insertion of indwelling urethral catheters and intermittent catheterization protocols every 6-8 hours have been standard care for our patients. Following discovery of a significant percentage of UTIs in our patients, we realized a correlation with GI based organisms, female gender and prolonged length of stay in these patients We designed pathways to address both incontinence and urinary retention for the neuroscience patient to decrease hospital length of stay, as well as readmissions. Bladder scan technology and mobilization for toileting has not been evaluated in a comprehensive, evidence-based protocol driven methodology. The average adult urine production is 60 mL per hour and a risk for urinary tract infections increases with a bladder volume of 180-300 mL. However, most bladder management protocols only evaluate urinary status every 6-8 hours. Our research team has developed and validated urinary management algorithms for stroke patients in five different clinical applications. We will feature these essential state of the art evidence-based algorithms to evaluate urinary elimination in defined patient conditions every four hours, using non-invasive technology, which ultimately reduces the potential risk for infection, and outline a statistically significant reduction in UTIs for our patients.We will also discuss challenges as well as solutions for changing current paradigms in nursing and physician care, physician order sets and application in practice at the bedside. over time on quality indicators for The Miriam Hospital (TMH), a hospital certified as a primary stroke center by The Joint Commission (TJC) and a participating hospital of the American Heart Association and American Stroke Association (AHA/ASA) Get with the Guidelines program. TMH tracks a number of indices, one called a composite index. The defect-free measure is used to evaluate how well the hospital did in providing all appropriate interventions to every patient. The hospital's proportion of patients who received interventions they were eligible, is calculated. The data time period is January 2006 to December 2009. A concurrent review process was implemented at TMH in June of 2008. Purpose: To evaluate the effectiveness of concurrent review on stroke center measures. Method: A dedicated quality improvement nurse coordinator launched the pilot June 2008. The design included: concurrent review plan, paper & electronic data collection tools, process for evaluating data, strategies to communicate with clinicians. The primary method for concurrent review is the daily examination of admitted patients using a combination of paper and electronic records. Information is transferred to a data collection tool to form a patient profile and to use to communicate with the responsible clinicians and nurses. This strategy was implemented beginning in June 2008. Data was reviewed regularly from the Outcome Science Database repository. Reports were generated and results were trended. Changes in composite scores over time were compared using a generalized estimating equation with a logit link function to fit a piecewise regression with an inflection point at the time TMH implemented concurrent review. Results: Composite scores for TMH overall showed significantly increasing trends in the composite scores for the time period January 2006 andApril 2008 (pϽ.0001). TMH increased at a faster rate (pϭ0.0013) and these trends further increased significantly between May 2008 and August 2009 for TMH, following implementation of concurrent review (pϽ.0001). The difference between these increases was statistically significant (pϽ.0001). Conclusions: Concurrent review at TMH provides an advantage and improves stroke center measures over time.

Author Disclosures: J.T. Machan: None. C. Gomes McGillivray: None.

W P291 In-house Stroke Code Team Leads To Quicker Assessment, Evaluation And Treatment Of Acute Strokes

Sheila Erickson, Tracy Plume, Gail Lighthizer, Erin Ward; Sharp Grossmont Hosp, La Mesa, CA Background and Purpose: After researching best practice it was decided a unit specific to the care and treatment of the acute stroke patient would greatly improve outcomes and help in the prevention of secondary stroke. Sharp Grossmont Hospital designated a stroke specific unit in 2005; February 2006 the hospital obtained Joint Commission (JC) certification as a stroke center. During the establishment of the unit research was also found that indicated 6.5 to 15% of first time strokes occur in patients already hospitalized for other reasons. There was a fine-tuned algorithm for managing stroke patients presenting to the ED, the same rapid assessment plan did not exist for patients suffering a stroke while already in the hospital. The concept of an In-House Stroke code was born to improve recognition, early intervention, and treatment of stroke in the in-patient population. As a result of our efforts the hospital received the Silver Plus 'Get With the Guidelines' for stroke awards in October of 2009. During the JC recertifications in 2008 and 2010 the hospital received no recommendations for improvement. Methods: Stroke unit nurses educated nursing staff throughout the hospital on the recognition of stroke and how to activate the in-house stroke code prior to implementation and yearly there after. The physicians and ancillary staff where educated as well. To activate the hospital emergency response system the nurse dials *** when a stroke is suspected on other units. The hospital operator pages the on call neurologist and stroke code nurse as well as CT, Lab, EKG, and X-Ray. The stroke code nurse immediately evaluates the patient then collaborates with the on call neurologist to decide the appropriate actions. The patient is then given priority in obtaining a CT scan and a stat lab panel is drawn to evaluate for early intervention and eligibility for t-PA. Results: Since implementation of an in-house stroke code procedure in 2005, 110 potential stroke patients have been identified and transferred to the stroke unit ensuring that these patients benefited from best practice in stroke care. There has also been an increase in the number of in-house patients treated with t-PA. In the four years since implementation, 16 patients have received t-PA compared to only four patients in the five years prior to the in-house stroke code program. In 2008, 83% of in-house stroke patients were evaluated in less than 15 minutes either by phone or at bedside by a neurologist. Conclusion: Success of the program is evidenced by the increase in early recognition, evaluation and treatment of in-house strokes. Bedside nurses are knowledgeable about the signs and symptoms of stroke and how to activate a stroke code rapid response team dedicated to this population of patients Author Disclosures: S. Erickson: None. T. Plume: None. G. Lighthizer: None. E. Ward: None.

W P292 Baptist Hospital of Miami: Our Multidisciplinary Collaborative Journey to Primary Stroke Certification

Marguerite Guignard, Baptist Hosp of Miami, Miami, FL; Baptist Hosp of Miami Stroke Team Members, Maria Gauthreaux; Baptist Hosp of Miami, Miami, FL Baptist Hospital of Miami: Our Multidisciplinary Collaborative Journey to Primary Stroke Certification. Background and Issue: We hold the statement, 'Time is Brain' as our daily mantra in providing efficient and quality stroke patient care. Baptist Hospital of Miami, a Magnet Hospital, has developed a multidisciplinary collaborative approached to stroke care. In our pursuit of primary stroke certification, we have designed our processes to provide the most efficient quality care for stroke patients. Through the development of the Baptist Emergency Stroke Team (B.E.S.T.), we have developed an immediate response to care for stroke patients regardless of point of entry or location within the hospital. The stroke response is coordinated and led by a B.E.S.T. Responder Registered Nurse from the Neuroscience Unit who receives training on the National Institute of Health (NIH) Stroke Scale. A team of doctors and nurses initiate and complete laboratory, imaging, consultations, medication administration and provide interventional services in the appropriate timeframe as required by the Clinical Practice Guidelines of the American Heart Association and The Joint Commission. Through the inclusion and collaboration with departments such as, Laboratory Services, Rehabilitation Services, Care Management Services, and many others on Neuroscience Committees, we have been able to provide a continuum of care that has contributed greatly to our certification as a Primary Stroke Care Center. Purpose: To share our outcomes and multidisciplinary collaborative approach to stroke care at Baptist Hospital of Miami. Method: The performance metrics for the Baptist Hospital Stroke Program focus on the National Hospital Stroke Quality Measures and the turnaround performance times required by our clinical guidelines and The Joint Commission. The program uses quantitative data collection methods to analyze both performance metrics to evaluate our success and opportunities for improvements. Results: Through ongoing improvements of our stroke algorithms and analysis of our performance data, we have seen significant improvements in our national quality data and turnaround performance times. Our National Hospital Quality Stroke Measures goal is ninety percent compliance for all measures. We have been able to maintain this goal since March, 2010. Our turnaround performance times have also shown significant improvements achieving and in some areas exceeding the best practice, in all but two areas as of May 2010. Conclusion: Through exemplary multidisciplinary collaboration, we received our official notice of Primary Stroke Certification without recommendations for improvements on June 17 th , 2010 by the Joint Commission. We were strongly encouraged to publish and present our program and it's outcomes at conferences to help other organizations become certified.

Author Disclosures: M. Guignard: None. M. Gauthreaux: None.

W P293 Partnership for Stroke How an Honor Roll Top 20 Hospital System, an East Texas Community Hospital, and a Foundation, created a Primary Stroke Center. The Journey

Suzanne Monsour, Univ of Pittsburgh, Pittsburgh, PA; Kim Deaton, Texas A&M Univ, College Station, TX; Raegan Jones, Our Lady of the Lake, San Antonio, TX; Amber Loggins, Le Mar, Beaumont, TX; Jan Flewelling, Univ of Houston, Houston, TX; Joan Censullo; Georgetown Univ, Washington, DC Backround: The East Texas region has been identified as having a 'need' for quality stroke care in view of stroke incidence and mortality rates. This region is located in the 'Buckle' of the proverbial Stroke Belt. Additionally, this region along with the border communities of Texas, have high rates of uninsured and underserved populations. The East Texas Stroke Initiative is a project funded by the TLL Temple Foundation, and pairs Memorial Health System East Texas ( a small non-profit community hospital system located in Lufkin, Texas), with The Methodist Hospital-Houston to create a Joint Commission certified Primary Stroke Center, to implement a widespread community education initiative for stroke prevention, and to reduce the devastating effects of stroke for the residents of the East Texas community and their families. The ultimate goal would create a 'ripple effect' from Lufkin, Texas across the entire region, dedicated to improving the health of the residents of the beautiful 'piney woods'. Need The stroke prevelence rate in Angelina County, which is where Lufkin is located is 5.2% compared to the state rate of 2.8%. The incidence of smoking and high cholesterol are a full 6 percentage points above the state rates. Other modifiable risk factors are just above, or just below the state rates. Age adjusted mortality rates in Angelina County are double for gender, both male and female and race, both caucasion and african american. This is not a voluntary project-but a medical emergency! Partnering The t-PA administration rate for the region was .003% at project initiation, and .007% for Memorial. The project married The Methodist Hospital, specifically the expertise of the Eddy Scurlock Stroke Center with Memorial Health System East Texas, to see what could be done to remedy the situation. Through project management, education both in-hospital and community-wide, quality initiatives, performance improvement, best practices modeling, evidence-based medicine, and good old fashioned dedication and hard work, the Stroke Program in Lufkin, was certified on August 16, 2010 with a 'clean' report, and praise from the surveyor. Almost 6,000 individuals have received stroke education in a variety of venues and a variety of ways. The surveyor stated that; 'It is the best community education initiative I have seen'. The t-PA administration rate closed the year 2009 at 5%, and through June, 2010 rests at 6.25%. The program has received an 2010 Outstanding Program Award, by the Texas Council on Cardiovascular and Stroke-one of only four outstanding awards given. Summation We would very much like to tell our story, and what our journey entailed. We are proud of the accomplishments thus far, and grateful for the opportunity that the TLL Temple Foundation provided. Maybe it will help reduce the human and financial toll, and give others the initiative and motivation to partner and succeed.

Author Disclosures: S. Monsour: None. K. Deaton: None. R. Jones: None. A. Loggins: None. J. Flewelling: None. J. Censullo: None.

W P294 Project To Improve Availability Of Stroke Patient Satisfaction Data And Capture Perceptions Of Care During Hospitalization

Melissa Richardson; Univ Hosps Geauga Med Cntr, Chardon, OH Background and Purpose: In addition to the stroke committee's existing process for evaluating the hospital's stroke program through the American Heart Association's Get With the Guidelines Performance Measures, it was identified that an effective method for obtaining disease specific patient satisfaction data was needed. Because such data represents the patient's perception of the stroke program, it would offer significant insight regarding the delivery of stroke care through the eyes of the person who matters most -the patient. In an attempt to obtain patient satisfaction data, Press Ganey results were pulled and reviewed based on the DRG for stroke. This process revealed minimal data on which to base improvements to the program. The purpose of this project was to identify a process to obtain more patient satisfaction data and thus develop performance improvement projects for the stroke program.

Methods: A process existed for a Registered Nurse to contact patients after discharge for the purpose of assessing potential clinical needs, specifically medication compliance, ability to make follow up appointments, and support/services at home. This provided an opportunity to reinforce stroke education as well as assist the patient with needed community resources, such as transportation issues and prescription assistance. It was decided to also use this telephone call to ask patients about their satisfaction with, and perceptions of, care received during the hospital stay. Five questions were developed relating to stroke care, including education, participation in discharge planning, communication by nurses and physicians, services provided by the rehabilitation department, and recommendation of hospital for stroke care. These questions were asked during the follow-up telephone calls placed between 4-5 weeks after discharge. Results: Significant improvement in obtaining patient satisfaction data was identified. Comparing 1 st and 2 nd quarters of 2009 with 2010, the committee saw an increase from 3 satisfaction surveys using the Press Ganey surveys (7% of stroke patients) to 20 satisfaction surveys using follow-up telephone calls (43% of stroke patients). This represents an increase of 36%. From the responses in 2010, the stroke committee was able to identify performance improvement projects specific to stroke education and communication. Conclusions: The project to ask additional questions related to patient satisfaction during follow-up telephone calls provided the stroke committee with an increase in responses and feedback from stroke patients. This supplied the stroke committee with meaningful data on which to develop performance improvement projects relevant to the patient experience.

W P300 Prognostic Value of Silent Brain Infarcts and Leukoaraiosis Following First-Ever Ischemic Stroke in Young Adults

Jukka Putaala, Elena Haapaniemi, Minna Kurkinen, Helsinki Univ. Central Hosp, Helsinki, Finland; Oili Salonen, Helsinki Med Imaging Cntr, Helsinki Univ. Central Hosp, Helsinki, Finland; Markku Kaste, Turgut Tatlisumak; Helsinki Univ. Central Hosp, Helsinki, Finland Background: Prior findings are conflicting regarding the impact of silent brain infarcts (SBIs) and leukoaraiosis (LA) on outcome after ischemic stroke. Moreover, prognostic relevance of silent brain infarcts and leukoaraiosis in young ischemic stroke patients is largely unknown. Methods: We included consecutive MRI-scanned patients aged 15 to 49 with first-ever ischemic stroke treated in the Helsinki University Central Hospital, 1994-2007 (the Helsinki Young Stroke Registry). Follow-up was conducted between November 2009 and January 2010. Stroke severity was assessed with the NIH Stroke Scale and etiology classified according to TOAST criteria. Outcome measures were (1) nonfatal or fatal ischemic stroke, (2) composite endpoint of any nonfatal or fatal vascular event, and (3) death of any cause. Results: Of our 655 patients (mean age 40.0Ϯ8.0; 58.8% males; mean follow-up in surviving patients 8.7Ϯ3.8 years), 86 (13.1%) had SBIs and 50 (7.6%) LA. Cumulative risks of recurrent ischemic stroke (28.1% at 10 years; log rank PϽ0.001) and composite vascular endpoint (34.7%; Pϭ0.003), but not of mortality (13.8%; Pϭ0.054), were higher in patients with SBIs compared with those without SBIs (10-year risks 11.0%, 19.4%, and 9.0%, respectively). Cumulative risks of recurrent ischemic stroke (21.2% at 10 years; Pϭ0.031) and mortality (31.9%; PϽ0.001), but not of composite vascular endpoint (30.0%; Pϭ0.088), were higher in patients with LA than in those without LA (10-year risks 12.3%, 8.4%, and 20.5%, respectively). SBIs were independently associated with risk of recurrent ischemic stroke (odds ratio 1.92; 95% confidence interval 1.10-3.36) adjusted for age, gender, risk factors, stroke subtype, and presence of LA. LA was, in turn, associated with increased risk of death (3.87; 2.05-7.31) after adjustment for age, gender, risk factors, initial stroke severity, subtype, and presence of SBIs. Neither SBIs nor LA associated with the composite vascular endpoint. Conclusions: SBIs were predictor of recurrent ischemic stroke whereas LA was associated with increased long-term risk of death in young adults after first-ever ischemic stroke. These relationships persisted after adjustment for important prognostic factors such as age, stroke severity and subtype, and diabetes.

Author Disclosures: J. Putaala: None. E. Haapaniemi: None. M. Kurkinen: None. O. Salonen: None. M. Kaste: None. T. Tatlisumak: None.

W P301 Patterns of Antihypertensive Medication use and Persistence in Stroke patients

DaiWai Olson, Duke Univ, Durham, NC; Cheryl Bushnell, Wake Forest Univ, Winston Salem, NC; Margueritte Cox, Eric Peterson; Duke Univ, Durham, NC Background: Current guidelines recommend diuretics and angiotensin-converting enzyme inhibitors (ACE-I) as antihypertensive medications of choice for stroke secondary prevention. We evaluated stroke prevention blood pressure regimens after stroke in the Adherence eValuation in Acute Ischemic stroke_Longitudinal (AVAIL) registry to determine patterns of antihypertensive medication use at discharge, and up to 1-year post-discharge. Methods: The AVAIL registry is a prospective observational study of medication persistence following hospital discharge from an acute stroke or TIA. Medication persistence was determined via telephone by trained interviewers at 3 months and 12 months. Patient, provider, and system-level factors associated with persistence with antihypertensive classes of drugs at 12 months were modeled using logistic generalizing estimation equations (GEE). Results: The analysis included 2,007 AVAIL subjects enrolled at 101 sites participating in GWTG_Stroke who were discharged on any blood pressure medication. Of those prescribed antihypertensive medications, beta blockers were most commonly prescribed (56.1% or nϭ1140), whereas 52.2% (Nϭ1062) were prescribed ACE-I and 34.9% (Nϭ709) diuretics. Medication use at discharge, 3 months, and 12 months for each class are shown in the figure. Persistence at 3 and 12 months was 81.1% and 64.7%, respectively for ACE-I and 74.2% and 60.6% for diuretics. Factors independently associated with 12-month persistence with ACE-Is and diuretics include prior blood pressure medication use (ACE-I: OR 1.52; 95% CI 1.13-2.06; Diuretics: OR 2.00, 1.11-3.63) understanding how to refill medications (1.97, 1.09-3.40; 2.96, 1.36-6.02), and why medications are taken (OR1.53, 0.96-2.43; OR 2.24, 1.10-4.56). Working status was associated with persistence with ACE-Is (OR 1.56, 1.09-2.24) but associated with non-persistence with diuretics (OR 0.59, 0.36-0.98). Conclusions: Despite evidence-based guidelines, diuretics, in particular, are least prescribed at discharge and have the lowest long-term persistence of any antihypertensive class. Patient experience with antihypertensive medications prior to the stroke, and knowledge about why specific classes of medications are taken and how to refill them are important indicators of long-term use.

W P302 Pharmacist Telephone Interventions Improve Adherence to Stroke Preventive Medications and Reduce Stroke Risk Factors: A Randomized Controlled Trial

Viet-Huong V Nguyen, John Poon, Lisa Tokuda, Jeffrey Sayers, Roi-Ann Wallis, Sunita Dergalust; VA Greater Los Angeles, Los Angeles, CA Background: Adherence to stroke preventive medications and reduction of stroke risk factors have been shown to significantly reduce the recurrence of stroke. Our objectives were to determine if a telephone intervention conducted by a clinical pharmacist could improve medication adherence in stroke patients and optimize stroke prevention goals. Methods: Patients with a history of stroke were recruited from stroke clinic and randomized to a pharmacist intervention group or a usual care group. Patients in the pharmacist intervention group received telephone follow-up calls at 3 months and 6 months from time of randomization. The telephone follow-up call included evaluation of medication adherence based on pharmacy refill history as well as continuing stroke education and reassessment of stroke prevention goals with the patient. Recommendations for medication therapy and relevant clinical studies or laboratories were communicated to the primary care provider and/or stroke provider when appropriate. Results: Thirty patients were enrolled in the trial. At the end of 6 months, patients in the pharmacist intervention group were more likely to be fully adherent to all medications compared to the usual care group (56% vs. 36%). Adherence to antithrombotics specifically was also increased in the pharmacist intervention group at 6 months ( 100% vs. 88%). Patients in the pharmacist intervention group were also more likely to achieve stroke prevention goals than patients in the usual care group including blood pressure goals (73% vs. 57%), LDL-C goals (75% vs. 50%), and blood glucose control (75% vs. 50%). These improvements were maintained and actually continued to improve at one year. At one year, 88% of patients in the pharmacist intervention group were able to achieve blood pressure goals, 80% were able to achieve LDL-C goals, and 80% were able to achieve blood glucose goals. Only 54% percent of patients were able to achieve blood pressure, LDL-C, and blood glucose goals in the usual care group at one year. Conclusions: A telephone intervention conducted by a clinical pharmacist has significant impact on medication adherence and can optimize achievement of stroke prevention goals. Furthermore, the intervention has long-lasting effects as seen at one year. These findings suggest that clinical pharmacists should play a definitive role in secondary stroke prevention and can greatly improve quality of stroke care.

Author Disclosures: V.V. Nguyen: None. J. Poon: None. L. Tokuda: None. J. Sayers: None. R. Wallis: None. S. Dergalust: None.

W P303 Effect of Medications on Outcome after Ischemic Stroke

Brett M Kissela, Heidi Sucharew, Kathleen Alwell, Charles J Moomaw, Daniel Woo, Pooja Khatri, Matthew L Flaherty, Opeolu Adeoye, Samir Belagaje, Simona Ferioli, Joseph P Broderick, Dawn Kleindorfer, Christopher J Lindsell; Univ of Cincinnati, Cincinnati, OH

Introduction:

We previously derived a model using variables available to the clinician on day 1 post stroke to predict 3 month functional outcome (assessed by the modified Rankin Scale, mRS). The model included age, diabetes, severe white matter disease, pre-and post-stroke functional status, and stroke severity; mRS was further modified by occurrence of comorbid medical conditions. Whether the predicted mRS is affected by the comorbidities or the medications used to treat these conditions has not been elucidated. Goldstein et al showed that some classes of medications significantly impact post-stroke outcomes without considering the associated medical comorbidities. Following Goldstein's findings, we hypothesized that benzodiazepines and anticonvulsant would be associated with worse outcome, while antidepressants and stimulants would be associated with better outcomes after adjusting for known confounders. Methods: We used data from a cohort of 460 patients with an ischemic stroke that occurred in 2005 and for whom 90 day survival and mRS were available. Medications being taken at 3 months were divided into medication classes similar to those of Goldstein. We included whether or not a patient received a medication from within each class into our model of post-stroke outcome to ascertain its contribution to outcome variability. Given the large number of medication classes examined (30), a conservative critical p value would be Ͻ 0.0017 for any individual medication class. Results: Patients were 48% female, 25% black and mean age was 67 years. Common drug use in this cohort included antiplatelet agents (82%), statins (54%), beta blockers (48%), ACE inhibitors (42%), proton pump inhibitors (36%), diuretics (35%), calcium channel blockers and anticoagulants (29% each), and antidepressants (25%); benzodiazepines (8%) and stimulants (2%) were less commonly used. No class had a significant effect on 3 month mortality. Anticonvulsants were associated with worse functional outcome (p ϭ 0.0026), while antidepressants and stimulants were also associated with worse outcome (p ϭ 0.026 and 0.0054 respectively). These medication classes explained between 5 and 10% of outcome variability (associated R2 of 0.06-0.10). No medication classes were significant at the Bonferroni corrected critical p value. Conclusions: Our results do not match those of Goldstein et al. We cannot rule out that medication use is important, but medications may be a surrogate for medical comorbidities, which are highly associated with outcomes. Further research in this area is needed to clearly define the independent effects of medications on post-stroke outcomes.

W P304 Early And Late Recurrence After Ischemic Stroke; What Is the Difference?

Nayoung Kim, Soo Hyun Park, Mi Hwa Yang, Myung Suk Jang, Chang Wan Oh, Sang Yun Kim, Moon-Ku Han, Seoul National Univ Bundang Hosp, Seongnam-si, Korea, Republic of; Wook-Joo Kim, Ulsan Univ Hosp, Ulsan-si, Korea, Republic of; Youngchai Ko, Eulji Univ Hosp, Daejeon-si, Korea, Republic of; Jung-Hyun Park, Dongguk Univ Gyeongju Hosp, Gyeongju-si, Korea, Republic of; Kyung Bok Lee, Soonchunhyang Univ Hosp, Seoul-si, Korea, Republic of; Hee-Joon Bae; Seoul National Univ Bundang Hosp, Seongnam-si, Korea, Republic of Background & objective: Recurrence is a major determinant of prognosis after stroke. It has been suggested that early and late recurrence have different risk factors. However there were few MRI-based studies comprising both early and late recurrence. The purpose of this study is to elucidate recurrence rates captured from immediately after stroke onset and to characterize the difference between early and late recurrence. Methods: From a prospective stroke registry, a consecutive series of patients, who were hospitalized due to ischemic stroke within 7 days from onset between November 2006 and February 2010, were collected. Each patient's clinical status was followed up to 1 year after onset. Recurrence was categorized into early (Յ 21 days from onset) and late (Ͼ21 days from onset). Early recurrence was defined as any new neurologic deficits, which occurred after a period neurologic stability or improvement lasting at least 24 hours and were not attributable to edema, mass effect, hemorrhagic transformation, or other medical causes or which were confirmed by a new discrete lesion outside the index lesion on subsequent diffusion MRI. Late recurrence was defined same as for the index stroke. The cumulative risk of the recurrence was calculated using the Kaplan-Meier method and the clinical characteristics of patients with early recurrence were compared to those with late recurrence. Results: Among 1726 patients (age, 67.4Ϯ12.9 years; male, 58.5%), 164 (9.5%) had experienced a recurrent stroke. The cumulative risk of recurrence was 4.6% at 7 days, 5.5% at 21 days, 6.9% at 3 months, 7.9% at 6 months and 9.7% at 1 year. More than half of recurrence within one year after onset developed in the early period compared to the late (5.5% vs. 4.1%). Patients with early recurrence were more likely to have large artery atherosclerosis and to receive thrombolytic treatment than those with late recurrence (p'serosclerosis (3.37; 1.42 to 8.00), and thrombolytic treatment (2.55; 1.53 to 4.26) increased the risk of early recurrence, while age (1.02; 1.00 to 1.05) and history of stroke or transient ischemic attack (1.70; 1.02 to 2.84) raised the risk of late recurrence. Conclusions: This study shows that the risk of recurrent stroke is highest in the first week and rapidly declines after then. And it suggests that large artery atherosclerosis and thrombolytic treatment increase the risk of recurrence just after stroke onset, whereas previous history of stroke does in the later stage. This can be linked to the necessity of the different prevention strategy as time goes after stroke.

of [2003][2004] Medicare claims data showed a 30-day readmission rate of 19.5% for all conditions. Centers for Medicare and Medicaid services may reduce reimbursements for hospitals with higher 30day readmission rates. Hypothesis: Stroke patients are disabled and may need readmissions for non-neurological conditions such as infections and falls. We sought to determine the frequency and causes of readmissions for ischemic stroke patients. Methods: Consecutive patients admitted to a JCAHO certified primary stroke center with a diagnosis of ischemic stroke or transient ischemic attack (TIA) over nine months were included. Electronic records were reviewed and data regarding demographics, TOAST mechanism, stroke risk factors, treatments administered and discharge outcome in terms of disability and discharge destination were collected. Charts were reviewed up to 30 days after discharge for readmissions to any hospital within the same healthcare system. In case of readmissions, the reason for admission and outcomes in terms of disability and discharge destination were determined. Results: In all, 265 patients (50.9% male; 79.6%African American; mean age 60.9 years) were included in the study. There were 205 (77.4%) radiologically confirmed strokes and 60 (22.6%) TIAs. Thirteen (5%) patients died during their first admission. Of the remaining 252 patients, 25 (9.9%) were readmitted within 30 days. The reason for readmission was determined to be neurological in 8/25 patients (32%; 4 ischemic strokes, 1 hemorrhagic stroke and 3 TIAs); and non-neurological in 17/25 patients (68%). The frequent non-neurological reasons for readmission were infections (6/25), metabolic/electrolyte disturbances (3/25) and trauma related to falls (2/25). The patient's age, race, TOAST mechanism, use of intravenous tPA or interventions, use of antiplatelets or statins, and traditional stroke risk factors did not predict readmission. Patients who were readmitted were more likely to have coronary artery disease (CAD) and congestive heart failure (CHF) than those who were not readmitted (45.5% vs 14.7%; pϭ 0.001 for CAD and 22.7% vs 8.8%; p value ϭ 0.05 for CHF) An NIH stroke scale Ն10 predicted readmission (p value 0.02). Patients discharged home or to acute rehabilitation units were less likely to be readmitted than those discharged to subacute rehabilitation units or nursing homes (p valueϭ0.01). Conclusion: Disabled ischemic stroke patients and those with cardiac disease are more likely to be readmitted, and the reason is often non-neurological. Demographic features, conventional risk factors, stroke mechanism and treatments administered do not help us predict readmission.

Author Disclosures: P. Bhattacharya: None. D. Khanal: None. R. Madhavan: None. S. Chaturvedi: None.

W P306 Clinical-Radiological Severity Mismatch Phenomenon: Patients with Severe Neurological Deficits without Matching Infarction on Computed Tomographic Scan

Adnan I Qureshi, M. Fareed K Suri, Mustapha A Ezzeddine; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Objective: To determine the long-term outcome of patients with severe neurological deficits without a large infarction on computed tomographic (CT) scan. Background: Anecdotal observations suggest that some patients can manifest severe neurological deficits associated with small volume of cerebral infarction. Methods: We analyzed the prospectively collected data as part of the randomized, placebo controlled trial in patients with ischemic stroke presenting within 3 hours of symptom onset. Volume of infarction was measured from CT scan acquired at 3 months. Favorable outcome defined by no significant or slight disability on modified Rankin scale at 12 months. We determined the outcome of patients with National Institutes of Health Stroke Scale score (NIHSSS) Ն 10 at 24 hours after symptom onset with infarct volume of less than 20 cc. Results: Of the 598 patients who had 12 month outcome data available, 91 (15%) met the criteria of clinical-radiological severity mismatch (mean age Ϯ standard deviation of 65Ϯ12;51% were men). Compared with patients with NIHSSS Ն10 with infarct volume Ն20 cc, the patients with NIHSSS Ն10 and infarct volume Ͻ 20 cc were older (mean age 65 versus 69 years, pϭ0.009) but there was no difference in the gender, race or vascular risk factors. Patients with clinical-radiological severity mismatch were more likely to have a favorable outcome at 12 months compared with those without mismatch (21 % versus 3.3%, PϽ0.001). Conclusion: We observed that approximately one-fifth of patients have clinical-radiological severity mismatch. Such patients appear to have a high rate of favorable outcomes at 1 year.

Author Disclosures: A.I. Qureshi: None. M.K. Suri: None. M.A. Ezzeddine: None.

W P307 Validation of a Model Predicting Post-stroke Outcomes

Brett M Kissela, Univ of Cincinnati, Cincinnati, OH; Heidi Sucharew, Cincinnati Children's Hosp, Cincinnati, OH; Kathleen Alwell, Charles J Moomaw, Daniel Woo, Pooja Khatri, Matthew L Flaherty, Opeolu Adeoye, Univ of Cincinnati, Cincinnati, OH; Samir Belagaje, Emory Univ, Atlanta, GA; Simona Ferioli, Joseph P Broderick, Univ of Cincinnati, Cincinnati, OH; Jane Khoury, Cincinnati Children's Hosp, Cincinnati, OH; Dawn Kleindorfer, Christopher J Lindsell; Univ of Cincinnati, Cincinnati, OH Introduction: We previously derived models predicting short and long term mortality and functional outcome (assessed by the modified Rankin Scale, mRS) based on a cohort of 451 ischemic stroke patients identified in 1999. The models were designed to address questions frequently posed by stroke patients and their families about survival and outcome in the short and long term, and included data readily available to the clinician. For example, the model for 3 month mortality included age and pre-stroke disability, while the model for 3 month mRS included age, diabetes, severe white matter disease, pre-and post-stroke functional status, and stroke severity. We sought to validate these models in an independent cohort of 460 ischemic stroke patients identified in 2005. Methods: The Greater Cincinnati/Northern Kentucky Stroke Study is a population based stroke epidemiology study that ascertains all ischemic strokes in our region every 5 years. Cohorts of physician-confirmed ischemic stroke subjects were prospectively recruited during 1999 and 2005 to study factors related to outcomes. We validated 4 models that predicted: 3 month mortality and mRS, and long term mortality and mRS. Long term mortality and mRS were assessed at 4 years in the derivation cohort, and at 3 years in the validation cohort. Logistic regression and generalized linear models were used to predict mortality and functional outcome, respectively. Models were first tested by predicting outcomes in the 2005 validation cohort using the 1999 model parameter estimates. The predicted and observed outcomes were compared; the C-statistic or R 2 were used as measures of model fit. Subsequently, we refit the models allowing parameter estimates to vary but retained the same variables, and model fit was again assessed. Results: The validation cohort of 460 subjects with ischemic stroke was 48% female, 25% black. Mean age was 67 years. A total of 431 subjects survived to 3 months and 393 of these had a 3 month follow up mRS; 345 survived to 3 years and 172 of these had 3 year follow up mRS. Results are shown in the table. The model fit was similar in the validation cohort as the derivation cohort. Model performance was not significantly improved when parameters were allowed to vary. Conclusions: The simple models previously derived for predicting post-stroke outcomes performed well in an independent cohort. While a significant proportion of behavior remains unexplained, outcomes epidemiology allows us to build models that provide insight into important factors determining post-stroke survival and functional outcome. Background: 'Home Time' (HT) refers to the number of days over the first 90 after stroke onset that a patient spends residing in their own home or relative's home, versus any institutional care. It is an accessible and objective parameter, free from subjective bias, with potential as an outcome measure in acute stroke trials. We sought to validate HT and assess treatment responsiveness using independent data. Methods: We estimated HT in the SAINT I neuroprotection trial. We compared outcomes between thrombolysed (T) and non-thrombolysed comparators (C) employing HT and modified Rankin Scale (mRS). For our primary analysis we adjusted for baseline covariates that significantly influence HT, and in sensitivity analyses considered all variables that differed between groups at baseline. We report ordinal logistic regression and analysis of covariance with 95% confidence intervals (CI). We describe the relationship of HT with baseline NIHSS and its components and with day 90 mRS and Barthel Index. Results: SAINT I included 1699 patients from 23 countries, of whom 28.7% received alteplase. Home Time was explained by age, baseline severity, alteplase use, side of ischemic lesion, presence of diabetes, and country of patient enrolment (each PϽ0.05). We found an association between use of alteplase with better adjusted outcomes by either measure: odds ratio for extended HTϭ1.36, 95% CIϭ1.08-1.72, pϭ0.009; ANCOVA pϭ0.007 with 5.5 day advantage; odds ratio for more favorable mRS ϭ1.6, 95%CI 1.28-2.00, PϽ0.0001, CMH pϭ0.046. HT was significantly associated with baseline NIHSS and each component of NIHSS except level of consciousness, dysarthria and ataxia. HT was significantly associated with day 90 mRS and Barthel index. Conclusions: Home Time is a responsive measure for use in multinational acute stroke trials. Its inclusion as a complementary outcome is reasonable. We propose treatment effects are adjusted for age, baseline NIHSS, side of stroke lesion, country of enrolment, and the presence of diabetes.

W P308 Home Time Is Extended In Ischemic Stroke Patients Who Receive Thrombolytic Therapy: A Validation Study Of Home Time As An Outcome Measure

W P309 Return Home: A Practical Measure of IV-tPA Efficacy

Don B Smith, Colorado Neurological Institute, Englewood, CO; Paul Murphy, Colorado Stroke Alliance, Denver, CO; William Jones, Ethan Cumbler; Univ of Colorado, Aurora, CO Introduction/Hypothesis: Years after regulatory approval, debate lingers about the effectiveness of intravenous tissue plasminogen activator (tPA) for acute ischemic stroke, perhaps because standard outcome measures (clinical outcomes at 3 months) are logistically & economically challenging. Alternative outcomes may be useful in monitoring tPA's effectiveness. Methods: We queried the Ͼ8,700 ischemic strokes in the Colorado Stroke Registry (CSR), to see whether tPA affects the likelihood of home discharge (DC-Home). Selected patients arrived from the scene by EMS or private means, had onset in a community setting between 1/1/06 and 5/31/10, and had data on DC & tPA status. We excluded transfers between other hospitals and intra-arterial or research treatments. We used recursive partitioning to select cut points for variables in a logistic model of DC-Home. Results: 5,550 patients met inclusion/exclusion criteria. Our model included: age, National Institutes of Health Stroke Scale (NIHSS), arrival by private means rather than by EMS, and whether tPA was given. Data were missing in at least one field (almost exclusively NHISS) in 49% of records. These were excluded from multivariant analysis. No values were imputed or assigned. The analysis was based on complete data from 2,812 patients. Of them, 415 (14.7%) received IV-tPA & 1443 (51.3%) were DC-Home. The model's discrimination was good (AUC; 95% CI ϭ 0.81; 0.795-0.825). In unadjusted analysis, tPA was negatively associated with DC-Home: OR; 95% CI ϭ 0.71; 0.59-0.85. However, in the multivariate model it was positively associated: OR; 95% CI ϭ 2.03; 1.54-2.67. This gives a risk ratio (95% CI) of 1.36 (1.2-1.48), increasing the probability of DC-Home from 52.4% to 71.4%. The number-needed-to-treat (NNT) is 5.3. Conclusions: Standard measures of tPA effectiveness are often unavailable. DC information is more readily available, and calling DC-Home a "good outcome" is reasonable, when the alternatives are rehabilitation, nursing facility, hospice or death. Thrombolysis is more likely to be administered to severe strokes. These are less likely to allow DC-Home, but when data are adjusted for age and stroke severity, the NNT for DC-Home is similar to the value for 3-month clinical outcomes, suggesting DC-Home may be a practical measure of tPA efficacy. Our conclusions are tempered by recognition of limitations that include the observational nature of our data and the incidence of missing data for NIHSS (particularly in non-treated patients). Additional analysis does not indicate that missing NIHSS values would alter our conclusions, but we cannot exclude the possibility. Finally, ours is a less-than-perfect model. There may be other determinants of DC-Home that would alter our results. We encourage others to attempt to replicate our findings with independent data.

W P310 Concurrent Validity of the National Stroke Project Stroke Severity Score

Nada El Husseini, Larry B Goldstein; Duke Univ Hosp, Durham, NC Background: The National Stroke Project (NSP) is a retrospective cohort of Medicare beneficiaries hospitalized with stroke or TIA. The NSP included an assessment of stroke severity (NSP-SS) that can be easily extracted from the medical record based on summing the number of up to four impairment domains (vision, speech, motor and sensation; range 0-4). The scale may be useful to adjust for stroke severity in outcome studies primarily using administrative data. Purpose: We aimed to determine the concurrent validity of the NSP-SS in comparison to the NIH-Stroke Scale (NIH-SS), a widely used and validated ischemic stroke impairment level scale. Methods: The NSP-SS and NIH-SS were retrospectively determined from the records of the same initial Emergency Department (ED) or in-hospital neurological examinations of 100 consecutive patients with a final diagnosis of ischemic stroke. The NIH-SS score was assigned using a previously validated algorithm. Values are meansϮSD. Results: The patients mean age was 66.9 Ϯ15.9 years (49% women; 33% African American; 75% initially evaluated in the ED.; NIH-SS range 0-22, mean 7Ϯ5, median 6; NSP-SS range 0-4, median 2,IQR(1-3). Agreement between the scores was moderate (Spearman rϭ0.65, 95% CI (0.52 -0.76) PϽ0.0001). When the scale results were dichotomized (NSP 0-1 mild, 2-4 severe; NIH-SS Ͻ6 mild, Ͼ6 severe), the two scales were concordant for 68% of cases; 27% of NSP-SS severe patients were mild based on the NIH-SS; 5% of NSP-SS mild patients were categorized as severe based on the NIH-SS. Logistic regression (dichotomized NSP-SS) found that 27% of the variance in the NSP-SS was explained by the NIH-SS (r 2 ϭ0.27; pϽ.0001). Conclusion: Although the correlation between scales was only moderate, the full NSP-SS may be useful as an adjustment for initial stroke severity for stroke outcome studies. The adjustment, however, may be compromised by differences in patient populations related to impairment domains not fully captured by the NSP-SS (e,g.level of consciousness, aphasia vs. dysarthria, hemispatial neglect). This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: N. El Husseini: None. L.B. Goldstein: None. ; in these circumstances information is derived from interview with a proxy. The properties of proxy assessment have not been described. Methods: Over a five week period, a team of undergraduate students trained and certified in mRS assessed a convenience sample of consenting stroke survivors at a University Hospital. Using a standard mRS approach, paired researchers (blinded to each other's scores) performed independent interviews of patients and appropriate proxies. Reliability was described using kappa statistics (with 95 % confidence interval [CI] ) and percentage agreement with chi-square testing. Results: Seventy-nine stroke survivors were assessed (median age 79 years [IQR:72-85]). Proxies were family members, nurses or physiotherapists. Median mRS from patient derived interview was 3 (IQR:2-4); median mRS from proxy derived interview was 3 (IQR:2-4). Inter-observer variability for assessment of stroke survivors was moderate and similar to previous studies of mRS reliability (kϭ0.54, CI:0.65-0.75), [67% matched]. Inter-observer variability for paired assessment of proxies was moderate (kϭ0.40 CI:0.36-0.46), [52% matched], with greatest variability in therapist interviews(Table ) but no difference in overall agreement rates (pϭ0.53). Comparing scores from patient and proxy interview, suggested no difference between groups in patient agreement (pϭ0.76); kappa statistics described overall agreement as fair (kϭ0.28, CI:0.24-0.32) [45% matched], with poorest agreement for therapist derived proxy scores (Table ). Conclusions: Proxy derived mRS scores may differ from direct assessment of stroke survivors and trialists should be cautious in interpretation of these scores. Of the various parties that may be used for proxy assessment, no group was significantly more reliable or valid in their assessment, although there was a trend towards less variability with nurse derived scores. Table : Reliability of paired assessments of mRS pϾ Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

W P311 Reliability and Validity of Proxy Derived Modified Rankin Scale Assessment

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Background: For measuring a disease burden or an interventional efficacy with a patientcentered common metric, two approaches have been widely employed. One is based on patients' or general population's preference, which elicits quality weight (QW) and qualityadjusted life years (QALY). The other is based on disease experts' consensus, which generates disability weight (DW) and disability-adjusted life years (DALY). The correlation between the patients'-deriving and the experts'-deriving outcomes has not been explored in a stroke population. Methods: We prospectively compiled the data for baseline characteristics, 3-month modified Rankin disability Scale (mRS), and 3-month EuroQol in patients with acute ischemic stroke who admitted within 7 days from onset to a tertiary hospital between June 2006 and Jul 2007. For each patient, QALY lost and DALY lost were derived from the data of age, gender, 3-month mRS outcome, mRS-specific DW derived from a prior study, and QW derived from EuroQol which patients directly indicated. Two sets of QALY lost were generated: one was calculated by assuming QW of healthy individual as 1 (QALY 1 lost), and the other by employing age-specific QW obtained from Korean general population (QALY 2 lost). Similarly, two sets of DALY lost were generated by incorporating age-weighting (DALY[3,1] lost) or not (DALY[3,0] lost). Then, we analyzed the correlations between two sets of QALY and DALY lost values, and investigated whether the correlations remain robust across different age, gender, and initial stroke severity. Results: 1524 patients were included in this study: age, 66.7Ϯ12.5(SD); median NIHSS (interquartile range), 4 (2-7); male 60.6%; DALY[3,1] lost, 3.64Ϯ0.06; QALY 1 lost, 3.85Ϯ0.09; QALY 2 lost, 3.04Ϯ0.09. The Pearson's correlation coefficients were 0.857 (pϽ0.001) between QALY 1 and DALY[3,1], 0.892 (pϽ0.001) between QALY 1 and DALY[3,0], 0.846 (pϽ0.001) between QALY 2 and DALY[3,1], and 0.878 (pϽ0.001) between QALY 2 and DALY[3,0] (Figure ). Interaction analyses revealed that the correlations between QALY and DALY vary by age, gender, and initial stroke severity (pϽ0.1 for all). However, those interactions were quantitative rather than qualitative. Conclusion: This study demonstrated that an expertderiving DALY lost was closely correlated with a patient-deriving QALY lost. As being a more comparable and externally validated measure, the DALY lost would be a good alternative to QALY lost for a health policy-decision making in stroke field.

Author Disclosures: K. Hong: None. H. Bae: None. M. Yang: None. M. Jang: None. M. Han: None. J. Lee: None. J. Saver: None.

W P314 Quality Of Life After Stroke And Its Correlation With Severity Of Impairment And Functional Status

Irene Katzan, Eric Novak, Nancy Obuchowski, Michael Modic; Cleveland Clinic Founda, Cleveland, OH There is an increasing national emphasis on measuring health-related quality of life and other patient-reported outcomes of care. It is unclear ow these measures correlate with other traditional stroke outcome measures assessing functional status and severity of impairment, which are typically reported by the provider. The aim of this study was to determine the correlation between the generic health-related quality of life measure -European Quality of Life (EQ5D) and the following stroke outcome measures: Stroke Impact Scale 16 (SIS-16), modified Rankin (mRS), National Institutes Health Scale Score (NIHSS), Barthel Index (BI) as well as the depression scale Patient Health Questionnaire 9 (PHQ9). Methods: Several patient-reported measures have been systematically collected from all stroke patients seen in the Cleveland Clinic's cerebrovascular clinic using electronic tablets since August 2008. Spearman correlations were computed between EQ5D and each stroke outcome measure overall and after stratification by TOAST stroke mechanism. Tests were conducted to identify if correlations were different than zero, indicating no linear relationship. Correlations were computed using the first available visit per patient. Results: There were 741 patients identified with stroke representing 1,115 visits to the outpatient stroke clinic. Of those, 47.7% were female, 75.5% were Caucasian, and 47.2% were Ͼ 60 yrs old. Mean EQ5D score was 0.73 [95%CI .71-.75]. Median Rankin score was 2. Patients with TOAST stroke mechanism of "Other determined etiology" had lowest EQ5D score (0 .68 [.62-.74]), while those with 'small vessel disease' had the highest EQ5D (0.78 [.74-.82]). Overall, there were moderately strong correlations between the EQ5D and each of the functional status measures (see Table ). Negative correlations were seen with PHQ9 (r s ϭ -0.657), Rankin (r s ϭ -0.604), and NIHSS (r s ϭ -0.463), indicating that quality of life improved as each of these measures decreased (less depression and less severe disabilities). ). Highest correlation occurred with SIS16 (r ϭ.704) and lowest occurred with NIHSS (rϭ-.463). Conclusion: Patients with stroke being seen in a tertiary care center's outpatient stroke clinic had reasonable quality of life. Correlations with EQ5D and other stroke functional and impairment scales were moderate -and was the highest for the Stroke Impact Scale and lowest for the NIHSS. The QoL measure was not redundant with these stroke outcomes scales. Addition of an overall Quality of Life metric should be considered when evaluating overall outcomes after stroke.

W P315 Depression After Stroke -Association With Patient Characteristics And Functional Status

Irene Katzan, Eric Novak, Johanna Morton, Kay Bielawski, Michael Modic; CLEVELAND CLINIC FOUNDA, Cleveland, OH Depression is common occurrence after stroke and negatively impacts stroke outcomes. The aims of this study were to (1) determine the frequency of depression in patients seen in stroke clinic, (2) identify specific demographic and clinical factors associated with depression following stroke (3) evaluate the correlation between depression and functional status after stroke, and (4) explore the association of specific neurological impairments as defined by NIHSS with depression. Methods: Patient-reported PHQ9 scale was systematically collected using electronic tablets on all patients seen in the Cleveland Clinic's Cerebrovascular Clinic beginning August 2008. To evaluate the association of specific factors with depression, regression models were built using generalized estimating with the PHQ9 score as the dependent variable. Spearman correlations were calculated to evaluate correlation of PHQ9 score with the following stroke outcome measures: modified Rankin Scale (mRS), Stroke Impact Scale 16 (SIS-16), Barthel Index (BI), and the NIHSS. To explore the relationship of somatic symptoms, which may occur after stroke, with the PHQ9 score, analysis of individual PHQ9 elements and outcome scale scores was also performed. Results: PHQ9 scores were available from 804 clinical visits, representing 599 patients with mean age ϭ 58.4, mean NIHSS ϭ 1.7, median mRS of 1. Mean PHQ9 score was 5.9% (95CI% 5.4 6.4); 23.4% had PHQ9 Ͼ10 suggesting moderate depression and 11.4% had PHQ9 Ͼ15 suggesting severe depression . Females were more depressed than males (pϭ.0005) as were new patients over established patients (pϭ0.004). There was no association with PHQ9 and time since stroke (pϭ0.17). There were moderately strong correlations between the PHQ9 and other functional status measures, indicating higher depression with higher degrees of disability. Correlation was smallest with NIHSS. [See table]. Among individual PHQ9 questions, highest correlation occurred with Q1 ( "interest in activities") and Q4 ( "fatigue"), both of which may be due to direct stroke effects, although total PHQ9 score had highest correlation with other outcome scales. There was a significant association with PHQ9 and each individual NIHSS item except "vision" and "best language". Conclusion: Depression as identified by PHQ9 occurred in 23.4% of stroke patients seen in an outpatient setting, despite the relatively low disability in this cohort. There is a correlation with disability and less so with severity of impairment. Systematic collection of depression may provide a significant opportunity to improve overall outcomes after stroke.

Author Disclosures: I. Katzan: None. E. Novak: None. J. Morton: None. K. Bielawski: None. M. Modic: Consultant/Advisory Board; Modest; Analogic.

W P316 The Psychosocial Impact of Stroke on Patients and their Primary Family Caregivers: The Caring for Adults Recovering from the Effects of Stroke (CARES) Project

David L Roth, Univ of Alabama at Birmingham, Birmingham, AL; William E Haley, Univ of South Florida, Tampa, FL; Olivio J Clay, Virginia G Wadley, George Howard; Univ of Alabama at Birmingham, Birmingham, AL Background and Purpose: The negative effects of stroke on depression and other measures of psychosocial functioning have been well described in previous research, but less is known about the effects of stroke on primary family caregivers. In this project, race and gender differences in psychosocial outcomes were examined using an epidemiologically-derived sample of first-time stroke survivors and their primary family caregivers recruited from the national REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Methods: REGARDS participants who experienced verified incident stroke events and their primary family caregivers (N ϭ 139) were enrolled in the CARES project and interviewed by telephone approximately 9 months after the stroke event. Individually-matched stroke-free controls from the REGARDS sample and noncaregiving family member controls were also enrolled. Stroke and control dyads were matched on race, gender, age of stroke survivor (Ϯ 5 years), relationship, and co-residence status. The interviews collected data on general physical health, psychosocial functioning, health care utilization, and the severity of any stroke-related impairments. The Center for Epidemiological Studies Depression scale (CESD) and the Mental Composite Summary (MCS) of the 12-item Short Form provided measures of mental health functioning for all participants. Analyses of covariance were used to examine stroke vs. control, race, and gender effects for both stroke survivors and caregivers. Results: Consistent with previous research, stroke survivors reported significantly more depressive symptoms and poorer mental health functioning than matched controls (ps Ͻ .0001), with no evidence of a differential impact by race or gender (ps Ͼ 0.05). Caregivers also reported significantly more depressive symptoms and poorer mental health functioning than noncaregiving controls (ps Ͻ .05). Standardized effect sizes indicated a similar impact of stroke on the mental health functioning of caregivers and stroke survivors. Female caregivers reported more mental health problems than men, but no differential caregiving effects were found by race. Caregiver depressive symptoms and mental health functioning were significant predictors of stroke survivor depressive symptoms and mental health functioning, respectively (Bs ϭ 0.40 and 0.35, respectively, ps Ͻ .0001). Conclusions: A stroke event has similar impacts on mental health functioning for both patients and their primary family caregivers. Deleterious mental health effects appear to be linked between caregivers and stroke survivors, and female caregivers are at heightened risk for poor psychosocial outcomes. Background: Mortality, as an outcome indicator for public reporting, is in demand by consumer agencies. The Agency for Healthcare Research and Quality (AHRQ) has proposed methods for calculation of unadjusted raw stroke mortality that were accepted by the National Quality Forum for CMS implementation. We explored the implications of using AHRQ methodology at a Comprehensive Stroke Center. Methods: Administrative data from 2009 was used to identify cases with a principal diagnosis of stroke and ICD-9 codes meeting AHRQ criteria. Cases lacking disposition and those not associated with infarction or hemorrhage were excluded. No attempt to correct ICD-9 codes was made from their original assignment. Recorded disability and prognostic measures were verified against documented clinical exams and imaging. Results: The sample consisted of 386 cases (Table ). Age was 59Ϯ16 yrs; 191 (49.5%) cases were transfers. Neurosurgery admitted 168 (43.5%), stroke neurology admitted 163 (42%) of which 61% were ICH, and the remaining 55 (14%) were admitted by others. Unadjusted stroke mortality was 22% (nϭ86). Hemorrhage accounted for 92% (nϭ79) of stroke mortality (n: 46 IPH; 14 SDH; 19 SAH); transfers accounted for 17% of deaths. Neurosurgery had 31 (18.5%) deaths, stroke neurologists had 38 (23%), and other service physicians had 17 (31%); pϭns. Age (r ϭ.166; pϭ.001), GCS (r ϭ -.756; PϽ.001), NIHSS (r ϭ.652; PϽ.001), ICH score (r ϭ.689; PϽ.001), Hunt & Hess (r ϭ.722; PϽ.001), and Fisher score (r ϭ.493; PϽ.001) were significantly correlated with stroke mortality. Exclusion of patient transfers with GCS Ͻ 8 reduced mortality to 16.6%, while exclusion of cases with ICH scores Ͼ 4 decreased mortality to 14.7%. Due to our large volume of hemorrhages, a logistic regression model was constructed to predict the effect of GCS and transfers on mortality; for each 1 point GCS increase, the survival OR doubled. Conclusions: Raw unadjusted stroke mortality is likely to favor both non-stroke center designated hospitals and primary stroke centers that do not admit, or transfer hemorrhage and severe ischemic stroke patients, potentially misleading public perception of stroke center quality. Methods that incorporate ICH score or GCS for non-ICH hemorrhage, NIHSS score and Hunt & Hess score for severity adjustment should be explored.

Introduction: Hospital staffing may be reduced in spectrum on weekends. Prior studies of weekend disparities in stroke care have focused on in-hospital mortality. We hypothesized that 90-day mortality was higher in stroke patients hospitalized on weekends versus weekdays, and that this difference would be minimized in certified stroke centers. Methods: We used the Myocardial Infarction Data Acquisition System (MIDAS) database, which includes demographic and clinical data on patients discharged with a primary diagnosis of cerebral infarction from all non-federal acute care hospitals in New Jersey between 1996 and 2007. Out-of-hospital deaths were assessed by matching MIDAS records with New Jersey death registration files. The primary outcome variable was all-cause mortality within 90 days of hospital admission. The primary independent variable was weekend versus weekday admission. Covariates included patient demographics, comorbid conditions, year of admission, intravenous tPA, and New Jersey stroke center designation. Measures of initial stroke severity were not available. Multivariable logistic-regression models were used to adjust for available confounding variables. Statistical significance was defined as a p-value Յ 0.01. Results: 134,441 patients were admitted with a primary diagnosis of cerebral infarction during the study period. 23.4% were admitted to a comprehensive stroke center, 51.5% to a primary stroke center, and 25.1% to a non-stroke center hospital. Baseline patient characteristics were similar for all groups. Intravenous tPA was given more often on weekends than weekdays (1.62% vs. 1.34%, PϽ0.0001). 90-day mortality was greater in stroke patients admitted on weekends compared to weekdays (17.24% vs. 16.52%, pϭ0.001). The overall adjusted odds of death at 90 days were significantly greater for weekend admission (OR 1.05, 95% CI 1.02-1.09). Admission to a New Jersey certified stroke center was independently associated with a reduction in mortality (Table 1). No difference in mortality was observed for patients admitted to comprehensive stroke centers on weekends versus weekdays (16.43% vs. 16.60%, pϭ0.7). Conclusions: Stroke patients admitted on weekends to New Jersey hospitals had a significantly higher risk of death by 90 days. However, no such difference in mortality was observed at comprehensive stroke centers. Mortality after stroke was lower in certified stroke centers. Background: As developing countries such as Vietnam experience the health transition to chronic disease, the morbidity and mortality from stroke contribute a huge burden on the health of the people. Objectives: We sought to investigate patient characteristics associated with Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation.

stroke mortality in hospitalized patients in Da Nang, Vietnam. Methods: In a collaboration between the Da Nang Ministry of Health and the University of Washington, Seattle, a stroke registry was recently developed and implemented at Da Nang Hospital utilizing the WHO Stoke STEPS instrument. Physicians and nurses from the ICU, Cardiology, or General Internal Medicine units collected the information which was entered into a computer system on-site. Results: Data from April, May and June, 2010, resulted in a total of 210 strokes defined as definite based on CT imaging. Of these, 97 were classified as ischemic (46.2%), 90 as hemorrhagic (42.9%), and 23 were unspecified (11.0%). Mean age of stroke patients was 48.2 (SD 16.8) years and 84 (40%) occurred in females. Of these, 143 (65.1%) were discharged from the hospital after a mean length of stay of 22.5 (SD 14.6) days. Eleven patients (5.2%) died in hospital and an additional 56 (26.7%) were in grave condition/dying and family or patient requested that he/she be released to die at home. Of those who either died in hospital or were released to die at home, 77.6% had hemorrhagic strokes while only 22.4% were ischemic (pϽ.001). Mortality did not differ by age although a higher percent of men (37.3%) than women (21.5%) either died or went home to die (pϭ.01). Higher rates of atrial fibrillation and diabetes but not hypertension were reported in patients with mortal strokes. In multivariate logistic regressions models adjusted for age, gender and previous stroke, persons with hemorrhagic strokes were almost 8 times as likely to subsequently die compared to those with ischemic strokes (OR: 7.69, 95% CI: 3.76-15.73). Men were twice as likely to die from stroke as women (odds ratio 2.00, 95% CI: 1.05, 3.80) adjusted for age and previous stroke. In adjusted models, the following factors were found to significantly predict mortality: modified Rankin scale prior to stroke, presence of atrial fibrillation, diabetes mellitus, hypercholesteremia, and current tobacco use. While presence of hypertension at admission was not associated with mortality, the maximum blood pressure reached during the hospital stay was significant (p Ͻ.001). Conclusions: These data document the high case fatality from stroke in Vietnam (over 30%). Efforts to document out-of-hospital deaths and to address the risk factors related to mortality after a stroke event are urgently needed.

W P321 Neurological Morbidity And Mortality Following Attendance At A Transient Ischaemic Attack Clinic

Jesse Dawson, Alan C Cameron, Matthew R Walters, Terence J Quinn, Kate S McArthur, Kennedy R Lees; Institute of Cardiovascular and Med Sciences, Univ of Glasgow, Glasgow, United Kingdom Introduction: Half of patients who attend transient ischaemic attack (TIA) clinics do not have cerebrovascular disease and have an alternative explanation for their symptoms. This may be an underlying neurological disorder that will later become manifest. We examined the risk of future non-stroke neurological death or hospital admission in a large cohort referred with suspected TIA. Methods: Data from the West Glasgow Stroke Registry were used. The Registry contains data on patients attending our TIA clinic from August 1992 onwards. We dichotomised clinical diagnoses at baseline as being TIA (including minor stroke) or non-TIA. Subjects were followed up by record linkage to death and hospital discharge records until 27 December 2006. Our endpoint was the next occurrence of any non-stroke neurological event, defined using ICD-10 and ICD-9 classifications. We compared outcomes between the groups using a Cox proportional hazard model adjusted for age, sex and further potential confounding variables. Results: We studied 3533 patients who attended the TIA clinic between August 1992 and January 2005: 1631 (46.2%) were male and mean (SD) age was 64.7 (13.6) years. 1890 (53.5%) had a baseline diagnosis of TIA and 1643 had non-TIA. There was a minimum of 24 months follow-up for each patient and median (IQR) follow-up was 165 (84.2 to 246.3) months. 514 patients (14.5%) suffered a non-stroke neurological event during follow-up. Of those with non-TIA at baseline, 252 (15.4 %) later suffered a non-stroke neurological event, compared to 262 (13.9%) with TIA (HR 1.37, 95% CI 1.10 to 1.69, pϭ0.003 after adjustment). Compared to patients with TIA at baseline, a greater proportion of those non-TIA later suffered admission or death with epilepsy (46 (2.8%) vs. 23 (1.2%), pϭ0.001), nerve, nerve root and plexus disorders (29 (1.8%) vs. 16 (0.8%), pϭ0.015) and demyelinating diseases (8 (0.5%) vs. 1 (0.1%), pϭ0.01). Inflammatory neurological disorders, atrophies, movement disorders and the dementias were similarly common between groups. Other disorders of the nervous system not covered in the above categories were also more common in those with non-TIA at baseline ( 22(1.3%) vs. 10 (0.5%), pϭ0.01). Conclusion: Patients who attend TIA clinics with transient neurological symptoms but not TIA are at slightly greater risk of future non-stroke neurological events than those with TIA. Further work should aim to help better identify such individuals at first TIA clinic attendance as this may allow earlier diagnosis and treatment of underlying neurological disorders. Objectives: Several studies have shown that an expedited outpatient evaluation of patients presenting with TIA symptoms is effective and safe. We investigated whether the community costs of TIA evaluation using an outpatient TIA clinic triage strategy are lower compared to the costs of an inpatient evaluation. Methods: The TIA Workup as Outpatient: Assessment of Clinical Evaluation and Safety (TWOACES) study prospectively enrolled three groups of patients: direct referral to TIA clinic from a primary care physician, emergency department (ED) evaluation followed by referral to outpatient TIA clinic, and ED evaluation followed by hospitalization. We retrospectively identified a representative sample (15%) of Medicare reimbursed patients in each group to compare costs for patients who had an inpatient TIA evaluation vs. an outpatient evaluation. The assessment included reimbursements for all services and procedures related to TIA diagnosis ordered by the attending physician. Any tests ordered to evaluate concomitant diagnoses other than TIA were excluded. We estimated potential cost savings by comparing costs of the TWOACES triage strategy with hypothetical costs of hospital admission for all TIA patients. Costs were compared using Mann-Whitney U test. Differences between medians in costs were computed using Hodges-Lehman estimates. Results: During the 2.5-year period of the TWOACES study, there were 43 patients with direct referral to TIA clinic from primary care, 157 with ED to TIA clinic referral, and 67 with ED evaluation followed by hospitalization. The median per patient Medicare cost for direct referrals to TIA clinic was $1,884 (IQR $1,866-$1,897), for ED to TIA clinic $4,049 ($3,594-$4,756), and ED to hospitalization $5,804 ($4,027-$7,173). The median Medicare cost for hospitalized patients was $3,587 (95% CI $1,450 -5,396, pϭ0.006) greater than the cost of direct referrals to TIA clinic and $1,427 (-$326 -$3,088, pϭ0.108) greater than the cost of ED to TIA clinic referrals. Therefore, the annual healthcare cost reductions obtained in the TWOACES study are estimated to be $151,312 ($4,467-$286,738) compared with the hypothetical cost of hospitalization of all patients. Distributing these cost reductions across all 267 TIA patients enrolled in TWOACES, the healthcare cost reduction per TIA patient encountered was $1,417 ($42-$2,685). Conclusions: Our analysis demonstrates that the TWOACES TIA triage strategy is cost saving from the community perspective. We estimate that Medicare saved more than $1,000 per patient using this triage approach. A TIA clinic does not require a significant investment and may be particularly desirable for a hospital that runs near full capacity because of the opportunity to admit other patients into beds freed up by the outpatient evaluation of TIA patients.

Author Disclosures: M. Mlynash: None. J. Castle: None. J. Olivot: None. C. Wolford: None. N.E. Schwartz: None. M.G. Lansberg: Research Grant; Significant; NIH. G. Edwards: None. S. Kemp: None. G.W. Albers: Research Grant; Significant; Boehringer Ingelheim.

W P323 Brain Magnetic Resonance Imaging is Utilized in Less than One-third of Admitted Transient Ischemic Attacks Patients in the United States

Shyam Prabhakaran, Maggie McNulty, Bichun Ouyang; Rush Univ Med Cntr, Chicago, IL Objective: To investigate the utilization of brain magnetic resonance imaging (MRI) among admitted transient ischemic attack (TIA) patients in United States (US) hospitals between 2003 and 2007 Background: MRI is superior to CT imaging in the detection of acute infarcts and its application has lead to a new definition of TIA and ischemic stroke. However, due to costs, availability, and contraindications, MRI may be more difficult to obtain. Methods: We used the Nationwide Inpatient Sample (NIS), representative of 20% of inpatient admissions in the US, to identify adult (Ն18 years old) patients admitted with a discharge primary diagnosis of transient ischemic attack (DRG code 524) between 2003 and 2007. We then selected only those in whom procedures were coded and calculated the proportion of brain MRI use (ICD-9-CM procedure code 88.91) for each year. Trend statistics were performed using the Cochran-Armitage test. For 2007, we also assessed individual patient and hospital characteristics in univariable analyses. Significant candidate variables were then analyzed in a multivariable stepwise logistical regression model to determine odds ratios (OR) and 95% confidence intervals factors associated with brain MRI use following TIA. A p-value Ͻ 0.05 was considered significant. Results: Between 2003 and 2007, there were 185,172 patients diagnosed with TIA in the NIS. Among these, 45,173 (24.2%) were adults who had procedure codes recorded. The use of brain MRI in these admitted TIA patients increased each year (p Ͻ 0.001 for trend): 2003: 21. 6%; 2004: 22.6%; 2005: 24.7%; 2006: 26.5%; and 2007: 29.3%. In a multivariable model, the following were independently associated with utilization of brain MRI after TIA in 2007: younger age (adj. OR 0.996, 0.992-1.000), non-elective admission (adj. OR 2.25, 1.53-3.30), lower illness severity subclass (highest class: adj. OR 0.19, 0.08-0.48), lower mortality subclass (highest class: adj. OR 0.43, 0.19-0.97), teaching hospital status (adj. OR 1.69, 1.50-1.89), eastern US (adj. OR 1.44, 1.29-1.62), urban location (adj. OR 1.29, 1.05-1.60), and large hospital size (adj. OR 1.61, 1.33-1.95). Insurance status, race, and sex were not significantly associated with MRI utilization following TIA. Total hospital charges were not different between those who underwent MRI and those who did not (p ϭ 0.131).

W P324 One Year Outcomes of Acute Ischemic Stroke and TIA Patients undergoing CT-versus MRI-based Evaluations: A Retrospective Comparison

Hebah M Hefzy, Henry Ford Hosp, Detroit, MI; Elizabeth Neil, Univ of Cincinnati, Cincinnati, OH; Patricia Penstone, Meredith Mahan, Panayiotis Mitsias, Brian Silver; Henry Ford Hosp, Detroit, MI Background: Many clinicians advocate for MRI-based work-ups for patients with ischemic cerebrovascular symptoms asserting that patient management is improved. Previous studies have shown that MRI is more sensitive and specific than CT in the diagnosis of acute stroke.

The American Stroke Asssociation guidelines for TIA evaluation state that an MRI, including DWI, is the preferred brain diagnostic imaging modality. The basis for this recommendation is that MRI-based evaluations offers improved prognostic information. There are no studies evaluating the outcomes of patients who undergo CT-versus MRI-based evaluations. We sought to compare one-year outcomes of stroke and TIA patients who underwent different imaging modalities. Methods: Patients were identified from a prospectively collected database of stroke and TIA patients. All patients discharged from a single institution between January 1, 2008 and Dec 31, 2008 were included. Electronic medical records were used to collect demographic, clinical, and diagnostic testing data. Death, stroke, and myocardial infarction within one year of admission were compared between patients who had CT alone, MRI alone, or CT and MRI during hospitalization. Multivariable analysis was performed to identify independent predictors of death, recurrent stroke, and myocardial infarction within one year. Results: 727 patients were identified: 1 did not have CT or MRI and was excluded, 161 had CT alone, 29 had MRI alone, and 536 had CT and MRI. On univariate analysis, patients who had both CT and MRI were significantly less likely to die while those who had MRI alone were more likely to have a recurrent stroke at 1 year follow-up. After adjusting for age, gender, admission NIHSS, treatment with tissue plasminogen activator, atrial fibrillation, coronary artery disease, diabetes mellitus, hyperlipidemia, and hypertension, use of an MRI during hospitalization was not associated with any outcome measure at one year. Variables that were significantly associated with death at 1 year included NIHSS and age. Conclusions: In this retrospective analysis, use of an MRI during hospitalization was not associated with a reduced risk of death, recurrent stroke, or myocardial infarction with one year. The results suggest that treatment strategies may not necessarily have been influenced by imaging modality or that changes in treatment strategy based on MRI did not improve outcome. A randomized trial of different imaging modalities may be warranted.

W P325 Stroke Etiology Significantly Influences Inpatient Cost

Marco Fossati-Bellani, Kamal R Shah, Tulane Univ Sch of Medicine, New Orleans, LA; Karen C Albright, Univ of Alabama -Birmingham, Birmingham, AL; Stephanie E Rogers, James E Siegler, Sheryl Martin-Schild; Tulane Univ Sch of Medicine, New Orleans, LA Background: Evaluation of patients with acute ischemic stroke (AIS) is tailored to patient demographic characteristics and the likelihood of the etiology. The etiology could impact stroke severity and management, affecting length of stay and cost. We hypothesized that the cost of inpatient care and the distribution of costs for an acute ischemic stroke (AIS) would be dependent on stroke etiology. Methods: We identified patients admitted with AIS to the stroke service by retrospective chart review. Gross total patient charges were analyzed, as were costs subdivided into pharmacy, imaging, diagnostic, interventional, rehabilitation, and facility fees and compared in patients based on TOAST classification. We adjusted for factors that affect outcome (age, baseline NIHSS score, and admission glucose level) and length of stay (LOS). Results: 209 patients were included in the analyses; 59.3% were male. The figure shows the distribution of total cost and the total and subgroup costs in the each TOAST classification category relative to each corresponding median value for the whole population. About 1/3 of the total cost was due to imaging. There was significant variation in LOS among stroke etiologies (pϭ0.012). The total cost per day, however, was highest in the large vessel and cryptogenic "more than one cause" and "no cause" groups. Independent predictors of total cost included age (0.029, negative relationship), NIHSS (Ͻ0.001), LOS (Ͻ0.001), and stroke etiology (0.020), gender was not (pϭ0.538). Stroke etiology was an independent predictor of diagnostic (pϭ0.008), facilities (pϭ0.013), and rehab costs (pϭ0.016). Conclusions: Stroke etiology is an independent predictor of total cost of hospitalization for AIS. Large vessel strokes may absorb more health care dollars, and cryptogenic strokes may be associated with additional diagnostic testing. Since length of stay is a significant independent predictor of all domains of inpatient cost, inefficiencies in diagnostic evaluation of patients without a clear etiology at onset should be avoided.

Author Disclosures: M. Fossati-Bellani: None. K.R. Shah: None. K.C. Albright: None. S.E. Rogers: None. J.E. Siegler: None. S. Martin-Schild: None.

W P326 Influence Of Chads2 Score In The Severity And Prognosis Of Ischemic Strokes Due To Atrial Fibrillation

Eva Giralt-Steinhauer, Elisa Cuadrado-Godia, Jordi Jimenez-Conde, Ana Rodriguez-Campello, Sara Jimena, Miguel A Rubio, Angel Ois, Eva Garcia-Ramallo, Jaume Roquer; Hosp Del Mar, Barcelona, Spain Objectives. To determine the prognostic value of CHADS2 score in first-ever ischemic stroke (IS) due to atrial fibrillation (AF). Methods: We analyzed 372 consecutive patients with IS without previous disability (mRSϾ2) and known AF admitted between 1995-2009. Variables studied were: CHAD2 score (0 to 4), prevalence of vascular risk factors, congestive heart failure (CHF), ischemic heart disease (IHD), peripheral arterial disease, concomitant intra or extracranial stenosis Ն50%, antithrombotic treatment, stroke severity according NIH stroke scale and 90-day poor outcome . Association between CHAD2 score and poor outcome was assessed using logistic regression models adjusted for variables tested in univariate analysis and PϽ0.1. Results: 75.3% of patients had CHAD2Ն2 and 28.3% were using oral anticoagulants (only 33 % had INRϾ2). Increasing CHAD2 score was associated with higher stroke severity and worse 90-day outcome. Age, female gender, stroke severity, CHF, current smoking and IHD were associated with poor outcome in univariate analysis. Stroke severity

W P327 Guideline Discordant Periprocedural Interruptions in Warfarin Therapy are Frequent among Patients with Atrial Fibrillation

Lesli E Skolarus, Lewis B Morgenstern, James B Froehlich, Lynda D Lisabeth, Devin L Brown; UNIV MICHIGAN, Ann Arbor, MI Background and Purpose: Periprocedural interruptions in warfarin therapy increase stroke risk in atrial fibrillation patients, and are not indicated for all procedures. Current guidelines recommend continued warfarin therapy in patients undergoing colonoscopy, cataract removal, dental and dermatologic procedures. We sought to determine the indications for and frequency with which patients on warfarin for atrial fibrillation are requested to interrupt their therapy temporarily for a medical or dental procedure. Methods: An anonymous postal survey was sent in October and November of 2009 to all patients followed for over one year by the University of Michigan Anticoagulation service (nϭ2,133). The survey queried demographics, vascular risk factors, and indications for taking warfarin. Patients were also asked how many times in the prior 12 months they were requested to interrupt warfarin therapy for a medical or dental procedure or test, and the specific indication for the requested interruption in warfarin therapy. Descriptive statistics were used to assess patient demographics and presence of vascular risk factors (yes vs. no and missing). The frequency of at least one request for interruption in warfarin therapy was calculated overall and for each procedure. Results: Of the 1,686 respondents (79% response rate), 966 (57%) who used warfarin for atrial fibrillation were available for analysis. Their mean age was 74 years (sdϭ11 years). The majority were male (62%) and Caucasian (96%). Seventy percent reported a history of hypertension and 54% reported heart disease. There were a total of 798 periprocedural requests to interrupt warfarin therapy among 947 respondents (median 1, IQR 0-1). At least one request to interrupt warfarin therapy in the prior year was experienced by 481 of the 947 (51%). Fifty percent of requests to interrupt warfarin were for indications not supported by guideline statements. Among all requests for interruption of warfarin therapy, those for dental procedures (a combination of dental cleaning and other dental procedures) were the most common 25% (nϭ210), followed by surgery 19% (nϭ158), and colonoscopy 18% (nϭ153). Conclusion: Despite the high risk of stroke in patients with atrial fibrillation and well known benefit of anticoagulation, interruptions in warfarin therapy are frequent and often discordant with current guidelines. As a result, patients are left vulnerable to needless risk of stroke and other thrombotic events. Educational interventions targeting the patient, proceduralist, and anticoagulation manager focusing on guideline discordant periprocedural warfarin interruptions could have significant public health impact.

W P328 How Well do Recent Studies of AF Patients Reflect the Real World AF Patient?

Teresa A Simon, BMS, Princeton, NJ; Laurent Azoulay, Mc Gill Univ, Montreal, Canada; Marc Rosenman, Regenstrief, Indianapolis, IN; Ed Ewen, Chrisitana Care Outcomes Rsch, Newark, DE; Hugh Kawabata, BMS, Plainsboro, NJ; Samy Suissa; McGill Univ, Montreal, Canada As data from randomized clinical trials (RCTs) are applied in clinical practice settings, understanding how the patients with AF enrolled in recent large RCTs compare to patients with AF in the real world is important. A number of risk scores are available for risk stratification in AF. Gage's published CHADS 2 score is well established and used in treatment guidelines. Our objective was to compare the patients in recent AF trials to patients with AF in the real world, based on the CHADS 2 risk score along with other baseline characteristics. Methods: Patients with chronic non-valvular AF were identified in 4 data sources from diverse settings: electronic medical record (EMR) data from Christiana Care (CCHS) and Regenstrief Institute (RMRS), claims from United Health Care (UHC) in the US; and clinical data from GPRD from the UK. These cohorts with AF were then compared to those in recent studies of novel oral anti-coagulants (RE-LY and ROCKET AF) based upon overall CHADS 2 score, CHADS 2 components and other baseline characteristics. Results: See Table . All cohorts had similar distribution with respect to age and gender. UHC and RMRS have a slightly younger population, and CCHS has almost 50% females. The RCTs had fewer patients with CHADS2 1 than did the observational cohorts. ROCKET AF was almost entirely composed of patients with CHADS2 Ն 3. The differences observed between CHADS2 in real world and clinical trial populations may relate to requirements for additional risk factors in inclusion criteria for the trials. Observational studies may include incident or prevalent AFpatients, while RCTs tend to enroll prevalent patients. Conclusions: Demographic characteristics are similar across these data sources; females may be under-represented in the RCTs. The distribution of CHADS 2 scores is different between the real world populations and the RCTs. The RCTs enrolled fewer CHADS 0-1 patients and more CHADS 3-6 patients. The proportion of patients with CHADS 2 score Ն 3 was very high in ROCKET-AF and in RE-LY was higher than in 3 of the 4 observational cohorts. Observational studies tend to include a more heterogeneous population reflective of those ultimately prescribed a medication. The data suggest that the differences in the study populations should be taken into consideration when applying RCT results to clinical practice. marrow in response to stroke. Stromal Derived Growth Factor 1-Alpha (SDF1-A) along with its receptor CXCR4 is a potent chemo attractant released by areas of injury. SDF1-A has been shown to mobilize HSC/HPC from the bone marrow to the blood and lead to 'homing' of the cells to an area of injury. Methods: Animals underwent a murine intraluminal filament model of focal cerebral ischemia. Animals were divided into 4 groups (nϭ5 each): 4hrs sham surgery, 4hrs post reperfusion, 24hrs sham surgery, and 24hrs post reperfusion. Neurological deficit score was recorded prior to euthanasia and serum SDF1-A was assessed in all groups. HSC/HPC were enriched using nanoparticles tagged with LIN negative and SCA1 positive markers and counted on a hemacytometer. Results: Serum SDF1-A levels were elevated at 4hrs and 24 hours compared to sham controls (107Ϯ3.8% and 137Ϯ11% versus 100Ϯ0.04% and 100Ϯ0.06%, respectively; 4hrs vs sham: PϭNS, 24hrs vs sham: PϽ0.05). Bone marrow showed an increased production of HSC/HPC at 4 hrs (106Ϯ26%) and significantly higher at 24 hrs (272Ϯ35%). Mobilization of the HSC/HPC was slightly higher at 4 hrs (167Ϯ26%) and significantly higher at 24 hrs (606Ϯ91%; PϽ0.05). Neurological deficit score at 4hrs and 24hrs post reperfusion were 1.846Ϯ0.21 and 2.04Ϯ0.178, respectively. Conclusions: Serum SDF1-A levels significantly increased following cerebral ischemia, leading to increased mobilization of HSC/HPC from the bone marrow to the blood. These data suggests that SDF1-A mobilization of HSC/HPC in response to cerebral ischemia may be a relevant pathway for cerebral injury repair following stroke.

W P338 Therapeutic Modulation of Cerebral Microbleeds in Cerebral Amyloid Angiopathy

Vitaly Vasilevko, Giselle Passos, Daniel Quiring, Mark Fisher, David H Cribbs; Univ of California Irvine, Irvine, CA Cerebral amyloid angiopathy (CAA) is a common cause of intracerebral hemorrhage (ICH) in the elderly and is associated with MRI evidence of cerebral microbleeds. CAA may also coexist with ischemic stroke. Presence of CAA produces increased microbleeds and vasogenic edema after active (AN1792) and passive (bapineuzumab AAB-001) anti-amyloid-beta (A␤) immunotherapy. We investigated this phenomenon using old amyloid-precursor-protein-transgenic (APP-Tg) mice, a model which is characterized in part by CAA and cerebral microbleeds. In this model, anti-A␤ immunotherapy dramatically exacerbates CAA and microbleeds. We therefore used 20 month old APP-Tg2576 mice to investigate the effect of ischemic stroke prevention agent dipyridamole (effective in European Stroke Prevention Study 2 as monotherapy in its extended release formulation) on the anti-A␤ immunotherapy-induced cerebrovascular lesions. Old APP-Tg2576 mice with extensive CAA were passively immunized by a weekly dose of 10mg/kg (i.p.) per mouse using anti-A␤40 C-terminal specific monoclonal antibody for 9 weeks. Mice were fed a dipyridamole diet that included high-fat chow given ad libitum. Passive immunization of APP-Tg2576 mice reduced amyloid plaque load and microglial activation, but also produced 3-fold increase in cerebral microbleeds. Dipyridamole use had no effect on the number of microbleeds, had minimal effect on cerebral amyloid deposition, and was associated with no observable adverse events in immunotherapy-treated mice. Thus, immunotherapy produced marked increase in cerebral microbleeds in this mouse model of CAA, and treatment with dipyridamole did not worsen this phenomenon. These data suggest that dipyridamole, used clinically to prevent ischemic stroke, may have a therapeutic role in patients requiring ischemic stroke prevention in the presence of CAA and cerebral microbleeds.

W P339 The Novel TrkB Agonist, 7,8-Dihydroxyflavone Enhances Stem Cell Mobilization After Stroke

J Mocco, Aqeela Afzal, Nagheme Thomas, Zuha Warraich, Brian L Hoh, Edward W Scott, Jeffery A Kleim; Univ of Florida, Gainesville, FL Background: Increasing levels of circulating Hematopoietic Stem Cells (HSC)/Hematopoietic Progenitor Cells (HPC), bone marrow derived mononuclear cells that promote repair in areas of injury, have been demonstrated to correlate with improved neurological function following stroke, suggesting a potentially critical role for HSC/HPC's in limiting stroke injury and/or facilitating stroke recovery. Flavonoids, found in plants and fruit, exert anti-oxidative effects. Recent studies have demonstrated that 7,8 Dihydroxyflavone (DHF) is a potent TrkB agonist mimicking Brain Derived Neurotropic Factor, thus making it a powerful potential tool for treating neurological disorders. Stromal Derived Growth Factor 1-Alpha (SDF1-A) along with its receptor CXCR4 is a potent chemo attractant released by areas of injury. SDF1-A has been shown to mobilize HSC/HPC from the bone marrow to the blood and lead to 'homing' of the cells to an area of injury. We investigated the effect of DHF on HSC/HPC function following cerebral ischemia. Methods: Ischemic damage was induced in adult male Long Evans hooded rats (350-400g) with a peri-MCA injection of the vasoconstriction peptide ET-1. The rats were sacrificed at 24 hours post surgery and their bone marrow and blood HSC/HPC enriched using nanoparticles tagged with LIN negative and CD90 markers. Results: Stroked animals showed an increase in bone marrow production of HSC/HPC versus control animals (31.9Ϯ7 versus 2Ϯ0.5, PϽ0.05). The mobilization of the HSC/HPC from the bone marrow to the blood was also significantly higher in the stroked animals versus control animals (43Ϯ19 versus 3.6Ϯ0.3, PϽ0.05). Following stroke, DHF pre-treated HSC/HPC's demonstrated significantly improved migration along an SDF-1 gradient compared to controls (129Ϯ1.0 versus 108Ϯ1.15, PϽ0.05), despite the fact that DHF alone provided no independent migratory stimulus.

Conclusions:

The results suggest that DHF may be a viable compound to facilitate HSC/HPC migration post-stroke.

Author Disclosures: J. Mocco: None. A. Afzal: None. N. Thomas: None. Z. Warraich: None. B.L. Hoh: None. E.W. Scott: None. J.A. Kleim: None.

W P340 The Differential Genetic Expression in Unstable and Stable Carotid Plaques may be a Predictor of Stroke Risk

Ankur Aggarwal, Michelle Lennartz, Paul Kreienberg; Albany Med Cntr, Albany, NY International Stroke Conference 2011 Objective: Stroke is the third leading cause of death in the United States. As the majority of strokes result from plaque rupture, elucidating the pathways that contribute to plaque vulnerability is critical for therapeutic intervention. This study tested the hypothesis that immune complex stimulation of macrophages induces a pattern of gene expression present in vulnerable human carotid plaques and that the overall gene expression of vulnerable and stable carotid plaques, even within the same plaque, are different and will reveal novel differences in cellular composition. Study Design: a. Tissue analysis: Specimens were analyzed using trichrome staining to classify samples as histologically vulnerable or stable. b. Assessment of gene expression: Quantitative RT-PCR (Q-PCR) was used to compare human femoral plaques (stable) with proximal and distal regions of carotid plaques for 22 genes implicated in plaque rupture. Additionally, four samples each of stable and vulnerable carotid plaques were compared using gene array analysis and results were validated using Q-PCR. c. Recapitulation of unstable gene expression pattern in vitro: The effect of oxidized LDL, C-reactive protein, TNF-a ´, or immune complexes on gene expression in human macrophages was compared to that present in unstable carotid plaques. Results: Genes expression of stable carotid and femoral plaques were similar; paired comparison between vulnerable and stable regions of carotid plaques showed significant differences in 16 genes that impact plaque stability: 1) matrix metalloproteinases (higher in vulnerable), 2) matrix metalloproteinase inhibitors (lower in vulnerable) and activators (higher in vulnerable), 3) activating Fca ˜receptors (higher in vulnerable) and 4) Fca ˜receptor signaling molecules (higher in vulnerable). We investigated the effect of Fc receptor cross-linking on the expression of plaque instability genes in vitro. Ligation of Fca ˜R with immune complexes, but not oxidized LDL, C-reactive protein, or TNF-a ´, induced a gene expression profile similar to vulnerable plaques. Additionally, human genome array analysis and qPCR revealed novel genes differentially expressed between vulnerable and stable plaques, some of which are linked through pathways and proteins products that my impact stability. An example is coagulation cascade. Finding other biochemical links between these genes may help find proteins that can be measured in the bloodstream and be used as a predictor of stroke.

Author Disclosures: A. Aggarwal: None. M. Lennartz: None. P. Kreienberg: None.

W P341 In Critical Care Setting Brain Natriuretic Peptide is an Unreliable Marker for Assessing Congestive Heart Failure in Acute Stroke Patients

Mohammad Moussavi, Bryan Gershen, Daniel Korya, Akash H Patel, Jit H Brahmbhatt, Subasini Dash, Daniel Rosenblat, Martin Gizzi, Jawad Kirmani; New Jersey Neuroscience Institute, Edison, NJ Background and Purpose: Brain Natriuretic Peptide (BNP) is known to be released from cardiac tissue and to a lesser degree from the hypothalamus. BNP is known to correlate with the presence and severity of congestive heart failure (CHF). In the general population screening test for CHF using BNP level of 50 pg/mL as a cut-off has a sensitivity (SN) and specificity (SP) of 97% and 67%, respectively. While the SN and SP for a cut-off of 100 pg/mL are 90% and 76%, respectively. An elevation of BNP has been reported to occur during acute stroke. Our study aimed at determining the sensitivity and specificity of BNP as a test for CHF in patients with acute stroke. Methods: A retrospective analysis of prospectively collected data on patients who suffered an acute stroke between 2005-2009 was performed. Patients who presented with transient ischemic attack or no value for BNP were excluded. The patients were then subdivided into two groups, with CHF and without CHF based on echocardiogram. Statistical analysis was completed to determine the mean BNP values, and an independent samples t-test was used to establish equality of means. The data was then analyzed to determine SN, SP, positive predictive value (PPV), and negative predictive value (NPV) for CHF with BNP Ͼ50 pg/mL (Test A), Ͼ100 pg/mL (Test B), Ͼ300 pg/mL (Test C) and Ͼ 500 pg/mL (Test D). Results: Of 2958 patients 221 matched the study criteria. The mean BNP for stroke patients with CHF (Nϭ109, 21 ICH patients and 88 ischemic) was 1975.8 pg/mL, while the mean BNP for stroke patients without CHF (Nϭ112, 22 ICH patients and 90 ischemic) was 1075.9 pg/mL (pϭ .009 for the mean difference). For Test A the SNϭ94%, SPϭ15%, PPVϭ53%, NPVϭ74%. For Test B the SNϭ83%, SPϭ31%, PPVϭ54%, NPVϭ65%. For Test C the SNϭ61%, SPϭ45%, PPVϭ52%, NPVϭ60%. For Test D the SNϭ49%, SPϭ68%, PPVϭ60%, NPVϭ58%. A 10-fold increase of BNP is required to achieve a 68% specificity for CHF in stroke patients as compared to the general population (Ͼ500 pg/mL vs. Ͼ 50 pg/mL). Conclusion: Although BNP has been shown to be a valuable marker for diagnosing CHF and predicting patient outcomes, it is not a very sensitive or specific marker for assessing CHF in patients who have suffered ischemic or hemorrhagic strokes. Patent foramen ovale (PFO) is an independent stroke risk factor associated with more than 150,000 strokes per year. Clinical trials to investigate treatment options are ongoing, but controversies regarding PFO remain unresolved. Traditionally it is thought that PFOs are implicated in paradoxical embolism by allowing venous clots to travel directly to the brain. However, this simple explanation is likely incomplete, as only a small portion (10-17%) of PFO stroke patients have known hypercoagulable states. A better understanding is needed of the molecular landscape of this complex multi-organ disease involving the brain, heart and circulation. We conduct discovery proteome profiling of plasma markers in PFO patients undergoing clinical endovascular PFO closure, which is a good bedside model to study the direct effects of an open vs closed PFO on circulatory protein signaling. Methods: 53 PFO non-migraineur stroke patients were recruited per IRB-approved protocol, and plasma was collected at baseline, pre and post PFO closure in the left and right atrium. Samples were processed and data generated on Orbitrap XL MS. Intra-patient pre-vs post-closure proteomic profiles were compared, with each patient serving as their own control to reduce potential confounders. Data were analyzed by SIEVE and Ingenuity Pathways. Results: After successful PFO closure, the plasma protein profile changes dramatically. Ingenuity pathway analysis revealed a decrease of coagulation markers such as tissue factor (TF) and fibrinogen, synthesis of fibrinogen's various alpha (FGA) and gamma (FGG) chains, and differential expression of protease inhibitors such as alpha 2 macroglobulin (A2M) and SERPINA 1, important in vascular disease. Cell differentiation factors such as RLF (relaxin like factor or insulin-IGF relaxin factor), and factors that exert negative control of cell growth, such as PPP2R2A, are upregulated -perhaps suggesting a pattern of repair focused on cell differentiation rather than division. Conclusion: These findings demonstrate the feasibility and strength of direct quantitative proteomic exploration in human plasma, using a systems approach incorporating anatomical and temporal dimensions, in a bedside model with each patient as their own control to limit confounding medications and co-morbidities. As an initial step in understanding the molecular landscape of PFO-related circulatory physiology, our results highlight relevant changes in coagulation, cell-signaling and differentiation induced by PFO repair. However, these data are hypothesis generating and further studies are needed.

W P343 Elevated High-sensitivity C-reactive Protein in Acute Stage Cerebral Infarction Predicts Progression of Carotid Intima-media Thickness

Daiki Takano, Takashi Yamazaki, Tetsuya Maeda, Ken Nagata; Rsch Institute for Brain and Blood Vessels, Akita, Japan Objectives: Carotid artery intima-media thickness (IMT) is known as an index of arteriosclerosis and a risk of cardiovascular diseases. Some inflammatory markers are reportedly associated with atherogenesis. However, the association between the increased inflammatory markers in the acute stage stroke and future risk of atherosclerosis is not yet clarified. We tried to elucidate the relationship between the inflammation in acute stage ischemic stroke and progression of arteriosclerosis. Methods: We examined consecutive 107 acute ischemic stroke patients who were admitted within 72 hours from the onset. Their mean age was 71.6 years old, and 70 patients were male. Carotid IMT was measured by B-mode carotid ultrasound on both sides. The maximum IMT of the common carotid artery was defined as CIMT. We concurrently monitored atherogenic parameters including high-sensitivity C-reactive protein (hsCRP), IL-6, and oxidant LDL (oxLDL), and atherosclerotic markers including the ratio of LDL-cholesterol/HDL-cholesterol (LDL/HDL ratio), tryglyceride (TG), blood sugar, estimated GFR, and uric acids. Those parameters were compared according to the first, second and third tertiles of CIMT. Neurological severity was evaluated by NIHSS upon admission (a-NIHSS) and at discharge (d-NIHSS). According to the stroke etiology, the subjects were classified into 3 groups; atherothrombotic brain infarctions (ATBI), Lacunar infarctions (LI) and Cardiogenic embolisms (CE). To evaluate the progression of atherosclerosis, the CIMT measurements were repeated 6 months after the onset, and the difference in CIMT between the baseline and follow-up studies was defined as Delta-CIMT. We investigated the relationship between CIMT and those risk factors. Results: Forty-four patients were diagnosed as ATBI, 29 as LI and 34 as CE. The mean CIMT was significantly greater in ATBI group than in other 2 groups, and the mean Delta-CIMT was also significantly greater in ATBI group than in LI group (pϭ0.001). The oxLDL (pϭ0.005), LDL/HDL ratio (pϭ0.034) and hsCRP (pϭ0.033) were significantly greatest, and the estimated GFR (pϭ0.015) was significantly smallest in the third tertile of CIMT. IL-6 was significantly associated with a-NIHSS (pϭ0.006) and tended to correlate with CIMT. The hsCRP was positively correlated with CIMT in ATBI and LI groups (pϭ0.033) as well as with Delta-CIMT (pϭ0.014). The baseline IMT and TG were also significantly associated with Delta-CIMT. Conclusions: These results suggest that, in acute stage ATBI patients, some serum lipid and inflammatory markers are associated not only with carotid atherosclerosis as but also with its future progression. The measurements of serum lipid parameters and hsCRP will be useful in the assessment of the future risk of stroke patients.

Author Disclosures: D. Takano: None. T. Yamazaki: None. T. Maeda: None. K. Nagata: None.

W P344 Tissue Plasminogen Activator Impairs Hematopoietic Stem Cell Function, Thus Potentially Limiting Stroke Recovery

Aqeela Afzal, Saeed Ansari, Univ of Florida, Gainesville, FL; Christopher P Kellner, Univ of Columbia, New York, NY; Sergei A Sosunov, Columbia Univ, New York, NY; Brian L Hoh, Edward W Scott, Univ of Florida, Gainesville, FL; E Sander Connolly, Columbia Univ, New York, NY; J Mocco; Univ of Florida, Gainesville, FL Background: Intravenous Tissue Plasminogen Activator (tPA) is the only FDA approved pharmacological recanalization therapy for stroke, however tPA has been associated with deleterious effects on the blood brain barrier in experimental models. A potential contributor to vascular integrity and/or repair following stroke are Hematopoietic Stem Cells (HSCs)/ Hematopoietic Progenitor Cells (HPCs), circulating bone marrow derived mononuclear cells that promote repair in areas of injury. HSC/HPC's have recently been shown to mobilize to the peripheral circulation from bone marrow in response to stroke. Furthermore, increasing levels of circulating HSC/HPCs have been demonstrated to correlate with improved neurological function following stroke, suggesting a potentially critical role for HSC/HPC's in limiting stroke injury and/or facilitating stroke recovery. Stromal Derived Growth Factor 1-Alpha (SDF1-A) along with its receptor CXCR4 is a potent chemo attractant released by areas of injury. SDF1-A has been shown to mobilize HSC/HPC from the bone marrow to the blood and lead to 'homing' of the cells to an area of injury. We hypothesized that tPA inhibits HSC/HPC's function, potentially limiting tPA's beneficial effects in acute stroke therapy. Methods: Animals (nϭ10) were euthanized 24 hours post ischemia/reperfusion following a murine intraluminal filament model. Infarction was confirmed using TTC staining of 2 mm sections of the brain. HSC/HPC were harvested from bone marrow and blood using LIN negative and SCA1 Positive labeled nanoparticles. The harvested cells were counted using a hemacytometer; the HSC/HPC were then either left untreated or treated with 10nM TPA and migrated towards SDF1-A in a Boyden Chamber. The level of the SDF1-A receptor (CXCR4) was also assessed by real time PCR of the untreated and tPA treated HSC/HPC. Experiments, and their analysis, were performed in a blinded manner. Results: Mean infarct volume was 43Ϯ10%. Pre-treatment with 10nM tPA reduced HSC/HPC migratory capability towards SDF1-A (100Ϯ1.3% versus 173Ϯ1.0%, PϽ0.05). Pre-treatment with 10nM tPA also reduced expression of CXCR4 from 100Ϯ7.9% to 35.8Ϯ7.1%, PϽ0.05). Conclusion: These data indicate that exposure of HSC/HPC's to tPA abrogates their migratory response to SDF1-A. mRNA analysis of HSC/HPC cells following treatment with tPA demonstrates a down regulation of the CXCR4 receptor. These results suggest that tPA may reduce the ability of the HSC/HPC to home to ischemic brain following stroke and possibly interferes with repair mechanisms associated with HSC/HPC.

W P345 Higher Coated-platelet Levels are Associated with Stroke Recurrence Following Non-lacunar Brain Infarction

Calin Prodan, Julie A Stoner, Linda D Cowan, George L Dale; Univ of Oklahoma, Oklahoma City, OK Background: Coated-platelets are a subset of platelets with high procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with non-lacunar ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage compared to controls. Because prior findings suggested that extremes in coated-platelet potential may be associated with either thrombotic or hemorrhagic events, a study was initiated to investigate a possible relationship between coated-platelet levels and stroke recurrence in patients with non-lacunar ischemic stroke. Methods: Coated-platelet levels were determined in 140 consecutive patients with a diagnosis of non-lacunar stroke based on TOAST criteria. The clinical diagnosis was established by a neurologist who was unaware of the patient's coated-platelet levels. All patients underwent initial brain CT scan followed by brain MRI studies, or repeat brain CT (if MRI was contraindicated) within 24 hours to confirm the presence of cerebral ischemia. The individuals performing the coated-platelet assay were not aware of the clinical diagnosis. Stroke recurrence data were obtained through stroke clinic visits, chart reviews or telephone interviews performed at 3, 6, 9 and 12 months following the initial infarct. Results: Among the 140 patients with initial non-lacunar stroke, follow-up data were available for 132 patients (94%). Cumulative incidence of recurrent stroke at 12 months was 14% (95% CI: 9-23%, 16 recurrences). Coated-platelet levels (meanϮSD) in all stroke patients with follow-up were 40.6Ϯ13.7% (range 10.6-69.7%). Patients were separated into tertiles of coated-platelet levels (lowest 10.6-33.5%, middle 33.6-45.2% and highest 45.3-69.7%). The time to recurrent stroke differed significantly among the coated-platelet level tertiles (overall log-rank test, pϭ0.0092). Pair-wise comparisons (based on a Bonferroni-adjusted alpha level of 0.0167) suggested that the risk of recurrent stroke was higher in the highest and middle coated-platelet tertiles compared to the lowest tertile (pϭ0.0037 and pϭ0.0018, respectively), while the risk did not differ significantly between the middle and highest tertiles (pϭ0.76). Differences in risk were not explained by multiple potential confounding variables. Conclusions: Higher levels of coated-platelets are associated with stroke recurrence in patients with non-lacunar ischemic stroke. This work is supported by OCAST (Dr. Prodan) and AHA (Dr. Dale).

This research has received full or partial funding support from the American Heart Association, South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).

W P346 Coated-platelet Levels are Elevated in Patients with Transient Ischemic Attack Compared to Controls

Calin I Prodan, Univ of Oklahoma, Oklahoma City, OK; Andrea Vincent, Univ of Oklahoma, Norman, OK; George L Dale; Univ of Oklahoma, Oklahoma City, OK Background: Coated-platelets are a subset of platelets with high procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. While coated-platelet levels are elevated in cortical ischemic stroke, lower levels are present in patients with spontaneous intracerebral hemorrhage or with hemorrhagic transformation of ischemic stroke. Because the risk of subsequent ischemic stroke is increased in patients with transient ischemic attack (TIA), we undertook a study to investigate coated-platelet production in patients with TIA. Methods: Coated-platelet levels were determined in 60 patients with a diagnosis of TIA and 60 controls frequency-matched for gender and race and within the same age range as the patient population. The diagnosis of TIA was established by a board certified neurologist and was consistent with the most recent tissue-based definition of TIA: a transient episode of neurological dysfunction without acute infarction. The absence of infarction was demonstrated by normal diffusion-weighted MRI studies. The ABCD2 score, designed to stratify the short-term risk for recurrent stroke following TIA, was recorded in all patients. The individuals performing the coated-platelet assay were not aware of the clinical diagnosis, and the neurologists establishing the diagnosis of TIA were not aware of the patient's coated-platelet levels. Results: Coated-platelet levels were significantly higher in TIA patients compared to controls (mean Ϯ SD, 38.4 Ϯ 15.1% versus 31.0 Ϯ 13.2%, P ϭ 0.005). A significant positive linear correlation was detected between ABCD2 scores and coated-platelet levels in TIA patients (P ϭ 0.003, r ϭ 0.45). Conclusions: Coated-platelet synthesis is increased in TIA patients compared to controls. In addition, coated-platelet levels in TIA patients positively correlate with ABCD2 scores. These findings lend support to the hypothesis that TIA and ischemic stroke represent a spectrum of conditions dependent on similar prothrombotic processes. This work is supported by OCAST (Dr. Prodan) and AHA (Dr. Dale). This research has received full or partial funding support from the American Heart Association, South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).

Author Disclosures: C.I. Prodan: None. A. Vincent: None. G.L. Dale: None.

W P347 Peroxynitrite Disrupts Cerebrovascular Actin Cytoskeleton and Reduces Myogenic Reactivity in Diabetes after Oxygen-glucose Deprivation

Aisha Kelly-Cobbs, Med College of Georgia, Augusta, GA; Roshini Prakash, Univ of Georgia College of Pharmacy, Augusta, GA; Weiguo Li, Adviye Ergul; Med College of Georgia, Augusta, GA Diabetes is a risk factor for cerebrovascular disease and is a reliable predictor of poor stroke outcome. Elevated oxidative stress in diabetes contributes to endothelial dysfunction and heightened small-vessel resistance. It is unclear, however, how diabetes influences cerebrovascular reactivity, especially under ischemia/reperfusion (I/R) conditions. Purpose: We tested the hypothesis that in the presence of diabetes, I/R makes the affected brain more susceptible to edema and bleeding by augmenting peroxynitrite (ONOO -) levels in the vasculature, resulting in nitration of the vascular smooth muscle (VSM) actin cytoskeleton and reduction in cerebrovascular reactivity. Methods: Middle cerebral arteries from age-matched Wistar (nϭ6-8) and type 2 diabetic Goto-Kakizaki rats (nϭ6-8) were exposed to normoxia, oxygen-glucose deprivation (OGD), or OGD followed by acute treatment with the ONOO -decomposition catalyst, FeTPPs, then their vascular reactivity, nitrotyrosine levels and VSM actin content were determined. Results: Basal levels of ONOO -were increased in diabetes (41.0 Ϯ 7.8 vs. 19.8 Ϯ 3.1 pixels). ONOO -was increased in controls and remained high in diabetes after OGD (39.4 Ϯ 6.1 vs. 33.8 Ϯ 11.4) but were reduced in both groups after FeTPPs treatment (19.0 Ϯ 2.1 vs. 24.1 Ϯ 5.1). % myogenic tone was higher across the autoregulatory range (40-120 mmHg) in diabetes, compared to controls (21.5 Ϯ 2.2 vs. 15.3 Ϯ 1.7%). OGD reduced % myogenic tone in both groups (9.7 Ϯ 1.4 vs. 6.9 Ϯ 0.93%); however, basal levels were restored in diabetes but not controls following FeTPPs treatment (18.8 Ϯ 1.8 vs. 9.1 Ϯ 0.79%). Confocal imaging of VSM actin showed similar levels of filamentous (f-) actin in control and diabetes at baseline (46.2 Ϯ 2.2 vs. 44.9 Ϯ 1.4 arbitrary units). OGD reduced f-actin levels (23.9 Ϯ 5.1 vs. 35.4 Ϯ 4.9) but they were restored with FeTPPs treatment (39.0 Ϯ 0.90 vs. 42.8 Ϯ 4.9). At baseline, globular (g-) actin localization was uniform within the cytosol and periphery of VSM cells, whereas OGD concentrated g-actin within periphery in both groups. After FeTPPs treatment, g-actin relocated to the cytosol in diabetes but remained in the periphery in controls. Conclusions: These results suggest that ONOO -generated by OGD contributes VSM actin cytoskeleton disruption, resulting in reduced cerebrovascular myogenic reactivity, particularly in diabetes. Whether this effect contributes to increased edema and bleeding in diabetic animals after acute ischemic stroke needs to be confirmed by in vivo studies.

Author Disclosures: A. Kelly-Cobbs: None. R. Prakash: None. W. Li: None. A. Ergul: None.

W P348 Cigarette Smoke Induces Oxidative Stress and Phenotypic Modulation in Cerebral Vascular Smooth Muscle Cells

H. Kwang Yeoh, Thomas Jefferson Univ, Philadelphia, PA; Brian J Titus, Gary K Owens, Univ of Virginia, Charlottesville, VA; Robert H Rosenwasser, Aaron S Dumont; Thomas Jefferson Univ, Philadelphia, PA Molecular mechanisms by which cigarette smoke contributes to cerebral aneurysm pathology are unknown. We investigated the role of cigarette smoke-induced oxidative stress in the phenotypic modulation of cerebrovascular smooth muscle cells (CVSMC), which is a hallmark of aneurysm pathology. Methods: Human CVSMC's were treated with 4, 40 and 400ug/mL cigarette smoke extract (CSE) with or without 25U/mL polyethylene glycol-superoxide dismutase (PEG-SOD), a potent oxygen free radical scavenger. Oxidative stress was analyzed with 250uM lucigenin chemiluminescence using a luminometer and 2umol/L dihydroethidium using confocal microscopy. Fluorescence excitation was set at 480 nm with emission detection at 570 nm long pass filter. Smooth muscle cell (SMC) marker gene and protein expression was analyzed with RT-qPCR and western blotting, respectively. These were done in untreated cells, CSE treated CVSMC's and cells treated with concurrent CSE and PEG-SOD. Results: A dose-dependent increase in oxidative stress (not shown) was seen in CSE-treated CVSMC's that was reversible with PEG-SOD. CSE treatment produced profound dose-dependent phenotypic modulation in CVSMC with decreased expression of SMC marker genes (SM MHC, SM alpha-actin and SM 22-alpha) and myocardin and upregulation of matrix remodeling genes including MMP-3 (not shown) with RT-PCR. Western blot analysis demonstrated similar results with loading control alpha-actin. Strikingly, phenotypic modulation was prevented with concurrent treatment with PEG-SOD. Conclusion: CSE induces dose-dependent oxidative stress in cultured CVSMC that is prevented with PEG-SOD. Moreover, CSE induces profound phenotypic modulation in CVSMC including downregulation of SMC marker genes and myocardin as well as upregulation of matrix remodeling genes. This phenotypic modulation is abrogated with PEG-SOD treatment implicating a critical role for superoxide in this process. The present results have implications for the pathophysiology of cerebral aneurysms and this may represent a novel target for future therapy.

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W P349 Mechanisms of Natural Vitamin E, Alpha-Tocotrienol, in Pial Collateral Recruitment and Remodeling During Acute Ischemic Stroke

Laura A Peterson, Cameron L Rink, Savita Khanna, Mallory Heigel, Chandan K Sen; Ohio State Univ, Columbus, OH Background: Vitamin E is a generic term for tocopherols and tocotrienols. The lesser characterized isoform a ´-tocotrienol (T3) exhibits neuroprotective properties not shared by tocopherols (TP). Previous work in a large animal model of stroke demonstrated that prophylactic supplementation of T3, but not TP, attenuates stroke mediated brain injury and improves pial collateral circulation. In the clinical setting, pial collaterals have been documented to perfuse, via retrograde flow, the proximally occluded parent vessel and improve stroke outcomes. While improving pial circulation is a therapeutic target of recognized value, mechanisms of pial recruitment and remodeling during stroke are unknown. The paucity of experimental systems to test the significance of pial circulation in stroke has limited research efforts. Objective: To employ T3 as an experimental tool to identify mechanisms of pial collateral recruitment and remodeling during ischemic stroke. Method: Mice (C57/BL6, nϭ10) were randomized and supplemented with 200mg/kg of T3 or vehicle placebo (PBO) for 15wks prior to middle cerebral artery occlusion (MCAO). Following 30min of MCAO, and while ischemia persisted, mice were injected with 5l of fluorescent conjugated lectin (Lycopersicon esculentum) to visualize the perfused pial circulation in the stroke affected hemisphere. Immunohistochemistry directed laser microdissection pressure catapult (LMPC) of pials from the MCAO territory for downstream gene and protein analysis. Results: T3 supplemented mice had significantly smaller stroke lesion volume as compared to PBO controls and improved pial perfusion in the MCAO territory. This corresponded with improved functional recovery following stroke. Quantitative RT-PCR and Western blot protein expression analysis identified T3-induced pial targets including chloride intracellular channel 1 (CLIC-1), TIMP-1, and matrix metalloproteinase 2 (MMP-2). T3 supplementation increased expression of CLIC-1 and TIMP-1 and

W P350 The Protective Effect Of Spironolactone On Cerebral Ischemia/reperfusion Injury In Nicotine Exposed Mice

Nikola Sladojevic, Svetlana M Stamatovic, Bertram Pitt, Richard F Keep, Anuska V Andjelkovic; Univ of Michigan, Ann Arbor, MI Purpose: A substantial body of evidence suggests that cigarette smoking and nicotine enhance the process of "vascular aging" and has aggravating effect on cerebrovasuclar ischemic events. This study examined the effect of mineralocorticoid receptor inhibitor spironolactone (SPIRO) in reducing the nicotine induced-prestroke and poststroke changes in cerebrovascular endothelium. Methods: C57BL/6 mice were chronically exposed to nicotine (2 mg/kg/body weight) via s.c. implanted miniosmotic pumps for 14 days which resulted in plasma nicotine levels of ϳ100 ng/ml, reflecting plasma concentrations in average smokers. For analysing the prestroke effect of SPIRO in nicotine-exposed animals, the mice were treated with SPIRO (i.p., 0.02mg/kg body weight) from day 7 of nicotine exposure. For analyzing the postroke changes, the mice started to receive SPIRO (i.p., 0.02mg/kg body weight) either before (7 days) or after (2 hrs) transient middle cerebral artery occlusion (tMCAO, 30 min of occlusion followed by reperfusion 1-7 days). In both experimental conditions mice were sacrificed and were used for analysis of brain edema, blood brain barrier permeability, inflammatory response and infarct volume. Results: Nicotine exposure mice had significant proinflammatory changes of cerebrovasuclar endothelium associated with increased permeability of BBB for small molecules (inulin permeability) -prestroke changes, and also worse cerebrovascular injury that was reflected in increased infarct size, greater brain edema, higher mortality rate and worse neurological deficits than in non-nicotine exposed mice-poststroke changes. Application of SPIRO (0.02 mg/kg body weight per day, i.p.) during the chronic nicotine exposure markedly reduced infarct size and the neurological damage induced by tMCAO. Application of SPIRO after MCAO (2hrs) also affected the outcome of brain I/R injury (reduced infarct size, decreased mortality, improved neurological score). Screening of 62 different proinflammatory cytokines, chemokines and adhesion molecules by real time RT-PCR and antibody-based protein array, indicated that SPIRO added during nicotine exposure and after tMCAO significantly reduced the expression of some cytokines chemokines, adhesion molecules, that were upregulated by nicotine. There is also significantly reduced infiltration of leukocytes in brain parenchyma. Conclusions: SPIRO attenuated the detrimental effects of nicotine at BBB in prestroke condition as well as in brain I/R injury suggesting that SPIRO could be potential treatment for stroke in cigarette smokers.

W P351 Plasma Aldosterone Increases Rapidly After Cerebral Ischemia with Reperfusion Injury

Anne M Dorrance; Michigan State University, East Lansing, MI We, and others, have shown that inhibition of the mineralocorticoid receptor (MR) reduces the damage caused by cerebral ischemia in rats. Very little is known about how ischemia affects plasma aldosterone, the endogenous agonist for the MR. We tested the hypothesis that aldosterone would increase dramatically after cerebral ischemia / reperfusion injury. 12-weekold male Sprague Dawley rats underwent a middle cerebral artery (MCA) occlusion for 1 hour followed by 5 (nϭ6) or 23 (nϭ8) hours of reperfusion. Sham operated rats served as controls (nϭ6). Plasma was collected from these rats and aldosterone levels were measured by ELISA. We found a fifteen-fold increase in plasma aldosterone in the 5-hour reperfusion rats (31.66Ϯ9.23 vs 493.51Ϯ116.91pg/ml, sham vs control, PϽ0.05). Plasma aldosterone remained elevated 23 hours after reperfusion (299.57Ϯ64.38pg/ml, PϽ0.05 compared to sham). Aldosterone or MR activation has previously been linked to matrix metalloproteinase (MMP) activation, inflammation and cell proliferation in other parts of the cardiovascular system. We measured the mRNA expression of several markers of these pathways in the MCAs from the rats that underwent ischemia / reperfusion injury. The MCA that experienced ischemia was compared to the contralateral (control) MCA in a paired fashion, and the results were expressed is fold change from control and normalized to B2-microglobulin expression. After 5 hours of reperfusion there was a trend toward and increase in matrix metalloproteinase (MMP)-9 expression (1.01Ϯ0.00 vs 20.51Ϯ8.86, control vs ischemic, pϭ0.08), this became significant after 23 hours of reperfusion (1.01Ϯ0.01 vs 7.45Ϯ2.2, control vs ischemic PϽ0.05). MMP-12 expression was also elevated after 23 hours of reperfusion (1.07Ϯ0.03 vs 3.50Ϯ0.04, control vs ischemic, pϽ 0.5), and surprisingly, the expression of its substrate, elastin was reduced (1.01Ϯ0.00 vs 0.74Ϯ0.07, control vs ischemic, PϽ0.05). At this time, markers of cell proliferation and macrophage infiltration were also increased in the MCA that had been ischemic as evidenced by an increase in mKi67 (1.04Ϯ0.03 vs 3.27Ϯ0.46, control vs ischemic, PϽ0.05) and CD68 (1.00Ϯ0.00 vs 1.43Ϯ0.17, control vs ischemic PϽ0.05) respectively. We have previously reported that the structure of the MCA changes after reperfusion resulting in a vessel with a lumen diameter that is 20ı `m larger than a control vessel. MMP activation, inflammation and cell proliferation have all previously been implicated in the vessel remodeling process. Therefore, it is possible that aldosterone may stimulate vessel remodeling, macrophage infiltration, cell proliferation and intracellular matrix breakdown in the injured vessels post-stroke. This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: A.M. Dorrance: Research Grant; Significant; American Heart Association. Introduction: To evaluate the safety of treatment in a single arm ischemic stroke trial or in ongoing randomized trials, it is necessary to know the expected rate of neurologic adverse events (AEs) in control subjects. Hypothesis: The study determined whether prospectively evaluating all neurologic AEs and applying time from randomization criteria in the control arm could provide rates of expected safety events to compare against treatment arm events. Methods: As specified in the Data and Safety Monitoring Board (DSMB) charter, the DSMB adjudicated all neurologic AEs for the multi-center Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial, randomizing patients aged 18 years and older with National Institutes of Health Stroke Scale (NIHSS) scores of 5-18 within 14 hours of symptom onset with follow-up of 90 days. The current study determined control group rates for those events critical for trial safety determinations, including intracranial hemorrhage (ICH), cerebral edema, neurologic worsening/stroke progression and new ischemic stroke. An AE was classified as serious (SAE) if it resulted in neurologic deterioration considered clinically relevant by the DSMB, was associated with a 4-point NIHSS increase, was fatal, life threatening, required or prolonged hospitalization, or required intervention to prevent permanent impairment. The number of AEs occurring within the following defined time periods after randomization provided a basis for determining treatment relatedness: 24-hr (range 5-48 hrs) imaging for ICH (by AE forms and core lab), 7 days for cerebral edema and neurologic worsening/stroke progression, and 30 days for new stroke. Results: The SENTIS control group included 257 patients, 49.4% female with a mean age of 68.3 and median baseline NIHSS of 10.0. Any ICH during follow-up occurred in 27% (70/257), 63% (44/70) on the 24-hr scan of which 1.9% (5/257) were categorized as SAEs. Cerebral edema was seen in 6.6% (17/257), 94% (16/17) of events occurring within 7 days of randomization of which 3.5% (9/257) were categorized as SAEs. Neurologic worsening/stroke progression occurred in 22% (57/257), 74% (42/57) of events occurring within 7 days of which 13% (33/257) were SAEs. New ischemic stroke occurred in 4.7% (12/257), 83% (10/12) of events occurring within 30 days of which 1.9% (5/257) were SAEs. Conclusions: Prospective capture of neurologic safety events in the control group of the SENTIS acute stroke trial showed that ICH SAEs occurred in 1.9% on the 24-hour scan while cerebral edema SAEs occurred in 3.5% and neurologic worsening/stroke progression SAEs in 13% within 7 days and new stroke SAEs in 1.9% within 30 days of randomization. Knowing the expected neurologic AE rate will allow better assessment of safety in single arm and future stroke trials.

Th P1 Neurologic Safety Event Rates in the SENTIS Control Population

Author Disclosures: H.L. Lutsep: Consultant/Advisory Board; Significant; DSMB, Co-Axia. I.M. Altafullah: Consultant/Advisory Board; Significant; DSMB, Co-Axia. R.S. Roberts: Consultant/ Advisory Board; Significant; DSMB, Co-Axia. I.E. Silverman: Consultant/Advisory Board; Significant; DSMB, Co-Axia. M.A. Turco: Consultant/Advisory Board; Significant; DSMB, Co-Axia. A.G. Vaishnav: Consultant/Advisory Board; Significant; DSMB, Co-Axia. Background & Purpose: Low intensity transcranial ultrasound augments tPA-induced arterial recanalization. We aimed to evaluate normal volunteers in the first phase of a study of the safety and estimated peak negative pressure of an operator-independent ultrasound device developed to deliver ultrasound energy exposure levels administered in the CLOTBUST trial. Subjects & Methods: An 18-transducer 1-2.5 MHz emitting frequency head frame exposed both temporal windows and suboccipital window in volunteers free of cerebrovascular disease. The transmission characteristics were set to emulate the acoustic characteristics of commercially available transcranial Doppler systems and to never exceed the FDA-mandated ultrasound exposure limits. Volunteers underwent 2 hours of insonation with transducer activation one at a time. Estimated peak negative pressures were calculated based on our previously developed acoustic attenuation model. Measurements were taken in volunteers who received the insonation via the "best pair" temporal transducers placed on both sides of the skull. Safety was captured using serial neurological examinations (NIH Stroke Scale) and preand post-insonation multimodal with/without gadolinium MRI for detection of any lesions and the blood brain barrier (BBB) permeability interpreted by an independent expert using a specific algorithm. Results: A total of 15 healthy volunteers (40% men; 49Ϯ16 yrs; 27% African-Americans; NIHSS score 0) were continuously insonated for 2 hours with the device. Five volunteers received pulsed wave ultrasound via the "best pair" temporal transducers (group 1), 5 via sequential activation of the suboccipital transducers (group 2), and 5 via sequential activation of all bilateral temporal and suboccipital transducers (group 3). Group 1 volunteers had an average temporal bone thickness of 2.3 mm (range 1.5-3.0 mm). The mean estimated in vivo peak negative pressure at 3.2 cm intracranial depth was 59Ϯ17 kPa, and the maximum derated intensity (Ispta.3) levels did not exceed the 720 mW limit. All subjects were safely insonated with no adverse effects as indicated by the neurological examinations during, immediately after the exposure and at 24 hrs (all NIHSS scores 0), and no breach of the BBB was found on all MRI's. Conclusion: Our novel device was well tolerated by the healthy volunteers and did not cause any neurological dysfunction and did not affect the integrity of the BBB. The device delivered estimated peak negative pressures across the proximal vessels of the circle of Willis at Ͼ 19 kPa levels, the lower threshold needed for optimized microstreaming as the key factor in achieving sonothrombolysis. The safety of the device is currently being tested in stroke patients receiving IV tPA as part of a NIH-sponsored clinical trial.

Th P2 CLOTBUST-Hands Free Operator Independent Ultrasound Device: Initial Safety Testing in Healthy Volunteers

Th P3 Reduced Low Density Lipoprotein Cholesterol Fraction Is Not A Risk Factor For Hemorrhagic Transformation After Intravenous Thrombolysis Therapy For Acute Ischemic Stroke

Eoin P Flanagan, Mayo Clinic, Rochester, MN; Felix E Chukwudelunzu, Luther Midelfort Mayo Health System, Eau Claire, WI; Jay Mandrekar, Mayo Clinic, Rochester, MN; Bart M Demaerschalk, Mayo Clinic and Mayo Clinic Telestroke Network, Phoenix,, AZ; James F Meschia, Kevin M Barrett, Mayo Clinic, Jacksonville, FL; Kelly D Flemming, Mayo Clinic, Rochester, MN; Gregory T Pupillo; Franciscan Skemp Mayo Health System, LaCrosse, WI Background and Purpose: Current available data on the relationship between hemorrhagic transformation (HT) of acute cerebral ischemic stroke following intravenous tissue plasminogen activator therapy (IV-tPA) and reduced low density lipoprotein cholesterol (LDL-C) fraction is limited and available data show conflicting results. The primary purpose of this study was to assess this relationship and other potential factors that may influence hemorrhagic transformation of acute cerebral ischemic stroke after IV-tPA in a homogenous patient population. Method: We reviewed the medical records of 388 patients from a database of IV-tPA recipients (according to AHA/ASA guidelines) at four Joint Commission Certified Primary Stroke Centers and one community hospital with an active stroke unit. We included 189 patients that received IV-tPA alone and in whom pertinent clinical and laboratory information was available. Results: The mean age (Ϯstandard deviation [SD]) was 71.3 (Ϯ13.9) years and 54.3% were men. Treatment violation with IV-tPA occurred in 8 patients (4.2%). Twenty-two patients (11.6%) had any HT after IV-tPA treatment and in 9 patients (4.8%) it was symptomatic. There was no difference in the LDL-C level among patients with HT and those without HT (100.8 vs 95.3 mg/dl; OR1.004; 95% CI, 0.992 -1.016; pϭ0.5). However, a prior history of diabetes mellitus (31.8% vs 12.6%;OR 3.245;95% CI,pϭ0.02) or prolonged mean time from symptom onset to presentation at the emergency room (74.4 minutes vs 56.0 minutes; OR 1.015; 95% CI, 1.002-1.027; pϭ0.02) was associated with an increased risk of HT. Factors that were more prevalent in patients with HT compared to those without HT, but did not reach statistical significance on the univariate logistic regression analysis included: prolonged time (ϮSD) in minutes from symptom onset to IV-tPA administration (137.8 Ϯ29.6 vs 125.5 Ϯ37.2; pϭ0.14); total cholesterol (178.4 vs 168.1 mg/dl, pϭ0.26); triglycerides level (143.4 vs 121.0 mg/dl; pϭ0.18); history of hypertension (94.7% vs 78.7%; pϭ0.13); and aspirin intake (63.6% vs 47.9%; pϭ0.17). Conclusion: Prior history of diabetes mellitus and prolonged time of symptom onset to hospital arrival, but not reduced LDL-C, is associated with increased frequency of HT following IV-tPA after ischemic stroke.

Th P4 Microalbuminuria: An Independent Risk Factor For Intracerebral Hemorrhage After I.v. Thrombolysis For Acute Stroke

Andrea Rocco, Christoph Gumbinger, Marek Sykora, Jennifer Diedler, Peter Ringleb, Werner Hacke; Karls-Ruprecht Universita ¨t, Heidelberg, Germany Background: Intracerebral hemorrhage (ICH) represents one of the most feared complications of thrombolysis. Age, clinical stroke severity at admission, high blood pressure, hyperglycemia, and early CT changes are well known predictors of ICH. In recent years, the role of microalbuminuria (MA) as a risk factor for cerebrovascular disease has become apparent. The aim of our study was to determine the predictive value of MA for intracerebral hemorrhage after thrombolysis. Methods: Thrombolysed acute stroke patients were consecutively studied. Clinical data, early CT changes, vascular risk factors and other known predictors for ICH after thrombolysis were prospectively collected. Severity of stroke was assessed by NIHSS. ICH was categorized according to the SITS criteria. The urinary albumin excretion was measured in 24-h collection of urine. Results: Overall 55 patients were included. With 96%, the majority of patients had a previous history of hypertension, 45% had diabetes, 24% had atrial fibrillation, and 11% had a previous stroke. The median NIHSS at admission was 8 (range 3-34, IQR 8). Ten patients (18.2%) suffered from ICH after thrombolysis, 3 with HI1, 2 with HI2 and 5 with PH2. In the univariate analysis ICH was associated with MA (rϭ0.4, pϭ0.003), stroke severity (rϭ0.23, pϭ0.04), cholesterol level (rϭ-0.3, pϭ0.02) and ASA pretreatment (rϭ0.23, pϭ0.04). In the logistic regression analysis MA (OR 12.5,pϭ0.036) and cholesterol level (OR 0.97, CI 0.95-0.99, pϭ0.04) remained as independent predictors for ICH after thrombolysis. We didn't find any difference in MA between the HI and PH. Conclusion: In our study MA was independently associated with ICH after thrombolysis. We hypothesize that premorbid endothelial damage as suggested by increased microalbuminuria may contribute to the pathophysiology of hemorrhagic complications after i.v. thrombolysis.

Th P5 Telestroke Guided IV tPa Treatment Achieves Similar Clinical Outcome As Thrombolysis At Comprehensive Stroke Center

Syed F Zaidi, Mouhammad A Jumma, Maxim D Hammer, Vivek K Reddy, Tudor G Jovin, Lori Massaro, UNIVERSITY OF PITTSBURGH, Pittsburgh, PA; Ken Uchino, Cleveland Clinic, Cleveland, OH; Lin Ridwan, Lawrence R Wechsler; University of Pittsburgh, Pittsburgh, PA Background: Many acute ischemic stroke patients eligible for treatment with intravenous tissue plasminogen activator (IV tPA), never receive treatment due to lack of stroke expertise and experience. To fill this void, a telestroke network was established between the UPMC Stroke Institute and regional community hospitals to provide acute stroke expertise. Vascular neurologists provided 24/7 coverage using real time 2 way audio video telemedicine and neuroimaging access at these facilities. To assess the adequacy of this approach, we compared clinical outcomes following systemic thrombolysis at telestroke facilities versus treatment at comprehensive stroke center. Methods: All patients treated with IV tPA at 12 community hospitals by telestroke during an 19 month period were compared to patients similarly treated following face to face evaluation by the same group of vascular neurologists at a university tertiary care stroke center over the same time interval. Time to treatment and time from door to treatment and functional outcome at 90 days were obtained prospectively. Favorable outcome was defined as modified rankin score of Ͻ 2. Results: Between June 2008 and December 2009, eighty three patients were treated with IV tPA after a telestroke consultation and 59 patients received IV tPA at the stroke center. Favorable outcome rates were comparable between the groups at 42.1% in the telestroke group and 37.5% in patients treated at the stroke center (pϭ0.7). There was no significant difference between the groups in the rate of symptomatic (1% v. 5%, pϭ0.1) or asymptomatic hemorrhage (19% v. 16%, pϭ0.7). Time from stroke onset to treatment was similar in the 2 groups but time from door to treatment was significantly longer in the telestroke group. Conclusion: Telestroke guided IV tPA at community hospitals under supervision of stroke experts achieved similar clinical outcomes compared to treatment administered in person by the same physicians at a tertiary care stroke center. A delay in door to treatment time was introduced when using telestroke but this did not result in worse outcomes. Telestroke is a viable alternative to in person acute stroke evaluation when stroke expertise is not readily available.

Th P6 Antiplatelet and Anticoagulation Therapy Before an Ischemic Stroke Neither Precludes nor Complicates Intravenous Thrombolysis

Dimitriy Levin, Don B Smith, Ethan Cumbler, William Jones; Univ of Colorado, Aurora, CO Objectives: To ascertain the effect of baseline antiplatelet (AP), anticoagulation (AC), or dual antithrombotic (APϩAC) therapy on the likelihood of receiving intravenous thrombolysis with recombinant tissue plasminogen activator (tPA) after acute ischemic stroke and on subsequent hemorrhage rates. Methods: We queried the Colorado Stroke Registry, a shared database of 38 Colorado hospitals. Patients with complete records of outpatient ischemic stroke seen within 180 minutes of onset were included in the analysis. The CSA database tracks standard contraindications to tPA, including INR Ͼ 1.7. Results: Of the 15,625 records, 1,322 (8.5%) met inclusion criteria. The table shows INR and NIH Stroke Scale values for all patients in the groups of interest and for those without contraindications to tPA. Of the 777 patients (59%) without contraindications, 55% received tPA. AP patients were no more likely than controls (patients not previously on antithrombotics) to have tPA contraindications (39% vs. 40%, p ϭ 0.67), and eligible patients were as likely to receive tPA (58% vs. 54%, p ϭ 0.33). AC patients were more likely than controls to have tPA contraindications (66% vs. 40%, p Ͻ 0.0001), but eligible patients were as likely to receive tPA (70% vs. 54%, p ϭ 0.14). APϩAC patients were no more likely than controls to have tPA contraindications (50% vs. 40%, p ϭ 0.19), and eligible patients were as likely to receive tPA (43% vs. 54%, p ϭ 0.33). AP, AC, or APϩAC therapy did not increase the risk of symptomatic intracerebral hemorrhage (SICH), serious systemic hemorrhage (SSH), or other serious complications (OSC), as seen in the table. Conclusions: Pre-stroke AP, AC, or APϩAC therapy does not decrease the likelihood of IV tPA treatment in the absence of published contraindications. In contrast to some reports, eligible patients on AP, AC, or APϩAC therapy who receive IV tPA do not appear to have an increased risk of serious complications. We recognize, however, that numbers are small in some subgroups, and a type-II statistical error cannot be excluded.

minutes shorter (pϽ.0001) and K was 1 minute shorter (pϽ.0001) in AIS patients compared to controls after correcting for age. Delta averaged 0.6 Ϯ 0.6 minutes (vs 0.7-1.1 minutes in controls). All these findings indicate hypercoagulability in AIS. Nineteen AIS patients had elevated G values indicating platelet-rich clots (G ϭ 11.3 Ϯ 2.3 Kd/cm2) while the remaining patients had lower G values (G ϭ 7.9 Ϯ0.6 Kd/cm2) (pϽ.001) which, along with lower delta, indicates "red" clot with more thrombin contribution and less platelets (see figure 2). G significantly decreased post-tPA compared to baseline (pϽ.0001) confirming the fibrinolytic effect of tPA. Conclusion: AIS patients are hypercoagulable due to robust thrombin generation, and form clots with varying strength and composition, which undergo fibrinolysis by tPA. TEG may provide a way to monitor and adjust thrombolytic therapy so that it is safer and more effective, as well as individualized to the patient.

Th P8 Baseline Total Cholesterol Levels and Risk of Symptomatic Hemorrhagic Transformation after Intravenous Thrombolysis in Acute Ischemic Stroke Patients

Svetlana Lorenzano, La Sapienza Univ, Rome, Italy; Niaz Ahmed, Karolinska Univ Hosp, Stockholm, Sweden; Giuseppe Moretto, Az Osp Istituti Ospitalieri, Verona, Italy; Paolo Nichelli, Nuovo Ospedale Civile, Modena, Italy; Norina Marcello, Arcispedale, Reggio Emilia, Italy; Roberto Curro `-Dossi, Ospedale Centrale, Bolzano, Italy; Domenico Inzitari, Careggi Univ Hosp, Florence, Italy; Alessandro Rosselli, Ospedale S. Maria Annunziata, Florence, Italy; Giancarlo Comi, San Raffaele Univ Hosp, Milan, Italy; Mauro Furlan, Ospedale Imperia, Imperia, Italy; Donata Guidetti, Presidio Ospedaliero, Piacenza, Italy; Maria Rosaria Tola, Arcispedale S Anna, Ferrara, Italy; Claudio Pozzessere, Ospedale San Camillo, Rome, Italy; Francesco Perini, Ospedale Civile, Vicenza, Italy; Roberto Sterzi, Ospedale Niguarda Ca' Granda, Milan, Italy; Emilio Ursino, Osp. SS. Antonio e Biagio, Alessandria, Italy; Mauro Magoni, Spedali Civili, Brescia, Italy; Nils Wahlgren, Karolinska Univ Hosp, Stockholm, Sweden; Massimiliano Prencipe, Danilo Toni; La Sapienza Univ, Rome, Italy Objectives: There are evidences that low cholesterol levels (CLs) are associated with intracranial hemorrhage. Aim of this study was to evaluate if baseline CLs might have influence on the risk of symptomatic hemorrhagic transformation (HT) after i.v. thrombolysis in acute ischemic stroke (AIS). Methods: We analyzed all the data of AIS patients treated with i.v. rt-PA in Italy from 2003 to 2009 included in the international internet-based SITS-ISTR (Safe Implementation of Treatment in Stroke -International Stroke Thrombolysis Register). Symptomatic intracerebral hemorrhage (SICH) was defined as any type of hemorrhage associated with any clinical worsening at NIHSS (NINDS definition). We also considered ECASS and SITS-MOST definitions of SICH. CLs were generally obtained within 24 hours from thrombolytic treatment. Univariate and multivariate analyses were performed. Results: Overall, 4194 patients were included, for 2577 (61.5%) we have data on baseline total CLs. Median value was 191 mg/dl (80-499). We identified three different CLs based on percentiles 25, 50 and 75: Յ164 mg/dl (648/2577 patients, 25.1%), Յ191 mg/dl (1292/2577, 50.1%) and Յ221 mg/dl (1940/2577, 75.3%). Compared to those with higher levels, patients with CLs Յ164, Յ191 and Յ221 mg/dl were more likely to be male (pϭ0.001), older (pϽ0.01), with more diabetes, AF, congestive heart failure, on prior antiplatelet (pϽ0.0001), anticoagulant (pϽ0.01) and/or, only the subgroup Յ191 mg/dl, antihypertensive therapy (pϭ0.027). Moreover, they had lower baseline SBP (respectively, pϭ0.031, Ͻ0.0001, Ͻ0.0001), lower baseline DBP (only for the subgroups Յ191 and Յ221 mg/dl, respectively pϭ0.043 and 0.049), higher rate of cardioembolic stroke (pϽ0.0001), and early clinical improvement at 24 hours (only in the third subgroup, pϭ0.039), less use of aspirin and higher use of other antiplatelets and oral anticoagulants (pϽ0.01) during the hospital stay. There are not significant differences for the functional outcome at 3 months. Patients with CLs Յ164 mg/dl tend to have a higher mortality (pϭ0.006), but this data is not confirmed at the multivariate analysis. At the univariate analysis CLs Յ164 mg/dl were associated with SICH according to SITS-MOST definition (very severe SICH) (pϭ0.046). At the multivariate analysis CLs did not result as independent predictors of SICH according the different definitions. Conclusions: Our study did not show an association between lower baseline total CLs and the risk of HT after i.v. thrombolysis in AIS. More studies are necessary to address this issue, particularly considering also the LDL-CLs and the use of statins at stroke onset.

Th P9 Level Of Consciousness And Gaze Paralysis In The Baseline NIH Stroke Scale (NIHSS) Exam Are Independent Predictors Of Death After Ischemic Stroke

Vikas Gupta, Enrique Leira, Patricia Davis, Harold P Adams; Univ of Iowa, Iowa city, IA Background: The risk of death after an ischemic stroke depends on the patient's age, size and location of the infarction. The baseline NIHSS score, a marker of infarct size, is associated with the risk of death. We aimed to investigate whether abnormalities in individual items of the baseline NIHSS exam, might be independently associated with death at three months after a cerebral infarction. Methods: We retrospectively analyzed all subjects enrolled in the AbESTT-I and AbESTT-II trials (abciximab vs. placebo). All patients had a baseline NIHSS exam on admission. The occurrence of death in the 3 months following the stroke was recorded. We performed univariate comparisons between baseline NIHSS items and death. We also performed a multivariate logistic analysis using death as the dependent variable with each of the baseline NIHSS items as covariates. The analysis was adjusted for age, sex, race systolic blood pressure, abciximab use and total NIHSS score. Results: A total of 1204 patients were analyzed. The mean NIHSS was 9.7 (SD 5). 129 (10.7%) subjects died within 3 months of their stroke. Total NIHSS score and all the individual NIHSS items except limb ataxia were associated with increased mortality risk at 3 months. However, in multivariate logistic analysis only level of consciousness (pϭ0.007) and gaze paralysis on NIHSS (pϭ0.002), and to lesser degree language (pϭ0.03), were independently associated with mortality at 3 months. The risk of death in a patient with normal level of consciousness and gaze score was 5%. The risk increased to 59% if these 3 items were abnormal. Conclusion: The presence of an abnormal level of consciousness, horizontal gaze palsy and to a lesser degree language in the baseline NIHSS are associated with 3 months mortality after ischemic stroke. These are independent of the other elements of the NIHSS and confounders. We hypothesize that these three items are a marker of a multilobar MCA infarction with associated risk of hemorrhagic transformation, cerebral edema or increased intracranial pressure. Table1: Probability of death at 90 days with combinations of LOC, gaze & language.

Author Disclosures: V. Gupta: None. E. Leira: None. P. Davis: None. H.P. Adams: None.

Th P10 Normal CTA should raise suspicion of Stroke Mimics In Candidates for i.v. Fibrinolysis

Jason J Chang, Julian P Yang, Yazan Alderazi, Mohamed Teleb, Lucas Restrepo; Barrow Neurological Institute, Phoenix, AZ Background and Purpose: An increasing number of patients with stroke mimics (SM) receive treatment with intravenous fibrinolysis. Factors explaining this trend include greater familiarity Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from with rt-PA among clinicians, time constraints of therapy, and limited capacity for confirmatory diagnostic tests. Although an emerging body of literature indicates that SM rarely develop complications, these patients are exposed to the inherent dangers of fibrinolytic therapy without any expected benefits, and require observation in intensive care units. We report herein our experience with emergency CT angiography (CTA) in patients treated with i.v. rt-PA, and analyze its capacity to distinguish SM from acute ischemic strokes (AIS). Materials and Methods: Retrospective analysis of 193 patients treated with i.v. rt-PA between 2007193 patients treated with i.v. rt-PA between -2008. CTA of the head and neck was done in 163 of these patients during their initial Emergency Room assessment. The remainder of patients had MRA (nϭ18) or no vascular imaging (nϭ12). Patients were classified into 3 groups: AIS with confirmed brain ischemia on follow-up imaging (nϭ142), TIA or "aborted" stroke (AbS)_defined as cases of compelling AIS symptoms without diffusion-weighted imaging abnormalities (nϭ21), and SM (nϭ30). Arterial occlusion (AO) was defined as presence of Ն1 distal arterial cutoffs, and atherosclerosis as any region of arterial wall irregularity leading to focal stenosis on CTA. Chi-squared statistics and step-wise logistic regression analysis were used. Results: AO was noted in 78 AIS patients (57.8%) but in none of the AbS and SM cases (pϽ 0.001). Atherosclerosis was noted on 116 (86.6%) AIS patients, 10 (58.8%) AbS, and 6 (21.4%) SM. CTA did not distinguish SM from AbS, but advanced age and cardiovascular risk factors were significantly overrepresented in the latter (pϽ0.001). Overall, the finding of any arterial wall abnormality on CTA increased the odds of AIS over SM (ORϭ23.6, 95%CI: 8.43-66.2, PϽ0.001) and AIS over AbS (OR 4.51,PϽ0.01). None of the patients with SM had hemorrhagic complications. Conclusions: Emergency CTA may help discern whether i.v. rt-PA candidates truly need treatment. The finding of normal CTA should encourage clinicians to re-evaluate patients and may justify an emergency MRI to confirm diagnosis, if feasible. This study should be interpreted with caution, as further research is needed to validate our observations. Introduction: Central retinal artery occlusion (CRAO) or an eye stroke causes monocular vision loss with a poor chance of spontaneous recovery. A metanalysis of all reported cases suggests that vision improvement occurs in 48.5% of patients. We therefore hypothesize that the use of intravenous tissue plasminogen activator (tPA) would result in reperfusion of acute CRAO with improved VA. Methods: A multi centered, subject blinded, placebo controlled, randomized controlled trial (RCT) of 0.9 mg/kg of tPA was conducted in subjects with CRAO diagnosed by an ophthalmologist within 24 hours of symptom onset. The primary outcome was a change in VA of 3 lines or more equivalent to an increase of Ն0.3 log MAR score. Results: 16 patients were randomized. 2/8 (25%) of the tPA group achieved an improvement of VA of 3 lines or more as opposed to none in the placebo group; both receiving tPA within 6 hours of symptom onset. There was a significant improvement of the mean logMar VA of 0.4 at 3 months favouring tPA (pϭ0.02). One intracranial hemorrhage occurred post tPA and two had ocular neovascularization. Conclusion: This is the first randomized controlled trial that demonstrates the efficacy of IV tPA in CRAO if administered within 6 hours of symptom onset. The study provides sufficient signal to pursue a larger phase 3 RCT with a narrower therapeutic time window.

Author Disclosures: A. Lee: None. C. Chen: None. T. Lee: None. B. Campbell: None.

Th P14 Oxidative Damage In Ischemic Stroke. A Biomarker Study

Raymond C Seet, Jetty C Lee, Bernard P Chan, Vijay K Sharma, Hock-Luen Teoh, Benjamin K Ong, Barry Halliwell; National Univ of Singapore, Singapore, Singapore Introduction: The role of oxidative stress has been questioned following repeated failures of neuroprotective compounds with purported free-radical scavenging activities to improve stroke outcomes. We performed a detailed prospective study to evaluate the changes of multiple markers of oxidative damage in a cohort of ischemic stroke subjects and matched controls. Study Design: Consecutive patients diagnosed with acute ischemic stroke who presented within 6-hours following the onset of symptoms to the National University Hospital, Singapore, were included in this study. Peripheral blood and urine samples, obtained immediately on presentation and serially 6-hrs, 12-hrs, 18-hrs, days 1-4, 7 and 14 following the onset of stroke, were assayed for F 2 -isoprostanes, hydroxyeicosatetraenoic acids (HETEs), F 4 -neuroprostanes, 24-hydroxycholesterol, allantoin and uric acid. Results: Sixty-six subjects with ischemic stroke and 132 controls were included in this study. The mean (SD) age of stroke subjects was 65.2 (13.1) years, comprising 34 (52%) males and 32 (48%) females, who presented with NIHSS of 16.7 (7.2). A majority of these subjects had cardioembolic (nϭ34, 52%) and large artery atherothrombotic strokes (nϭ30, 46%), 31 (47%) of whom with left hemispheric, 28 (42%) right hemispheric and 7 (11%) brainstem strokes. Ninety days following stroke onset, 9 (6%) subjects developed symptomatic intracerebral hemorrhage and 10 (16%) had excellent outcomes (modified Rankin scale, one or less). The initial blood and urine samples were collected at a median of 171 minutes (range, 122-245 minutes) following symptom onset. Plasma F 2 -isoprostanes, HETEs, F 4 -neuroprostanes, 24-hydroxycholesterol and allantoin were altered to different extents immediately following stroke onset. A bimodal pattern of change was observed in the esterified and free forms of plasma F 2 -isoprostanes, as well as urinary F 2 -isoprostanes, highest immediately and on days 1-3 following the onset of stroke. The extent of rise in the esterified form of plasma HETEs was highest 6-12 hours following the onset of stroke, a finding that was similarly observed with plasma F 4 -neuroprostanes, 24-hydroxycholesterol and allantoin. By contrast, plasma uric acid was significantly lower on days 1-3 following the onset of stroke compared to controls. In multivariate analyses, elevated levels of urinary HETEs predicted the development of symptomatic intracranial hemorrhage, while elevated plasma esterified HETEs, uric acid and allantoin, and lower plasma free F 2 -isoprostanes, were associated with excellent functional recovery. Conclusions: Our data support the participation of oxidative damage in the pathogenesis of ischemic stroke and in predicting stroke outcomes. Depending on the time of sampling, different patterns of change can be observed in markers of oxidative damage following ischemic stroke.

Th P15 Tissue Plasminogen Activator for Acute Cerebellar Strokes

Amrou Sarraj, Sarah K Medrek, Nusrat Harun, Melvin R Sline, Renganayaki Pandurengan, George Lopez, Andrew Barreto, Nicole R Gonzales, James C Grotta, Sean Savitz; UT Houston, Houston, TX Background: Cerebellar infarction is an important subcategory of ischemic strokes. Tissue plasminogen activator (t-PA) remains the only proven treatment for ischemic stroke. We hypothesized that pure cerebellar strokes are less often treated with t-PA. We aimed to determine what percent of cerebellar strokes are treated with t-PA and what are the main causes why patients with cerebellar strokes are not treated with t-PA. Methods: Retrospective chart review of patients was conducted from our stroke registry from 01/03 to 06/10. We evaluated consecutive patients with pure cerebellar ischemic infarcts. Patients with additional infarcts of the brainstem or cerebral hemispheres were excluded. We collected demographics, National Institute of Health Stroke Scale (NIHSS) on admission, rates of symptomatic intracerebral hemorrhage (sICH), neurological worsening, and discharge modified Rankin Scale (mRS) outcomes. Results: Among 48 patients, 8 patients (17%) received IV t-PA within 4.5 hrs of symptom onset. None of the patients had hemorrhagic transformation. However, two patients had neurological worsening; one of them died and the other required surgical intervention because of brainstem compression. Thirteen patients (27%) arrived within 4.5 hrs of symptom onset but were not treated because of either rapid improvement (31%), no deficits on NIHSS (46%) leading to misdiagnosis as TIA, or because of a t-PA contraindication (23%) such as elevated INR or petechial hemorrhage on CT. Of the 7 patients who had either rapid improvement or were misdiagnosed as a TIA, they presented with dysarthria (75%), dizziness (75%), nausea (100%) and/or vomiting (100%). In both of these groups, dysarthria resolved but they continued to have dizziness, nausea, or vomiting. Two (29%) of these patients had disabling deficits at discharge. Half (56%) of all cerebellar patients arrived outside the 4.5 hrs window. The vascular distribution of the non-treated infarctions was: 44% PICA, 33% SCA 4% AICA, 2% branch of PCA and 19% multiple territories. In the t-PA group; 13% were PICA, 25% SCA and 62 % were multiple territory. Conclusions: Our data indicate that most patients with acute cerebellar strokes tend not to receive IV t-PA because they arrived outside the 4.5 hrs window or had minimal or non-detectable deficits on NIHSS. However, the latter patients continued to have significant symptoms and some were disabled at the time of discharge. No instances of sICH were found in the t-PA treated group but the small sample number precludes drawing definitive conclusions about safety and outcome of t-PA for acute cerebellar ischemic strokes.

Author Disclosures: A. Sarraj: None. S.K. Medrek: None. N. Harun: None. M.R. Sline: None. R. Pandurengan: None. G. Lopez: None. A. Barreto: None. N.R. Gonzales: None. J.C. Grotta: None. S. Savitz: None.

Th P16 Intravenous Thrombolysis for Ischemic Stroke in Patients with ongoing Acute Myocardial Ischemia

Vivek Misra, Nusrat Harun, Melvin Sline, Andrew D Barreto, George A Lopez, Nicole R Gonzales, James C Grotta, Sean I Savitz; UT MED SCHOOL AT HOUSTON, Houston, TX Background: Recent myocardial infarction (MI) is considered a contraindication for intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) due to risks of hemopericardium and tamponade. The American Heart Association guidelines recommend fibrinolytic therapy for ST-elevation MI upto 12 hours from symptom onset and upto 24 hours with persistent symptoms and ECG changes if percutaneous coronary intervention is unavailable. Pericardial effusion (PEF) is common following MI. Thrombolysis in patients with MI doesn't increase the prevalence and severity of PEF. Clinical trials in AIS exclude patients with acute MI and many neurologists do not consider IVT in such situations. We report the incidence of patients with AIS with ongoing acute myocardial ischemia presenting within 4.5 hours of onset and the safety of IVT in this population. Methods: We identified all patients from our stroke database who received IVT from 1/1/2008 till 12/31/2009 within 4.5 hours of AIS onset and were found to have ongoing acute MI. Demographics, stroke characteristics, troponin levels, ECG and investigative findings, treatment modalities, and outcomes were collected. Results: Of 359 patients treated with IVT for AIS, we identified 4 (1.1%) patients found to have elevated cardiac enzymes at the end of rt-PA infusion. The diagnosis of non-ST elevation MI was made by the on-call cardiologists in view of rising troponin levels on serial assessment and new ECG changes and they were jointly involved in close cardiac monitoring and treatment. All patients received IV anticoagulation 24 hours after IVT and received warfarin, aspirin, statin, beta-blocker and ACE-inhibitor at discharge. Patient-3 developed hemorrhagic conversion of the infarct, so IV heparin was stopped. He also developed bradycardia, felt to be related to metoprolol use and received transvenous pacing. He was subsequently discharged on coumadin and underwent pacemaker placement after 1 month. Patient-4, who had prior severe CHF, underwent tracheostomy for pulmonary edema. There was no mortality and no clinical or echocardiographic evidence of pericardial effusion or tamponade. Conclusions: IVT administered under close supervision at specialized tertiary centers may be safe in AIS patients with concurrent acute sub-endocardial ischemia.

Th P17 Intravenous t-PA for Patients with Minor Ischemic Stroke: A Single Stroke Center Experience

Branko N Huisa, Rema Raman, Karin Ernstrom, Thomas M Hemmen; UCSD, La Jolla, CA Background: Current guidelines do not recommend treatment with intravenous tissue plasminogen activator (IV-tPA) in patients with minor stroke. Minor stroke represents a common reason why patients after ischemic stroke are not treated with thrombolysis. However, there is no consensus definition of minor stroke and the outcome of patients with minor stroke is unknown. We compared clinical outcomes and safety in patients with minor stroke were, and those who were not, treated with IV t-PA. Methods: Patients with minor ischemic stroke presented within 3hrs form the stroke onset with 90 day modified Rankin Score (mRS) were selected from January 2004 to June 2010 using our prospective UCSD Stroke Center registry. Minor stroke was defined as patients with a National Institutes of Health Stroke Scale (NIHSS) score Յ5. The primary outcome was a 90 day mRS of 0-1. Secondary outcomes were Barthel index (BI) of 95 to 100 at 90 days, symptomatic intracranial hemorrhage (SICH) and death. Multivariable logistic regression was performed to determine the association between outcome (Day 90 mRS of 0-1 vs. 2-6, Day 90 BI of Ͻ95 vs. 95-100, 90-day mortality) and treatment group, adjusting for age, diabetes and initial NIHSS. Reasons for t-PA exclusion were obtained. Results: We identified 123 patients with minor ischemic stroke; 50 patients received IV-tPA (Group 1), 73 did not (Group 2). The reasons for treatment exclusion were: Rapid improving symptoms 33(45.2%); the patient or the family refused thrombolytic treatment 6(8.2%), patients were Ͼ3hrs at treatment time 5(6.8%), anticoagulation 5(6.8%), uncontrolled BP 1(1.4%), extreme glucose level 1(1.4%), stroke mimic 1(1.4%). Baseline characteristics (Age, gender, race, hypertension, A-fib, diabetes, tobacco use, pre stroke mRS) were similar in both groups with the exception of the initial NIHSS (meanϮSD); Group 1: 3.44Ϯ1.36, Group 2: 1.92Ϯ1.33, pϽ 0.0001. There were no statistically significant differences between IV-tPA and the untreated groups in 90-day mRS of 0-1 (50% vs. 68.5%; adjusted OR 0.68, 95% CI: 0.28-1.66, pϭ0.40) and BI of 95-100 (69.6% vs. 78.7%; adjusted OR 0.88, 95% CI: 0.31-2.45, pϭ0.81).There were 3 deaths (4.1%) in the untreated group and 3 deaths (6%) in the t-PA group (pϭ0.18). SICH was 6% in the treatment group. SICH was not recorded in the untreated group. Conclusions: Clinical and safety outcomes were similar between t-PA treated and untreated patients with minor stroke. A larger randomized clinical trial or observational study is needed confirm or reject these findings.

Author Disclosures: B.N. Huisa: None. R. Raman: None. K. Ernstrom: None. T.M. Hemmen: None.

Th P18 Outcome Of Intravenous rt-PA Treatment In Acute Stroke. Time To Administration And Baseline NIHSS Analysis

Diaz Otero Fernando, Gil-Nu ´n ˜ez Antonio, Garcı ´a Pastor Andre ´s, Stroke Unit, Hosp General 'Gregorio Maran ˜o ´n', Madrid, Spain; Alonso de Lecin ˜ana Marı ´a, Masjuan Jaime, Stroke Unit, Hosp General 'Ramo ´n y Cajal', Madrid, Spain; Simal Patricia, Egido Jose Antonio, Stroke Unit, Hosp Clinico 'San Carlos', Madrid, Spain; Fuentes Blanca, Diez-Tejedor Exuperio, Stroke Unit, Hosp General 'La Paz', Madrid, Spain; Reig Gemma, Vivancos Jose; Stroke Unit, Hosp Universitario 'La Princesa', Madrid, Spain Introduction: Previous studies have shown a worse rate of functional recovery and increased mortality in terms of greater baseline NIHSS score and a longer time window in the administration of IV rt-PA. It is unknown the cutoff NIHSS predictor of functional recovery and mortality, nor the effect of the combined variables of baseline NIH score and stroke onset to start treatment (OTT) outcomes. Objectives: To determine a baseline NIHSS value predictor for functional recovery and mortality in patients with stroke treated with rt-PA IV. To analyze the results by combining the baseline NIHSS variables and OTT and compared with the placebo arm of previous clinical trials. Patients/Methods: Prospective multicenter registry of IV rt-PA in five university hospitals with stroke unit. We included 967 patients with OTT Ͻ 270 minutes. We collected demographic, clinical, hemorrhagic transformation rate, mortality and functional recovery (Rankin scale 3 months). We used the data published in the placebo arm of ECASS I-III studies, ATLANTIS and NINDS to study differences between treatment and placebo. ROC curves, Pearson and Mann-Whitney test were done in the analysis of the results with the program SPSS, version 15.0. Results: The sensitivity and specificity of baseline NIHSS were studied whit the ROC curves. The NIHSS value of 14 was obtained as the value that correspond to the largest area under the curve (0.77, PϽ0.01) in predicting functional recovery (Rankin 3months 0-2) (positive predictive value (PPV) 63.1%, negative predictive value (NPV) 79.3%, sensitivity 74.6%, specificity 69.1%) and mortality (area under the curve 0.8, PϽ0.01, PPV 78.3%, NPV 3.5%, sensitivity 43.9%, specificity 14.4%). Patients treated with NIHSS Ն 14 and OTT 180 minutes did not show significant differences in recovery globally and mortality versus to the placebo group, and there was a worse recovery rates and higher mortality in the OTT Ͼ 180 minutes compared to the placebo group (Mann-Whitney U, pϭ0.258 (0-90 minutes), pϭ0.066 (91-180 minutes), pϭ0.004 (Ͼ 180 minutes), respectively. For OTT 91-180 minutes and NIHSS Ն 14, 12.8% of patients were on Rankin 0 and 11.4% on Rankin 1 versus 40% and 22% respectively for NIHSS Ͻ14. Mortality 22.6% for OTT 91-180 minutes and NIHSS Ն 14 versus 2.3% for NIHSS Ͻ14 (pϽ0.05)Conclusions: The baseline NIHSS Ն 14 is a predictor of low recovery rate and high mortality in patients treated with IV rt-PA. Patients with the score greater or equal 14 points on the baseline NIH scale treated before 180 minutes after onset of symptoms did not obtain significant differences compared with the placebo arm, and do not benefit from treatment with IV rt-PA. Further studies are needed to confirm these findings.

Objective: Intravenous tissue plasminogen activator (IV t-PA) is the only proven treatment for acute ischemic stroke but its efficacy diminishes with time. As a consequence, efforts are made to treat patients as quickly as possible. Data from the NINDS t-PA studies and subsequent pooled analyses showed that patients treated achieved better outcomes the earlier after stroke onset treatment was given. Many healthcare initiatives focus on treatment with IV t-PA in less than 2 hours. Our objective was to use the internal database at the University of California, San Diego Stroke Center to determine if patients treated before 2 hours achieved better outcomes than those treated between 2-3 hours. Methods: Using Fisher's Exact Test we compared 90 day modified Rankin Scales (mRS) in patients treated between 0-2 hours and 2-3 hours. Good outcome was defined as mRS 0 or 1 at 90 days. All patients received standard dose IV t-PA. We excluded patients who received adjuvant reperfusion therapy or were enrolled into clinical trials utilizing therapies other than IV t-PA. We adjusted for age, gender, hypertension, diabetes, personal history of stroke/TIA, prestroke mRS and baseline NIHSS. Results: Overall 209 patients (51% male, median age 75 years old) received IV t-PA. 88 patients were treated from 0-2 hours and 121 patients were treated between 2-3 hours. The early treatment group received treatment at a median of 105 minutes and the late treatment group at a median of 150 minutes (pϽ0.0001). The adjusted dichotomous 90-day mRS was not different between groups (pϽ0.9195, OR 1.05, CI 0.37-2.97). Conclusion: Despite prior evidence that treating patients earlier with IV t-PA is more effective, we could not demonstrate that patients treated between 0-2 hours achieved better 90 day functional outcomes than patients treated between 2-3 hours. Further studies with larger sample sizes are needed to prospectively investigate the relationship between outcome and time to treatment. Background&Purpose: The peak rarefaction pressure is the most dominant factor that influences both mechanical clot fragmentation and acceleration of enzymatic fibrinolysis. We sought to determine whether recanalization rate and functional outcomes in the Transcranial Ultrasound in Clinical SONothrombolysis (TUCSON) trial could be predicted by estimated in vivo peak rarefaction pressure. Subjects&Methods: We developed an acoustic attenuation model to estimate the in vivo peak negative pressures at the occlusion site within each subject of the TUCSON trial with CT scans eligible for measurements. Variables included temporal bone thickness, depths of occlusion location, and average attenuation of skin and brain tissues. Recanalization was defined as partial or complete using the Thrombolysis in Brain Infarction flow grades. Functional independence was assessed at three months using the modified Rankin Scale Score (mRS 0-1). Results: The peak rarefaction pressure was calculated in 20 acute ischemic stroke patients treated with sonothrombolysis (mean age 64Ϯ15 years, 65% men, median NIHSS score 13, interquartile range 6-17). The mean estimated peak rarefaction pressure was 30.2Ϯ15.5 kPa (range 8-68 kPa). A total of 6 patients (30%, 95%CI: 14%-52%) had peak rarefaction pressures less than 19 kPa which is considered the lower threshold for optimized microstreaming. Patients with persisting occlusion (nϭ6) tended to have lower peak rarefaction pressures (25.2ϩ/-8.0 kPa) compared to patients with any recanalization (nϭ14, 13 complete, one partial; 32.3ϩ/-17.7 kPa; pϭ0.228). Patients who were functionally independent (nϭ9) at three months tended to have higher peak rarefaction pressures compared to the rest (35.1Ϯ19.5 kPa vs. 25.9Ϯ11.2 kPa; pϭ0.217). After adjusting for baseline stroke severity, a 1 kPa increase in peak rarefaction pressure tended to be related to a higher likelihood of functional independence (OR: 1.05; 95%CI: 0.95-1.15; log OR: 0.4; pϭ0.360) at three months. After excluding patients with peak rarefaction pressures lower than 19 kPa, patients with functional independence had higher peak rarefaction pressures compared to the rest (45.7Ϯ14.0KPa vs. 30.7Ϯ9.6KPa; pϭ0.044). For the given effect size (log odds ratio of 0.4) a sample size of 110 patients would be needed to formally test this potential association with a power of 83% and a two-tailed alpha of 0.05. Conclusions: Our preliminary analysis underscores the importance of successful energy delivery above 19 kPA threshold to augment thrombolysis with 2 MHz ultrasound by demonstrating a trend towards higher peak negative pressures leading to recanalization and improved outcomes.

Author Disclosures: K.B. Barlinn: None. G. Tsivgoulis: None. C.A. Molina: Consultant/Advisory Board; Modest; Cerevast Therapeutics, Inc., Redmond, WA, USA. D.A. Alexandrov: Employment; Modest; Cerevast Therapeutics, Inc., Redmond, WA, USA. J. Alleman: Employment; Significant; Cerevast Therapeutics, Inc., Redmond, WA, USA. A.V. Alexandrov: Employment; Significant; Cerevast Therapeutics, Inc., Redmond, WA, USA. Consultant/Advisory Board; Significant; Cerevast Therapeutics, Inc., Redmond, WA, USA.

Th P21 Safety And Efficacy Of Intravenous Thrombolysis In The Treatment Of Acute Basilar Occlusion: A Prospective Observational Study

Georgios Tsivgoulis, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis, Greece; Hock L Teoh, Div of Neurology, Dept of Medicine, National Univ Hosp,, Singapore, Singapore; Ioannis Heliopoulos, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis, Greece; Bernard P Chan, Div of Neurology, Dept of Medicine, National Univ Hosp,, Singapore, Singapore; Konstantinos Vadikolias, Athanasia Patousi, Chrysi Bogiatzi, Charitomeni Piperidou, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis, Greece; Vijay K Sharma; Div of Neurology, Dept of Medicine, National Univ Hosp,, Singapore, Singapore Background&Purpose: Randomised Controlled Trials (RCTs) have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4•5 h of the onset of the symptoms of acute ischemic stroke (IS). Unfortunately, the results of these RCTs do not directly apply to patients with acute basilar artery occlusions (BAO) given the limited number of these patients included in RCTs and the low incidence of BAO among IS patients. The best available data guiding treatment decisions in this specific stroke subgroup comes from the Basilar Artery International Cooperation Study (BASICS), a prospective international observational registry. We evaluated the safety and efficacy of IVT in consecutive patients with BAO treated either with IVT or antithrombotic therapy (AT) in two tertiary care centers. Subjects&Methods: Consecutive patients with acute (24 hours) BAO were prospectively recorded over a four-year period. BAO was diagnosed by ultrasound, MR angiography or CT angiography in all cases. Reversed BA flow was prospectively documented. Baseline stroke severity was evaluated by the NIH Stroke Scale Score (NIHSS). Demographics and stroke risk factors were recorded in a standardized fashion. IVT was administered according to AHA recommendations within 4.5 hours from stroke onset, while intra-arterial thrombolysis was not offered in any patient given the unavailability of interventional radiologists in both centers. Symptomatic intracranial hemorrhage (sICH) was defined according to the SITS-MOST definition. Poor functional outcome at three months was assessed using the mRS-score according to BASICS definition (4-6 points). Results: Among 86 patients with acute BAO (mean age 64Ϯ12years, 58% men, median NIHSS-score 14 points, IQR 9-22), a total of 31 (36%) received IVT (mean age 61Ϯ10years, 52% men, median NIHSS-score 15 points, IQR 12-24) while the remaining were treated with AT (mean age 66Ϯ12years, 62% men, median NIHSS-score 13 points, IQR 8-20). Patients treated with IVT were older (pϭ0.034), had higher admission NIHSS-scores (pϭ0.041) and a lower prevalence of diabetes mellitus (pϭ0.007) compared to AT patients. The two groups did not differ in terms of gender, remaining risk factors, admission blood pressure and blood glucose values, site of basilar occlusion (proximal vs. distal) and reversed BA flow. sICH occurred in 7% of patients in both groups (pϭ0.886). Poor outcome tended to be less frequent in IVT patients (26% vs 43%; pϭ0.098). In the multivariate logistic regression analyses the following three factors were independent predictors of poor outcome: NIHSS-score (OR per 1-point increase: 1.18; 95% CI: 1.08-1.30; PϽ0.001), BA flow reversal (OR: 0.06; 95% CI: 0.01-0.30; pϭ0.001) and IVT (OR: 0.15; 95% CI: 0.04-0.61; pϭ0.008)Conclusions: IVT appears to be equally safe and more effective than AT in patients with acute BAO. Objectives Creatine is a tripeptide which has been shown to be neuroprotective in cerebral ischemia due to its antioxidant properties. Hemorrhagic transformation (HT) after rt-PA is related to the endothelial damage which is due, amongst other mechanisms, to the release of free radicals, suggesting that antioxidant therapies may be used to avoid this complication. This study investigates the participation of creatine kinase (CK), an enzyme which acts on creatine, in the development of HT in patients receiving rt-PA. Patients and Methods Levels of CK were analyzed in 357 patients with ischemic stroke Ͻ 4.5 h of evolution treated with rt-PA. HT was assessed in the cranial CT performed at 24Ϯ12 h after the administration of treatment and was classified in accordance with the ECASS II criteria. Results Of the 357 patients, 255 (71.4%) did not have HT, 69 (19.3%) had hemorrhagic infarction (HI) and 33 (9.2%) had parenchymal hemorrhage. The levels of CK were higher in patients with HT (74 [53,96] vs. 86 [62,125]) (pϭ0.04). In the logistic regression model, levels of CK were independent predictors of HT after adjusting for the rest of the variables related to this complication in the univariate analysis (OR, x 10 U/L 0.9; CI 95%, 0.52-0.95; pϭ0.04). Conclusions: CK levels are predictors of HT in patients treated with rt-PA, supporting the participation of oxidative mechanisms in the development of HT in patients receiving thrombolysis.

Author Disclosures: M. Castellanos: None. M. Jime ´nez: None. Y. Silva: None. J. Puig: None. S. Pedraza: None. E. Sanjua ´n: None. P. Sa ´nchez-Camacho: None. J. Serena: None.

Th P23 Intravenous rt-PA and Outcome after a Mild Stroke

Manoj Mittal, Univ of Kansas Med Cntr, Kansas City, KS; Marilyn Rymer, Saint Luke's Brain & Stroke Institute, Kansas City, MO; Sue-Min Lai Lai; Univ of Kansas Med Cntr, Kansas City, KS Background and Objective: Randomized clinical trials of IV rt-PA have excluded patients with low NIHSS scores, yet several studies have shown a substantial percentage of these patients had poor outcomes when treatment was withheld. This study determined whether mild stroke patients who received intravenous (IV) rt-PA had decreased mortality and morbidity after consideration of their stroke characteristics during hospitalization. Methods We analyzed 176 cases of ischemic stroke eligible for IV rt-PA by time criteria with NIHSS score Ͻ8 admitted to Saint Luke's Stroke Center from March, 2006through June, 2009. The NIHSS scores were further categorized as Ͻ4 and 4-7. Outcome was defined based on their discharge disposition. Discharge to home with or without home health or inpatient rehabilitation was defined as good outcome. Discharge to nursing homes or hospice homes or death were defined as poor outcome. Univariate analysis including t-test, Chi-square, and Fisher Exact test was used when appropriate. Relative risk regression was used to examine the effect of rt-PA and clinical characteristics that predisposed patients for not going home. Results One hundred and seventy six mild ischemic strokes (male to female: 1.7:1 and a median age of 68 yrs ranging from 30 to 95 yrs) were included in this study. Percent of patients treated with IV rt-PA was 46% and 14% for those with NIHSS 4-7 and NIHSS 0-3, respectively. Patients who did not received rt-PA had higher mortality (5%) then those who received it (4%) (pϾ0.05). In the untreated group, more patients were discharged to nursing homes (15% vs 2%, PϽ0.05) and fewer patients were discharged to inpatient rehabilitation units (12% vs 28%, PϽ0.05). Admission NIHSS score, prior to stroke mobility function, and recurring stroke during hospitalization were significant factors determining discharge disposition. Conclusion: IV rt-PA treatment in mild strokes is associated with lower mortality and morbidity. This patient population is worthy of a randomized controlled trial testing the safety and efficacy of IV rt-PA.

Author Disclosures: M. Mittal: None. M. Rymer: Speakers; Modest; Genentech, Inc.. S. Lai: None.

Th P24 Evaluation Of Patients Treated With IV tPA At Regional Stroke Centers vs. Community Hospitals: Is There Opportunity For A Wider Stroke Population To Be Treated?

Amie W Hsia, Richard T Benson, Washington Hosp Cntr -Stroke Cntr, Washington, DC; Marieta Pehlivanova, Medstar Health Rsch Institute, Washington, DC; Jose G Merino, Suburban Hosp Stroke Cntr, Bethesda, MD; Larry L Latour, Marie Luby, Shlee S Song, John K Lynch, Carsten H Ritter, Alex Katcheves, Steven Warach; NIH/NINDS, Bethesda, MD Background and Purpose: It is not known whether community hospitals (CH) and regional stroke centers (RSC) treat similar patients with IV tPA, and if the outcome of these patients is the same. The purpose of our study was to compare the baseline characteristics and outcomes of patients treated at CHs and then transferred to RSCs with those of patients initially treated at the RSCs. Methods: We performed a retrospective review of prospectively collected data from the NINDS Stroke Branch Registry of consecutive ischemic stroke patients treated with IV tPA at a RSC or referring CH who were admitted to one of two RSCs between January 2005 and October 2009. Patients' demographics, pre-treatment imaging modality, hemorrhage rates, and clinical outcomes were compared using univariate and multivariate logistic regression analyses to control for baseline variables. Results: Of 285 patients identified, 68% were treated with IV tPA at a RSC and 32% at a CH. Baseline stroke risk factors were similar between the two groups. Of patients treated at a RSC, 84% were screened with MRI compared to 4% of the patients treated at a CH. All the patients treated at a RSC but only 90% of those treated at a CH had a discharge diagnosis of ischemic stroke (pϽ0.0001). Patients treated at a RSC, compared with those treated at a CH, were older (mean age 71 vs. 64 years, pϭ0.0004), had longer symptom onset to treatment times (157 Ϯ24 vs. 146 Ϯ39 minutes, pϭ0.0217), and higher NIHSS scores (mean 13.5 vs. 11.3, pϭ0.0593). The rate of PH2 hemorrhagic transformation was similar for patients treated at the RSCs and CHs (7.2% vs. 7.7%,pϭ0.8860). Functional outcome at discharge (mRS 1: 23% vs. 29%, pϭ0.3603) and discharge disposition (pϭ0.8473) were also similar between the two groups. Conclusions: Though patients treated with IV tPA at RSCs and CHs had similar outcomes, patients treated with IV tPA at RSCs were older and had more severe strokes than patients treated at CHs. Patients treated at CHs were more likely to have a non-stroke etiology for their symptoms. Access to neurologists with expertise in stroke and the use of MRI as a screening tool may explain the more inclusive and accurate administration of IV tPA at these regional stroke centers.

Th P25 Stroke Complicating Trans-Catheter Aortic Valve Implantation

Ronen R Leker, Roni Eichel, Haim Lotan, Ami Werber, Jose E Cohen, Haim Dannenberg; Hadassah-Hebrew Univ Med Cntr, Jerusalem, Israel Background: Trans-catheter aortic valve implantation (TAVI) is an alternative to open heart valve replacement but carries an undefined risk for periprocedural stroke. Furthermore, the risk factors associated with stroke the attributes and outcome of these strokes are not known. Patients andMethods: All patients undergoing TAVI were included in a prospective database. Strokes complicating TAVI in the first 5 days following the procedure were documented and the differences between patients with and without stroke were studied. Results: Forty patients (17 men, mean age 79.3Ϯ7.1) underwent TAVI and were included. Of these, 6 (15%) had focal neurological deficits in the peri-procedural period (3 TIA, 3 stroke of which 2 were minor and one was major). Patients with stroke/TIA didn't differ from those without cerebral ischemia in baseline criteria or procedural variables. Five of the events were believed to be embolic resulting from dislodgement of calcific material from the aortic valve and one TIA was secondary to hypoperfusion during severe bradycardia. All patients with cerebral ischemia had involvement of the posterior circulation. One patient with basilar occlusion died but the remaining 5 patients survived and all had a modified Rankin score of 2 or less at 90 days post stroke. None of these patients had a recurrent stroke during the follow up period. Discussion: Peri-procedural cerebral ischemia following TAVI is not uncommon. There was no particular pre-TAVI or procedural risk factor profile that increased the risk for peri-procedural stroke. Further studies are needed to examine whether patients that are at higher risk for developing stroke after TAVI can be identified.

Author Disclosures: R.R. Leker: None. R. Eichel: None. H. Lotan: None. A. Werber: None. J.E. Cohen: None. H. Dannenberg: None.

Th P26 Pre-existing Statin Use Predicts Early Reperfusion in Hyper-Acute Ischemic Stroke

Andria L Ford, Washington Univ, Saint Louis, MO; Hongyu An, Univ of North Carolina, Chapel Hill, NC; Rosana Ponisio, Gina D'Angelo, Patrick Bushard, Katie D Vo, Washington Univ, Saint Louis, MO; William J Powers, Weili Lin, Univ of North Carolina, Chapel Hill, NC; Jin-Moo Lee; Washington Univ, Saint Louis, MO Background: Pre-existing statin use has been associated with improved neurological outcomes in ischemic stroke patients. Although several potential mechanisms have been examined in animal models, few have been examined in humans. We hypothesized that early reperfusion is enhanced in ischemic stroke patients taking statins at stroke onset. Methods: Acute ischemic stroke patients underwent two MR scans: within 4.5 (tp1) and at 6 hours (tp2) after stroke onset. Mean transit time (MTT) maps were generated to measure regions of perfusion deficit at tp1 and tp2. Regions of reperfusion were defined by perfusion deficits at tp1 which normalized at tp2. Four different thresholds were used to define "perfusion deficit" (MTT Ͼ 3, 4, 5, or 6 secs longer than the contralateral mean) to ensure that results were not spuriously based on an arbitrary threshold. Baseline characteristics, relative reperfusion, and change in NIH Stroke Scale between tp1 and 1 month follow-up (äNIHSS) were compared between patients taking statins on admission and those not taking statins. Wilcoxon Rank Sum was used for group comparisons unless D'Agostino test confirmed normality, in which case, t-tests were used. Two forward-selection multivariable linear regression models identified which clinical variables (of 10 considered) most strongly predicted: (1) relative reperfusion and (2) äNIHSS. Results: Thirty-one acute stroke patients were prospectively enrolled; 12 were taking statins, while 19 were not. Baseline characteristics did not differ between the two groups except more patients in the statin group had coronary artery disease (pϭ0.03). Pre-existing statin use resulted in significantly greater reperfusion compared to the untreated group across all MTT thresholds (Fig, A). For the 4-sec MTT threshold, median reperfusion was 50% (IQR 30%, 56%) in the statin group vs. 13% (IQR 5%, 36%) in the untreated group, pϭ0.014. Of 10 baseline clinical variables, the best-fitting model for prediction of reperfusion included: (1) pre-existing statin use (pϭ0.021), ( 2 Background and Significance: Hemorrhagic transformation (HT) is a well known complication of intra-venous tissue plasminogen activator (IV t-PA) treatment. Parenchymal hematoma (PH2) transformation post IV t-PA is the most severe and is associated with increased morbidity and mortality. Several predictors of PH2 transformation have been reported, but few have focused on baseline alcohol consumption. Methods: We reviewed the NINDS Stroke Branch Registry, which contains clinical and radiologic data, for all IV t-PA patients admitted to our facilities between January 2005 and November 2009. The NINDS Stroke Program is a multi-center, regional stroke program. Comparisons between putative stroke risk factors and HT subtypes were performed using univariate and multivariate regression analyses. Baseline alcohol intake was determined on admission and categorized as Յ 2 drinks or Ͼ 2 drinks per day. MRI and CT consensus readings performed within 1 week of t-PA treatment were used. Results: During this 5-year period, 285 patients were admitted to our hospitals after IV t-PA treatment. Demographically, 30.9% were Ն 80 years; their mean age was 68.8 Ϯ 15.83; 53.3% were women, 59.3% white; 36.5% black; and 4.2% other. In terms of risk factors, 71.9% had hypertension; 24.6% diabetes; 41.4% hyperlipidemia; 26% coronary artery disease; 24.2% atrial fibrilliation; 18.9% previous stroke; and 16.8% were current smokers. In terms of alcohol use, 87% drank Յ 2 drinks per day and 13% Ͼ 2 per day. Twenty-one patients had PH2, 14 PH1, and 64 "any other" HT. In univariate and multivariate regression analyses, intake of Ͼ 2 drinks per day was associated with PH2 transformation (pϭ0.0341; pϭ0.0083 after adjusting for NIHSS). No significant association was noted for PH1 alone or the combined of PH1, PH2 and "any other" HT. Conclusion: Heavy alcohol consumption is a well established risk factor for ischemic and hemorrhagic stroke. This study suggests that heavy alcohol consumption may also be associated with severe hemorrhagic transformation (PH2) after IV t-PA treatment. Background and Purpose: Recent studies showed that statin improved clinical outcome of ischemic stroke, but the effect of lipid levels on the outcome is controversial. We investigated whether baseline lipid levels were associated with clinical outcome at 3 months after IV recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke. Methods: Six-hundred consecutive patients who received IV rt-PA at ten stroke centers were registered in the SAMURAI rt-PA Registry. We assessed lipid levels on emergent visit; total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol. The primary outcome was favorable outcome at 3 months corresponding to the modified Rankin scale Յ1. The secondary outcome was any intracranial hemorrhage (ICH) within the initial 36 hours. We examined whether each lipid profile was predictive of these outcomes. Results: Of 600 patients, those with a premorbid modified Rankin scale Ն2 or those who had lack of any lipid profiles or initial MRI were excluded. Of 408 included patients (140 women, 70.9 Ϯ 11.1 years old), 48 patients used statins prior to stroke. One-hundred and fifty-eight patients (38.7%) had favorable outcome. HDL-C level in patients with favorable outcome was higher than in those with unfavorable outcome (1.40 Ϯ 0.40 mmol/l versus 1.32 Ϯ 0.37 mmol/l, pϭ0.025), whereas other lipid levels or frequency of prior statin use were not different between two groups. The patients with favorable outcome were gradually increased with HDL-C levels divided into tertiles (32.1%, 39.1%, 44.9%). After multivariate analysis, HDL-C level was only independently related to favorable outcome among lipid profiles (OR 1.89; 95%CI 1.02-3.50 per 1-mmol/L, pϭ0.043). For 164 non-cardioembolic patients, HDL-C level was also independently related to favorable outcome (OR 2.95; 95%CI 1.11-7.83, pϭ0.030), although it was not for 244 cardioembolic patients. Any ICH occurred in 76 patients (18.6%).

Th P27 Heavy Alcohol Consumption: A Novel Predictor of Symptomatic Intracerebral Hemorrhage After IV t-PA?

Introduction:

Recent studies show the potential of intravascular stem cell therapies for the treatment of stroke. Neural stem cell(NSC) homing in intravascular stem cell therapy and subsequent intraparenchymal migration relies on NSC expression of chemokines and their receptors. As these therapies come closer to clinical trials, it is essential to understand the interspecies differences of chemotaxis related receptor and ligand expression to expedite the transition from rodent research to human application. Here we use RT-qPCR to compare human neural stem cell (hNSC) and mouse neural stem cell (mNSC) chemokine receptor and ligand expression at basal levels. Furthermore, we compare hNSCs and mNSCs after exposure to MCP-1 to test the response of NSCs to a chemokine shown to be upregulated in the microenvironment of the ischemic brain. Finally, we explore the implication of these differences on cell migration. Methods: Human and mouse cells were grown as monolayers in their respective growth media. In pretreated cell groups, MCP-1 (20ng/mL) was introduced to cell media 1 hour prior to RNA extraction. RT-qPCR was performed on extracted RNA using microarray technology for chemokine receptors and ligands. The Boyden chamber migration assay was used to determine migration to SDF-1 at concentrations 0ng/mL, 100ng/mL, 500ng/mL, 1000ng/mL, and 1500ng/mL. Results: Analysis of baseline expression demonstrated that 18% of analyzed factors were different between hNPCs and mNPCs (pϽ0.001). The five factors with the largest fold regulation difference between hNSCs and mNSCs are CCL2, CCL7, CXCL12, CMLKR1, and CXCR4. After treatment with MCP-1 there was a 1.61% change in factor expression between human and mouse chemokine. Of the mRNA transcripts upregulated above 3 fold regulation, ligands accounted for 6 of 6 factors in mNPCs and 1 of 1 in hNPCs. Of the mRNA transcripts downregulated below -3 fold regulation, receptors accounted for 5 of 5 factors in mNPCs and 1 of 3 in hNPCs. Migration of hNSCs compared to mNSCs in response to SDF-1 was greater by 2.46 fold (pϽ 0.01), consistent with the greater expression of CXCR4 on hNSCs than mNSCs. Conclusion: Baseline chemokine receptor and ligand expression between human and mouse NSCs was significantly different, possibly resulting in interspecies differences in NSC response to the ischemic brain microenvironment. In the context of cell therapy for stroke, the implications of interspecies distinctions should be strongly considered when conclusions drawn from rodent research are translated to human treatment.

This research has received full or partial funding support from the American Heart Association, Western States Affiliate (California, Nevada & Utah).

Author Disclosures: N. Wang: None. S. Rosenblum: None. J.Y. Chua: None. J.K. Nathan: None. E. Westbroek: None. T. Smith: None. R. Guzman: None.

Th P30 Interleukin-6 Promoter Polymorphism Predicts Stroke Severity and Outcome in Acute Ischemic Stroke Patients from North India

Baidarbhi Chakraborty, Sarita Agarwal, Gaurav Vishnoi, Maulana Azad Med College, New Delhi, India; Debashish Chowdhury; Govind Ballabh Pant Hosp, New Delhi, India Introduction: Interleukin-6 (IL-6) plasma levels and function are genetically influenced. In particular, a guanine/cytosine substitution occurring in position -174 of IL-6 gene promoter changes the expression of IL-6 circulating proteins. IL-6 is known to be involved in the pathogenetic mechanisms of acute ischemic stroke. Studies in stroke, however, report conflicting data regarding the association of the frequency of GG/GC/CC genotypes and risk of stroke. Further, it is not known whether this gene polymorphism correlates with the severity and prognosis of stroke.Hypothesis:We studied the occurrence of IL-6 -174 G/C polymorphism in patients of acute ischemic stroke and correlated it with stroke severity and outcome. Methods: 59 patients with acute ischemic stroke and 120 age and sex-matched healthy controls were studied. IL-6 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis. Stroke was categorized by Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Severity was assessed clinically by National Institute of Health Stroke Scale (NIHSS) and by infarct volume on Diffusion Weighted Imaging on MRI. Outcome measures included mortality, Modified Rankin Scale (MRS) and Barthel index at 3 months. Serum levels of IL-6 were assessed in stroke patients (during acute phase) and in controls by ELISA. Results: Frequency of GG, GC and CC genotypes did not differ significantly between cases and controls [GG 63 % vs 71 %, (pϭ0.99), GC 22 % vs 21 %, (pϭ0.25) and CC 15 % vs 18 % (pϭ0.25)]. Of the two alleles, G allele was more common in both cases (73.7%) and control groups (81.2%). Patients with GG (rϭ0.263, pϭ0.04) and GC (rϭ0.258, pϭ0.04) genotypes had more severe stroke clinically. However, there was no radiological correlation. Serum levels of IL-6 following acute stroke (mean 4.4 Ϯ 1.6; median 4 days) were higher in cases than controls (14 pg/ml vs 2pg/ml) but did not correlate with presence of any genotype. No specific association was seen between frequency of genotypes and stroke subtypes. Only the patients with GC genotype were found to have significant worse outcome on MRS at 3 months (pϭ0.02). Of the patients with GG genotype, 3 patients died at 3 months [3/32 patients (9.3%)] compared to those with GC [4/13 patients (31%)] and CC [3/8 patients (37%)] genotypes. This difference was statistically significant(pϭ0.03). Conclusions: Frequency of IL-6-174 G/C promoter polymorphism did not differ between acute ischemic stroke patients and normal controls. Patients with GC genotype had worse outcome on MRS at 3 months. Patients with GG genotype had decreased mortality at 3 months when compared to those with GC and CC genotype which thus appears to be protective. Background: Brain plasticity is influenced by many factors in patients with lesions (e.g. tumor, vascular lesion). Age, gender, handedness, lesion location and volume are few of the putative factors that have been implicated. The proximity of lesions to functional cortex is also a significant factor influencing brain plasticity changes 1 . Objective: We investigated whether vascular lesions altered cortical language representation in right handed individuals. In a majority of normal right-handed subjects, the language function is lateralized to the left hemisphere 2 . However, this left hemispheric dominance for language has been known to shift depending on distance of lesion from functional areas involved in language 1,2 . Methods: We retrospectively analyzed data from right handed patients with vascular lesions (N ϭ 67, 38 females) who underwent preoperative functional imaging to locate their dominant language hemisphere. Vascular lesions were either AVMs, (N ϭ 42) or cavernomas (N ϭ 23) or other (Nϭ2). Forty-six patients had lesion in the left hemisphere. Functional changes were characterized using BOLD fMRI acquisition during the antonym word generation, letter word generation and text reading tasks. Lateralization Index (LI) was determined for Broca's and Wernicke's areas by measuring area of activation in left(L) and right(R) homologous brain regions and calculated using the formula (L-R)/(LϩR). Results: Distance from lesion to center of Wernicke's activation was significantly associated with language lateralization (p Ͻ .05). Patients with distance less than 10 mm had language lateralized to the right hemisphere. Distance from lesion to center of Broca's activation was not significantly associated with language lateralization. No significant associations were found between demographic variables such as age, gender or handedness. No significant associations were found between lesion characteristics such as volume, lesion type, and lesion location. Conclusions: These results suggest that patients with vascular lesions such as AVMs or cavernomas show a shift in hemispheric dominance for language with the homologous regions in the right hemisphere playing a greater role in language processing than is commonly observed in most healthy right handed normals. References: 1. Yetkin, F.Z., Swanson, S., Fischer, M., Akansel, G., Morris, G., Mueller, W., & Haughton, V. (1998). Functional MR of frontal lobe activation: Comparison with Wada language results. American Journal of Neuroradiology, 19, 1095-1098. 2. Springer JA, Binder JR, Hammeke TA, Swanson SJ, Frost JA, Bellgowan PS, Brewer CC, Perry HM, Morris GL, Mueller WM. Language dominance in neurologically normal and epilepsy subjects: a functional MRI study. Brain, 122, 2033Brain, 122, -46, 1999.

Th P32 Metabolic Profile Of Motor Cortex In Stroke

Sorin C Craciunas, Ali Bani-Ahmed, William M Brooks, Hoglund Brain Imaging Cntr, Kansas Univ Med Cntr, Kansas City, KS; Randolph J Nudo, Landon Cntr on Aging, Kansas City, KS; Elena A Popescu, In-Young Choi, Sang-Pil Lee, Carmen M Cirstea; Hoglund Brain Imaging Cntr, Kansas Univ Med Cntr, Kansas City, KS Non-invasive detection of sensitive metabolic markers could broaden our understanding of pathophysiological processes underlying post-stroke plasticity linked to neuronal-glial interactions. The goal of this study was to investigate whether certain metabolites, which are specific to neurons, glial cells, or the neuronal-glial neurotransmission system, in spared (radiologically normal-appearing) primary and non-primary motor areas in either the ipsilesional or contralesional hemisphere, are altered in stroke, and whether these alterations correlate with clinical motor severity. Survivors of a first ischemic stroke located outside the primary and non-primary motor areas and age-and sex-matched healthy controls were included. N-acetylaspartate, myo-inositol, and glutamate/glutamine were measured by using proton magnetic resonance spectroscopy (1H-MRS) in spared gray matter of the hand representation area, identified by functional MRI, in the primary motor cortex (M1), dorsal premotor cortex (PMd), and supplementary motor area (SMA), bilaterally measured. Studies were carried out during the chronic stage (Ͼsix months post-onset), and differences in metabolite concentrations relative to those of healthy controls were evaluated, as well as analyses of metabolite correlations within each region of interest. Relationships between metabolites concentrations and arm motor impairment were also evaluated. Primary findings revealed significant metabolite differences across hemispheres and regions of interest between stroke and controls for N-acetylaspartate and myo-inositol, but not for glutamate/glutamine. In the ipsilesional hemisphere, we found decreased N-acetylaspartate along with stronger correlations between N-acetylaspartate and glutamate/glutamine within M1, increased myo-inositol within PMd, and decreased N-acetylaspartate and stronger correlations between all metabolites within SMA. In the contralesional hemisphere, we found significant changes only within M1, i.e., increased mI and stronger correlations between N-acetylaspartate and glutamate/glutamine. Ipsilesional N-acetylaspartate and glutamate/glutamine within M1 and N-acetylaspartate within PMd were positively correlated with arm motor impairment while contralesional N-acetylaspartate with time post-stroke. Our preliminary results demonstrated that in chronic phases of stroke, significant alterations of the neuronal-glial interactions occur in primary and non-primary motor areas, with the largest changes occurring in the ipsilesional hemisphere. The 1H-MRS approach proposed here can be used as a valuable tool in the study of metabolite concentrations and metabolic connectivity patterns within spared motor areas post-stroke. This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Th P33 MR Spectroscopic Analysis Of Stroke Patients Treated With Autologous Mononuclear Cells Shows Increased NAA/Cr Suggestive Of Neurogenesis

Mallikarjunarao Kasam, Divya Reddy Danda, Vivek Misra, James C Grotta, Sean I Savitz; Univ of Texas, Houston, Houston, TX Background and Purpose: N-acetylaspartate (NAA) is a potential marker of neurons, on Magnetic Resonance Spectroscopy (MRS) of the brain. Studies have found that NAA decreases in the peri-infarcted regions of the brain within 2 weeks after stroke followed by a continued, slow decline in NAA during the chronic stages over years. Animal models of stroke suggest that bone marrow mononuclear cells (MNCs) reduce infarct lesion maturation, promote neurogenesis, and improve neurological outcome. We are conducting a safety and feasibility study of autologous MNCs administered to stroke patients within 24 to 72 hrs after symptom onset. We are conducting serial MRS imaging on all study patients in order to identify potential biological activity that MNCs may exert within the brain. We analyzed our MRS data to address the hypothesis that MNCs reduce neuronal death and/or promote neurogenesis in the peri-infarct area after stroke. Methods: As part of a clinical trial, 10 ischemic stroke patients underwent bone marrow harvest and intravenous transplantation of autologous mononuclear cells within 24 to 72 hrs after symptom onset. Single voxel proton Magnetic resonance spectroscopy on a 3T scanner at baseline and on days 30, 90, 180 were performed to measure different metabolites such as NAA, Choline (Cho), and Creatinine in the peri infarct region. Results: Figure 1 shows the mean changes of various metabolite ratios in the peri-infarct region for all the enrolled patients. There was a significant increase in NAA/Cr and NAA/Cho from day 30 to day 180 whereas the Cho/NAA showed a significant decrease during this period. We were not able derive base line data for most of the enrolled patients for this study and could not address if MNCs reduce neuronal death within 30 days after stroke. Conclusion: Our preliminary results demonstrate that autologous bone marrow MNCs administered in the subacute stages of stroke might prevent neuronal loss and might promote neurogenesis or repair in the peri-infarct area after 30 days. These findings potentially may confirm animal studies that mononuclear cells could be cytoprotective and/or enhance neurogenesis. However, it remains unproven that NAA/Cr or other spectroscopic metabolites can be used as a marker to investigate neuroprotection or neurogenesis. These findings may also reflect recovery of neuronal metabolism, restoration of function of existing neurons, or possibly increased dendritic sprouting or synaptogenesis. These results are preliminary and limited by the small sample size.

Author Disclosures: M. Kasam: None. D. Danda: None. V. Misra: None. J. Grotta: None. S. Savitz: None.

Th P34 Suppression Of Infarct Expansion In Stroke Patients Administered Autologous Bone Marrow Mononuclear Cells

Mallikarjunarao Kasam, Divya Reddy Danda, Vivek Misra, James C Grotta, Sean I Savitz; Univ of Texas, Houston, Houston, TX Background and Purpose: Animal studies suggest that bone marrow mononuclear cells when administered in the first few days after stroke improve neurological outcome by reducing infarct maturation. We therefore studied the changes in lesion volume in patients with acute ischemic stroke enrolled in a clinical trial testing the safety of autologous bone marrow mononuclear cells. Methods: As part of a clinical trial, 10 patients with MCA ischemic strokes underwent bone marrow harvest and transplantation of autologous mononuclear cells within 24 to 72 hrs after symptom onset. Multimodal MRI on a 3T scanner with T1/T2, DWI, FLAIR and perfusion imaging are being performed at baseline and on days 30, 90, 180, and 360 to assess for structural changes. Over the same time period, 10 patients with MCA ischemic stroke meeting inclusion criteria for our study were retrospectively selected as controls from our prospectively collected stroke database for which the baseline DWI was performed at 24 hrs after stroke and a T2/FLAIR was performed at 30 days after stroke. 31 lesion volumes from 9 study patients and 20 lesion volumes from 10 control patients were calculated using a published method of hand drawn region of interests (ROI) multiplied by the slice thickness by a single rater with extensive experience in neuroimage data processing to avoid inter-rater variability. The infarct expansion ratio (IER) was calculated as the ratio of the lesion volume on FLAIR at 30 days compared with the initial DWI lesion volume at baseline. Results: Fig 1 shows the lesion volume changes to date of all the patients enrolled (nϭ10) in the bone marrow study. Except for two patients who underwent elective hemicraniectomy 4 days after stroke (patient 3 and 10), none of the study patients showed infarct expansion. However, the stroke patients that were retrospectively collected from our database had expansion of the lesion volume at 30 days. The mean IER at 30 days in the these "control patients" was 1.6Ϯ0.4 and in the cell treated patients was 0.9Ϯ0.2 (pϽ0.05). Conclusions: Our preliminary results demonstrate that in patients with subacute stroke receiving autologous bone marrow mononuclear cells, the lesion volume does not expand but even decreases over time. These findings suggest that autologous bone marrow mononuclear cells may suppress infarct expansion and may confirm animal studies reporting that mononuclear cells are cytoprotective and reduce infarct maturation. The results are limited by their preliminary nature and the small sample size.

Author Disclosures: M. Kasam: None. D. Danda: None. V. Misra: None. J. Grotta: None. S. Savitz: None.

Th P35 Alternation of Functional Connectivity after Corticospinal Tract Infarction -A Longitudinal Case-control Functional MRI study-

Yohei Takenobu, Kyoto Univ HBRC, Kyoto, Japan; Takuya Hayashi, RIKEN Cntr for Molecular Imaging Science, Kobe, Japan; Hiroshi Moriwaki, Akihide Yamamoto, National Cerebral and Cardiovascular Cntr, Osaka, Japan; Hiroaki Naritomi, Senri-Chuo Hosp, Osaka, Japan; Hidenao Fukuyama; Kyoto Univ HBRC, Kyoto, Japan Background: The physiological process during motor recovery after stroke still remains uncertain. The aim of this study was to characterize the alternation of functional connectivity compensating the motor dysfunction in stroke patients. Methods: Ten right-handed patients with pure motor hemiparesis due to supratentorial corticospinal tract infarction of first-ever stroke (9 men, mean age of 72.7 years) were prospectively examined and compared with 10 matched controls. The patients underwent serial functional MRI of finger tapping tasks with a 3T-MRI scanner at 3 time points; within 2 weeks (Scan1), at 1 month (Scan2) and at 3 months (Scan3) after stroke onset. Chronological and case-control comparisons of each of conditional (rest vs. task) analyses and psychophysiological interaction (PPI: functional connectivity) analyses were conducted in a voxelwise manner. Results: In conditional analyses of paretic hand task, in Scan1 of patients, both sides of supplementary motor areas (SMA), contralesional primary motor area (M1), dorsal premotor area (PMd), ventral premotor area (PMv) and ipsilesional PMd showed greater activity than controls, and in Scan2 and Scan3 of patients, activity of both sides of SMA, ipsilesional PMd, PMv, contralesional cerebellum became greater. In PPI analyses, functional connectivity between ipsilesional M1 and PMd become greater during the course. Contralesional motor related areas ,such as M1, PMd, and PMv, acquired greater functional connectivity with ipsilesional PMd, not directly with ipsilesional M1 in the first 2 weeks, and this functional coupling decreased during the later course of recovery. Conclusions: These results indicate that cortical reorganization compensating impaired motor network dynamically occurs through acute and chronic phases, and this alternation is not in an unidirectional manner over time. Staged rehabilitative intervention according to time course after stroke may contribute to effective achievement of successful motor recovery.

Author Disclosures: Y. Takenobu: None. T. Hayashi: None. H. Moriwaki: None. A. Yamamoto: None. H. Naritomi: None. H. Fukuyama: None.

Th P36 Axonal Outgrowth And Myelination In The Cortical Peri-infarct Area After Human And Experimental Stroke

Yuji Ueno, Michael Chopp, Li Zhang, Benjamin Buller, Zhongwu Liu, Norman L Lehman, Xianshuang Liu, Cynthia Roberts, Zheng Gang Zhang; Henry Ford Hosp, Detroit, MI Background & Purpose: Axonal remodeling is critical to brain repair after stroke. Phosphorylated neurofilament (pNFH) participates in axonal growth. We analyzed the pNFH levels and myelination in ischemic rat and human brains after stroke. Methods: Adult rats subjected to middle cerebral artery occlusion (MCAO) were sacrificed at 7, 28, and 56 days after stroke (nϭ5/group). Sham operated rats (nϭ4) were used as a control group. Human brain samples of acute (nϭ3) and chronic (nϭ2) ischemic cerebral infarction were also studied. The pNFH and myelin basic protein (MBP, a marker of oligodendrocytes) expression were measured immunohistologically. The percentages of axonal density within the total areas were calculated using Image J. In vitro, a Standard Neuron Device, which separates axons from neuronal cell bodies, was used to measure axonal changes in rat cortical neurons challenged by oxygen-glucose deprivation (OGD) (nϭ3). Co-culture of neurons with differentiated N20.1 cells, an oligodendrocyte progenitor cell line, was employed for analysis of axonal myelination. Results: Analysis of confocal images revealed that sham-operated rats exhibited pNFH (33Ϯ14%) immunoreactivity in the cortex and the majority of pNFH was myelinated as measured by co-localization with MBP. Stroke in rats decreased pNFH to 25Ϯ11% and MBP immunoreactivity in the cortical ischemic boundary at 7 days (pϽ0.01). However, 56 days after stroke, pNFH density levels reached 33Ϯ13%, which was concurrent with an increase of MBP immunoreactivity compared with 7 days after stroke (78Ϯ6% vs 50Ϯ12%, PϽ0.01), indicating that these axons are remyelinated. In vitro, neurons challenged by OGD exhibited a reduction of axons at 24h (3.4, PϽ0.01), whereas regrowth of axons (2.7, PϽ0.01) and an increase in pNFH protein levels (2.7, PϽ0.05) were detected at 96h after OGD. In addition, these axons were myelinated by oligodendrocytes. Furthermore, in human brains, pNFH substantially increased in peri-infarct areas of chronic infarction compared to acute infarction (42Ϯ10% vs 23Ϯ6%, PϽ0.01). Many of pNFH axons detected in chronic infarction were co-localized to MBP immunoreactivity. Conclusions: The present study indicates that during stroke recovery, axonal outgrowth and myelination occur in the ischemic boundary regions of rodent and human ischemic brains. This research has received full or partial funding support from the American Heart Association, National Center.

Th P37 Direct Generation Of Neurosphere-like Cells From Human Dermal Fibroblast

Soon-Tae Lee, Kon Chu, Keun-Hwa Jung, Young-Mi Song, Hyun Park, Daejong Jeon, Kyoung-Mook Kang, Manho Kim, Sang Kun Lee, Jae-Kyu Roh; SEOUL NATIONAL UNIV HOSP, Seoul, Korea, Republic of Background and Purpose: Although a number of experimental evidences have shown that transplantation of neural stem cells (NSCs) can promote neurologic recovery after stroke, the lack of autologous NSCs prevented clinical trials so far. Reprogramming of human fibroblast by delivering four factors (Oct3/4, Sox2, Klf4, and c-Myc) generate pluripotent stem cells (iPS) resembling embryonic stem cells (ESCs). Currently, developing non-tumorigenic alternative methods for the induction of iPS and controlling its differentiation are the key issues. However, the direct generation of NSCs from human fibroblast has not been successful. Here we describe a direct induction of neurosphere-like cells from human fibroblast without genetic manipulation. Methods: Primary human fibroblasts were cultured from skin tissues, and immortalized human NSCs were prepared from human fetal telencephalon cultures via a retroviral vetor encoding v-myc. We generated iNS by transfecting proteins from the human NSCs into human fibroblasts, and by maintaining the cells in neurosphere culture conditions. The cells were used for various in vitro and in vivo validations, and were further differentiated into neurons. Results: The fibroblasts were transformed into sphere morphology and generated secondary and tertiary neurospheres. These induced neurosphere-like cells (iNS) expressed NSC markers, such as Sox2 and musashi1, and had full demethylations of Sox2 regulatory regions, which has been observed in NSCs. Genetic fingerprints and chromosomes of iNS were identical to those of the skin donor. iNS were differentiated to express neural and glial markers spontaneously, and expressed sodium channels in a forced differentiation into neuron. However, iNS still had some genetic characteristics of fibroblast as determined by the gene expression profiles, and thus were likely to be partially-reprogrammed. Conclusion: Our results provide a novel concept for the direct generation of autologous neurosphere-like cells from human skin tissue. After further studies to optimize the reprogramming method, iNS can be used to regenerate the damaged brain after stroke.

Author Disclosures: S. Lee: None. K. Chu: None. K. Jung: None. Y. Song: None. H. Park: None. D. Jeon: None. K. Kang: None. M. Kim: None. S. Lee: None. J. Roh: None.

Th P38 Stroke Survivors Employ Different Stiffness Control Strategies during Learning of Reaching Movements in a Dynamic Environment

Panagiotis Koutakis, Mukul Mukherjee, Univ of Nebraska at Omaha, Omaha, NE; Pierre Fayad, Univ of Nebraska at Med Cntr, Omaha, NE; Nicholas Stergiou; Univ of Nebraska at Omaha, Omaha, NE Background: Performing reaching movements in a dynamic environment requires accurate control of endpoint stiffness. With learning, significant changes occur in the orientation and the area of the endpoint stiffness ellipse. Stroke results in sensorimotor abnormalities that can affect control of such movements. The purpose of this study, supported by the AHA (#0820136Z), was to determine if endpoint stiffness control during learning of reaching movements in a dynamic environment is affected by stroke. Methods: Chronic stroke subjects performed reaching movements using Inmotion2 robotic system (Interactive Motion Tech Inc., MA). Reaching movements were performed with the affected arm in a velocity-dependent force field that deviated the movement perpendicular to the direction of motion. All subjects received actual feedback of their movement. The effect of the learning period (baseline, early and late dynamic training) was tested for each of the eight targets (located at 90°, 135°, 180°, 225°, 270°, 315°, 0°and 45°with respect to the positive x-axis). The dependent variables were the stiffness ellipse orientation and area. Results: A significant effect of the learning period was revealed for the stiffness area for the targets at 270°(pϭ0.021) and 315°(pϭ0.020). Post-hoc tests revealed that for the target at 270°, dynamic training increased the stiffness area while at 315°, it reduced the stiffness area. A significant effect of learning period was revealed for the orientation for the targets at 270°(pϭ0.022) and 315°(pϭ0.020). Post-hoc tests showed that for target at 270°, dynamic training caused the stiffness orientation to shift towards the perturbation axis while at 315°, the shift was towards the movement direction. Conclusions: Stroke survivors demonstrated significant stiffness control for learning movements towards themselves than away from the body. This is expected because the effects of stroke symptoms like muscle weakness and spasticity are higher for movements away from the body than towards. During learning of reaching movements in dynamic environments, stroke survivors employ different stiffness control strategies for different directions probably because the direction of muscle activations are affected by the stroke symptoms. In some directions, learning is achieved by increasing the amount of stiffness (increased area) and directing the stiffness towards perturbation while in others, learning is achieved by reducing stiffness and directing it towards the direction of motion. These results provide useful information for designing specific force fields for stroke rehabilitation. This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).

Author Disclosures: P. Koutakis: None. M. Mukherjee: None. P. Fayad: None. N. Stergiou: None.

Th P39 Study of NTx®-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Acute Ischemic Stroke Patients (REGENESIS Trial)

Steven C Cramer, Univ of California, Irvine, Irvine, CA; Michael D Hill, Univ of Calgary, Calgary, Canada; the REGENESIS investigators Introduction: Preclinical studies suggest that certain growth factors given in the early days after stroke can improve long-term behavioral outcome. An earlier study ("BETAS trial") found that 3 doses of b-hCG followed by 3 doses of erythropoietin was safe. The current trial (NCT00938314) examined this sequential growth factor study in a Phase IIa, placebocontrolled, double-blind, randomized trial. Methods: Entry criteria included NIHSS 8-20, supratentorial ischemic stroke, 24-48 hr post-stroke at start of therapy; tPA administration was an exclusion criterion. Patients received 3 QD doses of SQ b-hCG (10,000 IU) followed by 3 QOD doses of IV erythropoietin (EPO). There were 3 equally sized cohorts, each randomized to active:placebo in a 3:1 ratio: in Cohort 1, EPO doseϭ4,000 IU; Cohort 2, 12,000 IU; Cohort 3, 20,000 IU. Primary outcome measure was change in NIHSS from enrollment to d90. Secondary outcome measures included modified Rankin Score (mRS) and Barthel Index at day 90, plus an array of exploratory assessments. Due to financial constraints, enrollment was reduced to 96 patients and moved to India (18 sites). Results: A total of 8 patients died during the trial, the distribution of which did not differ by treatment assignment. All but 4 living patients received all 6 study doses as planned. Patients were 65 M/21 F, mean (SD) age ϭ 58 (12) yr. At least one 15 minute session of post-stroke OT was provided to 25% of patients; PT, to 81%; and ST, to 29%. Median NIHSS at baseline, prior to therapy, was 12.7, decreasing to 7.9 at d30 and 6.0 at d90. There was no significant difference between active therapy and placebo in any endpoint, whether the 3 Cohorts were examined separately or together. Among those patients who received OT, both the change in NIHSS and the mRS were significantly better among those receiving active therapy as compared to placebo. Discussion: The current trial did not find that sequential growth factor therapy initiated 24-48 hours after stroke onset was associated with improved outcome at 90 days based upon the primary outcome measure. The current trial did demonstrate that, in the setting of moderate to severe acute ischemic stroke, sequential hCG and EPO are safe at the EPO doses examined. Future studies might restrict enrollment to those subjects likely to receive physiotherapy.

Author Disclosures: S.C. Cramer: Research Grant; Significant; Research grant to perform study. M.D. Hill: Research Grant; Significant; Research grant to perform study.

Th P40 Difference In Platelet Activation Pattern Between Patients With Ischemic Stroke And Those With Obstructive Sleep Apnea Syndrome

Mie Shimizu, Shunya Takizawa, Dept of Neurology, Tokai Univ Sch of Medicine, Isehara Kanagawa, Japan; Ichiro Kuwahira, Dept of Medicine,Tokai Univ Tokyo Hosp, Yoyogi, Tokyo, Japan; Saori Kohara, Dept of Neurology, Tokai Univ Sch of Medicine, Isehara Kanagawa, Japan; Yusuke Kondo, Dept of Respiratory Medicine, Tokai Univ Sch of Medicine, Isehara Kanagawa, Japan; Shigeharu Takagi; Dept of Neurology, Tokai Univ Sch of Medicine, Isehara Kanagawa, Japan Difference in platelet activation pattern in stroke and sleep apnea Background: Platelets play a crucial role in the pathogenesis of acute ischemic stroke (AIS). Obstructive sleep apnea syndrome (OSAS) is also associated with platelet hyperaggregability, resulting in high cardiovascular morbidity and mortality. However, state of platelet activation in OSAS is not fully understood and may be different from that in AIS. Purpose: The aim of the present study is to assess platelet function in AIS and OSAS with the use of flow cytometry and to determine the difference in the pathogenesis between the two diseases. Methods: Sixty three AIS patients (M/F 40/23, 67Ϯ16 y/o, Subtype atherothrombosis, 2-23 days after onset), 47 OSAS patients (M/F 41/6, 50Ϯ12 y/o), and 50 non-AIS/non-OSAS controls (M/F 21/29, 53Ϯ14 y/o) were studied. Platelet activation was detected for white blood cells-platelet aggregates (WBC-plt) and platelet-platelet aggregates (Plt aggre) by using 3 color flow cytometry. Results: Amount of WBC (median(25-75%) counts/l in blood) in each group was 4905(4000-6075)in controls, 7300(5800-8400) in AIS, 5700(4900-6450) in OSAS, respectively. WBC counts in both AIS and OSAS increased significantly compared to those in controls. Circulating WBC-plt increased in AIS, however those in OSAS did not. Plt aggre in both AIS and OSAS increased significantly compared to those in controls. The magnitude of the increase in Plt aggre in OSAS was significantly higher than AIS. Conclusion: The results indicate that process of platelet activation in OSAS is different from that in AIS, and suggest that platelet activation in OSAS is not due to vascular inflammation and atherosclerotic changes observed in AIS. Platelet activation in OSAS might be due to increased plasma catecholamine levels resulting in vascular contraction during apnea.

Author Disclosures: M. Shimizu: None. S. Takizawa: None. I. Kuwahira: None. S. Kohara: None. Y. Kondo: None. S. Takagi: None.

Introduction: Genome-wide association studies of stroke have failed to yield any findings that consistently replicate across studies. However, family based designs have yielded estimates of heritable risk suggesting there are genetic factors involved in the etiology of ischemic stroke. The goal of SWISS is to further refine family based studies of stroke by employing an affected sibling-pair (ASP) design to attempt to discover novel loci for ischemic stroke, as well as for specific stroke subtypes (using TOAST criteria). These results are based on a recruitment of 300 ASPs. Materials andMethods: Probands were recruited at 65 US medical centers and 5 Canadian medical centers including adult (Ͼ18 years old) men and women presenting with a neurologist-confirmed ischemic stroke. Stroke-affected siblings of the probands (concordant siblings) were recruited using proband-initiated contact. DNA was extracted from peripheral blood. A total of 286 cases and 93 controls were successfully assayed using Illumina Linkage III panels. Standard genotyping quality control was conducted prior to analyses, and yielded a total of 5,699 SNPs. Transmission disequilibrium (sib-TDT) test based on clustered-analyses of sibship concordance and discordance of phenotypes incorporating the Cochran-Mantel-Hantzel procedure were used to compare within and between clusters of participants. We estimated the Bonferroni corrected threshold for significance at 8.78 x 10 -6 . Results and Conclusions: In these preliminary results, we did not detect any results passing Bonferroni correction, although we have identified candidate loci that we will pursue as part of a sequencing effort to identify familial/rare variants associated with stroke. Currently, we are adding over 412 samples as recruitment is ongoing for the genetic component of SWISS, allowing for the pursuit of more evasive risk variants with an increased sample size yielding greater statistical power.

Author Disclosures: J.F. Meschia: Research Grant; Significant; CREST-R01 NS038384. M. Nalls: None. S. Rich: None. A. Singleton: None. J. Hardy: None. T. Brott: Research Grant; Significant; CREST-R01 NS038384. R. Brown, Jr.: None. B. Kissela: None. B. Worrall: None. Background: Mutations within the NOTCH3 gene are responsible for the disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). NOTCH3 contains 33 exons; however, mutations causing CADASIL appear to be restricted to the first twenty-four exons and result in the gain or loss of a cysteine amino acid. The role of common exonic NOTCH3 variation and mutations in exons 25-33 in stroke remains unresolved. Methods: All 33 exons of NOTCH3 were sequenced in 275 probands from the Siblings With Ischemic Stroke Study (SWISS). SWISS is an affected sibling pair study in which probands were enrolled across the US and Canada. SWISS participants were excluded from enrollment if they were known to have had CADASIL on clinical grounds. Results: One of 275 probands (0.4%) was identified as carrying a known CADASIL mutation (p.R558C). This was a case of a 57-year-old Caucasian man with a TOAST subtype of small-artery occlusion. Nine novel non-synonymous variants were identified in exons both before and after exon 24. One of the novel variants in exon 4 results in a histidine-to-arginine substitution (p.H170R) that is adjacent to known CADASIL mutants (p.R169C and p.G171C). The p.H170R mutation occurred in a 75-year-old Caucasian woman with a TOAST subtype of 'other determined etiology'. She had an extensive medical history consisting of more than three ischemic strokes, bilateral carotid endarterectomies, diabetes mellitus, and coronary artery disease. Conclusion: Variants outside the first 24 exons of NOTCH3 and those that do not alter a cysteine residue deserve further study in relation to ischemic stroke. Novel variants are being screened in other affected siblings in SWISS and in a 'sporadic' case-control series. The results of this sequencing in familial patients, assessed pathogenicity of the novel variants and the association of common variation at the NOTCH3 locus with ischemic stroke will be presented.

Th P42 Results of NOTCH3 Sequencing in Siblings with Ischemic Stroke Study Probands

Th P43 Image analysis of participants in the Siblings With Ischemic Stroke Study (SWISS)

Benison C Lau, Aparna R Baheti, Rodney S Smith, UVA HEALTH SYSTEM, Charlottesville, VA; Kathryn M Powell, Univ of South Florida, Tallahassee, FL; Carlos Leiva Salinas, UVA HEALTH SYSTEM, Charlottesville, VA; Thomas G Brott, Mayo Clinic, Jacksonville, FL; Robert D Brown, Jr, Mayo Clinic, Rochester, MN; Brett M Kissela, Univ of Cincinnati, Cincinnati, OH; Max Wintermark, UVA HEALTH SYSTEM, Charlottesville, VA; James F Meschia, Mayo Clinic, Jacksonville, FL; Natalia S Rost, Massachusetts General Hosp, Boston, MA; Bradford B Worrall; UVA HEALTH SYSTEM, Charlottesville, VA Background: White matter hyperintensity (WMH), or leukoaraiosis, is a radiographic marker of small cerebral vessel disease associated with lacunar stroke and intracerebral hemorrhage in stroke-affected populations. Limited data are available on WMH burden in families with symptomatic cerebrovascular disease. We sought to characterize WMH volume (WMHV) in participants in SWISS. Methods: SWISS is a pedigree-based study recruiting adults with confirmed ischemic stroke and their stroke-affected and unaffected siblings. Clinical images from participants are centrally adjudicated with MRI scans converted to Analyze format using MRIcro software (University of Nottingham School of Psychology, UK). Axial FLAIR images were used for computer-assisted volumetric analysis of WMH. DWI was used to measure acute infarct volumes. WMHV was calculated by doubling WMHV from the stroke-unaffected hemisphere for supratentorial infarcts and summating WMHV from both hemispheres for infratentorial infarcts. All WMHV measurements were adjusted to head size. Two readers blinded to clinical data evaluated each study. A radiologist reviewed a subset of scans and compared to the readers' values for estimates of inter-rater reliability. Results: A total of 26 sibling pairs and 148 individuals without a scan from a sibling pair were analyzed. Correlations for volumetric estimates across readers (rϭ0.96-0.97) as well as with the radiologist (rϭ0.96-0.98) were excellent. The table includes summary data for the 26 sibling pairs. Infarct and WMH volumes were not normally distributed. After log transformation, acute stroke volumes in probands and concordant siblings showed strong correlation (rϭ0.79-0.84). Across the cohort, WMHV significantly differed by stroke subtype (pϭ0.00013). Median WMHV for those with cardioembolic mechanism was 1.93 cm 3 , large artery atherosclerosis 2.06 cm 3 , small vessel disease 2.87 cm 3 , and undetermined ϭ 3.36 cm 3 . For concordant siblings, 20/44 (45%) had undetermined stroke subtype compared with 36/154 (23%) probands. Conclusions:

The SWISS imaging repository expands the exploratory potential of this unique genetic database in relationship to complex cerebrovascular phenotypes. Using a validated, semiautomated method with high inter-rater correlation estimates, we demonstrated that acute infarct volumes are highly correlated in siblings with stroke, likely attributable to heritability of specific mechanisms of cerebral ischemia. The novel finding of a within-family correlation of acute infarct volume requires replication.

Th P44 Ischemic Stroke Exome Pilot Study

John W Cole, Baltimore VA, UMD SOM, Baltimore, MD; Abhishek Pratap, Luke J Tallon, Lisa. K Sadzewicz, O. C Stine, Nicole Dueker, Yuching Cheng, UMD SOM, Baltimore, MD; Marcella A Wozniak, Barney J Stern, Baltimore VA, UMD SOM, Baltimore, MD; James F Meschia, Mayo Clinic, Jacksonville, FL; Braxton D Mitchell, UMD SOM, Baltimore, MD; Steven J Kittner, Baltimore VA, UMD SOM, Baltimore, MD; Jeffrey R O'Connell; UMD SOM, Baltimore, MD Background and Purpose: The genetic architecture of ischemic stroke is complex and likely to include rare or low frequency variants with high penetrance and large effect sizes. Such variants are likely to provide more important insights into disease pathogenesis compared to common variants with very small effect sizes. Because a significant portion of human functional variation may derive from the protein-coding portion of genes we undertook a pilot study to identify variation across the human exome (i.e., the coding exons across the entire human genome) in 10 ischemic stroke cases. Methods: To maximize the genetic contribution to stroke risk, 10 cases were selected based upon their early age-of-onset, a positive family history of stroke, and the presence of no (or minimal) standard stroke risk factors. These cases included 8 African-Americans and 2 Caucasians; and 5 lacunar, 2 cryptogenic, 2 dissection, and 1 cardioembolic subtypes. Agilent SureSelect technology was used to capture all predicted human exons after constructing 75bp paired-end Illumina sequencing libraries. The fragments were then sequenced using the Illumina Genome Analyzer IIx platform and aligned to UCSC Human Genome build 18 (NCBI build 36.1) using Burrows-Wheeler Aligner. Results: Each sequenced sample generated an average of 3.8Gbp over 25.5 million read pairs with 97% of the reads aligning uniquely and 71% mapping to ϩ/-200bp of the targeted regions. After applying quality filters, African-Americans showed greater variation with an average of ϳ24.5K variants compared to ϳ22.4K for Caucasians, as expected from the literature; the number of novel variants (not in dbSNP) was 2839 (11.6%) vs.1105 (4.9%), respectively. Pursuing the hypothesis that stroke susceptibility genes may be enriched for novel variants across cases, we identified 70 genes where each African-American case had at least one rare variant but only 48 when the 2 Caucasian cases were included. Under a double-hit hypothesis of two novel variants in the same gene, only 6 genes were identified. Three of the six genes are involved in carbohydrate and/or lipid metabolism, and of these, one was previously associated with diabetes. Of the three remaining genes, one is involved in the inflammatory response, one is solely expressed in the CNS, and the function of the last is unknown. Conclusions: We obtained high capture efficiency and excellent coverage of the exome in our 10 case samples. African-Americans had greater coding diversity than Caucasians as expected. We identified 48 genes where each case had at least one-novel variant and 6 genes with at least two. Exome sequencing will be a valuable tool for uncovering rare coding variants contributing to stroke risk.

Th P45 Genome-wide SNP Association For Cerebral Vasospasm In Subarachnoid Hemorrhage Patients

Hyungsuk Kim, NINR, Bethesda, MD; Elizabeth Crago, Univ of Pittsburgh, Pittsburgh, PA; Mirim Kim, NINR, Bethesda, MD; Yvette Conley, Paula Sherwood, Univ of Pittsburgh, Pittsburgh, PA; Samuel Poloyac, Mary E Kerr; NINR, Bethesda, MD Objectives: In the United States, 10 per 100,000 people a year suffer from an aneurysmal subarachnoid hemorrhage (aSAH). aSAH is a destructive disease that occurs primarily in women and is associated with a 30% mortality and 30% morbidity rate. Cerebral vasospasm (CV) is a common and serious complication involving the constriction of cerebral arteries after aSAH. Brain damage from secondary ischemic deficit due to this vasospasm can lead to cerebral infarction and may cause poor outcomes. Despite therapies targeted toward the primary mechanisms associated with CV, controversy continues regarding the underlying pathogenesis of this condition; hence an effective therapy remains elusive. We examined an association of genetic variants across the entire human genome in aSAH patients to decipher the molecular-genetic mechanisms of altered cerebral blood flow velocity. Methods: Genotyping with Affymetrix SNP 6.0 array was performed at the National Institutes of Health with 279 patients with aSAH (197 females and 81 males, 53.1 Ϯ 11.4 years old) recruited from University of Pittsburgh. This microarray-based technology allows whole genome screening with 1 million single nucleotide polymorphisms (SNPs) without specific functional genetic hypotheses prior to undertaking analysis. Clinical data was prospectively collected, including severity of injury (admission Hunt and Hess and Fisher scores), measurement of cerebral blood flow with the first 14 days of injury [cerebral angiography, daily transcranial Dopplers, mean flow velocity and lindegaard ratio (LR) and CT scans], and clinical evidence of neurological deterioration. Data potentially representing the CV were tested in association with genotypes. Results: The strongest significant associations were between rs10279206 in chromosome 7q36.3, rs6760279 and rs16865932 in chromosome 2p25.1 (pϭ1.46 x 10 -2 , pϭ4.56 x 10 -2 and pϭ4.99 x 10 -2 respectively) with LR with the multiple test corrections of Bonferroni threshold Ͻ 0.05. Conclusion: Despite the relatively small sample size used in this study, significant genetic loci of chromosome 7q36 and 2p25 were associated with an increased cerebral blood flow velocity detected by the LR in aSAH patients. This result implicates the role of genetics in altered cerebral blood flow velocity, which can influence on the prognosis of aSAH.

Introduction: Carotid intima-media thickness (IMT) has been increasingly a subclinical marker for cardiovascular disease. However, few studies have examined the association of IMT with stroke and ischemic heart disease (IHD) in Asia. We assessed the hypothesis that carotid atherosclerosis was a predictor for stroke and IHD events in a general urban Japanese population. Methods: We studied 5,331 Japanese individuals (mean age 55.3 years, without stroke or IHD) who completed a baseline survey and carotid atherosclerosis in the Suita Study, and were then followed for 8.7 years on average. Carotid atherosclerosis was evaluated by high-resolution ultrasonography with atherosclerotic indexes of IMT in the common carotid artery (CCA), carotid artery bulb, and internal and external carotid arteries. Mean IMT was defined as the mean of the IMT of the proximal and distal walls for both sides of the CCA at a point 10 mm proximal to the beginning of the dilation of each carotid artery bulb. Max-CCA and Max-IMT were defined as the maximum IMT in the CCA and the entire scanned area, respectively. Low-density lipoprotein cholesterol (LDL) was estimated using the Friedewald formula. The risks of stroke and IHD across carotid atherosclerosis were compared by the use of multivariable-adjusted Cox proportional-hazards model. Results: In 46,561 person-years of follow-up, we documented 124 cerebral infarctions, 49 hemorrhagic strokes, 12 unclassified strokes, and 125 IHD events. The multivariable-adjusted hazard ratios (HRs; 95% confidence intervals, 95% CI) in the fourth quartile (Ͼ0.95 mm) of the mean IMT for all strokes, cerebral infarction, and IHD were 2.48 (1.12 to 5.52), 3.66 (1.05 to 12.70), and 2.94 (0.99 to 8.70), respectively, compared with the first quartile (Ͻ0.75 mm). The adjusted HRs (95% CI) in the fourth quartile (Ͼ1.70 mm) of Max-IMT for all strokes, cerebral infarction, and IHD were 1.93 (1.09 to 3.41), 1.79 (0.87 to 3.69), and 2.29 (1.12 to 4.69), while those in the fourth quartile (Ͼ1.15 mm) of Max-CCA were 1.67 (1.01 to 2.76), 2.15 (1.07 to 4.32), and 2.41 (1.24 to 4.69), respectively, compared with the first quartile (Ͻ1.0 mm for Max-IMT and Ͻ0.9 mm for Max-CCA). The adjusted HRs (95% CI) for all strokes, cerebral infarction, and IHD were 3.32 (1.01 to 10.76), 2.17 (0.52 to 9.04), and 13.7 (3.90 to 48.2) in 0.1mm of mean IMT, while they were 1.32 (1.03 to 1.68), 1.42 (1.07 to 1.87), and 1.61 (1.30 to 1.99) in 0.1mm of Max-CCA, respectively. The HRs (95% CI, P value) of cerebral infarction and IHD combined in 0.1mm of Max-CCA were 2.39 (0.89 to 6.40, Pϭ0.1) with the use of an antihypercholesterolemic drug (statin in almost all cases), 1.47 (1.08 to1.98, Pϭ0.01) with LDLϾ130 mg/dL and a non-antihypercholesterolemic drug, and 1.56 (1.21 to 2.01, Pϭ0.002) with LDLConclusions: Carotid IMT, especially Max-CCA is a strong predictor for stroke, cerebral infarction, and IHD in Asia.

Author Disclosures: Y. Kokubo: None. K. Toyoda: None. M. Watanabe: None. A. Higashiyama: None. Y. Ono: None. K. Nagatsuka: None. T. Okamura: None.

Th P47 B-Type Natriuretic Peptide Level is a Better Predictor of Stroke Risk in Patients with Atrial Fibrillation

Vijaiganesh Nagarajan, John H Stroger Hosp of Cook County, Chicago, IL; Heather Gage, Anna Demopoulos, George Karam, Rush Univ Med Cntr, Chicago, IL; Rami Doukky; Rush Univ Med Cntr and John H Stroger Hosp of Cook County, Chicago, IL Background: Nonvalvular atrial fibrillation (AF) is the most common cardiac dysrhythmia. It is well known that left atrial appendage thrombus (LAAT) is the most frequent source of embolic stroke (ES) in AF patients. Currently, the CHADS2 score is widely utilized to predict stroke risk. We observed that left ventricular diastolic dysfunction (DD) is prevalent among patients with risk factors constituting CHADS2 score (cardiac failure, hypertension, age, diabetes, stroke). It is plausible that DD with subsequent elevation of left ventricular filling pressure (LVFP) mediates blood stasis and the formation of LAAT. We evaluated whether BNP, a surrogate for LVFP, is a better predictor of LAAT than the CHADS2 score. Hypothesis: BNP level is superior to-and independent of the CHADS2 score in predicting LAAT. Methods: We conducted a retrospective cohort study of 275 consecutive nonvalvular AF patients who underwent transesophageal echocardiography (TEE) to exclude LAAT. Pre-TEE data was collected, including CHADS2 score, BNP level and use of aspirin or warfarin. A 2-sided T-test was used to compare mean BNP levels in LAAT(ϩ) vs. LAAT(-) patients. A multivariate logistic regression analysis (MVLRA) was used to demonstrate whether BNP predicts LAAT independent of known confounders. An ROC curve was used to identify a cutoff value for BNP, below which LAAT is highly unlikely. Results: Among 275 subjects, 23 (8.3%) were LAAT(ϩ) by TEE and 67% of patients had BNP levels available for analysis. Baseline characteristics in LAAT(ϩ) and LAAT(-) patients were similar; including CHADS2 score (2.53 vs. 2.3, pϭNS), antiplatelet use (73% vs. 70%, PϭNS) and warfarin use (87% vs. 70%, pϭNS). Mean BNP levels were significantly higher in LAAT(ϩ) than LAAT(-) subjects (2082 vs. 457, P ϭ0.02). MVLRA demonstrated that BNP is predictive of LAAT independent of the CHADS2 score and its individual components (pϭ0.009), as well as the use of antiplatelet and warfarin. The ROC curve showed that BNP has a higher discriminatory capacity in predicting LAAT than the CHADS2 score (AUC 0.94 vs. 0.54) and that none of the patients with BNP Ͻ or ϭ450 pg/dl had LAAT, regardless of the CHADS2 score [LR (-) ϭ 0]. Discussion: These preliminary data suggest that BNP is both independent of-and superior to the CHADS2 score in predicting the formation of LAAT. Our study is limited by a low LAAT event rate, retrospective design and unavailability of BNP data from all subjects. If proven by a prospective controlled outcome study, BNP has the potential to replace or complement the CHADS2 score in predicting stroke risk and determining the need for anticoagulation therapy. Furthermore, it may be possible to identify a cutoff value for BNP (Ͻ or ϭ 450 pg/dl) below which LAAT formation and ES are highly unlikely, eliminating the need for anticoagulation in many patients.

Author Disclosures: V. Nagarajan: None. H. Gage: None. A. Demopoulos: None. G. Karam: None. R. Doukky: None.

Th P48 Newly Diagnosed Atrial Fibrillation among Different Subtypes of Ischemic Stroke and Transient Ischemic Attack

Patricia M Riccio, Francisco Klein, Luciano A Sposato; FAVALORO FOUNDATION, Buenos Aires, Argentina Background and Purpose: Newly diagnosed atrial fibrillation (NDAF) i s the atrial fibrillation (AF) detected after ischemic stroke (IS) or transient ischemic attack (TIA) in patients with previous sinus rhythm. Most studies on NDAF are limited to patients with cryptogenic events (TOAST group 5). However, NDAF can also occur in other subtypes of IS or TIAs. Our objective was to assess the frequency of detection of NDAF in the 5 TOAST subtypes of IS and TIA. Methods We assessed every patient admitted with IS and TIA between 01/01/2007 and 12/31/2009. We excluded periprocedural events (n ϭ 103) because of the known relationship between surgery and the occurrence of NDAF, hemorrhagic strokes (n ϭ 16), and patients with known AF (n ϭ 45). We classified the remaining TIA and IS cases into TOAST subtypes. Every patient underwent continuous electrocardiographic monitoring for at least the first two days after admission. We compared the frequency of NDAF between the 5 groups (Ϭ2, P Ͻ 0.05). As this is a descriptive study, not intended to infer causality between TOAST subtypes and occurrence of NDAF, we did not compare risk factors and other variables between TOAST subtypes. We described age, gender, frequency of diabetes and the severity of stroke according to the NIH stroke scale in the five groups. Results We assessed 172 patients with IS or TIA without prior AF, 103 men (64.4%), aged 68Ϯ14 years. We detected 19 NDAFs (11.0%, 95%CI 7.2-16.6). The frequency of NDAF in the five TOAST subgroups were: large vessel disease: 5/37 cases (13.5%), non-AF cardioembolic: 6/31 cases (19.4%), small vessel disease: 0/32 cases (0.0%), other causes: 3/13 cases (23.1%), and cryptogenic: 5/59 cases (8.5%), P ϭ 0.32. We found no gender differences (P ϭ 0.27) between the five groups. Age (P ϭ 0.001), frequency of diabetes (P ϭ 0.002), and severity of stroke (P ϭ 0.009) were different in the 5 groups: large vessel disease 69Ϯ11, 17.7% and 6.5Ϯ6.6; cardioembolic 61Ϯ15, 34.1% and 7.8Ϯ6.9; small vessel disease 66Ϯ11, 15.2% and 2.5Ϯ2.0; other causes 58Ϯ16, 6.1% and 7.2Ϯ5.9, cryptogenic 72Ϯ11, 26.8% and 6.2Ϯ6.1, respectively. Conclusions: NDAF was detected in every TOAST subgroup with the exception of small vessel disease. We suggest that NDAF screening with continuous electrocardiographic monitoring should not be limited to cryptogenic IS and TIA. hyperintensities are common in patients with heart failure. However, not much is known about the relationship between heart failure and cerebral gray matter injury. Chronic cerebral hypoxia may have pathologic and clinical consequences that are not fully elucidated. Objective: To quantify cerebral gray and white matter volumes in patients with low left ventricular ejection fraction (LVEF) compared to unaffected, age-matched controls with normal LVEF. Methods: This was a cross-sectional pilot study. Subjects with low LVEF (Ͻ50%) and normal LVEF (Ͼ50%), demonstrated on transthoracic echocardiogram, were included in the study. All patients had brain MRI scans as part of transient ischemic attack evaluations. MRI scans demonstrating restricted diffusion or old stroke were excluded. T1-weighted spin-echo axial sequences were used for brain extraction, volume calculation and segmentation of gray and white matter; using a fully automated brain volume and segmentation program SIENAX (v2.2). Analyses were performed blinded to the subjects' LVEF status. Results: 28 subjects including 14 cases with low LVEF (mean EF 34.2 Ϯ7.7) and 14 controls with normal LVEF were examined. Baseline demographics were well-matched in both group. The median grey matter volume was 537.5 ml (mean 507.4 Ϯ 166.3; range 265.7-790.2) in the low LVEF group and 542.0 ml (mean 541.3 Ϯ 167.2; range 317.8-795.4) in the control group (pϭ0.57). The median white matter volume was 941.8 ml (mean 966.7 Ϯ 203.3; range 536.3-1313.7) for the low LVEF group and 843.5 ml (mean 916.1 Ϯ 206.2; range 600.0-1284.4) in the normal LVEF (pϭ0.40). There was a positive correlation between grey matter volumes and low LVEF: [Pearson's correlation coefficient: 0.51; p value 0.06] (Figure ) not seen with white matter volumes or in the control group. Further analysis using regional gray matter voxel-based morphometry is ongoing to delineate regional gray matter areas that may be more susceptible to injury in patients with low LVEF. Conclusion: These preliminary observations indicate that low LVEF may lead to preferential injury of the cerebral gray matter compartment. This may have significant clinical implications and also assist in designing interventions to reduce grey matter injury. Larger studies including multi-modal MR imaging and neuropsychological assessments are warranted to explore this potential mechanism of gray matter injury in patients with low LVEF.

Author Disclosures: P. Bhattacharya: None. F. Bao: None. M. Shah: None. G. Ramesh: None. R. Madhavan: None. O. Khan: None.

Th P51 Frequency and Progression of Cerebral Microbleeds among Patients with Stroke Due to Endocarditis

Hermelinda G Abcede, Jeffrey L Saver, Latisha K Ali, Sarah Song, Radoslav Raychev, Peter Adamczyk, Noriko Salamon, David S Liebeskind; UCLA Stroke Cntr, Los Angeles, CA Background: Cerebral microbleeds (CMBs) are most commonly ascribed to microvascular injury of hypertension or amyloid angiopathy, but also may arise from other bleeding prone angiopathies. Although isolated reports have described CMB in endocarditis, the risk of hemorrhage with such findings has not been detailed. Our objective was to describe CMBs in a large case series of stroke patients with endocarditis and to identify whether they had an increased risk for hemorrhage compared to those without CMBs. Methods: Patients admitted or referred to the stroke service at a tertiary care center from January 2002 to June 2010 were reviewed to identify those who were diagnosed with endocarditis -infective or marantic and who underwent at least one MRI with a gradient refocused echo (GRE) sequence. All available MRI scans at presentation and thereafter were analyzed for presence, number, and location of CMBs. Results: Among 57 patients with endocarditis, 43 had MRIs with GRE sequences. In these 43 patients, average age was 58.3, range 14-91, and 55.8% were female. Presenting clinical diagnoses were ischemic stroke in 86.0%, intracerebral hemorrhage in 9.3%, transient ischemic attack in 2.3%, limb ischemia in 2.3%, and narcolepsy in 2.3%. One patient presented with an ischemic stroke and a subdural hematoma. Among the ischemic stroke patients, 73.0% had no hemorrhagic transformation (HT) of the ischemic field at the time of first MR imaging and 27.0% did have HT at first imaging. Overall, CMBs were found in 28 patients (65.1%). 27 patients (62.8%) had at least one CMB present on first MR imaging. Among patients with CMBs, the mean number of CMBs was 4.5 (range 1 -26). Patients with CMBs had 1 or more in the following locations: cortical gray-white junction region -78.6%, subcortical white matter -39.3%, cerebellum -32.1%, thalamus -10.7%, basal ganglia -10.7%, pons -3.6%, and medulla -3.6%. Among patients with any CMB at first imaging, 11.1% developed HT and 3.7% developed subsequent intracerebral hemorrhage, while among those without any CMB at first imaging, 12.5% developed subsequent HT and 0% developed subsequent intracerebral hemorrhage. Ten of the patients with CMBs at first imaging had at least one subsequent MRI with GRE performed and 6 (60%) developed new microbleeds on subsequent scans. Conclusion: MRI GRE-imaging is useful to assess and monitor the evolution of bleeding-prone cerebral angiopathy in endocarditis. Cerebral microbleeds are common at presentation, present in nearly two-thirds of patients, with the cortical gray-white junction region the most common site. Among patients with CMBs at presentation, over half will develop additional CMBs over subsequent days.

Author Disclosures: H.G. Abcede: None. J.L. Saver: None. L.K. Ali: None. S. Song: None. R. Raychev: None. P. Adamczyk: None. N. Salamon: None. D.S. Liebeskind: None.

Th P52 High Incidence of Vascular Risk Factors and Small Vessel Disease in Young Patients with Stroke

William J Hicks, II, Nusrat Harun, Renganayaki Pandurengan, Tzu-Ching Wu, Vivek Misra, George Lopez, Nicole R Gonzales, Andrew D Barreto, James C Grotta, Sean I Savitz; Univ of Texas Health Science Cntr at Houston, Houston, TX Objective: Ischemic strokes in the young can be devastating to patients, families, and clinicians alike. Historically, stroke in the young has been attributed, in large part, to cryptogenic, genetic, autoimmune, and cardiac etiologies. Recently at our center, we have seen in younger patients many vascular risk factors that traditionally develop in older patients. We aimed to review epidemiological data from ischemic stroke patients 45 years old and younger (young), versus those over 46 (old), to identify specific trends in vascular risk factors and classic TOAST etiologies in young patients. We hypothesized that within our large metropolitan stroke center, young stroke patients share more in common with older patients with respect to etiologies and risks than previously known. Methods: Using our stroke registry (07/04 -06/10), we retrospectively identified patients with ischemic strokes treated at our institution. Demographics and risk factors were collected. Young and old patients were further subdivided by gender, ethnicity, and stroke etiology (using TOAST criteria). Results: 2409 patients were identified, 170 within the young group. Subgroup analysis is shown in table 1 between young and old patients. The percentage of small vessel disease in the young was identical to that found in the older group. Given the unexpected percentage of small vessel disease in the young, we further investigated this group (Table 2). There were a higher percentage of African American and Hispanic stroke patients in the younger age group, especially small vessel stroke patients (25% and 23%, respectively). Smoking was seen in a higher percentage within the young stroke population, particularly with young Caucasian patients. Over half of the young patients had hypertension, more so within the young African American patients. Diabetes and coronary artery disease disproportionally affect African American patients as well. Further analysis has also shown an increase over the years in the incidence of small vessel strokes in the young.

Conclusion:

Young stroke patients at our center have high incidences of traditional stroke risk factors. In support of these findings, the percentage of young patients with small vessel strokes is particularly striking, considering that this is a sign of end-organ damage from vascular disease. Our data call for stronger educational programs and primary care aimed at reducing modifiable risk factors for stroke in young patients, particularly minorities but also amongst Caucasians.

linked to small vessel disease; however, long-term impairment of cerebral perfusion due to significant exracranial (EC) and intracranial (IC) atherosclerosis may affect the severity of leukoaraiosis. We sought to determine whether, independently of stroke subtype, burden of WMH is associated with the radiographic evidence of EC or IC atherosclerosis in patients with acute ischemic stroke (AIS). Methods: We retrospectively identified 141 prospectively enrolled AIS subjects with CT angiogram (CTA) of head and neck and a brain MRI on admission from 2008-2009. EC was defined as evidence of Ն 50% stenosis in the extracranial internal carotid artery, and IC as Ն 50% stenosis in either the middle, anterior, or posterior cerebral arteries on CTA, contralateral to the side of AIS. WMH volume (WMHV) was determined using validated, semi-automated protocol. To avoid confounding by the presence of focal white matter damage caused by the index stroke, total WMHV was measured from the hemisphere unaffected by AIS (Figure). Multiple logistic regression was used to assess the relationship between WMHV and radiographic evidence of EC/IC atherosclerosis. Results: There were a total of 71 patients with EC and 70 patients with IC in this group (mean age 70.2 years, 54% women), with 24 (18%) demonstrating evidence of both. Median WMHV was 13.7 cc in subjects with EC, 9.8 cc in subjects with IC, and 7.9 cc in subjects with both. In univariate analysis, age (pϽ0.0001), diagnosis of hypertension (HTN), (pϭ0.01), hyperlipidemia (pϭ0.004), IC (pϭ0.009) but not EC (pϭ0.12) independently predicted WMHV. In multivariate regression model including EC, only age (pϽ0.0001) and HTN (p ϭ 0.025) demonstrated independent effects on WMHV. Evidence of IC showed a significant trend towards association with higher WMHV (coefficient: 0.35, Standard Error: 0.20) after adjustment for age and history of HTN; however, this effect was not statistically significant (p ϭ 0.07). Conclusions: Only HTN determined severity of leukoaraiosis measured as WMHV in patients with EC admitted for evaluation of AIS. Whereas EC was not associated with WMHV, the trend towards association between IC and WMH burden warrants further investigation in a larger group of subjects to maximize the power. Understanding the role of atherosclerosis in chronic cerebrovascular injury presenting as MR-detectable WMH may offer novel preventive and management strategies in the future.

Introduction:

The Berlin Cream&Sugar Study is the first prospective observational study in acute ischemic stroke patients that aims to determine if parameters of postprandial glucose and triglyceride (TG) metabolism predict recurrent stroke. MRI imaging of Cream&Sugar participants revealed that cerebral white matter disease (WMD) was frequently present after acute ischemic stroke. Hypothesis: This substudy of the Berlin Cream&Sugar Study tests the hypothesis that fasting and postprandial TG and glucose levels are associated with WMD. Methods: We performed a combined oral triglyceride (OTTT) and glucose tolerance test (OGTT) in 36 patients within 3 to 7 days after first ischemic stroke to simultaneously determine postprandial glucose and triglyceride tolerance under standardized testing conditions. Glucose and triglyceride levels were measured before, during, and 5 hours after the test. Severity of WMD was assessed on fluid attenuated inversion recovery sequences of a 3T MRI scanner using Wahlund scores. Patients were stratified into two groups according to their Wahlund scores, high (above median Wahlund score) and low (equal or below median). We performed a non-parametric test to compare levels of glucose and triglycerides between both strata. Results: Of 36 patients (mean age 66 years, SD 12.66, median NIHSS 2.5, IQR 0-11), the median Wahlund score was 5 (IQR 2 -8). Fasting glucose levels differed significantly between 21 patients with high and 15 patients with low Wahlund scores (median 113 mg/dl, IQR 70 -145 mg/dl vs. median 88 mg/dl, IQR 71 -128 mg/dl; Mann-Whitney-U Test, PϽ.05). Moreover, median glucose levels 2 hours after the OGTT differed significantly between patients with high and low Wahlund scores (189 mg/dl , IQR 145 -198 mg/dl vs.142 mg/dl, IQR 124 -160 mg/dl; Mann-Whitney-U Test, PϽ.05). In contrast, fasting TG and TG levels 5 hours post-OTTT did not significantly differ between patients with high and low Wahlund scores. Conclusion: In conclusion, both elevated fasting and non-fasting glucose, but not TG levels are associated with more severe WMD in patients with ischemic stroke.

Th P55 Soda Consumption and Risk of Vascular Events in the Northern Manhattan Study

Hannah Gardener, Tatjana Rundek, Clinton Wright, Univ of Miami Miller Sch of Medicine, Miami, FL; Julio Vieira, Mitchell S Elkind, Columbia Univ, New York, NY; Ralph L Sacco; Univ of Miami Miller Sch of Medicine, Miami, FL Previous studies have shown a positive association between diet soda consumption and risk of the metabolic syndrome and diabetes, which are important vascular risk factors. The goal of this study is to examine the association between soda consumption and risk of stroke, myocardial infarction (MI), or vascular death. The study population included participants from the Northern Manhattan Study, a multi-ethnic population-based cohort study to examine the incidence and risk factors for stroke, with data on soda consumption available (Nϭ2564, 36% men, mean age 69 Ϯ 10 years, 20% white non-Hispanic, 23% black non-Hispanic, 53% Hispanic). Diet and regular soda consumption were assessed by self-report using a semi-quantitative food frequency questionnaire at baseline, and were examined categorically: no soda (Ͻ1/mo) (Nϭ901, referent), moderate regular only (1/mo-6/wk) (Nϭ761), daily regular only (Nϭ286), moderate diet only (Nϭ214), daily diet only (Nϭ116), moderate diet and any (1ϩ/mo) regular (Nϭ239), daily diet and any regular (Nϭ47). Cox models were used to examine the association between soda consumption and incident vascular events (stroke, MI, or vascular death) controlling for sociodemographics and vascular risk factors. During a mean of 9.3 years of follow-up, 559 vascular events accrued. After controlling for age, sex, race/ethnicity, smoking, physical activity, alcohol consumption, and calories consumed per day, a 61% increased risk of vascular events was observed among those who drank daily diet soda only as compared to those who drank no soda (95% CI 1.13-2.30), and this association persisted after additionally controlling for the metabolic syndrome, peripheral vascular disease, and cardiac disease history (RRϭ1.48, 95% CI 1.03-2.12). A marginally significant increased risk of vascular events was also observed among those who consumed diet soda daily and regular soda once or more per month (adjusted RRϭ1.74, 95% CI 0.96-3.16). There was no significant increased risk of vascular events among those who consumed moderate or daily regular soda only (vs. no soda: moderate regular only adjusted RRϭ0.93, 95% CI 0.74-1.16; daily regular only adjusted RRϭ1.20, 95% CI 0.91-1.59). This study suggests that diet soda is not an optimal substitute for sugar-sweetened beverages, and may be associated with a greater risk of stroke, MI or vascular death than regular soda. Further studies are needed to explore potential mechanisms for the association between diet soda consumption and vascular events.

Author Disclosures: H. Gardener: None. T. Rundek: None. C. Wright: None. J. Vieira: None. M.S.V. Elkind: None. R.L. Sacco: None.

Th P56 Subclinical Stroke Symptoms and Diabetes in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Monika M Safford, George Howard, Univ of Alabama at Birmingham, Birmingham, AL; James Meschia, Mayo clinic, Jacksonville, FL; Linda Williams, Roudebush VA Med Cntr, Indianapolis, IN; Ronald Prineas, Wake Forest Univ, Winston-Salem, NC; Virginia Howard, Univ of Alabama at Birmingham, Birmingham, AL; Brett Kissela, Univ of Cincinnati, Cincinnati, OH; Paul Muntner; Univ of Alabama at Birmingham, Birmingham, AL Introduction: Individuals with diabetes are at increased risk of CVD events, which are not always clinically recognized, hampering optimal secondary prevention efforts. We examined the prevalence of stroke symptoms that had not been diagnosed by a physician as stroke (subclinical stroke symptoms) for participants with diabetes, pre-diabetes and neither in a large national cohort study. Methods: The REGARDS study includes 30,239 participants recruited between 2003-7 who are being followed prospectively. The community-dwelling sample was age Ͼ45 years at baseline and designed to be balanced on race and sex; the final sample was 55% female and 41% black. Participants were examined for prevalence of stroke symptoms using 6 validated questions (sudden weakness, numbness, painless loss of vision in one/both eyes, loss of half vision, loss of ability to understand people, and loss of ability to express oneself verbally/in writing). Diabetes was defined by report of physician diagnosis, receipt of diabetes medications, fasting glucose Ն126 mg/dL, or random glucose Ն200 mg/dL. Pre-diabetes was defined as fasting glucose 110-126 mg/dL or random glucose 140-199 mg/dL among those without diabetes. On those free of stroke or TIA at baseline, we calculated multivariable adjusted odds ratios (OR) for subclinical stroke symptoms associated with diabetes and pre-diabetes compared to neither, adjusting for sociodemographics and baseline stroke risk factors. Results: Of the 25,696 participants included in the analysis, 23.6% had diabetes and 15.6% had pre-diabetes. Subclinical stroke symptoms were reported among 22.7% of those with diabetes, 15.6% of those with pre-diabetes, and 14.9% of those with neither. After adjustment, participants with diabetes still had a 32% higher OR for reporting clinically unrecognized stroke symptoms than those with pre-diabetes or neither (Table ).

Conclusion:

Nearly one in four diabetic individuals with no recollection of a stroke diagnosis nevertheless reported symptoms suggestive of stroke. A better understanding of the mechanisms leading to residual excess stroke risk after controlling for stroke risk factors in individuals with diabetes is needed, and interventions to improve stroke detection in persons with diabetes may be warranted.

Th P60 Mortality Prediction Across Stroke Type: Does Including CT Findings for ICH Cases Improve Model Performance?

Darin B Zahuranec, Brisa N Sanchez, Devin L Brown, Jeffery J Wing, William J Meurer, Lewis B Morgenstern, Lynda D Lisabeth; UNIV MICHIGAN HEALTH SYSTEM, Ann Arbor, MI Background: Ischemic stroke (IS) and intracerebral hemorrhage (ICH) are distinct diseases, yet these two stroke types are often combined in outcome studies. CT findings, such as ICH volume, location, and intraventricular hemorrhage (IVH), are key predictors of mortality in ICH. However, CT findings for ICH are often unaccounted for in studies of mixed stroke type as they have no correlate in IS and are unavailable in administrative datasets. We investigated the impact of adding CT data for ICH cases on multivariable model performance for mortality prediction in a population of mixed stroke type. Methods: All cases of first ICH or IS (2000)(2001)(2002)(2003) in Nueces County, Texas were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project. Logistic regression models were developed to predict 30-day mortality. All-cause mortality was determined from state and national databases. The base model covariates (Model 1) included National Institutes of Health Stroke Scale (NIHSS) and a stroke type indicator (ICH or IS). Model 2 added CT data (ICH volume in cc; IVH yes/no; infratentorial ICH yes/no) using interaction terms with stroke type. This method accounted for the CT data in ICH cases only and avoided the need for separate models stratified by stroke type. Model performance was assessed with area under the curve (AUC) and an alternate test of model fit, the unweighted sum of squared residuals (S). AUC and S were corrected for overfitting with multiple bootstrapped samples. Results: A total of 1,296 cases were included (IS 1,088 (84%), ICH 208 (16%)). Mean age was 71.0 (SD 12.5), 52% were female, 53% were Mexican American, 68% had hypertension, 35% had diabetes, and 29% had coronary disease. Median NIHSS was 4 (inter-quartile range (IQR) 2, 8) overall; 3 (IQR 1, 7) for IS; and 9.5 (IQR 3, 21) for ICH. Thirty-day mortality was 16% overall; 11.3% for IS; and 39% for ICH. AUC and S for the two models are shown in the Table . Adding CT findings to the model resulted in no significant change in AUC or S when all stroke types were included. Even when the analysis was restricted to ICH only, there was no change in model performance with addition of CT data, though there was a trend toward increased AUC. Conclusions: In this mixed cohort of IS and ICH, addition of CT data for ICH cases did not improve model performance for 30-day mortality prediction over a simpler method using NIHSS and stroke type as predictors. These findings have implications for the design of studies that combine IS and ICH, suggesting that the resources needed to obtain CT data for ICH cases may not be needed to improve mortality prediction.

Th P61 Association Between Cerebral And Peripheral Artery Atherosclerosis In Patients With Ischemic Stroke

Jinkwon Kim, Dong Hyun Lee, Hyo Suk Nam, Young Dae Kim, Myoung Jin Cha, Ji Hoe Heo; Yonsei Univ College of Medicine, Seoul, Korea, Republic of Background Peripheral arterial disease (PAD) in patients with acute ischemic stroke is associated with recurrent vascular events and high cardiovascular mortality. However, PAD in stroke patients is often underdiagnosed due to asymptomatic clinical features. Ankle brachinal index (ABI) is a simple and efficient method in identifying both symptomatic and asymptomatic patients with PAD. Objective We investigated the frequency of PAD and relationship between cerebral atherosclerosis and PAD in terms of location and burden of cerebral artery atherosclerosis in ischemic stroke patients. Methods Among 2273 patients who were registered to the single hospital-based stroke registry between January 2007 and May 2010, there were 1461 patients with acute cerebral infarction or transient ischemic attack who were free of potential cardio-embolic sources of embolism and other rare causes of stroke. Of them, 938 patients (64.2%) undertook ABI examination. After excluding two patients who did not have cerebral angiography and five patients with ABI Ͼ1.3, 931 patients were included for the analysis. An ABI ϭϽ0.9 was considered as the presence of PAD. Results Demographic characteristics were not different between patients with ABI performed and those without except higher frequency of previous cerebral infarction history in the latter group. Of 931 patients, 81 patients (8.7%) were found to have PAD. Cerebral atherosclerosis, which was defined as arterial stenosis Ͼϭ50% were found in 551 patients (59.2%). The presence of PAD was associated with that of cerebral atherosclerosis (OR:3.04, 95% CI:1.73-5.35). The number of cerebral arteries with atherosclerosis was greater in patients with PAD than those without(pϽ0.001). In the multivariate analysis, patients with PAD were older and more likely to have low body mass index, diabetes mellitus, hypercholesterolemia, previous cerebral infarction, coronary artery disease and the number of cerebral arteries with atherosclerosis when comparing with those without PAD. Among cerebral arteries, atherosclerosis of the extracranial internal carotid artery was associated with PAD (OR:3.49, 95% CI:2.02-6.04). Twenty six percent of patients with atherosclerosis of the extracranial internal carotid artery had PAD. Conclusions: The presence of PAD was associated with that of cerebral atherosclerosis. Acute ischemic stroke patients with cerebral atherosclerosis, particularly of the extracranial internal carotid artery, should be closely examined and screened for the presence of PAD.

Author Disclosures: J. Kim: None. D. Lee: None. H. Nam: None. Y. Kim: None. M. Cha: None. J. Heo: Research Grant; Significant; This work was supported by a grant of the Korea Healthcare Technology Research and Development Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A060171, A 085136).

Th P62 Low Ankle-brachial Index Is A Predicting Factor For Initial Severity Of Acute Ischemic Stroke

Dong Hyun Lee, Jinkwon Kim, Young Dae Kim, Hyo Suk Nam, Ji Hoe Heo; Severance Hosp, Seoul, Korea, Republic of Backgroud & objective : Ankle-brachial index (ABI) is a simple and non-invasive method to evaluate atherosclerotic stenosis or occlusion in peripheral arteries of the lower extremities. A Low ABI is predictive of the presence of peripheral arterial occlusive disease (PAOD). Patients with PAOD demonstrate higher cardiovascular mortality during follow-up than those without. However, reasons of the association between poor clinical outcome and PAOD remain unknown. Initial stroke severity is a strong predictor of long-term outcome in stroke patients. We investigated whether a low ABI is associated with initially severe stroke presentation in patients with acute ischemic stroke. Methods : The subjects for this study were consecutive ischemic stroke patients who underwent ABI measurements during admission from January 2007 to May 2010. All subjects had a brain infarction of less than 7 days after symptom onset. All ischemic strokes were subtyped based on the Trial of ORG 10172 in Acute Stroke Treatment classification. ABI values, which were lower than 0.90, were considered abnormal. According to the ABI values, patients were categorized into the normal (Ն9) and the abnormal (Ͻ0.9) groups. Demographic characteristics and initial National Institutes of Health Stroke Scale (NIHSS) scores at admission were compared between the groups. We also compared initial NIHSS scores between the groups within each subtype of stroke. Results : Of the 1346 patients enrolled, ABI was abnormal (Ͻ0.9) in 129 (9.6%) patients.. When comparing with the normal group, the abnormal group was older, had lower body mass index (BMI) and more frequent histories or illnesses of previous ischemic stroke, previous coronary artery disease, diabetes, and atrial fibrillation. Mean initial NIHSS score was higher in the abnormal group (6.99 Ϯ 6.69, PϽ0.001) than the normal ABI group ((4.43 Ϯ 4.95, PϽ0.001). Median NIHSS scores were higher in the abnormal group in the stroke subtypes of large artery atherosclerosis (4 vs 3, pϭ0.038), cardioembolism (5 vs 3, pϭ0.017), and undetermined etiology due to more than two causes identified (4 vs 2, pϭ0.001). In the multivariate analysis using multiple linear regression, low BMI (pϽ0.001), abnormal ABI (pϽ0.001), no diabetes (pϭ0.018), no smoking history (pϭ0.027), large artery atherosclerosis (pϽ0.001) and cardioembolsim (pϽ0.001) were associated with the higher NIHSS scores. Conclusion: A low ABI was an independent factor associated with severe stroke at admission. Although the mechanism of association between ABI and stroke severity is uncertain, previous observations of poor clinical outcome in patients with PAOD may be partly explainable by severe stroke in them.

Th P63 Reversed Robin Hood Syndrome Is Associated with Early Risk of Stroke Recurrence

Georgios Tsivgoulis, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis,, Greece; Paola Palazzo, Neurologia Clinica, Universita `Campus Bio-Medico,, Rome, Italy; Clotilde Balucani, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham Hosp,, Birmingham, AL; Ioannis Heliopoulos, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis,, Greece; Kristian Barlinn, Luis Cava, Limin Zhao, Yi Zhang, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham Hosp,, Birmingham, AL; Dimitrios Athanasiadis, 3rd Surgical Dept, Vascular Unit, Attikon Teaching Hosp, Univ of Athens, Athens, Greece; Konstantinos Vadikolias, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis,, Greece; Anne W Alexandrov, Andrei V Alexandrov; Comprehensive Stroke Cntr, Univ of Alabama at Birmingham Hosp,, Birmingham, AL Background&Purpose: Reversed Robin Hood syndrome (RRHS) was recently identified as one of the mechanisms of early neurological deterioration in acute ischemic stroke (AIS) related to arterial blood flow steal from ischemic to non-affected brain. We hypothesized that this acute, symptomatic hemodynamic compromise could also predispose to stroke recurrence. Subjects&Methods: Consecutive patients with AIS or transient ischemic attack (TIA) affecting the anterior circulation were prospectively evaluated with serial NIHSS assessments and bilateral transcranial Doppler (TCD) monitoring with breath-holding test. RRHS was defined according to previously validated criteria as the documentation of intracranial steal phenomenon during voluntary breath-holding on TCD coupled with neurological deterioration by Ͼ2 NIHSS points. The outcome-event of interest was recurrent stroke during the follow-up period with brain imaging being mandatory to support the clinical diagnosis of recurrent stroke. Results: A total of 364 patients (185 women, mean age 62Ϯ15years) had an ischemic stroke (80%) or TIA (20%) in the anterior circulation, and 32 (9%) had RRHS. During a mean follow-up period of 6 months (range 1-24) a total of 18 (5%) recurrent strokes (17 ischemic; 1 hemorrhagic) were documented. The cumulative recurrence-rate was higher in RRHS patients (25%; 95%CI:6%-43%) compared to the rest (14%; 95%CI:1%-27%; PϽ0.001 by log-ranktest). All recurrent strokes in RRHS patients were ipsalateral cerebral infarcts to the index event anterior circulation vascular territory. The underlying mechanism of recurrent stroke in all RRHS patients was large vessel atherosclerotic infarction. The mean elapsed time between the index and the recurrent stroke tended to be shorter in RRHS patients (1.0Ϯ1.5months) compared to the rest (4.9Ϯ6.5months; pϭ0.075). The 1-month stroke recurrence rate was six-fold higher in RRHS (19%; 95%CI:3%-35%) compared to the rest (3%; 95%CI:1%-5%; PϽ0.0001 by log-rank test). After adjusting for demographic characteristics, vascular risk factors and secondary prevention therapies RRHS was independently associated with a higher stroke recurrence risk (HR: 6.25; 95%CI:1.94-20.14; pϭ0.001). Conclusions: RRHS was associated with a higher risk of early stroke recurrence among patients with the anterior circulation cerebral ischemia independently of demographic characteristics, vascular risk factors and secondary prevention therapies. This recently described vascular steal phenomenon may constitute a novel risk factor for recurrent stroke in AIS patients.

Background and Purpose: Fish consumption has been found to be protective against cardiovascular disease in some studies. However, Japanese, whose diets are rich in fish, have a relatively lower heart disease rate but a higher stroke incidence than other ethnic groups. The purpose of the present study is to use the unique data of the Multiethnic Cohort to study how fish consumption factors contribute to the observed differences in these diseases among African-Americans, Whites, Japanese, Native Hawaiians, and Latinos. Methods: We examined the relationship of fish consumption to the risk of stroke mortality, overall and by subtype, through the end of 2005 in 89,052 men and 109,090 women aged 45-75, residing in Hawaii and Los Angeles and free of stroke at recruitment between 1993 and 1996. Using Cox regression, we calculated relative risks (RRs) overall and by sex and ethnicity for the intake of total dietary u `3 fatty acids (u `3), fish, and preparation methods, adjusting for known risk factors including hypertension at baseline. Results: There were 1,789 stroke deaths during an average of 11.9 years of follow-up. Overall, u `3 was inversely associated with stroke mortality (4 th vs. lowest quintile: RR ϭ 0.74, 95%CI ϭ 0.58-0.94), as was canned tuna fish (3 rd vs. lowest tertile: RRϭ0.84, 95%CIϭ0.77-0.99). Baked, boiled and raw fish had inverse relationships in all groups (3 rd vs. lowest tertile: RR ϭ 0.84, 95%CI ϭ 0.72-0.97), except for Japanese men with an interaction p-value of 0.0014. Salted and dried fish was positively related to hemorrhagic but not ischemic stroke mortality (eaters vs. non-eaters: RRϭ1.41, 95%CIϭ1.06-1.87). Among men, although no effect from total fish was observed, fried fish (eaters vs. non-eaters: RRϭ1.18, 95%CIϭ1.00-1.38) were positively associated with stroke risk. Among women, total fish (4 th vs. lowest quintile: RRϭ0.75, 95%CIϭ0.58-0.98) was inversely associated with stroke death. Conclusion: Dietary u `3 may have a protective effect against stroke mortality. Consumption of fish with high salt content was related to a higher risk of stroke, especially hemorrhagic stroke. Perhaps the high salt use in fish preparation led to Japanese men not exhibiting the protective effect for fish seen in other groups.

This research has received full or partial funding support from the American Heart Association, Pacific/Mountain Affiliate (Alaska, Arizona, Colorado, Hawaii, Idaho, Montana, Oregon, Washington & Wyoming).

Author Disclosures: L. Meng: Research Grant; Significant; AHA Predoctoral Fellowship. L. Wilkens: None. S. Murphy: None. B. Henderson: None. L. Kolonel: None.

Th P66 Smoking Is The Most Difficult Risk Factor To Manage In Stroke; 5 Years Follow Up Study

So-Hyun Kim, Yoonjae Choi, Il-Gon Kim, Chang-Seok Song, Im-Tae Han, Chang-Gi Hong, Jeong-Jin Park, Na-Young Ryoo, Hee-Kwon Park, Joung-Ho Rha; Inha Univ Hosp, Incheon, Korea, Republic of Background: To prevent the stroke recurrence, proper risk factor management is important. We investigated the management status for the stroke risk factors five years after ischemic stroke. Method: We recruited subjects who admitted in Inha University Hospital due to acute ischemic stroke or transient ischemic attack. On admission, baseline data about demographic features and risk factors were registered. Five years later, two trained research nurses investigated the patients' management status of the stroke risk factors and smoking through telephone interview and medical records. Results: We analyzed 651 consecutive patients from September 2003 to February 2005. Among them, the information of 499 (74.8%) patients could be collected by telephone survey or medical record if also available. The mean interval between discharge and follow-up were 4.8 years. Upon investigation, 115 patients (23.0%) were identified to expire during the follow up period. We could contact with 384 (77.0%) patients on the telephone or medical records. The mean age on admission was 61.9Ϯ11.1 and the male was 199 (51.8%). At the time of follow up investigation, 312 patients (81.3%) were taking antithrombotics; 265 (69.0%) antiplatelets, 39 (10.2%) anticoagulants, and 8 (2.1%) combination of both. Among 303 patients with hypertension, 277 (91.4%) were taking antihypertensive agent, 113 of 125 (90.4%) with diabetes were taking oral hypoglycemic agent or insulin, and 155 of 188 (82.4%) with dyslipidemia were taking lipid lowering agent including statin. Contrary to the other risk factor management status, only 57 of 123 smokers (46.3%) on admission stopped smoking after stroke (ex-smokers) and 40 patients (32.6%) were still smoking until recently. Among 40 current-smokers, 12 smokers (9.8%) tried but failed to maintain smoking cessation, and most of them restarted smoking three or four years after stroke (mean interval to resmoke, 3.4 years). Conclusion: Our results suggest that many patients with ischemic stroke did not manage their risk factors actively, particularly for smoking. There is a need for more vigorous effort for secondary prevention and education for patients and their family, and more active smoking cessation program is needed for the stroke patients.

Th P72 Sex Differences in Blood Pressure Control 6 Months after Ischemic Stroke

Nancy K Hills, S. Claiborne Johnston, Stephen Sidney, Jeffrey Klingman, Mai Nguyen-Huynh; UC SAN FRANCISCO, San Francisco, CA Introduction: Overall, women over the age of 65 have been shown to be more likely than men to have uncontrolled hypertension. Whether this gender difference is also present after ischemic stroke, when the indication for blood pressure control is particularly compelling, is unknown. Methods: We utilized data from QUISP, a randomized quality improvement trial focused on secondary stroke prevention that included all patients admitted with ischemic stroke from 2004 through 2006 to 14 hospitals in a Northern California integrated health care plan. For this study, we included only those with hypertension (defined as prior history, discharge diagnosis, or active prescription for antihypertensive medications) who were discharged alive and not to hospice care. Extensive electronic records were supplemented with chart abstraction on a sample of patients to determine living and marital status, socioeconomic status, insurance, pharmacy coverage, and number of antihypertensive medications prescribed at discharge, post-discharge, and blood pressure (BP) control (Ͻ140/90 mmHg) 6ϩ/-2 months after stroke. We examined the relationship between gender and uncontrolled BP, adjusting for factors predictive of BP control and those significantly different by gender. All analyses were conducted using mixed logistic models with hospital as random effect. Results: We included 1346 patients with ischemic stroke who met entry criteria. Women comprised 53.6% of the cohort. Six months after stroke, 54% of women compared to 64% of men had controlled blood pressure (OR 0.66, 95% CI 0.53-0.82, PϽ0.0001), a difference that persisted when adjusted for both age and race (OR 0.69 95% CI 0.55-0.86, pϭ0.001). Women were significantly older than men, twice as likely to live alone, three times as likely to be widowed or divorced, had higher mean systolic BP at discharge, and were less likely to be current alcohol users or have diabetes. However, none of these factors explained the difference in blood pressure control: female sex remained independently associated with being less likely to have controlled blood pressure at 6 months (OR 0.70 95% CI 0.55-0.89, pϭ0.004) even with adjustment for these covariates in a multivariable model. No differences were observed in prescribing patterns of antihypertensives either at discharge (pϭ0.60) or at six months (pϭ0.72) or in adherence with post-stroke visits (pϭ0.57). Conclusion: Hypertension is less well controlled in women compared to men after ischemic stroke. Aggressiveness of drug therapy, adherence with follow-up care, and social factors do not appear to account for this difference. Drug potency or physiological differences are possible explanations but further studies are required.

Author Disclosures: N.K. Hills: None. S. Johnston: None. S. Sidney: None. J. Klingman: None. M. Nguyen-Huynh: None.

Th P73 Use of a Regional Health Information Exchange (HIE) to Facilitate Outcomes Epidemiology

Brett M Kissela, Peter J Embi, Kathleen Alwell, Charles J Moomaw, David Hoskins, Robert Witzke, Jane Khoury, Dawn Kleindorfer; Univ of Cincinnati, Cincinnati, OH Introduction: The Greater Cincinnati/Northern Kentucky Stroke Study is a periodic (1993-94, 1999, 2005, and now 2010), study of stroke incidence and case fatality in a 5-county region of 1.3 million. An outcomes arm, involving interviews of 500 acute ischemic stroke subjects at baseline and 3 months, was added for 1999 and 2005. For 2010, we partnered with HealthBridge, an HIE containing regional healthcare information, to study whether HIE use improves efficiency of participant identification. As an HIE, HealthBridge mobilizes healthcare information electronically across all adult hospital systems in our study region (except the VA hospital), and facilitates health information delivery to all providers involved in a patient's care. Methods: In 2005, finding subjects with possible stroke involved screening hospital admission records' chief complaint terms. Some facilities securely transmitted daily electronic admission log data to us, while other facilities required travel to examine logs on site. Study nurses were then dispatched to review medical records of potential cases, but due to uncertainty about whether stroke had occurred, significant on site medical record review was often required to confirm subject eligibility. For 2010, our University of Cincinnati (UC) Informatics group established a secure interface between UC and HealthBridge to receive real-time Health Level 7-formatted Admission/Discharge/Transfer (ADT) data feeds and populate a dedicated database with likely stroke subjects' data, including admit date, chief complaints, demographics, facility, and room number, for further study team review. We also remotely accessed facilities' electronic medical records via HealthBridge to review imaging and admission notes, to increase likelihood of ischemic stroke before dispatching nurses to consent subjects. Person-hours of effort from both periods were captured, and the data were descriptively analyzed. Results: For 2005, recruitment of 502 subjects required an average of 14 coordinator and 26 study nurse hours daily over 12 months; 42 subjects were excluded as non-strokes after physician review. During the first 5 months of 2010, recruitment of 250 subjects required an average of 10 coordinator and 21 study nurse hours daily; only 1 case was excluded as a non-stroke. Thus, daily effort hours were reduced by 22.5% in 2010, and recruitment over the first 5 months was 16.8% higher than expected based on 2005 estimates. Conclusion: Use of an HIE can enable access to and review of real-time healthcare data across a region in a secure fashion. It allowed for greater efficiency and accuracy of study subject identification and recruitment than traditional approaches in this pilot study. HIE-based approaches have the potential to greatly facilitate population-based epidemiology and outcomes studies, and further study of their potential is needed.

Author Disclosures: B.M. Kissela: Research Grant; Significant; This work supported by NIH-NINDS R-01 NS30678, "Hemorrhagic and Ischemic Strokes Among Blacks and Whites. P.J. Embi: None. K. Alwell: None. C.J. Moomaw: None. D. Hoskins: None. R. Witzke: None. J. Khoury: None. D. Kleindorfer: None.

Th P74 Stroke and the Stars of Hollywood: Analysis of the Burden of Stroke Among Oscar Nominees

Hannah H Smith, Rana Fiaz, Jeffrey L Saver; UCLA, Los Angeles, CA Background: Hollywood stars shape and reflect American society, including the frequency and impact of disease. The 2011 International Stroke Conference, the first to take place in Los Angeles/Hollywood, is an appropriate occasion to investigate the frequency and impact of stroke among leading Hollywood actors. Methods: We compiled a list of all nominees for the Best Actor/Actress Oscars since award inception in 1927 through 2009. Lifetime reports of nonfatal and fatal stroke and myocardial infarction were identified by internet search of public records and of prior medical studies of all-cause mortality among Oscar nominees. Impact of stroke and MI occurrence upon career and productivity was investigated by analysis of film and TV appearance frequencies before and after event, as listed in the Internet Movie Database (IMDb). Results: During 82 years of Oscar competition, 409 actors/actresses have been nominated for Best Actor/Actress Awards and 140 (34.2%) have won at least once. Nonfatal or fatal strokes have been reported in 30 (7.3%), MIs in 39 (9.5%), and stroke or MI in 65 (15.9%). The average age at which nominees with stroke were first nominated was 35.6 and age at first stroke 67.8. Women were more likely to develop stroke than men [18/30 (60%)]. Stroke severity was fatal in 6 (20%), nonfatal in 24 (80%). Career productivity was impaired by vascular events. Annual number in movies/TV in the 3 years post-event, compared with the 3 years pre-event, was reduced by 73% after first stroke and 69% after first MI. Strokes were equally frequent in nominees who won a Best Actor Oscar, vs non-winners, but occurred longer after first nomination among winners (mean 31.1 vs 26. 8 yrs, p Ͻ .002). Exemplar nominees (N) or winners (W) from each decade who experienced stroke include Mary Pickford (W 1929), Bette Davis (N 1934, W 1935), James Cagney (N 1938, W 1942), Cary Grant (N 1942), Kirk Douglas (N 1950), Richard Burton (N 1954), Grace Kelly (W 1954), Elizabeth Taylor (N 1957, W 1960), Patricia Neal (W 1963), Liza Minnelli (N 1970, W 1973), Dudley Moore (N 1982), James Garner (N 1985), andSharon Stone (N 1995). Conclusions: Stroke and cardiovascular disease have exacted an enormous toll upon Hollywood stars, as upon Americans generally, with loss of career productivity and loss of life. These findings may be useful to promote healthier, disease-avoiding lifestyle behaviors among influential film actors and actresses and their worldwide public.

Author Disclosures: H.H. Smith: None. R. Fiaz: None. J.L. Saver: None.

Th P75 Simultaneous Detection Of NR2 Peptide And Antibody Differentiate Ischemic Stroke And Reveal Intracerebral Hemorrhage Accompanied With Ischemic Complications Within 4.5 Hours Of Hyper-acute Stroke

Svetlana A Dambinova; Kennesaw State Univ, Kennesaw, GA Introduction: To speed up ruling in or ruling out of patients assignment for thrombolytics using a blood test combined with CT imaging in the Emergency Department could be extremely beneficial in this critical treatment window. European multicenter trials (Dr.C. Foerch, PI, Goethe University, Frankfurt am Main, Germany)were conducted to evaluate diagnostic accuracy of NR2 peptide and antibody biomarkers for rapid differentiation of cerebral ischemia vs intracerebral hemorrhage. Methods: Plasma specimens collected at 13 clinical sites (NCT00916864) were tested using NR2 peptide and NR2 antibody assays. Of 186 patients recruited between June 2009 and January 2010, 94 had acute and 43 had prior and/or multiple ischemic stroke. To define tissue-based evidence of injury, all patients had CT. Blood samples were drawn within 0.5-4.5 hours of acute hemispheric stroke onset. Results: In this 186-patient cohort, prevalence of intra-cerebral hemorrhage by CT was 25%. In adult patients Ͼ18 years old NR2 peptide measurements Ͼ 0.5 ng/mL indicates acute hemispheric ischemic stroke within 4.5 h of onset.NR2 peptide showed sensitivity of 88% and specificity of 99% within 3.0-4.5 hours of hyper-acute stroke. Detection of NR2 antibody (cut off of 2 .0 ng/mL) determines prior and/or multiple ischemic events with sensitivity of 97% and specificity of 98%.Patients suffered intracerebral hemorrhage accompanied with ischemic complications (10.7%) had elevated both NR2 peptide and antibodies. Conclusion: The NR2 peptide and antibody brain biomarkers provide reliable measurements of stroke across a broad, clinically important range and should prove useful in urgent situations. Simultaneous detection of NR2 peptide and antibodies in patients with hyper-acute hemispheric stroke (i) improves diagnostic certainty of cerebral ischemia, (ii) helps to rule-out intracerebral hemorrhage, and (iii) reveals group of intracerebral hemorrhage accompanied with ischemic complications. The latter group of patients might be assigned for low doses thrombolytic therapy. penumbra core or collaterals. Objective: To test the predictive value of recanalization, collaterals, penumbra and core of ischemia for functional outcome in a large group of patients with MCA occlusion. Method: Consecutive events included prospectively in the Acute Stroke Registry and Analysis of Lausanne from April 2002 to April 2009 with an acute stroke due to proximal MCA occlusion (M1) were considered for analysis. Acute CTA were reviewed to grade the collaterals (dichotomized in poor Ͻϭ50% or good Ͼ50% compared to the normal side) and localization of M1 occlusion (proximal or mid-distal). Acute CTP were reviewed and reconstructed to determine penumbra, core and stroke index (penumbra/penumbraϩcore) of brain ischemia. Good outcome was defined by mRS 0-2 at 3 months. Results: Among 242 events (115 male, mean NIHSS 18.1, SD 5.8, mean age 66, SD 15), 42% were treated with intravenous thrombolysis, and 3% with intraarterial thrombolysis. Collateral status was rated as poor in 53% of events and proximal M1 occlusion was present in 64%. Recanalization determined at 24 hours with CTA was complete in 26% events and partial/absent in 54%.CTP was available for 212 events. Mean penumbra was 88.6 cm 3 (median 84.4, SD 53.8), mean core was 54.1 cm 3 (median 46.2, SD 45.7) and stroke index was 64% (median 68%, SD 25%). Good outcome was observed in 87 events (36%) and was associated in multivariate logistic regression with thrombolysis (pϭ0.02, ORϭ2.5, 95% CI 1.2-5.4), recanalization (pϽ0.001, ORϭ4.1, 95% CI 1.9-8.9), lower NIHSS (pϽ0.001, ORϭ0.84, 95% CI 0.78-0.91), male gender (pϭ0.01, ORϭ2.8, 95% CI 1.3-5.9), mRS prior to stroke (pϭ0.02, ORϭ0.5, 95% CI 0.28-0.9) and good collateral status (pϭ0.005, ORϭ3, 95% CI 1.4-6.4). Nor penumbra, nor core, nor stroke index were significant in the multivariate model, even if an association was present in the univariate model between good functional outcome and penumbra (pϭ0.004, ORϭ1.008, 95% CI 1.003-1.01), core (pϽ0.001, ORϭ0.98, 95% CI 0.976-0.99) and strokeindex (pϽ0.001, ORϭ16.7, 95% CI 4.6 59.9). Conclusion: MCA recanalization is the best predictor for good functional outcome, followed by collateral status. CTP data did not predict the functional outcome in our large group of M1 occlusion.

Author Disclosures: C. Odier: None. P. Michel: Research Grant; Significant; Paion, Lundbeck. Speakers; Modest; Boehringer-Ingelheim. Consultant/Advisory Board; Modest; Boehringer-Ingelheim. Consultant/Advisory Board; Significant; Servier, Lundbeck.

Th P77 Prediction of Recurrent Vascular Events Following Transient Ischemic Attack: DWI, PWI and Serum Biomarkers of Brain Ischemia

Christen D Barras, Aleksandra M Pavlovic, Soren Christensen, Natalia Perez de la Ossa, Brian M Tress, Patricia M Desmond, Ian Gordon, Peter J Hand, Stephen M Davis; Univ of Melbourne, Melbourne, Australia Background: Transient ischemic attack (TIA) patients are at increased stroke risk, but clinical assessment alone is unreliable and new techniques of risk prediction are urgently needed. We hypothesised that Stroke MRI and serum brain ischemia biomarkers could predict recurrent vascular events following TIA and minor stroke, with 12 months of follow-up. Methods: Sixty-four eligible, consecutive TIA/minor stroke patients (NIHSSՅ3) prospectively received DWI, PWI, MRA and FLAIR within 48 hours of symptom onset. A 41 patient subset had acute measurement of four serum brain ischemia biomarkers: BNP, D-dimer, S100␤ and MMP-9. Follow-up included day 90 FLAIR imaging and clinical assessment at 30, 90 days and 12 months. Imaging assessment was independently performed by three experienced readers, including one neuroradiologist. The primary outcome measure was recurrent vascular events at 12 months. Statistical methods included Kaplan-Meier survival and Cox regression analysis. Results: TIA (nϭ47) and minor stroke (nϭ17) patients were recruited. Males comprised 42/64 (65%). Median age was 66.5y ). Acute DWI lesions, 40% multiple, were found in 32/64 (50%) and in 19 (40%) of TIA patients; intracranial vascular lesions in 18/58 with available MRA (31%); PWI lesions in 13/36 (30%). New FLAIR lesions occurred in 12/56 (21%). There were 24 clinical outcome events, but only 3% of patients had a stroke. For every 5mL increase of DWI volume, the hazard ratio (HR) for recurrent event was 1.12 (95%CI 1.04-1.19; Pϭ0.002). DWI positivity and intracranial vascular lesions were associated with an increased risk of recurrent vascular events at 1 year (HR 4.8,; Pϭ0.01), independent of clinical risk (ABCD 2 score). PWI positivity (HR 3.47 (95% CI 1.28-9.4, Pϭ0.012) and D-dimer increment (1000ng/mL) (HR 1.6, 95%CI 1.04-2.45, Pϭ0.03) were also associated with increased risk of recurrent event when considered in isolation. Conclusions: DWI positivity and intracranial vascular lesions predict increased risk of vascular events following TIA/minor stroke, beyond clinical risk scores. These results suggest that MRI findings are integral to prognosis after TIA/minor stroke. In addition, PWI and serum brain ischemia biomarkers have potential application in risk stratification of TIA patients. CT perfusion (CTP) may improve the performance of NCCT. We aim to describe prevalence and predictors of pathological CTP in a large series of consecutive stroke patients and to determine its accuracy in predicting infarction on follow-up imaging. Methods: All consecutive patients arriving within 24 hours in our hospitals and then admitted to the stroke unit and/or intensive care were entered in a prospective registry (Acute STroke Registry and Analysis of Lausanne, ASTRAL). All patients with a good quality CTP (usually 4 or 16 slices) performed within 24 hours from January 2003 to March 2010 were included in the present analysis. Demographic, clinical, radiological and follow-up imaging (CT and/or MRI Ͼ 24h after initial imaging) were analysed. We used univariate logistic regression analysis to test the association of different factors associated with focal hypoperfusion on CTP. Significant predictors (at PϽ20%) were used to fit a multivariable model. Results: Of 1296 patients undergoing acute CTP, 455 (35%) had early ischemic changes on NCCT, and 943 (73%) had a focal hypoperfusion on CTP. Initial NIHSS, aphasia and neglect, cardioembolic stroke mechanism, bilateral carotid territory strokes, other non-lacunar supratentorial territories, increased glucose level, quicker time from symptoms onset to CT, early ischemic changes on NCCT, presence of silent infarcts, and presence of significant arterial pathology were independently associated with a positive CTP. The calculated sensitivity of CTP with regards to an infarction on follow-up imaging was 80.5% and the specificity was 51.3% . Conclusion: Focal hypoperfusion on CTP is frequent in acute ischemic stroke and is predicted by higher NIHSS, earlier imaging, non-lacunar cardiogenic supratentorial infarcts, increased glucose levels, and the presence of arterial pathology in the ischemic territory. Sensitivity for subsequent infarct is high, and specificity moderate. Adding CTP to acute CT-based imaging may improve recognition of stroke and its localization, interpret arterial pathology, and therefore improve stroke management.

Author Disclosures: N.M. Ina ´cio: None. R. Meuli: None. P. Maeder: None. M. Faouzi: None. M. Wintermark: None. P. Michel: None.

Th P79 Persistence of Hyperdense Middle Cerebral Artery Sign on Follow-up CT Scan is Associated with Poor Outcome in Ischemic Stroke Patients Treated with Intravenous Thrombolysis

Prakash R Paliwal, Aftab Ahmad, Shen Liang, Leonard L Yeo, Pei K Loh, Kay W Ng, Lily Y Wong, Su Jie, Mahendran Maliapen, Benjamin K Ong, N Venketasubramanian, Hock L Teoh, Vincent F Chong, Eric Tan, Arvind K Sinha, Bernard P Chan, Vijay K Sharma; National Univ Hosp, Singapore, Singapore Background-Significant numbers of acute ischemic stroke (AIS) patients recover with optimal care and timely-administered intravenous thrombolysis with tissue plasminogen activator (IV-TPA). However, the rates and extent of recovery remain highly variable. Considering the scarce and costly resources, early identification of reliable predictors for functional outcomes is important for planning interventions and rehabilitation strategies. Hyperdense middle cerebral artery sign (HMCAS) on pre-treatment unenhanced CT scan represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome. However, it is reliable only in AIS patients managed conservatively. In thrombolyzed patients, it may disappear (representing clot dissolution) or persist (persisting clot) on the follow up CT scan. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up scan can predict the final outcome. Methods-Data from consecutive AIS patients treated with IV-TPA, in a standardized protocol, from Jan2007 to March2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation strokes were excluded. HMCAS was assessed by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by modified Rankin Scale (mRS) at 3-months were dichotomized as good (mRS 0-1) and poor (mRS 2-6). The data were analyzed for the early predictors of function outcome with SPSS version 16 for Windows. Results: Of the total of 1918 AIS patients admitted to our center, 189 (9.9%) eligible cases were treated with IV-TPA during the study period. Baseline data included mean age 64Ϯ13 years; 102 (59%) males; mean onset-to-treatment time 157Ϯ38 minutes and median NIHSS 16 points. Hypertension was the commonest vascular risk factor in 144 (76%) while 63 (33%) patients suffered from atrial fibrillation (AF). HMCAS was observed on the pre-treatment scan in 95 (50%) patients and persisted in 47 (50%) of them. Overall, 96 (51%) patients achieved good functional outcome (mRS 0-1 at 3 months). On the univariable anlaysis, age, atrial fibrillation, pre-TPA NIHSS score and HMCAS on the follow-up CT scan were associated with poor functional outcome. However, only pre-TPA NIHSS score (OR1.09;95%CI 1.04-1.16,pϭ0.001) and HMCAS on the follow-up CT scan (OR 22.93;95%CI 8.81-54.52,p Conclusion: Persistence of hyperdense middle cerebral artery sign on the follow up CT scan in acute ischemic stroke patients treated with IV-TPA can be used as an early predictor of poor functional outcome.

Th P81 Prognostic Value of Whole Brain Volume Perfusion CT in Acute Stroke <6h after Symptom Onset

Peter Schramm, Sarah Fischer, Ramona Schramm, Marios N Psychogios, Univ Medicine Goettingen, Goettingen, Germany; Ernst Klotz, Siemens Healthcare Sector, Forchheim, Germany; Klaus Jung, Univ Medicine Goettingen, Goettingen, Germany; Gunter Erb, Bracco Imaging Deutschland GmbH, Konstanz, Germany; Michael Knauth; Univ Medicine Goettingen, Goettingen, Germany Purpose: In acute ischemic stroke rapid diagnosis and efficient treatment is indispensable for the patient's outcome. Aim of this study was to evaluate the prognostic value of infarct lesion volumes according to whole brain volume perfusion CT in acute stroke within the first six hours after symtom onset. Method and Materials: Patients were included in this prospective study, if they had been admitted to our department within the first 6 hours after symptom onset of acute stroke. A total of 28 patients first received a non-contrast CT of the brain to exclude intracerebral hemorrhage. After that, whole brain volume perfusion CT was performed. Lesion volumes were determined manually on colour coded 3D parameter maps of cerebral blood flow (CBF) and cerebral blood volume (CBV). Volumes of reduced CBF (Ͻ20 ml/100ml/min) were determined automatically. Final infarct volume was identified on follow up non enhanced CT 72 h later. Absolute lesion volumes were analyzed using multiple regressions and Mann-Whitney-U-tests. Results: Mean value of manually determined CBF lesions was 70.4 cc, mean value of manually determined CBV lesions was 55.4 cc. Automatical delineation of lesions with CBF Ͻ 20 ml/100 ml/min resulted in a mean volume of 63.2 cc. Mean final infarct volume was 66.4 cc. For manually defined lesion volumes, positive correlation was found both for CBF (correlation coefficient R2ϭ0.72) and for CBV (R2ϭ0.75). Automatically determined lesion volumes of reduced CBF (Ͻ 20 ml/100 ml/min) also showed high correlation with final infarct volumes (R2ϭ 0,74). Age, sex and stroke severity (NIHSS) had no significant influence on correlation quality. Conclusion: In acute stroke whole brain perfusion CT has a high prognostic value regarding final infarct volumes. Both manually and automatically delineated lesion volumes determined from volume perfusion CT showed high correlations with final infarct volumes, the highest predictive value was found for manually defined CBF lesions according to colour coded 3D maps (yϭ1.0335x).

/no were compared to the qualitative reads. The agreement between the TBS and qualitative decisions were determined along with the positive predictive values of the TBS decisions. Results: Ninety patients (68Ϯ15 years, 43 females) met the inclusion criteria. Patients had a median NIHSS of 9 (IQR 5-18) and median onset to MRI time of 129 minutes (IQR 89-175). ADC threshold decisions were in agreement with the qualitative read of ischemia in 74% (64/86) of the scans with a positive predictive value of 97%. Tmax threshold decisions were in agreement with the qualitative read of perfusion deficit in 88% (73/83) of the scans with a positive predictive value of 96%. Conclusion: TBS, using an ADC value of 615 mm 2 /seconds and Tmax value of Ͼ 6 seconds, is strongly correlated with qualitative reads of acute stroke MRI scans and demonstrates potential for use in acute intervention decision making. Future studies of this large MRI dataset are planned to further explore TBS decisions.

Author Disclosures: M. Luby: None. S. Boparai: None. J.K. Lynch: None. J.G. Merino: None. L.L. Latour: None. S.S. Song: None. A.W. Hsia: None. S. Warach: None.

Th P85 E-learn CT Angiography: a Virtual Training Ground Prepares for Stroke Imaging

Inger Havsteen, Anders F Christensen, Jens K Nielsen, Derk Krieger, Louisa Christensen, Hanne Christensen; Copenhagen Univ Hosp Bispebjerg, Copenhagen, Denmark Introduction: Imaging methods including CT-angiography (CTA) are increasingly available and may support decision-making in acute stroke treatment. We developed a three-step e-learning concept after the principle test-teach-test and tested it in two stroke related subjects, vascular occlusion and spot sign, on two groups of volunteers. We assessed the hypothesis that an e-learning program trains learners with varying experience in basic CTA interpretation skills in a stroke setting. Methods: We developed an HTML-based program with a teaching segment and two matching test segments within the two subjects. Tests were taken before and after the teaching segment and tests were 40% of the size of the teaching segment, 15 vs. 40 cases in the vascular occlusion series and 6 vs. 10 cases in the spot sign series. The vascular occlusion series required correct answers for type of pathology (4 choices) and location (5 choices). Spot sign was answered with presence or absence. Learners were also asked how confident they felt about their diagnosis. The number of correct answers and the ratings of self-perceived diagnostic confidence were analyzed to quantify the learning potential of each series. Results: Four neurological consultants and four radiological residents completed the program. The vascular occlusion teaching segment increased diagnostic correctness from 42% to 68%, pϭ 0.005. The neurological consultants showed significant progress with average scores 50% vs. 75%, pϭ 0.027, and the radiological residents with average scores 33% vs. 60% showed near-significant progress, pϭ 0.081. Spot sign was detected correctly by 69% before the teaching segment and by 92% afterwards, pϭ0.009. In the spot sign series the group reported a median self perceived diagnostic certainty in 50% of cases vs. 75% after the teaching segment, pϭ 0.030. Self perceived diagnostic certainty showed no significant increase in vascular occlusion. Conclusions: We show improved diagnostic accuracy and confidence through a teaching segment for both inexperienced and trained personnel in two targeted topics of varying difficulty. Teaching vascular occlusion yielded best results with some prior knowledge, whereas the spot sign recognition required none to achieve diagnostic accuracy above 90% and self perceived diagnostic certainty in 75% of cases through a teaching segment. We conclude that the e-learning tool is a useful educational approach for users of varying experience, e.g. for investigators in clinical trials and for clinicians, and that the teaching course is useful for certification.

Background and Purpose: Infarct growth is used as a surrogate for clinical outcome in early phase stroke trials. Assessment of infarct growth earlier than the traditional 90 days may be equally accurate and yield practical advantages. We aimed to correlate 24 hour and day 90 infarct volumes. Methods: Patients presenting to two institutions with acute ischemic stroke within 6 hours of onset were imaged with a protocol that included MRI at 24hours and 90 days. Infarct volume was assessed on diffusion-weighted-imaging (DWI) at baseline and 24 hours after stroke onset and on FLAIR images at day 90. The DWI and FLAIR lesions were manually outlined to their maximal visual extent by two independent stroke neurologists and the volumes averaged. Inter-rater consistency was assessed using the median difference in lesion volume between raters and Bland-Altman plot. The relationship between 24hr and day 90 infarct volumes was assessed using linear regression, Pearson's correlation and Lin's concordance co-efficient (n ˜) as well as a Bland-Altman plot. Results: Imaging data were available for 83 patients, mean age 69 years (SD 10), median baseline NIHSS 14 (IQR 10), 77 (93%) treated with tPA. The median time from onset to "24hr" MRI was 25.9hr (IQR 4) and median time to follow-up was 91 days (IQR 8). The DWI infarct volume at 24 hours had strong linear correlation with day 90 FLAIR infarct volume (rϭ0.98, 95%CI 0.97-0.99, Lin's n ˜ϭ0.93). The 95% limits of agreement of the Bland-Altman plot were -9.1 to 30.5mL. The baseline DWI to day 90 correlation (assessable in 40 patients) was significantly lower (rϭ0.92, 95%CI 0.85-0.96). Infarct growth occurred between baseline and 24hours (mean 15mL absolute, 224% relative). Significant infarct shrinkage occurred from 24 hours to day 90 (mean volume 11mL, st dev 8.3mL, paired Wilcoxon PϽ0.001) and this was reflected in the regression equation: FLAIR lesion volume (mL) ϭ 0.85xDWI lesion volume (mL) -5.1 mL with R 2 ϭ0.96. The median ROI volume discrepancy between raters was smaller for DWI than for FLAIR (1.4mL (8%) vs 1.8mL (17%), pϭ0.002) and the Bland-Altman limits of agreement were narrower for DWI (-5.6 to 4.1mL) compared with FLAIR (-10.2 to 6.4mL). Visual review did not identify any patients with expansion of infarction between 24hrs and day 90. Conclusions: Infarct growth occurs early such that DWI lesion volume at 24 hours accurately reflects the final infarct volume at day 90. DWI is more reproducible than FLAIR. The use of an earlier assessment has the potential to reduce loss to follow-up and the resultant bias in trials.

Th P89 Utility of the NIHSS Exam and Cortical Score to Predict New Cortical Stroke on MRI

Sean I Savitz, Univ of Texas -Houston, Houston, TX; Karen C Albright, Univ of Alabama -Birmingham, Birmingham, AL; Sheryl Martin-Schild; Tulane Univ Sch of Medicine, New Orleans, LA Background: The NIHSS exam is routinely used to identify stroke and determine stroke severity. Studies targeting cortical strokes often require advanced neuroimaging, which can delay intervention and limit potential study sites. Our prior exploratory study demonstrated that the cortical score (total points given on NIHSS for findings of gaze palsy, visual field deficit, aphasia, and neglect) of Ն2 points yielded a positive predictive value (PPV) for a cortical stroke of 88%. We sought to validate this finding in a second population of patients with acute ischemic stroke (AIS) qualifying for intravenous thrombolysis (IV tPA). Methods: All patients admitted to our center from 7/2008 -12/2009 with a final diagnosis of AIS who were treated with IV tPA within the first 3 hours of stroke onset were identified from our stroke registry. Patients were excluded if they did not have admission NIHSS exam or received intra-arterial therapy. MRI diffusion weighted images (DWI) were reviewed to determine the presence of acute infarction. Patients with DWI lesions were divided into two groups depending on the presence or absence of cortical involvement. Various combinations of NIHSS exam components and the cortical score were evaluated for sensitivity, specificity, and PPV for identifying the presence of an acute cortical stroke. Results: 60 patients meeting inclusion criteria had DWI evidence of new infarction. 55 patients (91.7%) had cortical findings on NIHSS and 46 patients (76.7%) had cortical involvement on DWI. The median NIHSS was 12 (1-29). 93% of patients with a cortical stroke had at least one cortical sign or NIHSS Ն4 points. The PPV of a cortical stroke was 78% for a cortical score of Ն2 and 83% for a cortical score of Ն3. Forced gaze, global aphasia, and complete neglect each yielded a PPV Ͼ88%. When excluding patients with a prior history of stroke (nϭ15), the PPV for a cortical score Ն2 did not improve. Discussion: Not all patients who demonstrate cortical findings on the NIHSS exam will complete a cortical infarct. The PPV herein likely underestimates the true value in patients treated with thrombolysis, since the cortex might be saved by recanalization and reperfusion in some patients. Severe deficits in the individual NIHSS exam cortical elements can predict cortical stroke with higher reliability than the cortical score, but the cortical score can be generalized to the entire population of AIS patients. A larger study of patients with AIS should be performed to determine if the cortical score can serve as a surrogate marker for a cortical stroke.

Author Disclosures: S.I. Savitz: None. K.C. Albright: None. S. Martin-Schild: None.

Th P90 Whole Brain CT Perfusion Using Time-to-Peak Maps in Evaluation of Minor Stroke

Muhammad Ejaz Ahmed, Santanu Chakraborty, Dariush Dowlatshahi, Grant Stotts; Univ of Ottawa, Ottawa, Canada Background: The use of thrombolysis in minor stroke is controversial. Treatment decisions may be influenced by identifying patients with large areas of tissue at risk and distinguishing patients with stroke mimics. Whole brain CT perfusion allows for possible assessment of these parameters and is not limited to discrete areas of brain coverage as in previous generations of CT scanners. Whole brain CT perfusion maps can be rapidly generated on the Toshiba 320 Aquilon ® CT without additional contrast or scanning time over standard CT angiogram acquisition, making it an ideal tool in acute stroke settings. Time-to-peak (TTP) maps have been identified as a sensitive parameter for assessment of ischemia. We analyzed the ability of TTP maps to predict eventual infarcts in patients with mild stroke presentations. Methods: We retrospectively reviewed the clinical and imaging data of 134 consecutive patients presenting with acute stroke in less than 6 hours from onset of symptoms irrespective of the use of IV thrombolysis. Patients presenting with a NIH Stroke Scale score Ͻ5 were subjected to subgroup analysis. Whole brain perfusion scans were acquired on the 320 detector CT scanner. TTP perfusion deficit with delays of more than 3 seconds were considered significant for underlying ischemia. The sensitivity, specificity, positive and the negative predictive values were estimated for perfusion parameters in predicting the presence of ischemia based on follow-up imaging and NIHSS at 24 to 48 hours. Results: 134 consecutive patients were included in the study. 41 patients were excluded due to inadequate studies (nϭ14) and no follow up scans (nϭ27). 38 of remaining 93 patients had minor neurological deficits (NIH Ͻ 5) at presentation. 31 of the 38 patients were followed up with MRI and the remaining patients had an unenhanced CT. Seven patients received iv-tPA. The TTP map had the highest level of sensitivity in detecting small infarcts (91%), followed by CBV and CBF (51%, 51%), and MTT had a lower sensitivity compare to others (49%). Importantly, TTP analysis provided a very high negative predictive value (93%). However, there was a relatively lower specificity (63%) and a tendency to overestimate the size of infarct. Conclusion: TTP perfusion is highly sensitive in predicting small regions of ischemic infarct in patients with minor stroke. Just as importantly, the high negative predictive value may be helpful in differentiating between stroke and stroke mimics.

Author Disclosures: M. Ahmed: None. S. Chakraborty: None. D. Dowlatshahi: None. G. Stotts: None.

Th P91 Can We Rely On Negative Diffusion Weighted Imaging?

Benjamin A Hotter, Anna Kufner, Uwe Malzahn, Gerhard J Jungehuelsing, Jochen B Fiebach; Charite ´Univ Hosp Berlin, Berlin, Germany Background -Sudden focal neurological deficits call for urgent clinical and radiological evaluation. If acute radiological screening is negative, doubt about the finding's reliability often leads to diagnostic uncertainty. This holds true for CT but also diffusion weighted MRI (DWI), especially when it comes to infratentorial infarction. We hypothesized that patients without neurologic symptoms would not show infarction in a follow up examination. We thought the NIH stroke scale (NIHSS) would be a valid tool to screen and triage those patients. Methods -Adult patients with suspected cerebral ischemia underwent stroke MRI (T2*, high resolution DWI, MRA, FLAIR, perfusion imaging) and NIHSS examinations acutely and on the following day. Patients with negative acute DWI were eligible for this analysis. We calculated odds ratios to assess strength of association between DWI shown ischemia on follow up scans and dichotomized NIHSS (0 vs. Ͼϭ1), as well as possible confounders. Multivariate analysis was not performed due to sample size. To assure usability as a screening tool we calculated the negative predictive value (NPV) for a dichotomized NIHSS. Results & Discussion: Regardless of the final diagnose, 151 patients had negative acute DWI, 63 subjects received a follow up MRI. DWI was positive in 11.1 % of patients on the second day. Median admission NIHSS score was 0. We found a strong association between dichotomized NIHSS and DWI on the second day (OR 17.50 95% CI 2.83-108.12). NPV of dichotomized NIHSS score on the second day for infarction as shown by DWI was 0.96. A borderline association could also be shown for atrial fibrillation and delay between onset of symptoms and imaging (p-value 0.1 for Mann-Whitney-U-test). This study was underpowered to safely exclude those variables as confounders. However, even after Bonferroni adjustment for multiple testing the association of NIHSS score on the second day and the follow up DWI remained significant. Conclusion: Based on our data set, we found the NIHSS to be a good screening tool to determine whether or not a second MRI is necessary to establish cerebral infarction via DWI.

Th P92 Hyperintense ICA Sign: A Marker For Worse Stroke Outcome

Peter Adamczyk, Jeffrey L Saver, Qing Hao, UCLA Med Cntr, Los Angeles, CA; Nerses Sanossian, Univ of Southern California, Los Angeles, CA; Noriko Salamon, Rana Fiaz, Latisha K Ali, Doojin Kim, Bruce Ovbiagele, Sidney Starkman, Paul Vespa, Sarah Song, Radoslav Raychev, Hermelinda G Abcede, Nestor Gonzalez, Satoshi Tateshima, Reza Jahan, Gary R Duckwiler, Fernando Vinuela, David S Liebeskind, UCLA Med Cntr, Los Angeles, CA; UCLA Stroke Investigators Background: Fluid-attenuated inversion recovery vascular hyperintensities (FVH) on MRI may be seen proximal and distal to occlusions in acute stroke. These findings, suggestive of slow flow, may carry different prognostic information in proximal versus distal vessel segments. We evaluated the presence of proximal FVH in the internal carotid artery (ICA) and hypothesize that this finding may be associated with worse angiographic and clinical outcomes in patients undergoing intervention for acute ischemic stroke. Methods: We analyzed consecutive patients between January 1, 2007 and July 31, 2010 who presented with acute strokes from ICA or middle cerebral artery (MCA) occlusions and underwent angiography for any potential endovascular intervention. Patients who received intravenous tPA (IV-tPa) prior to angiography were included. The presence of proximal FVH in the intracranial ICA and the number of segments (petrous, cavernous, clinoid, terminal) based on consensus MRI review by two investigators. These findings were compared to angiographic recanalization scores (AOL and TICI) and functional status at discharge [modified Rankin Scale (mRS)]. Results: Among 89 patients, median age was 66 (range 22-95), 63% were female, and occlusion locations were ICA in 32 (36%) and MCA in 57 (64%). Interventions included mechanical thrombectomy in 65 patients, acute angioplasty with stenting in 14, partial aortic occlusion treatment in 8, IA lytics in 7 and IV-tPA in 17. Proximal FVH was noted in 29 (32.6%) cases of which the median number of ICA segments with hyperintense signal was 3 (IQR 2 -4). Frequency of segment involvement was: petrous -96.6%, cavernous -86.2%, clinoid -79.3%, terminal -34.5%. The presence of proximal FVH was associated with worse discharge functional outcome (mRS median 5 vs 4, PϽ0.001). Greater number of ICA segments involved similarly correlated with higher discharge mRS scores (r ϭ 0.22, pϽ 0.05). Among patients who underwent endovascular recanalization, a significant association between proximal FVH was not found with AOL and TICI scores. Proximal FVH did not affect recanalizaton success, with TICI 2b or higher achieved in 50% with FVH vs 51.1% without, pϭ 0.54. As expected, mRS scores were inversely associated with recanalization AOL scores (r ϭ -0.30, pϭ0.01) and TICI scores (r ϭ -0.32, PϽ0.05) in this study. Conclusions: The hyperintense ICA sign, a marker of delayed flow below an occlusion, is present in one-third of patients and is a potential prognostic sign for worse functional outcome in patients with MCA and ICA occlusions.

Th P93 Optical Measurements of Cerebral Hemodynamics in Acute Cortical Stroke

Christopher G Favilla, Rickson Mesquita, Meeri Kim, Joel H Greenberg, John A Detre, Arjun G Yodh, Michael T Mullen, Neelofer Shafi, Scott E Kasner; Univ of Pennsylvania, Philadelphia, PA Background and Purpose: A major goal in the care of acute ischemic stroke (AIS) is optimization of cerebral blood flow (CBF) in order to salvage as much of the ischemic penumbra as possible. CBF becomes dependent on cerebral perfusion pressure due to impaired autoregulation, but clinically there is no realtime bedside method for monitoring CBF available. Current guidelines recommend a flat head-of-bed (HOB) position to maximize CBF following AIS, based on blood velocity data measured by transcranial Doppler (TCD) ultrasonography. Diffuse correlation spectroscopy (DCS) is a novel technology for non-invasive transcranial measurement of CBF. We sought to determine if DCS is sensitive to changes in CBF with manipulation of HOB angle, and if CBF changes are comparable to those in blood velocity measured by TCD. Methods: We explored the utility of DCS to measure the effect of HOB positioning at 30°, 15°, 0°, and -5°in patients with AIS. We enrolled patients with unilateral acute middle cerebral artery cortical infarction within 72 hours of onset. Measurements were made simultaneously with TCD and DCS bilaterally, and each contralesional hemisphere served as a control. Results: 13 subjects were prospectively enrolled. HOB positioning at 15°resulted in a 9% decrease (95% CI: 5-13%; pϭ0.0007) in CBF ipsilesionally and 30°resulted in 15% decrease (95% CI: 6-24%; pϭ0.003) in CBF ipsilesionally, relative to a flat HOB. Similarly, a 30°HOB angle resulted in an a 6% decrease (95% CI: 2-11%; pϭ0.011) in blood velocity relative to a flat HOB in the ipsilesional hemisphere. Similar directions of relative flow and velocity changes were observed in the contralesional hemisphere, but differences were smaller and non-significant. Linear regression demonstrated that HOB angle is strongly correlated with CBF ipsilesionally (Adj R 2 :0.40; coef:-0.52 per degree; PϽ0.001) and contralesionally (Adj R 2 :0.22; coef:-0.33 per degree; PϽ.001). HOB angle was also correlated with blood velocity both ipsilesionally (Adj R 2 :0.40; coef:-0.23; PϽ0.001) and contralesionally (Adj R 2 :0.36; coef:Ͻ-0.16; PϽ0.001). Additionally, CBF and velocity were found to correlate both ipsilesionally (Rho:0.46; pϭ0.0008) and contralesionally (Rho:0.34; pϭ0.046). Conclusions: Both DCS and TCD demonstrate impairment of cerebrovascular autoregulatory mechanisms in the region of the infarct. Further, a flat or -5°HOB angle maximizes perfusion of the infarcted region for the majority of patients. Blood velocity and CBF strongly correlate across a range of HOB angles, but CBF changes exceed velocity changes, suggesting DCS measurements of CBF may be more sensitive. Real time noninvasive monitoring of CBF may allow for individual optimization of HOB position and other hemodynamic parameters during the acute management of stroke.

Th P94 Anterior Choroidal Artery Diffusion-Weighted Imaging Patterns at Onset Predict Disability from Carotid Occlusion

Meng Lee, Chang Gung Memorial Hosp, Chiayi, Taiwan; Jeffrey L Saver, Qing Hao, Sidney Starkman, UCLA Stroke Cntr, Los Angeles, CA; Noriko Salamon, UCLA Med Sch, Los Angeles, CA; Latisha K Ali, Doojin Kim, Bruce Ovbiagele, Sarah Song, Radoslav Raychev, Radoslav Raychev, Linda Abcede, Rana Fiaz, David S Liebeskind, UCLA Stroke Cntr, Los Angeles, CA; UCLA Stroke Investigators Background: The prognosis of acute internal carotid artery (ICA) occlusion may be difficult to predict. Although extensive baseline diffusion-weighted imaging (DWI) lesions are known to sway outcome, the predictive role of specific DWI patterns in critical regions such as the anterior choroidal artery (AChA) remains unknown. Early AChA infarction may reflect extensive ICA thrombus extending to the AChA origin and/or poor collateral status. We hypothesized that spared or minimal AChA infarction following ICA occlusion predicts fair outcome, defined as modified Rankin Scale (mRS) 0 to 3, at discharge. Methods: We studied consecutive acute ICA occlusion patients evaluated between January 2002 through August 2010, who underwent MRI followed by catheter angiography. Pattern of AChA involvment on initial DWI was categorized as spared, partial, and full. Partial involvement of AChA was further categorized into 6 subgroups: mesial temporal (MT), posterior limb of internal capsule (PIC), posterior part of peri-ventricle (PPV), MTϩPIC, MTϩPPV, and PICϩPPV. Two neurologists independently labeled the AChA infarct pattern. The association of AChA infarct pattern and fair outcome at discharge was calculated by logistic regression with adjustment of age, admit NIHSS scores, time between last known well and MRI, and recanalization status. Results: Among the 60 patients meeting study entry criteria, mean age was 68.3 years, mean pretreatment NIHSS was 17.7 and mean time from last known well to MRI was 361 minutes. AchA territory was spared in 19 patients, partially involved in 26, and fully involved in 15. Among patients with spared AchA infarct, 52.6% had fair discharge outcome while 34.6% of AChA partially involved patients and 13.3% of AChA fully involved patients had fair discharge outcome. The infarct pattern of AChA was independently associated with fair discharge outcome after adjustment (Pϭ0.028). Among patients with partial AChA infarct, infarct restricted to MT had 50% fair outcome while infarct beyond MT had 33.3% fair outcome. When we categorized AChA infarct pattern as spared and MT only vs. other partial infarct pattern and full infarct, the former was independently associated with fair discharge outcome after adjustment (51.9% vs. 21.2%, Pϭ0.017).

Conclusion:

In acute ICA occlusion, spared or AChA infarction restricted to the mesial temporal field on baseline DWI independently predicts fair discharge outcome. Analysis of AChA infarct patterns on DWI may improve early prognostication and decision-making. cerebral blood flow (rCBF), and normal or increased cerebral blood volume (rCBV). The value of CT-P abnormalities in identifying patients with transient ischemic attack (TIA) at risk for subsequent ischemic stroke is not known. Objective: To determine the role of CT-P imaging in the diagnostic imaging of patients with TIA within 24 hours of symptom onset. Methods: A review of 400 consecutive patients with a pre-admission diagnosis of TIA (ICD-9 435.9) admitted to two University affiliated stroke medical centers was performed. The patterns of MTT, rCBF and rCBV on the initial CT-P were categorized as either preserved (no change), increased or decreased. We evaluated the relationship between CT-P abnormalities and infarction on subsequent magnetic resonance imaging (MRI) and new stroke within 48 hours of TIA. Results: A total of 83 patients (mean ageϮstandard deviation, 66Ϯ15 years, 40(48%) were men) of 400 patients with TIAs underwent CT-P study within 24 hours of symptom onset. The following patterns of the CT-P were observed: The risk of new stroke within 48 hours of TIA was not different among patients with preserved CT-P parameters (0 of 73) compared with those with abnormalities in one or more of the parameters (0 of 10). Among the 73 patients with preserved CT-P parameters, 63(86%) had a subsequent cranial MRI and 11(15%) were found to have infarctions. A total of 10(12%) patients had changes on the CT-P with 5 of the patients having subsequent cranial MRI that did not show any infarction. Conclusion: Abnormalities on CT-P are infrequent among patients with TIAs and were not associated with either MRI demonstrated infarction or new stroke within 48 hours of TIA.

Th P103 Optimizing Arterial Input Functions In Acute Stroke MRI -A Comparison With O15-Water-PET

Olivier Zaro-Weber, Wolf-Dieter Heiss, Max-Planck-Institute for Neurological Rsch, Cologne, Germany; Jan Sobesky; Cntr for Stroke Rsch and Dept of Neurology, Charite

´, Universita ¨tsmedizin Berlin, Berlin, Germany Background: The arterial input function (AIF) is a precondition for MR perfusion imaging. However so far there is no validation of the optimal localisation of the AIF in acute stroke. We assessed the different AIF's from the M1, M2 and M3 branches of the Middle Cerebral Artery (MCA) to detect the penumbral flow threshold defined by 15O-water positron emission tomography (CBF-PET) (Ͻ20 ml/100g/min). Methods: In acute and subacute stroke patients, the CBF-PWI maps generated with AIF's from the different MCA branches (M1, M2, M3) contralateral to the ischemic hemisphere were compared on a voxel based approach with CBF-PET. In a receiver operating comparison (ROC-analysis), the influence of the AIF on PW derived maps was assessed using quantitative CBF-PET maps as the gold standard with respect to penumbral flow Ͻ20ml/100g/min. The performance of the AIF to define the penumbral flow was calculated for each MCA branch. Results: In an analysis of 8 stroke patients (median time MRI to PET: 66 minutes; patients imaged within 22 hours after stroke) the best MCA branch for the definition of the AIF with the highest area under the curve (AUC) to identify penumbral flow (Ͻ20ml/100g/min on CBF-PET) was the M3 segment. Median AUC was 0.94 (IQR 0.87-0.96), 0.91 (IQR 0.84-0.95), 0.86 (IQR 0.79-0.90) in M3, M2 and M1 respectively. Discussion: Quality in terms of AUC was enhanced in more distal MCA branches. In conclusion, our data support that AIF's for the generation of PW-CBF maps in acute stroke should be defined via selection of distal branches of the MCA.

Author Disclosures: O. Zaro-Weber: None. W. Heiss: None. J. Sobesky: None.

Th P104 Delayed Perfusion Predicts The Volume Of The Perfusion Lesion

Andrew Bivard, Christopher Levi, Neil Spratt, Mark W Parsons; Univ of Newcastle, Newcastle, Australia Intro: There is current speculation over the most accurate method of identifying the ischemic penumbra using imaging. The Perfusion techniques used show a great deal of variability in their definition of the perfusion lesion, both for MRI and CTP. This project aims to add to the body of knowledge attempting to predict the volume of tissue destined for infarction should reperfusion not occur in an ischemic stroke. Methods: Acute CTP was coregistrerd and compared to subacute MRI-DWI images in 76 hemispheric ischemic stroke patients without rperfusion. A pixel-based Receiver Operator Characteristic cure analysis was used to determine which CTP threshold would best predict the follow-up MRI-DWI lesion on the CTP map. Results: A Tmax (time to peak of the residual function) of ϩ 2 seconds showed the greatest level of accuracy (AUC 0.82, Sensitivity 0.89, Specificity 0.78, Positive Predictive Value 0.79) in predicting the extent of tissue death in a setting of no reperfusion. Discussion: Tmax thresholds, particularly a threshold of ϩ2 seconds compared to contralateral hemisphere baseline Tmax is the best predictor of the perfusion lesion. , 2010). Transient application of hyperoxia during T2*-weighted MRI precipitates signal increases in healthy tissue, exaggerated signal increases in likely 'penumbral' tissue, and attenuated signal increases in infarct core, thus reflecting underlying deoxyhaemoglobin concentration. In this voxel based study we further examined the influences on T2*-weighted signal changes. Methods Data from subjects for whom there was a measurable lesion detectable by imaging and who had PWI and Oxygen Challenge data acquired were analysed (nϭ12; median NIHSS ϭ 12; median time to imaging ϭ 20h). Two slices which showed the largest lesions were selected from each subject giving 53 955 voxels incorporating unaffected tissue (nϭ12 subjects), hypoperfused DWI lesion (nϭ9), reperfused DWI lesion (nϭ3), and PWI-DWI mismatch tissue (nϭ6). For each voxel, cerebral blood volume (CBV), perfusion state (TMAX) and apparent diffusion coefficient (ADC) were recorded and if necessary transformed to achieve Gaussian distribution. Data were entered into a multivariate linear regression model to predict the percentage signal change (PSC) after Oxygen Challenge. Results Univariate analyses showed that all 3 predictors were significantly correlated with PSC ('natural log' CBV, Rhoϭ0.3, PϽ0.0001; reciprocal TMAX, Rho ϭ 0.15, PϽ0.0001; ADC, Rhoϭ0.19, PϽ0.0001). When all 3 predictors were entered into a multiple linear regression model only transformed CBV (rϭ0.2, PϽ0.0001) and ADC (rϭ0.1, PϽ0.0001) were independently predictive of PSC (R 2 ϭ7.2%). A multiple linear regression analysis using only voxels from within the DWI lesion (nϭ8280) demonstrated that all 3 predictors were statistically significant (transformed CBV, rϭ0.19, PϽ0.0001; reciprocal TMAX, r ϭ 0.02, pϭ0.047; ADC, rϭ0.12, PϽ0.0001). Conclusions: In addition to CBV, parameters which are likely to be related to tissue metabolic state, such as diffusional state (ADC), and possibly the depth of hypoperfusion (TMAX), are independent predictors of the Oxygen Challenge response. Oxygen extraction fraction is likely to account for much of the unexplained variance. PSC after Oxygen Challenge is dependent on deoxyhaemoglobin concentration and thus provides an integrated measure of the haemodynamic and metabolic state of the tissue and may potentially image the penumbra.

Th P106 DWI-ASPECTS vs.CT-ASPECTS In Hyper-acute Stroke Patients

Mutsumi Mitomi, Hiratsuka Kyosai Hosp, Hiratsuka, Japan; Junya Aoki, Yasuyuki Iguchi, Kazumi Kimura; Dept of Stroke Medicine, Kawasaki Med Sch, Kurashiki, Japan Background and Purpose: There were few reports of the direct comparison of ischemic detection between CT-ASPECTS and DWI-ASPECTS within 3 hours of stroke onset. Our aim is to assess the utility of DWI-ASPECTS against CT-ASEPCTS in hyper-acute stroke patients eligible for thrombolysis. Methods -Consecutive anterior circulation stroke patients underwent DWI and CT within 3 hours of stroke onset. Two observers independently assessed CT and DWI findings blind to backgrounds of patients apart from side of stroke symptoms. Firstly, we examined the presence and absence of ischemic lesion on DWI and CT. Secondly, we assessed the points of DWI-ASPECTS and CT-ASPECTS, and calculated kappa statistics to examine reliability between two scores. In addition, when we set the each DWI-ASPECTS regions (10 points) as a gold standard, sensitivity and specificity of presence of the ischemic lesions at each CT-ASPECTS region were calculated. Results: The subjects consisted of 130 consecutive patients with stroke (71 males; median age, 75 years). The mean interval between symptom onset and imaging study was 1.9 hours for CT and 1.6 hours for DWI. DWI more frequently demonstrated the fresh ischemic lesions than CT (76.9% vs. 30.0%, Pϭ0.001). Median CT-ASPECTS score was 10 while median DWI-ASPECTS score was 7 (pϽ0.001). CT-ASPECTS had poor agreement with DWI-ASPECTS in patients with hyper-acute stroke (0.06 of kappa values). The highest-detectable region on DWI-ASPECTS was insular cortex (77 of 130 cases, 59.2%) and the lowest was internal capsule (9 cases, 6.9%). On the other hand, in CT-ASPECTS, the highest was lentiform nucleus (26 cases, 20%) and the lowest was caudate head (1 case, 0.8%). When DWI-ASPECTS as a gold standard, the sensitivity and specificity of the presence of the ischemic lesions at each CT-ASPECTS region were as follows; insular cortex, 0.25 of sensitivity/0.98 of specificity; caudate head, 0.06/1.00; internal capsule, 0.00/0.98; lentiform nucleus, 0.37/0.93; M1, 0.20/0.99; M2, 0.12/1.00; M3, 0.11/1.00; M4, 0.19/0.99; M5, 0.21/0.99; M6, 0.12/0.99. Overall, sensitivity of CT-ASPECTS was extremely low in comparison with DWI-ASPECTS. Conclusion: In hyper-acute stroke, DWI-ASPECTS is a practical scoring method for assessing the presence of fresh ischemic lesions compared with CT-ASPECTS.

Author Disclosures: M. Mitomi: None. J. Aoki: None. Y. Iguchi: None. K. Kimura: None.

Th P107

Test-Retest Reproducibility of Cerebral Blood Flow Measurements Using Pseudo-continuous Arterial Spin labeling at 1.5T chul-ho sohn, Ji-Hoon Kim, Seung Hong Choi, Moon Hee Han, Kee-Hyun Chang, In-chan Song, Seoul National Univ Hosp, Seoul, Korea, Republic of; Geon-Ho Jahng, East-West Neo Med Cntr, Kyung-He university, Seoul, Korea, Republic of; Tae-Jin Yun; Seoul National Univ Hosp, Seoul, Korea, Republic of Test-Retest Reproducibility of Cerebral Blood Flow Measurements Using Pseudo-continuous ASL at 1.5T introduction non-invasive whole-brain cerebral blood flow (CBF) quantification has become practically feasible. The purpose of this study was to investigate the reproducibility of a pseudo-continuous ASL (PCASL) imaging sequence. Subjects andMethods: MRI was performed on a 1.5T whole body scanner (body coil for transmit; 12-channel head coil for receive). Pulsed continuous ASL was performed using a back ground suppressed 3D FSE readout with the following parameters: TR/TE 13250/5 ms; FOV 24 cm; 5mm slice thickness, 1.9 mm in-plane resolution; Label time/post-label delay: 1500/2000 ms; imaging time 5 min. For spatial coregistration and normalization a T1-weighted FSPGR (voxel size 1x1x1 mm 3 ; 130-160 slices) were acquired in the same session. Calculation of CBF-maps was performed. Resting CBF maps were obtained from 16 subjects (9 female, 27Ϯ1.8 y). The study consisted of two scanning sessions per subjects, separated by one week on average. All subjects underwent 4 PCASL scans. Two perfusion measurements were obtained during each session and during the first session, the second scan was repeated without any repositioning of the subject, whereas for session 2 the second scan was acquired after repositioning the volunteer in the scanner. Spatial preprocessing, calculation of CBF-maps and statistical analysis were performed with custom programs written in MATLAB and SPM5 (http://www.fil.ion.ucl.ac.uk/ spm). Repeatability was assessed using Bland-Altman methods. Reliability was computed as an intraclass correlation coefficient (ICC). Results: ICCs in the global brain, gray matter, and white matter area are 0.8399, 0.8403, and 0.8389 respectively. In Bland-Altam plot tests (Ϯ 1.96 SD), there is no bias between PCASL session 1 and 2, and within each sessions. Mean and stdev of CBF(ml/100gm/min) on the whole brain are followed in the 4 sets of PCASL: 1st session 1 st t scan 44.75 Ϯ 7.02, 1st session 2 nd scan 43.0 Ϯ 7.49, 2 nd session 1 st scan 44.3Ϯ 7.85, 2 nd session 2 nd scan 43.

Th P109 Validation of an Automated Perfusion-Diffusion Lesion Assessment Tool

Trevor A Steve, Negar Asdaghi, Thomas Jeerakathil, Michael E Knash, Bilal Hameed, Christian Beaulieu, Ashfaq Shuaib, Derek Emery, Kenneth S Butcher; Univ of Alberta, Edmonton, Canada Background and Purpose: Penumbral imaging with perfusion (PWI) and diffusion-weighted (DWI) MRI volume assessments in the clinical setting are generally qualitative, but previous investigations have shown that these estimates are inaccurate relative to quantitative volume measurements. Manual planimetric measurements are accurate but are time intensive and impractical in the emergent setting. In this validation study, we aimed to test the accuracy of semi-automated PWI-DWI assessment software (Perfscape) against planimetric measurements. Methods: Patients presenting with acute ischemic stroke symptoms who were imaged with PWI-DWI were included. Customized software was used to generate Tmax maps thresholded to ϩ4s using a deconvolution algorithm and a manually selected arterial input function. Planimetric measurements of the Tmaxϩ4s maps and DWI lesion volumes were made using the Analyze software package. The Perfscape software package was used to independently generate Tmaxϩ4s maps, using an automated AIF selection algorithm. This software also calculated Tmaxϩ4s deficit, DWI lesion (based on an apparent diffusion coefficient threshold) and penumbral (Tmaxϩ4s-DWI) volumes automatically. Linear regression and Bland-Altman analyses were used to calculate the accuracy of the Perfscape automated measurements. Results: A total of 76 patients were included. The median time from onset to MRI was 9.48 hours (IQRϭ 5.81,17.43). DWI volumes calculated automatically (17.3Ϯ41.0 ml) were strongly correlated with manually determined volumes (29.1Ϯ57.9 ml); rϭ0.69 [95% CI, 0.66, 0.73]). Automated DWI lesion volumes were generally smaller than manually measured volumes (mean difference -11.8 ml, 95% limits of agreement -51.6, 28.0 ml). Similarly, automated (31.7Ϯ42.8 ml) and manual Tmaxϩ4s perfusion deficit (52.6Ϯ68.2 ml) volumes were strongly correlated (rϭ0.57 [0.52, 0.63]). Automated Tmaxϩ4s PWI deficit volumes were generally smaller than manually measured volumes (mean difference -20.9, 95% limits of agreement -88.7, 46.9 ml). Finally, automated (14.3Ϯ26.4 ml) and manual mismatch volumes (23.5Ϯ51.3 ml) were correlated (rϭ0.42 [0.35, 0.49]. Mismatch ratios assessed automatically (7.0Ϯ17.1) were also correlated with those derived from manually calculated volumes (6. 88Ϯ22.6; rϭ0.38 [0.23, 0.53]). The automated software detected the presence of a mismatch ratio of Ͼ1.2 with sensitivity of 81.6% and specificity of 78.9%. Sensitivity and specificity increased to 92.3% and 84.0% respectively for a mismatch ratio of Ͼ2.0. Conclusions: Automated DWI lesion and PWI deficit volume assessment is feasible. The Perscape tool generally underestimates DWI and PWI volumes, relative to manual planimetric measurements. Despite this, mismatch ratios were quite similar. This automated tool may facilitate treatment decisions based on penumbral imaging patterns.

Background and Purpose:

A secondary signal change of the substantia nigra on diffusionweighted imaging (DWI) in subacute phase of ipsilateral striatal infarction is known as a pitfall because it may be misdiagnosed as a recurrence of stroke. However, clinical factors related to such a signal change and a decrease of apparent diffusion coefficient (ADC) of the substantia nigra remains unclear. [Methods] We prospectively recruited consecutive stroke patients with acute ischemic lesions in hemilateral caudate nucleus, putamen, globus pallidus, external capsule or internal capsule on MRI on admission. ADC of the bilateral substantia nigra obtained from follow-up MRI were analyzed; ADC ratio (lesion side/contralateral side) ysis of normal control subjects, was regarded as a significant decrease of ADC. We investigated clinical factors related to significantly decreased ADC on the lesion side. [Results] Out of 90 patients, 18 patients who underwent follow-up MRI within 3 days of stroke onset were excluded because none of them revealed significant ADC changes; residual 72 patients (median 79 years, 35 male and 37 female) were analyzed. Twenty-seven (38%) patients demonstrated a significant decrease of ADC. Patients with significant decreased ADC revealed higher NIHSS score on admission than patients without decreased ADC (median 16 vs. 9, P ϭ 0.008). Ischemic lesions in globus pallidus (82% vs. 11%, P P ϭ 0.001) were more frequent in patents with decreased ADC, whereas lesions in putamen, external capsule, or internal capsule were not different between the two groups. In patients with decreased ADC, dyslipidemia was less frequent (4% vs. 29%, P ϭ 0.009), while emboligenic diseases (78% vs. 13%, P ϭ 0.010) and recanalization of the occluded middle cerebral artery on follow-up (63% vs. 16%, P ysis, globus pallidus lesions (OR 6.93,) and emboligenic diseases (OR 5.43, were independently related to the ADC decrease of the ipsilateral substantia nigra. There was no significant association between decreased ADC and patients' outcome. Conclusions: Ischemic lesions in globus pallidus and embolic mechanism may be related to a secondary signal change of the ipsilateral substantia nigra. Purpose: Mismatch between volumes of stroke core and critically underperfused tissue is used to identify patients that could benefit from advanced reperfusion therapies. The core can be identified either on ADC maps from MR-DWI, or it can be outlined in regions where perfusion is lost. However, CBV is not always lowered in regions with low ADC, although CBF seem to be always reduced there. We hypothesized that combining regions with reduced CBF and CBV could improve equivalence between perfusion and diffusion stroke cores and thus could allow more consistent identification of mismatch. Methods: 36 acute stroke cases imaged with an optimized MR-DWI/DSC-MR-PWI protocol 0-6 hours after stroke onset were analyzed. Patients were scanned 0.5-3 hours after tPA was administered and before mechanical thrombectomy was executed. rCBV, rCBF and Tmax maps were obtained using delay-independent deconvolution. DWI and PWI were spatially coregistered. Stroke cores were segmented based on Th P112 Simultaneous Multiple Lacunar Infarction: Is it different disease entity from Single Lacunar Infarction ?

Joon Hwa Lee, Young Jin Kim, Yeonsil Moon, Hahn Young Kim; Konkuk Univ Hosp, Seoul, Korea, Republic of Backgrounds: Stroke mechanism other than small artery disease has been reported in patients with lacunar infarction. We hypothesized that acute simultaneous multiple lacunar infarction (sMLI) may have different clinical characteristics from acute single lacunar infarction (SLI). Methods We retrospectively reviewed stroke patients with acute simultaneous multiple lacunar infarction or acute single lacunar infarction in the prospectively collected stroke registry from March 2008 to February 2010. Clinical characteristics including risk factors, premorbid cognitive and functional state, and outcome were assessed. Imaging characteristics including white matter ischemic changes, previous lacunes, micro or macrohemorrhage, and concomitant intra or extracranial stenosis were assessed. SLI was defined as a solitary hyperintense signal identified in the diffusion weighted MRI, Ͻ2.5cm in diameter, located in the subcortex and perforating artery territories. sMLI was defined as simultaneously identified two or more acute SLI. Results Of 548 acute ischemic stroke patients, sMLI were 23 (4.1%) and SLI were 148 (27%). Vascular risk factors including hypertension, diabetes mellitus, dyslipidemia, smoking or rheological risk factors including D-dimer, fibrinogen, hs CRP, BUN/Cr ratio showed no difference between two groups. Previous history of stoke was more prevalent in sMLI group (38% vs. 16%, PϽ0.05). In sMLI group, age was older (68.4Ϯ11.2 vs. 63.1Ϯ11.5, PϽ0.05) and premorbid functional state was poorer (mRS 1.3Ϯ1.5 vs. 0.4Ϯ0.9, PϽ0.05). sMLI group showed more white matter ischemic changes (Fazeca scale for periventricular white matter hyperintensities, 1.3Ϯ0.9 vs. 0.9Ϯ0.7, PϽ0.05; deep white matter hyperintensities, 1.4Ϯ0.8 vs. 0.8Ϯ0.8, PϽ0.01), number of microbleeds (6.9Ϯ11.4 vs. 1.0Ϯ2.9, PϽ0.05), number of previous lacunes (2.6Ϯ2.5 vs. 0.8Ϯ1.1, PϽ0.01). Cardioembolic mechanism was rare in both groups. Generalized atherosclerosis such as peripheral artery occlusive disease (17.4% vs. 1.4%, PϽ0.01), symptomatic carotid disease (8.7% vs. 1.4%, PϽ0.05) was more prevalent in patients with sMLI than SLI. Although age variant was adjusted, sMLI had significantly higher deep white matter ischemic score (pϽ0.01), number of microbleeds (pϽ0.001), number of previous lacunes (pϽ0.001) and prevalence of preipheral occlusive disease (pϽ0.01) than SLI. Conclusions: Mechanism of sMLI might be a small vessel disease rather than other stroke mechanisms. However, clinical and imaging characteristics suggest that sMLI might be a distinct more severe small vessel disease entity from small vessel disease with SLI.

Author Disclosures: J. Lee: None. Y. Kim: None. Y. Moon: None. H. Kim: None.

Th P113 CT Perfusion Source Images are Superior to CT Angiography for Rapid Evaluation of Collateral Status

David S Liebeskind, UCLA, Los Angeles, CA; Nerses Sanossian, USC, Los Angeles, CA; Qing Hao, Noriko Salamon, Jeffrey L Saver, UCLA, Los Angeles, CA; for the UCLA Collateral Investigators Background: Numerous CT angiography (CTA) scales have been advanced for rapid, noninvasive evaluation of collateral status, yet validation with collateral circulation on digital subtraction angiography (DSA) has not been performed. CT perfusion (CTP) source images offer a potential advantage as they contain temporal, and not just spatial, resolution like CTA. We evaluated the use of previously reported CTA scales separately on source images of CTA (CTA-SI) and CTP (CTP-SI), including validation with contemporaneous DSA in acute ischemic stroke. Methods: Consecutive acute MCA ischemic stroke cases with CTA or CTP and DSA. All previously reported CTA collateral scales (including from 3-5 grades) were used to score collateral status separately on CTA-SI and the late phase CTP-SI. DSA collateral grade (ASITN/SIR) was then used to validate all CTA and CTP collateral scores. Results: Six distinct CTA collateral scales were identified and evaluated in 36 cases (mean age 69Ϯ19 years; 21 men, 15 women) with acute MCA stroke. DSA collateral grades were evenly distributed from 0-4, median 2. CTA-SI were graded in 33 cases, late phase CTP-SI in 28, with both CTA and CTP in 26. Collateral scores revealed poor discrimination on CTA-SI, with only 3/6 scales demonstrating even binary classification of cases (pϽ0.05) for the presence or absence of any collaterals. Use of all 6 scales on CTP-SI, however, correlated with presence or absence of collaterals (all 6, PϽ0.01). Collateral scores of all 6 scales on CTP-SI exhibited superior discrimination of DSA collateral grade compared with the use of CTA-SI (pϽ0.01). CTA-SI (left) lack temporal resolution and therefore overestimate collateral status, whereas CTP-SI (right) have both temporal and spatial resolution that better defines the nature of downstream collaterals in this example of right MCA stroke. Conclusions: CTA collateral scales principally evaluate the mere presence or absence of collaterals, with poor discrimination of the spatial and temporal extent evident on DSA. Use of the same scales, however, on the late phase CTP-SI may rapidly provide such detailed information.

Th P114 Delay in Evaluation and Treatment of Posterior Circulation Stroke Compared with Anterior Circulation Stroke

Amrou Sarraj, Sarah K Medrek, Alexandra Garza, John F Pruit, Jeffery Rhodes, Nusrat Harun, Susan Alderman, Melvin R Sline, Renganayaki Pandurengan, Ramy El Khoury, Tzu-Ching Wu, George Lopez, Andrew Barreto, Nicole R Gonzales, James C Grotta, Sean Savitz; UT Houston, Houston, TX Background: Lack of recognition of early symptoms of acute posterior circulation cerebral ischemia might delay timely diagnosis and treatment. We investigated whether there were differences in symptom onset to arrival at our emergency department (ED), arrival to Neurology evaluation, and ED arrival to treatment between patients with posterior circulation ischemia (PCI) versus anterior circulation ischemia (ACI). We also assessed if various symptoms were associated with differences in time to evaluation or time to treatment between ACI and PCI. Methods: Retrospective chart review of patients was conducted covering the period from January 2008 to May 2010. We evaluated consecutive patients with ACI and PCI, who received standard IV thrombolysis within 4.5 hours from time of onset. We collected demographics, different time intervals in the ED, and symptoms. Results: Among 252 patients treated with IV t-PA, 12% had PCI. The demographics and risk factors are shown in Table 1. There were significantly longer intervals in arrival-to-treatment and ED physician evaluation-to-neurology evaluation. There were no statistical differences in symptom onset to ED arrival, time of arrival to CT, or time of neurology evaluation to t-PA administration. There was no statistical significance in outcomes based on neurological worsening, rate of symptomatic intracerebral hemorrhage (sICH), length of stay (LOS), or discharge modified Rankin Scale (mRS). There were significantly higher percentages of nausea, vomiting, and dizziness in the PCI group. The presence of these symptoms was associated with a longer time from ED evaluation to neurology evaluation. The odd ratio for longer time to neurology evaluation was (OR: 3.7, 95%CI: 1.6-8.1, P-valueConclusions: Our data indicate that PCI patients had a 15.5 minute delay after initial ED evaluation to neurology evaluation (P-valueϭ0.0084) and a 20 minute delay (P-valueϭ0.0026) in IV t-PA administration compared with ACI patients. There may be difficulties in rapidly recognizing the symptoms of PCI, in contrast to ACI, in the emergency department. However, it may also be that the neurology response time to evaluating patients with PCI was slower than ACI patients. More education may be needed to increase early recognition of posterior circulation and shorten delays to t-PA treatment. Our study is limited by the small sample of PCI patients.

tertiary-care emergency departments. Patients with symptom duration greater than 24 hours and individuals and in whom the speech disturbance could not be classified by direct examination by a physician were excluded. Patients with isolated dysphasia were identified if the clinical record revealed an isolated language deficit; expressive or receptive. Potential cardiac sources for embolism were defined as atrial fibrillation identified on history, ECG, holter monitor; or thrombus on echocardiography. Proportions were compared using Fisher's exact test. Results: 2574 patients were enrolled in the study; 1369 arrived in the ED with symptoms and were included in the final analysis. Of these patients, 48 were identified as having isolated dysphasia. Both groups had a similar proportion of males (50.1% vs. 60.4%, pϭ0.187) although those with isolated dysphasia tended to be older (67.1 Ϯ 14.4 vs. 73.0 Ϯ 10.4, pϭ0.007). There was no difference in the rate of hypertension (60.7% vs. 70.3, pϭ0.098), coronary artery disease (19.4% vs. 33.3%, pϭ0.062), history of atrial fibrillation (8.1% vs. 14.6%, pϭ0.112), diabetes (20.2% vs. 20.8%, pϭ0.856), or previous stroke (14.5% vs. 16.7%, pϭ0.676) between the two groups however patients with isolated dysphasia were more likely to have congestive heart failure (2.5% vs. 8.3%, pϭ0.038). In both groups the symptoms lasted for more than one hour (86.2% and 87.5%, pϭ0.488). Patients with isolated dysphasia were twice as likely to have a potential cardiac source of embolism (10.0% vs. 20.8%, pϭ0.026). In contrast, there was no difference between the groups in the rate of any carotid stenosis (41.1% vs 41.7%, pϭ0.862) or severe (Ͼ70%) stenosis (4.3% vs. 8.3%, pϭ0.259). Conclusion: In patients with TIA, isolated dysphasia is associated with a high rate of potential cardiac sources of embolism; the most common being atrial fibrillation. The identification of isolated dysphasia in individuals with speech disturbance is helpful in determining etiology and warrants rapid screening for a cardioembolic source. Joji Inamasu, Masashi Nakatsukasa; Saiseikai Utsunomiya Hosp, Utsunomiya, Japan Background. Headache is one of the most frequent presenting symptoms of non-traumatic intracranial hemorrhage, which is also a common cause of cardiac arrest and/or sudden death in adults. History of sudden headache preceding collapse may be a helpful clue to estimate the cause of out-of-hospital cardiac arrest (OHCA). Methods: This is a retrospective study conducted in a single teaching hospital. The witnesses of OHCA patients' collapse were interviewed in the emergency department (ED), and the information of when and how they collapsed was recorded in an institutional database. The database was reviewed to identify those who experienced sudden headache preceding collapse, and their incidence was reported. Brain CT scan is obtained prospectively in our institution, immediately after OHCA patients achieve return of spontaneous circulation (ROSC). CT diagnoses of those who collapsed complaining of sudden headache were also reviewed. Results: From April 2007 to March 2009, a total of 179 patients who sustained a witnessed non-traumatic OHCA were treated in our institution. Among them, 103 (58%) collapsed without complaining of any pain, and 8 (4%) complained of sudden headache preceding collapse. Seven of the 8 patients achieved ROSC after cardiopulmonary resuscitation. Post-resuscitation CT scan showed that all of the 7 patients had a fatal intracranial hemorrhage: Five had a severe subarachnoid hemorrhage (SAH), whereas the other two had a massive cerebellar hemorrhage. None of the 7 patients were discharged alive. On the other hand, 52 of the 103 (50%) patients who collapsed without complaining of any pain achieved ROSC and underwent brain CT scan. Among them, another 8 patients were found to harbor a SAH. Thus, a total of 15 among the 179 witnessed non-traumatic OHCA patients (8%) were found to harbor a fatal intracranial hemorrhage. Post-resuscitation brain CT scan was obtained safely in all patients, with an average ED door-to-CT table time of 40 min. Conclusions: While OHCA patients who collapse complaining of a sudden headache are rare, with the frequency of 4%, the presence of prodromal headache strongly suggests the diagnosis of fatal intracranial hemorrhage. Their prognosis is extremely poor, although they are easily resuscitated in the ED. In addition, approximately half of patients whose OHCA are caused by an intracranial hemorrhage collapse without preceding headache. Brain CT scan obtained immediately after resuscitation can be performed safely, and it can identify those with "neurogenic" cardiac arrest, in whom aggressive treatment such as therapeutic hypothermia may not be indicated.

Author Disclosures: J. Inamasu: None. M. Nakatsukasa: None. Background: Although studies have described rates of clinical deterioration in hospitalized stroke patients, we know of none which evaluated rates and predictors of clinical deterioration among patients assessed in the field during first two hours after symptom onset. Objective: To determine how often stroke patients clinically deteriorate in the first hours after symptom onset. Methods: The study population is comprised of subjects enrolled in the NIH-funded FAST-MAG (FM) clinical trial, a randomized placebo-control phase 3 study of paramedic-initiated magnesium sulfate vs. placebo for patients with stroke symptom onset ϭ 2 points on the GCS in between the prehospital and emergency room evaluation. Clinical, demographic, and initial radiographic data were compared in those with and without deterioration. Last known well time (LKWT) was confirmed by FM study nurse in the ED. Results: A total of 987 consecutive subjects were administered the GCS in the field a median of 46 minutes after LKWT. Mean age was 69 and 41% were female. The median field GCS score was 15, IQR14-15. Overall 12% of patients (120/987) experienced clinical deterioration by Ͼϭ 2 points between the prehospital and ED GCS. The second GCS exam was performed a median of 108 minutes following the paramedic evaluation GCS. Intracerebral hemorrhage (ICH) was noted on initial imaging in 23% of subjects (Nϭ229). Age, gender, ethnicity, time from LKWT to paramedic evaluation were not associated with CD. On univariate analysis, predictors of CD were higher initial blood pressure (SBP 171 vs. 159,PϽ0.001,DBP 95 vs. 90,pϭ0.004), history of hypertension (87% vs. 74%, pϭ0.018), history of diabetes (29% vs. 20%, pϭ0.019), and ICH on initial imaging (40% vs. 7%, PϽ0.0001). Predictors of non-deterioration were atrial fibrillation and valvular heart disease. In multivariate analysis, independent predictors of clinical deterioration were: ICH on initial imaging (OR ϭ 5.75) and a history of diabetes (OR ϭ 1.89). Conclusions: Hemorrhage stroke subtype and history of diabetes predict early clinical deterioration between paramedic arrival on scene and examination in the ED. Among ICH patients, 4 of 10 experience clinical deterioration. The FAST-MAG clinical trial will be able to assess the effects of prehospital neuroprotective therapy upon early CD.

Th P119 Early Clinical Deterioration of Stroke Patients Assessed in the Field within Two Hours of Symptom Onset

Th P120 Association between Time Spent in the Emergency Department and Stroke Outcome

Alexandros Georgiadis, Muhammad Ansar, Saqib A Chaudhry, Fahd Sultan, Silvina B Tonarelli, Michael Tibbs, Gabriela Vazquez, Laura C Dees, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr,Univ of Minnesota, Minneapolis, MN Background: Early initiation of close monitoring of neurological status and of measures such as control of blood pressure, serum glucose levels, and body temperature is considered to be essential to improve outcome in acute stroke patients. Initiation of these measures may be delayed in patients who spend more time in the emergency department (ED). Objective: To assess whether the length of time that stroke patients spend in the ED correlates with worse outcome. Methods: Data of ischemic and hemorrhagic stroke patients treated at a comprehensive stroke center between January 2009 and May 2010 were abstracted from a prospective registry (Minnesota Stroke Registry). Unfavorable outcome was defined as death or non-ambulatory status at the time of discharge. We analyzed whether demographic factors, stroke risk factors, stroke type (ischemic vs. hemorrhagic), and stroke severity [National Institutes of Health Stroke Scale Score (NIHSSS) for ischemic stroke and Glasgow Coma Scale (GCS) for hemorrhagic stroke] were associated with time spent at ED using logistic regression after adjusting for potential confounders. ED time was expressed in quartiles. Results: We analyzed the data of 363 patients, 167 (46%) women. Mean age was 63 Ϯ 15 years and most patients (nϭ274, 75.5%) had ischemic strokes. Among ischemic stroke patients mean NIHSSS was 6.8 Ϯ 5.4 and among hemorrhagic stroke patients mean GCS was 13 Ϯ 3.4. Median ED time (interquartile range) was 146 minutes (range 76-289 minutes). Time spent at the ED was inversely associated with age (pϭ0.006) and NIHSSS (pϭ0.003) and directly associated with GCS (Ͻ0.0001). Ischemic stroke patients spent more time in the ED than hemorrhagic stroke patients (pϽ0.0001). Unfavorable outcome was observed in 135 (37%) patients. Time spent at ED was inversely associated with unfavorable outcome (pϭ0.002, test for trend). Conclusion: Contrary to our hypothesis, longer ED times are associated with favorable outcome from stroke. This is a reflection of the fact that younger patients and patients with less severe strokes tend to spend more time in the ED. Our data suggest that ED time is not useful as a surrogate for quality of care for stroke. Fresh frozen plasma (FFP), intravenous or oral vitamin K are the standard ways of reversing INR. However, both treatments may take hours to reverse coagulopathy. rFVIIa is easy to mix and administer but costly ($1,600-7,800). To reverse INR with rFVIIa has been reported in a small series. The dose range to effectively correct INR has not been well established. We here report so far the largest series of reversing INR with rFVIIA in patients on warfarin and developed ICH's. Knowing rFVIIa was costly and higher doses (80 mcg/kg) would cause thrombotic events, only 1-2 vials were used at our center regardless to how high the INR was elevated. Method This is a retrospective study. Records of all patients with diagnosis of ICH and received rFVIIa were reviewed. Data tabulated include demographics, taking or not taking warfarin, doses of rFVIIa, length of stay (LOS), mortality and discharge destination. Patients with available INR data and ICH or IVH or SAH on CT findings both pre and post rFVIIa were included. Descriptive statistics were used to analyze the data. Results From 1/2006 to 7/2010, 554 patients had ICH's. Seventy four (13%) patients received rFVIIa. Forty two (57%) were male and 32 female. Average age was 66 (20-91). Forty seven (64%) had ICH's, 23 (31%) had ICHϩIVH's and 4 (5%) had IVHϩSAH's. The average dose of rFVIIa was 1.4 mg. Forty three had CT scans pre and post rFVIIa. In 26 (35%) patients on warfarin, the average INR on admission was 3.17 and post rFVIIa was 1.18. Only an INR of 20 was not corrected to Ͻ1.4. Eight (35%) on warfarin had IVHϩICH's and 5 (19%) died. In 48 (65%) not on warfarin, 13 (27%) had ICHϩIVH and 2 (4%) died. The average size of hematoma pre rFVIIa was 4.1x3.5 cm and post rFVIIa 4.4x3.3 cm. Of these, 21 patients were on warfarin with the average initial ICH size of 6.2x3.6 cm compared to 3.8x2.8 cm in 32 patients not on warfarin. The average LOS was 10 days. Including hospice care, 19 (25%) died at discharge and 8 (42%) were on warfarin. Five (6%) patients went home; 33 (45%) to rehabilitation; 17 (24%) to skilled nursing facility. Conclusion: In our experience, low dose rFVIIa effectively reversed the elevated INR's induced by warfarin to a normal range. However, the size of hematoma was not reduced and the mortality rate was higher in the warfarin group. Normalized INR would not equate to improved outcome. Our study confirmed the finding that patients on warfarin usually had larger ICH's and higher mortality, especially if ICH patients also had IVH's. If elevated INR needs to be corrected quickly, one vial of rFVIIa (1.2mg) instead of using weight based dosage plan may work for INR level Ͻ 20. The significance of these findings and the related medical economics may need to be studied further in a larger prospective trial.

Th P123 Multimodal Predictors of Massive Ischemic Stroke.

Olivier Bill, Philippe Zufferey, Mohamed Faouzi, Patrik Michel; CHUV, Lausanne, Switzerland Introduction: Severe stroke carries a high short and long term disability and fatality rate. Nevertheless, the profile of these patients in the acute phase is poorly defined. The aims of this study are to determine the characteristics of patients with severe ("massive") ischemic stroke at onset regarding a large range of clinical and paraclinical parameters. Methodology: Using a prospectively constructed acute ischemic stroke databank (Acute STroke Registry and Analysis of Lausanne, ASTRAL), we compared all patients with massive stroke defined as a NIHSS Ն 20 at admission with all other patients. The variables included in a univariate and then in a multivariate analysis included demographic factors, vascular risk factors, clinical presentation, stroke mechanism, previous clinical or silent ischemic events, medication and acute radiological and metabolic findings. Results: Among 1915 acute ischemic patients, 243 (12.7%) had massive strokes. On multivariate analysis massive stroke patients had higher prestroke modified Rankin Scale (ORϭ1.28, 95%CIϭ1.04/1.56, PϽ0.019), more unknown onset (Ͼ1h but less than 24h) (ORϭ2.35, 95%CIϭ1.14/4.83, PϽ0.02), more early ischemic CT/MRI findings (ORϭ2.65, 95%CIϭ1.79/3.92, PϽ0.000), less chronic radiological infarcts (ORϭ0.43, 95%CIϭ0.25/0.71, PϽ0.001), more arterial occlusions in the ischemic territory on admission vascular imaging (ORϭ0.03, 95%CIϭ0.01/0.08, PϽ0.000), lower Hb concentration (ORϭ0.97, 95%CIϭ0.96/0.98, PϽ0.000), higher WBC (ORϭ1.05, 95%CIϭ1.00/1.11, PϽ0.045), and more cardio-embolic stroke mechanism (ORϭ1.74, 95%CIϭ1.19/2.54, PϽ0.004), With this profile, the area under the ROC curve showed a trade-off between sensitivity and specificity of 86%. Conclusion: Stroke severity is predicted by multiple clinical, radiological and laboratory anomalies of which several are modifiable. Interestingly, unlike previous on the topic, age, admission blood pressure and past history are not associated with severe stroke. This study confirms the necessity to consider a broad range of clinical and laboratory values in the acute phase of ischemic stroke, including detailed neuroimaging. The predictors of poor or good outcome in these patients still need to be studied.

Author Disclosures: O. Bill: None. P. Zufferey: None. M. Faouzi: None. P. Michel: None.

Th P124 Factors Affecting Inequality In Acute Stroke Care In An Urban Hospital

Jose R Romero, Helena Lau, Aleksandra Pikula, Haroot Artinian, Thanh Nguyen, Mathew Ogrodnik, Feliks Koyfman, Carlos S Kase, Viken L Babikian; Boston Univ Sch of Medicine, Boston, MA Objective To investigate trends in racial and socioeconomic disparities in acute stroke care which may affect the decision for intravenous tPA (IV-tPA) use in an inner-city hospital providing care to an underserved population. Background Previous studies suggest that minorities have higher risk of stroke and stroke severity. The acute phase of stroke care is an important period affecting stroke severity. Prompt presentation to emergency rooms affects the decision for treatment with IV-tPA and stroke outcomes. Previous studies have suggested racial and socioeconomical inequalities in health care. We sought to evaluate patients presenting within the expanded acute window for treatment with IV-tPA (i.e. 4.5 hours), and describe the role of socioeconomic status and race in this phase of acute stroke care. Design/Methods We evaluated consecutive patients presenting to our stroke center with an acute stroke alert between January and May of 2010. Symptom onset to ER arrival time, ER arrival to CT scan time, and door to needle time for IV-tPA were studied. These measures were stratified by race and insurance status (used as a proxy for socioeconomic status). Race and insurance status were stratified in 4 groups and descriptive statistics are presented. Results Eighty seven (87) patients presented to the ER with stroke symptoms within 4.5 hours during the study period. The youngest group (mean age) were Hispanics (52yrs, nϭ5), followed by other ethnic groups (59yrs, nϭ10), Blacks (61yrs, nϭ41), and Whites (68yrs, nϭ31). Mean time from symptom onset to ER arrival was longest for Hispanics (117min) and other ethnic groups (94min) as compared to Whites (71min) and Blacks (71mins). Uninsured patients showed the longest time to arrival to ER from symptom onset (104min, nϭ10) when compared to patients on Medicaid (75min, nϭ19), Medicare (80min, nϭ32), and Private insurance (80min, nϭ26). In addition, uninsured patients had the longest ER arrival to CT scan times (114min) in comparison with Medicaid (55min), medicare (38min), and patients with private insurance (59min). Only 9% of patients received IV-tPA. Conclusions: Our findings suggest race and socioeconomic disparities play a role in the acute phase of stroke care. While our study is limited by its small sample size and study design, our preliminary data warrants further investigation to assess potential reasons for these differences such as cultural factors, language barriers, awareness of stroke symptoms, patient's monetary concerns, and physician biases.

Objective: To describe the structure and function of a telestroke program established to offer acute stroke care to patients in rural hospitals across the state of Arkansas. Background: Telestroke programs have emerged as important links in the evaluation and treatment chain of acute stroke, thus filling in a gap created by shortage of stroke neurologists. The number of telestroke networks is on the rise, however establishing and funding such programs is challenging, and self-support is even more difficult. Design/Methods: We describe the establishment, structure, and function of the Arkansas SAVES telestroke program. Results: The AR SAVES telestroke program operates under the auspices of the University of Arkansas for Medical Sciences Center for Distance Health. It was created by a grant from the Arkansas Department of Human Services; its goal is to offer evidence-based acute stroke care, ultimately to most rural hospital in the state, thus increasing the rate of intravenous thrombolysis, improving outcome, and cutting direct and indirect costs of stroke care. It was launched in November 2008. It utilizes the TANDBERG®, point-to-point video-conferencing systems connecting through T1 lines across the state. Three stroke neurologists, from both the private and academic sectors participate in the program. They are part of two hub PSC, covering calls 24/7 for which they are remunerated. Spoke hospitals are screened for basic capabilities and are brought on board sequentially following a period of on and off-site training, by dedicated health educators and outreach nurses, and mock telestroke runs that continue later after joining the program; nurses train and certify in administering the NIHSS; furthermore, the program funds different community education activities across the state. Neither spoke hospitals nor patients incur extra costs. Conversely, the program covers part of the salary of a nurse liaison and an information technologist at the spoke hospitals. A call center serves as the link between rural hospitals and hubs and arrange for patient transfers when needed. A central imaging repository allows spoke hospitals to push brain CT for the stroke neurologists to review. To date, 20 rural hospitals in 20 of 73 medically underserved counties in Arkansas have become part of the program. We have completed 276 consults of which 57 patients were treated with IV thrombolysis. We plan to add nine to twelve hospitals every year, while increasing our workforce to match the demand that rises with these additions. Conclusions: Telestroke programs have different structures and belong to different models. Government funding could be a viable alternative to the classic business model, especially if overall cost cutting to the system could be achieved. Furthermore, private and academic neurologists could form a pool of physicians to cover calls in a telestroke network.

Author Disclosures: S. Keyrouz: None.

Th P133 Prevent Controversial Stroke Trial Results by Better Balancing Baseline Covariates

Wenle Zhao; Med Univ of South Carolina, Charleston, SC It is well known that the primary outcome in stroke trials is highly dependent on baseline conditions, such as baseline NIH Stroke Scale, age and time from stroke onset to treatment. The results of some large trials such as the National Institute of Neurological Disorder and Stroke Recombinant Tissue PlasminogenActivator (NINDS rtPA) trial were controversial due to serious imbalance of important baseline covariates. However, balancing of these covariates was often ignored in the randomization algorithm. This is mainly due to the belief that baseline covariate distributions will tend to be balanced for trials with a large sample size, and a randomization algorithm balancing multiple baseline covariates, both categorical and continuous, is not available in most commercially developed clinical trial management systems. In this presentation, we define two goals for subject randomization in clinical trials: prevention of selection bias and protection of compatibility between study groups. Failure to reach both of these goals seriously impacts trial validity. We propose a randomization strategy that simultaneously controls serious imbalance for multiple baseline covariates of different types, including categorical, ordinal and continuous, while maintaining a high level of randomness for treatment allocation. Performance of this new randomization strategy has been evaluated with computer simulation based on subject randomization sequence and baseline covariate data of the National Institute of NINDS rtPA trial, and are compared with commonly used randomization methods, i.e. permuted block randomization stratified by clinical site. Results show that even with large samples, exclusion of important baseline covariates in the randomization algorithm can lead to serious imbalance of these baseline covariates between treatment arms, and hurt the compatibility of the two treatment groups. Implementation of this new randomization strategy in two large multi-center phase III trials conducted within the Neurological Emergen-cies Treatment Trials (NETT) network funded by the National Institute of Neurological Disorder and Stroke will be presented.

Introduction:

Glutamate is a major excitatory transmitter and plays an essential role in brain insults such as stroke. Clinically, the global antagonist of N-methyl D-aspartate (NMDA) glutamate receptor such as MK-801 proved ineffective. Among NMDA receptor subfamilies, NR2A and NR2B subunits are considered as the main types of functional NMDA receptor. While activation of NR2A receptors is involved in synaptic plasticity and cell survival, activation of NR2B is shown to promote neuronal death. The present study is aimed to investigate whether the selective inhibition of NR2B is neuroprotective in in vitro oxygen glucose deprivation (OGD) model and in vivo permanent MCA occlusion (MCAO) model. Methods: Primary cortical neuronal cultures were prepared from 16-day-old Wistar rat embryos and used 10 to 12 days in vitro. As in vitro ischemia, neurons were exposed to 210-minute OGD or 15-minute 100 M glutamate. Cells were treated after OGD with one of the following chemicals: global NMDA receptor antagonist MK-801 (10 M), non NMDA receptor antagonist CNQX (10 M), L-type calcium channel blocker nifedipine (5 M), NR2A-specific antagonist NVP-AAM077 (200 nM), and NR2B-specific antagonist Ro25-6981 (100 nM). Neuronal death was quantified 24 hours later by measurement of lactate dehydrogenase released by dead neurons into the bathing medium. For in vivo ischemia model, adult male Wistar rats were anesthetized with halothane, and right MCA was occluded permanently by introducing a 4-0 nylon monofilament suture. Animals were divided into Ro and Vehicle group. Ro group rats were given Ro25-6981 (6mg/kg) intraperitoneally 3 hours after MCAO. Vehicle group rats were given vehicle in a same way. Those rats were sacrificed 12 hours after MCAO, and cerebral cortex was dissected into the core of MCA, the peripheral area of MCA and the ACA area. The level of fodrin proteolysis was analyzed by Western blotting. The other rats were sacrificed 24 hours later, and infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining. Results: Treatment with Ro25-6981 was protective in vitro as well as MK-801 compared with vehicle treatment in both lethal OGD (pϭ0.004) and glutamate toxicities (pϽ0.001). In contrast, other antagonists such as CNQX, nifedipine, and NVP-AAM077 did not influence the cell injury after OGD and glutamate exposure. Treatment with Ro25-6981 resulted in a significant reduction in infarct volume compared with vehicle treatment in permanent MCAO model (250Ϯ101 vs. 354Ϯ50 mm 3 , meanϮs.d, pϭ0.008). In Ro group rats, the proteolysis of fodrin was significantly attenuated compared with vehicle group in the penumbra area 12 hours after MCAO. Conclusions: In conclusion, NR2B inhibition shows a marked reduction of neuronal injury both in vitro OGD and glutamate exposure and in vivo MCAO model.

Author Disclosures: Y. Terasaki: None. T. Sasaki: None. M. Kawamura: None. Y. Sugiyama: None. N. Oyama: None. E. Omura-Matsuoka: None. Y. Yagita: None. K. Kitagawa: None.

Th P142 White Matter Damage After Stroke And The Effect Of Matrix Metalloproteinases In Type-two Diabetic Mice

Jieli Chen, Xu Cui, Alex Zacharek, Yicheng Cui, Cynthia Roberts, Michael Chopp; HENRY FORD HOSPITAL, Detroit, MI Objective: Diabetes mellitus (DM) is a major health problem, leads to higher risk of ischemic stroke, and increases the extent of the cerebral injured area and results in worse outcome after stroke compared to the general population. Diabetic subjects are more prone to develop more and earlier white matter high-intensity lesions. Understanding the changes and mechanisms underlying the adverse effects of diabetes on the impaired white matter after stroke is important in developing new treatments for stroke in diabetic patients. We therefore, investigated white matter damage and associated molecular events after stroke in type-two DM mice. Methods: BKS.Cg-m ϩ/ϩ Lepr db /J (db/db) type-two DM mice and mϩ/ϩ db non-DM mice were subjected to middle cerebral artery occlusion (MCAo). Mice were sacrificed at 24h after MCAo. A battery of functional outcome tests, immunostaining, zymography, Western blot and real time PCR were employed. Results: DM mice exhibited significantly increased lesion volume, brain hemorrhagic transformation and neurological deficit compared to non-DM mice (nϭ12/group, PϽ0.05). To test whether DM enhances white matter impairment, SMI-31 (a Pan-axonal neurofilament marker), Bielshowsky silver (a marker for axons), Luxol fast blue (myelin marker) and NG2 (oligodendrocyte progenitor cell marker) immunostaining were performed. SMI-31, Bielshowsky silver, Luxol fast blue and NG2 expression were significantly decreased, indicating white matter damage, and matrix metalloproteinase 9 (MMP9) expression and activity were significantly increased in the ischemic brain of DM mice compared to non-DM mice (pϽ0.05). To investigate the mechanism underlying DM induced white matter damage, oxygen-glucose deprivation (OGD)-stressed premature oligodendrocyte and primary cortical neuron (PCN) cultures were employed. Lactate dehydrogenase (LDH) and 3-(4,5dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays were performed. High glucose (HG) increased MMP2, MMP9, cleaved-Caspase-3 levels and apoptotic cell number as well as decreased cell survival and dendrite outgrowth in cultured PCN (nϭ6/group, PϽ0.05) were measured. HG increased MMP9 gene and protein expression, increased cell death and cleaved-Caspase-3 level and decreased cell proliferation in cultured oligodendrocytes (pϽ0.05). Inhibition of MMPs by GM6001 treatment significantly decreased HG-induced cell death and apoptotic cell number in cultured PCN and oligodendrocytes (nϭ6/group, PϽ0.05), but did not regulate dendrite outgrowth in cultured PCN (pϾ0.05). Interpretation: DM mice exhibit increased lesion volume, brain hemorrhagic transformation and injured white matter compared to non-DM mice after stroke. MMPs upregulated in DM mice may at least partially exacerbate white matter cerebral damage after stroke in DM mice.

Author Disclosures: J. Chen: None. X. Cui: None. A. Zacharek: None. Y. Cui: None. C. Roberts: None. M. Chopp: None.

Th P143 An experimental Model of Stroke under Oral Anticoagulant Treatment

Waltraud Pfeilschifter, Daniel Spitzer, Bozena Czech, Helmuth Steinmetz, Christian Foerch; Goethe Univ, Frankfurt, Germany Introduction: The prevalence of oral anticoagulant therapy (OAT) for stroke prevention in patients with atrial fibrillation is rising and 30% of all cardioembolic ischemic strokes occur in anticoagulated patients. We therefore aimed to establish a mouse model of ischemic stroke occurring under OAT to assess the frequency and characteristics of hemorrhagic transformation (HT) and the effects of a reversal of anticoagulation with prothrombin complex concentrate (PCC). Methods: C57BL/6 mice (n ϭ 21) were treated with warfarin (2 mg/kg for 24 h) to achieve an INR value of 2.9 Ϯ 0.9 SD. Untreated mice (n ϭ 20) served as controls. Middle cerebral artery occlusion (MCAO) was induced by filament occlusion of the right MCA for 3 h and infarct size and HT were evaluated macroscopically at 24 h. Hemorrhagic blood volume was quantitatively assessed in additional 6 vs. 6 mice with a photometric hemoglobin assay. In a second experiment, we tested whether the rapid reversal of anticoagulation in warfarin mice 1 h after MCAO reduces the risk of HT compared to mice whose coagulation cascade was not restored (6 vs. 6 mice). Results: OAT at the onset of ischemia led to HT in all anticoagulated animals while only 14.3 % of the control animals showed HT. The mean hemorrhagic blood volume was 20-fold higher in the brains of warfarin mice after MCAO (5.9 Ϯ 3.6 l SD) compared to controls (0.3 l Ϯ 0.4 SD; p Ͻ 0,01). Reversal of OAT with PCC reduced hemorrhagic blood volume by 75 % compared to warfarinized mice without substitution (1,1 l Ϯ 0,6 SD vs. 4,5 l Ϯ 1,4 SD, p Ͻ 0,001). Conclusion: We present a mouse model of ischemic stroke under OAT. Warfarin pretreatment dramatically increased the risk of HT 24 h after MCAO. Reversal of anticoagulation with PCC 1 h after stroke onset was able to prevent excessive hematoma formation.

Th P144 Downregulation Of Endothelial Nitric Oxide Synthase Phosphorylation Contributes To Infarct Expansion After Focal Cerebral Ischemia

Yoshiki Yagita, Tsutomu Sasaki, Naoki Oyama, Yukio Sugiyama, Yasukazu Terasaki, Emi Omura-Matsuoka, Kazuo Kitagawa; OSAKA UNIVERSITY GRAD SCHOOL, Osaka, Japan Background and Purpose: Endothelial nitric oxide synthase (eNOS) exerts a brain protective effect against brain ischemia. Suppression of eNOS expression or activity exacerbates ischemic brain injury. It was reported that ischemic insult itself increased eNOS expression. However, profile of eNOS phosphorylation in the ischemic brain is not fully elucidated. Because eNOS function is regulated by some phosphorylation sites, such as Ser1177, it is important to investigate eNOS phosphorylation profile after cerebral ischemia. The objectives of this study are; 1) to investigate the expression and phosphorylation profiles of eNOS after transient focal cerebral ischemia, 2) to evaluate the effect of pharmacological modulation of eNOS phosphorylation on infarct size after transient focal cerebral ischemia. Methods -Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) with the use of a 4-0 nylon monofilament and reperfusion 80 min after induction of ischemia. Tissue damage and localization of eNOS protein were evaluated by immunohistochemistry. Western blot (WB) was performed using phospho-specific antibody of eNOS (Ser1177), eNOS and ␤-actin. Brain tissue samples for WB were taken from the distinct MCA perfusion area in the ischemic hemisphere, as "MCA core", "MCA peripheral area" and "ACA area" at 6 hours, 24 hours and 48 hours after MCAO. Previously, we reported that Rho-kinase inhibitor can increase eNOS phosphorylation. Thus, Rho-kinase inhibitor, fasudil (2 or 10mg/kgBW) was administered after MCAO to increase eNOS phosphorylation. Infarct size was evaluated by using 2,3,5-triphenyltetrazolium chloride staining 2 days later. Results: After cerebral ischemia, eNOS immunoreactivity was preserved even in the MCA core area. Almost all eNOS signals were localized in vascular endothelial cells. WB analysis revealed upregulation of eNOS expression in the whole ischemic hemisphere. In contrast, phospho-eNOS signals were clearly decreased in the MCA core and peripheral area. Inhibition of Rho-kinase activity can acutely enhance eNOS phosphorylation in the brain. Fasudil treatment can suppress infarct expansion after transient focal ischemia (infarct volume: Vehicle 198.2Ϯ20.7mm3, fasudil-2mg/kgBW 108.1Ϯ15.3mm3, fasudil-10mg/kgBW 133.4Ϯ16.8mm3; nϭ9 in each group). Conclusions: Although protein expression of eNOS was increased, phospho-eNOS was decreased in the ischemic hemisphere after transient focal cerebral ischemia. Enhancement of eNOS phosphorylation by fasudil leads to suppression of infarct expansion. These findings suggest eNOS function is impaired in the ischemic brain and pharmacological modulation of eNOS phosphorylation may be effective to prevent infarct expansion.

Introduction: Tissue plasminogen activator (tPA) is the only FDA-approved drug for the treatment of acute ischemic stroke. Emerging data suggest that exogenous tPA may have pleiotropic actions in the brain: a number of studies have shown that exogenous tPA may have cerebral vasoactivity. For the first time, we performed a dynamic MRI study to investigate cerebral vasoreactivity in response to intravenously administered tPA in a permanent focal stroke model of rats. Methods: To characterize cerebral vascular reactivity, 7 Wistar male rats (ϳ270 g) underwent MRI scans (Bruker 9.4T) 2 hours after permanent suture occlusion of middle cerebral artery. T2-and T2*-weighted images were acquired before and after administering blood pool superparamagnetic iron oxide nanoparticles (SPION: 36 mg/kg). For continuous monitoring of cerebrovascular parameters, we alternated gradient (GE) and spin echo (SE) echo planar imaging acquisitions (TR/TE ϭ 3000/12 for GE and 3000/25 ms for SE). Time courses of äR2*(t) (ϭ 1/T2*(t) (post-SPION) -1/T2*(pre-SPION)) and äR2(t) (ϭ 1/T2(t) (post-SPION) -1/ T2 (pre-SPION)) maps were created. Then, cerebral blood volume (CBV(t) ϳ äR2*(t)) and microvascular volume (MVV(t) ϳ äR2(t)) were calculated, from which vessel size index (VSI(t)) maps (ϳäR2*(t) / äR2(t)) were quantified assuming one GE SE epoch as one time point. CBV, MVV and VSI responses were measured during intravenous tPA injection for 30 min (10mg/kg in 3 rats and 1mg/kg in 4 rats) and hypercapnia (5% CO2, 47.5% air, 47.5% oxygen for 5 min) before and after the tPA administration. Linear mixed model was used to assess temporal changes of cerebrovascular parameters. Results: Every rat showed significantly increased CBV, MVV and VSI responses during the first hypercapnia before tPA injection, although response magnitudes were smaller in ipsi-lesional hemisphere than in contralateral side. On the contrary, CBV, MVV and VSI continuously decreased after tPA injection in all rats (pϽ0.0001). The decremental response was more prominent in higher dose (10mg/kg) tPA group than in lower dose (1mg/kg) group (pϽ0.0001). CBV, MVV, and VSI still showed incremental response to the second hypercapnia after tPA injection, but the response magnitudes were significantly lower than those measured in the first hypercapnia. Conclusions:These data showed that tPA may cause cerebral vasoconstriction and impair vasodilation, even at the low dose. The findings suggest that cerebral vasoactivity might be one of important pleiotropic actions of tPA in the ischemic brain, especially to those with poor reperfusion efficacy. Development of neuroprotective strategies in targeting tPA cerebral vasoactivity may improve outcomes of tPA thrombolytic therapy.

Author Disclosures: D. Kang: None. X. Fan: None. W. Shim: None. K. Baek: None. S. Yun: None. S.J. Kwon: None. I. Jeong: None. J. Kim: None. J. Jeong: None. X. Wang: None. Y.R. Kim: None.

Th P147 Elevated Serum Levels of S-100B Reflect Brain Damage and Successful Treatment Effects in a Rabbit Model of Acute Ischemic Stroke

Sean D Woods, Rene Flores, John D Lowery, William C Culp; Univ of Arkansas for Med Sciences, Little Rock, AR Background: The astroglial protein S-100B has been implicated as a potential biomarker for the diagnosis of ischemic stroke. Elevated concentrations of S-100B have been reported in patients and some animal models, but studies are limited that evaluate S-100B as a marker of cerebral tissue damage and treatment effects in a rabbit embolic stroke model. Objective: To investigate the relationship between S-100B and percent stroke volume in a rabbit model of acute ischemic stroke, and determine if these measurements reflect a benefit from therapeutic intervention. Methods: New Zealand White Rabbits (nϭ31; 5.2Ϯ0.04 kg) were embolized with one blood clot (4.0x0.6 mm) injected into the internal carotid artery following a subselective angiographic procedure. Clot was produced in glass tubing at 37°C for 6-hr followed by incubation at 4°C for 72-hr. Follow-up angiography confirmed the occlusion of branches of the internal carotid artery, and treatment was initiated 1-hr post-embolization. Rabbits were randomly assigned to one of three groups: Control (nϭ8, embolization only), tissue plasminogen activator (tPA) (nϭ12), and Perflutren Lipid Microbubbles (MB)ϩUltrasound (US) (nϭ11). MB were administered IV (0.6 mg/kg) over 30 minutes; ultrasound was applied transcranially for 1-hr (1-MHz pulsed-wave, 0.8 W/cm 2 ); tPA (0.9 mg/kg) was administered IV over 1-hr. Blood samples were collected before embolization (baseline) and at 3-and 24-hr post-embolization to determine concentrations of S-100B. Serum concentration of S-100B was determined by enzyme-linked immunosorbent assay. Rabbits were euthanized following the final blood sample (24-hr) and infarct volume was measured by vital stains on 4-mm coronal brain sections. Results: The S-100B fold increase over baseline was influenced by time (Pϭ0.0002) and treatment (Pϭ0.04). Control rabbits had a 3.1-fold increase in S-100B at 24-hr, and this increase differed from baseline (Pϭ0.001). Similarly, rabbits treated with tPA had a 3.0-fold increase in S-100B at 24-hr which differed from baseline (Pϭ0.0002). Treatment with MBϩUS, however, resulted in only a 1.6-fold increase in S-100B at 24-hr which did not differ from baseline (Pϭ0.221). Infarct volume averaged 4.76% for control rabbits, 2.25% for rabbits treated with tPA, and 0.79% for rabbits treated with MBϩUS (Pϭ0.015 compared to control). Concentrations of S-100B at 24-hr were positively correlated with percent infarct volume (rϭ0.59, Pϭ0.0004). Conclusions: Serum levels of S-100B at 24-hr following embolization were greater than baseline values. 24-hr levels were positively correlated with percent infarct volume, and reflected the reduced stroke volume with microbubble therapy. S-100B can be measured in rabbits and correlates with damage from stroke and successful response to treatment. administration of TAK-937 at 2 g/kg/hr plus 0.8 g/kg loading (nϭ7) or vehicle (nϭ7) was started 30 min after clot injection and continued for 24 hr. Cerebral infarct size was determined by 2, 3, 5-triphenyltetrazolium chloride staining method and concentration of S-100␤ in cerebrospinal fluid (CSF) was measured with ELISA kit 24 hr after MCA occlusion. Physiological parameters including body temperature, blood pressure and heart rate were continuously measured using a telemetry system throughout the experiment. Results: TAK-937 showed trend to reduce the infarct volume by 40% and S-100␤ levels in CSF by 40% compared with vehicle-treatment. S-100␤ levels in the CSF were positively correlated with infarct volume (r ϭ 0.81). TAK-937 lowered body temperature by about 1.5 °C, but did not change blood pressure or heart rate. Conclusion: TAK-937 exerts a neuroprotective effect in a non-human primate stroke model without effects on vital signs. That S-100␤ levels in the CSF were reduced by TAK-937 in correlation with infarct volume suggests that this may be a good biomarker for the neuroprotective effects of TAK-937.

Introduction: Electrical stimulation of the vagus nerve in the neck reduces infarct volume by approximately 50% after transient middle cerebral artery occlusion in rats. VNS, however, is not a feasible intervention in setting of acute ischemic stroke because it requires positioning of an electrode after surgical exposure of the nerve in the neck. In the present study, we explored whether stimulation of vagus nerve dermatome in the external ear reduced infarct size in rats. Methods: Stimulating electrodes were implanted on the left auricular concha (cymba concha or cavum concha) to stimulate the auricular branch of the vagus nerve (ear stimulation or ES) in adult male Wistar rats. CBF was measured by laser Doppler flowmeter. Ischemia was produced by filament occlusion of the right middle cerebral artery for 2 hours, followed by reperfusion. In the stimulation group, square pulses were delivered for 30 sec at every 5 minutes for 1 hour starting 30 minutes after the induction of ischemia. In the control group, all the procedures were duplicated but no stimulus was delivered. Animals were euthanized and cerebral infarct volume was determined 24 hours after the onset of ischemia. Results: ES did not change the heart rate, arterial blood pressure, blood gases and pH, and temperature. There was an increase in CBF with each stimulation pulse which gradually decreased by the end of the 30 seconds stimulation period and completely returned back to baseline following the cessation of stimulation. The mean maximum increase in CBF was 134.02% Ϯ 43.87% baseline. CBF elevated 20% from baseline in 5 of the 6 ES-treated animals. The mean infarct volume and SEM was 37.97 Ϯ 2.43 % of the contralateral hemispheric volume in control (nϭ6) and 32.31 Ϯ 3.93 % (nϭ6) in ES-treated animals (pϭ0.258). There was a correlation between the magnitude of CBF response to ES and infarct volume (R 2 ϭ0.745); as the CBF response increased, the infarct size decreased. Infarct size was smaller in ES-treated animals with positive CBF response as compared with the controls (28.99 Ϯ 2.59 % of the controlateral hemisphere, nϭ5; pϭ0.037). Conclusion: Electrical stimulation of the vagus nerve dermatome in the external ear causes a specific response characterized by variable increase in CBF. Reduced infarct volume in ES-responders suggests that ES promises to be a practical novel treatment for cerebral ischemia. Further refinement of the technique and validation are needed.

Author Disclosures: I. Ay: None. H. Ay: None. A. Sorensen: None.

Th P152 Demonstration of Ischemic Preconditioning in White Matter: Critical Role for Toll-like Receptor-4

Margaret A Hamner, Anna Savos, Jamie Colman, Bruce R Ransom, Jonathan R Weinstein; Univ of Washington, Sch of Medicine, Seattle, WA Background: Ischemic preconditioning (IPC) is a robust protective phenomenon in which a brief period of ischemia confers transient tolerance to subsequent ischemic challenge. White matter (WM) injury is critical in the pathophysiology of human stroke. The effect of IPC in experimental models of ischemic injury in WM is unknown. Toll-like receptor-4 (TLR4), a key receptor in innate immunity, mediates robust pro-inflammatory responses and has been mechanistically implicated in IPC. TLR4 is expressed in WM by microglia and astrocytes. TLR4 is activated by endogenous "danger associated molecular patterns" such as heat shock proteins that are released in ischemic brain. We hypothesize that: (i) IPC induces functional protection in WM ischemic injury and (ii) TLR4 signaling is required for this protection. Methods: We performed 15 m common carotid artery ligation or sham surgery on 3 mo old male WT and TLR4-/-mice to induce IPC in the ipsilateral (Ip) optic nerve (ON). After 72 h, we sacrificed the mice. Ip and contralateral (Cn) ONs were removed, equilibrated in normoxic/ normoglycemic (N/N) artificial cerebral spinal fluid (aCSF), and exposed to 45 m of oxygen-glucose deprivation (OGD) in aglycemic/anoxic aCSF followed by 5 h in N/N aCSF. Compound action potentials (CAP) were evoked and ON function was monitored and quantified. Results: In WT, preconditioned (IPC-Ip) ON recovered significantly better (31Ϯ3 % baseline) than either sham (21Ϯ4, *pϽ0.05) or IPC-Cn (17Ϯ3, *pϽ0.05) controls. In TLR4-/-mice, recovery in the preconditioned ON (19Ϯ4 % baseline) was not significantly different from that in either the sham (16Ϯ4, NS) or IPC-Cn (15Ϯ5, NS) control ON (Fig) . Relative protective effect Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

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International Stroke Conference and Nursing Symposium Poster Presentations e299

by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from of IPC was 2.1-fold greater in WT than in TLR4-/-ON. Conclusions: These findings demonstrate that: (i) IPC induces a robust protective effect in WM and (ii) this effect is at least partially dependent on functional TLR4 signaling. This novel experimental paradigm will improve our mechanistic understanding of IPC and WM injury.

Th P153 Akt Activation Mediates Human Umbilical Cord Blood Cell Protection

Derrick Rowe, Lisa Collier, Alison Willing, Keith Pennypacker; UNIVERSITY OF SOUTH FLORIDA, Tampa, FL Background: Systemic administration of human umbilical cord blood (HUCB) cells reduces infarct volume and behavioral deficits in rats following ischemic injury. In previous studies, we reported that HUCB cells release soluble factors that protect oligodendrocytes (OL)s subjected to oxygen glucose deprivation (OGD) by increasing survival associated gene expression. Administration of HUCB cells following permanent middle cerebral artery occlusion (MCAO) elevated the protein products of these genes in OLs. Many of these factors activate gene expression via Akt kinase, which is linked to cell survival. Purpose: In the present study, we investigated the role of phosphorylated Akt (P-Akt) in HUCB cell mediated oligoprotection. Methods andResults: OL cultures were subjected to 24 hrs OGD or normoxia while coincubated with HUCB cells, HUCB cellsϩAkt inhibitor IV, or vehicle. OL viability was assessed using lactase dehydrogenase assay. As previously reported, HUCB cell coincubation rescued OLs subjected to 24 hrs OGD (nϭ6, PϽ0.05); this protection was completely blocked by the presence of Akt inhibitor IV (nϭ6, PϽ0.05). Immunohistochemistry showed that the presence of HUCB cells increased P-Akt in OLs exposed to OGD (nϭ3, PϽ0.05), whereas Akt inhibitor IV reduced this phosphorylation. P-Akt was not altered under normoxic conditions. Next, we evaluated P-Akt in the white matter of rats subjected to MCAO. HUCB cells (1x10 6 ) or vehicle were administered systemically 48 hrs post MCAO. Animals were sacrificed 6, 24, or 48 hrs following HUCB cell treatment. Immunohistochemical analysis showed a gradual increase in P-Akt in the white matter ipsilateral to the infarct which peaked at 48 hrs following HUCB cell treatment (nϭ3, PϽ0.05). P-Akt in sham and MCAO vehicle rats was unchanged (nϭ3, pϾ0.05). Because P-Akt inhibits apoptosis, we also examined activated caspase 3 in the white matter following MCAO. Caspase 3 activation was elevated at 54 and 74 hrs following MCAO (nϭ3 PϽ0.05, PϽ0. Background: Stroke in the immature brain usually presents 12-24 hours after the insult with seizures. Post-stroke neurogenesis in the SGZ of the immature brain is decreased and may contribute to the long-term cognitive impairments seen. Objective: To determine if chronic histone deacetylase inhibition after stroke in an immature brain enhances post-stroke neurogenesis. Methods: Two drug administration protocols were used. In the first (Protocol 1), unilateral carotid ligation of P12 CD1 mice was followed by trichostatin A (TSA, 5 mg/kg i.p.) or DMSO injections twice a day for 2 weeks from P17-P29, BrdU was administered from P18-P20, and animals perfused at P42. In the second (Protocol 2), TSA (2.5 mg/kg) or vehicle was given from P16-P28, BrdU administered from P24-P26, and perfusions at P42. Immunohistochemistry was performed and total counts of BrdU-labeled cells in the dentate gyrus of the hippocampus done. Results: Pilot data from protocol 1 did not indicate any significant change in DG neurogenesis in either injured or uninjured animals. Protocol 2 resulted in significant increases in DG neurogenesis (total counts) in both injured (mean ipsilateral counts: TSA (nϭ9) ϭ 85.6 Ϯ19.3 versus DMSO (nϭ4) ϭ 40.2 Ϯ 4.9, pϭ 0.049; mean contralateral counts: TSAϭ 99.6 Ϯ 15.2 versus DMSOϭ 49.9 Ϯ 3.4, pϭ 0.011) and uninjured animals (mean ipsilateral counts: TSA (nϭ5)ϭ86.6 Ϯ 3.4 versus DMSO (nϭ5) ϭ 43.7 Ϯ 2.2, pϭ0.000; mean contralateral counts: TSAϭ 97.6 Ϯ 6.1 versus DMSOϭ 45.8 Ϯ 4.2, pϭ0.000). Conclusions: The impact of TSA in this model is likely to depend on the age of the animal, duration of TSA treatment before BrdU labeling, and/or the stage in the evolution of the injury. Further work is being done to determine the extent of histone deacetylation and to determine the long-term impact of TSA-enhanced neurogenesis upon long-term functional outcomes. Improving recovery from neonatal stroke is an important long-term goal. Masaki Mogi, Fei Jing, Li-Juan Min, Jun Iwanami, Kana Tsukuda, EHINE UNIV GRADUATE SCHL MED, Tohon Ehime, Japan; Thomas Unger, Cntr for Cardiovascular Rsch, Institute of Pharmacology, Charite ´Univ Medicine, Berlin, Germany; Björn Dahlöf, Sahlgrenska Univ Hosp/Östra, Univ of Gothenburg, Gothenburg, Sweden; Masatsugu Horiuchi; EHINE UNIV GRADUATE SCHL MED, Tohon Ehime, Japan Background: Our previous studies indicate that relative stimulation of angiotensin (Ang) II type 2 (AT 2 ) receptor signaling using Ang II and Ang II receptor blockers enhances neurite outgrowth and neural differentiation, resulting in the prevention of cognitive impairment. Recently, a newly developed direct AT 2 receptor agonist, compound 21 (C21), has been reported to improve cardiac function after myocardial infarction in mice, and expected to be effective to other pathological conditions. Here we assessed the possible effects of C21 on cognitive function. Methods: Male 8 week-old C57BL6 and AT 2 receptor-null (Agtr2 -) mice were treated with C21 (0.001, 0.003, 0.01 mg/kg/day) intraperitoneal injection once a day once a day for 2 weeks. Then, mice were subjected to the Morris water maze test for 5 days to evaluate spatial memory. Cerebral blood flow was measured by 2 dimensional laser-Doppler. Excitatory post-synaptic potential (EPSP) was assessed by electrophysiological techniques. Neurite elongation was assessed using hippocampal neurons from GFP-transgenic mouse. Results: Blood pressure and mRNA expression of AT 1 and AT 2 receptors were not significantly changed between mice with or without C21 treatment. Interestingly, treatment with C21 significantly improved spatial learning in C57BL6 mice, but this effect was not observed in Agtr2 -mice. C21-mediated cognitive improvement in C57BL6 mice was attenuated by co-administration of bradykinin B2 receptor antagonist, icatibant. Cerebral blood flow was significantly increased in C57BL6 mice with C21 treatment. Furthermore, administration with C21 dose-dependently enhanced hippocampal EPSP in C57BL6 mice but not in Agtr2 -mice. C21 treatment also promoted neurite elongation. Conclusion: These results suggest that a direct AT 2 receptor agonist, C21, is expected to improve cognitive function at least in part via an increase in cerebral blood flow and an enhancement of EPSP with neurite elongation involving bradykinin 2 receptor activation.

Author Disclosures: M. Mogi: None. F. Jing: None. L. Min: None. J. Iwanami: None. K. Tsukuda: None. T. Unger: None. B. Dahlöf: None. M. Horiuchi: None.

Th P156 Pharmacologic Hsp70 Induction Confers An Anti-inflammatory Response And Protects Brain-derived Endothelial Cells From Microglial Activation

Rachid Kacimi, Midori A Yenari; UCSF, San Francisco, CA HSP70 has been shown to improve outcome from experimental stroke. We previously showed that one mechanism of its protective effect is through the inhibition of the inflammatory response accompanying ischemic stroke. In order to explore the translational relevance of HSP70 induction, we tested whether its pharmacological induction by geldanamycin (GA) or its analogues, 17AAG and radicicol might be anti-inflammatory and protective. These compounds all induce HSP70 by its inhibitory effects on HSP90. Since GA has some toxicity in humans, we also studied 17AAG and radicicol, analogues having already been studied at the clinical level in cancer patients and found to have better tolerability. Microglial BV2 cells were activated with lipopolysaccharide (LPS) plus treatment with the various HSP70 inducing compounds. Treatment was begun an hour prior to LPS application to allow for sufficient HSP70 induction. 24hr later, media and cell extracts were assayed for NO and iNOS protein; injury was examined by viability assays. Treatment of BV2 cells with GA or any of its analogs induced HSP70 in a dose dependent manner. Treatment also markedly prevented microglial activation as assayed by iNOS/NO accumulation. LPS-stimulated BV2 cells induced injury to brain derived endothelial cells (EC), and this was prevented by GA treatment (pϽ0.01). A similar protective effect was observed with both17AAG and radicicol. Our data together, showed that GA and its analogs induce HSP70 and inhibit immune responses in microglia. HSP70 induction protects endothelial Introduction: Under stroke-induced conditions of hypoxia/ischemia and nutrient deprivation, autophagy supports neuronal survival by recycling cytoplasmic proteins and organelles to regenerate amino acids and ATP. Autophagy-modulating pre-clinical in vivo studies have produced intuitively contradictoryResults: stroke lesion size is decreased when autophagy is induced or it is inhibited. Methods: To determine a mechanism for autophagy-mediated neuroprotection, PC12 cells were neuronally-induced with nerve growth factor (NGF) and transfected with siRNA against key autophagy regulatory proteins: mTOR, Beclin-1, and Bcl-2. Following siRNA transfection, the cells were treated with either the autophagic inducer rapamycin or the autophagic inhibitor chloroquine, or in combination. We hypothesized that Bcl-2 and Beclin-1 were keys to neuroprotective autophagy and that rapamycin's observed neuroprotection was a result of an increase in Bcl-2. Autophagy was induced with 1mM H2O2, simulating reperfusion injury ROS production. Samples were then used for western immunoblot to determine autophagic induction based on levels of p62 and LC3. Results: H2O2 increases LC3II and p62; treatment with rapamycin further increases these autophagy markers. Chloroquine reduces LC3II but allows the accumulation of p62, suggesting proteosomal and chaperone-mediated autophagy clearance of ROS damaged proteins has increased, whereas Macroautophagy is blocked. Rapamycin decreases the apoptosis marker cleaved LaminA. siRNA knockdown of Beclin-1 increases autophagy markers and decreases the apoptosis markers. In contrast siRNA knockdown of Bcl2 increases apoptosis (LaminA cleavage) and decreases autophagy. The levels of Bcl-2 and Beclin-1 and the ratio of these two interacting proteins may be the key to cell survival and the determinant of cytoprotective vs cytodestructive autophagy and apoptotic induction. We further postulate that the previously-observed neuroprotective effects of rapamycin may act through modulation of the levels of Bcl-2, increasing the ratio of Bcl-2:Beclin-1 during rapamycin-induced autophagy. This suggest the enhancement of cytoprotective autophagy as a potential neuroprotective therapeutic approach.

Th P158 Acute Rosiglitazone Treatment during Reperfusion is Neuroprotective of Hyperglycemic Stroke but Does Not Limit Edema

Marilyn J Cipolla, Julie G Sweet; Univ of Vermont, Burlington, VT Objectives: Hyperglycemic (HG) stroke is thought to worsen outcome through enhanced oxidative and inflammatory processes. We tested the hypothesis that acute rosiglitazone (Rosi) treatment, a PPAR gamma agonist with anti-inflammatory and anti-oxidant properties, during reperfusion would limit stroke damage. Methods: Male Wistar rats (350-380g) that were normoglycemic (NG, nϭ36) or HG (blood glucose 280-350 mg/dL) for 5-6 days by STZ injection (nϭ36) underwent 2 hours of MCA occlusion followed by 2 hours of reperfusion. Animals were treated IV with either Rosi (1 mg/kg), Rosi ϩ Tempol (50 mg/kg) or vehicle (saline) 10 minutes prior to reperfusion. Infarct and edema were measured using TTC and wet:dry weights, respectively. CBF was measured using laser Doppler. Blood gases were maintained within normal physiological ranges. Results: In vehicle treated animals, HG stroke increased infarction vs. NG (corrected for edema: 17.2Ϯ3.2% vs. 5.2Ϯ3.1%; PϽ0.01). Acute Rosi treatment decreased infarction in HG animals to 8.5Ϯ2.5% (pϽ0.05 vs. HG vehicle) but had no effect on NG animals (6.5Ϯ2.7%; pϾ0.05 vs. NG vehicle). The combined treatment of RosiϩTempol eliminated the protection as this group had similar infarct as vehicle treatment (16.5Ϯ4.5%; pϾ0.05 vs. HG; Figure 1). All groups had increased water content in the ipsilateral vs. contralateral hemisphere, but neither treatment had any effect of edema as the percent water content of the ipsilateral hemispheres were similar between vehicle, Rosi and RosiϩTempol groups (81.4Ϯ0.03%, 81.7Ϯ0.3% and 80.6Ϯ.9%; PϽ0.01 vs. Ipsi; pϾ0.05 vs. vehicle). The lack of protection with the combined Rosi ϩ Tempol treatment was associated with limited reperfusion suggesting an effect on CBF that caused greater ischemia. Conclusions: These results suggest that acute Rosi treatment during reperfusion is neuroprotective, but not vascular protective, during HG stroke as infarction decreased but edema was not affected. The combination of Tempol ϩ Rosi increased infarction, possibly due to an effect on CBF that increased the perfusion deficit. The damaging effect of RosiϩTempol under these conditions may be due to a more pro-oxidative state that altered the effectiveness of these compounds.

Author Disclosures: M.J. Cipolla: Research Grant; Significant; NIH. J.G. Sweet: None.

Th P159 Mineralocorticoid Receptor Activation Is Involved In Middle Cerebral Artery Remodeling In Life-long Obesity In Sprague-dawley Rats

Paulo W Pires, Jonathon L McClain, Anne M Dorrance; Michigan State Univ, East Lansing, MI Obesity is a risk factor for the development of hypertension, and chronic hypertension leads to middle cerebral artery (MCA) remodeling and increased damage after cerebral ischemia. The mineralocorticoid receptor (MR) is linked to MCA remodeling, and we have previously shown that plasma levels of the mineralocorticoid aldosterone are increased 4-fold in our model of obesity. Hence, we hypothesized that MR antagonism would reduce MCA remodeling and damage after cerebral ischemia in rats fed a diet rich in fat and carbohydrates. Three week-old male Sprague-Dawley rats were fed a high-fat (HF) diet containing 36% fat and 36% carbohydrate (nϭ7), or HF plus the MR antagonist canrenoic acid (the active metabolite of spironolactone, HFϩCanr, nϭ8) or regular chow (RC, nϭ 7) for 18 weeks. MCA tone generation and passive structure were analyzed by pressure myography over a range of intralumenal pressures. Pial blood flow pre-ischemia, post-ischemia and 24 hour post-ischemia was measured by scanning laser Doppler and is expressed as percentage of the contralateral hemisphere blood flow (%CBF). Permanent cerebral ischemia was performed by MCA occlusion (pMCAO) for 24 hours and infarct size was measured as % of the infarcted hemisphere (%IH). Data were analyzed by Two Way Repeated Measures ANOVA (MCA structure) or by One Way ANOVA (pMCAO), and are presented as meanϮSEM. At 80 mmHg, HF treatment promoted an increase in MCA wall thickness (RC,15.1Ϯ0.6;HF,21.8Ϯ1.3;HFϩCanr,15.3Ϯ0.9m,PϽ0.001), wall cross-sectional area (RC, 12654Ϯ470; HF, 17238Ϯ943; HFϩCanr, 12630Ϯ652m2, PϽ0.05) and wall-to-lumen ratio (RC, 0.06Ϯ0.002; HF, 0.10Ϯ0.007; HFϩCanr, 0.06Ϯ0.005, PϽ0.001). MR antagonism prevented these alterations. HF caused a trend towards a decrease in lumen diameter and Canr prevented this (RC, 251Ϯ7; HF, 231Ϯ5; HFϩCanr, 248Ϯ9m). Tone generation was not different between experimental groups (RC,39.3Ϯ8;HF,49.1Ϯ9;HFϩCanr,47.7Ϯ8,%tone). Pial blood flow 24 hours post-ischemia was significantly decreased in HF, and there was a trend towards improvement in HFϩCanr (RC, 71Ϯ3; HF, 55Ϯ4; HFϩCanr, 64Ϯ3; %CBF, pϭ0.007 RC vs HF). Similarly, there was a trend towards an increase in infarct size after pMCAO in HF, and canrenoic acid prevented it (RC,32.0Ϯ4;HF,46.1Ϯ8;HFϩCanr,32.7Ϯ5,%IH,pϭ0.09). These results suggest that the elevated aldosterone plasma observed in obese rats is a major contributor for MCA wall hypertrophy. The increase in wall hypertrophy, even without reducing lumen diameter, was sufficient to reduce pial blood flow 24 hours post-ischemia in HF and promote an increase in infarct size. Importantly, MR antagonism attenuated these trends, suggesting a potential protective role against damage after permanent cerebral ischemia. Therefore, MR antagonism might be a valuable therapy for primary prevention of ischemic stroke.

This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: P.W. Pires: None. J.L. McClain: None. A.M. Dorrance: None.

Th P160

The Role of Mammalian Target of Rapamycin in Focal Cerebral Ischemia: The Link between TSC2 and mTOR Signaling Pathway Yong-Joo Ahn, Seo-Kyoung Hwang, BWH/HMS, Cambridge, MA; Sang-Yeul Han, Michael A. Moskowitz, MGH/HMS, Boston, MA; James K. Liao, Hyung-Hwan Kim; BWH/HMS, Cambridge, MA Background: Mammalian target of rapamycin (mTOR) mediates various functions such as cell survival, obesity, and cellular responses to injury including the pathologenic response to ischemic stroke. However, the signaling mechanism linking mTOR inhibition to focal cerebral ischemia is unknown. We postulate that the activation of mTOR may induce neuroprotective effects via TSC2/mTOR/S6 pathway. Methods: To investigate whether activation of mTOR is neuroprotective, we used a transient focal cerebral ischemia model. Wild-type and TSC2ϩ/mice (20-22g) were administered either vehicle or rapamycin (5 mg/kg, i.p., 1d and 5d), before MCAo. After 2 hrs of MCAo followed by 22 hrs of reperfusion, infarct size was determined with TTC staining and protein levels of TSC2, mTOR, and S6 were assessed in the ischemic core and contralateral (non-ischemic core) hemisphere region. Results: Compared to vehicle, mTOR/S6 level was decreased in ischemic regions during ischemia (0.5, 1, 2h MCAo). After reperfusion (after 2h MCAo), phospho-S6 was rapidly upregulated. Acute administration of rapamycin had no effect on cerebral infarct size in WT mice but chronic administration of rapamycin exhibited significantly increased infarct size and higher NDS following MCAo. Compared to vehicle, TSC2ϩ/-mice showed increased mTOR/S6 levels in the brain and reduced cerebral infarct size (64.2 Ϯ 5.96; nϭ7 vs 92.6 Ϯ 6.08, nϭ7, PϽ0.01). Conclusions: These findings indicate that the inhibition of mTOR worsens cerebral infarct size while the activation of mTOR in TSC2ϩ/mice reduces cerebral infarction. Therefore, TSC2 provides an important link between neuroprotection and the mTOR signaling pathway in focal cerebral ischemia.

Author Disclosures: Y. Ahn: None. S. Hwang: None. S. Han: None. M. Moskowitz: None. J. Liao: None. H. Kim: None.

Th P161 Apyrase, APT102, Improves the Beneficial Effect of rt-PA In Experimental Thromboembolic Stroke

Guanghua Sun, Xiurong Zhao, James C Grotta, Sean Savitz, Univ of Texas-Houston, Houston, TX; Ridong Chen, APT Therapeutics Inc, St Louis, MO; Jaroslaw Aronowski; Univ of Texas-Houston, Houston, TX Background: Inhibition of platelets after ischemic stroke could help to maintain vascular patency and assist rt-PA in recanalization. However, use of available platelet inhibitors may be associated with the increased risk of intracerebral hemorrhage (ICH). Objective: To demonstrate in a clinically relevant model of thromboembolic stroke whether novel genetically engineered soluble human apyrase APT102, which has improved enzymatic activity and more potent platelet inhibition capacity than the wild-type form, has therapeutic effect without increased risk for ICH, and also whether APT102 has a synergistic effect with rt-PA without increased risk for ICH. Method: Long Evans rats subjected to thromboembolic stroke were randomly divided into 4 treatment groups: (1) control (saline treated); (2) APT102 at 2.25 mg/kg, (3) rt-PA (at 10 mg/kg) and (4) APT102 at 2.25 mg/kg plus rt-PA. All treatments were initiated at 2 hours following thrombus injection into the internal carotid artery. Infarct volume, incidence of ICH and behavioral deficit were assessed at day 3 after the stroke. Results: While APT102 alone did not produce significant effect on stroke outcome as compared to saline control (123.1ϩ/-19.9 vs. 119.9ϩ/-26.4mm 3 ). APT102 combined with rt-PA significantly reduced infarct volume (71.2ϩ/-16.1) compared to rt-PA alone and saline treated rats (pϽ0.05). Analysis of behavioral deficit was performed on the same groups and APT102 combined with rt-PA reduced behavioral deficit as compared to rt-PA alone and saline treated rats (pϽ 0.05). Visual analysis of brains demonstrated that 2 out of 11 rats with saline and 5 out of 11 animals treated with rt-PA alone demonstrated petechial hemorrhages within the ischemia-affected aspects of the brain. In contrast, no hemorrhage was observed in any of 10 rats treated with APT102 with or without rt-PA. Conclusions: This study provides the first evidence that synthetic apyrase used to inhibit platelets after ischemic stroke may be useful in improving the effect of rt-PA without increasing the risk of ICH.

Author Disclosures: G. Sun: None. X. Zhao: None. J.C. Grotta: None. S. Savitz: None. R. Chen: Other Research Support; Significant; NIH grant. Ownership Interest; Significant; yes. J. Aronowski: Research Grant; Significant; NIH grant.

Th P162 Synergistic Memory Impairment Through The Interaction Of Chronic Cerebral Hypoperfusion And Amlyloid Toxicity In A Rat Model Of Combined Injury

Hahn Young Kim, Bo-Ryoung Choi, Neurology Konkuk Univ. Hosp, Seoul, Korea, Republic of; Jung-Soo Han; Konkuk Univ, Seoul, Korea, Republic of Background Clinical studies have demonstrated that Alzheimer's disease (AD) and vascular dementia share common cardiovascular risk factors. Further, vascular and AD-related pathology have been shown to coexist in the brain of dementia patients. We investigated how cognitive impairment could be exacerbated in a rat model of combined injury through chronic cerebral hypoperfusion and amyloid ␤ (A␤) toxicity. Methods Wistar rats received permanent ligation of bilateral common carotid arteries (BCCAo), modeling chronic cerebral hypoperufison at 12 weeks. Additional bilateral intracerebroventricular A␤ used to model A␤ toxicity was injected at 15 weeks in the combined injury group. The experimental animals were divided into four groups using a two-by-two table of BCCAo or A␤ toxicity, including a sham group, as well as BCCAo, A␤ toxicity and BCCAo-A␤ toxicity groups (nϭ7 per group). Four weeks after sham operation or BCCAo, a Morris water maze task was performed to evaluate spatial memory. Six weeks after sham operation or BCCAo, histologic study including thionin staining, neuroinflammatory markers (OX-6, GFAP), and AD-related pathology (A␤, amyloid precursor protein, tau-2) was performed. Results Spatial memory impairment was synergistically exacerbated in BCCAo-A␤ toxicity group compared to BCCAo or A␤ toxicity group (pϽ0.001). Neuroinflammation with astroglial and microglial activation was observed in multiple white matter lesions and the hippocampus in BCCAo and BCCAo-A␤ toxicity groups. In rats with BCCAo and BCCAo-A toxicity group, APP and tau-2 staining showed relatively enhanced immuno-reactivity with sporadic cellular or clustered patterns in the cortical or deep gray matter and sporadic cellular patterns in the cortical gray matter, respectively. Conclusions: Our experiment supported experimental evidence for the clinical hypothesis of the deleterious interaction between chronic cerebral hypoperfusion and A␤ toxicity. Chronic cerebral hypoperfusioninduced impaired clearance of endogenous or exogenous A␤ may exacerbate cognitive impairment through the pertubated equilibrium between the brain and blood compartments in AD-related pathology.

Author Disclosures: H. Kim: Research Grant; Modest; Korea Research Foundation Grant funded by the Korean Government (KRF-2008-331-E00298). B. Choi: None. J. Han: None.

Th P163 Reperfusion rather than Ischemia drives the Formation of Ubiquitin Aggregates in the Mouse Neocortex after Middle Cerebral Artery Occlusion

Karin Hochrainer, Katherine Jackman, Timo Kahles, Lidia Garcia-Bonilla, Josef Anrather, Costantino Iadecola; Weill Cornell Med College, New York, NY Background: The ubiquitin-proteasome system (UPS) is the main cellular pathway for degradation of short-lived and misfolded proteins. Thus, target proteins are constantly tagged for selective destruction in proteolytic complexes called proteasomes by covalent attachment of ubiquitin molecules. In brain as in other organs the UPS is fundamental for normal cellular function. In the brain, disruption in the UPS resulting in protein aggregation has mostly been associated with neurodegenerative diseases, but some reports have shown that cerebral ischemia-reperfusion leads to accumulation of ubiquitinated protein aggregates as well (Stroke 38:3230, 2007). However, the factors triggering ubiquitination and their relationship to the outcome of cerebral ischemia remain poorly understood. Here we used a mouse model of middle cerebral artery occlusion (MCAO) to investigate the relationship between ubiquitination and duration of the ischemic insult, presence or absence of reperfusion and tissue damage. Methods: The MCA was occluded for 15 min, 30 min or permanently in male C57BL6 mice (nϭ3-5/group) using an intravascular filament. Ubiquitination in ipsilateral neocortex and striatum was assessed by western blotting at different time points after ischemia. Results: Mice sacrificed immediately after 30 min of MCAO (with no reperfusion) had no detectable ubiquitin aggregates, like the sham-operated group. However, 30 min of MCAO followed by reperfusion led to substantial ubiquitinated protein aggregates, which were stably elevated at 1, 3, 6, 9 and 12 hours, and declined at 24 and 72 hours. Ubiquitin-aggregate formation was restricted to the cortex and to a lesser extent the striatum. 15 min of MCAO with reperfusion, which produces only minimal tissue damage, resulted in levels of ubiquitination indistinguishable from those produced by 30 min MCAO, which results in substantial damage (infarct volume at 72 hours: 57Ϯ8mm3; JCBFM 29:66, 2009). In contrast, in permanent MCAO no ubiquitin aggregates were observed after 1, 3, 6 and 24 hours, despite the development of massive tissue damage (infarct volume at 24 hours: 72Ϯ6mm3; JCBFM 29:66, 2009). Conclusions: Reperfusion rather than ischemia leads to the appearance of ubiquitinated proteins. The molecular mechanism by which the re-establishment of blood flow triggers ubiquitination remains to be elucidated, but they may include formation of free radicals. Presence of ubiquitinated proteins may be a marker of reperfusion and may identify potentially salvageable tissue.

Author Disclosures: K. Hochrainer: None. K. Jackman: None. T. Kahles: None. L. Garcia-Bonilla: None. J. Anrather: None. C. Iadecola: None.

Th P164 Moderate Hypothermia Attenuates Peripheral Immunodepression Caused by Stroke in Rats

Lijuan Gu, Xiaoxing Xiong, Takashi Ito, Jessica Lee, Sheri Krams, Gary K Steinberg, Heng Zhao; Stanford Univ, Stanford, CA Background and Purpose: Stroke results in peripheral (extracerebral) immunodepression occurs with a corresponding reduction in spleen size, while robust inflammation appears in the injured brain. We used a focal ischemic rat model to investigate the protective effects of moderate hypothermia (30 o C), a robust inhibitor of ischemic infarction, on the inflammatory response in the brain and peripheral immune suppression. Methods: Focal ischemia in the cerebral cortex was induced by permanent occlusion of the left distal MCA and 60 min occlusion of the bilateral CCA under intra-ischemic normothermia (37 o C) and moderate hypothermia (30 o C) in SD rats. We used quantitative RT-PCR to quantify mRNA expression levels of various cytokines and chemokines in the brain, spleen, liver, and lung at 5, 24, 72h after stoke, and flow cytometry to characterize lymphocyte subpopulations and macrophages at 72h after stroke. We then detected the proliferative response of splenocytes in vitro with a [ 3 H] thymidine incorporation assay. At last, subcutaneous injection of Ovalbumin (OVA) was used to measure a delayed-type hypersensitivity (DTH) reaction in the ears, which represents immune function in vivo. Results: In the ischemic brain, stroke increased genes expression of IL-1␤, TNF-␣, IL-2, INF-␥, IL-10, MIP-2, iNOS (PϽ0.05), and tended to increase IL-4 and COX-2. Hypothermia inhibited expression of the former group, but had no significant effects on the latter two genes. No significant changes in gene expression were seen in the spleen, liver and lung, except for IL-4 in the spleen, which significantly decreased 72h after stroke, and Introduction: The effect of the statin pre-treatment (SP) on the outcome of patients with intracerebral hemorrhage (ICH) is inconsistent across published studies. We evaluated whether an association exists between prior treatment with statins and mortality. Moreover, we included our results in a meta-analysis with other reported studies. METHODS We prospectively studied consecutive patients with spontaneous supratentorial ICH within the first 24 hours after stroke onset. As prognostic predictors we analyzed age, volume of the hemorrhage, Glasgow coma scale (GCS) score, and current treatment with any statin. We performed bivariate analyses and a logistic regression analysis, the dependent variable being death at 3-months follow-up. We also performed a meta-analysis by adding our results to five previously published studies providing data on SP and mortality after ICH. RESULTS We studied 109 patients, with a mean age of 74.6Ϯ10.6 years, 51% of them were men. Mortality at 3 months was 30%, and 21% were currently receiving statins at the time of stroke. In bivariate analysis, increasing age (pϽ0.0001), higher hematoma volume (pϭ0.001) and lower GCS (pϽ0.0001) were associated with increased mortality. Mortality was non-significantly increased in the SP group compared to the non-SP group (43.5% vs 27%, pϭ0.13). Independent predictors of mortality in the logistic regression analysis were: Age (OR 1.099 per year, pϭ0.023), Volume (OR 1.022 per ml, pϭ0.015) and GCS (OR 0.694 per point, PϽ0.0001). Prior treatment with statins was not an independent risk factor for death (OR 2.11,pϭ0.32). The meta-analysis of Background and Purpose: Intraventricular extension of intracerebral hemorrhage (IVH) is a critical disease severity factor and an independent predictor of poor outcome. Surgical Trial in ICH (STICH) and NovoSeven trial have recently underscored the impact of IVH volume and its alteration on recovery and survival after ICH. Routine measurement of IVH volume, however, has been impeded by difficult characterization of clots and requirement for time consuming computer-based planimetric analysis. The IVH Score (IVHS) was developed by Hallevi et al (2009) to assess severity of IVH and to rapidly estimate IVH volume at bedside. The aim of this study was to prospectively evaluate the external validity of the IVHS as a useful tool for assessing IVH volume in the setting of ICH. Methods: Spontaneous ICH patients with IVH on admission computed tomography (CT) scan were prospectively enrolled into the study between February 2009 and May 2010. All CT scans performed within 6 days of onset were evaluated for IVHS according to the methods described by Hallevi et al (1). IVH volumes were estimated based on IVHS and compared to IVH volumes measured with computer-assisted planimetric analysis. Results: A total of 126 CT scans were performed on 51 patients during the study period. The mean estimated IVH volume was not significantly different from the mean measured IVH volume (15.45 Ϯ 18.57 ml versus 14.88 Ϯ 15.55 ml, respectively; p ϭ 0.499). Regression analysis revealed a strong exponential relationship between IVHS and measured volumes (R2 ϭ 0.795, p Ͻ 0.001) and a strong linear relationship between estimated and measured IVH volumes (R2 ϭ 0.743, p Ͻ 0.001). Furthermore, they were comparable to those reported by Hallevi (R2 ϭ 0.75, PϽ0.001 and R2 ϭ 0.8, PϽ0.001, respectively). Conclusions: To our knowledge, this is the first study to validate the performance of the IVHS as a tool for rapid approximation of IVH volume in the setting of spontaneous ICH. The strengths of association between IVH scores and estimated volumes, and between estimated and measured volumes are similar to those of Hallevi et al, suggesting that the IVHS can be used with reasonable reliability among different centers. ( 1

Th P175 Perihematoma Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: a CT Perfusion Study

Alexander Tamm, Troy Bornes, Thomas Jeerakathil, Negar Asdaghi, Derek Emery, Kenneth Butcher; Univ of Alberta, Edmonton, Canada Background: Although global cerebral perfusion pressure (CPP) can be estimated by the difference between mean arterial pressure (MAP) and intracranial pressure, local CPP is more predictive of regional tissue fate. Hypothetical decreases in CPP in the perihematoma region have been cited as a rationale for a conservative approach to acute blood pressure (BP) control as aggressive antihypertensive use may further reduce CPP resulting in ischemia in this region.

Local CPP has been shown to be proportional to the ratio of cerebral blood flow (CBF) to cerebral blood volume (CBV). We assessed local CPP in acute intracerebral hemorrhage (ICH) patients, using CT perfusion (CTP) source data. Given that cerebral blood flow decreases in the perihematomal region, we hypothesized that cerebral perfusion pressure would concomitantly decrease. Methods: CTP imaging was performed in acute ICH patients. All patients were acutely hypertensive and systolic blood pressure was treated to a target of mmHg or mmHg prior to the CTP scan. Maps of CBF and CBV were generated using a singular value deconvolution algorithm. In addition, maps of CPP were calculated as CBF/CBV. Region of interest analysis was completed in a 1 cm perihematoma region, contralateral homologous regions and both hemispheres. Results: 22 patients were imaged with a median time from onset to CTP of 15.2 ) hrs. The mean (ϮSD) hematoma volume was 16.8Ϯ20.2 mls. The mean systolic and diastolic BP at the time of the CTP scan were 155Ϯ14 and 80Ϯ13 mmHg respectively. Perihematoma CBF (31.5Ϯ5.5 ml/100g/min) was lower than that in contralateral regions (34.1Ϯ6.1 ml/100g/min, PϽ0.001). Similarly, there was a reduction in perihematoma CBV (2.83Ϯ0.56 ml/100g) compared to contralateral regions (3.08Ϯ0.55 ml/100g, PϽ0.001). Perihematoma CPP (13.9Ϯ2.3 min -1 ) was not significantly different than that in the contralateral homologous regions (13.8Ϯ2.5 min -1 ; pϭ0.73). Ipsilateral hemispheric CPP (14.0Ϯ2.6 min -1 ) was also comparable to the contralateral hemispheric CPP (13.8Ϯ2.1 min -1 , pϭ0.28). There was no relationship between perihematoma CPP and hematoma volume (rϭ0.02, [-0.70,0.10]) or BP at the time of the CTP scan (systolic BP,rϭ0.02,0.10];diastolic BP,rϭ0.03,0.11]); or MAP, rϭ0.03, [-0.06,0.13]). In addition, treatment of blood pressure did not appear to affect CPP as perihematoma CPP was not related to changes in systolic (rϭ-0.01, [-0.07,0.05]), diastolic (rϭ0.04, [-0.03,0.12]) or mean arterial pressure (rϭ0.03, [-0.06,0.11]) between initial presentation and the time of the CTP scan. Conclusions: Perfusion pressure of tissue surrounding the hematoma is maintained in acute ICH patients. Hematoma volume and blood pressure management do not affect perihematoma CPP. These results provide further support for the safety of early blood pressure treatment in ICH.

Introduction and hypothesis:

Currently it is unclear which patients with an intracerebral hemorrhage (ICH) may benefit from intracranial vascular imaging. We hypothesized that characteristics of the appearance of the ICH on non contrast CT (NCCT) may help in discriminating between patients with and without a identifiable vascular malformation. Methods: We selected patients with primary ICH (PICH, ICH without a macroscopic vascular lesion detected, nϭ30) and secondary ICH (SICH) caused by rupture of an AVM (nϭ25) or an aneurysm (nϭ30). ICH location and relation to the ventricles, subarachnoid space, subdural space, frontal operculum, Sylvian fissure or interhemispheric fissure were assessed, as were features of the ICH itself: volume, shape, density, regularity of the border, and presence of mass effect and edema. Each admission NCCT was assessed independently by two observers who were blinded for demographics and underlying etiology. Subsequently they were asked to list the most likely cause of the ICH. We investigated differences in characteristics between SICH and PICH by calculating relative risks (RR) with 95% confidence intervals (CI). Results: A deep location was not observed in aneurysmal ICH and less frequent in AVM ICH (24%) than in primary ICH (60%;RR 0.4, 95% CI 0.2-0.8). Extension to the Sylvian fissure was observed more often in secondary ICH than in PICH (RR 3.8,). Extension to the frontal operculum was exclusively seen in SICH (67% of aneurysmal ICH and 16% of AVM ICH). No differences in shape (RR 1.0, 95% CU 0.95-1.02), density (RR 1.2 (95% CI 0.7-1.8), regularity of the border (RR 1.0, 95% CI 0.7-1.5) and presence of edema (RR 1.1, 95% CI 0.9-1.5) were found between SICH and PICH. The majority of aneurysmal ICH (97%) and PICH (93%) was diagnosed correctly on NCCT, whereas sixteen AVM-ICH were not identified (64%). Conclusions: SICH and PICH do not differ regarding hematoma characteristics, but do differ in location and extension of the hematoma. AVM as underlying cause of the hematoma goes often undetected on NCCT.

Author Disclosures: C.J.J. van Asch: None. A.C.M. Kool: None. G.J.E. Rinkel: None. C.J.M. Klijn: Research Grant; Significant; This study was supported by a Netherlands Heart Foundation grant (number 2007B048, to C.J.M. Klijn)..

Th P177 Impact of Interhospital Transfer on Complications and Outcome after Intracranial Hemorrhage

Ashley Catalano, Surekha Jadhav, Errol Gordon, H. R. Winn, Jennifer A Frontera; MOUNT SINAI SCHOOL OF MEDICINE, New York, NY Introduction: Interhospital transfer of patients with intracranial hemorrhage to tertiary centers can offer improved care, but comes at the cost of potential morbidity and mortality related to transfer. Prolonged time of transfer may further worsen outcome. In this study, we assess the effect of transfer and transfer time on admission clinical status, hospital complications, length of stay (LOS) and 3-month neurological outcome. Methods: A prospective study was conducted between 2/2008-6/2010 of patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) and subdural hemorrhage (SDH), admitted to the neuro-ICU at a tertiary-care academic hospital. Demographic data, clinical history, ICU admission clinical status (assessed by NIHSS, GCS and APACHE-2), transfer hospital distance, time to transfer, medical complications and LOS were recorded. Functional outcome was assessed at 3-months using the Barthel Index, Modified Rankin Scale (mRS), Lawton Instrumental Activities of Daily Living Scale and the Telephone Interview of Cognitive Status (TICS). Results: Of 257 total patients, 120 (47%) were transferred and 137 (53%) were admitted directly from our ED. Eighty-six (34%) had SAH, 80 (31%) had ICH and 91 (35%) had SDH. The median age was 62 (22-94), 37% were white, 38% employed and 86% insured. The median transfer hospital distance was 7.4 miles (1.4-159). The median transfer time was 190 minutes 446). Initiation of transfer during business hours predicted a shorter time to bed assignment (Pϭ0.048), but hospital distance and weekend/holiday transfers did not impact transfer time. Transferred Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

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International Stroke Conference and Nursing Symposium Poster Presentations e305

by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from patients were significantly less educated, less likely to be insured, and more frequently had SAH as a diagnosis than directly admitted patients (all PϽ0.05). Admission GCS, NIHSS and APACHE-2 scores did not differ between transfers and direct admits and were not significantly related to transfer time. Complications did not differ between transferred and directly admitted patients, however, longer transfer time was associated with aneurysm rebleed (OR 1.0, 95%CI 1.0-1.1, Pϭ0.030), hydrocephalus requiring drainage (OR 1.0, 95%CI 1.0-1.1, Pϭ0.041), tracheostomy (OR 1.0, 95%CI 1.0-1.1, Pϭ0.039) and peg placement (OR 1.0, 95%CI 1.0-1.1, Pϭ0.004). Overall, transferred patients had worse cognitive outcome at 3 months (OR 4.1, 95% CI 1.2-14.0, Pϭ0.025) and longer ICU LOS (8 versus 5 days; Pϭ0.003) compared to direct admits. Longer transfer time was not associated with neurological outcome or LOS. Conclusions: Despite similar admission clinical status, transferred patients had worse 3-month cognitive outcomes and longer ICU LOS compared to directly admitted patients. Prolonged time to interhospital transfer was associated with a small, but significant risk of aneurysm rebleed, hydrocephalus requiring treatment, tracheostomy and peg placement. Background and Purpose: Non-ambulatory patients with acute intracerebral hemorrhage (ICH) are at high risk of developing deep venous thrombosis (DVT). DVT prophylaxis in these patients is a core measure for the Joint Commission (TJC) certified Primary Stroke Centers in the U.S.. Little is known about DVT prophylaxis after ICH in China. We sought to assess the use of DVT prophylaxis after ICH in Chinese urban hospitals, and to explore the potential reasons associated with non-compliance with this measure. Methods: China National Stroke Registry (CNSR) was nationwide stroke registry funded by the Chinese government that included a representative sample of 132 urban hospitals across China. From June 1, 2007, through May 31, 2008, we abstracted data from CNSR prospectively to determine DVT prophylaxis status in consecutive ICH patients, including any reasons for non-compliance with DVT prophylaxis. Compliance was defined as pharmacological prophylaxis such as unfractioned heparin, low molecular weight heparin and heparin analog, or physical prophylaxis such as intermittent pneumatic compression, compression stockings and early mobilization. The reasons for failing to perform DVT Prophylaxis consisted of contraindication for anticoagulation, contraindication for intermittent pneumatic compression and patient or relative refusal. Results: A total of 5136 patients with a diagnosis of ICH were included, of which 39.3% were female. The average age was 65.0 Ϯ 12.6 years. Among these, 3655 (71.2%) were non-ambulatory, of whom 685 (18.7%) received DVT prophylaxis, including 7(1.0%) with unfractioned heparin, 7(1.0%) with low molecular weight heparin, 1(0.1%) with heparin analog, 86 (12.4%) with intermittent pneumatic compression, 21 (3.1%) with compression stockings, 540 (78.8%) with early mobilization. Among the 2651(72.5%) who were not placed on DVT prophylaxis, the vast majority (nϭ2556, 96.4%) was due to physicians' opinion that ICH was a contraindication for anticoagulation or concerns of hemorrhage extension and extracranial hemorrhage after anticoagulation. Only 21 (0.8%) patients had documented real contraindication for anticoagulation. Other reasons for non-use of DVT prophylaxis included patient or relative refusal (nϭ13, 0.5%), and contraindication for intermittent pneumatic compression (nϭ61, 2.3%). Conclusions: In China, the proportion of patients with ICH receiving DVT prophylaxis was extremely low, especially pharmacological prophylaxis. Concern of hemorrhage extension after anticoagulation by physicians and failing to adherence to the guidelines in China for the management of ICH was main reason of non-use of DVT prophylaxis. Further studies are needed to elucidate specific barriers to DVT prophylaxis and to develop targeted quality improvement strategies that may target physicians as well as Chinese healthcare system.

Background: Cerebral microbleeds (CMBs) detected by T2*-weighted MRI have been described as an indicator of hypertension, hemorrhagic stroke, and small vessel diseases. The association between infective endocarditis and CMBs has been reported recently, but the clinical significance of CMBs in patients with infective endocarditis has not been clarified. Methods: Among 53 patients with definite infective endocarditis admitted to two medical centers in Osaka, Japan, between January 2006 and June 2010, 26 consecutive patients who underwent brain MRI including T2*-weighted sequences were enrolled. We hypothesized that CMBs in patients with infective endocarditis would associate with vascular vulnerability such as mycotic aneurysm or infectious angitis. We therefore examined incidence of intracerebral hemorrhage (ICH) after the MRI examination and investigated the association between ICH and CMBs or other clinical characteristics. Results: ICH was observed in 9 patients (35%) within 30 days after the MRI examination. CMBs were identified in 14 patients (54%) and 66% of CMBs existed in cortical region. There were more CMBs observed in patients who developed ICH than those without ICH (pϽ0.001) (Figure). In univariate analyses, the presence of preceding ICH (odds ratio, 9.4; 95% confidence interval, 1.3-67.6) and the number of CMBs Ն3 (16.3; 2.2-121.4) were significantly associated with the incidence of ICH. In multivariate logistic regression model, adjusted odds ratio of CMBs per unit was 1.15 (1.01-1.40; pϭ0.035). Conclusions: In addition to preceding ICH, the presence of CMBs was a strong predictor of impending intracerebral hemorrhage in patients with infective endocarditis. CMBs might represent vascular vulnerability attributed to infective endocarditis.

Th P180 Glomerular Filtration Rate Is Not Associated With Hematoma Volume Or In-Hospital Mortality In Spontaneous Intracerebral Hemorrhage

Shawna Cutting, Chloe Castro, Vivien H Lee, Shyam Prabhakaran; Rush Univ Med Cntr, Chicago, IL Objective: To determine if intracerebral hemorrhage (ICH) patients with kidney dysfunction (as evidenced by low glomerular filtration rate, GFR) have increased hematoma volume or in-hospital mortality compared to those with normal kidney function. Introduction: There is growing interest in the association between abnormal kidney function and spontaneous ICH. Patients with low GFR are known to have endothelial and platelet dysfunction. Those with low GFR are at greater risk for hemorrhagic than ischemic stroke and experience worse long-term outcomes following stroke. It is unclear if patients with a low GFR have larger volume hemorrhages or worse short-term outcome than those with normal kidney function. Design/ Methods: We retrospectively reviewed the charts of 617 consecutive patients diagnosed with spontaneous ICH at our institution between 2006 and 2010. We collected data on patient demographics, admission creatinine, size and location of bleed, and disposition at discharge. Patients with end-stage renal disease (ESRD) and acute kidney injury (defined as rise in creatinine of 0.3 over baseline) were excluded from our analysis. GFR was calculated using the MDRD equation, and patients were divided into two groups based on GFR (Ͼ 60 vs. Ͻ 60). Results: Of 617 patients, 143 with acute kidney injury or ESRD were excluded, leaving 474 patients for analysis (mean age 61 years; 51% female; 55% black; mean GFR 74.3; 24.3% had GFR Ͻ 60). The median volume of hemorrhage was 11.4 (IQR 3.4-35.0) mL. Two hundred and twenty eight (48.1%) hemorrhages were in the basal ganglia; 71 (15.0%) were infratentorial; and 175 (36.7%) were lobar. There was no correlation between admission GFR and volume of hemorrhage (r s ϭ 0.016, p ϭ 0.737), irrespective of hemorrhage location and those with GFR Ͻ 60 vs. Ͼ 60 had similar ICH volumes (p ϭ 0.825). Mean GFR was similar in those with survived or died (74.3 vs. 74.3, p ϭ 0.981) and there was no significant association between GFR and discharge disposition. Conclusions: Although some studies have suggested that low GFR is associated with poor outcome following hemorrhagic stroke, we were unable to substantiate this relationship in a large cohort of ICH patients. Furthermore, hematoma volume was not correlated with GFR. Future studies should explore whether there is a relationship between GFR and acute hematoma expansion.

Th P185 Analysis Of The Predicting Factors In The Deterioration Of Acute Ischemic Stroke On Demographic, Clinical Characteristics And Neuro-radiological Findings

Nobukazu Miyamoto, Yasutaka Tanaka, Yuji Ueno, Ryota Tanaka, Nobutaka Hattori, Takao Urabe; Dept of Neurology, Juntendo U, Tokyo, Japan Introduction:; One third of patients with acute ischemic stroke develop early neurological worsening, a situation associated with increased mortality and long-term functional disability. The underlying basic mechanisms involved are not completely understood, although biochemical factors have been suggested. It is important to prevent patients with acute ischemic stroke from deteriorating. Age, blood pressure, diabetes mellitus, clinical symptoms, and duration of symptoms have been reported to be correlated with stroke after TIA. We investigated the predicting factors for the deterioration of acute ischemic stroke within 1 week from onset. Methods; We retrospectively investigated 537 patients who were admitted within 2 days of the occurrence of an acute ischemic stroke, between April 2007 and March 2009. Deterioration of neurological findings was defined as the worsening of 3 points or more on the National Institute of Health Stroke Scale (NIHSS) score during admission to the hospital within 1 week. We retrieved the demographic and clinical characteristics of stroke patients, medications, stroke subtypes, and functional status upon discharge. All variables with a PϽ0.2 on univariate analysis were entered into logistic regression analysis. Result; Out of 537 patients, deterioration was noted in 64 patients (11.9%; deterioration group). Multivariate analysis demonstrated that the factors associated with worsening were the history of myocardial infarction (MI) (pϽ0.001), NIHSS score 8 or more at onset (pϽ0.001), increase of WBC count (Pϭ0.035), LDL-chol 140mg/dl or more (Pϭ0.002) and HbA1c 7% or more (Pϭ0.006). In the deterioration group, Branch artheromatous disease was more frequent than the non-deterioration group, and over 90% of patients with deterioration either were discharged to nursing home care or died. In radiological analysis, multivariate analysis demonstrated that the factors associated with worsening were internal carotid artery occlusion (pϽ0.001), middle cerebral artery occlusion at M1-2 portion (pϽ0.001), striate-capsular infarction (Pϭ0.030), pontine infarction (Pϭ0.047) and the 15-30mm size of lesion (Pϭ0.011). Conclusion: Deterioration in patients with stroke was more likely to occur in those with high LDL levels, high HbA1c level on admission, history of MI and high NIHSS scores. It is important to predict deterioration in patients with minor ischemic stroke and those with many risk factors for deterioration should be given the best possible treatment. Careful attention should be paid to acute stroke patients with these risk factors.

Author Disclosures: N. Miyamoto: None. Y. Tanaka: None. Y. Ueno: None. R. Tanaka: None. N. Hattori: None. T. Urabe: None.

Th P186 Moderate Blood Pressure Reduction does not Reduce Cerebral Blood Flow in Acute Ischemic Stroke

Negar Asdaghi, Trevor Steve, Derek Emery, Thomas Jeerakathil, Ken butcher; Univ of Alberta, Edmonton, Canada Background: Elevated blood pressure is common after stroke and is associated with poor prognosis. Early treatment is controversial due to concerns that this may reduce cerebral blood flow (CBF) in the ischemic penumbra. It has been hypothesized that nitric oxide donors may increase CBF in stroke patients. We aimed to assess the CBF response to acute BP reduction with labetalol and the nitric oxide donor nitroglycerin. Methods: Patients presenting with ischemic stroke, Ͻ72 hours after onset were enrolled. Those with mean arterial pressure (MAP)Ͼ100 mmHg received nitroglycerin (sublingual/topical) or intravenous labetalol, aiming for MAP reduction of 10%. Patients with MAP Յ100 mmHg were not treated. All patients underwent MRI with Perfusion (PWI) and Diffusion-weighted (DWI) imaging before and after BP treatment. PWI deficit and DWI lesion volumes were measured planimetrically. Results: Of 28 patients enrolled, 22 had MAPϾ100 (median 115.5 mmHg, IQRϭ19.91) and 6 had MAP of Յ100 (medianϭ93.33 mmHg, IQRϭ9.75). The median time between first and second perfusion was 24 min (IQRϭ 63.5). In treated patients, mean penumbral CBF was not affected by antihypertensive therapy (pre-treatment 31.7Ϯ11.5 vs post treatment 33.1Ϯ11.4 ml/100g/ min, pϭ0.685). Similarly, ischemic core CBF (28.7Ϯ11.9 vs 30.2Ϯ11 ml/100g/min, pϭ0.659) and hemispheric CBF (39.0Ϯ6.2 vs 39.6Ϯ5 ml/100gr/min, pϭ0.698) were not affected by treatment. The change in penumbral CBF in patients treated with antihypertensives (medianϭ -2.1, IQRϭ 9.3 ml/100g/min) was not different from that in untreated patients (medianϭ 3.7, IQRϭ15.2 ml/100g/min, pϭ0.502). Similarly, the change in ischemic core CBF (medianϭ -2.7, IQRϭ11.6 vs 3.5, IQRϭ15.0 ml/100g/min, pϭ0.538) and hemispheric CBF (medianϭ -2.4, IQRϭ12.3 vs 3.9, IQRϭ16.6 ml/100g/min, pϭ0.502) was similar in treated and untreated patients. There was no correlation between change in MAP and change in penumbral CBF (Rϭ0.07, pϭ0.74). Patients who received nitroglycerin did not show improvement in penumbral CBF (median CBF changeϭ -0.5, IQRϭ 12.2 ml/100g/min) relative to those who did not receive nitroglycerin (median CBF changeϭ -3.0, IQRϭ 10.7 ml/100g/min, pϭ 0.30). There was no difference in DWI lesion volume growth, between patients receiving antihypertensives (medianϭ 0.3, IQRϭ 4.3) and those who were not treated (median ϭ3.8, IQRϭ 12.5, pϭ0.71). Patients who were treated with antihypertensives did not show worsening of neurological status by day 7 (median NIHSS changeϭ-1, IQRϭ2.3) relative to those who were untreated (median NIHSS change ϭ 3, IQRϭ12, pϭ0.67). Conclusion: Antihypertensive therapy does not result in further reductions in penumbral, core or hemispheric CBF in acute stroke. Nitroglycerin treatment does not appear to be associated with an improvement in CBF. These results support the safety of moderate blood pressure reduction in the early post stroke period.

Author Disclosures: N. Asdaghi: Research Grant; Significant; CIHR. T. Steve: None. D. Emery: None. T. Jeerakathil: None. K. butcher: Research Grant; Significant; CIHR, AHFMR,HSFA.

Th P187

The Brush Sign on 3-Tesla T2*-Weighted MRI as a Potential Predictor of Hemorrhagic Transformation after tPA-Induced Recanalization Yuka Terasawa, Koji Fujita, Nobuaki Yamamoto, Dept of Neurology, Tokushima university, Tokushima-city, Japan; Ryoma Morigaki, Dept of Neurosurgery, Tokushima university, Tokushima-city, Japan; Yuishin Izumi, Dept of Neurology, Tokushima university, Tokushima-city, Japan; Junichiro Satomi, Dept of Neurosurgery, Tokushima university, Tokushima-city, Japan; Masafumi Harada, Dept of Radiology, Tokushima university, Tokushima-city, Japan; Shinji Nagahiro, Dept of Neurosurgery, Tokushima university, Tokushima-city, Japan; Ryuji Kaji; Dept of Neurology, Tokushima university, Tokushima-city, Japan Background: The brush sign (BS) is the hypointensity findings of medullary veins depicted on 3-Tesla T2*-weighted MRI. The brush sign is reported to be seen in patients with ischemic stroke due to major cerebral artery lesions. However, the clinical relevance of the brush sign in acute stroke patient remains unclear. We assessed the hypothesis that the brush sign detected before treatments correlates with poor outcome after thrombolysis. Methods: We enrolled patients with anterior circulation ischemic stroke who had major artery occlusions and were treated with IV t-PA from October 2005 to June 2010. We classified the patients into two groups according to the presence of BS: the patients positive for the brush sign (P-BS) and the patients negative for the brush sign (N-BS). We investigated the differences in the clinical outcomes (NIHSS and mRS) and MRI findings (recanalization and hemorrhagic transformation) between the two groups. Results: The subjects consisted of 30 consecutive patients (male 14; mean age, 74 years). Eight patients (27%) had ICA occlusions, 14 (47%) had M1 occlusions, and 8 (27%) had M2 occlusions. Of the 30 patients, 22 (66%) were classified as P-BS and 8 (34%) were as N-BS. NIHSS scores had no significant difference between P-BS and N-BS (median NIHSS on admission, 15 vs 12, pϭ0.170; 24 hours after t-PA, 11 vs 4, pϭ0.170). Good outcome (mRS 0 to 1) at discharge was 23% in . Recanalization was observed in 13 (59%) patients in P-BS and 7 (88%) patients in N-BS (pϭ0.210) at 24 hours after t-PA. Of the 20 patients with recanalization, hemorrhagic transformation on MRI were observed more frequently in P-BS than in N-BS (69% vs 14%; pϭ0.057). Conclusions: The brush sign may predict the hemorrhagic transformation after recanalization in the patients treated with IV t-PA.

Author Disclosures: Y. Terasawa: None. K. Fujita: None. N. Yamamoto: None. R. Morigaki: None. Y. Izumi: None. J. Satomi: None. M. Harada: None. S. Nagahiro: None. R. Kaji: None.

Th P188 Acute-phase Hyperglycemia Negatively Impacts Outcome and Recovery of Ischemic Stroke

Renzo Figari, Richard Salazar, Mei Lu, Patricia Penstone, Panayiotis Mitsias; HENRY FORD HOSPITAL, Detroit, MI Introduction: Hyperglycemia is a frequent accompaniment of acute ischemic stroke. It is uncertain whether hyperglycemia negatively influences stroke outcome or simply is a marker of stroke severity. Clinical trials investigating strict control of acute hyperglycemia failed to show positive results on stroke outcome. Objectives: To define the impact of acute-phase hyperglycemia on outcome and clinical recovery after acute ischemic stroke. Main hypothesis: Hyperglycemia on admission and during hospitalization will correlate negatively with recovery after acute ischemic stroke at discharge (DC) and subsequent outpatient (OPD) follow-up. Methods: We analyzed prospectively collected data from the stroke registry of a large acute-care tertiary hospital. Demographic data, stroke risk factors, admission NIHSS score, DC and OPD modified Rankin score (mRS) were recorded. Serum glucose (Glu) data were obtained directly from the hospital electronic medical record system. Spearman correlation coefficients between admission-, 24-hour-, and entire hospitalization mean-glucose values and discharge and outpatient mRS were computed. We then categorized Glu values as: hyperglycemia (Glu Ͼ120 mg/dL), normoglycemia (Glu Ͼ50 and Ͻ120 mg/dL), and hypoglycemia (Glu 12, the OPD mRS was 0-3. The study was approved by the Institutional IRB. Results: We studied 245 patients. The mean age was 67 (Ϯ13) years, 49% were women, 66% were African-Americans. There were significant correlations between: admission Glu (r: 0.23, pϭ0.0004, nϭ223), 24-hour Glu (r:0.25, PϽ0.0001, nϭ223), the mean hospitalization Glu levels (r:0.26, PϽ0.0001, nϭ223) and DC mRS. There were significant correlations between admission Glu (r:0.20, pϭ0.0038, nϭ196), 24-hour Glu (r:0.22, PϽ0.0013, nϭ196), the mean hospitalization Glu levels (r:0.27, PϽ0.0001, nϭ196) and OPD mRS. There was strong correlation between the occurrence of hypoglycemia at any time during hospitalization and DC mRS (r;0.26, pϭ0.0018, nϭ135). On univariate logistic regression analysis, there was a negative impact of hyperglycemia during hospitalization on good stroke recovery [OR:0.29 (CI:0.15-0.55), PϽ0.0001]. The occurrence of hypoglycemia was also associated with poor clinical recovery [OR for good recovery:0.02 (CI: 0.003-0.21), PϽ0.001). Conclusions: Acute-phase hyperglycemia has a negative impact on outcome and clinical recovery from acute ischemic stroke. The occurrence of hypoglycemia at any point during hospitalization for acute ischemic stroke also influences negatively stroke recovery. Clinical trials should aim at producing a sustained normoglycemic effect.

Th P191 Lower Admission Hemoglobin Levels are Associated with Larger Stroke Volumes and Greater Infarct Expansion

W. Taylor Kimberly, Ona Wu, E. Murat Arsava, Priya Garg, Ruijin Ji, Mark Vangel, Aneesh Singhal, Hakan Ay, A. Gregory Sorensen; Massachusetts General Hosp, Boston, MA Hemoglobin tetramers are the major oxygen carrying molecule within the blood. We hypothesized that lower hemoglobin level and its reduced oxygen-carrying capacity would associate with an increased risk of infarction within the penumbra of acute ischemic stroke patients. We studied 135 consecutive patients with acute ischemic stroke and perfusion brain MRI. We explored the association of admission hemoglobin and estimated viscosity with initial infarct volumes on acute images and the volume of infarct expansion on follow-up images. Bivariate analyses showed a significant inverse correlation between hemoglobin and initial DWI volume (r ϭ -0.20, P ϭ 0.02), final infarct volume (r ϭ -0.22, P ϭ 0.01) and absolute infarct growth (r ϭ -0.20, P ϭ 0.02). Estimated viscosity measurements were not significantly associated with these metrics. Multivariable linear regression modeling revealed that hemoglobin remained independently predictive of larger infarct volumes acutely and at follow-up (P Ͻ 0.001). Lower hemoglobin levels were also associated with greater infarct expansion (P Ͻ 0.05) after adjusting for other known variables that influence infarct growth. Hemoglobin level at the time of acute ischemic stroke predicts both larger infarcts and increased infarct growth, whereas estimates of whole blood viscosity do not. This raises the possibility that blood transfusion in a subset of acute stroke patients may be worthwhile investigating as a therapy. Objective: We performed a systematic review of standardized swallowing screening protocols in patients with acute stroke to assess ease of administration, reliability, and validity. Methods: Screening was defined as a brief assessment by someone other than a speech language pathologist (SLP) of patients' ability to swallow safely, namely whether the patient could eat or needed further evaluation of swallowing function. Criteria for review included: patients were in the early stage of hospitalization for acute stroke, screening items were described in sufficient detail, reliability was measured, and criterion validity was assessed. We searched MEDLINE, EMBASE and Cochrane databases with the strategy: (swallow* OR dysphagia) AND (screening OR evaluation OR assessment) AND (stroke OR cerebrovascular accident). Additional references were located by reviewing bibliographies of relevant papers, references for guideline publications, and manual search of the table of contents for the journals Stroke and Dysphagia for the past five years. Results: We found 730 papers in the MEDLINE search, of which 64 were reviewed in detail. From review of these papers and other sources, including the same search in EMBASE, we identified 36 papers detailing a protocol for non-SLP professionals to screen swallowing. Of these, seven met criteria detailed above: the Standardized Swallowing Assessment (SSA), the Massey Bedside Swallowing Screen, the Gugging Swallowing Screen (GUSS), a swallowing screen conducted by emergency physicians, the Toronto Bedside Swallowing Screen (TOR-BSST©), the modified Mann Assessment of Swallowing Ability (MMASA), and the Acute Stroke Dysphagia Screen (ASDS). Four screens were designed to be administered by nurses; two by physicians; and one by any specifically trained health care professional. Six of the seven included assessment with water swallows, one in conjunction with pulse oximetry. The gold standards used were clinical evaluation by an SLP (nϭ3), videofluoroscopic evaluation (nϭ1), fiberoptic endoscopic evaluation (nϭ1), and clinical observation and chart review for indications of dysphagia and complications (nϭ2). Where provided, administration time ranged from two to ten minutes. Inter-rater reliability ranged from k of 0.76 to 0.9. Sensitivity of these instruments ranged from 76 to 100%, and specificity from 56 to 100%. Discussion: Despite recommendations for their use by several organizations, few swallowing screens were available that met even minimal criteria. Three of the seven protocols that met criteria reported limited reliability testing or were described as preliminary with small sample sizes limiting their generalizability. Further work is needed to achieve the goal of swallowing screens to reduce the risk of aspiration pneumonia after stroke.

Author Disclosures: S.K. Schepp: None. D.L. Tirschwell: None. R.M. Miller: None. W.T. Longstreth: None.

Th P193 Correlation Of Neuroanatomical Location And Dysphagia Pattern By Using Videofluoroscopic Function Scale In Patients With Acute Ischemic Stroke

Yeong-Bae Lee, In-Hye Jeong, Ju Kang Lee, Gachon Univ, Sch of Medicine, INCHEON, Korea, Republic of; Hyun Young Kim, Hanyang Univ, College of Medicine, SEOUL, Korea, Republic of; Ju-Hun Lee; Hallym Univ, College of Medicine, SEOUL, Korea, Republic of Background & objectives Dysphagia is a common neurological sign and a main cause of aspiration pneumonia, which is a fatal complication in acute stroke patients. Recently, the videofluoroscopy study (VFSS) is considered to be an useful way of measuring severity and predicting prognosis of the dysphagia. We investigated the correlation between the location of brain lesion and dysphagia pattern by using subitems of videofluoroscopic functional dysphagia scale. Methods Subjects were acute ischemic stroke patients with dysarthria or dysphagia. The sites of brain lesion were classified to unilateral cortex, subcortex, cortex with subcortical extension and brainstem. All patients were underwent diffusion weighted magnetic resonance image and videofluoroscopic functional dysphagia scale were measured within 30 days. The parameters rated during the VFSS were lip closure, bolus formation, reside in oral cavity and oral transit time, triggering of pharyngeal swallow, laryngeal elevation, nasal penetration, residue in valleculae, residue in pyriform sinuses, coating of pharyngeal wall after swallow and pharyngeal transit time. For the analysis of correlation of lesion sites and parameters, Kruskal-Wallis and Mann-Whitney tests were performed. Results Sixty nine subjects were enrolled (Mϭ48, Fϭ21). Total score for oral phase and score for residue in oral cavity were different depending on lesion sites(oral phase p Ͻ 0.05, residue in cavity p Ͻ0.01). The oral phase score, especially residue in oral cavity, in patients with cortex, subcortex and cortex-subcortex involvement was higher than patients with brainstem involvement (mean score 5.00, 2.83, 2.85 and 0.24, respectively). Score for residue in oral cavity in patients with cortex-subcortex involvement was higher than patients with brainstem involvement (mean score 1.10 vs 0.29, p Conclusion: The oral phase score in patients with cortex, subcortex and cortex-subcortex involvement was higher than patients with brainstem involvement in this study. The subitems of videofluoroscopic functional dysphagia scale may be useful to evaluate the correlation of neuroanatomical location and dysphagia pattern in acute ischemic stroke patients.

Author Disclosures: Y. Lee: None. I. Jeong: None. J. Lee: None. H. Kim: None. J. Lee: None.

Th P194 The Cleveland Clinic Experience: Stroke And Timing Of Valve Surgery In Infective Endocarditis

Dolora Wisco, Joseph F Sabik, Eugene Blackstone, Irene Katzan; Cleveland Clinic Foundation, Cleveland, OH Background: The incidence of stroke in patients with infective endocarditis (IE) is 10-20%. The timing of surgery in IE complicated by stroke is difficult because surgery can exacerbate the patient's neurologic condition. The risk of peri-operative stroke in these patients is unclear. Objective: To determine the optimal timing of valve surgery in patients with IE and stroke. Method: Cohort study of peri-operative neurological complications in patients with IE and history of prior stroke admitted at Cleveland Clinic from 2007 to 2009. Subjects were identified from the Cleveland Clinic Cardiovacular Information Database, and stratified by the timing of their stroke in relation to surgery: 0-7 days before surgery (Group 1), 8-14 days (Group 2), 15-30 days (Group 3), 31-90 days (Group 4), and Ͼ90 days (Group 5). Result: Of the 364 patients admitted to Cleveland Clinic with IE during this period, 99 had prior stroke, including 35 (9.6%) who had stroke within 14 days, and 64 (17.5%) who had stroke greater than 14 days. Seventy were included in final analysis. The overall incidence of peri-operative stroke in IE subjects with any prior stroke was 10% (7 of 70) and tended to occur more frequently in the subjects with recent stroke: 3 (4.3%) in Group1, 1 (1.43%) in Group 2, 1 (1.43%) in Group 3, 0 in group 4, and 2 (2.9%) in Group 5. Thirteen of prior strokes were associated with hemorrhages. Eight (11.3%) occurred in Group 2: 4 hemorrahagic conversion without shift, 2 petechial, 1 subarachoid hemorrhage, 1 abscess. The MCA and PCA territories were commonly involved both in the pre-and peri-operative strokes. The mechanism of peri-operative stroke was commonly cardioembolic (71%), with the one hemorrhagic conversion (14.2%). The average length of stay for the study cohort was 24 days, and was not significantly different in patients with peri-operative stroke. Conclusion: In this large single-center cohort of IE patients and prior stroke, the incidence of peri-operative recurrent stroke was highest in subjects with recent stroke occurring within 7 days of surgery (5.7%) and declined if surgery was delayed for at least 7 days (1.43%). Peri-operative hemorrhagic stroke was surprisingly rare, occurring mostly in subacute strokes (8-14 days), and most of these were hemorrhagic conversion of previous embolic stroke, not primary hemorrhages. Given these findings, recent stroke does not need to be considered a contraindication for valve surgery in IE patients. . Medical records were reviewed of patients with cardiac arrest either from primary cardiac causes or secondary to respiratory causes and who had a brain MRI. Neurological examination on admission, SSEP results and CK-BB levels were also recorded. SSEPs and CK-BB were not tested in all patients, nor on all the same patients. An abnormal brain MRI was defined as a radiology read of any abnormality. Abnormal SSEPs were either slow or absent. These were compared with if the patient awoke or not. Statistics were nonparametric. Results: 35 patients were identified, with mean age of 50.3 (SD 16.9), 34% female. The arrest was primary cardiac in 28, respiratory in 6, and unknown 1. MRI of the brain was performed an average of 7.6 days (SD 5.3) after resuscitation and was abnormal in 19 (54%). CK-BB in CSF was measured in 15 patients and ranged from 8-1764 U/L. SSEP was performed in 18 patients, 9 were abnormal, but only 2 with bilateral absent cortical responses. Out of the 35 patients 16 awoke. MRI abnormality was not associated with awakening (P ϭ 0.25). There were correlations between SSEP results and awakening (P ϭ 0.046), CK-BB levels and awakening (P ϭ 0.02), and CK-BB levels and MRI results (P ϭ 0.048). The 4 patients with minimal CK-BB levels all had normal MRIs and awoke. The 2 patients with the highest CK-BB levels (965, 1764 U/l) had severe and diffuse MRI abnormalities, prolonged SSEPs, and neither awoke. Intermediate levels of CK-BB abnormality showed a less consistent relationship to MRI findings. Conclusion: Despite small numbers, our results represent a proof in principle that a biomarker with a continuous association with severity of brain injury after resuscitation from cardiac arrest (CK-BB) is correlated with brain MRI findings. To the best of our knowledge this is the first study to compare CK-BB levels and brain MRI in post arrest patients. Further research, especially in the hypothermia treatment era, is needed to examine this correlation and its possible utility in prognosis in the post resuscitation cardiac arrest patient. This research has received full or partial funding support from the American Heart Association, Pacific/Mountain Affiliate (Alaska, Arizona, Colorado, Hawaii, Idaho, Montana, Oregon, Washington & Wyoming).

Author Disclosures: A. Tkach: None. J. Lundeen: None. S. Khot: None. T. Youn: None. W. Longstreth: None. D. Tirschwell: None.

Th P196 Surgical Variability and Radiological Predictors of Outcome or Reoperation in Patients that Undergo Hemicraniectomy for Malignant Middle Cerebral Artery Infarction

Tzu-Ching Wu, Jeanie Choi, Elliot Friedman, William Ashley, Jr., Preeti Sahota, Nusrat Harun, Renganayaki Pandurengan, Navdeep Sangha, Nicole R Gonzales, George A Lopez, James C Grotta, Sean I Savitz, Andrew D Barreto; UT Houston Med Sch, Houston, TX Objective: Hemicraniectomy (HC) has been shown not only to be lifesaving but it also improves clinical outcomes in the setting of malignant middle cerebral artery infarction (MMCA). We hypothesized that variation in surgical technique could contribute to suboptimal decompression, potentially contributing to poor outcomes or the need for re-operation. We reviewed all cases of HC performed for MMCA at our institution to assess clinical and predefined radiological features (RF) that may influence clinical outcomes or need for re-operation. Methods: We retrospectively reviewed our registry from 07/2003 to 02/2010 and identified consecutive patients diagnosed with MMCA that underwent HC. Two independent neuroradiologists reviewed all pre and post-operative CT scans and documented three predefined RF extrapolated from published surgical recommendations: 1) removal of bone flap Ͼ12 cm; 2) removal of bone Յ 2cm to the sagittal suture; 3) bone removal within 1cm of the middle cranial fossa floor. Outcome measures included good clinical outcome defined as discharge mRS of 0-4, and need for re-operation for progressive malignant edema. Results: We identified 70 patients that met our inclusion criteria, with a median age of 52 years (16-80) and median admission NIHSS of 18 (6-40). Age was the only clinical factor that correlated with good outcome, (mean age 46yrs_good outcome vs mean age 54yrs_poor outcome, pϭ0.04) and we found that 96% of the HC patients achieved 1 out of the 3 RF, 56% achieved 2 out of the 3 RF, but only 26% achieved all 3 RF. No clinical factor other than lobectomy during initial HC, showed a trend towards a need for re-operation (pϭ0.055). There was an observed trend towards re-operation when fewer RF were achieved (Figure). Conclusions: Despite recommendations on surgical technique for HC, only 1 out of 4 patients received complete decompression. Incomplete decompression may be associated with need for re-operation, but is not associated with short-term clinical outcomes. Younger patients are more likely to achieve a good outcome after HC for MMCA, and lobectomy during initial HC may increase the need for re-operation. Our study is limited by its retrospective nature, small sample size, and lack of long-term outcomes but suggests that standardization of surgical technique may obviate the need for re-operation.

Th P197 Infarct Volume of Cerebellar Strokes Predicts Neurosurgical Intervention

Navdeep S Sangha, Renganayaki Pandurengan, Mallikarjunarao Kasam, Tzu-Ching Wu, Nicole Gonzales, Vivek Misra, James Grotta, Sean Savitz; Univ of Texas, Houston, Houston, TX Background and Purpose: The decision for neurosurgical intervention in cerebellar strokes is often based upon the degree of clinical deterioration. Past studies of cerebellar stroke have shown that infarct volume may not predict clinical deterioration. However, these studies did not use diffusion weighted imaging (DWI), and infarct volume was calculated more than 2 days from symptom onset. We addressed whether infarct volume and the percent volume of infarcted cerebellum measure on DWI within 24 hours of symptom onset predicts the need for neurosurgical intervention. Methods: A retrospective review was conducted of our stroke registry from 09/2003 to 06/2010. 125 patients were collected with cerebellar infarction on DWI within 24 hours of symptom onset. The patients were divided into 2 groups: surgery and no surgery. Surgical intervention was defined as either the placement of an EVD or a suboccipital decompressive craniectomy (SDC), with or without strokectomy. Volume analysis of the cerebellum and the infarct was performed using a semi-automated region of interest based analysis. Baseline characteristics were also studied. Data was analyzed using Pearson chi square, t-test and Mann-Whitney test. Results: Sixteen patients underwent surgical intervention and 113 patients were treated with medical therapy only. Four patients who had surgery could not be included because their MRI's were performed greater than 24 hours. Mean infarct volumes in patients who required surgical intervention compared to those who did not were 49.0 ml and 12.0 ml, respectively. Mean percent of infracted cerebellum in patients who required surgical intervention compared with those who did not were 30.3% and 8.4 %, respectively. The surgical procedures were ventriculostomy only (nϭ5), ventriculostomy ϩ SDC (nϭ5), SDC (nϭ2). Nine patients underwent surgery because of subsequent, depressed mental state and 3 because of subsequent imaging findings that showed brainstem compression. There were no significant differences in baseline characteristics between the two groups. Conclusion: Quantitative measurement of infarct volume and percent of infarct volume on DWI within 24 hours may help to accurately identify patients with cerebellar ischemic strokes who may require neurosurgical intervention. Measuring the infarct volume may aid clinical decisions to pursue surgical management. These results raise the need for a prospective analysis to investigate the factors that predict need for surgical intervention for cerebellar ischemic stroke.

Background and Purpose: Body temperature is a modifiable risk factor in the treatment of acute ischemic stroke, early rises being associated with worse outcome at 90 days. Higher body temperature has been hypothesized to enhance performance of alteplase. Such temperature dependency would undermine future trials of induced hypothermia, however. We have examined the impact of baseline temperature on outcome according to alteplase exposure. Methods: We identified 5832 patients with acute ischemic stroke in the Virtual International Stroke Trials Archive, of whom 2097 received alteplase (T) and 3735 were not thrombolysed (C), according to local standard of care. Age and baseline severity were similar (68.0Ϯ13.0 versus 69.9Ϯ12.3 years, NIHSS 14.2Ϯ5.2 versus 13.0Ϯ5.6). We compared outcome in T versus C, testing for significance and extent of interaction of baseline temperature on 90 day mRS using the Cochran-Mantel-Haenszel test and estimation of odds ratios for improved functional outcome from ordinal logistic regression. All analyses were adjusted for age and baseline severity. We also examined the temperature profile over 7 days after stroke, by treatment group. Results: Alteplase was associated with improved outcome, OR 1.49 (95% CI 1.35-1.65, PϽ0.0001). Baseline temperature was not significantly associated with the estimated alteplase treatment effect, pϭ0.14. Point estimates for alteplase treatment effect were greatest and showed significant benefit evident in each temperature category from 35.5-37.5C, but showed a negative trend above 37.5C (Figure). Alteplase did not influence the temperature profile over the first 7 days after stroke. Conclusion: There is no evidence of an influence of body temperature on alteplase treatment response. These controlled but non-randomized results offer preliminary reassurance that induction of modest hypothermia should not compromise the therapeutic effect of alteplase in acute ischemic stroke, but require prospective confirmation.

Author Disclosures: J.S. Lees: None. N.K. Mishra: None. M. Saini: None. P.D. Lyden: None. A. Shuaib: None.

Th P201 Baseline Creatinine Levels Are Not Needed Prior to CTA/CTP Imaging in Acute Ischemic Stroke Evaluation

Vincent Truong, Jignesh Shah, Rori Spray, Anand Vaishnav, Craig Ziegler, Kerri Remmel, Alex Abou-Chebl; Univ of Louisville Sch of Medicine, Louisville, KY Objective: Computerized tomography perfusion imaging is emerging as an important adjunct to acute stroke therapeutic decision making. However, at many centers CTA/CTP imaging is not performed until Creatinine levels are obtained resulting in potential delays in treatment. We sought to determine the renal safety of CTA/CTP at a single stroke center. Methods: Using an IRB-approved prospectively collected acute ischemic stroke (AIS) database, we identified patients who had CTA and/or CTP (total volume 140ml Optiray™ contrast) as part of initial evaluation during a 2year period. Patients who received subsequent contrast, other than cerebral angiography, were excluded. All AIS patients receive hydration via 1-2liter NS bolus and infusion of Ն150cc/hr. Data collected included patient demographics, DM, HTN, chronic kidney disease (CKD), use of Metformin, ACE-I, ARB, and/or diuretics, baseline and highest Creatinine values in the following 5days. An increase of Creatinine Ͼ25% from baseline was considered significant. Results: 91 patients (54% men) with mean age of 61Ϯ13.5years were included, of whom 31(34%) had cerebral angiograms with 109.3Ϯ42ml of additional contrast. DM and CKD were reported in 31(34%) patients and 69(75%) patients had HTN. Forty-five patients (49%) were on Metformin, ACE-I/ARB, and/or diuretics. The mean baseline Creatinine was 0.95Ϯ0.41. No patient had Ͼ25% increase in Creatinine and no patient needed dialysis. There was no clinically or statistically significant difference in baseline vs. peak Creatinine in 60(66%) patients who had CTA/CTP only (0.9Ϯ0.28 vs. 0.86Ϯ0.37, pϭ0.

Th P202 Does Gender Influence The Evolution Of Patients Treated With Intraarterial Procedures?

Olga Maisterra, Jr., Marc Ribo, Manuel Quintana, Joao Sargento, Marta Rubiera, Jorge Pagola, David Rodriguez-Luna, Estevo Santamarina, Carlos Alberto Molina, Jose A ´lvarez-Sabı ´n; Vall d'Hebron hospital, Barcelona, Spain Background: Previous studies have suggested gender differences in the response to intravenous thrombolysis for acute stroke. We aimed to evaluate whether gender differences may also influence recanalization, early and long-term outcome and mortality in acute stroke patients treated with intraarterial (IA) reperfusion procedures. Methods: Consecutive stroke patients treated with IA procedures between September 2006 and August 2010 were analyzed. Baseline clinical characteristics, different endovascular approaches and response to endovascular procedures (recanalization, clinical evolution, hemorrhagic transformation, mortality and functional outcome) were evaluated according to gender. Recanalization was defined as TIMI 2-3. Clinical improvement was considered if a decrease in NIHSS Ͼ4 points was achieved, and good functional outcome if modified Rankin scale at 3 months was Յ2. Results: A total of 121 patients were included; mean age 70.4Ϯ12.1 sd and 57(47.1%) were women(W). W were older ( 74 vs 67.2; pϭ0.002), presented more atrial fibrillation (61.4% vs 39.1%; pϭ0.014) and previous treatment with coumadin (35.7% Vs 15.6%; pϭ0.01). No gender differences were observed in baseline NIHSS score (median W 19 vs men(M) 20; pϭ0.946), symptoms to groin-time (W 217.5 min vs M 232.8 min, pϭ0.512) or door to groin-time (W 85.3 min vs M 75.7 min, pϭ0,25). The occluded vessels and clot locations were also similar in both groups. Rate of pre-treatment with iv tPA was lower in W (47.3% vs 67.64%, pϭ0.047). During IA procedure 10.2% W vs 10% M were treated with tPA alone, 18.4% vs 34% with isolated mechanical procedures and 71.7% vs 56% required more than one IA technique to achieve recanalization (pϭ0.199). Recanalization rate after IA procedures was similar between W and M (72.7% vs 71.7%, pϭ0.899) and occurred at a comparable symptoms-to-recanalization time (W 329.9min vs M 338.1min, pϭ0.778). No differences were found in clinical improvement at discharge (W 47.1% vs M 49.1%, pϭ0.830), hemorrhagic transformation (34.6% vs 30.4%, pϭ0.637), symptomatic intracranial hemorrhage (3.7% vs 10.3%; pϭ0.274) or in-hospital mortality (32.1% vs 35% pϭ0.745). At 3 months, 31.9% of patients achieved a good outcome in both genders (pϭ1). Conclusions: Despite the older age and the higher prevalence of atrial endovascular therapy is a relatively safe and efficacious strategy for patients with acute ischemic stroke secondary to distal MCA clots in our experience.

Author Disclosures: J. Sharma: None. S. Mehta: None. S. Chowdhry: None. N. Tummala: None. A. Nanda: None. K. Blackham: None.

Th P207 Acute Stroke Trials in the 1st decade of the 21th Century

Keun-Sik Hong, ILSAN PAIK HOSPITAL INJE UNIV, Goyang, Korea, Republic of; Meng Lee, Chang Gung Memorial Hosp at Chiayi, Chang Gung Univ College of Medicine, Chiayi, Taiwan; Soo Joo Lee, Eulji Univ Hosp, Dajeon, Korea, Republic of; Qing Hao, David Liebeskind, Jeffrey Saver; UCLA Stroke Cntr, Univ of California, Los Angeles,, Los Angeles, CA Background: Instructed by past successes and failures, numerous acute ischemic stroke trials have been conducted during the 1 st decade of the 21 th century. The evolution of trial designs during this epoch has not been systematically delineated. Methods: Systematic search of MEDLINE and clinical trial registries was performed to identify all acute ischemic stroke trials published between Jan 2000 and Dec 2009. Data for trial designs, interventions, baseline characteristics, and results were abstracted and analyzed. Results: 104 acute ischemic stroke trials were identified, enrolling 36,059 patients (median, IQR: 117, 41-403), including 9 phase 1, 56 phase 2, 7 phase 2b/3a and 31 phase 3 trials. A total of 66 agents or interventions were tested. Fifty trials tested neuroprotectives, 38 reperfusion therapies, 7 antithrombotics, and 9 others. Eighty-three (79.8%) trials were randomized, including 62 double-blind, 14 PROBEdesign, 2 single-blind, and 5 non-blinded. Initial stroke severity was measured by NIHSS in 88 (84.6%) trials and employed as an inclusion criterion in 85 (81.7%) trials. Modified Rankin Scale was the most common outcome scale, employed in 74 trials, of which 20 used analytical techniques other than a simple mRS dichomization. Intravenous TPA was tested or allowed to be combined with tested interventions in 27 trials. Baseline characteristics of enrolled patients were: mean age, 67.6Ϯ5.0; male, 54.9%; median NIHSS (IQR), 13 (9.5-14.9); median onset to treat, 5.5 h (4.1-12.3). Twenty-five trials were early terminated due to futility, safety concerns, slow enrollment or other reasons. Among phase 3 trials, 5 (16%) were positive on the primary efficacy outcome. However, two failed on replication (NXY-059 and ancrod); one tested statin withdrawal rather than new therapy addition; and one was single-center, open-label, evaluator-blinded (minocycline). Intravenous TPA between 3-4.5 h from onset was the only well-validated positive trial. Hemicraniectomy for malignant infarction, though individual trials failed to meet the primary efficacy endpoints, was another intervention of which the efficacy was demonstrated by a pooled analysis. Conclusion: Acute ischemic stroke trials during the opening decade of the 21 th century were larger in size, had earlier treatment initiation, and used more nuanced outcome analysis than previously. RCT results added intravenous TPA between 3-4.5 h and hemicraniectomy for malignant infarction to the arsenal of proven therapies for acute ischemic stroke.

Background and purpose:

The management of blood pressure (BP) in acute stage of ischemic stroke has been a matter of debate. Based on the equivocal evidence and marked variations in clinical practice, we designed a prospective, randomized, open-labeled, blinded endpoints, multi-center study to evaluate the Valsartan Efficacy oN modesT blood pressUre REduction in Acute Ischemic Stroke (VENTURE). Methods: Eligible patients were randomly assigned to receive valsartan or no anti-hypertensive agents during 7 days after symptom onset by the central computerized system. Inclusion criteria were 1) age older than 18 years, 2) admission within 24 hours from onset, 3) treatment initiation within 48 hours, 4) NIHSS 2-21, and 5) Systolic BP 150-185 mmHg. Primary endpoint was death or dependency measured as modified Rankin Scale (mRS) score Ն 3 at 90 days. Safety endpoints were early neurological deterioration within 7 days and mortality at 90 days. Thirty centers have participated in this trial since October 2008. We conducted planned interim analysis after capture of 50% of primary endpoint from all enrolled patients. Analysis was based on intention to treat. This study is registered, number NCT00874601. Results: At the time of interim analysis, the adjudicated primary endpoints were obtained from 147 patients of the valsartan group and 143 patients of the control group were evaluated in this interim analysis. During the first 7 days, BP reduction was greater in valsartan group than in control group: mean reduction of diastolic BP was 2.82 mmHg (95% confidence interval [CI] -4.94 ϳ-0.88, pϭ0.005); and mean reduction of systolic BP was 1.93 mmHg (95% CI -7.06 ϳ0.72, Pϭ0.055). However, there was no difference in the primary endpoint, combined death or dependency at 90 days, between valsartan (nϭ34, 23.4%) and control (nϭ35, 24.6 %) groups (risk ratio [RR] 0.94, 95% CI 0.55-1.61; pϭ0.812). In addition, the safety endpoints, early neurological deterioration within 7 days, mortality at 90 days, did not differ between the two groups (RR 1.86, 95% CI 0.83-14.17; pϭ0.13). Conclusion: This interim analysis shows that early BP reduction with valsartan did not increase dependency or mortality at 90 days. VENTURE trial will continue to establish the efficacy and safety of modest BP reduction in patients with acute ischemic stroke.

Th P212

Imaging Criteria as a Surrogate Marker for Outcomes after Intra-arterial Thrombolysis.

Jacob Kitchener, Saint Louis Univ, Saint Louis, MO; Mouhammad Jumaa, Univ of Pittsburgh Med Cntr, Pittsburgh, PA; Sushant Kale, Amer Alshekhlee, Ritesh Kaushal, Tagann Chaisam, John Chibnall, Aninda Acharya, Paisith Piriyawat, Eli Feen, Salvador Cruz-flores, Charlie Callison, Randall Edgell, Saint Louis Univ, Saint Louis, MO; Tudor Jovin, Univ of Pittsburgh Med Cntr, Pittsburgh, PA; Nirav Vora; Saint Louis Univ, Saint Louis, MO Background: We sought to determine which neuro-imaging parameters during intra-arterial (IA) thrombolysis can predict good functional recovery. Methods: With institutional approval from each center (Saint Louis University and University of Pittsburgh Medical Center), we retrospectively reviewed cases of anterior circulation acute ischemic stroke treated with IA thrombolysis from January 2006 to March 2010. We excluded patients who sustained a symptomatic intracerebral hemorrhage or who did not have available pre-treatment neuroimaging. We also excluded those without a pre-treatment collateral score based on the protocol described below. We assessed time from symptom onset to end of procedure as well as imaging parameters including: the extent of infarction, based on the Alberta Stroke Program Early CT Score (ASPECTS), site of angiographic occlusion, succesful recanalization (defined as a Thrombolysis in Myocardial Infarction score of Ͼ2), and extent of intracranial collaterals. Collaterals were stratified according to a previously published classification system based on the most proximal reconstitution of the middle cerebral artery (MCA) segments. Hence, any reconstitution of the M1 segment was given a score of 1, any reconstitution upto the M2 segment was given a score of 2, etc. A score of 5 represented absent collaterals. Other parameters studies were recanalization with an ASPECTS score Ͼ 8 and recanalization with a collateral score Ͻ2 and Ͻ3 respectively. Our endpoint was good functional outcome defined as a modified Rankin Score Ͻ2. A step-wise logistic regression analysis was performed to determine imaging predictors of a good outcome. Results: A total of 83 patients were reviewed with complete imaging assessments. The mean National Institutes of Health Stroke score was 12 (s.d. 4). Treatment was completed within 545 minutes (mean, s.d. 338 minutes). Of these 83 patients, 20 had concomitant tandem occlusions of the internal carotid artery (ICA) origin and either the intracranial ICA or M1 or M2 MCA segments. Other sites of occlusion included M1 MCA only (34), M2 MCA only (7), and intracranial ICA only ( 22). Recanalization occurred in 49 patients (59%). Good outcome was observed in 22 patients (26%). In the regression model, duration of ischemia, baseline ASPECTS score, site of occlusion, extent of collaterals, and successful recanalization did not predict good recovery. Only recanalization in the setting of a pre-treatment ASPECTS score Ͼ 8 predicted good outcome (OR 5.4, 1.8-16 95% CI, pϭ0.002). Conclusions: Good outcome after IA thrombolysis is likely to occur when patients with minimal signs of infarction are selected for therapy. This study suggests that imaging-based criteria may be more meaningful for IA thrombolysis patient selection than time-based assessments. Successful recanalization in selected patients may serve as a surrogate marker for subsequent studies. Pe ´rez de la Ossa N, Ribo ´M, Pagola J, Milla ´n M, Gomis M, Silva Y, Aleu A, Rodrı ´guez-Campello A, Cuadras P, A ´lvarez-Sabı ´n J, Da ´valos A. Soft Hyperdense Areas on CT Scan after Endovascular Treatment in Acute Ischemic Stroke of the Anterior Territory: a Sign of Successful Recanalization and Good Outcome. Hyperdense lesions (HDL) on CT scan 24h after endovascular treatment (EVT) may differ from those observed after intravenous thrombolysis since contrast extravasation contribute to the lesions. We aimed to assess the patterns of HDL and their predictive value on clinical outcome. Methods: Retrospective analysis of 109 patients with anterior territory AIS treated with EVT in two comprehensive stroke centers. CT scans at 24h were reviewed by two independent observers and HDL were classified according to location, morphology and maximum Hounsfield units as (1) soft HDL within the infarct area (HU65) and (3) subarachnoid HDL. Good outcome at 3 months was considered as a Rankin scale 0-2. Results: 35/109 (32.1%) patients showed HDL: soft HDL in 12 (11%), bright in 15 (13.8%) and subarachnoid in 8 (7.3%). Age, gender, risk factors, prior antithrombotic therapy, vital signs, site of arterial occlusion, early CT signs of ischemia and bridging therapy with iv tPA were not different between groups, but admission serum glucose levels were higher in all HDL groups compared with the non-HDL group (pϭ0.02). Good outcome at 3 months was achieve in 40% of non-HDL, 64% of soft, 0% of bright and 25% of subarachnoid HDL patients (pϭ0.004). Using non-HDL as reference group, soft HDL pattern had an OR 7.9 (IC95% 1.4-44.8) of good outcome, and bright and subarachnoid HDL patterns combined had an OR 6.9 (IC95% 0.8-61) of poor outcome after adjustment for stroke severity and serum glucose. Non-HDL and soft HDL patterns were associated with a similar rate of complete recanalization (57% vs 68%), higher than in bright (13%) and subarachnoid (37%) patterns (pϭ0.01). Accordingly, hypodensity volume at 24 h was smaller in the non-HDL (median 25mL) and soft (26mL) groups than in the bright (100mL) and subarachnoid (187mL) groups (pϭ0.005). Conclusion: Soft HDL on 24h follow-up CT after EVT are associated with higher rate of complete recanalization and good clinical outcome. In contrast, bright parenchymal and subarachnoid HDL may be considered as clinically significant complications of the endovascular procedure. Background and Purpose: Carotid occlusion is present in 10-15% of acute stroke patients. The risk of recurrent stroke in this condition is related to the adequacy of collateral supply. A number of external carotid to internal carotid artery anastomoses have been described. No previous study has delineated the frequency of these anastomotic sites in carotid occlusion. Methods: We retrospectively identified subjects with carotid occlusion diagnosed on digital subtraction angiography between July 2009 and June 2010. We collected data on demographic variables; past medical history; and the cause of occlusion. The type of external to internal carotid artery anastomosis was categorized into one of 9 categories based on review of the digital subtraction angiogram. Patients were also divided into those with ipsilateral ischemic symptoms and those with no ischemic symptoms. Results: Thirty-seven patients were identified; the average age was 57 ϩ/-12 years and 22 (59%) were male. Twenty-one patients (67%) had external to internal carotid artery anastomoses; all of these were through branches of the internal maxillary artery. Eleven (52%) anastomoses arose from the mandibular segment of the internal maxillary artery (middle meningeal to recurrent meningeal artery ϭ 7; middle meningeal to inferolateral trunk ϭ 4; accessory meningeal to vidian artery ϭ 1) and 9 arose from the pterygopalatine segment (artery of the foramen rotundum to pertrous internal carotid ϭ 4; other pterygopalatine branch to ophthalmic ϭ 5). Those presenting with ischemic symptoms were numerically less likely to have external to internal carotid collaterals (13/28; 46% versus 3/9; 33%; NS). Conclusion: External to internal carotid artery anastomoses are numerically more common in those presenting incidentally than in those presenting with ischemic stroke symptoms. The internal maxillary artery branches were the source of collateral supply in all patients in who external to internal carotid artery anastomoses were identified. This important potential source of hemispheric collateral must me carefully evaluated in patients with atherosclerotic carotid occlusion and those being considered for therapeutic internal maxillary or internal carotid sacrifice.

Th P216 Mutant Erythropoietin without Erythopoietic Activity is Neuroprotective Against Ischemic Injury

Juan Xing, Ruth A Stetler, Yu Gan, Feng Zhang, UNIVERSITY OF PITTSBURGH, PITTSBURGH, PA; Yanqin Gao, Fudan Univ, Shanghai, China; Jun Chen, Guodong CAO; UNIVERSITY OF PITTSBURGH, PITTSBURGH, PA EPO has robust neuroprotective effects both in animal models of ischemic brain injury and stroke patients. However, treatment of stroke with EPO requires large doses and multiple administration, which may potentially result in multiple high risk factors for stroke patients. Alternate strategies to reduce erythropoietic activity and other potential side effects of EPO will greatly improve its clinical applications for the treatment of stroke patients. We have successfully generated a novel mutant EPO (MEPO) containing a single amino acid mutation which completely lacks erythropoietic activity. The objective of this study is to test the neuroprotective effect of MEPO in the clinically relevant middle cerebral artery occlusion (MCAO) model. Both an in vitro EPO-dependent proliferation assay and an in vivo mouse model assessed the loss of erythropoietic activity. MEPO completely lost the ability to induce myeloid proliferation, even at high concentration (100U/ml, equivalent to 25 nM). MEPO does not induce increased hemoglobin concentration even when continuously present at high concentrations for 4 weeks, while wild-type EPO increases hemoglobin concentration significantly at week 2 and 4, indicating a loss of erythropoietic function. To determine whether MEPO has neuroprotective effects, we first tested it in the primary neuronal culture model of NMDA neurotoxicity. Primary cortical neurons were pretreated with MEPO at 1U/ml, and then challenged with 200 M of NMDA. Pre-treatment with MEPO significantly decreased the necrotic cell death as determined by LDH release and the number of neurons that contained condensed apoptotic-like nuclei following NMDA toxicity. The neuroprotective effects of MEPO were further determined in the murine model of focal ischemia and reperfusion. Intraperitoneal administration with MEPO (5000U/kg) at the onset of post-ischemic reperfusion significantly reduced the infarct volume (pϽ0.01 versus vehicle), and improved neurological deficit scores assessed at 72 hr following ischemia (pϽ0.05), with a similar efficacy as the wild type EPO. MEPO does not change physiological parameters and cortical blood flow. Taken together, our study shows that MEPO is non-erythropoietic, but neuro-protective against ischemic brain injury. Thus, MEPO may be potentially used as a safe therapeutic agent in stroke as well as in other neurological diseases.

This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: J. Xing: None. R.A. Stetler: None. Y. Gan: None. F. Zhang: None. Y. Gao: None. J. Chen: None. G. Cao: None.

Th P217 Evidence of Bias and the Bias of Evidence in Neurothrombectomy for Stroke

David S Liebeskind, Meng Lee; UCLA, Los Angeles, CA Background: Endovascular therapies for acute ischemic stroke, including neurothrombectomy, have been limited by evidence for safety and efficacy. Randomized controlled trials (RCTs) provide a means to establish these critical aspects, yet these studies are shaped by regulatory agencies and guidance documents. We analyzed the United States Food and Drug Administration (FDA) guidance document on neurothrombectomy to ascertain levels of evidence for each element in proposed use for developing clinical trial protocols. Methods: Details of the most recent guidance document on neurothrombectomy were analyzed to identify specific elements. These variables were classified as selection criteria, baseline stroke features, randomization, angiography details, baseline clinical measures, imaging methodology, adverse events, outcome parameters, and analysis techniques. Literature search identified all publications on endovascular therapy prior to and after the 2007 guidance document. AHA/ASA levels of evidence (A-C) were established for each variable. Results: Identified guidance document variables included 22 selection criteria, 9 baseline stroke features, presence of randomization, 7 angiography details, 3 baseline clinical measures, 8 imaging methods, 15 adverse events, 17 outcome parameters, and 5 on analysis techniques. Levels of evidence for use of these 87 variables were determined from 78 reports (nϭ2,743) before and 54 reports (nϭ2,535) after the 2007 guidance was issued.

Th P218 Rapid Formation Of Cerebral Microbleeds After Carotid Artery Stenting

Shoji Matsumoto, Ichiro Nakahara, Kousuke Kakumoto, Keiichi Tsuji, Nozomu Murai, Tsukasa Sato, Yoshihiko Watanabe, Yosihisa Fukushima, Yutaka Fukushima, Masahiro Takezawa, Yujiro Tanaka, Kokura Memorial Hosp, Kitakyushu, Japan; Takeshi Yamada; Saiseikai General Hosp, Fukuoka-shi, Japan Background A recent study showed that new microbleeds (MBs), comprising small areas of signal loss on T2*-weighted gradient-echo (GRE) MRI, can develop rapidly after acute ischemic stroke. We hypothesized that MBs may develop rapidly after carotid artery stenting (CAS), and investigated the frequency of new MBs after CAS. Methods We retrospectively examined 78 consecutive patients who underwent CAS for carotid stenosis and MRI before and after CAS between April 2009 and June 2010. We defined new MBs as those that newly appeared on follow-up GRE MRI. Results Among the 78 patients, 21 (26.9%) had baseline MBs and 9 (11.5%) developed new MBs. Among the 9 patients with new MBs, 6 had no MBs on baseline MRI and 3 had MBs on baseline MRI. The presence of baseline MBs was not significantly associated with the formation of new MBs (Pϭ0.696). Conclusions: The results of this study suggest that new MBs can develop rapidly after CAS. Therefore, particular attention should be paid to patients at risk of cerebral hyperperfusion, which is a cause of cerebral hemorrhage.

Th P219 The Usefulness Of DWI-aspect Score As A Predictor Of Short And Long-term Clinical Outcome Following Emergency Reperfusion Therapy In Severe Acute Ischemic Stroke Patients

MASAHITO NAKAZAKI, Takahisa Mori, Hiroyuki Tajiri, Tomonori Iwata, Yuichi Miyazaki; Shonan Kamakura General Hosp, kamakura, Japan Object: It is unclear whether or not DWI findings on admission in patients presenting serious neurological symptoms due to acute internal carotid artery (ICA) or middle cerebral artery (MCA) occlusions can predict their clinical outcome following reperfusion therapy. The purpose of our retrospective study was to investigate whether or not DWI-Albert stroke program CT (ASPECT) score before initiating reperfusion therapy can be a predictor of clinical outcome. Methods We retrospectively analyzed the ischemic stroke patients 1) who were admitted to our institution from 2004 to 2009, 2) with serious neurological symptoms of GCS of 12 or less, or NIHSS score of 10 or more, 3) who had total occlusion of the ICA or MCA displayed by MRA, and 4) who underwent emergency reperfusion therapy including intravenous rt-PA therapy or endovascular therapy within 6 hours from stroke onset. Patient's baseline features, MRI/DWI findings before initiating reperfusion therapy using DWI-ASPECT score, MRA findings, stroke subtypes, onset-to-treatment time (OTTT), NIHSS score on admission (AD-NIHSS),and the 7th day (7D-NIHSS), and mRS at 3 months (3M-mRS) were evaluated. We used univariate and multiple regression analysis to assess whether or not 7D-NIHSS and 3M-mRS were correlated with patient's baseline features, DWI-ASPECT score, stroke subtypes, OTTT and AD-NIHSS. Result Seventy six patients were analyzed, median age was 77, women were 37, median follow-up period was 6 months(range: 1-72 months), median AD-NIHSS was 18, median DWI-ASPECT score was 7, median OTTT was 2.67 hours, seventeen patients underwent intravenous rt-PA therapy within 3hours, and fifty-nine patients endovascular reperfusion therapy. Median 7D-NIHSS was 10,median 3M-mRS was 3.5. DWI-ASPECTscore on admission was significantly correlated with 7D-NIHSS and 3M-mRS (rsϭ-0.39,pysis demonstrated the DWI-ASPECTscore was the only independent predictor for 7D-NIHSS (␤ϭ-0.39 tϭ-3.36, Pϭ0.001 ), and also one of the independent predictors for 3M-mRS (␤ϭ-0.28 tϭ-2.53, Pϭ0.014) . Conclusion: In severe ischemic stroke patients who underwent emergency reperfusion therapy for the ICA or MCA occlusion within 6 hours, DWI-ASPECTscore before initiating the therapy was the independent predictor for NIHSS score on 7th day and mRS at 3month following reperfusion therapy. The higher DWI ASPECT score can predict favorable 7-day and 3-month clinical outcome.

Author Disclosures: M. Nakazaki: None. T. Mori: None. H. Tajiri: None. T. Iwata: None. Y. Miyazaki: None.

Th P220 Does Arrival By Ambulance Predict Acute Stroke Intervention In Young Adults?

Nandakumar Nagaraja, Pratik Bhattacharya, Gregory Norris, William Coplin, Sandra Narayanan, Andrew Xavier, Kumar Rajamani, Seemant Chaturvedi; Wayne State Univ / Detroit Med Cntr, Detroit, MI Background: The incidence of stroke in young adults is less common and increasing age is a potent risk factor for stroke. It is important to identify young patients presenting with stroke symptoms to the ED to institute intravenous t-PA or intra arterial intervention and minimize long term disability. Objective: We hypothesized that arrival to ED by ambulance would increase the chances of acute stroke intervention with intravenous t-PA or intra arterial procedures. We also assessed other variables as predictors of receiving acute stroke therapy, including initial presentation to a Primary Stroke Center (PSC). Methods: Seventy seven patients aged 15-49 years diagnosed with ischemic stroke by vascular neurologists and followed at a Comprehensive Stroke Clinic from 2001-2010 were enrolled into the study. Data was collected on age, race, gender, arrival to ED by ambulance, whether brain MRI was done within 48 hours of admission, if the initial hospital at presentation was a PSC and intervention by intravenous t-PA or intra arterial procedures. Results: Seventy seven patients with mean age of 37.9 years were reviewed which included 57.1% women. Caucasians composed 57.1%, African Americans 37.7% and 3.9% were others. 48.3% of patients arrived by ambulance, 53.2% got MRI brain within 48 hours of admission, and 23.4% initially presented to a PSC. Twelve (15.8%) patients had acute stroke intervention -7 intravenous tPA, 3 IA tPA and 2 mechanical thrombectomies. The results of the univariate analysis by Fisher's exact test are listed in the table Multivariable analysis (n ϭ 57) showed that the age (p ϭ 0.991), male sex (p ϭ 0.894) and primary stroke certification (p ϭ 0.937) was not significantly associated with patients getting acute stroke intervention. Arrival by ambulance was significantly associated with acute stroke intervention in young adults (p ϭ 0.016). Patients who received intervention were less likely to get MRI within 48 hours of admission (p ϭ 0.049). Conclusion: Young adults with stroke symptoms were more likely to receive acute stroke intervention if they arrived by ambulance. Factors such as increased awareness of stroke symptoms, patient's decision to call 911, evaluation of patients by EMS personnel and their communication to the ED staff for preparedness and prompt action on arrival may play a role in increased rate of stroke intervention in young stroke patients who arrive by ambulance to the ED. Larger, multi-center studies should address whether PSCs are more likely to provide either IV thrombolysis or interventional therapies.

Author Disclosures: N. Nagaraja: None. P. Bhattacharya: None. G. Norris: None. W. Coplin: None. S. Narayanan: None. A. Xavier: None. K. Rajamani: None. S. Chaturvedi: None. 77 identified TO patients, all of whom received proximal stenting, 18/77 (23.4%) patients experienced FR. Successful recanalization was observed in 18/18 (100%) patients in the FR group vs. 42/59 (71.2%) patients in the non-FR group (pϽ0.01). FR was more likely to occur with tandem M1 or M2 MCA occlusions than with carotid terminus occlusions (OR 5.5, 95% CI [1.15, 26.1], PϽ0.01). PH occurred in 3/18 (16.6%) FR cases vs. 6/59 (10.2%) non-FR cases (pϭ0.52). Good clinical outcome was achieved in 9/18 (50.0%) FR patients vs. 23/59 (39.0%) non-FR patients (pϭ0.78). Conclusions: In TO patients treated with endovascular therapy consisting of initial proximal recanalization, FR occurs in nearly a quarter of patients in whom further (intracranial) intervention is no longer necessary. FR is associated with a statistically significant higher incidence of successful recanalization and a non-statistically significant higher incidence of good clinical outcome compared to patients without FR. FR represents one of the advantages of proximal recanalization as the first step in endovascular treatment of TO. Background: Endovascular reperfusion trials for acute stroke show up to 60-80% recanalization(RE) rates but good functional outcome in only 30-40% of cases. Definition of RE is usually considered as final Thrombolysis In Myocardial Infarction(TIMI) 2-3 score. We hypothesized that clinical course, infarct volume and outcome vary widely across TIMI grades in successful RE as defined in IA trials. Patients&Methods: Consecutive patients treated with IA reperfusion therapy after acute intracranial occlusion were analyzed. Vascular occlusion and RE were classified according to TIMI grade. Infarct volume was measured on 24h CT. Early clinical evolution was determined by NIHSS at baseline, after 24h and at discharge. Clinical improvement was defined as a decrease Ն4 from baseline NIHSS. Long-term outcome was evaluated by modified Rankin Scale at 3months(Good functional outcome: mRSՅ2). Results: 120 patients were included; 56(46.6%) female, mean age 70.5Ϯ11.8y and median baseline NIHSS 19 . Arterial occlusions were: 62(51.6 %) MCA, 42(35.8%) TICA, 13(10.8%) BA and 2(1.7%) PCA. At the end of IA procedure, 81(67.5%) patients achieved RE defined as TIMI 2-3. Patients who RE had better clinical evolution after 24h(55.6 vs 16%), at discharge(64.4 vs 12%), smaller infarct(mean 111.6Ϯ153 vs 239.8Ϯ168.2 cc), lower mortality(25.3 vs 56.7%) and better functional outcome(41.5 vs 3.8%) than patients who didn't (pϽ0.01). However, significant differences between TIMI grades were detected in the RE group(Table ). Patients who achieved TIMI 3 had 5-times smaller infarct and 2-times better early clinical course than those with TIMI 2a. The rate of futile RE (RE without achievement of good functional outcome) was: 81%, 70.4% and 36.4% in TIMI 2a, 2b and 3 respectevely (pϽ0.01).In patients who RE, achievement of TIMI 3 independently predicted good functional outcome after adjusting for baseline NIHSS and time to RE(OR 5.8; 95% CI 1.4-23.9; pϭ0.014).

Conclusion

Th P227 2D-3D Computational Fluid Dynamics Add Novel Dimension to Recanalization Scores in Acute Middle Cerebral Artery Occlusion

David S Liebeskind, Fabien Scalzo, Qing Hao, UCLA, Los Angeles, CA; Yiemeng Hoi, Univ of Toronto, Toronto, Canada; Kenneth R Hoffmann, Univ at Buffalo, Buffalo, NY; Xiao Hu, UCLA, Los Angeles, CA; for the UCLA Stroke Investigators Background: Angiographic scores for recanalization, or restoration of arterial patency in proximal segments after endovascular therapy, remain limited to categories of either partial or full. Hemodynamic changes at the site of recent thrombosis and catheter manipulation are unexplored. We implemented a method to convert static 2D, or standard biplane, angiography images to 3D and run computational fluid dynamic (CFD) calculations to depict subtle hemodynamic features in recanalized segments of the proximal (M1) middle cerebral artery (MCA) in acute stroke. Methods: Consecutive acute ischemic stroke cases treated with endovascular therapies for M1 MCA occlusion were analyzed. A single angiography frame from corresponding AP and lateral projections was used from a subset of 40 cases with angiographic scores of full recanalization, or Arterial Occlusive Lesion (AOL) of 3. Dedicated software was used for 3D reconstruction of orthogonal biplane images followed by post-processing with the Vascular Modeling Toolkit. Numeric simulations conducted with ANSYS CFX on a Cray supercomputer rapidly provided 3D images of velocity streamlines, wall shear stress, and shear strain rate. Results: Hemodynamic simulations from the AOL 3 recanalization cases following endovascular therapy revealed numerous distinctions on an individual case basis. Uniform velocity streamlines and evenly distributed shear stress was noted in some cases, yet other cases revealed focal abnormalities.

Such subtle hemodynamic perturbations were not evident on review of the standard biplane angiography images. Interestingly, downstream perfusion showed considerable variability despite "full" proximal recanalization at AOL 3. Conclusions: 2D-3D conversion of biplane angiography images may be used to generate CFD calculations of velocity, wall shear stress and shear strain rate from routine angiograms. 3D depictions of subtle hemodynamic abnormalities may distinguish seemingly identical cases of AOL 3 recanalization. The impact of these hemodynamic features on downstream perfusion remains to be explored.

Author Disclosures: D.S. Liebeskind: Research Grant; Significant; K23NS054084. Consultant/ Advisory Board; Modest; CoAxia, Inc.. F. Scalzo: None. Q. Hao: None. Y. Hoi: None. K.R. Hoffmann: None. X. Hu: None.

Th P228 Poorer Outcomes and Mortality in Elderly Patients treated with Intra-arterial Therapies for Acute Ischemic Stroke

Dolora Wisco, Shazia Alam, Alex Spiotta, Ken Uchino, Ferdinand Hui, Irene Katzan, Muhammad S Hussain; Cleveland Clinic, Cleveland, OH Background: Intra-arterial therapies for acute ischemic stroke are more commonly being used. While these therapies improve recanalization and are generally thought to improve outcomes, the relative benefit in the elderly population Ͼ/ϭ 80 years of age) is unknown. As the population ages and increasing numbers of elderly patients are being seen, it is important to assess the impact of intra-arterial therapies in this population. Objective: To assess procedural factors and outcomes, particularly mortality, in elderly patients undergoing intra-arterial therapies for acute ischemic stroke. Methods: From a prospective maintained database, patients undergoing intra-arterial therapy for acute ischemic stroke at Cleveland Clinic Foundation from June 2007 -February 2010 were retrospectively reviewed. Demographic information, imaging characteristics, procedural factors, and periprocedural and long-term outcomes were collected. Univariate and multivariate analysis was performed (JMP, SAS, Cary, NC)Results: 77 patients (median age 79, 55% females) had outcome data and were included in the analysis. 43 (56%) patients were Ͼ/ϭ 80 years. Characteristics and baseline NIHSS were similar between the elderly group (age Ͼ/ϭ 80 years) and non-elderly group, with the exception of a large proportion of atrial fibrillation seen in the elderly group (62.5% vs. 43.9%, PϽ0.05). Intravenous tissue plasminogen activator (tPA) was less commonly received by the elderly patients (17.6% vs. 31.0%, PϽ0.05). Elderly patients had the Penumbra aspiration device (Penumbra Inc., Alameda, CA) more commonly attempted as the first device (54.6% vs. 18.2%, PϽ0.05). Stroke etiology was less commonly large artery atherosclerosis (16.1% vs. 51.5%, PϽ0.05) and more commonly cardioembolic (77.4% vs. 40.5%, PϽ0.05). Discharge NIHSS score (17 vs. 8, PϽ0.05), discharge modified Rankin scale score (4.1 vs. 2.5, pϽ 0.05), and mortality at 90 days (42.4% vs. 18.4%, PϽ0.05) were higher in the elderly group. In multivariate analysis, age (OR 4.5) and having not received IV tPA (OR 4.8) were significant predictors of increased mortality (pϽ0.05). Conclusion: Elderly patients treated with intra-arterial therapy appear to have significantly worse outcomes as compared to non-elderly patients. Prospective studies and randomized trials focusing on this subgroup are required to assess the best treatment strategy in this population.

Author Disclosures: D. Wisco: None. S. Alam: None. A. Spiotta: None. K. Uchino: None. F. Hui: None. I. Katzan: None. M.S. Hussain: None.

Th P229 Safety of Periprocedural Heparin in Acute Ischemic Stroke Endovascular Therapy: The Multi MERCI Trial

Fadi Nahab, Emory Univ, Atlanta, GA; Gary Walker, Concentric Med, Inc., Mountain View, CA; Jacques E Dion, Emory Univ, Atlanta, GA; Wade S Smith; Univ of California, San Francisco, San Francisco, CA Background: There are limited data on the safety of periprocedural heparin in acute ischemic stroke endovascular therapy. Methods: We performed a post-hoc analysis of patients enrolled in the Multi MERCI trial to compare baseline characteristics and clinical outcomes between patients who received periprocedural heparin (HEPϩ) with patients who did not receive periprocedural heparin (HEP-). Results: Of 164 patients enrolled in the Multi MERCI trial, 51 (31%) had documentation of periprocedural heparin use (nϭ24) or non-use (nϭ27); median dose of periprocedural heparin was 3000 U. Baseline and procedural characteristics were similar between the two groups though HEPϩ patients were more likely to have vertebral or basilar occlusion than HEP-patients (16.7% vs 0%, pϭ0.04). There was no significant difference in rates of all intracerebral hemorrhage, symptomatic intracerebral hemorrhage, parenchymal hemorrhage type 2, clinically significant procedural complications or 90-day mortality between the two groups. In multivariable analysis, a 90-day good outcome (mRS 0-2) was associated with age (OR, 0.92; 95% CI, 0.86 to 0.98; pϭ0.0104), final revascularization success (OR, 6.86; 95% CI, 1.39 to 33.81; pϭ0.0179) and periprocedural heparin use (OR,5.89;95% CI,1.34 to 25.92;pϭ0.0189). Conclusions: In this small subgroup of the Multi MERCI trial, periprocedural heparin use in acute ischemic stroke endovascular therapy was not associated with increased rates of intracerebral hemorrhage or 90-day mortality.

Th P230 Multiple Merci Passes And Endovascular Treatment Outcomes: A Single Center Experience

Jitendra Sharma, Sonal Mehta, Shakeel Chowdhry, Ashish Nanda, Neelima Tummala, Kristine Blackham; Univ Hosps Case Med Cntr, Cleveland, OH Objectives: To evaluate the safety and efficacy of mechanical thrombectomy in acute ischemic stroke (AIS) patients using multiple attempts of the MERCI device. Background: The MERCI retrieval device is an FDA approved clot retrieval device used to treat AIS. Often patients need more than one attempt using this device to achieve revascularization of the occluded vessel. There is little data regarding the influence of the number of attempts on outcomes. Methods: Retrospective chart review was performed between 2005 and 2009 of patients with AIS. Patients who underwent treatment with MERCI device were selected for further review (nϭ37). We divided our study population into three groups -those who had one pass, 2 passes, or greater than 2 passes of the MERCI device for thrombectomy. This study included 13 males and 24 females with mean age of 67.8Ϯ14.96. 89.2% (nϭ33). The primary outcome measures following the intervention were recanalization rate, intracranial hemorrhage (ICH) rate and mortality rate. Results: All the patients had lesions in the anterior circulation (16 internal carotid and 21 proximal middle cerebral artery). 29 received intra-arterial tPA in addition to MERCI and 22 received a combination of IV and IA tPA. Penumbra device was used additionally in 6 patients -1 each being in group 1 and 2, while 4 patients were in Group 3. Amongst our study group, 40.5% (nϭ15) had one pass (group1), 27% (nϭ10) had 2 passes (group 2), 32.4% (nϭ12) had 3 or more passes (group 3). Group 1 (Pass 1): Partial-to-complete recanalization (TIMI 2-3) was achieved in 80% (12/15) patients. Post procedure symptomatic hemorrhages were found in 13 % (nϭ2) patients. The mortality rate was 20 % (nϭ3). Group 2 (2 passes): Partial-to-complete recanalization (TIMI 2-3) was achieved in 70% (7/10) patients. Post procedure symptomatic hemorrhages were found in 30% (nϭ3) patients. The mortality rate was 20 % (nϭ2). Group 3 (Ͼ2 passes): Partial-to-complete recanalization (TIMI 2-3) was achieved in 66% (8/12) patients. Post procedure symptomatic hemorrhages were found in 33% (nϭ4) patients. The mortality rate was 41.6 % (nϭ5). Conclusions: Patients in whom revascularization is achieved with one attempt of the MERCI device tend to have better out comes than those requiring multiple passes and had lesser rates of symptomatic hemorrhages and mortality.

Conclusions: CBV and CBF may have the potential to differentiate infarct core from ischemic penumbra in patients undergoing ERT. Further prospective study of these parameters in patients experiencing successful revascularization will be required to further refine these thresholds.

Author Disclosures: S. Mangla: None. Z. Li: None. B. Smoller: None. A. Cherney: None.

Th P232 Endovascular and Surgical Management of Symptomatic Rotational Vertebral Artery Compression Resulting from Cervical Spondylosis

Stanley H Kim, Anant I Patel, Neurosurgery, Endovascular, and Spine Cntr, Austin, TX; Kent T Ellington, Austin Neurological Clinic, Austin, TX; Muhammad Munir; Greater Austin Neurology Clinic, Austin, TX Background: Cerebral ischemia due to cervical spondylosis causing vertebral artery (VA) compression during rotation of the head has been rarely described in literature. The authors describe endovascular and surgical management of three patients with symptomatic rotational VA compression from cervical spondylosis. Methods: From 2003 to 2010, the authors encountered three patients who presented with vertebrobasilar insufficiency (VBI) or stroke and demonstrated VA compression during dynamic VA angiogram performed with the patient's head turned to the right, left, and in neutral position. We reviewed the pre-operative computed tomography (CT) scan of cervical spine to identify the cervical spondylotic bone spur and the level of the VA foramenal compression. We reviewed the angiographic and clinical outcome as determined by Modified Rankin Scale (mRS) at 90 days. Results: Pre-operative CT scan of the cervical spine showed that all three patients (mean age 60.6 ϩ 3.2) had compression of VA by cervical spondylotic bone spur at the level of the C4-5 uncinate process. Two patients developed left VA compression and near occlusion when the head was turned to left beyond 30 degrees during VA angiogram. One patient developed near occlusion of the right VA when the head was turned to right beyond 30 degrees. Two patients underwent endovascular stent placement in the symptomatic VA. One of these patients had intra-procedural complication of transient thrombosis of the stent requiring intra-arterial thrombolysis with complete recanalization. Second patient treated with stent developed recurrent symptomatic rotational VA compression at 6 months requiring angioplasty followed by left posterior cervical C4-5 and C5-6 foraminotomy at 2 years. The third patient underwent left posterior cervical C4 facetectomy and C3-5 lateral mass fixation. All patients had immediate angiographic resolution of rotational VA compression after initial treatment. Favorable outcome (mRS of 0-1) at 90 days was observed in two patients. The mean clinical follow up period was 23 ϩ 21 months (range 3 to 41 months) with no recurrent stroke. Conclusions: Endovascular stent placement and open surgical decompression of VA may be performed to treat symptomatic rotational compression of VA due to cervical spondylosis. Dynamic cerebral angiogram or computed tomographic angiogram (CTA) should be performed for accurate diagnosis. Open surgical decompression of VA with or without fusion may provide more long-term durability than endovascular treatment using stents.

Author Disclosures: S.H. Kim: None. A.I. Patel: None. K.T. Ellington: None. M. Munir: None.

Th P233 Cerebral Blood Volume Reversibility Within Infarcted Lesions: The Need for Lengthened Scan Times

Christopher D d'Esterre, Univ of Western Ontario, London, Canada; Richard Aviv, Sunnybrook Health Science Cntr, Toronto, Canada; Matthew Hogan, Ottawa General Hosp, Ottawa, Canada; Ting Yim Lee; Univ of Western Ontario, London, Canada Objective: During the first few hours of stroke onset, the use of multimodal neuroimaging to delineate penumbra from dead tissue could aid in the crucial decision to use thrombolytics. This study examined the temporal profile of CT perfusion (CTP)-derived cerebral blood volume (CBV) within confirmed infarcted lesions from admission, 24 hours and 5-7 days post stroke to determine if reduced CBV could normalize. Methods: Twelve patients underwent a NCCT, CTP/CTA scan within 6 hours of stroke onset, CTP/CTA at 24 hours, and CTP, NCCT at 5 to 7 days post stroke. Final infarct volumes were manually traced on 5 to 7 day NCCT images. These infarct regions of interest (ROIs) were superimposed onto admission, 24 hour and 5 to 7 day post CTP-derived perfusion weighted (PW) and CBV functional maps. Using custom software, PW maps were used to segment gray and white matter in the infarct ROIs. A weighted average CBV for gray and white matter was calculated from the averages of all infarct ROIs. Additionally, intra-patient CBV differences were observed. At each time point, time-density curves (TDC), taken from the ipsilateral hemisphere of each patient, were examined for truncation of the contrast wash out phase; CBV is underestimated when TDC truncation is present. Results: CBV (mean Ϯ stdev; ml/100g) for gray and white matter within infarcts at admission and 24 hours and 5 to 7 days were 1.8Ϯ0.71, 1.6Ϯ0.27, 1.8Ϯ0.51 and 1.1Ϯ 0.47, 1.2Ϯ0.46, 1.2Ϯ0.44, respectively when averaged over all patients. Unpaired t-tests showed no significant differences in CBV between time points for both brain tissue types (p Ͼ0.05). However, a repeated measures ANOVA displayed a statistically significant within-subjects effect (pϽ0.05) with a Greenhouse-Geisser correction. These differences were observed in patients whose TDC was truncated at any time point. Conclusion: Within tissue that progressed to infarction, we showed that CTP derived CBV, averaged over all patients, remained consistently low out to 7 days. Examining within patient differences, CBV was underestimated with increasing TDC truncation. We speculate this truncation is not physiological, and likely associated with insufficient scan time length. As such, low CBV lesions do not normalize and, when scan time is properly managed, could aid with final infarct volume quantification.

Th P235 Implementation Of A Patient Selection Protocol For Intra-arterial Therapy Increases Treatment Rates In Acute Ischemic Stroke

Natalia S Rost, Raul G Nogueira, Albert J Yoo, Joshua A Hirsch, Lee H Schwamm; Massachusetts General Hosp, Boston, MA Background: Limited evidence supports current patient selection for intra-arterial therapy (IAT) in acute ischemic stroke (AIS) and selection strategies are highly variable. Patients who present with proximal intracranial artery occlusion (PAO), small infarct volume, and large volume of tissue-at-risk may be most likely to benefit (LTB) from intra-arterial intervention. We sought to determine characteristics of protocol adoption and treatment rates in association with implementation of a service-wide patient selection protocol for IAT. Methods: We conducted a retrospective review of our prospectively acquired Get With the Guidelines Stroke (GWTG-S) database from 01/2007-06/2009. All patients underwent clinical evaluation by a vascular neurologist, diagnostic neuroimaging, and laboratory testing on admission. The protocol for IAT patient selection was implemented in 03/2008. Patients were defined as LTB if they had brain imaging completed within 6 hours from last known well (LKW), had NIHSS score Ն8, baseline infarct volume Յ 100 cc, and evidence of PAO (internal carotid artery or middle cerebral artery M1 or proximal M2 segments). Results: Among the 1,348 AIS patients who presented to our hospital within the study period, 118 subjects (8.7%) met criteria for LTB (mean age 66Ϯ14.8 years; 40% women; 93% Caucasian). Of those LTB, 62 (52%) underwent IAT. There was a significant increase in rates of IAT after protocol implementation (61% vs. 40%, PϽ0.02). Compared with those who were not treated, patients selected for IAT were older (75Ϯ14 vs. 70.3Ϯ15 years, PϽ0.03), received IV tPA prior to IAT more often (58.6% vs. 41.4%, PϽ0.02), had shorter median LKW to arrival time (2.7 vs. 3.5 hours, PϽ0.02), and were less often diabetic (11.3% vs. 26.8%, PϽ0.03). Among LTB patients, univariate predictors of IAT were increasing LKW to arrival time (OR 0.8, 95%CI 0.6-0.9 per hour), increasing number of calendar months within the study period (OR 1.1, 95%CI 1.02, 1.2, per month), IV tPA use (OR 0.6, 95%CI 0.4, 0.9), and diabetes (OR 0.4, 95%CI 0.1, 0.9). Following multivariable adjustment, only age (OR 0.9, 95%CI 0.8, 0.9 per year) remained an independent predictor of IAT. The predominant reason for no IAT in the LTB group was late presentation in the intervention window or concerns about reliability of the reported LKW time (21%). There was no association between use of IAT and either the individual stroke staff involved (nϭ12) or their years of experience (pϭ0.6). Conclusions: Most AIS patients did not meet our criteria for LTB, and only 52% of those defined as LTB overall received IAT. Adoption of the protocol increased use of IAT over time, across all stroke staff members. Further exploration of factors associated with the reasons for non-treatment, and the impact of IAT on outcomes, is necessary.

to poor outcomes after thrombolysis in these patients. Methods: We retrospectively identified all AIS patients age Ͼ 80 yr who received IV or intra-arterial thrombolysis (IAT) in our Get With the Guidelines Stroke (GWTG-S) database from 2/02-12/09. Vascular risk factors, symptomatic ICH (sICH) and discharge destination were abstracted from the full medical record, using GWTG-S definitions. Dementia was recorded when listed in the past history or when under medical treatment. The primary outcome was discharge destination dichotomized into "good" (discharge to home or rehabilitation facility) vs. "poor" outcome (discharge to skilled nursing facility, hospice, or death). Statistical analyses were Wilcoxon rank sum or Fisher's Exact test, and multivariate logistic regression (with variables PϽ0.2), as appropriate. Results: There were 154 AIS patients age Ͼ 80 who received either IV tPA (nϭ110), IAT (nϭ54), or both (nϭ11). Mean age was 85.8 Ϯ 4.6 years (range 80-103), 13.6% had pre-stroke dementia, 31.2% were men, 88.3% were white, and 98% were ambulatory prior to admission. Median NIHSS score on admission was 16 . Ten patients (6.5%) had sICH, of whom 3 (30%) had pre-stroke dementia, 6 (60%) received IV tPA alone, 2 (20%) received IAT alone, and 2 (20%) received both. Good outcome occurred in 84/154 (54.5%) patients, of whom 64 (59%) received IV tPA, 22 (41%) received IAT, and 3 (3.5%) received both. In-hospital mortality rate was 35% (57% in IV tPA, 54% in IAT, and 11% in IVϩIAT group). In univariate analysis, the odds of good outcome were decreased with increasing age (OR 0.94 per year above 80, 95%CI 0.1-1.01), NIHSS (OR 0.89 per point, 95%CI 0.84-0.95) as well as with sICH (OR 0.08, 95%CI 0.01-0.7), IAT (OR 0.4, 95%CI 0.2-0.8), and pre-stroke dementia (OR 0.4, 95%CI 0.1-0.9). There was a trend for good outcome among the elderly who received IV tPA (OR 1.7, 95%CI 0.83-3.4). Following adjustment for age, NIHSS, sICH, IV tPA, IAT, and pre-stroke dementia, only NIHSS (OR 0.9 per point, 95%CI 0.85-0.96) and dementia (OR 0.3, 95%CI 0.11-0.94) independently predicted the decreased odds of good outcome. Furthermore, in a multivariable logistic regression model, only pre-stroke dementia was an independent predictor of in-hospital mortality (OR 13.1, 95%CI 1.2-146) among the elderly treated with thrombolysis. Conclusions: Among the elderly, diagnosis of pre-stroke dementia is a powerful independent predictor of poor outcome and in-hospital mortality. This study emphasizes the importance of incorporating dementia into the baseline stroke assessment when considering likely outcomes after thrombolysis. These data warrant future prospective investigations to determine efficacy of acute thrombolysis in the elderly. Background and Objective: Large vessel occlusion strokes are associated with high mortality (oddsodds ratio-4.5 [95% CI, 2.7 to 7.3; PϽ0.001]) and severe disability. Intravenous (IV) tissue plasminogen activator (rt-PA) results in good outcomes in only 19% patients with large vessel occlusion (internal cerebral artery and middle cerebral artery). Randomized controlled trials studying the role of mechanical embolectomy and intra arterial rt-PA have excluded patients with NIHSS less than 8 (mild ischemic strokes (MIS)). Some cases presenting with MIS symptoms may be harboring a large vessel occlusion and may worsen during hospitalization secondary to stroke progression or recurrent stroke resulting in higher morbidity and mortality. We share our center's experience in the aggressive treatment of MIS patients with large vessel occlusion. Methods We identified cases of ischemic stroke eligible for IA rt-PA or mechanical intervention by time criteria with NIHSS score Ͻ8 admitted to Saint Luke's Stroke Center from March, 2006through April, 2010.We studied the type of intervention done and the outcome. Outcome was defined based on discharge disposition. Discharges to home with or without home health or inpatient rehabilitation were defined as good outcomes. Discharge to nursing homes or hospice homes or death were defined as poor outcomes. Univariate analysis including t-test, Chi-square, and Fisher Exact test was used when appropriate. Results Thirty five mild ischemic strokes (female to male: 1.1:1 and a mean age of 65Ϯ15 yrs ranging from 33 to 86 yrs) were included in this study. Percent of patients treated with IA rt-PA, mechanical embolectomy using the Merci Retriever and a combination of two were 60, 14 and 26 respectively. Only 4 patients (12%) deteriorated as measured by a change of 3 or more points on NIHSS at 24 hours from admission. Five patients (15%) had NIHSS worsening Ͻ2 points. There were no in-hospital mortalities. Internal carotid artery occlusion was seen in 29% patients who underwent angioplasty and stenting. Eighty six percent patients had good outcome. Conclusion: Large vessel occlusions can present as mild strokes. Aggressive treatment of these patients can result in good outcome. Randomized controlled trials are needed to test the safety and efficacy of IA rt-PA and mechanical intervention in this patient population.

Author Disclosures: M. Mittal: None. N. Akhtar: None. C. Martin: None. W. Holloway: None. R. Sugg: None. M. Rymer: Speakers; Modest; Genentech, Inc..

Th P240 Subacute Angioplasty And/or Stenting For The Stroke Patients Deteriorating Due To Vertebrobasilar Stenosis

Tomonori Iwata, Takahisa Mori, Hiroyuki Tajiri, Yuichi Miyazaki, Masahito Nakazaki; Dept of Stroke Treatment, Shonan Kamakura General Hosp, Kamakura, Japan Background: When acute stroke patients deteriorated neurologically due to vertebrobasilar stenosis, it is not established how to treat them in a subacute stroke stage and how to improve their clinical outcome. The purpose of our retrospective studies was to investigate the feasibility, safety, and effectiveness of subacute angioplasty and/or stenting for the stroke patients deteriorating due to vertebrobasilar stenosis. Methods: Included for our retrospective analysis were patients (1) who were admitted in our institution within 72 hours of stroke onset from August 2004 to August 2009, (2) without large diffusion-weighted imaging lesions, (3) with vertebrobasilar stenosis (the degree of stenosis Ͼ 50%) and (4) who developed neurological deterioration within 7 days of onset despite intensive medical treatment (an increase of 2 or more points on the National Institutes of Health Stroke Scale (NIHSS)). Some patients gave written informed consent and underwent endovascular treatment (ET) of angioplasty and/or stenting for the vertebrobasilar stenosis from 7 to 14 days after onset (group E) and others not (group C). NIHSS on admission, 7-day NIHSS after admission, NIHSS on discharge, time from onset to admission, hospitalization periods and 3-month modified Rankin Scale (mRS) were investigated between two groups and procedural success rate in group E. Results: During study periods, 12 patients were included for analysis. Among them, 4 patients underwent ET (group E) for the vertebrobasilar stenoses, which were successfully dilated. The procedural complications did not occur, whereas other 8 patients did not undergo ET (group C). There were no significant differences in NIHSS on admission, 7-day NIHSS after admission, NIHSS on discharge, time from onset to admission and hospitalization periods between two groups, whereas 3-month mRS (median) was 1.5 in group E and 3.5 in group C (pϽ0.05). Conclusion: Subacute angioplasty and/or stenting for the stroke patients deteriorating due to vertebrobasilar stenosis may be feasible, safe and effective in achieving favorable long-term clinical outcome.

Author Disclosures: T. Iwata: None. T. Mori: None. H. Tajiri: None. Y. Miyazaki: None. M. Nakazaki: None.

Th P241 Elderly Chronic Stroke Survivors Benefit From Aerobic Treadmill Exercise: A Randomized, Controlled Trial

Christoph Globas, Univ Zurich, Zurich, Switzerland; Clemens Becker, Robert-Bosch-Hosp, Stuttgart, Germany; Joachim Cerny, Judith M Lam, Univ Zurich, Zurich, Switzerland; Ullrich Lindemann, Robert-Bosch-Hosp, Stuttgart, Germany; Larry W Forrester, Richard F Macko, Univ of Maryland, Baltimore, MD; Andreas R Luft; Univ Zurich, Zurich, Switzerland Objective: To investigate the effects of 3 months aerobic treadmill training in geriatric chronic stroke survivors on cardiovascular fitness and endurance walking (primary endpoints), and on short distance gait speed, balance, functional leg strength, self-rated mobility and quality of life (secondary endpoints). Design: Randomized-controlled trial (with crossing-over of control patients, www.clinicaltrials.gov: NCT00614224) with 1-year follow-up. Setting: Outpatient rehabilitation center in a large German city. Methods: 38 stroke survivors aged 60 years or older with mild to moderate residual hemiparetic gait disturbance were enrolled 6 or more months after their stroke. Participants were randomized to receive 3 months (3x/week) progressive, high intensity aerobic treadmill exercise (TAEX) or conventional care physiotherapy (1-3x/week). Primary outcome measures were cardiovascular fitness (VO2 peak) and sustained walking capacity in 6-minute-walks (6MW). Secondary measures were gait velocity in 10-m walks, Berg Balance Scale, functional leg strength (5 chair-rise), self-rated mobility (Rivermead Mobility Index, RMI) and quality of life (SF-12). Results: Thirty-six participants completed the study (18 TAEX, 18 controls). The trial was positive in its primary endpoints: TAEX but not conventional care improved peak exercise capacity (relative improvement in VO2 peak, 30% vs. -1%, PϽ0.0001) and 6MW (22% vs. -1%, PϽ0.0001). Likewise, maximum walking speed (13% vs. -6%, pϭ0.01), RMI (pϽ0.05) and the mental subscore of the SF12 (pϽ0.05) improved more after TAEX than control. Gains in VO2 peak (r2ϭ0.2, pϭ0.008) but not gains in measures of walking correlated with the degree at which training intensity (percent heart rate reserve) could be progressed in the individual participant. In contrast, better walking was related to the individual progression in treadmill velocity and training duration (6MW: r2ϭ0.52; PϽ0.0001; maximum walking speed: r2ϭ0.37; pϭ0.0001). VO2peak and 6MW performance was still higher one year after the end of training as compared to baseline, but for endurance walking (6MW) lower than immediately after training (pϭ0.002). Conclusion: This randomized controlled trial demonstrates that aerobic treadmill exercise effectively improves cardiovascular fitness, gait, balance and quality of life in geriatric chronic stroke survivors. Fitness improves as a function of training intensity, gait improves by the number of repetitions (ϭsteps) as can be expected for task-specific exercises. Therapy effects were maintained at 1-year follow-up.

Objective: To compare the effects of ASAP to a dose-equivalent usual and customary arm therapy group and a observation only usual and customary group on functional outcomes at 12 mos post randomization. To achieve this we must randomize 360 participants at multiple sites across 3 regional centers (California, Georgia, Wash DC). Since initiating ICARE, we completed a 9-mo (08/01/08-5/31/09) start-up to procure enrollment feasibility, and 13 mos of active recruitment activities (06/23/09-08/11/10). To meet our proposed objectives, we must randomize 3 patients/center/month and continue that pace for ϳ 44 mos. Method: Working with our Data Management and Analysis Center (DMAC), we developed a comprehensive real-time tracking system to enable enrollment projections from start-up census data and early screening activities. Activities from 01/01/09 to 04/19/09 showed a total of 422 Express Chart Screens (ECS), representing an aggregate number of all new stroke admissions to inpatient rehabilitation units. From this, we estimated an aggregate annual stroke admission rate of 1447, which was 20% lower than the 2007 proposal estimate. Early low recruitment over the first 4 months was due to additional observed variations from our original proposal including: 1) continuously shortening inpatient rehabilitation stays; 2) patients discharged home directly from acute stroke unit; 3) Non-English language as sole reason for ECS exclusion is 14.1% aggregate; Ͼ 50% at one site with a majority Spanish language. These data combined with knowledge that approximately 80% of all clinical trials fail to meet recruitment goals provided impetus for the following: 1) expand enrollment window from original 1-3 mo to 14-106 days post-stroke; 2) support a Spanish translation effort; and 3) expand recruitment targets, including acute care. Results: Across 3 centers, we have performed 2979 ECS from varied sources now including 40.2% from acute, 56.8% from inpatient rehab; and we randomized 107/135 expected. Compared to an initial 4-mo 4.25/mo average randomization rate, the last 9 mos yielded an aggregate 9.4/mo rate. Conclusion: Close vigilance of site-specific and global fluctuations in recruitment, combined with a proactive and nimble administration and DMAC oversight are necessary to determine effective strategies for longer-range objectives. Carefully reasoned changes in recruitment strategies and close monitoring of dynamic changes in healthcare for stroke is essential for success in contemporary multi-site rehabilitation trials.

Background and Objective: Stroke patients can incur a loss of functional autonomy due to physical limitations from the stroke. They have persistent neurological deficits that impair daily activities, sensory disturbances and cognitive impairments that disrupt the quality of life. However, the impact on sleep-wake patterns to quality of life has not been considered as an important measure of therapeutic intervention. It is known that brain injuries can impact on both circadian and homeostatic sleep-wake processes. The manner in which these changes contribute to the quality of life in the stroke population needs to be more fully investigated. Thus, the aim of this study was to evaluate circadian and homeostatic changes in chronic stroke patients and then correlate with their quality of life. Methods:

The study analyzed 22 chronic stroke patients (55Ϯ12 yrs) and 24 healthy subjects (57Ϯ11yrs) of both genders. The instruments used were the NIHSS, IQSP, SF-36 and acthimetry assessment. Data were analyzed using the Student's t-test, Mann-Whitney, ANOVA and Spearman Correlation. Results: Findings of the study showed significant difference in sleep quality between patients and healthy, in which patients on average had a poor quality of sleep (patients: 8.4 Ϯ 3.4; healthy: 6.2 Ϯ2.5; pϭ 0.0001). With the analysis of quality of life, significant differences were also found between stroke patients and healthy subjects for all variables (pϽ0.01). With the analysis of quality of life, significant differences were also found between stroke patients and healthy subjects for all variables (pϽ0.01). Correlations showed associations between all components of quality of life and sleep quality (pϽ0.01). Among the circadian variables, the highest correlations were found between quality of life and the sum of activity (Rϭ0.48) with changes in the amplitude of the rhythm for the stroke patients (pϽ0.01). Regarding the homeostatic variables, sleep efficiency showed the highest coefficients (Table 1). Conclusions: Results suggest impairment of the circadian and homeostatic control of the sleep-wake cycle initiated mainly by the decreased level of activity from the stroke injury; thus, compromising the patients' quality of life. Therefore, it is suggested that the concerns of quality of life related to the temporal varation of activity and sleep efficiency be considered in the evaluation of stroke patients. This may provide for greater efficacy of treatment and therapeutic outcome.

Introduction:

Stroke patients show several patterns of dysphagia. The location of stroke is suggested as one of the determining factors of the dysphagia pattern. Objective: We assessed the hypothesis that the pattern of dysphagia is different according to the location of stroke lesions. Method: Two hundred ten patients with post-stroke dysphagia underwent a Videofluoroscopic Swallowing Study(VFSS). The pattern of dysphagia was assessed with parameters of swallowing process in each phases of swallowing. The character of the brain lesions were classified into infarction and hemorrhage by brain MRI or CT findings, and the location of the brain lesions was subdivided into right and left hemisphere, brainstem, and cerebellum. The dysphagia patterns of VFSS were analyzed according to stroke locations. Result: In oral phase of swallowing, patients with left hemisphere or cerebella stroke showed more frequent abnormal coordination of oral transfer (pϽ0.05). Delayed pharyngeal swallowing was seen more frequently in patients with stroke of the left hemisphere or brainstem (pϽ0.05). Drooling and biting were not different according to stroke locations. In pharyngeal phase, the range of laryngeal excursion decreased in brainstem or cerebella stroke. Bolus retention in vallecular and piriform sinuses were more frequent in left hemisphere stroke (pϽ0.05). Pharyngeal motility was reduced in patients with brainstem or cerebella stroke. Patients with brainstem stroke had a higher incidence of upper esophageal sphincter opening dysfunction(pϽ0.05). Aspiration was not different according to stroke locations. Conclusion: The pattern of dysphagia was different according to stroke locations. These results suggest that dysphagia patterns can be predicted by stroke location, and it will be beneficial to make therapeutic plans for dysphagia rehabilitation.

Author Disclosures: J. Lee: None. H. Lee: None. J. Jeong: None. K. Park: None. J. Kim: None. Y. Lee: None.

Th P247 Gender Differences Post Stroke In The Stroke Unit. Women Were More Often Aphasic

Joanna Stolzenburg, Claudia Jansen, Andrea Rocco, Werner Hacke, Peter Ringleb; Univ of Heidelberg, Heidelberg, Germany Background: Women with acute stroke are usually older, have more atrial fibrillation and higher NIH-Stroke Scale (NIHSS) scores. We wanted to know if the stroke patients in our stroke unit differ regarding stroke symptoms evaluated with the NIHSS. Methods: Between 1998 and 2006 we prospectively collected demographic data and detailed NIHSS scores from any patient admitted to our stroke unit. For this analysis we included every stroke patient with persisting symptoms and excluded patients with bilateral lesions. The remaining data set contains 3,048 patients. Univariate (Mann-Whitney U, t-or Fisher's exact test) und multivariate (logistic regression) analyses were applied using gender as dependent and age, NIHSS, type and site of stroke, aphasia, neglect, dysarthria, paresis and previous stroke in history as independent variables, in those variables having a p-value of variate tests. Results: 1,218 women and 1,830 men were included in the analysis. Women had severe strokes more frequently (median NIHSS 10 vs. 8, PϽ0.0001), were older (mean age 66.6 vs. 64.5 years; PϽ0.0001); were more often aphasic (46.0% vs. 40.1%; PϽ0.0001), more often showed a neglect (26.5% vs. 21.9%; pϭ0.004) and more often had a paresis (81.7% vs. 77.4%; pϭ0.004). There were no differences regarding type or site of stroke, presence of dysarthria or stroke in the history. Only age and aphasia remained as significant differences between men and women in this multivariate analysis (see figure). Conclusion: In this analysis we discovered that women admitted in our stroke unit with acute stroke, had a significantly higher rate of aphasia then men. There were no major differences regarding other relevant stroke symptoms. This could be an indication of gender differences of language function networks in a German population. The data gathered could prove to be useful in estimating future resources for language therapy in stroke unit patients.

Th P248 Is The Efficacy Of Low-frequency RTMS Combined With Intensive Occupational Therapy Influenced By Baseline Severity Of Upper Limb Hemiparesis In Post-stroke Patients?

Wataru Kakuda, Masahiro Abo, Kazushige Kobayashi, Toshimitsu Takagishi, Ryo Momosaki, Aki Yokoi, Akiko Fukuda, Hiroshi Ito, Ayumi Tominaga; Jikei Univ Sch of Medicine, Tokyo, Japan Background and purpose: Recently,15-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) has been applied as a therapeutic tool for post-stroke patients with upper limb hemiparesis at our department. So far, the intervention seems to be a safe and feasible approach, since all patients completed the protocol without any adverse effects. In addition, the intervention produced some functional improvement in almost all patients. The purpose of the study is to clarify the difference of clinical efficacy of the combination treatment featuring rTMS among post-stroke patients with various baseline severities of upper limb hemiparesis. Subjects and methods: Fifty-two post-stroke patients with upper limb hemiparesis (age at intervention: 57Ϯ19 years, time between onset and intervention: 52Ϯ31 months) were studied. In all subjects, motor recovery of the affected upper limb was considered to have reached a plateau state at admissions, and baseline severity of upper limb hemiparesis at admission was categorized as Brunnstrom stage 3-5 for hand-fingers. During 15-day hospitalization, each patient was scheduled to receive 22 sessions of 20-minute low-frequency rTMS to the non-lesional hemisphere and 120-minute intensive occupational therapy consisting of one-to-one training and self-training. Motor function of the affected upper limb was evaluated with Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) on the day of admission and discharge. For WMFT performance time, natural logarithm of the time was calculated to normalize the distribution of the data. According to Brunnstrom stage for hand-fingers at admission, subjects were divided into 3 groups such as Stage 3 group (nϭ13), Stage 4 group (nϭ20) and Stage 5 group (nϭ19). Among these 3 groups, the extent of changes in the measures with the intervention were compared. Results: Although significant score increase in FMA was found in all groups, Stage 4 group showed significantly larger score increase in FMA as compared with other 2 groups (2.5 points in Stage 3 group, 5.1 points in Stage 4 group, 2.3 points in Stage 5 group. all p Ͻ 0.05). Similarly, natural logarithm of WMFT performance time significantly decreased in all groups. However, the difference in decrease of the natural logarithm was significant between Stage 3 group and Stage 4 group, and between Stage 3 group and Stage 5 group (0.04 in Stage 3 group, 0.41 in Stage 4 group, 0.35 in Stage 5 group. all p Ͻ 0.01). Conclusions: The extent of motor improvement of the affected upper limb with the intervention was significantly influenced by baseline severity of upper limb hemiparesis after stroke. It seems that optimal candidates for the intervention are post-stroke patients with upper limb hemiparesis which is categorized as Brunnstrom stage 4-5 for hand-fingers.

Author Disclosures: W. Kakuda: None. M. Abo: None. K. Kobayashi: None. T. Takagishi: None. R. Momosaki: None. A. Yokoi: None. A. Fukuda: None. H. Ito: None. A. Tominaga: None.

Th P249 Comparison of High and Low Dose Oral Corticosteroid Therapy on Complex Regional Pain Syndrome Type I after Brain Injury

Ju Kang Lee, Jeom Sun Jeong, Chung Hwan Choi, Yeong-Bae Lee, Ok Kyung Lim; Gachon Univ Sch of Medicine, Incheon, Korea, Republic of Introduction: Complex regional pain syndrome (CRPS) type I is a disabling complication in patients with hemiplegia from brain lesion. It usually hinders functional recovery of involved upper extremity of hemiplegic patients. Objective: We assessed the hypothesis that there would be no difference of treatment efficacy between high and low dose oral corticosteroid therapy on CRPS type I after brain injury, and investigated the value of three phase bone scan(TPBS) as a follow-up marker for severity of CRPS type I. Materials andMethods: 17 hemiplegic patients diagnosed as CRPS type I after brain injury(strokeϭ13, traumatic brain injuryϭ4) were randomly treated with high dose(60mg, Nϭ7) or low dose(15mg, Nϭ10) oral corticosteroids(prednisolone) for 2 weeks. Clinical efficacy of treatment was measured with 'severity score' and 'Kozin's classification' by a blinded expert. TPBS was also done before and after oral corticosteroid therapy. Uptake ratio of hand and wrist was calculated by radioisotope count of affected side divided by radioisotope count of unaffected side in pooling and delayed phases. Results: All patients treated by high or low dose oral corticosteroids were improved on severity score(pϭ0.0003) and Kozin's classification(pϭ0.005). The treatment efficacy was not different between high and low dose oral corticosteroid therapy(pϾ0.05). Uptake ratio of radioisotope on TPBS was not changed after treatment(pϾ0.05), and showed no difference between high and low dose oral corticosteroid therapy(pϾ0.05). Conclusion: Low dose oral corticosteroid therapy was as effective as high dose therapy on CRPS type I after brain injury. TPBS is not recommended as a follow-up marker for severity of CRPS type I.

Author Disclosures: J. Lee: None. J. Jeong: None. C. Choi: None. Y. Lee: None. O. Lim: None.

Th P250 Body Mass Index Predicts Outcomes in In-patient Neuro-rehabilitation

Sahar Yazdani, khyber Med College, Peshawar, Pakistan; Nkiruka Arene; Johns Hopkins Univ, Baltimore, MD BACKGROUND and HYPOTHESIS: High body mass index (BMI) is a risk factor for multiple co-morbidities such as diabetes, hypertension, atherosclerosis and stroke, and patients with obesity are at an even higher risk for such medical complications, which often require inpatient rehabilitation as part of management and recovery. Although the link between high BMI and co-morbidities is well established, the relationship between high BMI and recovery in inpatient rehabilitation has not been fully elucidated but we hypothesize that it is likely to be detrimental. AIM: To evaluate the impact of BMI on functional outcomes during acute in-patient neuro-rehabilitation. Methods: A prospective, observational study of 214 patients in an acute inpatient neuro-rehabilitation setting. Diagnoses included traumatic and non-traumatic brain injuries and strokes. Functional Independence Measure (FIM) scores were used to measure outcomes. FIM scores were measured at admission and discharge from acute inpatient rehabilitation and at 3 months follow up. BMI was recorded at admission, and correlated with the FIM change at discharge and at 3 months. Obesity was regarded as BMI Ͼϭ30. Those with BMI 25-29 were considered overweight. Results: forty two percent of patients were overweight, while 27% were obese. Linear regression was used to seek an association between BMI and FIM change (i.e., the difference between discharge and admission FIM scores). Thirty percent of patients suffered a negative FIM change, i.e., a regression in FIM scores, while 70% had a positive FIM change. There was a statistically significant association between BMI and FIM change (pϭ0.034). High BMI was particularly associated with negative FIM changes (pϭ0.004). Obesity was associated with a negative FIM change (pϭ0.044). Conversely, lower BMI was associated with positive FIM changes (pϭ0.018), while obesity was not. At 3 months follow up, normal weight was associated with a positive FIM change (pϭ0.04), but there was a trend towards negative FIM changes for the obese (pϭ0.078).

Conclusion:

High BMI is associated with negative FIM change and hence a tendency towards worse rehabilitation outcomes for stroke and other neuro-rehabilitation patient, even at 3 months post discharge from inpatient rehabilitation. Greater emphasis should therefore be paid to nutritional management in primary prevention and rehabilitation practices.

Author Disclosures: S. Yazdani: None. N. Arene: None.

Th P251 Effect of Statins on Functional Rehabilitation Outcome in Stroke Inpatients in Convalescence Stage

Tomoko Kagiyama, Teruo Soeda, Yoko Yokoyama, Noriko Hagiwara, Yoshimasa Watanabe, Yoshihiro Ishimatsu, Nobuhiko Yokoyama, Kenji Kusuda, Tooru Kurokawa, Kaoru Onoyama, Setsuro Ibayashi; Seiai Rehabilitation Hosp, Onojo, Fukuoka, Japan Back ground and purpose: Statin is reported to have a role to improve neurological function during acute phase of ischemic stroke. Herein, we have shown that statin may have a role to improve neurological function during the subsequent rehabilitation period in convalescence stage. Methods: As a retrospective study, 301 ischemic stroke patients were admitted to our institute during June 2007 to May 2009. The patients who had in-hospital rehabilitation at least 28 days were enrolled to this study. The patients were divided into statin group (age 69.3Ϯ11.4 years; meanϮS.D., nϭ84) and non-statin group (age 72.7Ϯ12.9 years, nϭ219). Statin group was also divided into early-statin group; statin being started before or within 14 days of admission to our institute (nϭ70), and late-statin group (nϭ14); ibid., after 14 days of admission. The effects of neurological improvement were assessed by Functional Independence Measure (FIM) and Barthel Index (BI). Results: Cholesterol data of 2 groups were not different (T-Chol 175.4Ϯ40.2, LDL-Chol 106.1Ϯ34.3 mg/dl as statin group, and T-Chol 177.5Ϯ3.1, LDL-Chol 109.8Ϯ27.0 mg/dl as non-statin group). Systolic and diastolic blood pressure was not different (118.8Ϯ1.9 and 68.8Ϯ10.5 mmHg as statin group, 119.1Ϯ15.9 and 69.1Ϯ10.6 mmHg as non-statin group). Statin group showed a significant improvement in post-rehabilitation cognitive FIM score (25.5Ϯ8.0 to 28.0Ϯ7.4) as compared with that in non-statin group (24.2Ϯ9.1 to 25.8Ϯ8.8, PϽ0.05) and a better tendency of post-rehabilitation BI score (56.8Ϯ27.0 to 77.7Ϯ28.1, and 52.9Ϯ28.9 to 70.5Ϯ30.1, respectively, pϭ0.09). Although there were no differences on FIM gain (19.9Ϯ17.2 and 18.7Ϯ18.9) and BI gain (21.0Ϯ15.4 and 17.6Ϯ15.8). Late-statin group showed a higher improvement in cognitive FIM score gain as compared with that in early-statin group and non-statin group (5.4Ϯ5.7, 1.9Ϯ4.7 and 1.6Ϯ6.0, respectively, PϽ0.05) and BI gain (27.1Ϯ17.4, 21.2Ϯ15.9 and 17.1Ϯ16.4, respectively, PϽ0.05). Because early statin group had already better FIM scores in comparison to non-statin group (cognitive 26.3Ϯ7.7 and motor 52.1Ϯ17.9, as compared with cognitive 24.2Ϯ9.1 and motor 47.2Ϯ18.7, pϭ0.08 and pϭ0.058, respectively), there might be no significant gains. Conclusion: Statin group showed much more improvement in cognitive FIM score during post-rehabilitation periods. Because this is a retrospective study, functional scores on the admission period were not even, namely e.g., early statin group had already higher scores on the stage of admission. However, even late timing of administration of statin may have a role to improve neurological function on ischemic stroke patients in convalescence stage.

term effects of an intervention to enhance participants' adherence, health status, and quality of life for older adults with stroke.

Author Disclosures: Y. Park: Research Grant; Modest; This study was supported by the Korea Research Foundation Grant (810-20080029).. H. Chang: None.

Th P257 Code 20 Increases Identification and Treatment of In-Hospital Stroke

Deborah M Mastrolia, Kathleen Furlong; Hoag Hosp, Newport Beach, CA Background: Stroke is a medical emergency. In-hospital stroke (IHS) represents 6.5 -15% of all strokes. The treatment goal for acute ischemic stroke is to reperfuse ischemic brain tissue. Delay in recognition due to comorbidities and delay in brain imaging with neurologist evaluation are common. Unlike the response for cardiac arrest, most hospitals have no organized system in place for the patient having an acute stroke while hospitalized. Purpose: The purpose was to increase recognition of IHS, develop an organized acute stroke code process with rapid brain imaging and interpretation, increasing treatment rates and improving patient outcomes. Methods: FAST test was used to teach stroke recognition to all hospital employees. An online stroke education module, in-services and dedicated stroke champions on each unit helped reinforce the teaching. The Rapid Response Team (RRT) at Hoag Hospital consists of experienced critical care RNs. Stroke symptoms, establishing a "last time seen normal", NIH Stroke Scale, treatment options and IV tPA competencies were part of a class for all RRT RNs. A "Code 20" is called by RRT for any patient exhibiting the signs and symptoms of stroke, last time seen normal within 8 hours. This code pages Stroke Team, which provides a neurologist, Stroke Unit Charge Nurse and CT. Stroke Protocol Orders are initiated. The goal is to arrive at CT scan within 20 minutes of calling the code. The RRT RN discusses treatment plan with neurologist and transfers patient to the appropriate level of care to facilitate thrombolytic therapies as needed. Restrospective ongoing analysis of RRT Code 20 calls over the time period of 5/1/2008 -7/31/2010 was undertaken. This includes monthly reports to committee, case studies and immediate debriefing with the RNs involved. Results: A total of 160 Code 20s have been called since program rollout. 23% (37/160) were new IHS, 13% (21/160) were TIAs. 16% (6/37) IHS received IV tPA, 2.7% (1/37) IHS received IA tPA with Penumbra thrombectomy for a total of 19% (7/37) treatment rate for IHS. 2.5% (4/160) of Code 20s were acute ICH. Conclusions: RRT Code 20 is an effective tool for the management of acute in-hospital stroke. Ongoing education with real time feedback to the nurses involved with each case is needed to decrease the false positives called as Code 20s. Several other neurological emergencies were also rapidly identified and treated.

Author Disclosures: D.M. Mastrolia: None. K. Furlong: None.

Th P258 Feasibility of Screening Swallowing in Patients with Stroke Symptoms in the Emergency Department

Jane A Anderson, Nancy J Petersen, Stephanie K Daniels; Michael E. DeBakey VA Med Cntr, Houston, TX Background: Early detection of dysphagia is critical in acute stroke as it allows for immediate intervention thereby reducing morbidity, length of stay, and healthcare costs. Completing a swallowing screening test (SST) in the emergency department (ED) appears most logical given American Heart Association/American Stroke Association recommendations and the potential need for rapid administration of medication. Research has suggested that SSTs with trial water swallows are the most accurate in identification of patients with risk of dysphagia. Barriers to implementing a SST, particularly one with a water swallow component, in the ED are unknown Objective: The aims of this study were to: 1) implement a stroke dysphagia screening protocol in the ED, that included water swallows, and track clinicians' adherence with the protocol over time; 2) assemble ED nurses for focus group sessions to identify barriers and facilitator to administering a SST with water swallows; and 3) develop and implement a process improvement plan to address identified barriers to administering a SST with water swallows in the ED. Methods: A standard SST that incorporated water swallows was introduced in the ED. A process approach was utilized as follows: 1) education on SST administration to all ED nurses, 2) semi-structured interviews with a convenience sample of 9 ED nurses, and 3) implementation of suggestions obtained from focus groups. The number of screenings completed in the ED was tracked monthly from December 2009-June 2010. Results: The Cochran-Armitage Test was calculated to determine if there was a trend over time in the percent of patients who received the SST in the ED. Results indicated a statistically significant change over time, p ϭ 0.0173. Barriers identified from interviews were: 1) documentation of screening in computerized record system, 2) recall of screening items during administration, and 3) inconsistent method of SST administration. To address these identified barriers, the following were implemented: 1) documentation dysphagia screening template in the electronic medical record, 2) pocket cards with SST screening items and steps for water swallow test 3) a video training module of the SST procedure, and 4) continued focused staff education with demonstration feedback. Conclusions: Results indicate that it is feasible to administer a SST with a water swallow component in the ED. Involvement of ED staff in the implementation process is critical to success. Supported by: Department of Veterans Affairs HSR&D RRP-09-182 Author Disclosures: J.A. Anderson: None. N.J. Petersen: Research Grant; Modest; Dept of Veterans Affairs HSR&D. S.K. Daniels: Research Grant; Significant; Department of Veterans Affairs HSR&D.

Th P259 The Benefits of Multidisciplinary Stroke Grand Rounds on Ischemic Stroke Patient Length of Stay

Theresa Hall, Joyce Quijano, Cheryl Jastrzebski; MacNeal Hosp, Berwyn, IL Background and issues: Primary Stroke Centers employ American Stroke Association guidelines to achieve the best patient outcomes. A study by Furlong et al. (2007) states that Nursing Grand Rounds focuses on "a situation-based interpretive learning by identifying and describing knowledge for clinical practice and incorporating evidence into practice" (p. 288). There is no definitive evidence to support that Nursing Grand Rounds benefit patient care. At our institution, only an annual nursing continuing education credit for stroke was offered. Quarterly Multidisciplinary Stroke Grand Rounds were implemented to improve patient care through stroke awareness, promotion of enthusiasm, and highlighting best practices. Both Nursing and Medical Continuing Education credit was offered to participants. According to the American Heart Association, "stroke requires the efforts and skills of all members of the multidisciplinary team" (Summers et al., 2009(Summers et al., , p.2911)) Background and Purpose: Stroke is the third major cause of death and the leading cause of long term disability in the United States. Rapid entry into the Emergency Medical System, hospital transport, and Emergency Department (ED) and neurology evaluations is essential in assessing patient eligibility for thrombolytic therapy. Difficulty in obtaining CT brain imaging frequently result in treatment delays. The purpose of this project was to measure CT scan turnaround time delays and evaluate how shortening CT turnaround times significantly decreases the overall evaluation period of the patient. Methods: Directed by the LEAN methodology, a multidisciplinary project team was formed to develop and measure aspects of the current procedure, analyze data, investigate and identify the causes of any delays and form action plans to improve and hardwire a new process. CT scan turnaround times were defined and measured as the total time in minutes from when the CT was ordered to when the Radiologist interpreted the scan as evidenced by the posting of the final report in the electronic medical record. We included in the analysis CT stroke brain scans ordered from the ED along with those ordered for in-house stroke codes. All door to IV rt-PA times were included as part of the review. The data was collected and analyzed to identify delays and quantify their causes. Results: Upon reviewing and analyzing the four months of data, the project team members noted that the median CT brain stroke turnaround times for 16 patients was 28 minutes with 64% of patients receiving IV rt-PA within 60 minutes of arrival. CT delay variances included patient registration delays, a variation in the language used when requesting a CT stroke brain, a lack of uniform notification of CT personal of a stroke code, and in-house transportation delays. Action plans were developed to address rapid imaging in unregistered patients, differentiating stroke protocol stat CTs from non stroke stat CTs and accelerating transportation. This multidisciplinary quality improvement project resulted in a decrease in the median CT brain stroke turnaround time for 20 patients to 21 minutes with 86% of the patients receiving IV rt-PA within 60 minutes after triage. Conclusions: The project team was able to identify barriers, recommend process changes and ensure the implementation of change within the institution. Data collection and process revision is ongoing.

Author Disclosures: J.M. Mazabob: None. G. Brown: None. P. Stewart: None. S. Livesay: None. S. Freeborg: None. J. Suarez: None. E. Bershad: None. S. Smirnakis: None.

Introduction:

The Northeast Cerebrovascular Consortium (NECC) was established in 2006 in eight states in the Northeast (CT, MA, ME, NH, NJ, NY, RI & VT) to address the regional disparities in stroke care. The NIHSS is widely accepted as a standard clinical measure of stroke severity. We sought to analyze patterns of use and barriers to hospital based implementation of the NIHSS. Methods: The NECC surveyed all GWTG-Stroke hospitals in NECC region. Online surveys were sent to 240 stroke coordinators in June 2010. The surveys assessed use of the NIHSS and any need for additional NIHSS training. Response options allowed multi-selection of categories. Differences in responses were evaluated using Fisher's exact test. Results: A total of 77 stroke coordinators (32%) completed the survey, representing 7/8 NECC states (none in VT). Stroke severity assessment using the NIHSS was more common than using a modified NIHSS or other scale, 84.4% (65/77) vs. 5.1% (4/77), pϭ.0001. Ten percent (8/77) reported using no scale. Nurses were more frequently identified as performing the scale 41.5%, than emergency physicians (25.9%, p ϭ .06), neurologists (20.7%, p ϭ .009) and other staff (attending physicians, stroke program coordinators)( 3.8%, p ϭ .0001). Forty five percent (35/77) reported using on-line training; of the 35 sites, use of the American Heart Association on-line tool (77.1%)was significantly higher than use of the National Stroke Association on-line tool (17.1%), pϭ0.0001, and use of alternative tools or methods (5.7%),pϭ0.0001. Only 51% of all hospitals felt their hospital's present plan for NIHSS training met their needs, regardless of whether they currently use the NIHSS scale, and 70% expressed interest in assistance with formal training on the NIHSS by the NECC. Only 53.2% (41/77) indicated adequate administrative buy-in for NIHSS training, with the remainder reporting none (15.6%) or uncertain (31.1%) buy-in. Conclusions: A majority of hospitals in the Northeast are using the NIHSS to assess stroke severity, and the NIHSS is most often performed by nurses. Although hospitals are providing some NIHSS training, stroke coordinators identify a need for more staff training. Further research is required to determine the prevalence and causes of variations in administrative support for training in stroke assessment.

Th P262 No Association Between Post Stroke Emotional Dysfunction And A Tryptophan Hydroxylase 1 Gene A218C Polymorphism In a Korean Population

Smi Choi-Kwon, Seon Young Choi, Min Hee Suh, College of Nursing Seoul National Univ, Seoul, Korea, Republic of; Jong S. Kim; Dept of Neurology Asan Med Cntr, Seoul, Korea, Republic of Background and purposes: Emotional dysfunction is common in patients with stroke. There has been a body of literatures suggesting that serotonergic system dysfunction plays a role in the development of post stroke emotional dysfunction (PSED). There also has been some evidence which points to the involvement of tryptophan hydroxylase 1 (TPH1) gene in depression and anger-related traits in various psychiatric conditions. However, the role of a TPH1 gene A218C polymorphism responsible for 5-HT synthesis remains unclear in patients with PSED. Methods: A total of 539 patients with acute ischemic stroke admitted at Asan Medical Center were screened consecutively for post stroke depression (PSD), post stroke emotional incontinence (PSEI), and post stroke anger proneness (PSAP) at admission and 3 months after stroke. Blood samples were collected and genotyped from all participants for a TPH 1 A218C polymorphism. PSD was evaluated by Beck Depression Inventory, PSEI by Kim's criteria, and PSAP by modifications of Spielberg trait anger scale. Results: PSD was developed in 13.7 % and 16.0% whereas PSEI in 8.2% and 10.1%, and PSAP in 15.5 % and 23.6 % at admission and 3 months post-stroke, respectively. The distributions of the TPH1 A218C genotypes were in Hardy-Weinberg equilibrium. At admission, there were no significant differences in the TPH1 A218Cgenotype or allele frequencies between the patients with PSD, PSEI, PSAP (vs., those without), respectively. No differences were found between the patients who newly developed PSD, PSEI, PSAP at post-stroke 3 months and those who did not. No differences were also found between the patients who recovered from PSD, PSEI, or PSAP at 3 months and those who did not. Conclusions:Our data suggest that the A218C polymorphism of the TPH1 gene is not associated with PSD, PSEI, or PSAP at acute and sub acute stages.

Author Disclosures: S. Choi-Kwon: None. S. Choi: None. M. Suh: None. J. Kim: None.

Th P263 A Quality Initiative To Improve Stroke Education Compliance

Nadine F Lendzion, Jennifer Berry, Patricia H Miller, Terri J Kiernan; MAYO CLINIC HOSPITAL, Phoenix, AZ Patient education is a key component of optimal stroke care. Stroke survivors and their care givers benefit from education related to the diagnosis of stroke and secondary stroke prevention. Get With The Guidelines-Stroke (GWTG) identifies stroke education as a primary quality indicator. An analysis of data for the GWTG indicator for Stroke Education at Mayo Clinic Hospital showed an opportunity for improvement with a compliance rate of 28%. Initially, a workgroup was formed to develop an education packet containing stroke education that would meet the Joint Commission/GWTG required elements and allow for individualization to meet the patient's specific needs. These included education on stroke risk factors, understanding newly prescribed medications, the need for follow-up post hospital discharge, stroke signs and symptom identification and why the patient should access emergency assistance immediately. This resulted in a compliance improvement from 28% to 60% but it was evident that more work was needed. Over the course of the next year there was increased focus on staff education related to use of the stroke packets and documentation of education provided. This was accomplished through Team Days, educational flyers and mandatory online education. Additionally, nurses from the stroke workgroup audited charts daily to ensure patients received stroke education and reinforced the need for education with the nurse. Compliance increased from 60% to 81%. It was determined that education was being provided and stroke packets utilized, but consistent documentation was lacking. To facilitate an improvement in documentation, the workgroup created a reminder sticker which was placed on the front of the stroke packet to prompt the nurse to document stroke education provided. Recognizing the provider's role in stroke education, an admission/discharge dictation template was created to remind the team to document the core measures as well. As a result of these efforts, compliance increased to 92%. These improvements demonstrate the importance of focused interventions to address deficiencies that could potentially impact stroke outcomes. By employing different strategies and utilizing the multidisciplinary team, patient care improvements can be achieved and maintained over time.

Author Disclosures: N.F. Lendzion: None. J. Berry: None. P.H. Miller: None. T.J. Kiernan: None.

Th P264 Salt and High Blood Pressure-Is Motivation Enough?

Leigh Ann McCartney, Ghousia Wajida, Cathy Sila; Case Med Cntr, Cleveland, OH Objective: High blood pressure is the most important risk factor for cardiovascular disease yet only 20% of patients with high blood pressure are aware of the diagnosis and only 35% of patients with known high blood pressure report good control. We set out to raise public awareness about the effects of dietary sodium on blood pressure, heart attack, stroke and kidney disease and to develop an easily accessible curriculum for communities that discusses sodium content, concomitant lifestyle changes and nutritional strategies to reduce stroke risk factors. Methods: We developed a community education module of salt intake, dietary information, and blood pressure education in conjunction with blood pressure screenings at four local community centers in Cleveland, Ohio. Educational materials used included a short PowerPoint presentation, handouts, an illustrative poster identifying sodium content in popular foods, and a question and answer session. Participants completed short, anonymous and confidential questionnaires both pre-and post-education surveying their risk factors, willingness to change and knowledge of the topics. Results: A total of thirty-three participants completed all the activities. The frequency of hypertension was 33%. Willingness to change, assessed by a reported desire to cut back on their daily salt intake was reported by 63% of the participants; 82% of those with high blood pressure versus 50% in those with normal blood pressure (Pϭ 0.08). The majority (74%) reported reading food labels but the actual sodium content in their favorite foods were quite a surprise. Mastery of the key messages of the daily maximum of sodium equivalent to a teaspoon significantly improved following education from 24% (nϭ8) on the pre-test to 54% (nϭ18) on the post-test (Pϭ 0.016). Conclusions: Our study demonstrates that an interested and self-motivated group of participants who reported reading food labels had limited knowledge of the basic information on the sodium content of foods. Although there was substantial willingness to change, particularly among those with hypertension and significant improvement with the focused education, the mastery of simple key messages was still only achieved in half the participants. These findings support the April 2010 recommendations from the Institute of Medicine to reduce sodium content in foods to assist individuals in reducing their daily sodium intake.

Author Disclosures: L. McCartney: None. G. Wajida: None. C. Sila: None.

Th P265 Short-Term Compliance with a Stroke Prevention Education Program and Distribution of Sphygmomanometer in Hospitalized Patients

Lillie Hudson, Nerses Sanossian, Amytis Towfighi, Univ of Southern California, Los Angeles, CA; Eric Cheng, William Cunningham, Barbara G Vickrey, Univ of California Los Angeles, Los Angeles, CA; SUSTAIN Investigators and Coordinators Background: Hypertension is the most prevalent and one of the most potent modifiable risk factors for stroke. Underserved populations, including minorities, are less likely to achieve reductions of blood pressure to nationally recommended goals after stroke. Enhanced stroke prevention education prior to hospital discharge including education on how to monitor of blood pressure (BP) at home may help patients with awareness and control of hypertension. Objective: To report short-term results of a stroke prevention educational program highlighting the importance of monitoring BP at home combined with distribution of a sphygmomanometer. Methods: All patients participated in SUSTAIN (Systemic Use of STroke Averting Interventions), a novel stroke prevention care program, which incorporated features of the chronic care model, group clinics and care coordination by a physician assistant (Care Manager). The program emphasizes education on the importance of vascular risk factor reduction for secondary stroke prevention and instruction on using a home sphygmomanometer prior to discharge from acute stroke hospitalization. All patients were discharged home on antihypertensive therapy according to recommendations of the Joint National Committee 7th edition (JNC7), with a goal of normotension (BP Յ 120/80). Patients were asked to record their blood pressure twice a day and to report their BP readings to the Care Manager at a one week post-discharge follow-up telephone call. Results: A total of 13 patients (8 male, 5 female) participated in the educational Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

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International Stroke Conference and Nursing Symposium Poster Presentations e329

by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from program prior to discharge from transient ischemic attack/acute ischemic stroke hospitalization and were given a sphygmomanometer for use at home. Mean age was 57 (standard deviation 8, range 49-77) years old, 11 were Latino, 7 were diabetic and all 13 were dyslipidemic (defined as LDL Ն 100). Four individuals were pre-hypertensive and nine were hypertensive (5 stage 1, 4 stage 2). All patients made contact following discharge and 11 (85%) were within the desired BP range. The 13 patients recorded and reported a mean of 12 (range 7-13) individual BP readings. There were no reports of difficulty using the sphygmomanometer or recording BP readings at home. Conclusions: A hospital-based program of stroke prevention education and distribution of sphygmomanometers in hospitalized patients yielded high rates of short term compliance. The SUSTAIN clinical trial will be testing the long-term effects of this intervention on BP control. This research has received full or partial funding support from the American Heart Association, National Center.

Th P266 Risk Factor Profiles Differ in Very Elderly Stroke Patients

Mary P Amatangelo, Fabricio O Lima, Ashley K Birch, Rebecca E Green, Aaron R Rodriguez, Tijy Thankachan, Karen L Furie; Massachusetts General Hosp, Boston, MA Background: Risk factor screening and counseling are generally applied in a non-specific fashion. We sought to determine if the prevalence of stroke risk factors in a high risk population of stroke patients, in fact, varied by age. Methods: This is a cross-sectional study of consecutive acute stroke patients enrolled in a multicenter acute ischemic stroke biomarker project. Clinical and demographic data including NIHSS scores at baseline and 3 month mRS were collected. Patients were divided into quintiles based on age. Those in the highest quintile were compared to all other quintiles on baseline clinical, demographic, treatment, and outcome variables. Data analysis employed basic descriptive statistics. Hypothesis tests were performed using 2-tailed tests and the level of significance was set at aϽ 0.05. Results: We analyzed data on 464 subjects. There were 93 subjects in the highest age quintile (mean age 88.5, s.d. 3.1) and 371 in the remaining quintiles (mean age 66.6, s.d. 14.8). There were more women in the highest quintile, compared to the younger group (62% vs. 40%, pϭ0.0002) Compared to younger patients, those in the highest quintile had a higher prevalence of HTN (86% vs. 67%, pϭ0.0006), atrial fibrillation (59% vs. 24%, PϽ.0001) and a lower prevalence of smoking (52% vs. 35%, PϽ0.0001). Subjects in the highest quintile had a lower BMI (mean 22.7 vs. 27.7, PϽ.0001), more severe strokes (mean NIHSS 9.5 vs. 7.2, pϭ.0001) and higher 3-month mRS scores (pϽ.0001).There was no significant difference in the prevalence of prior stroke, prior TIA, DM, hyperlipidemia, carotid stenosis, CAD, or the use of tPA across the quintiles. Conclusions: Very elderly (Ͼ85 years) stroke patients have a higher prevalence of atrial fibrillation and hypertension compared with younger stroke patients. They are less likely to have a history of smoking or be obese. These very elderly patients have more severe strokes and poorer outcomes.

Author Disclosures: M.P. Amatangelo: None. F.O. Lima: None. A.K. Birch: None. R.E. Green: None. A.R. Rodriguez: None. T. Thankachan: None. K.L. Furie: None.

Th P267 Lack of Knowledge of the Risk of Stroke in Women using Hormonal Contraceptives

Angela N McCall-Brown, Atlantic Health-Overlook Hosp, Summit, NJ; Stephanie M Rizzo; Atlantic Health-Morristown Memorial Hosp, Morristown, NJ Lack of Knowledge of the Risks of Stroke in Women using Hormonal ContraceptivesIntroduction: Since the early 1960s, links between womens' use of oral contraceptives and increased risk for stroke have been established. With 100 million women worldwide using oral contraceptives, education and ongoing clinical monitoring of women's use of oral contraceptive users is essential (Gillum and Johnston 2004). Generally, risk-awareness originates from physican/nurse education during medical contact, package inserts and the popular media. The present study evaluated whether women who use of oral contraceptives who suffered stroke had been educated on the risk due to oral contraceptives. Methods: A retrospective chart review of twenty female patients with stroke aged 30-45 with a final primary diagnosis of ischemic or hemorrhagic stroke from 2008 to 2010. During post stroke education patients' were interviewed concerning their experiences of warnings on the risk of stroke due to oral contraceptives. Each chart was also reviewed for the correlation between the patient history of taking hormone components whether via oral contraceptives, IUD, or deprovera and if the patients had experienced a stroke. Results: 9/20 (45%) were diagnosed with ischemic stroke and 11/20 (55%) were diagnosed with either subarachnoid or intracerebral hemorrhagic stroke. None of the patients recall being educated specifically concerning increased risk of stroke related to women's use of oral contraceptive use. Of these twenty patients 5/20 (25%) were sent home without needing outpatient services, 3/20 (15%) were sent home needing outpatient services, and the remaining 12/20 (60%) needed to be referred to an inpatient rehabilitation setting. Conclusions: Stroke education in young women has routinely focused on hypertension, diet and obesity, hypercholesteremia, family history, irregular heartbeat, smoking and diabetes. The lack of specific understanding of the increased risk of stroke related to women's use of oral contraceptive use strongly indicates that better strategies to educate women at risk are needed. By being aware of the combination of risk factors may facilitate better preventative care and reduce the incidence of stroke.

Author Disclosures: A.N. McCall-Brown: None. S.M. Rizzo: None.

Th P269 A Descriptive Study of Cognitive Status Three Years Following Motor Stroke

Janice L Hinkle; The Catholic Univ of America, Washington, DC Stroke is the third leading cause of death in the United States and a leading cause of disability in the rapidly aging population. In the post-stroke period, intact cognition is needed to form new memories, devise problem solving strategies, or recognize dangerous situations. This is especially true for patients who have had a motor stroke, who most often have a short hospital stay and then return home to devise new strategies, cope with deficits, and attempt to make a good functional recovery. Furthermore, advanced age and decline in cognitive status are key factors in institutionalization following stroke yet cognitive status 3 years after one particular type of ischemic stroke, motor stroke, has received minimal attention. The purpose of this study, part of a larger 3 year follow-up study following patients after stroke, was to describe cognitive status 3 years following motor stroke. At 3 years of the 60 patients available, 11 had died, 30 consented to a home visit and 19 were interviewed by telephone. The mean age of patients at the time of follow-up was 64 years and cognitive status was measured using three instruments. The mean Mini-Mental State Examination (MMSE) score for the group was 27.53 (Ϯ 2.74); there were no statistically significant differences in men with a mean score of 27.29 (Ϯ 3.26) and women with mean scores of 27.75 (Ϯ 2.26). Mean scores on the Neurobehavioral Cognitive Status Examination (Cognistat) for the group were 69.67 (Ϯ 15.62); there were no statistically significant differences between men with a mean score of 69.50 (Ϯ 19.36) and women with mean scores of 69.81 (ϩ 12.10). The mean cognitive subscore of the Functional Independence Measure (FIM TM ) was 26.5(Ϯ 13.25); there were no statistically significant differences between men with a mean score of 25.87 (Ϯ 13.79) and women with mean scores of 27.13 (Ϯ 12.89). This study provides a rich description of the cognitive status of a group of individuals 3 years after motor stroke. Although limited by a small sample size health care professionals need to be aware that cognitive status may not decline in all subtypes of stroke patients.

Author Disclosures: J.L. Hinkle: Research Grant; Modest; Villanova University Summer Research Grant.

Th P270 Improving Door to Needle Times in a State-Wide Publically Funded Tele-stroke Program

Terri L Imus, Loretta Williams, Julie C Hall-Barrow, Tammy L Northcutt, Debra M Johnson; UNIV OF ARKANSAS, Little Rock, AR Background: AR SAVES (Arkansas Stroke Assistance through Virtual Emergency Support) is a dedicated system of providing education, diagnosis and treatment for acute ischemic strokes through technology launched in July 2008. A team of highly trained technology and stroke professionals have designed a streamlined system for the treatment of stroke in rural Arkansas. Through a contract with the Department of Human Services, Division of Medical Services and the University of Arkansas for Medical Services. This program is currently serving 23 hospitals (20 spoke, 3 hubs) in an effort to improve Arkansas' ranking of 1 st in Morbidity and Mortality from stroke. Aim: To create an efficient program, through quality improvement measures and assessment of all calls and consults. Through an integrated call center all aspects of the program are linked and data is tracked from time of call to the administration of t-PA. Method: A standardized checklist and performance review, that has provided hub trainer's and spoke site staff with step by step instructions on how to reach and maintain that crucial door to needle time line. This practice utilizes interactive video and on-site demonstrations providing discussions for continuous improvement. Result: A review of the first year indicated an average door to needle time of 115 minutes. With ongoing training of the new performance review the door to needle times were improved to 105.6 minutes. Conclusions: An efficient program, through quality improvement measures and assessment of all calls and consults using an integrated call center, all aspects of the AR SAVES program are linked and data is tracked from time of call to the administration of t-PA. The strategic area for review is the door to needle times of all AR SAVES consults. The evaluation team reviewed the pilot data and the aforementioned recommendations for improvement of the door to needle times.

Th P271 Building A Financial Case For Stroke Coordinator Resources

Debbie Lombardi Hill, FAHA; NeuStrategy, Inc., Chicago, IL Background Primary Stroke Center development spurred the creation of the "stroke coordinator" role in hospitals. While certification has outlined clear expectations for certain components of stroke care, it leaves the role of stroke coordinators undefined. Currently myriad "stroke coordinator" models exist with coordinator responsibility ranging from stroke clinical measure performance to stroke program oversight to facilitation of patient care. Hospitals struggle to determine the best approach to stroke center development, and the cost of dedicated resources is often at the root of debate on how to best deliver stroke care. Purpose To compare four different "stroke coordinator" models in Primary and Comprehensive Stroke Centers and to identify the incremental inpatient and outpatient stroke-related volume and/or inpatient length-of-stay improvements needed to rationalize the direct cost incurred for each model. Methods Four stroke coordinator models were identified. In each model the primary responsibility was noted as stroke measure data coordination, stroke center standards compliance or varying degrees of stroke care facilitation -partial (8 hrs/day, 5 days/wk) or full Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from (24 hrs/day, 7 days/wk). Full-time equivalents, qualifications, roles and responsibilities were outlined and direct costs (recruitment, salaries, benefits, equipment, support staff, etc.) were identified. Payer mix and current payer reimbursement scenarios for inpatient and outpatient services were developed, and cost-per-inpatient-day was estimated using a proprietary database. Results Incremental inpatient stroke volume needed to financially justify investment in dedicated stroke coordinator resources varies with the cost of coordinator resources and the estimated mix of new patients receiving stroke interventions, outpatient services and the estimated length-of-stay improvements. Conclusion: While a financial case alone is notably short-sided when considering the benefits of dedicated stroke coordinator resources, the need for one is admittedly more important in the midst of today's healthcare realities. Projecting new, incremental patient volume and/or operational improvements that are achievable can help rationalize the financial return on investment of new, dedicated coordinator resources. This type of future return should be realistic and presented in addition to the less quantifiable, yet equally important benefits associated with stroke care coordination.

Author Disclosures: D. Lombardi Hill: Consultant/Advisory Board; Modest; NeuStrategy, Inc..

Th P272

A Non-Teaching, Magnet Hospitals' Emergency Room Process Improvements Which Led to Stroke Center Accreditation Griselle Diaz, Ronald Burke; Baptist Hosp of Miami, Miami, FL The hospital goal was to achieve stroke center accreditation while improving stroke care. We created a collaborative team consisting of administrators, physicians, nursing departments, the laboratory department, and the radiology department; who worked towards a common goal of ensuring quality care relating to stroke patients. Our plan first encompassed ensuring all quality stroke measures: lab work, EKG, plain CAT scan of the Brain, and Chest X-ray (when medically necessary) were resulted within 45 minutes, 80% of the time. The Baptist Emergency Stroke Team (B.E.S.T.) was developed to help meet these goals. The team consists of a stroke certified nurse that responds to all suspected brain attacks, an emergency room physician, an emergency department triage and/or primary nurse, a neurologist, and a pharmacist. was the dysphagia screening, a tool to identify patients at risk for aspiration due to swallowing impairment post stroke. The data collection showed that at best we were accomplishing screening no better than 60% of the time, sometimes as low as 30%. PURPOSE: We needed to improve our compliance with the screening. It was recognized that most screening needed to take place in the ER before oral meds and nutrition were initiated. Methods: A team from both our stroke floor & ER met to tackle the problem. Two issues were identified. The first dilemma was to identify who needed the screening. The team developed a master list of diagnoses that may be related to stroke. They then linked this to a list of chief complaints (a statement about why a patient presents to the ER seeking treatment). Finally, our IT rep was able to attach the dysphagia screening to the appropriate CC, which caused it to automatically appear on our documentation screen. The second issue was documentation. Initially, the dysphagia screen was on paper, and the actual implementation was long and cumbersome. When this screen was computerized charting became a major effort, and compliance, which was erratic, fell. The prevailing philosophy was feed no one, and let the nurses upstairs do the screening. The team streamlined the actual screening to be more user-friendly while remaining in compliance with national guidelines. Through one-to-one interactions with ED managers, staff meetings and email/printed material, the ED staff was in-serviced to expect that the dysphagia screen would be appearing on documentation screens more frequently. The rationale for its addition as a required assessment for certain Chief Complaints, was also communicated. Results: We have over 90% compliance consistently & many months have even reached 100% perfection!Conclusions: In 2009, WPHC received the Gold Performance Achievement in Stroke Care for the 3 rd year in a row! Th P284 Graduating Neurology Residents' Experience with Intravenous tPA for Acute Stroke: a 10 Year Comparison Jonathan M Raser, Vera Fridman, Kate T Brizzi, Brett L Cucchiara; Hosp of the Univ of Pennsylvania, Philadelphia, PA Background: Intravenous tPA was approved as a treatment for acute ischemic stroke (AIS) in 1996. One potential barrier to increased use of tPA has been lack of experience and training among neurologists in the community. A survey of graduating neurology residents conducted in 2000 showed that many residents had limited experience and were not comfortable treating with tPA. We examined if graduating residents' experience using tPA has changed over the past decade. Methods: A 12 item survey was sent in March 2010 to all neurology residents in their final year of training as identified by AMA-GME files. Follow-up surveys were sent in April, May, and June to non-responders. Survey items established residents' experience and confidence with assessment of the acute stroke patient and treatment with tPA. Responses were assessed using a 5 point Likert scale. Questions were worded identically in the 2000 and 2010 surveys, and responses were compared between the two. Results: Of 493 residents for whom current addresses were available, 286 (58%) responded. There was a significant increase over the past 10 years in the percentage of residents who felt comfortable independently treating with tPA (73% to 94%, PϽ0.001), had observed the administration of tPA (88% to 99%, PϽ0.001), had personally treated with tPA (80% to 95%, PϽ0.001), and were involved in post-tPA care (89% to 98%, PϽ0.001). There was a substantial increase in the percentage of residents who were formally trained in the NIH stroke scale (65% to 93%, PϽ0.001) and who had dedicated stroke teams at their institution (84% to 93%, PϽ0.001). As in 2000, the vast majority of residents were confident in their ability to identify hemorrhage (99% to 100%, pϭNS) or early infarct signs (94% to 98%, pϭ0.03) on CT. While 94% of residents somewhat or strongly agreed they felt comfortable independently treating with tPA, only 65% strongly agreed. Personal experience treating a patient with tPA was associated with strongly agreeing (68% with vs. 20% without experience, PϽ0.001). In those residents with prior experience, treating a patient without direct faculty supervision was associated with strongly agreeing (78% without direct supervision vs. 52% only with direct supervision, PϽ0.001). There was no association between career plans (i.e. academics versus private practice) and any of the items assessed. Conclusion: Neurology residents' experience and comfort treating acute ischemic stroke with tPA increased significantly between 2000 and 2010. Resident exposure to stroke teams and formal training in the NIHSS has also increased substantially during this time period.

Author Disclosures: J.M. Raser: None. V. Fridman: None. K.T. Brizzi: None. B.L. Cucchiara: None.

Th P285 Requirement for Emergent Neurosurgical Procedures Following Neuro-endovascular Procedures in Contemporary Practice

Rakesh Khatri, Muhammad Ansar, Fahd Sultan, Shujaat Khalil, Saqib A Chaudhry, Ramachandra P Tummala, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: Provision to provide an emergent neurosurgical procedure has been considered a mandatory component for centers that perform neuroendovascular procedures. We sought to determine the need for emergent neurosurgical procedures following neuroendovascular procedures in two comprehensive stroke centers in settings with such provision. Methods: Prospectively collected data supplemented by chart review, was reviewed to identify any patients who may have required immediate (before the termination of the procedure) or adjunctive (within 24 hours of the procedure) neurosurgical procedures related to neuroendovascular procedure complication. The types of neurosurgical procedures and in-hospital outcomes of identified patients are reported as aggregate and per endovascular -procedure type analyses. Results: We reviewed 2474 procedures (1359 diagnostic angiograms and 1115 interventional procedures, see Table ) performed over 3 .5 years (2006-2010). There was a need for neurosurgical procedures in 9 (0.4%) patients (mean age 46 years, 7 were women); the procedures were categorized as 6 emergent and 3 adjunctive procedures. There were 5 in-hospital deaths (55%) in these 9 patients. Major procedures performed were external ventricular drainage placement in 6 (67%) patients and decompression hemicraniectomy in 3(33%) patients. Conclusions: The need for emergent neurosurgical procedures is low among patients undergoing neuroendovascular procedures. Mortality in such patients is quite high.

Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Methods: We searched our prospective Stroke Center database for the 2 year period July 2008 -June 2010 for patients admitted with a diagnosis of ischemic stroke. Data obtained included, demographics, admission source, medical history, smoking status, BMI, admission HbA1c and serum creatinine, admission NIHSS, ambulatory status by day 2, UTI occurrence, and clinical outcome. For clinical outcome we used a combination of discharge location and ambulatory status at discharge, whereby any ambulatory patient discharged to home or to a rehabilitation hospital was considered to have had a good outcome. Results: A total of 842 patients were analyzed. 541 patients (64%) were admitted from the community, while the remainder were transfered from another healthcare facility. The overall rate of UTI was 12% (103 patients). Of these, 67 patients (8% of total and 65% of UTI) had a UTI present on admission, with the vast majority of these coming from community settings (61 patients). Female gender (OR 3.6 95%CI2.3-5.7, PϽ0.0001) and smoking (OR 0.3 95%CI0.1-0.6, Pϭ0.0013) were significantly associated with UTI. Increasing age (pϽ0.001) and higher admission NIHSS (Pϭ0.004) were also significantly associated with UTI. BMI, HbA1c and admission serum creatinine were not associated with UTI. When comparing community acquired UTI (cUTI) to hospital acquired UTI (hUTI), those who were not ambulatory by day 2 (OR 3.3 95%CI1.0-10.5, Pϭ0.0463) and those that were not ambulatory at discharge Pϭ0.0172) were more likely suffer a hUTI. Increasing age (pϭ0.013) and higher admission NIHSS (Pϭ0.01) were also associated with the presence of a hUTI as compared to a cUTI. In univariate outcome analysis, UTI showed a significant association with poor outcome (OR 3.0 95%CI1.8-5.0, PϽ0.0001) and cUTI patients were more likely to have a good outcome when compared to hUTI patients (OR 3.5 95%CI1.1-11.2, Pϭ0.0376). However, in the multivariate models, UTI variables did not remain as significant independent predictors of outcome. Conclusions: Our results suggest that UTI is a common problem among ischemic stroke patients, but that the majority of UTI seen in these patients are actually community acquired and present on admission. In addition, it appears that UTI is not independently associated with a poor outcome after ischemic stroke. These results have implications for hospital infection recording and tracking. Carotid and transcranial ultrasonography with systemic evaluation were done. The baseline data, including BMI, cholesterol, and triglyceride levels, were collected. We defined extracranial or intracranial stenosis as the area stenosis over 50%. There were 174 patients (28.3%) who had CAD. Male gender, hypertension, diabetes mellitus, atrial fibrillation, and other non-ischemic heart disease were significantly more prevalent in the patients with CAD than those without CAD (65.5% vs 54.7%, Pϭ0.015; 81% vs 70.5%, Pϭ0.008; 52.3% vs 37.0%, Pϭ0.001; 22.4% vs 14.5%, Pϭ0.022; 32.2% vs 20.2%, Pϭ0.002, respectively). The prevalence rate of extracranial carotid stenosis was also significantly higher in the CAD than the non-CAD groups (14.7 vs 6.58%, Pϭ0.005). During the 12-months follow-up period, the incidence rate (by Kaplan-Meier method) of cardiovascular death, non-fatal ischemic heart event, major adverse cardiac event (MACE), and major adverse cardiac and cerebral event (MACCE) were significantly higher in the patients with CAD than those without CAD (4.02% vs 1.13%, Pϭ0.045; 4.6% vs 0.45%, Pϭ0.001; 8.62% vs 1.59%, PϽ0.0001; 14.94% vs 5.58%, Pϭ0.002, respectively). Conclusion: The study showed a higher incidence rate of cardiovascular death, non-fatal ischemic heart event, MACE, and MACCE during the 12-month follow-up in the ischemic stroke patients with CAD than those without CAD in Taiwan. It is implied that the workup for CAD may be useful to identify the group of higher risk of recurrent cardiovascular events in the patients with ischemic stroke in Asian population.

Author Disclosures: J. Yin: None. R. Chen: None.

Th P291 Albumin-Corrected Calcium Level is Associated with Mortality after Acute Ischemic Stroke

Jong-Won Chung, Wi-Sun Ryu, Beom Joon Kim, Seung-Hoon Lee, Byung-Woo Yoon; Seoul National Univ, College of Medicine, Seoul, Korea, Republic of Background: Influx of calcium ion into intracellular component is known to initiate ischemic cell death pathway. However, the association between serum calcium level and consequences of acute ischemic stroke has not been reported in detail. We aimed to investigate whether acute ischemic stroke patients with elevated serum calcium are at increased risk of mortality. Methods: Among a total of 1,957 patients screened between October 2002 and September 2008, 1,921 subjects were included in the final analysis after excluding 36 patients whose calcium level, height or NIH Stroke Scale (NIHSS) was not documented. Demographic and clinical information including cardiovascular risk factors, laboratory informations and NIHSS at admission were collected during hospitalization. Mortality status of each patient was ascertained from the Korean National Death Certificates on December 31, 2008. As calcium level is alleged to be affected by serum albumin and albumin-bound calcium is considered as physiologically inactive, we used albumin-corrected calcium calculated by the following Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from formula: [0.8 X (average albumin -patient's albumin(g/dL)) ϩ measured calcium(mg/dL)]. Cox proportional hazard models were constructed to investigate the effect of serum calcium level on the post-stroke mortality, adjusted for relevant covariates that were significant on univariate analyses. Results: Among a total of 1,921 acute ischemic stroke patients, the mean (ϮSD) of albumin-corrected calcium was 9.07 (Ϯ0.49) mg/dl. The mean follow-up period was 918.4Ϯ609.8 days and 334 (17.4%) patients died until December 2008. Albumin-corrected calcium level was associated with increased risk of mortality (HR, 1.49 per 1-mg/dL increase; 95% CI, 1.18-1.88) after adjusting for age (HR, 1.05; 95% CI, 1.04-1.06), body-mass index (HR, 0.95 per 1-Kg/m 2 increase); 95% CI, 0.92-0.99), previous stroke history (HR, 1.23; 95% CI, 0.97-1.56), hyperlipidemia (HR, 0.75; 95% CI, 0.54-1.04), cardiogenic embolism risks (HR, 1.28; 95% CI, 1.02-1.61), serum glucose (HR, 1.03 per 10-mg/dL increase; 95% CI, 1.002-1.05), total cholesterol (HR, 0.96 per 10-mg/dL increase; 95% CI, 0.94-0.995), total protein (HR, 0.94 per 1-mg/dL increase; 95% CI, 0.80-1.10), systolic blood pressure (HR, 0.93 per 10-mm Hg increase; 95% CI, 0.90-0.97), and NIHSS at admission (HR, 1.07 per 1-point increase; 95% CI, 1.06-1.09). Conclusions: Elevated albumin-corrected calcium is associated with an increased risk for mortality after acute ischemic stroke, when adjusted for relevant covariates including serum total protein and cholesterol levels. Further prospective studies with a direct measurement of ionized calcium are warranted.

Author Disclosures: J. Chung: None. W. Ryu: None. B. Kim: None. S. Lee: None. B. Yoon: None.

Th P292 The Relationship Between Blood Glucose Fluctuation And Neurological Outcome In Acute Ischemic Stroke Patients

Hiroki Fujii, Brain Attack Cntr Ota Memorial Hosp, Fukuyama, Hiroshima, Japan; Toshiho Ohtsuki, Hiroshima Univ Graduate Sch of Biomedical Sciences, Hiroshima, Japan; Satoshi Kubo, Kota Sato, Kazuhiro Takamatsu, Brain Attack Cntr Ota Memorial Hosp, Fukuyama, Hiroshima, Japan; Akiko Ota, Fukuyama Transporting Shibuya Longevity Health Foundation, Fukuyama, Hiroshima, Japan; Taisei Ota, Masaru Kuriyama, Brain Attack Cntr Ota Memorial Hosp, Fukuyama, Hiroshima, Japan; Masayasu Matsumoto; Hiroshima Univ Graduate Sch of Biomedical Sciences, Hiroshima, Japan Objective: Hyperglycemia in acute stroke is associated with a poor prognosis. We previously investigated whether poor prognosis of stroke was related to not only hyperglycemia but also variation of blood glucose levels among patients with severe cerebral hemorrhage. In the present study, we report the relationships between the mean and variation of blood glucose levels and outcome in acute ischemic stroke patients. Methods: Subjects were a total of 360 patients (mean age, 71.3Ϯ9.6 years; median age, 71 years) who were either already undergoing treatment for diabetes or had a hemoglobin A1c level of Ն5.8% at the time of admission among 2,597 acute stroke patients admitted within seven days of onset to our hospital between April 2006 and March 2009. In addition to patient attributes, the following items were measured: NIHSS score at admission and discharge, mean morning fasting blood glucose level (mean BG), and as an indicator of variation of blood glucose levels, successive variation (SV) ϭ (BGiϩ1-BGi) 2 /(n-1). Mean BG and SV were calculated from the seven consecutive morning measurements. Patients in whom the NIHSS score increased by Ն4 points from admission to discharge were classified into the exacerbation group, while other patients were classified into the non-exacerbation group. Logistic regression analysis was performed using the exacerbation and non-exacerbation groups as dependent variables, and factors related to exacerbation were investigated. Results: The exacerbation and nonexacerbation groups included 18 (5%) and 342 (95%) patients, respectively. The nonexacerbation group had a higher proportion of men but no intergroup differences were observed for age, hypertension, hyperlipidemia, smoking history, or drinking history. Logistic regression analysis performed by including the above factors showed no relationship between mean BG and symptom exacerbation (ORϭ1.00, 95%CI:0.98-1.01, pϭ0.87), but a large SV was related to exacerbation (ORϭ1.03, 95%CI:1.00-1.05, pϭ0.02). Conclusion: Large variation of morning fasting blood glucose level, rather than its absolute value, was an independent risk factor correlated with exacerbation of neurological symptoms in patients with stroke complicated by diabetes. These findings suggest that variation of blood glucose levels worsens prognosis or induces impaired glucose tolerance in patients with symptom progression. Background: Most stroke survivors require rehabilitation (rehab) to maximize recovery, and studies have shown that patient outcomes vary depending on the structure and quality of post-stroke rehab provided. The aim of this study was to investigate the relationship of patient and facility characteristics to inpatient rehab discharge for veterans with ischemic stroke. Methods: We used the national OQP Stroke database, which includes veterans hospitalized for ischemic stroke at any VA medical center in FY2007. Patient and facility level data were collected via chart abstraction and were merged with other VA administrative data. For this analysis, we excluded subjects that were admitted from a nursing home, those with in-hospital death, and those that had comfort care measures or hospice discharge. We also excluded facilities with Ͻ 20 stroke admissions. Independent patient variables included: demographics, admission NIH Stroke Scale (NIHSS) score, and Charlson comorbidity score. Facility variables included: complexity score, stroke volume, and presence of a co-located inpatient rehab unit. Discharge destination was categorized as home, inpatient rehab, or extended care facility (ECF). We used ANOVA and Chi-square tests to assess relationships of candidate variables to discharge destination. We developed a multinomial hierarchical regression model to assess the independent relationship of patient and facility variables to the three discharge categories. Results: Of the 2655 subjects from 70 facilities, 2107 (79%) were discharged home, 432 (16%) to ECF, and 116 (4%) to inpatient rehab. Subjects discharged to inpatient rehab had similar age and comorbidity scores as those discharged home (mean age 64.9 and 65.8 years, mean Charlson 4.4 and 4.5); those discharged to ECF were older (mean age 72.8) and had greater comorbidity (mean Charlson 5.5). Stroke severity was similar in the inpatient rehab and ECF groups (mean NIHSS 5.9 and 6.2) but was less severe in those discharged home (mean NIHSS 2.8). Facility characteristics that differed in the inpatient rehab group included greater prevalence of a co-located inpatient rehab facility, increased hospital complexity, and moderate stroke admission volume (60-79 cases annually). In the hierarchical multinomial model, patient variables of age, NIHSS, race, marital status, and receipt of speech consult, and facility variables of complexity and stroke volume, remained significantly associated with discharge destination. Conclusions: Among veterans admitted to a VA facility for ischemic stroke, both patient and facility characteristics are associated with discharge destination. Since ideally patient factors would drive decisions about discharge, further work to explore the process of decision-making around stroke discharge is needed to ensure veterans have access to post-stroke care that will maximize their stroke recovery.. Objective: To determine the proportion of all stroke survivors who are appropriate candidates for inpatient rehabilitation and what services they actually receive within a universal healthcare system. Design: Descriptive study consisting of a retrospective chart audit using objective criteria to identify appropriate candidates for inpatient rehabilitation from all acute stroke admissions. Participants: All persons hospitalized with acute stroke (ICD10 codes 161-169) and discharged alive from eight community and rural hospitals over two calendar years; a sample of convenience. Main Outcome Measures: Modified Rankin Scale (mRS), Stroke Rehabilitation Candidacy Screening Tool (criteria include stroke severity, ability to follow commands, identified rehabilitation goals, demonstration of change over time and willingness to participate), Discharge Disposition. Results: Data were collected on a total of 788 subjects, 51.1% male, with a mean age of 73.7 ϩ/-12.4 years. The mean and median lengths of stay in acute care were 12.4 and 7 days respectively. Proportions of all stroke by mRS severity category were: mild or resolved (mRS 0-2) 29.4%; moderate (mRS 3) 15.6%; moderately severe (mRS 4) 37.8% and severe (mRS 5) 15.0%. Three hundred and one (38%) of the 788 met the criteria for inpatient rehabilitation while 9% of all charts audited had insufficient information to determine candidacy. From the 9%, if we assume that 23 patients with moderately severe stroke (mRS 4) were candidates, then 41% met the criteria for inpatient rehabilitation. One third of severe, two thirds of moderately severe, and half of moderate clients were identified as appropriate candidates for rehabilitation, as well as 5.6% from the mild category. For actual services received on discharge from acute care, only 75% of those who met the criteria for inpatient rehabilitation received it. The most frequently cited reason for not receiving inpatient rehabilitation was lack of access to an available bed. Conclusions: Of all acute stroke survivors, approximately 40% are appropriate candidates for inpatient rehabilitation when objective criteria are applied. Persons who met the candidacy criteria for inpatient rehabilitation were identified in all categories (mild to severe) of stroke severity. At the participating facilities, one in four stroke survivors who should receive inpatient rehabilitation did not receive it.

Author Disclosures: D.A. Willems: None. D. Bryant: None. C. O'Callaghan: None.

Th P295 Patterns of Rehabilitation Service use following Acute Stroke and its Association With Rehospitalization: The AVAIL Registry

Cheryl Bushnell, Wake Forest Univ, Winston-Salem, NC; Margueritte Cox, Jodi Hawes, Xin Zhao, Dai Wai Olson, Eric Peterson, Duke Univ, Durham, NC; Richard Zorowitz; Johns Hopkins Univ, Baltimore, MD Background: While the important role of rehabilitation (rehab) services following stroke is well established, prior studies have suggested that these services are often underutilized. We investigated the factors associated with stroke rehab service use, and whether use of rehab was associated with lower 12-month rehospitalization rates. Methods: The Adherence eValuation After Ischemic stroke -Longitudinal (AVAIL) was a multi-center registry of 101 U.S. hospitals participating in the AHA's Get With The Guidelines -Stroke program. We evaluated 2,035 ischemic stroke patients who were living independently prior to their stroke and survived Ͼ3 months post stroke. Participants were contacted at 3 and 12 months to determine use of rehab services, service type (inpatient, outpatient, or home), duration and follow-up hospitalizations, if any. A Generalized Estimating Equation (GEE) logistic model identified factors associated with rehab utilization. The association of rehab services with 12 month rehospitalization was also determined using GEE logistic regression after adjusting for clinical confounders. Results: Overall, 62.4% (nϭ1271) of stroke patients received rehab services within 3 months of their event: 32.2% (nϭ409) inpatient, 57.1% (nϭ726) outpatient, 31.7% (nϭ403) home; 248 patients (19.5%) received rehab services in more than one location. In the multivariate model, more severe strokes (modified Rankin Score (mRS) of 3, 4, or 5 vs. 2) and Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation.

International Stroke Conference and Nursing Symposium Poster Presentations e337

by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from failure to ambulate at discharge and increasing number of discharge medications were independently associated with rehab services use (Table ). Of the patients who received rehab services, 298 patients (23.4%) were rehospitalized at least once by 12 months. After adjustment, overall use of rehab services was not associated with rehospitalization (OR 1.098, 95% CI 0.843-1.428, pϭ0.488). Conclusions: In the AVAIL registry, nearly two-thirds of ischemic stroke patients received some form of rehab services, and the important predictors at baseline were number of medications and failure to ambulate. We were unable to demonstrate that rehab use reduced the odds for rehospitalization following stroke.

Th P301

Acute Stroke Care: Telestroke vs. On-site Stroke Specialist Care. Results from the Ontario Telestroke Experience Ferhana B Khan, Registry of the Canadian Stroke Network, Toronto, Canada; Ruth E Hall, Ontario Stroke Network, Toronto, Canada; Melissa Stamplecoski, Registry of the Canadian Stroke Network, Toronto, Canada; Andrew Calzavara, Institute for Clinical Evaluative Sciences, Toronto, Canada; Janice A Richards, Moira K Kapral, Registry of the Canadian Stroke Network, Toronto, Canada; Frank L Silver; Univ Health Network, Toronto, Canada Background Ontario's population is over 13 million with 15% living in rural areas. The Ontario Telestroke Program was launched in 2003 to increase access to thrombolytic therapy (tPA) for stroke patients living in remote areas. Currently, the program is supported by 15 neurologists who provide consultations for patients presenting to 13 hospitals with videoconferencing and imaging provided by the Ontario Telemedicine Network. Emergency physicians in participating hospitals call a provincial 1-800 service (Criticall) to be connected with the Telestroke stroke neurologist on-call. Methods We performed a chart audit of patients managed by Telestroke between April 1, 2006 andMarch 31, 2009 and compared the results with data from the 2008/09 provincial stroke audit from our Registry of the Canadian Stroke Network. Telestroke patients at seven referring sites were identified through a probabilistic match between the Criticall database and the Canadian Institute of Health Information (CIHI) emergency department and inpatient databases and using one Telestroke site's consultation log. Ethics approval was obtained from each participating hospital and identified charts were abstracted using the same methodology and case record form used in the provincial stroke audit. Results Over the study period, the number of Telestroke activations increased from 182 in 2007 to 241 in 2009. Our total sample consisted of 498 patient charts. Of the patients who received a Telestroke consultation 65% had an ischemic stroke, 4% a hemorrhagic stroke and in 13% the stroke type was undetermined. The mean patient age was 71 years. Amongst those with ischemic stroke 51% were treated with tPA. The median NIHSS of the tPA treated patients was 12 and the median door to needle time was 74 minutes. The rate of symptomatic secondary hemorrhage was 8.3%, median length of stay 6 days, and in-hospital mortality was 18.9%. In comparison, 137 patients that received tPA at a designated stroke centre with an on-site stroke specialist in our 2008/09 provincial stroke audit similar quality of stroke care and outcomes were observed (door to needle 72 minutes, median length of stay 8 days, symptomatic secondary hemorrhage 8.0% (Pϭ0.94) and in-hospital mortality 15.3% (P ϭ 0.41)). Conclusions: The Ontario Telestroke Program demonstrates that advanced stroke care and access to thrombolysis can be effectively provided for patients in remote areas by having one neurologist on-call for an entire province. Based on our experience, stroke quality indicators among patients managed with the assistance of Telestroke are comparable to patients treated by on-site stroke specialists. Objective: To assess the use of revascularization therapies for acute ischemic stroke (AIS) in Illinois from 2003 to 2009. Background: Prior studies have estimated that only 1.8-3.0% of AIS patients receive tissue plasminogen activator (tPA) while utilization of mechanical embolectomy (ME) is unknown. In August 2009, Illinois passed legislation that emphasized the importance of primary stroke centers (PSC) designation and improved access to acute stroke care in rural areas. Methods: A retrospective analysis of the Illinois Hospital Association CompData ® was performed, specifically, identifying those patients with primary discharge diagnosis of AIS based on 433.11,433.21,433.31,433.81,433.91,434.01,434.11,434.91,or 436). We analyzed the trends for utilization of acute revascularization therapies based on their ICD-9 procedure codes (tPA: 99.10; ME: 39.74). We employed univariable and multivariable logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for factors associated with use of acute revascularization therapy. Results: Between January 2003 and September 2009, there were 119,539 AIS discharges (mean age 72 years and 55.2% women) from Illinois hospitals. Over the study period, only 1.9% received treatment with tPA and 0.19% underwent ME. In 72 counties (68.7%), tPA was never used for AIS (Figure). Overall, tPA and ME utilization increased over time (tPA: 0.8% to 3.2%; ME: 0.0016% to 0.57%; p Ͻ 0.001 for both trends). In multivariable analysis, factors independently associated with increased tPA or ME utilization included PSC status (adj. OR 3.25,year of study (adj. OR 1.30,, emergency department (ED) source of admission (adj. OR 1.42, 1.26-1.59), hospital bed capacity greater than 200 (adj. OR1.19, 1.04-1.36), and possessing commercial insurance adj. (adj. OR 1.17, 1.06-1.30). Location in southern Illinois (adj. OR 0.23, 0.16-0.33) and increased age (adj. OR 0.989, 0.986-0.992) were associated with decreased odds of tPA or ME use. A significant interaction was noted between ED presentation and PSC status: PSC hospitals were more likely to provide tPA or ME than non-PSC hospitals but this was greater for ED vs. non-ED presentation (OR 9.1 vs. 2.9, p Ͻ 0.001). Conclusions: Though increasing over time, acute revascularization therapies are used in less than 4% of AIS patients in Illinois. Implementation of PSCs and preferential triage of AIS patients to them, especially in key regions in the southern part of the state, will likely provide Illinois residents more access to approved acute revascularization therapies.

identifying patients who need special attention to avoid delay in treatment. Delayed door-to-needle times in patients with atrial fibrillation in this analysis may reflect the additional time required to analyze coagulation parameters.

Author Disclosures: M.R. Frankel: None. M.S. Ido: None. K.A. Krompf: None. K.G. Bryant: None. L.J. Fehrs: None. Background: Primary Stroke Center (PSC) certification, involving the assessment of specific Brain Attack Coalition (BAC) criteria, is a mainstay of current stroke QI activities in the U.S. However, the degree to which these criteria are associated with better stroke care is still unclear. Our goal was to examine the relationship between hospital-level characteristics including BAC criteria and quality of stroke care in the Michigan Stroke Registry Quality Improvement Program (MiSRQIP). Methods: Data were collected on 4121 acute ischemic stroke and TIA admissions from 20 hospitals participating in MiSRQIP in 2008. Information on hospital-level variables, collected by questionnaire, included BAC criteria (i.e., acute stroke team, stroke unit, availability of neurology expertise, teaching status, written care orders, EMS notification) as well as stroke volume, bed size, residency programs, urban/rural, and PSC status. Information on 10 stroke performance measures (rt-PA treatment, antithrombotics within 24 hrs, DVT prophylaxis, dysphagia screening, smoking cessation, discharge antithrombotics, discharge anticoagulants, discharge lipid treatment, assessed for rehabilitation and stroke education) were summarized in a single composite measure of care defined as the percentage of all needed care opportunities given. GEE-based multivariable linear regression models were developed to identify hospital-level predictors of the composite measure of care, while adjusting for patient-level factors (i.e., age, race, sex, stroke type). Results: Of the 4121 admissions, the mean age was 70 years, 53% were female, and 70% were white. Almost 30% of the admissions were for TIA. Thirteen (65%) of the 20 hospitals were PSC certified. Overall performance across all 20 sites on the individual performance measures varied from 62% (rt-PA treatment) to 96% (antithrombotics at discharge). The average composite measure of care was 83%. Following adjustment for patient-level factors, only the presence of an acute stroke team was statistically associated with higher composite scores (P ϭ 0.08) were both marginally significantly associated with higher composite scores. Conclusions: The presence of an acute stroke team was the most important hospital-level characteristic associated with better quality of care although, evidence also pointed towards the value of PSC certification and neurology expertise.

Author Disclosures: M.J. Reeves: Consultant/Advisory Board; Modest; Michigan Department of Community Health. A. Nickles: None. R. Hurst: None. S. Roberts: None. J. Fiedler: None.

Th P306 Does Implementation of Critical Pathway improve the Clinical Outcomes on Acute Ischemic Stroke?

Wook-joo Kim, Ulsan Univ Hosp, Univ of Ulsan College of Medicine, Ulsan, Korea, Republic of; youngchai Ko, Eulji Univ College of Medicine, DaeJeon, Korea, Republic of; Jung Hyun Park, Dongguk Univ Gyeongju Hosp, Gyeongju, Korea, Republic of; Hae Min Kim, Mi Hwa Yang, Hui Lae Yeo, Myung Suk Jang, Stroke center, Seoul National Univ Bundang Hospc, Bundang, Korea, Republic of; Moon-Ku Han, Stroke center, Seoul National Univ Bundang Hospc, Bundang, Kyrgyzstan; Hee-Joon Bae; Stroke center, Seoul National Univ Bundang Hospc, Bundang, Korea, Republic of Background: Critical pathways (CP) are multidisciplinary plans of best clinical practice for specified group of patients that aid delivery of high quality care. It is not clear whether the implementation of the CP in acute ischemic stroke (AIS) improve the clinical outcomes. Methods Based on the prospective stroke registry, the consecutive series of stroke patients were selected who were hospitalized from Jan 2004 to Sep 2009 within 12 hours from stroke onset (first abnormal time, FAT) and diagnosed AIS by brain CT or MRI. Among them, the patients who were hospitalized between Sep 2006 and Mar 2007 were excluded due to incomplete implementation of CP. We also excluded the patients developed AIS during hospitalization or performed the thrombolytic therapy in another hospital. We defined the patients who entered the hospital between Jan 2004 and Aug 2006 as preCP group and the other patients as postCP group. The CP was characterized by multi-pathway (clear or unclear onset), multi-thrombolytic therapy use (intravenous (IV), intra-arterial (IA), combined) and image-based thrombolysis decision (Figure 1). We analyzed the arrival to admission time, the arrival to first image time and the arrival to IV or IA thrombolysis time as process indicators. The modified Rankin scale (mRS) at 3 months was adopted as an indicator of clinical outcome and dichotomized into 0 to 2 (favorable) and 3 to 6 (unfavorable). Results A total of 1170 patients met our eligibility criteria. Among them, 521 patients (age, 67.3Ϯ12.8; male, 61.6%) were enrolled as preCP group, and 649 patients (age, 68.0Ϯ12.7; male, 61.5%) were enrolled postCP group. Histories of TIA, atrial fibrillation, prior statin use, and prior antiplatelet use were more frequent in postCP group. However, NIHSS at hospitalization, mRS before stroke and symptom onset to hospital arrival time did not differ between two CP groups. The patients in the postCP group received thrombolysis more frequently (preCP vs. postCP, 16.7% vs. 26.0%). The arrival Objective: The implementation of a Neuroscience Intermediate Care Unit (NIU) offers "step-down" level of care with intensive monitoring and treatment while optimizing the hospital critical care resources. We studied quality indicators, cost and nursing productivity relative to acute stroke care both prior to and following the introduction of the NIU. Methods: With IRB approval, we prospectively analyzed data from all strokes (DRGs 61-69) discharged from University Hospitals Case Medical Center from January 1 through December 31, 2009 encompassing the NIU launch on June 1, 2009. Financial data obtained concurrently included total monthly direct and indirect costs. University HealthSystem Consortium© and the NDNQI® repository provided data on length of stay, readmission rates, in-hospital mortality indices, and discharge locations. Nursing productivity indices were derived from our Kronos® for Healthcare workforce management system and monthly self satisfaction surveys were submitted online by NIU nurses throughout the implementation. Results: Data was analyzed in periods of January to May (pre-NIU) and June to December (post-NIU). Of 723 total hospital wide stroke discharges in 2009, 314 were pre-NIU and 407 were post-NIU. Stroke discharges directly from our neuroscience ward increased from 38% (nϭ124) pre-NIU to 72% (nϭ292, PϽ0.001) post-NIU. For those patients spending at least one day in a critical care unit, the average direct cost per patient was $8,904.33 (SDϭ3172.30;pϽ0.001) post-NIU. There were no detectable differences in stroke mortality indices (0.91, 0.90; pϭ0.976), readmissions at 7, 14, and 30 days ( 1, 1, and 2 pre-NIU vs 1.4, 1.6, 1.6 post-NIU, pϭ0.614; 0.571; 0.707), mean total falls (5,7; pϭ0.175), unadjusted average lengths of stay (ALOS) for pre-NIU critical care patients (5.64 days, nϭ132), post-NIU critical care (5.92,nϭ130),or NIU patients (5.29,nϭ21,pϭ0.768) and NIU nursing productivity indices (0.997 vs 0.987, pϭ0.72). Conclusions: The implementation of the Neuroscience Intermediate Care Unit had an immediate and significant effect in reducing critical care bed usage while enhancing geographic localization of stroke patients to the neuroscience floor . Although mortality and readmission rates were low, there was no change following NIU implementation while per patient costs were significantly reduced. Nursing productivity had a slight but non-significant decline but remained high in both environments. Further studies are needed to define optimal utilization and other downstream effects on hospital resources after initiating an NIU. Background: There is no data concerning acute stroke care and outcome in Thailand. Methods: We performed a prospective multicenter countrywide study involving all level of health care providers composed of university hospitals, regional medical centers, and community hospitals. Patients' baseline characteristics including demographic data, type of public health insurance schemes, diagnosis, initial stroke severity, length of stay, and complications were recorded. Indicators of acute stroke care including acute stroke unit admission, rate of thrombolysis, aspirin initiation within 48 hours were collected. Ischemic stroke outcomes were measured at discharge and 3 months according to the modified Rankin Scale (mRS). Results: There were 1,512 acute stroke patients from 118 hospitals across the country enrolled between May 2008 and February 2010. Mean (ϮSD) age was 64.31Ϯ13.17 years. Male comprised of 55.64%. Patients were Thai nationality in 99.14%. Ischemic stroke composed of 80.89%. There were 60.91, 27.38, 2.38 and 9.33 % of patients under 4 different types of medical insurance schemes including Universal Coverage Scheme (UCS), Civil Servant Medical Benefit Scheme (CSMBS), Social Security Insurance (SSS), and Self Paid (SP) respectively. Median initial NIHSS was 7. Acute stroke treatments including intravenous thrombolysis, aspirin within 48 hours, and stroke unit/corner admission were given in 3.80, 71.18 and 23.25% respectively. Mean (ϮSD) length of stay was 7.17Ϯ9.17 days. Complications occurred in 14.88% and 3.71% of patients died at discharge. Factors predicting poor outcome (mRS 5,6) at discharge were as follows: age, decades (adjusted OR 1.53, 1.21-1.94), initial stroke severity (adjusted OR 1.53, 1.21-1.94), female sex (adjusted OR 1.89,. There was no statistically significance difference in regards to stroke outcome between different types of public health insurance schemes (pϭ0.13). Conclusion: Stroke management in centers participating in the TSR reaches standard acute stroke care in many domains but certain areas for improvement remain. Type of public health insurance schemes was not found to predict poor outcome in this stroke cohort. These findings are crucial for health care providers and policy makers to encourage improvements in stroke care delivery. Introduction: Pneumonia is a potentially devastating complication of stroke. A simple bedside dysphagia screen (DS) protocol can be used by healthcare providers to detect risk of aspiration in acute ischemic stroke (AIS) patients. Routine use of formal DS protocols has been associated with decreased rates of pneumonia and improved clinical outcomes. We sought to identify those characteristics of acute ischemic stroke (AIS) patients associated with use of DS prior to any oral intake in the Get With The Guidelines-Stroke (GWTG-S) program. Methods: Data from 1256 GWTG-S hospitals from 04/01/2003 to 03/30/2009 were analyzed. DS was defined as the use of a bedside swallow screen prior to any oral intake. Patients who were kept strictly without oral intake (NPO) the entire hospital stay were excluded. Univariate analyses (chi-square for categorical variables or Wilcoxon for continuous variables) and multivariate logistic regression analyses were performed to identify independent factors associated with use of DS in AIS patients, adjusting for patient and hospital characteristics. In multivariate analyses, NIHSS was not included due to high rates of missing data (55%). Results: Among 446,056 ischemic stroke patients, 300,874 (67.4%) had DS performance documented. When compared with patients without DS, those with DS were slightly older, had higher NIHSS (when measured) and more frequently arrived by EMS and had a history of atrial fibrillation. They were less often diabetics, and had similar rates of prior stroke/TIA, dyslipidemia, PVD, and current smoking. Among patients with mild stroke (NIHSS Ͻϭ2), rates of DS were less than 11% (Table 1). In multivariate analysis, factors independently associated with DS were age (OR 1.06 [1.05-1.07] per 10 years increase), presence of multiple medical comorbidities ), admission to an academic hospital ), and geographic region (Table 2). Discussion: National guidelines recommend DS before any oral intake in all AIS but the overall rate remains low (67.4%). Patients with increased age, Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. To document the quality of stroke care in the VHA, a sample of 5,000 acute ischemic stroke admissions to 131 VA facilities in FY2007 underwent chart abstraction. Fourteen quality indicators were adapted from standard Joint Commission definitions and exclusions. Although patients receiving 'comfort measures only' were included in the sample, they were excluded from the calculation of most of the quality indicator measures. DNR code status was identified on the basis of specific documentation of DNR code status including "no code," "no CPR," or "no resuscitation." Quality indicator rates were compared between subjects with and without DNR code status. Results: Among 3965 ischemic stroke patients, 535 (13.5%) had DNR code status. In 71%, DNR orders were first documented within 1 day of admission. Of 145 patients designated as 'comfort measures only', 96% (nϭ 139) were also DNR. Compared to patients without DNR orders, those with DNR orders were significantly older (age 74.6 vs. 66.8 years), more likely to be white (71.8% vs. 61.8%), had more comorbidities (Charlson score 5.9 vs. 4.6), had greater stroke severity (NIHSS 9.3 vs. 3.8), were more likely to be 'comfort measures only' (26.0% vs. 0.2%), and were more likely to die or be discharged to hospice (29.7% vs.1.0%). Patients with DNR were less likely to receive recommended processes of care for 6 of the 14 quality indicators: tPA treatment, NIHSS recorded, ambulation by hospital day 2, fall risk assessment by hospital day 2, cholesterol treatment at discharge, and stroke education. (Table )Conclusions: Although DNR orders were a very strong risk factor for death or discharge to hospice, they were associated with relatively limited differences in the quality of inpatient stroke care.

Author Disclosures: M.J. Reeves: None. L. Myers: None. L.S. Williams: None. D. Ordin: None. D.M. Bravata: None.

Th P311 Palliative Care in Acute Stroke and its Effects on Symptom Management and Family Satisfaction: A Systematic Review

Dylan Blacquiere, Mukul Sharma; Univ of Ottawa, Ottawa, Canada Background: Stroke is an abrupt and frequently devastating event. It is the third leading cause of death, but guidelines for palliative care following acute stroke are few. We undertook a literature review to evaluate the effects of palliative care following acute stroke; specifically, on the effects of palliative management on the frequency and severity of common symptoms such as pain and respiratory distress, and on how palliative management affected the satisfaction and concerns of family members following acute stroke. Data Sources: A search strategy was developed with the help of an information specialist. Records from MEDLINE, CINAHL, EMBASE and PsycINFO from 1950 to the end of April 2010 were eligible. Study Selection: We included studies in English language and which dealt with provision of palliative care in hospital for adults who died following acute stroke (ischemic, intracerebral and subarachnoid hemorrhage). We did not restrict study type, but studies had to include provision of palliative care, including discontinuation of non-palliative medications and interventions and active management of pain, respiratory secretions, and restlessness. Studies were also included if family satisfaction with palliative care was examined by direct observation, chart review, or retrospective questionnaire. Results: 1491 studies were screened. 10 studies ultimately met eligibility criteria, reflecting data from 905 patients. These data suggest that most patients receiving palliative care following acute stroke have similar care needs, with relatively consistent strategies for management of symptoms; however, the needs of families in these circumstances has been examined only in small studies, with family concerns regarding feeding and hydration, symptom management, and the nature of palliative care being common points of concern for family members. Satisfaction was most likely when families felt that symptoms were appropriately managed or when they were involved in decision-making regarding the palliative care process. Conclusions: A limited number of studies have examined patient needs and the needs of patients and determinants of family satisfaction in the palliative care of individuals with stroke. Death due to stroke is a frequent event and more work is required regarding to ensure appropriate guidelines are developed to reduce the burden of suffering in this process.

Author Disclosures: D. Blacquiere: None. M. Sharma: None.

Th P312 Follow-up Neuroimaging in Perinatal Arterial Ischemic Stroke

Whitney Hoover, Timothy J Bernard, Neil A Goldenberg, Marilyn Manco-Johnson, Jennifer L Armstrong-Wells; Univ of Colorado, Aurora, CO Objective: Perinatal arterial ischemic stroke (PAS) is a leading cause of childhood disability. We sought to determine if there is indication for follow-up neuroimaging (MRI) in PAS given the low rate of progression or recurrence in this population. Methods: We studied all newborns within our prospective cohort study (Colorado Pediatric Stroke Program) with PAS from 08/01/2000 -04/30/2009. Radiologically confirmed PAS cases were identified in our cohort database and confirmed with chart review by a pediatric stroke neurologist. Results: Of the 27 cases of PAS in our cohort, 63% were male with ethnic distribution reflective of the Rocky Mountain Region. Stroke was identified within 72 hours of birth in 59%; nearly all cases presented with seizure (85%). Over one-half of newborns had initial CT imaging (56%); MRI was obtained within 72 hours of presentation for most newborns (59%). Strokes were commonly left-sided (59%) with two cases of bilateral involvement. All 27 cases involved the anterior circulation with only one case involving both the anterior and posterior circulation. The majority were in the MCA distribution (85%). Imaging follow-up ranged from 5.69 months -15.78 years (median 11.64 months). One-third of newborns received follow-up MRI at 1 year; only one child received MRI for clinical indication (infantile spasms). There were no new MRI findings among those cases receiving follow-up neuroimaging. There was no stroke symptom progression or recurrence in the entire cohort (Table ). Conclusions: In our cohort, there was neither radiological or clinical progression -nor stroke recurrence -in newborns who received routine follow-up MRI. Our findings suggest that there is no indication for subsequent MRI in asymptomatic children with prior perinatal arterial ischemic stroke.

Th P314 Diagnosis Of Moyamoya Disease Using Multidetector Row CT

Toshiya Sugino, Takeshi Mikami, Satoshi Iihoshi, Sapporo Med Univ, Sapporo, Japan; Kiyohiro Houkin; Hokkaido Univ, Sapporo, Japan Background Due to the remarkable recent advances in magnetic resonance imaging technology, magnetic resonance angiography (MRA) is now acknowledged as a reliable diagnostic tool with high sensitivity and specificity. Moreover, MRA is a non-invasive method that can be repeated after surgery as a follow-up procedure. Occasionally, however, the extent of stenosis and that of occlusion are over-estimated when MRA is used. The purpose of this study was to establish a method of evaluating these factors using multidetector row computed tomography (MDCT). Methods Twenty-four patients (48 sides) with moyamoya disease diagnosed by MRA were evaluated by means of computed tomography angiography (CTA) using MDCT during the past 2 years. MRA and CTA scores were assigned based on the severity of occlusive changes in the internal carotid artery, the horizontal portion of the middle cerebral artery, the anterior and posterior cerebral arteries and the signals of the distal branches of these arteries. Total scores ranged from 0 (normal) to 10 (most severe). The MRA and CTA scores were classified into four grades for more convenient evaluation of the progress of the disease (MRA and CTA grades 1-4). CT examination was performed using a multidetector row CT scanner (GE LightSpeed VCT; GE Healthcare, Milwaukee, WI, U.S.A.). The following three-dimensional CT angiography (3DCTA) scanning parameters were used: tube voltage 120 kV, collimation 0.625 mm x 32, slice thickness 0.625 mm, slice interval 0.312 mm. A total of 1-1.2 mL/kg Iopamidol (Iopamiron 300; Bayer Healthcare, Leverkusen, Germany), a lowosmolar iodinated contrast material, was administered intravenously using a bolus tracking method via an 18-20 gauge catheter positioned in an antecubital vein. Results CTA scores (0-10) were significantly correlated with MRA scores (pϽ0.0001, R2ϭ0.796). The detection rate of moyamoya-affected vessels at the level of the basal ganglia was significantly higher on CTA. Suzuki's stages could be evaluated in all cases. Moreover, our detailed and comprehensive analysis of the 3D images proved very helpful in establishing a good surgical strategy. Conclusions: CTA scores measured using an MDCT can serve as a reliable alternative to MRA scores. In the evaluation of Suzuki's stages, angiography does not necessarily relate to clinical severity or to cerebral blood flow. CTA can be performed quickly, which provides a great boon for patients with moyamoya disease, particularly pediatric patients.

Author Disclosures: T. Sugino: None. T. Mikami: None. S. Iihoshi: None. K. Houkin: None.

Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Nomazulu Dlamini, Ivanna Yau, Andrea Kassner, Robyn Westmacott, Gabrielle Deveber; Hosp For Sick Children, Toronto, Canada Objective: To describe the influence of chronic unilateral steno-occlusive arteriopathy on cerebrovascular reactivity (CVR) assessed by blood oxygen level dependent (BOLD) functional MRI Background: Transient cerebral arteriopathy (TCA) is one of the commonest causes of arterial ischemic stroke (AIS) in childhood. Recurrent infarction is rare beyond the acute (Ͻ3 months) phase after initial stroke despite persistence of long-term arterial stenosis. Neuropsychological sequelae have been related to the initial ischemic injury. However, the additional consequences of persistent stenosis on cerebral blood flow and cognition in this group are not well understood. MRI based CVR studies allow assessment of the ability of cerebral vasculature to increase blood flow under conditions of stress, such as hypercapnic challenge, and can provide information on tissue at increased risk of infarction or neurocognitive demise. Methods: We reviewed the images of 44 number of children diagnosed with transient cerebral arteriopathy (TCA) between 1990 and 2007, with moderate to severe (greater than 50%) stenosis of the middle cerebral artery (4/4) and distal internal carotid artery (2/4) on conventional angiography over two time points (range 4.33yrs -14.5yrs). Children with subcortical or deep white matter infarcts were selected for CVR studies. Children with large cortical strokes were excluded. Follow-up clinical and educational information was obtained (mean 6.81 years; range 4.1 -14.3 years). Results: Four children (7 years 5 months -17 years 4 months age) evaluated at 4.3-14.5 years following an acute arterial ischemic stroke had a persistent stenosis. None of the children had had further ischemic events. Four children with formal neuropsychometry had learning disability with variable attention, visuo-spatial, auditory processing and working memory difficulties. Three out of four had serial testing. All children showed reduced reactivity particularly in areas corresponding to the persistent stenosis and previous stroke. Impaired reactivity was mostly confined to the deep white matter with relative sparing of the cortex. Conclusion: In children with TCA and Ͼ 50% residual arterial stenosis cerebral blood flow appears to be chronically impaired even years after the acute ischemic event. Abnormal CVR does not appear to be associated with long term recurrent stroke in these children. However further studies are required to determine whether neurocognitive deficits were consistent with the initial stroke lesion or chronically impaired cerebral blood flow.

Author Disclosures: N. Dlamini: None. I. Yau: None. A. Kassner: None. R. Westmacott: None. G. Deveber: None.

Th P316 Inhibition Of The Sodium-Hydrogen Exchanger After Neonatal Hypoxia-Ischemia Results In Sparing Of White Matter Injury And Improved Memory And Learning

Peter Ferrazzano, Pelin Cengiz, Pinar Kendigelen, Kutluay Uluc, Erinc Akture, Chihwa Song, Louise Zhang, Jihae Lee, Vishal Chanana, Beth Hutchinson, Beth Meyerand, Dandan Sun; Univ of Wisconsin, Madison, WI Objective: Neonatal hypoxia ischemia is a major cause of brain injury in infants, affecting as many as 6 in 1000 live births in the US. Few treatment options are available, and survivors suffer from chronic morbidities such as cerebral palsy, learning disability, and seizure disorders. After cerebral ischemia, over-stimulation of the sodium-hydrogen ion exchanger isoform 1 (NHE1) contributes to cell swelling and ischemic injury. We have previously shown that inhibition of NHE1 is neuroprotective after focal ischemia in adult mice; however, little is known about the effect of NHE1 inhibition in neonatal hypoxia ischemia. Methods: Hypoxiaischemia was induced in 9 day old C57/Black6 mice by unilateral carotid artery ligation and subsequent exposure to 8% oxygen for 55 minutes. Mice were treated with HOE 642, a potent inhibitor of NHE1, at 10 minutes following hypoxia-ischemia and again at 24 and 48 hours following the injury. Experimental groups consisted of HOE treated (nϭ8), vehicle treated (nϭ9), and sham operated (nϭ5) mice. Rotarod and Morris Water Maze tests were performed 2 months following the injury. T2 MRI was performed using a 4.7 Tesla Varian small animal MRI scanner. Animals were sacrificed and brains were perfusion fixed for ex-vivo Diffusion Tensor MRI scanning and immunohistochemistry. Results: HOE treated animals demonstrated improved performance on Rotarod (pϽ0.05) and Morris Water Maze tests (probe trial: 23.3 Ϯ 12.8s vs. 9.1 Ϯ 9.0s, pϭ 0.02 ). T2 MRI demonstrated a spectrum of injury in both HOE treated and untreated mice, from large cyst formation and cerebral atrophy to mild venticulomegaly. The degree of hemispheric volume loss on the in-vivo T2 MRI correlated well with performance on Morris Water Maze test (rϭ0.713, pϭ0.004). However, despite the improved performance on behavioral testing seen in the HOE treated animals, no significant difference in hemispheric volume loss was seen in the injured hemisphere between groups (17% vs 19%). Ex-vivo DTI demonstrated a decrease in fractional anisotropy values in the corpus callosum of the control mice compared to sham (pϭ0.02), which was not seen in the HOE treated animals. Conclusion: NHE1 inhibition after neonatal hypoxia-ischemia leads to improved memory and learning at 2 months following the injury. There is no significant difference in hemispheric volume loss in treated animals, indicating that improved performance cannot be explained solely by an acute effect on neuronal survival after the injury. Decreased FA in corpus callosum of vehicle treated animals suggests white matter injury which is spared in the HOE treated group. Immunohistochemistry will serve to further characterize the effect of NHE1 inhibition on white matter injury after neonatal hypoxia-ischemia. This research has received full or partial funding support from the American Heart Association, National Center.

Th P317 Thromboprophylaxis With Antiplatelet Agents Prevents Cerebral Thromboembolism In Patients With Mechanical Aortic Prostheses

Raul Garcia-Rinaldi; Mayaguez Med Cntr, Mayaguez, PR Objective: Cerebral thromboembolism (TE) is the most serious complication of aortic mechanical prostheses (AMP). Thromboembolism is secondary to platelet activation due to shear forces and release of ADP from fractured RBC. Warfarin, the anticoagulant "of choice" does not fully prevent thromboembolism in patients with AMP because it lacks platelet inhibitory activity. If thromboembolism from AMP is a platelet mediated event; thromboprophylaxis with antiplatelet agents should prevent cerebral TE. Methods: Since 2001, 160 patients who underwent aortic valve replacement with AMP alone or in combination with another cardiac or thoracic aortic procedure were treated with clopidogrel and aspirin as sole thromboprophylaxis. Platelet inhibition (PI) was maintained at Ͼ40-50%, measured with Accumetrics® and thromboelastography platelet mapping (TEG-PM) since 2006 and 2007. Patients were followed with 2D echocardiograms every six months. Results: The total follow up was 5,809.6 months (484.3 patients years (pt yrs). The average follow up was 36.8 Ϯ 27.8 mo. Eighteen patients (11%) died, 8 from coronary artery disease and 3 from valve related causes. Five patients bled (3.1%) (1.03%/pt yrs). From 2001 to 2007, 7 patients had strokes (4.3%) (1.45%/pt yrs). Five had stopped clopidogrel and aspirin. Of these, 3 were on warfarin. Of the remaining 2, 1 was a non responder to clopidogrel and the other occurred in a non tested, compliant patient. Two patients had TiA's, 1 in an excellent clopidogrel responder and the other is a non responder. During the last 2.5 years none of the patients has sustained a neurologic event. 20 patients demonstrated clopidogrel poor responsiveness. With reloading, stopping statins or proton pump inhibitors, use of cilostazol or ticlopidine, we were able to increase the degree of PI in most hyporesponders. Since September 2009 we converted 16 hyporesponders to prasugrel. All patients responded well to this medication. All patients were responsive to aspirin when tested by Accumetrics and TEG-PM. Patients who had any response to clopidogrel and were responsive to aspirin were protected from strokes. Conclusion: Platelet activation causes TE in patients with AMP. If the patient responds to the antiplatelet agents, is compliant, has normal sinus rhythm and a small left atrium, TE in patients with AMP can be prevented. Clopidogrel hyporesponders achieved excellent PI on prasugrel. Antiplatelet thrombophylaxis for patients with AMP is effective if one blocks the synthesis of thromboxane A 2 and partially blocks the P 2 Y1 2 receptor on the platelet. Background and Objective: Soft, lipid-containing carotid plaques have been associated with increased ischemic stroke risk and appear echolucent on ultrasound evaluation. Stabilization of carotid plaques by pharmacologic intervention, including statins, is a promising strategy for stroke prevention. Our objective was to assess the change in carotid plaque echolucency following short-term treatment with atorvastatin. Subjects andMethods: We treated 40 subjects over 45 years of age (mean age: 70Ϯ7 years, 60% women) with 80 mg atorvastatin daily for one month. High-resolution carotid ultrasound was performed to detect plaques in long axis in any segment of carotid arteries at baseline and 30 days after treatment. Computerassisted gray scale densitometry (GSD) index, a measure of echogenicity, was calculated from the normalized images off-line. Absolute GSD index changes were compared by a paired t-test (one-tailed difference was considered significant at alphaϽ0.05). Any increase in an individual GSD index was considered a positive change or plaque stabilization effect. Logistic regression was used to assess the mediation effect of LDL cholesterol on plaque stabilization after adjusting for age, sex, and smoking. Results: The average median number of carotid plaques was 2 (range 0-5, 24 subjects with carotid plaque) at baseline and did not change 30 days following treatment. The maximal carotid plaque thickness did not significantly change between baseline and the follow up (1.78 mm vs. 1.69 mm). The mean GSD index was 73Ϯ16 (range 1-125) at baseline and 89Ϯ15 (range 1-137) at 30 days (pϽ0.05). Of 24 study participants, 4 (17%) showed a reduction of GSD levels and 14 (60%) showed GSD increase. The adjusted odds ratio for the positive GSD plaque index change (vs. no change or decreased GSM index) was 1.71 (95% confidence interval; 1.1, 7.6). This association was independent of the baseline levels of LDL as well as LDL reduction. Conclusion: We observed decreased echolucency (increased echodensity) of carotid artery plaques after short-term treatment with atorvastatin. Further studies are needed to determine whether decreased echolucency leads to plaque stabilization and reduction of risk of stroke and other vascular events. cerebrospinal fluid (CSF) and serum levels of sEng in patients with SAH are associated with VS in SAH patients. This study included adult controls (nϭ5) and Fisher-3 SAH patients (nϭ16). Controls were individuals with no prior history of neurological disorders but who underwent lumbar puncture for headache workup and had normal CSF studies. Demographics, medical history, and history of exposure to elicit drugs were documented. Patients were followed prospectively and samples of CSF and serum were obtained between days 5 and 7 post-bleed. sEng levels were determined using commercially available ELISA test (R&D). Protein levels in the CSF and serum were measured and utilized to calculate CSF sEng index. SAH subjects were subcategorized into those with sVS and those who did not develop symptomatic VS (noVS). sVS was defined as a neurological deterioration in the setting of angiographically proven VS and in the absence of other active conditions that could explain the occurrence of neurological decline. The levels of sEng in both groups were compared using the nonparametric Mann-Whitney U test. Age, history of hypertension, exposure to elicit drugs, RBC count in the CSF and proteinorrachia were not statistically different within sVS and noVS. The mean CSF level of sEng was (0.031Ϯ0.006) pg/mL in the control group, (0.1410Ϯ0.069) pg/mL in the noVS group, and (0.547Ϯ0.233) pg/mL in the sVS group (pϽ0.021). CSF sEng in the sVS and in the noVS groups was Ͼ2 indicating this mediator was produced intrathecally. Elevated levels of intrathecally synthesized sEng are observed in SAH patients, particularly in those with sVS. These results suggest sEng may participate in the pathogenesis of VS. When performed in suspected aSAH, simultaneous CTA/CTP allows simultaneous assessment of the arterial tree as well as cerebral perfusion. The purpose of our pilot study was to determine: 1. if changes in arterial diameter on CTA are associated with altered perfusion 2. if there is decreased perfusion when pts develop symptomatic vasospasm 3. if the use of intra-arterial milrinone & hemodynamic augmentation for vasospasm improves perfusion. Materials & Methods: Pts with aSAH who had whole-brain baseline CTA/CTP were included . Followup CTA/CTP was performed if pts clinically deteriorated, had TCD evidence of vasospasm(vasospasm group) or at d 7-14 if asymptomatic(without vasospasm). All individuals with TCD evidence of vasospasm were treated with hemodynamic augmentation & intra-arterial milrinone(per institutional protocol). A total of 31 automated ROIs/hemisphere placed at 6 standard levels covering the entire brain measured serial perfusion parameters: CBF, CBV, MTT, TTP. Individual ROIs were then grouped to evaluate perfusion in the MCA, ACA, PCA territories. Arterial diameters were measured in the terminal ICA, MCA(M1,M2) & PCA(P1,P2). A Pearson-correlation coefficient was used to evaluate the relationship between artery diameter & perfusion. To evaluate the effect of treatment, a t-test was used to compare perfusion pre-& post-vasospasm therapy. Because of the exploratory nature of the analysis, no correction was performed for multiple comparisons. Results: There 10 pts without(total 20 CTP/CTA) and 6 pts with vasospasm(total 17 CTP/CTA) who had perfusion studies for comparison. Changes in arterial diameter were significantly correlated with changes in MTT(rϭ-0.58, pϭ0.02) & TTP(rϭ-0.54, pϭ0.01)i.e. pts who developed angiographic vasospasm had prolongation of MTT & TTP. Pts who developed vasospasm had decreased CBF from baseline in MCA & ACA territories (pϽ0.05). For vasospasm pts treated with milrinone, there was a significant improvement in MTT(pϭ0.02) & trends towards improved CBF(0.07) & TTP(pϭ0.07) Conclusion: : Changes in perfusion are seen with changes in arterial diameter from vasospasm. Pts who develop vasospasm had significant changes from baseline CBF in the MCA and ACA territories. There was improvement in perfusion seen with intra-arterial treatment. This pilot study suggests a larger prospective study is required to determine the most appropriate perfusion parameter to follow.

Author Disclosures: C. Lum: Honoraria; Modest; received from Siemens for lecture given at 2009 WFITN meeting. M. Bussiere: None. E. Ahmed: None. M. Hogan: None. L. Garnett: None. J. Hooper: None. J. Sinclair: None. M. Sharma: None.

Th P332 Correlation between Anemia and Delayed Cerebral Ischemia (DCI) in aneurysmal subarachnoid haemorrhage.

Muhammad A Taqi, Kaiz Asi, Khaled Asif, Michel Torbey; Med College of Wisconsin, Milwaukee, WI Title Correlation between Anemia and incidence of Delayed Cerebral Ischemia(DCI) in aneurysmal subarachnoid haemorrhage. Introduction: Delayed cerebral ischemia(DCI) is the most important determinant of the morbidity associated with aneurysmal subarchnoid hemorrhage after aneurysm is secured. Higher clinical grades (fisher or WFNS) are associated with higher incidence of cerebral vasospasm and DCI. Conventional treatment to prevent DCI consists of hypertension, hypervolemia and hemodilution (HHH therapy). Changes in hematocrit can potentially affect the brain tissue oxygenation in two ways: higher hematocrit increases oxygen carrying capacity and lower hematocrit decreases viscosity and hence facilitate cerebral blood flow. This optimal hematocrit is unknown. Recent studies have shown that blood transfusion increases cerebral blood flow and decreases O2 extraction ratio in subarachnoid patients. We analyzed relationship of hematocrit with incidence of stroke in our subarachnoid population. Methods Retrospective chart review. Results 86 patient with aneurysmal subarach-noid hemorrhage were identified from July 2009-June 2010. 19 delayed cerebral ischemic events occurred in 19 patients. One was periprocedural and was therefore excluded. DCI were diagnosed clinically and were confirmed by either CT head or MRI brain. Patients were divided among three groups based on their lowest hematocrit during the first 21 days: group A Hematocrit 30%(nϭ60). Incidence of delayed cerebral ischemia in group A ϭ9/15(60%), group Bϭ 3/12(25%) and group Cϭ 7/60(11.6%). All patients had higher fisher grades (II, III and IV). Conclusions: Although lower hematocrit decreases blood viscosity and theoretically should increase cerebral blood flow, at lower levels it significantly decreases the oxygen carrying capacity of blood and therefore could result in ischemia of brain tissue. In our cohort of patients, the highest incidence of DCI. while keeping the clinical grade constant, was observed in patients with a hematocrit of Ͻ26%. This suggest that severe anemia predisposes patients with aneurysmal subarachnoid to DCI. Since blood transfusion is also related with morbidities, the best approach is to avoid blood loss in these patients by limiting the surgical blood loss and daily blood draws for unnecessary routine labs.

Author Disclosures: M.A. Taqi: None. K. Asi: None. K. Asif: None. M. Torbey: None.

Th P333 Identification of Predictors Differentiating Reversible Cerebral Vasoconstriction Syndrome with Subarachnoid Hemorrhage from Aneurysmal Subarachnoid Hemorrhage

Susanne Muehlschlegel, Bruce A Barton, Univ of Massachusetts Med Sch, Worcester, MA; Mehmet A Topcuoglu, Haceteppe Univ, Ankara, Turkey; Joshua Fok, Chinese Univ, Hong Kong, Hong Kong; Aneesh B Singhal; Massachusetts General Hosp, Harvard Med Sch, Boston, MA Introduction: Reversible Cerebral Vasoconstriction Syndrome (RCVS) mimics aneurysmal subarachnoid hemorrhage (aSAH) with thunderclap headache at onset in nearly 90% and SAH in up to 42%. RCVS with SAH (RCVS-SAH) is often initially misinterpreted as aSAH, subjecting patients to unnecessary imaging, invasive procedures and prolonged ICU stay. Our objective was to identify predictors that can reliably differentiate RCVS-SAH from aSAH. Methods: Clinical and imaging features were compared between 515 consecutive aSAH and 35 consecutive RCVS-SAH patients at Massachusetts General Hospital. Data were analyzed using student's T-test, Chi-Square or Fisher's Exact test, as appropriate. To avoid overfitting due to the small number of events, we limited our logistic regression models to four predictors each. We compared the fit to multivariable logistic models using exact estimation methods containing the same variables with age dichotomized at the mean to predict RCVS-SAH. Results: Univariate analysis: RCVS-SAH patients were younger (43Ϯ12 vs. 55Ϯ14 years; PϽ0.001), with a higher proportion of women (87% vs. 71%; pϭ0.04), prior self-reported migraine (47% vs. 8%), depression (45% vs. 8%), alcohol abuse (34% vs. 9%), COPD (32% vs. 43%) and drug abuse (21% vs. 5%; all p Ͻ 0.001). RCVS-SAH had lower Hunt & Hess (HH) and Fisher scale (median 2 (IQR 2;2) vs. 3 (1;3); PϽ0.001 and 2(2;2) vs. 3(2;3); PϽ0.001). No difference in smoking status was present (37% vs. 36%; pϭ0.99). Imaging analysis showed that RCVS-SAH had a higher proportion of hypodensities on admission CT (63% vs. 35%; PϽ0.001) and angiographic vasospasm (100% vs. 62%; PϽ0.001); more arteries affected by vasospasm (6 (6;9) vs. 2 (0;4); PϽ0.001), bilateral vasoconstriction (89% vs. 36%, PϽ0.001), and earlier occurrence of vasospasm (day 1 (1;1) vs. 6 (5;8); PϽ0.001). After ruling out colinearity between migraine and depression, multiple logistic regression showed the following predictors of RCVS-SAH: model 1: age (OR 0.93 [95% CI 0.9-0.97]), prior migraine ), depression .1], COPD ); model 2: HH grade (OR 0.4 [95% CI 0.2-0.7, Fisher scale (OR 0.1 [95% CI 0.05-0.296], bilateral vasoconstriction ), number of affected arteries ). The EXACT logistic model did not improve the model fit. After controlling for prior antidepressant use, migraine and depression remained significant. Conclusion: : We identified important clinical and imaging differences between RCVS-SAH and aSAH, which may improve correct diagnosis, treatment and resource utilization with a potential to decrease length of stay. This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Th P334 Systemic Hemodynamics Is Different Between Clipping And Coiling After Aneurismal Subarachnoid Hemorrhage -SAH Picco Multicenter Study-

Nobutaka Horie, Shunsuke Ishizaka, Dept of Neurosurgery, Nagasaki Univ, SAH Picco study group Japan, Nagasaki, Japan; Kentaro Hayashi, Kazuhiko Suyama, Dept of Neurosurgery, Nagasaki Univ, Nagasaki, Japan; Izumi Nagata; Dept of Neurosurgery, Nagasaki Univ, SAH Picco study group Japan, Nagasaki, Japan Background and Purpose: Volume management is critical for the assessment of the vasospasm after aneurismal subarachnoid hemorrhage (SAH). We have registered 62 patients in SAH Picco multicenter study, and prospectively analyzed the hemodynamic parameters postoperatively until Day 14. Here, we investigate the difference of the systemic hemodynamics between surgical clipping and endovascular coiling after the treatment. Methods: Multiple parameters were calculated by single indicator transpulmonary thermodilution (Picco, PULSION medical systems) system in real time. This modality enables us to evaluate multiple parameters including global end diastolic volume (GEDI) and intrathoratic blood pressure (ITBI) as an indicator of preload, cardiac index (CI), systemic vascular resistance index (SVRI) and mean arterial pressure (MAP) as an indicator of afterload, and extravascular lung water index (ELWI). These parameters were analyzed Background and Purpose: Although recent studies have found that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment and dementia in population-based cohorts, the cause of cognitive impairment in CKD subjects is unclear. In the present study, we conducted a population-based, cross-sectional analysis of brain magnetic resonance imaging (MRI) findings and vascular risk factors including CKD in relation to cognition particularly frontal lobe function. Methods: We examined 506 elderly subjects (192 men and 314 women) aged 60 years or older, who were living independently at home without apparent dementia. Frontal lobe dysfunction was defined as the most prolonged fifth quintile of the modified Stroop test for each given decade. Glomerular filtration rate (GFR) was estimated with the new Japanese equation modified from the Modification of Diet in Renal Disease Study equation. Subclinical lacunar infarction was shown as low signal intensities on T1-weighted images, and their size was 5-15 mm. Deep white matter lesions (DWMLs) and periventricular hyperintensities (PVHs) were defined as isointense with normal brain parenchyma on T1-weighted images, and high signal intensity areas on T2-weighted images. The data were analyzed with the SPSS Statistics 18.0. Results: The frequency of CKD was 16.4%. Subclinical lacunar infarction, DWMLs and PVHs were detected in 79 (15.6%), 217 (42.9%) and 150 (29.6%) of 506 subjects, respectively. The frontal lobe dysfunction group tended to have higher blood pressure (BP) (146.0/80.0 vs. 140.0/78.0 mmHg), less education (8.0 vs. 9.0 years), more history of minor stroke (6.8% vs. 1.7%), higher creatinine (61.9 vs.59.2 mol/L), and lower GFR (72.8 vs. 75.3 mL/min/1.73 m2). When possible confounders were entered into the multivariate logistic regression model (the forward stepwise method), the independent predictors of frontal lobe dysfunction were diastolic BP (odds ratio 1.023; 95% CI 1.001 to 1.045 per 1 mmHg), GFR (odds ratio 0.848; 95% CI 0.737 to 0.975 per 10 mL/min/1.73 m2), and number of lacune(s) (odds ratio 1.471; 95% CI 1.135 to 1.908). The score of Stroop test was compared according to the GFR category with ANCOVA adjusted for age and diastolic BP. The mean of logarithmic-transformed scores of Stroop test in the GFRϽ60 mL/min/1.73 m2 group was 1.376 (95%CI 1.301-1.451), which was significantly higher (worse) than 1.250 (95%CI 1.214-1.285) in the GFR 60-89 mL/min/1.73 m2 group (pϭ0.009). CKD was not related to global cognition defined by Mini-Mental State Examination. Conclusions: The present study showed that CKD, high blood pressure, and subclinical lacunar infarction might contribute to frontal lobe dysfunction. The intervention directed at treatment and prevention of CKD, and silent ischemic brain lesions particularly lacune(s) would be beneficial to attenuate the frontal cognitive decline in healthy elderly subjects.

  Author Disclosures: T.G. Abud: None. J. St.-Maurice: None. D.G. Abud: None. A. Nguyen: None. Z. Szatma ´ry: None. M. Mazighi: None. A. Bisdorff: None. E. Enesi: None. L. Chiumarulo: None. D. Bresson: None. A. Aymard: None. E. Houdart: None.

  Author Disclosures: C.P. Kealey: None. H.H. Babiker: None. Y. Chun: None. S. Lin: None. K. Mohanchandra: None. D.A. Rigberg: None. G.P. Carman: None. D.S. Levi: None. D.H. Frakes: None.

Figure 1

 1 Figure 2 Author Disclosures: M. McNamara: None. C. Fogle: None. C. Oser: None. D. Gohdes: None. T. Harwell: None. S. Helgerson: None. N. Okon: None. D. Dietrich: None. D. Rodriguez: None.

  Figure: Neurological score (A) and infarct volume (B). * PϽ0.05; ** PϽ0.01; *** PϽ0.001.

  Author Disclosures: L.M.B.C. Souza: None. S. Payabvash: None. A. Kemmling: None. R. Gonzalez: None. R. Nogueira: None. M.H. Lev: Research Grant; Modest; 2010 -2012 Principal Investigator. Other Research Support; Modest; GE Healthcare.

  Author Disclosures: J.H. Lichtman: None. S.B. Jones: None. Y. Wang: None. E. Watanabe: None. E.C. Leifheit-Limson: None. L.B. Goldstein: None.

  Author Disclosures: H. Zacharatos: None. A.E. Hassan: None. S.A. Chaudhry: None. R. Husain: None. M. Qureshi: None. M.K. Suri: None. M.A. Ezzeddine: None. A.I. Qureshi: None.

  Author Disclosures: W.N. Kernan: Research Grant; Significant; National Institutes of Health. C.M. Viscoli: None. L.M. Brass: None. M.P. Amatangelo: None. A. Birch: None. W. Clark: None. R. Conwit: None. K.L. Furie: None. M. Gorman: None. E. Hinnau: None. D. Kleindorfer: None. A.M. Lovejoy: None. J. Osborne: None. S. Silliman: None. R.M. Zweifler: None. R.I. Horwitz: None.

  This research has received full or partial funding support from the American Heart Association, National Center. Author Disclosures: S.H. Chou: None. M. Ning: None. R.G.J. Konigsberg: None. S. Simmons: None. D. Bauer: None. E. Loesch: None. S.K. Feske: None. E.H. Lo: None.

  Data included: A) clinical profile: age and gender, median BP and ICP; Hunt and Hess grade (HHG), conventional VSP risk factors (HTN, DM, smoking, ethanol intake, antiplatelet therapy, illicit drug use); B) imaging profile: initial CT (Fisher grade [FG]); CTA; CTP (quantitative CBF, CBV, MTT maps (mean days 1.5Ϯ1); location, size, multiplicity of aneurysm; TCD (mean days 2.5Ϯ0.7); C) laboratory profile: white and red cell blood counts; serum Na, K, Ca, Mg and albumin concentrations. Multivariate linear regression analysis was performed to create the VSP prediction model. Results: Of 75 patients the mean HHG was 2.25ϩ1.03 and FG 2.89ϩ0.78. Angiographic VSP occurred in 35% (26/75) and clinical vasospasm 31% (23/75) at a mean of 7.5Ϯ2.2 and 5.8Ϯ2.1, respectively. Of 31 patients diagnosed by TCD with flow abnormalities during days 1-3, 42% (13) developed clinical and 48% (15) angiographic VSP. Of 25 patients with CTP abnormalities during days 1-3, 64% (16) developed clinical/angiographic VSP. Notably, the following test showed a strong correlation with VSP development: FG (pϭ0.006), CTP deficit (pϽ0.00), and abnormal TCD (pϭ0.03). No other admission profiles showed a VSP correlation. The overall value to predict VSP was R2ϭ0.363 using (0.484xCTP deficit)ϩ(0.227xTCD abnormality)ϩ(0.047xFG)-0.825. The likelihood ranged for patients with both normal CTP and TCD and a FG of 1 (best scenario) was -0.067, while those with both abnormal CTP and TCD and a FG of 4 (worst scenario) had 0.785. Conclusion: Using the presented prediction model and the results of 3 admission factors (CT Perfusion, TCD, and Fisher grade) we were able to delineate a range of likelihoods for developing VSP after aneurysmal SAH. This model will help to risk stratify SAH patients for VSP early on in their disease course. Author Disclosures: A. Rosengart: None. S. Park: None. H. Mangat: None. H. Riina: None. D. Lahm: None. A. Segal: None. M.E. Fink: None. P.C. Sanelli: None.

  Josser E Delgado Almandoz, Bharathi D Jagadeesan, Mallinckrodt Institute of Radiology, Washington Univ, Saint Louis, MO; Ralph G Dacey, Jr., Dept of Neurological Surgery, Washington Univ, Saint Louis, MO; Christopher J Moran, DeWitte T Cross, III, Mallinckrodt Institute of Radiology, Washington Univ, Saint Louis, MO; Michael R Chicoine, Keith M Rich, Dept of Neurological Surgery, Washington Univ, Saint Louis, MO; Michael N Diringer, Dept of Neurology, Washington Univ, Saint Louis, MO; Colin P Derdeyn, Mallinckrodt Institute of Radiology, Washington Univ, Saint Louis, MO; Gregory J Zipfel; Dept of Neurological Surgery, Washington Univ, Saint Louis, MO Purpose: To determine the yield of CT and MR angiography for the detection of causative cerebral aneurysms in patients with subarachnoid hemorrhage (SAH) who have a negative initial catheter angiogram. Methods: From January 1st, 2005, until July 31st, 2010, we instituted a prospective protocol in which patients who presented with SAH documented by non-contrast CT (NCCT) or cerebrospinal fluid (CSF) xanthochromia and had a negative initial catheter angiogram were also evaluated with CT and MR angiography to assess for causative cerebral aneurysms. Two neuroradiologists evaluated the NCCTs to determine the pattern of SAH (perimesencephalic or not) and the CT and MR angiograms (CTA, MRA) to assess for the presence of causative cerebral aneurysms. Differences in reader interpretation were resolved by consensus. Results: 76 patients were included in our study, with a mean age of 53.4 years (median 54 years, range 19-88 years). 49 patients were female (64.5%) and 27 male (35.5%).

  Author Disclosures: C.B. Wright: Research Grant; Significant; AHA NSDG. C. Dong: None. T. Rundek: None. S. Cespedes: None. M.S.V. Elkind: None. C. DeCarli: None. R.L. Sacco: None.

  Interact to Influence Outcome of Ischemic Stroke After Treatment with rt-PA Pitchaiah Mandava, Baylor College of Medicine & VA Med Cntr, Houston, TX; Melody Munoz, Karthik Sarma, Michael A Brooks, Baylor College of Medicine, Houston, TX; William Dalmeida, Jane Anderson, Roderic Fabian, Baylor College of Medicine & VA Med Cntr, Houston, TX; Thomas A Kent; Baylor College of Medicine, Houston, TX

  Author Disclosures: T. Wu: None. M. Kasam: None. D.R. Danda: None. P. Sahota: None. R. Pandurengan: None. W. Hicks: None. A.D. Barreto: None. N.R. Gonzales: None. G.A. Lopez: None. J.C. Grotta: None. S.I. Savitz: None.

  Author Disclosures: T. Wu: None. C. Sitton: None. P. Sahota: None. A. Sarraj: None. N. Harun: None. R. Pandurengan: None. N.R. Gonzales: None. A.D. Barreto: None. G.A. Lopez: None. J.C. Grotta: None. S.I. Savitz: None.

  -INR (pϽ 0.01). Neurological severity on admission, as assessed by NIHSS, was less in patients with PT-INR Ն1.6 (NIHSS 4 (IQR 2-10)) than in those with PT-INR Ͻ 1.6 (NIHSS 7 (3-16)) (pϽ 0.01). Conclusions: CE during anti-coagulation therapy is often associated with lower PT-INR values, while it can develop in spite of good PT-INR values in patients with VHD. The other subtypes of BI can occur even when anti-coagulation is effective. Neurological severity may be alleviated in patients with higher PT-INR values (Ն1.6) on admission. Author Disclosures: A. Nakamura: None. T. Ago: None. K. Nakamura: None. T. Kuwashiro: None. H. Sugimori: None. M. Kamouchi: None. T. Kitazono: None. studies were conducted at 27 hospitals twice, from January 2005 through March 2007 (Period A) and from January 2008 through December 2009 (Period B).

  Author Disclosures: A. Ahmad: None. P.R. Paliwal: None. S. Liang: None. L.L.L. Yeo: None. K.W.P. Ng: None. P.K. Loh: None. H.L. Teoh: None. N. Venketasubramanian: None. B.K.C. Ong: None. V.F. Chong: None. E. Tan: None. M. Maliapen: None. A.K. Sinha: None. B.P.L. Chan: None. V.K. Sharma: None.

  Author Disclosures: G.S. Nakiri: None. O.M. Pontes-Neto: None. A.C. Santos: None. T.G. Abud: None. D.G. Abud: None.

  3. Am J Neuroradiol AJNR 2007; 28:1395 Author Disclosures: A.K. Wakhloo: Consultant/Advisory Board; Modest; Codman Neurovascular. C.F. Silva: None. G. Spilberg: None. I. Linfante: None. E.A. Duhamel: None. M.J. Gounis: Consultant/Advisory Board; Modest; Codman Neurovascular.

  Author Disclosures: G.L. Britton: None. D. Cattano: None. H. Kim: None. D.D. McPherson: None. S. Huang: None.

  Author Disclosures: T. Peng: None. S.T. Laing: None. H. Kim: None. D.D. McPherson: None. S. Huang: None.

  Author Disclosures: T. Tang1: None. X. Liu1: None. L. Zhang1: None. C. Chen1: None. H. Kassis1: None. L. Karp1: None. M. Chopp1,2: None. Z. Zhang1: None.

  Author Disclosures: M. Gutie ´rrez Ferna ´ndez: None. J. A ´lvarez Grech: None. B. Rodriguez Frutos: None. M. Expo ´sito Alcaide: None. M. Vallejo Cremades: None. J. Merino: None. E. Dı ´ez Tejedor: None.

  Author Disclosures: B. Oh: None. J. Beom: None. T.R. Han: None. D. Kim: None. N. Paik: None.

  Author Disclosures: K. Yigitkanli: None. A. Pekcec: None. S. Pallast: None. A. Antipenko: None. D. Nikolov: None. E.H. Lo: None. K. Van Leyen: None.

  Author Disclosures: J. Shi: None. D. Wang: None. T.I. Lam: None. R.A. Swanson: None. S.M. Massa: None.

  Author Disclosures: M.L. Flaherty: None. B.M. Kissela: None. H. Sucharew: None. K. Alwell: None. C.J. Moomaw: None. D. Woo: None. P. Khatri: None. A. Opeolu: None. S. Ferioli: None. J.P. Broderick: None. D. Kleindorfer: None.

  Author Disclosures: D.S. Liebeskind: Research Grant; Significant; K23NS054084. Consultant/ Advisory Board; Modest; CoAxia, Inc.. M. Lee: None. N. Sanossian: None. Q. Hao: None. R. Fiaz: None. L.K. Ali: None. D. Kim: None. B. Ovbiagele: None. S. Starkman: None. P.M. Vespa: None.

  Author Disclosures: F. Wang: None. B. Uretsky: None. Y. Kuo: None. D. Esterbrooks: None. A. Mooss: None. S. Mohiuddin: None.

  Methods: We assessed every patient undergoing CEA at our institution between 01/01/2006 and 12/31/2009. We classified the diagnoses that prompted to CEA in: 1) Diagnosis of carotid stenosis during preoperative evaluation of coronary artery bypass grafting, valve replacement or coronary angioplasty [D1], 2) diagnosis during routine examination [D2], 3) Dizziness [D3], 4) Cerebrovascular events not occurring within 120 days before surgery [D4] 5) Diagnosis of carotid stenosis during assessment of a cerebrovascular event of contralateral carotid territory [D5], 6) Diagnosis during evaluation of peripheral vascular disease [D6], 7) Carotid bruit [D7], 8) Progression of previously diagnosed carotid stenosis [D8], 9) Syncope [D9] 10) Other causes [D10], and 11) Dizziness and syncope [D11]. We compared the combined outcome of ischemic stroke (IS), myocardial infarction (MI) and/or death between patients with D4 and the rest of the cohort (2 tests). Results Overall, 221 CEA were performed, 190 in asymptomatic individuals: 141 men (74.2%), mean age 69Ϯ8 years.

  Author Disclosures: P.M. Riccio: None. F.R. Klein: None. H. Raffaelli: None. R. Zamora: None. L.A. Sposato: None.

  Author Disclosures: S. Domingues-Montanari: None. I. Ferna ´ndez-Cadenas: None. A. del Rio-Espinola: None. M. Mendioroz: None. P. Delgado: None. A. Penalba: None. M. Rubiera: None. M. Ribo ´: None. A. Rosell: None. J. Alvarez-Sabı ´n: None. J. Montaner: None. W P91 Polymorphisms in the Thrombomodulin -Endothelial Cell Protein C Receptor System and the Risk of Cerebral Infarction in a Biracial Population: The Genetics of Early Onset Stroke Study Nicole Dueker, John Cole, Yuching Cheng, Jeffrey O'Connell, O.Colin Stine, Marcella Wozniak, Barney Stern, Braxton Mitchell, Steven Kittner; Univ of Maryland Baltimore, Baltimore, MD

  Author Disclosures: C.D. Anderson: None. M.A. Nalls: None. A. Biffi: None. N.S. Rost: None. S.M. Greenberg: None. A.B. Singleton: None. J.F. Meschia: None. J. Rosand: None.

  , UVA HEALTH SYSTEM, Charlottesville, VA; Fang-Chi Hsu, Wake Forest Univ, Winston-Salem, NC; Bradley L Pemberton, Michele M Sale, Bradford B Worrall; UVA HEALTH SYSTEM, Charlottesville, VA

  Author Disclosures: S.D. Elkhatib: None. F. Hsu: None. B.L. Pemberton: None. M.M. Sale: None. B.B. Worrall: None.

  Author Disclosures: M.C. Zurru ´: None. C. Alonzo: None. L. Brescacı ´n: None. F. Ortega: None. S. Brienza: None. D. Gil: None. J. Montecchia: None. M. Carretero: None. L. Ca ´mera: None. G. Waisman: None. E. Cristiano: None. B. Ovbiagele: None. W P95 Racial Differences in Blood Pressure Levels and Management Among Patients with TIA, Acute Ischemic Stroke and ICH Karen C Albright, Limin Zhao, Univ of Alabama -Birmingham, Birmingham, AL; Ellen M Dauchy, Kamal R Shah, Marco Fossati-Bellani, Tulane Univ Sch of Medicine, New Orleans, LA; Andrei V Alexandrov, Univ of Alabama -Birmingham, Birmingham, AL; Sheryl Martin-Schild; Tulane Univ Sch of Medicine, New Orleans, LA Background & Purpose: Previous epidemiologic studies demonstrated that despite greater awareness of the diagnosis of arterial hypertension (HTN) and increasing HTN treatment rates, fewer Blacks achieve target blood pressure (BP) levels. Subjects & Methods:

  Author Disclosures: J. Gutierrez: None. H. Gardener: None. A. Bagci: None. C. Marquez: None. T. Rundek: None. C. DeCarli: None. M.S.V. Elkind: None. N. Alperin: None. R.L. Sacco: None. C.B. Wright: None.

  Author Disclosures: J. Bugnicourt: None. C. Leclercq: None. J. Chillon: None. Z. Massy: None. S. Canaple: None. C. Lamy: None. O. Godefroy: None.

  Author Disclosures: R. Ji: None. L.H. Schwamm: Consultant/Advisory Board; Modest; MA Dept of Public Health; Lundbeck Intl Steering Cmte DIAS-4. Other; Modest; Chair AHA GWTG. M. Pervez: None. A.B. Singhal: None.

  Author Disclosures: F. De Los Rios La Rosa: None. J. Khoury: None. K. Alwell: None. C.J. Moomaw: None. D. Kleindorfer: None. J.P. Broderick: None. D. Woo: None. M.L. Flaherty: None. P. Khatri: None. O. Adeoye: None. S. Ferioli: None. J. Eilerman: None. B.M. Kissela: Research Grant; Significant; This work supported by NIH-NINDS R-01 NS30678.

  Author Disclosures: J. Ruiz-Sandoval: None. E. Chiquete: None. L. Ban ˜uelos-Becerra: None. C. Torres-Anguiano: None. C. Gonza ´lez-Padilla: None. A. Arauz: None. C. Cantu ´: None. L.M. Murillo-Bonilla: None. J. Villarreal-Careaga: None. F. Barinagarrementeria: None.

  Author Disclosures: B. Kim: None. E. Lee: None. Y. Do: None. S. Lee: None. D. Kang: None. S. Kwon: Research Grant; Significant; This study was supported by a grant (A060171) of the Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affairs, Republic of Korea.

  Author Disclosures: J.H. Lichtman: None. S.B. Jones: None. Y. Wang: None. E. Watanabe: None. E.C. Leifheit-Limson: None. L.B. Goldstein: None.

  Figure: Kaplan Meier Curves examining risk of stroke in the REGARDS study by history of stroke, TIA or stroke symptoms. Author Disclosures: S.E. Judd: None. D.O. Kleindorfer: Speakers; Modest; Genetech. L.A. McClure: None. J.D. Rhodes: None. M. Cushman: None. V. Howard: None. G. Howard: None.

  Author Disclosures: L. Cormier: None. N. Carrier: None. S. Lepage: None. J. Roux: None. F. Ayala-Paredes: None. A. Jean: None. H. Do: None. B. Essadiqi: None. P. Farand: None.

  Author Disclosures: X. Guan: None. J.L. Saver: None. N. Salamon: None. F. Buxey: None. N. Poursohi: None. Q. Hao: None. N. Sanossian: None. D.S. Liebeskind: None. W P125 SPOTRIAS: Hyperacute C-Reactive Protein Levels Predict Stroke Outcome in Mild Stroke Aurauma Chutinet, Natalia S Rost, Alona Muzikansky, Massachusetts General Hosp, Boston, MA; Rebecca A Betensky, Harvard Sch of Public Health, Boston, MA; Michael K Parides, Mount Sinai Sch of Medicine, New York, NY; Fabricio O Lima, Leonardo Batista, Ahmad Bayrlee, Lauren M Nentwich, Matthew B Maas, Massachusetts General Hosp, Boston, MA; Steven K Feske, Brigham and Women's Hosp, Boston, MA; Karen L Furie; Massachusetts General Hosp, Boston, MA

  Author Disclosures: A. Chutinet: None. N.S. Rost: None. A. Muzikansky: None. R.A. Betensky: None. M.K. Parides: None. F.O. Lima: None. L. Batista: None. A. Bayrlee: None. L.M. Nentwich: None. M.B. Maas: None. S.K. Feske: None. K.L. Furie: None.

  Author Disclosures: L. Heitsch: None. J. Khoury: None. H. Sucharew: None. K. Alwell: None. C.J. Moomaw: None. O. Adeoye: None. D. Woo: None. M.L. Flaherty: None. P. Khatri: None. S. Ferioli: None. J.P. Broderick: None. B.M. Kissela: None. D.O. Kleindorfer: Research Grant; Significant; NIH R01 NS30678. W P133 Expanded Operational Classification of Early Neurological Deterioration (END) Maruthi Kesani, Clotilde Balucani, Kara A Sands, Michael J Lyerly, Kristian B Barlinn, Limin Zhao, Luis F Cava, J Ivan Lopez, Karen C Albright, Anne W Alexandrov, Andrei V Alexandrov; Comprehensive Stroke Cntr, Univ of Alabama Hosp, Birmingham, AL Background&Purpose: A novel hypothetical classification (Stroke 2009; 40:e443-50) describes 3 types of diffusion weighted imaging (DWI) appearance of ischemic brain lesions and proposes likely mechanisms leading to early neurological deterioration (END). We applied this classification to consecutive stroke patients to evaluate if all early deteriorations fall under the original imaging classification. Subjects&Methods: Consecutive ischemic stroke patients were evaluated for subsequent neurological deterioration (NIHSSϾϭ4 points) within the first 72 hours from symptom onset. Etiologies leading to deterioration were classified as systemic causes and neurological causes. Intracranial hemodynamic steal was diagnosed according to previously published criteria using transcranial Doppler. DWI lesions detected at the first MRI scan were classified as END-A, B, C, or other, and the latter DWI patterns were analyzed. Outcomes included discharge NIHSS, mortality and modified Rankin Scores at 3 months. Results: Among 600 consecutive patients (51% male, age 62Ϯ15yrs, baseline median NIHSSϭ11, range 0-42), 44 patients (7%) had experienced END including 26 without cardio-pulmonary decompensation or other systemic causes. We identified five additional DWI imaging patterns termed END-Watershed, END-Subcortical, END-Posterior, END-Lacunar and END-Zero that describe patient initial imaging prior to deterioration. Baseline NIHSS, DWI findings and stroke outcomes are summarized in Figure. Among patients with END, 65% had documented hemodynamic steal vs. 3% of those without END (pϽ0.0001). Proximal occlusions were common: END-A, B, and C 57% vs. other END 50% (pϭ1.00) with re-occlusion/reembolization detected in 40% END-W and 20% END-C (pϭ0.16). Outcomes tended to be better with END-0, L, P, S, W types compared to END-A, B, C (pϭ0.068). Conclusions: We have identified 5 additional DWI patterns on initial imaging prior to END. Certain patterns-END-0, L, P, S and W have lesser stroke severity and show a trend toward better clinical outcomes than previously proposed END-A, B and C. Of particular interest, most early END events occurred in the presence of intracranial hemodynamic steal and re-occlusion. Author Disclosures: M. Kesani: None. C. Balucani: None. K.A. Sands: None. M.J. Lyerly: None. K.B. Barlinn: None. L. Zhao: None. L.F. Cava: None. J. Lopez: None. K.C. Albright: None. A.W. Alexandrov: None. A.V. Alexandrov: None. W P134 Wall Shear Stress in the Internal Carotid Siphon In Healthy Volunteers Assessed Using High Speed Phase Contrast 3D-Radial Velocimetry Warren Chang, Benjamin Landgraf, Steven Kecskemeti, Yijing Wu, Kevin Johnson, Oliver Wieben, Charles Mistretta, Patrick Turski; Univ of Wisconsin Sch of Medicine and Public Health, Madison, WI Introduction: Cardiovascular disease is the leading cause of death in industrialized countries. Abnormal wall shear stress (WSS) is prevalent at sites prone to atherosclerosis and aneurysm formation. Therefore, WSS analysis may have prognostic value in finding areas vulnerable to both atherosclerosis and aneurysms. A limitation of prior investigations of WSS using magnetic resonance angiography (MRA) is insufficient resolution to visualize the boundary zone (BZ) within clinically-useful scan times. We have developed PC HYPRFlow, an advanced 3D radial imaging modality capable of acquiring whole brain angiograms with scan times of ϳ5 minutes and spatial resolution more than 40 times higher than conventional techniques, allowing better BZ visualization. The internal carotid siphon (ICS) is of interest because aneurysms and atherosclerotic plaques are commonly found in the siphon; We examine WSS in four segments (C2, C3, C4, and C5) of the ICS in 10 healthy volunteers. Materials & Methods: 10 healthy volunteers (6 female, 4 male) were scanned using a GE Discovery 750 3.0T MR Scanner using PC-VIPR. The images were imported into Ensight where cutplanes axial to the vessels of interest were made. The velocity data was then imported into a custom Matlab runtime environment developed at the University of Freiburg, Germany, which used B-spline interpolation with Green's Theorem to calculate time-average WSS from velocity measurements from PC-VIPR. Results: The time average WSS for all subjects in the C2 segment of the ICS was 1.19 Ϯ 0.32 Pa. The WSS in C3 was 1.11 Ϯ 0.33 Pa, the WSS in C4 was 1.03 Ϯ 0.34 Pa, and the WSS in C5 was 0.86 Ϯ 0.30 Pa. These values are consistent with values found in the literature for WSS measured with PC-MRA. A WSS map of the left ICS is shown in Figure 1. Streamlines derived from velocity information from PC-VIPR are shown in Figure 2. Conclusion:

  Author Disclosures: K. Dani: None. C. Santosh: None. D. Brennan: None. C. McCabe: None. W. Holmes: None. B. Condon: None. D. Hadley: None. M. Macrae: None. K.W. Muir: None. W P137 Characteristics of Stroke Subtype in a Stroke Registry in Da Nang, Vietnam Quang V Ngo, Ministry of Health, Da Nang, Viet Nam; Kiet A Ly, Univ of Washington, Seattle, WA; Tung T Vo, Ministry of Health, Da Nang, Viet Nam; Thanh G Ton, David L Tirschwell, W. T Longstreth, Jr., Univ of Washington, Seattle, WA; Chien H Pham, Ministry of Health, Da Nang, Viet Nam; Annette L Fitzpatrick; Univ of Washington, Seattle, WA

  Author Disclosures: Q.V. Ngo: None. K.A. Ly: None. T.T. Vo: None. T.G. Ton: None. D.L. Tirschwell: None. W.T. Longstreth: None. C.H. Pham: None. A.L. Fitzpatrick: None.

  Author Disclosures: T.A. Steve: None. M.E. Knash: None. N. Asdaghi: None. T. Jeerakathil: None. A. Shuaib: None. D. Emery: None. C. Beaulieu: None. K.S. Butcher: Research Grant; Significant; Alberta Heart and Stroke Foundation.

  Results To Patient Demographics And Clinical Findings Nadia khan, Dept of Neurosurgery, Stanford Univ Sch of Medicine, 300 Pasteur Drive, Stanford, California, Stanford, CA; Michael P Marks, Dept of Neuroradiology, Stanford Univ Sch of Medicine, 300 Pasteur Drive, Stanford, California, Stanford, CA; Jacob Petralia, Elma Tunovic, Gary K Steinberg; Dept of Neurosurgery, Stanford Univ Sch of Medicine, 300 Pasteur Drive, Stanford, California, Stanford, CA Background: Moyamoya (MM) disease is a progressive angiopathy involving the entire circle of Willis. Suzuki and Takaku in 1969 and then later Mugikura et al in 2002 presented a staging system emphasizing progression of disease in the anterior and posterior circulation. We present a modified staging system paying special attention to changes in the anterior, middle and posterior cerebral arteries. Additionally changes in occurrence of MM collaterals and in the cervical ICA defined as the "bottleneck sign" were reviewed and correlated to patient demographics and clinical findings. Patient Selection: Preoperative cerebral angiographies of 215 moyamoya patients undergoing surgical revascularization at our institute were reviewed and a new staging method applied. Mean age of was 32.5 years (1 to 69 years). This included 22% children, 78% adults, 75% females, 25% males, 31% Asians, 58% Caucasians. Unilateral to bilateral disease ratio was 1:1.8. Results: The distribution of the modified staging system was as follows: Stage 1a: intracranial ICA stenosis/occlusion ϭ 12%, Stage 2a: segmental ICA involvement and ACA/MCA stenosis/occlusion ϭ 35%, Stage 3a: A1 and M1 occlusion ϭ 33% Stage 4a: supraclinoidal ICA occlusion with continued filling to the level of ophthalmic artery ϭ 11%. Stage 1p: focal involvement of PCA ϭ 5%, Stage 2p: segmental involvement of PCA ϭ 10%, Stage 3p: disappearance of PCA ϭ 2%, Stage 4p: proximal involvement of SCA or basilar artery ϭ 3%. In 15% of the patients extracranial ICA stenosis in the form of a "bottle neck" was present at the level of its origin from the common carotid artery. This was always associated with Stage 4a of the disease. Typical MM collaterals were observed with Stage 1a to Stage 2a, disappearing with disease progression to Stage 4a. Stage 4a was more frequently seen in Caucasians. Stage 2a and 3a were the most common presentations in both children and adults. Females presented more often with bilateral disease and posterior circulation disease. Children presented more often with Stage 3a and posterior circulation disease. Stage 2a most commonly correlated to side of presenting TIA and Stroke. Conclusion: Using this modified staging system progression of disease was evaluated in both the anterior and posterior circulations. Appearance/disappearance of collaterals could be quantified. Late changes in the cervical ICA were documented and specific demographic and clinical correlations were made. Author Disclosures: N. khan: None. M.P. Marks: None. J. Petralia: None. E. Tunovic: None. G.K. Steinberg: None.

  Author Disclosures: A.W. Alexandrov: Research Grant; Modest; HRSA-NEPR. T. Baca: Research Grant; Modest; HRSA-NEPR. K.C. Albright: None. S. DiBiase: Research Grant; Modest; HRSA-NEPR. A.V. Alexandrov: None.

  Author Disclosures: B. Diamond: None. D.A. Murphy: None. Q. Shah: None. C.J. Reif: None. B.S. Nash: None. W P162 Hospital Pre-notification of Stroke Patients by Emergency Medical Services Improves Stroke Time Targets James S McKinney, UMDNJ -RWJMS, New Brunswick, NJ; Judith Lane, Virginia Roberts, Robert Wood Johnson Univ Hosp, New Brunswick, NJ; Win Toe, UMDNJ -RWJMS, New Brunswick, NJ; Pamela Ohman-Strickland, UMDNJ -Sch of Public Health, Piscataway/New Brunswick, NJ; Mark A Merlin; UMDNJ -RWJMS, New Brunswick, NJ Introduction: Pre-arrival notification to hospitals by emergency medical services of patients with suspected stroke is recommended to reduce delays in time-dependent therapies. We hypothesized that hospital pre-notification would reduce stroke time targets recommended by the National Institute of Neurological Disorders and Stroke (NINDS)

  Author Disclosures: J.S. McKinney: None. J. Lane: None. V. Roberts: None. W. Toe: None. P. Ohman-Strickland: None. M.A. Merlin: None. W P163 Paramedics and Prehospital Stroke Research Trials: Effective Education Strategies Theresa Haley, Miranda Gordon, Kanika McCall, Randy Sanoff, Michael Lee, Ann Tran, Fiona Chatfield, UCLA, Los Angeles, CA; Robin Conwit, NIH, Baltimore, MD; Marc Eckstein, UCLA, Los Angeles Fire Dept, CA; Sam Stratton, Orange County EMS Agency, Santa Ana, CA; Frank Pratt, LA County Fire Dept, Los Angeles, CA; Sidney Starkman, Jeffrey Saver, UCLA, Los Angeles, CA; FAST-MAG Investigators and Coordinators

  Solutions: Paramedics are knowledgeable professionals who can perform prehospital research procedures reliably and efficiently. Knowledge of paramedic concerns permits refinements in study design and training. The addition of research principles in paramedic education curricula would provide basic knowledge about research, promote paramedic enthusiasm to conduct research and encourage initiation of their own research. Author Disclosures: T. Haley: None. M. Gordon: None. K. McCall: None. R. Sanoff: None. M. Lee: None. A. Tran: None. F. Chatfield: None. R. Conwit: None. M. Eckstein: None. S. Stratton: None. F. Pratt: None. S. Starkman: None. J. Saver: None.

  Author Disclosures: T. Miyagi: None. M. Koga: None. J. Nakagawara: None. Y. Shiokawa: None. E. Furui: None. K. Kimura: None. H. Yamagami: None. Y. Okada: None. S. Okuda: None. Y. Hasegawa: None. K. Kario: None. T. Nezu: None. K. Maeda: None. K. Endo: None. K. Minematsu: None. K. Toyoda: None.

  Author Disclosures: N. Sanossian: None. M.A. Kim: None. S. Hamilton: None. S. Starkman: None. D.S. Liebeskind: None. M. Eckstein: None. S. Stratton: None. F. Pratt: None. R. Conwit: None. J.L. Saver: None.

  Author Disclosures: R. Cadena: None. O. Adeoye: None. C. Lindsell: None. K. Alwell: None. C.J. Moomaw: None. E. Grise: None. M.L. Flaherty: None. S. Ferioli: None. D. Woo: None. P. Khatri: None. J.P. Broderick: None. B.M. Kissela: None. D.O. Kleindorfer: None. W P180 tPA Contributes To Impairment of ATP and Ca Sensitive K Channel Mediated Cerebrovasodilation After Piglet Photothrombosis Through Upregulation of JNK MAPK William Armstead, John Riley, Douglas Cines, Vladimir Muzykantov, Abd Higazi; Univ of Pennsylvania, Philadelphia, PA Introduction:

  05). It was estimated that as initial CBF decreases 20% or final thrombi extent increases 150 pixels, infarct size increases by approximately 4%. Conclusion: The combined technique of LDF monitoring and thrombi imaging will serve as a useful tool in animal stroke research by directly (exclusion of modeling-failure cases) or indirectly (post-hoc statistical adjustment of infarct size) reducing data variability, consequently increasing statistical power of a study. Author Disclosures: D. Kim: None. J. Kim: None. B. Kang: None. J. Choi: None. D. Lee: None. W. Choi: None. S. Jeong: None. K. Kim: None. I. Kwon: None.

  Author Disclosures: J. Li: None. S. Benashski: None. T. Ribar: None. A. Means: None. L.D. McCullough: None.

  Discussion and Conclusion: The results provide an in vivo evidence of neuroprotection in acute stroke by a biomimetic stable form of LysoPC-DHA solubilised in plasma, AceDoPC. Enhanced brain accumulation is further suggested by decreased oxidative stress. MRI may play an important role for the controlled evaluation of new stroke treatments and thus help translate experimental findings into the clinic. Author Disclosures: F. Chauveau: None. T. Cho: None. M. Perez: None. M. Guichardant: None. A. Riou: None. P. Aguettaz: None. M. Picq: None. M. Lagarde: None. Y. Bertheze `ne: None. N. Nighoghossian: None. M. Wiart: None.

  Author Disclosures: M. Fujioka: None. K. Hayakawa: None. K. Mishima: None. T. Nakano: None. C. Muroi: None. T. Miyata: None. K. Okuchi: None. M. Fujiwara: None. B.K. Siesjo: None. W P200 Cytokine Expression in the Brains and Serum of MyD88-/-and TRIF mutant mice following permanent Middle Cerebral Artery Occlusion Bolanle M Famakin, National Institutes of Health, NINDS, Stroke Branch, Bethesda, MD; Yongshan Mou, Christl A Ruetzler, National Institutes of Health, Bethesda, MD; Modinat M Lawal, National Institutes of Health, NINDS, Stroke Branch, Bethesda, MD; John M Hallenbeck; National Institutes of Health, Bethesda, MD Background: Toll-like Receptor (TLR) signaling plays an important role in cerebral ischemia.

  3) Modulation of autophagy may offer a new therapeutic avenue for stroke. Author Disclosures: S. Herberg: None. N. Hoda: None. J.R. Barrett: None. S. Periyasamy-Thandavan: None. W.H. Jackson: None. D.L. Hess: None. D.C. Hess: None. P.V. Schoenlein: Research Grant; Modest; NIH RO1. W. Hill: Research Grant; Modest; VA Merit Award.

  Author Disclosures: C. Graffagnino: Research Grant; Significant; The Medicines Companyfunding for the ACCELERATE Trial. S. Bergese: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial. J. Love: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial. D. Schneider: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial. C. Lazaridis: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial. M. LaPointe: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial. K. Lee: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial. G. Lynch: Research Grant; Significant; The Medicines Company -funding for the ACCELERATE Trial.

Prediction of 1

 1 Year Functional Outcome in Patients With Intracerebral Hemorrhage: The "Functional ICH Score" Michael Mlynash, Christine A Wijman, Stanford Univ Med Cntr, Stanford Stroke Cntr, Palo Alto, CA; on behalf of the DASH investigators

  Author Disclosures: R. El Khoury: None. Y. Esquenazi: None. M. McIntosh: None. R. Pandurengan: None. J. Choi: None. A. Sarraj: None. M. Sline: None. N. Gonzales: None. A. Barreto: None. J. Grotta: None. N. Tandon: None. S. Savitz: None.

  Background and Purpose: Progressive stroke is associated with poor outcome. External counterpulsation (ECP) increases cerebral blood flow non-invasively. We aim to investigate the therapeutic and hemodynamic effects of ECP in progressive stroke patients with large artery occlusive disease. Methods: Progressive stroke was defined as 2 or more NIHSS points worsening of motor function in the affected arm and leg within 7 days of symptom onset. In this retrospective cohort study, 29 consecutive progressive stroke patients admitted between 2005 and 2009 and received 35 one-hour sessions of ECP plus best medical therapy were recruited. Twenty-nine age and sex-matched patients from either FISS-tris trial (www.strokecenter.org/trials, number 493) or admitted to acute stroke unit whom developed further motor deterioration served as the controls.

  Author Disclosures: J. Kang: None. H. Bae: None. M. Han: None. M. Jang: None. J. Park: None. T. Park: None. K. Lee: None. Y. Ko: None. S. Lee: None. K. Jung: None. Y. Cho: None. K. Yu: None. B. Lee: None. J. Lee: None. J. Cha: None. J. Lee: None.

  Park, Dept of Neurology, Eulji General Hosp, Seoul, Korea, Republic of; Jaseong Koo, Dept of Neurology, Seoul St. Mary's Hosp, Seoul, Korea, Republic of; Young A Kim, Dept of Pathology, Seoul City Boramae Hosp, Seoul, Korea, Republic of; Kyusik Kang; Dept of Neurology, Eulji General Hosp, Seoul, Korea, Republic of Background:

  Author Disclosures: V.K. Sharma: Research Grant; Significant; The study is funded by an Individual Research grant from NMRC Singapore. G. Tsivgoulis: None. A. Ahmad: None. P.R. Paliwal: None. H.L. Teoh: None. L.Y.H. Wong: None. S. Jie: None. N. Venketasubramanian: None. M.T. Wee: None. H. Cheng: None. P.A.S. Ping: None. V.F. Chong: None. K.W.P. Ng: None. P.K. Loh: None. L.L.L. Yeo: None. B.K.C. Ong: None. B.P.L. Chan: None. A.K. Sinha: None.

  Author Disclosures: K. Lee: None. Y.D. Kim: None. S.H. Oh: None. S.H. Ahn: None. S.H. Kim: None. S.W. Han: None.

  Author Disclosures: A.E. Hassan: None. H. Zacharatos: None. M.K. Suri: None. G.J. Rodriguez: None. J.T. Miley: None. A. Maud: None. G. Vazquez: None. R.A. Taylor: None. D.C. Anderson: None. A.I. Qureshi: None.

  Author Disclosures: J.M. Meunier: None. C.K. Holland: None. T.M. Porter: None. C.J. Lindsell: None. G.J. Shaw: None.W P245 Telestroke Facilitates Access to Fibrinolytic Treatment for Patients with Ischemic Stroke.Alfredo Palomino; Hosp Universitario Virgen del Rocı ´o, Seville, Spain Both TELE-STROKE and rtPA have been demonstrated to improve the outcome of patients with acute ischemic stroke in health centres without Stroke Units or a specialized team on stroke care. In the framework of a competitive research project, TELE-STROKE was developed to manage the treatment of acute ischemic stroke with rtPA within the first 4.5 hours of symptom onset. The study was carried out in an urban reference hospital (RH) serving a population of 1,000,000 inhabitants; and two community hospitals (CH-1, CH-2) with different demographic and geographic characteristics. We analysed the results of patients treated with TELE-STROKE between January 2009 and May 2010. CH-1 serves a metropolitan population of over 200,000 inhabitants and CH-2, which is located in a hill area, provides health care coverage for 80,000. They are 10 and 68 miles from the RH respectively. 12 patients were treated, 6 between January and May 2010. CH-1: 9 out of 52 potentially treatable patients (excluding hemorrhagic stroke and those over 80 years old); initial median NIHSS score was 15.7 (range 8 to 24) and 10.7 (0-22) at discharge; time for fibrinolysis from symptom onset (TF) 149 (120-210) and door-to-needle (DN) time 65 (33-119), in minutes. CH-2: 3 out of 18 potentially treatable patients; NIHSS 16.7 (11-23) and 14.7 (10-18); TF 160 (130-205) and DN 100 (40-118). CH-1ϩCH-2: 12 patients; NIHSS 15.7 (8-24) and 10.7 (0-22); TF 154.5 (120-210) and DN 69 (33-119). No hemorrhagic complications occurred within the first 36 hours after rtPA. Intrahospital mortality 1/12 (initial NIHSS 16, malignant cerebral edema, CH-2); 5/10 Rankin Ͻ 3 at hospital discharge with a mean length of hospital stay of 1 week (2/10 Rankinϭ0) without variations after 6 months (2 remain unevaluated); mortality at 6 months after hospitalization 3/11 (2 CH-1: 1 for new stroke, 1 CH-2, residual pseudobulbar syndrome and aspiration pneumonia) and 1/12 protocol violation with no complications (platelet antiaggregant therapy and prevention of thromboembolic disease during 24 hours after fibrinolysis). In our pilot project, TELE-STROKE demonstrates improved access to safe and efficient treatment for patients with acute ischemic stroke supervised by stroke experts. At present, we are implementing TELE-STROKE in new health centres to provide coverage for a larger population. Author Disclosures: A. Palomino: None. , Joseph P Broderick, Judith A Spilker, Thomas A Tomsick, Univ of Cincinnati Academic Health Cntr, Cincinnati, OH; Michael D Hill, Univ of Calgary, Calgary, Canada; Edward C Jauch, Med Univ of South Carolina, Charleston, SC; Peter Mitchell, Bernard Yan, Royal Melbourne Hosp, Melbourne, Australia; Alex Abou-Chebl, Univ of Louisville, Louisville, KY; Kevin M Cockroft, Pennsylvania State Med Sch, Hershey, PA; David M Brown, HOAG MEMORIAL HOSPITAL PRESBYTERIAN, Newport Beach, CA; Peter D Panagos, Washington Univ, St. Louis, MO; Raul G Nogueira, Massachussetts General Hosp, Boston, MA; Peter Keller, Neuroscience Trials Australia, Heidelberg Heights, Victoria, Australia; Pooja Khatri, Univ of Cincinnati Academic Health Cntr, Cincinnati, OH; IMS III Investigators

  Author Disclosures: O.V. Spataru: None. T. Jovin: Speakers; Modest; IV3, CONCENTRIC MEDICAL, MICRUS. Ownership Interest; Modest; NIT. L. Wechsler: Ownership Interest; Modest; NIT. M. Horowitz: Speakers; Modest; consultant IV3. A. Malik: None. L. Ridwan: None. M. Jumaa: None. Z. Syed: None. A. Aleu: None. W P248 Midterm Clinical and Angiographic Follow Up for the First FDA-approved Prospective, Single-arm Trial of Primary Stenting for Stroke: SARIS (Stent-Assisted Recanalization for acute Ischemic Stroke)

  Author Disclosures: L. Cava: None. K.C. Albright: None. K. Barlinn: None. C. Balucani: None. M. Kesani: None. L. Zhao: None. K. Sands: None. M. Lyerly: None. A.W. Alexandrov: None. M.R. Harrigan: None. J.A. Horton: None. E. Underwood: None. D. Patterson: None. A.V. Alexandrov: None.

  Author Disclosures: M.E. Klegerman: Ownership Interest; Significant; EchoDynamics, Inc.. M.R. Moody: None. H. Kim: None. B. Smulevitz: None. S. Huang: None. C.K. Holland: None. D.D. McPherson: None. S.T. Laing: None. W P255 THR-18 Peptide, a Modulator of tPA action: A Summary of Preclinical and Clinical Studies Abraham Nimrod, Michael Krakovski, Vadim Polianski, Arnon Aharon, Thrombotech Technologies Ltd, Nes Ziona, Israel; Abd el Roof Higazi, Ronen R Leker, Hadassa Med Sch, Jerusalem, Israel; Itschak Lamensdorf; Thrombotech Technologies Ltd, Nes Ziona, Israel

  Author Disclosures: A. nimrod: None. M. Krakovski: None. V. Polianski: None. A. Aharon: None. A. Higazi: None. R.R. Leker: None. I. Lamensdorf: None. W P256 The SPEED Trial: A Study of the Penumbra Early Evacuation Device Don Frei, Swedish Med Cntr, Englewood, CO; A. Turk, Med Univ of South Carolina, Charleston, SC; D. Heck, Forsyth Med Cntr, Winston Salem, NC; F. Hui, Cleveland Clinic, Cleveland, OH; G. Joseph, Presbyterian Hosp, Charlotte, NC; R. Jahan, UCLA Med Cntr, Los Angeles, CA; J. Carpenter, West Virginia Univ Med Cntr, Morgantown, WV; T. Grobelny, Christ Hosp, Oak Lawn, IL; J. Goddard, Fairview Southdale Hosp, Edina, MN; B. Leader, A. Bose, S.P. Sit; Penumbra, Inc., Alameda, CA Introduction: The Penumbra System is an aspiration-based mechanical thrombectomy device indicated for the revascularization of large vessel occlusion in acute ischemic stroke. Reported herein are results of a proof of concept study to assess the extent to which a reperfusion catheter with a larger internal diameter (0.054 inch) affects on-the-table aspiration efficiency/ speed, accessibility and safety of the System. Methods: This was a retrospective case review of 53 consecutive patients with large vessel occlusion in the brain who were treated with the larger Penumbra System 054 catheter at 9 centers in the U.S.. Main inclusion criteria were presentation within 8 hours of symptom onset and an occlusion of a treatable cerebral vessel. The primary endpoints were time of aspiration and rate of complete revascularization as measured by the TIMI scale. Results from the Penumbra Pivotal* trial that utilized the smaller catheters (0.026 to 0.041 inch) were used as the historical control. Results: Stroke 2009;40:2761-2768 **PϽ 0.05 vs. PIVOTAL Conclusion: Increasing the internal diameter of the Penumbra Reperfusion Catheter to 0.054 inch can enhance aspiration efficiency and speed, leading to a shorter aspiration time and a more complete revascularization without affecting accessibility or safety. Author Disclosures: D. Frei: Honoraria; Modest; Penumbra, Inc.. A. Turk: None. D. Heck: None. F. Hui: None. G. Joseph: None. R. Jahan: None. J. Carpenter: None. T. Grobelny: None. J. Goddard: None. B. Leader: Employment; Significant; Penumbra, Inc. A. Bose: Employment; Significant; Penumbra, Inc. S. Sit: Employment; Significant; Penumbra, Inc..

  Author Disclosures: N.R. Gonzales: None. A.D. Barreto: None. N. Harun: None. T. Wu: None. P. Sahota: None. A. Sarraj: None. R. El khoury: None. W. Hicks: None. N.S. Sangha: None. V. Misra: None. G.A. Lopez: None. S.I. Savitz: None. J.C. Grotta: None.W P260 Failure of Conscious Sedation Among Patients Undergoing Neuro-Endovascular ProceduresAmeer E Hassan, Rizwan Husain, Gabriela Vazquez, Gustavo J Rodriguez, M. Fareed K Suri, Ramachandra P Tummala, Robert A Taylor, Mustapha A Ezzeddine, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: Neuro-endovascular procedures are performed under conscious sedation (local anesthesia) in varying proportion of patients in various institutions. It is known that in certain patients conscious sedation may be inadequate during the procedure and an unplanned conversion to general anesthesia may be necessary. Objective: To ascertain the rate of failure of conscious sedation in patients undergoing neuro-endovascular procedures and compare the prognosis of patients that were converted from conscious sedation to general anesthesia to those initiated with general anesthesia. Methods: All 1971 endovascular treated patients were identified through a prospective database maintained from two comprehensive stroke centers between 2006-2009. Favorable outcome (modified Rankin score of 0-2), death, and patients' clinical and procedural characteristics were obtained and reviewed. Results: The rate of failure of conscious sedation in 265 patients (387 procedures) undergoing neuro-endovascular procedures under conscious sedation was 2.3%. Demographics, risk factors, outcomes and procedure type are provided in the tables below. (Tables

  Author Disclosures: A. Flores: None. J. Sargento-Freitas: None. M. Rubiera: None. J. Pagola: None. D. Rodriguez-Luna: None. S. Pin ˜eiro: None. O. Maisterra: None. J. Montaner: None. J. Alvarez-Sabin: None. C. Molina: None. M. Ribo: None. Rene Flores, Paula Roberson, Aliza Brown, John Lowery, Michael Borrelli, William C Culp; Univ. of Arkansas for Med Sci, Little Rock, AR

  Author Disclosures: S. Mangiafico: None. V. Saia: None. I. Romani: None. V. Palumbo: None. G. Pracucci: None. S. Nappini: None. P. Nencini: None. F. Ricciardi: None. M. Nesi: None. D. Inzitari: None.

  Author Disclosures: S.F. Zaidi: None. A. Aghaebrahim: None. M.A. Jumma: None. O.V. Spataru: None. M.D. Hammer: None. V.K. Reddy: None. L.R. Wechsler: None. M. Horowitz: None. T.G. Jovin: None.

  Author Disclosures: M.B. Alves: None. J.J. Carvalho: None. G.S. Silva: None. C.B. Machado: None. G.A.A. Viana: None. B.F.C. Santos: None.

  Author Disclosures: J. Fussner: None. E. Supan: None. L. McCartney: None. M. Richardson: None. C. Garrett: None. C. Sila: None.

  Author Disclosures: L. Sosa: None. R.E. Martinez: None. L. Shen: None. N. Harun: None. R. Sline: None. N. Sangha: None. T. Wu: None. H. Indupuru: None. V. Misra: None. A. Sarraj: None. S. Alderman: None. M. Hess: None. T. Fontenot: None. R. El Khoury: None. M. Kasam: None. W. Hicks: None. P. Sahota: None. A. Barretto: None. J. Grotta: None. S. Savitz: None. G. Lopez: None. N. Gonzales: None.

  Figure showing trends in medication use overall and for five classes of antihypertensives.

  Author Disclosures: B.M. Kissela: Research Grant; Significant; This work supported by NIH-NINDS R-01 NS30678. H. Sucharew: None. K. Alwell: None. C.J. Moomaw: None. D. Woo: None. P. Khatri: None. M.L. Flaherty: None. O. Adeoye: None. S. Belagaje: None. S. Ferioli: None. J.P. Broderick: None. D. Kleindorfer: None. C.J. Lindsell: None.

  Author Disclosures: B.M. Kissela: Research Grant; Significant; This work supported by NIH-NINDS R-01 NS30678. H. Sucharew: None. K. Alwell: None. C.J. Moomaw: None. D. Woo: None. P. Khatri: None. M.L. Flaherty: None. O. Adeoye: None. S. Belagaje: None. S. Ferioli: None. J.P. Broderick: None. J. Khoury: None. D. Kleindorfer: None. C.J. Lindsell: None.

  Author Disclosures: D.B. Smith: None. P. Murphy: None. W. Jones: None. E. Cumbler: None.

  Kate S McArthur, Instutute of Cardiovascular and Med Sciences, Univ of Glasgow, Glasgow, United Kingdom; M L Beagan, A Degnan, R C Howarth, K A Mitchell, F B McQuaige, M A Shannon, Undergraduate Med Sch, Univ of Glasgow, Glasgow, United Kingdom; Terence J Quinn; Institute of Cardiovascular and Med Sciences, Univ of Glasgow, Glasgow, United Kingdom Background and Purpose: The modified Rankin scale (mRS) is the most prevalent functional outcome measure in acute stroke trials. Cognitive or communication issues may preclude standard mRS interview

  Author Disclosures: D.L. Roth: None. W.E. Haley: None. O.J. Clay: None. V.G. Wadley: None. G. Howard: None. W P317 Acute Stroke Mortality as a Measure of Program Quality: Does Unadjusted Mortality Rate Paint a Clear Quality Picture for Public Reporting? Anne W Alexandrov, Kara Sands, Kristian Barlinn, Tiffany Pineada, Michael Lyerly, Luis F Cava, Daniel K Vrazel, April Sisson, Alexis Jernigan, Hayden Long, Mark Harrigan, Andrei V Alexandrov, Karen C Albright; Univ of Alabama at Birmingham, Birmingham, AL

  Author Disclosures: J.S. McKinney: None. Y. Deng: None. S.E. Kasner: None. J.B. Kostis: None. W P320 Mortality Due to Stroke in Da Nang, Vietnam Annette L Fitzpatrick, Univ of Washington, Seattle, WA; Quang V Ngo, Ministry of Health, Da Nang, Viet Nam; Kiet A Ly, Thanh G Ton, David L Tirschwell, W. T Longstreth, Jr., Univ of Washington, Seattle, WA; Tung T Vo, Chien H Pham; Ministry of Health, Da Nang, Viet Nam

  Author Disclosures: A.L. Fitzpatrick: None. Q.V. Ngo: None. K.A. Ly: None. T.G. Ton: None. D.L. Tirschwell: None. W.T. Longstreth: None. T.T. Vo: None. C.H. Pham: None.

  Author Disclosures: J. Dawson: None. A.C. Cameron: None. M.R. Walters: None. T.J. Quinn: None. K.S. McArthur: None. K.R. Lees: None. W P322 TIA Clinic Triage Strategy Reduces the Cost of TIA Evaluation Michael Mlynash, Stanford Stroke Cntr, Stanford Univ Med Cntr, Palo Alto, CA; James Castle, Dept of Neurology, NorthShore Univ HealthSystem, Pritzker Sch of Medicine, Evanston, IL; Jean-Marc Olivot, Connie Wolford, Neil E Schwartz, Maarten G Lansberg, Stanford Stroke Cntr, Stanford Univ Med Cntr, Palo Alto, CA; Gail Edwards, Dept of Finance, Stanford Hosp and Clinics, Stanford, CA; Stephanie Kemp, Gregory W Albers; Stanford Stroke Cntr, Stanford Univ Med Cntr, Palo Alto, CA

  Conclusions: Despite recommendations by major organizations and evidence to support the role of MRI in acute TIA evaluation, less than one-third of patients admitted with TIA are evaluated with brain MRI in this large inpatient sample. Several patient-related and hospital-related factors may influence MRI utilization following TIA. More physician education and study of limiting factors including availability and cost are needed. Author Disclosures: S. Prabhakaran: None. M. McNulty: None. B. Ouyang: None.

  Author Disclosures: E. Giralt-Steinhauer: None. E. Cuadrado-Godia: None. J. Jimenez-Conde: None. A. Rodriguez-Campello: None. S. Jimena: None. M.A. Rubio: None. A. Ois: None. E. Garcia-Ramallo: None. J. Roquer: None.

  Author Disclosures: L.E. Skolarus: None. L.B. Morgenstern: None. J.B. Froehlich: Research Grant; Modest; Sanofi-Aventis. Speakers; Modest; Sanofi-Aventis, Pfizer, Merck/Shering-Plough. Honoraria; Modest; Sanofi-Aventis, Pfizer, Merck/Shering-Plough. Consultant/Advisory Board; Modest; Sanofi-Aventis, Pfizer. L.D. Lisabeth: None. D.L. Brown: None.

  Author Disclosures: A. Afzal: None. S. Ansari: None. C.P. Kellner: None. S.A. Sosunov: None. A. Wolfe: None. B.L. Hoh: None. E. Scott: None. E. Connolly: None. J. Mocco: None.

  Author Disclosures: M. Moussavi: None. B. Gershen: None. D. Korya: None. A.H. Patel: None. J.H. Brahmbhatt: None. S. Dash: None. D. Rosenblat: None. M. Gizzi: None. J. Kirmani: None.

  Author Disclosures: M. Ning: None. F. Buonanno: None. M. Athenas: None. D. Sarracino: None. B. Krastins: None. Z. Demirjian: None. I. Inglessis-Azuaje: None. D. McMullin: None. G. Dec: None. I. Palacios: None. M. Lopez: None. E.H. Lo: None.

  Author Disclosures: A. Afzal: None. S. Ansari: None. C.P. Kellner: None. S.A. Sosunov: None. B.L. Hoh: None. E.W. Scott: None. E. Connolly: None. J. Mocco: None.

  Author Disclosures: C. Prodan: None. J.A. Stoner: None. L.D. Cowan: None. G.L. Dale: None.

  stroke.ahajournals.org/ Downloaded from This research has received full or partial funding support from the American Heart Association, Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC). Author Disclosures: H. Yeoh: None. B.J. Titus: None. G.K. Owens: None. R.H. Rosenwasser: None. A.S. Dumont: None.

  attenuated MMP-2 activity. Conclusion: This work identifies for the first time an experimental system for invoking pial collateral circulation during stroke. T3 supplementation improves stroke affected pial circulation and attenuates post-stroke outcomes. Author Disclosures: L.A. Peterson: None. C.L. Rink: None. S. Khanna: None. M. Heigel: None. C.K. Sen: Research Grant; Modest; NIH NS42617.

  Author Disclosures: N. Sladojevic: None. S.M. Stamatovic: None. B. Pitt: None. R.F. Keep: None. A.V. Andjelkovic: None.

  Helmi L Lutsep, Oregon Health & Science Univ, Portland, OR; Irfan M Altafullah, Minneapolis Clinic of Neurology, Minneapolis, MN; Robin S Roberts, McMaster Univ, Hamilton, ON; Isaac E Silverman, Hartford Hosp, Hartford, CT; Mark A Turco, Washington Adventist Hosp, Takoma Park, MD; Anand G Vaishnav, Univ of Louisville, Louisville, KY; for the Sentis Investigators

  Kristian B Barlinn, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham, Birmingham, AL; Andrew D Barreto, Stroke Program, the Univ of Texas-Houston Med Sch, Houston, TX; April Sisson, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham, Birmingham, AL; David S Liebeskind, David Geffen Sch of Medicine, Dept of Medicine, UCLA, Los Angeles, CA; Limin Zhao, Luis F Cava, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham, Birmingham, AL; John F Rothrock, Comprehensive Stroke Cntr, Dept of Neurology, Univ of Alabama at Birmingham, Birmingham, AL; Mark E Schafer, Sonic Tech, Inc., Philadelphia,, PA; John Alleman, Cerevast Therapeutics, Inc., Redmond, WA; James C Grotta, Stroke Program, the Univ of Texas-Houston Med Sch, Houston, TX; Andrei V Alexandrov; Comprehensive Stroke Cntr, Univ of Alabama at Birmingham, Birmingham, AL

  Author Disclosures: A. Rocco: None. C. Gumbinger: None. M. Sykora: None. J. Diedler: None. P. Ringleb: None. W. Hacke: Other; Modest; Editor of 'Journal of Stroke'.

  Author Disclosures: S.F. Zaidi: None. M.A. Jumma: None. M.D. Hammer: None. V.K. Reddy: None. T.G. Jovin: None. L. Massaro: None. K. Uchino: None. L. Ridwan: None. L.R. Wechsler: None.

  Author Disclosures: J.S. Wetzel: None. A.M. Elliot: None. C.M. Wallace: None. S. Duong: None. E.G. Pivalizza: None. N. Harun: None. M. Hess: None. J.C. Grotta: None.

  Author Disclosures: S. Lorenzano: None. N. Ahmed: None. G. Moretto: None. P. Nichelli: None. N. Marcello: None. R. Curro `-Dossi: None. D. Inzitari: None. A. Rosselli: None. G. Comi: None. M. Furlan: None. D. Guidetti: None. M. Tola: None. C. Pozzessere: None. F. Perini: None. R. Sterzi: None. E. Ursino: None. M. Magoni: None. N. Wahlgren: None. M. Prencipe: None. D. Toni: None.

  Author Disclosures: R.C. Seet: None. J.C. Lee: None. B.P. Chan: None. V.K. Sharma: None. H. Teoh: None. B.K. Ong: None. B. Halliwell: None.

  Author Disclosures: V. Misra: None. N. Harun: None. M. Sline: None. A.D. Barreto: None. G.A. Lopez: None. N.R. Gonzales: None. J.C. Grotta: None. S.I. Savitz: None.

  Author Disclosures: A. Stemer: None. R. Raman: None. K. Ennstrom: None. P. Lyden: None. T.M. Hemmen: None. Th P20 Estimated Peak Rarefaction Pressure Predicts Recanalization and Outcome in the Transcranial Ultrasound in Clinical SONothrombolysis (TUCSON) Trial Kristian B Barlinn, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham, Birmingham, AL; Georgios Tsivgoulis, Dept of Neurology, Democritus Univ of Thrace, Sch of Medicine, Alexandroupolis, Greece; Carlos A Molina, Neurovascular Unit, Dept of Neurology, Hosp Vall d'Hebron, Barcelona, Spain; Dmitri A Alexandrov, John Alleman, Cerevast Therapeutics, Inc., Redmond, WA; Andrei V Alexandrov, Comprehensive Stroke Cntr, Univ of Alabama at Birmingham, Birmingham, AL; Tucson Investigators

  Author Disclosures: G. Tsivgoulis: None. H.L. Teoh: None. I. Heliopoulos: None. B.P. Chan: None. K. Vadikolias: None. A. Patousi: None. C. Bogiatzi: None. C. Piperidou: None. V.K. Sharma: None. Th P22 Levels of Creatin Kinase in Blood are Predictors of Hemorrhagic Transformation in Patients Treated with rt-PA Mar Castellanos, Marı ´a Jime ´nez, Yolanda Silva, Josep Puig, Salvador Pedraza, Estela Sanjua ´n, Pilar Sa ´nchez-Camacho, Joaquı ´n Serena; Hosp Universitari Dr Josep Trueta, Biomedical Rsch Institute of Girona, Girona, Spain

  Author Disclosures: A.W. Hsia: None. R.T. Benson: None. M. Pehlivanova: None. J.G. Merino: None. L.L. Latour: None. M. Luby: None. S.S. Song: None. J.K. Lynch: None. C.H. Ritter: None. A. Katcheves: None. S. Warach: None.

  ) volume of perfusion deficit at tp1 (pϭ0.024), and (3) admission mean arterial pressure (pϭ0.040). Patients taking statins had greater äNIHSS (8.8 points) at one month compared with untreated patients (4.4 points), pϭ0.028 (Fig, B). The best-fitting model for prediction of äNIHSS included only two variables: pre-existing statin use (pϭ0.010) and age (pϭ0.015). Conclusion: Statin use prior to ischemic stroke onset is associated with early reperfusion and improved outcome. This raises the hypothesis that statin use may improve clinical outcome by enhancing early reperfusion. Author Disclosures: A.L. Ford: None. H. An: None. R. Ponisio: None. G. D'Angelo: None. P. Bushard: None. K.D. Vo: None. W.J. Powers: None. W. Lin: None. J. Lee: None.

  Author Disclosures: R.T. Benson: None. A.W. Hsia: None. M. Pehlivanova: None. J. Merino: None. L. Latour: None. M. Luby: None. S. Song: None. J. Lynch: None. C.H. Ritter: None. A. Katcheves: None. S. Warach: None. Th P28 High-density Lipoprotein Cholesterol Level is a Predictor of Outcome after Intravenous Recombinant Tissue Plasminogen Activator Therapy for Acute Stroke: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rt-PA Registry Noriko Makihara, Yasushi Okada, Dept of Cerebrovascular Disease, Cerebrovascular Cntr and Clinical Rsch Cntr, National Hosp Organization Kyushu Med Cntr, Fukuoka, Japan; Masatoshi Koga, Dept of Cerebrovascular Medicine, National Cerebral and Cardiovascular Cntr, Suita, Japan; Yoshiaki Shiokawa, Dept of Neurosurgery and Stroke Cntr, Kyorin Univ Sch of Medicine, Mitaka, Japan; Jyoji Nakagawara, Dept of Neurosurgery and Stroke Cntr, Nakamura Memorial Hosp, Sapporo, Japan; Eisuke Furui, Dept of Stroke Neurology, Kohnan Hosp, Sendai, Japan; Kazumi Kimura, Dept of Stroke Medicine, Kawasaki Med Sch, Kurashiki, Japan; Hiroshi Yamagami, Dept of Neurology, Stroke Cntr, Kobe City General Hosp, Kobe, Japan; Yasuhiro Hasegawa, Dept of Neurology, St. Marianna Univ Sch of Medicine, Kawasaki, Japan; Kazuomi Kario, Div of Cardiovascular Medicine, Dept of Medicine, Jichi Med Univ Sch of Medicine, Shimotsuke, Japan; Satoshi Okuda, Dept of Neurology, National Hosp Organization Nagoya Med Cntr, Nagoya, Japan; Masaki Naganuma, Kazunori Toyoda; Dept of Cerebrovascular Medicine, National Cerebral and Cardiovascular Cntr, Suita, Japan

  Author Disclosures: B. Chakraborty: None. S. Agarwal: None. G. Vishnoi: None. D. Chowdhury: None. Th P31 Brain Plasticity Changes In Patients With Vascular Lesions Vivek Prabhakaran, UW-Madison Hosp & Clinics, Madison, WI; Dovile Baniulis, Nicole Kornder, UW-Madison Sch of Medicine and Public Health, Madison, WI; Jed Voss, Veena A Nair, Bornali Kundu, UW-Madison, Madison, WI; Joel Wood, Amy Utter, UW-Madison Sch of Medicine and Public Health, Madison, WI; Tom Gallagher, Ahmad Atassi, Chad Moritz, UW-Madison Hosp & Clinics, Madison, WI; Elizabeth Meyerand; UW-Madison, Madison, WI

  Author Disclosures: S.C. Craciunas: None. A. Bani-Ahmed: None. W.M. Brooks: None. R.J. Nudo: None. E.A. Popescu: None. I. Choi: None. S. Lee: None. C.M. Cirstea: None.

  Author Disclosures: Y. Ueno: None. M. Chopp: None. L. Zhang: None. B. Buller: None. Z. Liu: None. N.L. Lehman: None. X. Liu: None. C. Roberts: None. Z. Zhang: None.

  Owen A Ross, Alexandra I. Soto-Ortolaza, Christophe Verbeeck, Mayo Clinic, Jacksonville, FL; Stephen S. Rich, Cntr for Public Health Genomics, Univ of Virginia, Charlottesville, VA; Andrew Singleton, Molecular Genetics Section; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD; John A. Hardy, Dept of Molecular Neuroscience, Institute of Neurology, Univ College London, London, United Kingdom; Thomas G. Brott, Mayo Clinic , Dept of Neurology, Jacksonville, FL; Robert D. Brown, Jr., Mayo Clinic, Dept of Neurology, Rochester, MN; Brett Kissela, Univ of Cincinnati, Dept of Neurology, Cincinnati, OH; Bradford B. Worrall, Depts of Neurology and Public Health Sciences, Univ of Virginia, Charlottesville, VA; James F. Meschia, Mayo Clinic, Dept of Neurology, Jacksonville, FL; for the SWISS Investigators.

  Author Disclosures: O.A. Ross: None. A. Soto-Ortolaza: None. C. Verbeeck: None. S. Rich: None. A. Singleton: None. J. Hardy: None. T. Brott: Research Grant; Significant; NINDS R01 NS38384. R. Brown, Jr.: None. B. Kissela: None. B. Worrall: None. J. Meschia: Research Grant; Significant; NINDS R01 NS038384.

  Author Disclosures: B.C. Lau: None. A.R. Baheti: None. R.S. Smith: None. K.M. Powell: None. C. Leiva Salinas: None. T.G. Brott: None. R.D. Brown: None. B.M. Kissela: None. M. Wintermark: None. J.F. Meschia: None. N.S. Rost: None. B.B. Worrall: None.

  Author Disclosures: J.W. Cole: None. A. Pratap: None. L.J. Tallon: None. L.K. Sadzewicz: None. O.C. Stine: None. N. Dueker: None. Y. Cheng: None. M.A. Wozniak: None. B.J. Stern: None. J.F. Meschia: None. B.D. Mitchell: None. S.J. Kittner: None. J.R. O'Connell: None.

  Author Disclosures: C.O. Leonards: None. J.B. Fiebach: None. C. Werner: None. U. Laufs: None. M. Endres: None. M. Ebinger: None.

  Author Disclosures: D.B. Zahuranec: None. B.N. Sanchez: None. D.L. Brown: None. J.J. Wing: None. W.J. Meurer: None. L.B. Morgenstern: None. L.D. Lisabeth: None.

  Author Disclosures: D. Lee: None. J. Kim: None. Y. Kim: None. H. Nam: None. J. Heo: Research Grant; Significant; This work was supported by a grant of the Korea Healthcare Technology Research and Development Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A060171, A 085136).

  Author Disclosures: C.D.J. Barras: None. A.M. Pavlovic: None. S. Christensen: None. N. Perez de la Ossa: None. B.M. Tress: None. P.M. Desmond: None. I. Gordon: None. P.J. Hand: None. S.M. Davis: None. ´cio, Hosp Fernando Fonseca, Amadora, Portugal; Reto Meuli, Philippe Maeder, CHUV -Service of Diagnostic and Interventional Radiology, Lausanne, Switzerland; Mohamed Faouzi, Institute of Social and Preventive Medicine, Lausanne, Switzerland; Max Wintermark, Dept of Radiology, Div of Neuroradiology, Charlottesville, VA; Patrik Michel; CHUV -Neurology Service, Lausanne, Switzerland Introduction: Diagnosis, localization and acute treatment of acute ischemic stroke is most frequently based on noncontrast cerebral CT (NCCT).

  Author Disclosures: P.R. Paliwal: None. A. Ahmad: None. S. Liang: None. L.L.L. Yeo: None. P.K. Loh: None. K.W.P. Ng: None. L.Y.H. Wong: None. S. Jie: None. M. Maliapen: None. B.K.C. Ong: None. N. Venketasubramanian: None. H.L. Teoh: None. V.F. Chong: None. E. Tan: None. A.K. Sinha: None. B.P.L. Chan: None. V.K. Sharma: None.

  Author Disclosures: B.C.V. Campbell: None. H.T.H. Tu: None. S. Christensen: None. P.M. Desmond: None. C.R. Levi: None. C.F. Bladin: None. N. Hjort: None. M. Ashkanian: None. C. Solling: None. G.A. Donnan: None. S.M. Davis: None. L. Østergaard: None. M.W. Parsons: None.

  Author Disclosures: B.A. Hotter: None. A. Kufner: None. U. Malzahn: None. G.J. Jungehuelsing: None. J.B. Fiebach: None.

  Author Disclosures: P. Adamczyk: None. J.L. Saver: None. Q. Hao: None. N. Sanossian: None. N. Salamon: None. R. Fiaz: None. L.K. Ali: None. D. Kim: None. B. Ovbiagele: None. S. Starkman: None. P. Vespa: None. S. Song: None. R. Raychev: None. H.G. Abcede: None. N. Gonzalez: None. S. Tateshima: None. R. Jahan: None. G.R. Duckwiler: Ownership Interest; Modest; Concentric Medical. Consultant/Advisory Board; Modest; Concentric Medical. F. Vinuela: None. D.S. Liebeskind: None.

  Author Disclosures: A. Bivard: None. C. Levi: None. N. Spratt: None. M.W. Parsons: None. Th P105 Oxygen Challenge MRI Provides a Measure of the Underlying Haemodynamic and Metabolic State of the Tissue Krishna Dani, Rosario Lopez, Celestine Santosh, David Brennan, Christopher McCabe, William Holmes, Univ of Glasgow, Glasgow, United Kingdom; Barrie Condon, Donald Hadley, Institute of Neurological Sciences, Glasgow, United Kingdom; Mhairi Macrae, Keith Muir; Univ of Glasgow, Glasgow, United Kingdom Background We recently presented pilot results for the development of Oxygen Challenge MRI (Santosh et al, JCBFM, 2008; Dani et al Annals of Neurology

  Author Disclosures: K. Dani: None. R. Lopez: None. C. Santosh: None. D. Brennan: None. C. McCabe: None. W. Holmes: None. B. Condon: None. D. Hadley: None. M. Macrae: None. K. Muir: None.

  4 Ϯ7.89. Conclusion: Perfusion measurements based on PCASL show good reproducibility. Author Disclosures: C. sohn: None. J. Kim: None. S. Choi: None. M. Han: None. K. Chang: None. I. Song: None. G. Jahng: None. T. Yun: None.Th P108 The Superiority of MRI over CT in the Diagnosis of Acute Ischemic Stroke Increases with Patient AgeCarsten H Ritter, National Institutes of Health, Bethesda, MD; Julio A Chalela, Med Univ of South Carolina, Charlston, SC; John A Butman, National Institutes of Health, Bethesda, MD; Andrew M Demchuk, Michael D Hill, Foothills Med Cntr, Calgary, Canada; Nicholas Patronas, Steven Warach; National Institutes of Health, Bethesda, MD Background: Age related changes in the brain cause hypoattenuation on CT. Chronic as well as acute ischemia also appear as hypoattenuation on CT, whereas on DWI-MRI acute ischemia causes a hyperintense signal and chronic ischemia an iso-or hypointense signal. In a previous study DWI-MRI has been shown to be superior to CT in the diagnosis of acute ischemia unrelated to time from symptom onset to scan or stroke severity. Since chronic changes in the brain increase with age, we investigated whether age is related to the superiority of DWI-MRI over CT in the detection of acute ischemic stroke. Methods: Clinical data and imaging reads of a previously conducted single-center, prospective, blind comparison of non-contrast CT and DWI-MRI in a consecutive series of patients with suspected stroke were evaluated. A logistic regression model was used to examine the association of age with DWI-MRI positive/CT negative scans. The scans had been interpreted independently by four experts, who were unaware of clinical information, MRI-CT pairings, and follow-up imaging. Results: 356 patients, 190 of whom had a final diagnosis of acute ischemic stroke, were assessed. The median age was 76. DWI-MRI detected acute ischemic stroke in 164 of 356 (46%, 95% CI 41-51%) patients, CT in 35 of 356 (10%, 95% CI 7-14%). DWI-MRI was positive and CT negative for acute ischemic stroke in 132 of 356 (37%, 32-42%). In a logistic regression model age showed a significant association with DWI-MRI positive/CT negative scans (OR 1.019, 95% CI 1.002-1.036, pϭ0.03). The graph shows the distribution by age group of patients who were positive for acute ischemic stroke on DWI-MRI but negative on CT. Interpretation: Age is related to the superiority of DWI-MRI over CT in the diagnosis of acute stroke. We hypothesize that white matter background disease increasing with age and causing hypoattenuation on CT may make the diagnosis of acute ischemic stroke more difficult on CT as compared to DWI-MRI. Author Disclosures: C.H. Ritter: None. J.A. Chalela: None. J.A. Butman: None. A.M. Demchuk: None. M.D. Hill: None. N. Patronas: None. S. Warach: None.

  Author Disclosures: M. Nakajima: None. Y. Inatomi: None. T. Yonehara: None. T. Hirano: None. M. Uchino: None.Th P111 Acute Stroke Core on Perfusion and Diffusion ImagesMatus Straka, Stanford Univ Dept of Radiology, Stanford, CA; Maarten G Lansberg, Michael Mlynash, Stephanie M Kemp, Demi Thai, Gregory W Albers, Stanford Stroke Cntr, Stanford, CA; Roland Bammer; Stanford Univ Dept of Radiology, Stanford, CA

  Author Disclosures: D.S. Liebeskind: Research Grant; Significant; K23NS054084. Consultant/ Advisory Board; Modest; CoAxia, Inc.. N. Sanossian: None. Q. Hao: None. N. Salamon: None. J.L. Saver: None.

  Author Disclosures: J.K. Wasserman: None. J.J. Perry: None. D. Dowlatshahi: None. G. Stotts: None. M. Sivilotti: None. A. Worster: None. M. Emond: None. J. Sutherland: None. I. Stiell: None. M. Sharma: None. Th P118 Sudden Headache Preceding Cardiac Arrest: Frequency and Underlying Cause Evaluated with Post-Resuscitation CT Scan.

  Author Disclosures: N. Sanossian: None. S. Starkman: None. S. Hamilton: None. D.S. Liebeskind: None. M. Eckstein: None. S. Stratton: None. F. Pratt: None. L. Restrepo: None. L.K. Ali: None. R. Conwit: None. J.L. Saver: None.

  Author Disclosures: A. Georgiadis: None. M. Ansar: None. S.A. Chaudhry: None. F. Sultan: None. S.B. Tonarelli: None. M. Tibbs: None. G. Vazquez: None. L.C. Dees: None. A.I. Qureshi: None. Th P121 Low dose rFVIIa Could effectively Reverse Elevated INR but Did not Chang The Outcome of Patients on Warfarin who Developed Intracerebral hemorrhages David Z Wang, OSF/INI/UNIV OF ILLINOIS COLL OF MED, Peoria, IL; Ammie K Hodges, OSF Saint Francis Med Cntr, Peoria, IL; Deepak S Nair, OSF/INI/UNIV OF ILLINOIS COLL MED, Peoria, IL; Jan L Jahnel, Maureen L Mathews, Judi M Beck, OSF/INI/SFMC, Peoria, IL; Mikalynn Katlack, Richwoods High Sch, Peoria, IL; Arun V Talkad; OSF/INI/UNIV OF ILLINOIS COLL OF MED, Peoria, IL Background To quickly and effectively reverse elevated International Normalized Ratio (INR) in patients on warfarin who developed intracerebral hemorrhage (ICH) is urgent but of challenge.

  Author Disclosures: D.Z. Wang: None. A.K. Hodges: None. D.S. Nair: None. J.L. Jahnel: None. M.L. Mathews: None. J.M. Beck: None. M. Katlack: None. A.V. Talkad: None. Th P122 Oral Anticoagulant Use and Decreasing Hematocrit are Significantly Associated with Discrepant ED Point-of-care INR Results in Patients with Acute Cerebrovascular Disease Sunanda Nanduri, Allegheny General Hosp, Pittsburgh, PA; Gajanan Hegde, Univ of Pittsburgh, Katz Graduate Sch of Business, Pittsburgh, PA; Arvind Venkat, Sandy Daley, Jack Protetch, Melissa Tian, Ashis Tayal; Allegheny General Hosp, Pittsburgh, PA Background: Previous studies comparing point-of-care (POC) INR accuracy relative to central laboratory (CL) INR in emergency department (ED) patients with acute ischemic stroke (AIS), transient ischemic attack (TIA) or intracerebral hemorrhage (ICH) suggest that significant discrepancy between the two values can be detected that may confound rapid treatment decision making in patients with acute cerebrovascular disease. Purpose: We hypothesized that specific clinical and operational variables were associated with POC INR discrepancy versus CL INR in ED patients with AIS, TIA or ICH and that the incidence of discrepancy decreased over time as a marker of effective quality assurance. Methods: A consecutive series of 637 patients with a final diagnosis of AIS (nϭ427), TIA (nϭ105) or ICH (nϭ105) underwent both POC INR and CL INR testing during ED presentation at our institution. All patients were tested by trained technicians using the i-STAT © POC analyzer (Abbott, NJ) with a quality assurance program. Patients with POC INR results more than 0.25 INR units from the CL INR were considered discrepant. We analyzed potential predictors of POC INR discrepancy including demographic (age, gender, race), clinical (NIH stroke scale, smoking status, antiplatelet, oral anticoagulant, hypertensive, cholesterol or diabetic medication use, hematocrit, glucose, aPTT, platelet count, body mass index) and operational (ED patient census on presentation) variables using multivariate logistic regression. We evaluated the change in incidence of POC INR discrepancy over 30 months using Ϭ 2 methodology. Results: Discrepant POC INR results were found in 21.5% (137/637) of patients and 17.3% (110/637) were taking oral anticoagulants. The mean bias between POC INR and CL INR was 0.02Ϯ0.73 (range -11.3 to 10.5) INR units. Significant covariates of POC INR discrepancy were anticoagulant use (ORϭ3.00, CI 1.34-6.59, pϭ0.01), hematocrit (ORϭ0.94, CI 0.89-1.00, pϭ0.04), and aPTT (ORϭ1.06, CI 1.01-1.11, pϭ0.01). Oral anticoagulant use most significantly contributed to POC INR discrepancy [41.8% discrepancy in anticoagulated patients (46/110) versus 17.3% discrepancy non-anticoagulated patients (91/527), z statisticϭ5.5, pϽ0.001]. The incidence of POC discrepancy decreased over time (39% discrepancy during the first 7.5 months to 14% discrepancy during the last 7.5 months, Ϭ 2 ϭ29.8, PϽ0.001). Conclusion: Anticoagulant use, decreasing hematocrit and increasing aPTT were significantly associated with ED POC INR discrepancy in patients with AIS, TIA or ICH. The incidence of POC INR discrepancy decreased over time, suggesting quality assurance efficacy. Author Disclosures: S. Nanduri: None. G. Hegde: None. A. Venkat: None. S. Daley: None. J. Protetch: None. M. Tian: None. A. Tayal: None.

  Author Disclosures: W. Pfeilschifter: None. D. Spitzer: None. B. Czech: None. H. Steinmetz: None. C. Foerch: None.

  Author Disclosures: M.A. Hamner: None. A. Savos: None. J. Colman: None. B.R. Ransom: None. J.R. Weinstein: None.

  01) and returned to basal levels 96 hrs post surgery (nϭ3, pϾ0.05). HUCB cell treatment blocked caspase 3 cleavage, where levels remained comparable to sham (nϭ3, pϾ0.05). Conclusion: The present results demonstrate that Akt activation is an integral and necessary component of HUCB cell mediated white matter protection. Our data suggest HUCB cell induced P-Akt protect OLs following MCAO by reducing caspase 3 activation. Author Disclosures: D. Rowe: None. L. Collier: None. A. Willing: None. K. Pennypacker: None.Th P154 Trichostatin A Impact Upon Post-stroke Neurogenesis In The Immature Brain Is Dependent Upon The Time-point After Injury Being AssessedShilpa D Kadam, Saba Raja, Natasha D Irving, Geoffrey J Markowitz, Kennedy Krieger Institute, Baltimore, MD; Charles Rohde, Johns Hopkin Sch of Public Health, Baltimore, MD; Anne Comi; Kennedy Krieger Institute, Baltimore, MD

  Author Disclosures: S.D. Kadam: None. S. Raja: None. N.D. Irving: None. G.J. Markowitz: None. C. Rohde: None. A. Comi: None. Th P155 Systemic Treatment With Direct Angiotensin Ii Type 2 Receptor Agonist, Compound 21, Improved Cognitive Function Via Increase In Cerebral Blood Flow And Enhancement Of Excitatory Post-synaptic Potential With Neurite Elongation

  Author Disclosures: R.C. Kirks: None. S. Periyasamy-Thandavan: None. S. Herberg: None. J.R. Barrett: None. W.H. Jackson: None. A. Zhu: None. D.C. Hess: None. P.V. Schoenlein: Research Grant; Modest; NIH RO1. W. Hill: Research Grant; Modest; VA Merit Award.

  ) Hallevi H, Dar NS, Barreto AD, Morales MM, Martin-Schild S, Abraham AT, Walker KC, Gonzales NR, Illoh K, Grotta JC, Savitz SI. The IVH score: a novel tool for estimating intraventricular hemorrhage volume: Clinical and research implications. Crit Care Med. 2009; 37: 969-e1. Author Disclosures: B.Y. Hwang: None. G. Appelboom: None. S.S. Bruce: None. A.M. Carpenter: None. R. Deb-Sen: None. C.P. Kellner: None. P. Gigante: None. M. Piazza: None. E. Connolly: None.

  Author Disclosures: A. Catalano: None. S. Jadhav: None. E. Gordon: None. H. Winn: None. J.A. Frontera: None.Th P178 DVT Prophylaxis after ICH in China: Results from China National Stroke Registry (CNSR)Yilong Wang, Hao Li, Zixiao Li, Beijing Tian Tan Hosp, Beijing, China; N. Nguyen-Huynh Mai, Univ of California, San Francisco, CA; Xingquan Zhao, Chunxue Wang, Yong Zhou, Liping Liu, Yongjun Wang; Beijing Tian Tan Hosp, Beijing, China

  Author Disclosures: S. Okazaki: None. M. Sakaguchi: None. B. Hyun: None. K. Nagano: None. M. Tagaya: None. Y. Sakata: None. T. Sakaguchi: None. K. Kitagawa: None. M. Tagaya: None.

  Author Disclosures: W. Kimberly: Research Grant; Significant; AAN Foundation Clinical Research Fellowship. O. Wu: None. E. Arsava: None. P. Garg: None. R. Ji: None. M. Vangel: None. A. Singhal: None. H. Ay: None. A. Sorensen: Research Grant; Significant; NIH R01-NS038477. Th P192 Swallowing Screens in Patients after Stroke: A Systematic Review Sara K Schepp, David L Tirschwell, Robert M Miller, W. T Longstreth, Jr.; Univ of Washington, Seattle, WA

  Author Disclosures: D. Wisco: None. J.F. Sabik: None. E. Blackstone: None. I. Katzan: None. Th P195 The level Of Creatine Kinase BB in CSF Correlates With Brain Mri Abnormalities In Post Cardiac Arrest Resuscitated Patients Aleksander Tkach, Jessica Lundeen, Sandeep Khot, Teddy Youn, William Longstreth, David Tirschwell; university of washington, seattle, WA Objective: To assess the association of the biomarker creatine kinase-BB (CK-BB) in cerebrospinal fluid and brain MRI in relation to the prediction of awakening after resuscitation from cardiac arrest. Methods: Retrospective cohort of patients admitted to Harborview Medical Center in Seattle, Washington between the years of 1998 and 2006

  Author Disclosures: T. Wu: None. J. Choi: None. E. Friedman: None. W. Ashley: None. P. Sahota: None. N. Harun: None. R. Pandurengan: None. N. Sangha: None. N.R. Gonzales: None. G.A. Lopez: None. J.C. Grotta: None. S.I. Savitz: None. A.D. Barreto: None.

  47) or in the 31(34%) patients having additional contrast (1.05Ϯ0.56 vs. 1.04Ϯ0.65, pϭ0.93). Similarly, no significant difference existed between baseline and peak Creatinine in patients with DM and CKD (0.94Ϯ0.45 vs. 0.93Ϯ0.51, pϭ0.92) or in those who were on Metformin, ACE-I/ARB, and/or diuretics (0.96Ϯ0.43 vs. 0.90Ϯ0.43, pϭ0.48). Conclusion: Emergent CTA/CTP and DSA are safe with no increase in follow-up Creatinine even in patients with DM and CKD or those who were on Metformin, ACE-I/ARB, and/or diuretics. We do not know if our hydration protocol contributed to the lack of observed renal toxicity. If confirmed by larger studies, our results suggest that baseline Creatinine values are not needed prior to obtaining emergent CTA/CTP in acute ischemic stroke patients. Author Disclosures: V. Truong: None. J. Shah: None. R. Spray: None. A. Vaishnav: None. C. Ziegler: None. K. Remmel: None. A. Abou-Chebl: None.

  Author Disclosures: K. Yu: None. M. Oh: None. K. Hong: None. D. Kang: None. J. Park: None. H. Bae: None. J. Koo: None. Y. Chu: None. B. Lee: None.

  Author Disclosures: J. Kitchener: None. M. Jumaa: None. S. Kale: None. A. Alshekhlee: None. R. Kaushal: None. T. Chaisam: None. J. Chibnall: None. A. Acharya: None. P. Piriyawat: None. E. Feen: None. S. Cruz-flores: None. C. Callison: None. R. Edgell: None. T. Jovin: None. N. Vora: None. Th P213 Soft Hyperdense Lesions on CT Scan after Endovascular Treatment in Acute Ischemic Stroke of the Anterior Territory: a Sign of Successful Recanalization and Good Outcome Natalia Pe ´rez de la Ossa, Hosp Universitari Germans Trias i Pujol, Barcelona, Spain; Marc Ribo ´, Jorge Pagola, Hosp Universitari Vall d'Hebro ´n, Barcelona, Spain; Mo ´nica Milla ´n, Meritxell Gomis, Hosp Universitari Germans Trias i Pujol, Barcelona, Spain; Yolanda Silva, Hosp Universitari Josep Trueta, Girona, Spain; Aitziber Aleu, Hosp Universitari Germans Trias i Pujol, Barcelona, Spain; Ana Rodrı ´guez-Campello, Hosp del Mar-IMIM, Barcelona, Spain; Patricia Cuadras, Hosp Universitari Germans Trias i Pujol, Barcelona, Spain; Jose Á ´lvarez-Sabı ´n, Hosp Universitari Vall d'Hebro ´n, Barcelona, Spain; Antoni Da ´valos; Hosp Universitari Germans Trias i Pujol, Barcelona, Spain

  Author Disclosures: N. Pe ´rez de la Ossa: None. M. Ribo ´: None. J. Pagola: None. M. Milla ´n: None. M. Gomis: None. Y. Silva: None. A. Aleu: None. A. Rodrı ´guez-Campello: None. P. Cuadras: None. J. A ´lvarez-Sabı ´n: None. A. Da ´valos: None.

  Author Disclosures: R. Kaushal: None. R.C. Edgell: None. N. Vora: None. R. Callison: None. E. Feen: None. P. Piriyawat: None. A. Acharya: None. S. Cruz-Flores: None.

  Further studies are required to investigate the factors associated with the formation of new MBs after CAS. Author Disclosures: S. Matsumoto: None. I. Nakahara: None. K. Kakumoto: None. K. Tsuji: None. N. Murai: None. T. Sato: None. Y. Watanabe: None. Y. Fukushima: None. Y. Fukushima: None. M. Takezawa: None. Y. Tanaka: None. T. Yamada: None.

  Author Disclosures: A.M. Malik: None. N.A. Vora: None. R. Lin: None. S.F. Zaidi: None. M.A. Jumaa: None. A. Aleu: None. B.T. Jankowitz: None. V.K. Reddy: None. M.D. Hammer: None. L.R. Wechsler: Ownership Interest; Modest; NeuroInterventional Therapeutics, Inc.. Consultant/ Advisory Board; Modest; Ferrer. M.B. Horowitz: Consultant/Advisory Board; Modest; ev3 Neurovascular. T.G. Jovin: Ownership Interest; Modest; NeuroInterventional Therapeutics, Inc.. Consultant/Advisory Board; Modest; ev3 Neurovascular. Th P225 MRI Turn-Around Time for Acute Stroke Imaging Remains Unchanged Over a 2 Year Time Period Tielong Pham, Tiesong Shang, Dalia Milan, Diogo Haussen, Philip Garza, Gustavo Ortiz, Dileep R Yavagal; UNIVERSITY OF MIAMI MILLER SCH, Miami, FLIntroduction: Advanced MRI imaging for acute ischemic (AIS) stroke is increasingly used for patient selection for endovascular therapy (ET) beyond the 3-4.5h window. Such studies increase the door-to-groin puncture time. The amount of time added and whether it decreases with practice over time is unclear. Hypothesis: We hypothesized that time added by advanced MRI imaging will decrease over time with practice. Methods: We analyzed MRI turn-around times in the MRI In Acute Management of Stroke (MIAMIS) study. MIAMIS is a single university center retrospective study that has enrolled consecutive suspected AIS patients with presenting NIHSS Ͼ 5 or aphasia with acute stroke 0 -14 hours from symptom onset undergoing emergent MRI imaging for possible ET. The MRI protocol included diffusion, perfusion, FLAIR, gradient echo and brain MR angiogram. No systematic review of MTAT was done on an ongoing basis. The MRI turnaround time (MTAT) was defined as MRI order time to time of last MRI image. We retrospectively analyzed MTAT over four consecutive six month time periods. We also analyzed the time taken for the actual MRI protocol as time taken from first image to last image. Statistical analysis was done with SPSS ver16.0 using one-way ANOVA. Results: From February 2008-February 2010, 87 patients (45 F, 42M) underwent acute advanced MRI selection for ET at our university medical center. Patients were evaluated by a neurology attending at 0 -8 hours and 8-14 hours from symptom onset in 81 patients (94.2%) and 7 patients (5.8%) respectively. The mean age was mean age 67 (range 28 -92) and median NIHSS 18 (range 6 -29) within 14 hours of symptom onset. The overall MTAT was a mean of 99.5Ϯ54.7 minutes. The MTAT in minutes was 87.5 Ϯ 28.33, 85.4 Ϯ21.01, 114.5 Ϯ20.05, 101.2 Ϯ 51.4, during the time periods of Feb'08-July'08, Aug '08-Jan'09, Feb'09-July'09, Aug '09-Jan'10 respectively. There was no significant difference in the MTAT amongst these time periods. The time from first to last MRI image in minutes for the overall time period was a mean of 27.7Ϯ24.5 and 29.9 Ϯ9.9, 26.1Ϯ12.3, 24.7Ϯ8, 29.1Ϯ15.2 over the same time periods as above. Again there was no significant difference amongst these times. Conclusions: The time added by advanced MRI imaging is substantial and remains constant despite practice over time. System strategies to shorten MRI order to MRI start time and technical advances to shorten time for MRI sequences are needed to decrease the delay added by advanced imaging. Author Disclosures: T. Pham: None. T. Shang: None. D. Milan: None. D. Haussen: None. P. Garza: None. G. Ortiz: None. D.R. Yavagal: None. Th P226 Different Clinical Evolution and Infarct Volume across Final TIMI grades in Endovascular Reperfusion Therapies for Acute Stroke. Should we Redefine Recanalization End-points in IA Trials? Marta Rubiera, Jorge Pagola, Hosp Universitari Vall d'Hebron, Barcelona, Spain; Joao Sargento-Freitas, Hosp Universitario de Coimbra, Coimbra, Portugal; David Rodrı ´guez-Luna, Pilar Coscojuela, Olga Maisterra, Socorro Pin ˜eiro, Pilar Meler, Francisco J Romero, Jose Alvarez-Sabin, Carlos A Molina, Marc Ribo; Hosp Universitari Vall d'Hebron, Barcelona, Spain

:

  RE after endovascular treatment is associated with clinical improvement but relevant differences are detected between TIMI grades. Patients with TIMI 2a have 2-times more frequently futile RE than TIMI 3 patients. More strict RE end-points in IA reperfusion trials are required to refine the translation of RE into good clinical outcome after endovascular procedures. Author Disclosures: M. Rubiera: None. J. Pagola: None. J. Sargento-Freitas: None. D. Rodrı ´guez-Luna: None. P. Coscojuela: None. O. Maisterra: None. S. Pin ˜eiro: None. P. Meler: None. F.J. Romero: None. J. Alvarez-Sabin: None. C.A. Molina: None. M. Ribo: None.

  Author Disclosures: C.D. d'Esterre: None. R. Aviv: None. M. Hogan: None. T. Lee: Consultant/ Advisory Board; Modest; Consultant for GE.Th P234 Post-intervention TCD Examination May Predict Outcome In Acute Ischemic Stroke Patients With Successful Intra-arterial InterventionJunya Aoki, Larry N Raber, Irene Katzan, Muhammad S Hussain, Ferdinand Hui, Ken Uchino; Cleveland Clinic, Cleveland, OH Background and Purpose: Arterial recanalization has been associated with improved outcomes after intravenous and intraarterial (IA) acute stroke therapy. We hypothesize that transcranial Doppler (TCD) finding after IA intervention might provide an important predictor of short-term clinical outcome among those with recanalization. Methods: From a prospective registry of acute ischemic stroke patients who underwent IA therapy, patients treated with internal carotid artery (ICA) or middle cerebral artery (MCA) lesions with follow-up TCD examination within 3 days after IA intervention were retrospectively analyzed. Only those with recanalization at thrombolysis in myocardial infarction (TIMI) flow grade 2 or better in MCA territory were included. TCDs were conducted to assess the mean flow velocity (MFV) of the MCA, and findings were classified into two categories based on thrombolysis in brain ischemia (TIBI) grading system: Poor Flow group was defined by TIBI grade Յ3 with MFV diminished by Ն30% compared to contralateral MCA. Normal Flow group included patients without decreased MFV compared to contralateral MCA (TIBI Ͼ3). Poor clinical outcome was defined as in-hospital death or decompressive craniectomy. Results: Forty-eight subjects were included from period March 2007 to February 2010. Twenty-three (48%) subjects had ICA lesions and 25 (52%) had MCA lesions, including 2 (4%) isolated M2 lesions. TCD examination was conducted at a median of 1 day after IA intervention. Poor Flow group had 9 (19%) patients and Normal group had 39 (81%) patients. Poor Flow group was older than Normal group(78 [56-83] versus 57 [47-70], pϭ0.023). National Institute of Health Stroke Scale [NIHSS] score was 16[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] in Poor Flow group and 16[10][11][12][13][14][15][16][17][18][19][20] in Normal group (pϭ0.959). Gender and the frequency of ICA occlusions were similar. Residual TIMI flow grade 3 was seen in 3 (33%) patients with Poor Flow group and 14 (36%) with Normal group (pϭ1.000). Three (33%) patients in Poor Flow group and 2 (5%) in Normal group died during hospitalization (pϭ0.039). Two (22%) patients in Poor Flow group and 2 (5%) patients in Normal group underwent decompressive craniectomy (pϭ0.155). Thus, poor in-hospital outcome was significantly more frequent in Poor Flow group than Normal group (44% versus 10%, pϭ0.031). After adjustment for age, Poor Flow group was significantly associated with worse outcome (Adjusted odds ratio: 11.1, 95% confidence interval: 1.5-80.1, pϭ0.012). Conclusion: Residual TIBI flow grade on follow-up TCD examination after IA intervention may predict patient outcome beyond angiographic residual TIMI flow.Author Disclosures: J. Aoki: None. L. Raber: None. I. Katzan: None. M. Hussain: None. F. Hui: None. K. Uchino: None.

  Author Disclosures: J. Stolzenburg: None. C. Jansen: None. A. Rocco: None. W. Hacke: Other; Modest; Editor Journal of Stroke. P. Ringleb: None.

  . Stroke Grand Round with multidisciplinary presenters (Physicians, Residents, Nurses, Physical therapists, Occupational therapists, Speech therapists, Dietitians, Pharmacists, and Social Service) and a multidisciplinary audience developed to address stroke patient care. Purpose To determine if Multidisciplinary Stroke Grand Rounds has an effect on Ischemic Stroke patients' lengths of hospital stay. Methods Ischemic stroke patient length of stay (LOS) prior to Multidisciplinary Stroke Grand Rounds was compared to LOS during the months that Multidisciplinary Stroke Grand were conducted. Sampling included Ischemic Stroke patients without end stage cancers and excluded patients for carotid interventions. Patients' lengths of stays were retrieved from online records in MIDAS. Multidisciplinary Stroke Grand Rounds were held in March and June 2010. Ischemic stroke average patient LOS from March and June 2010 was compared to the prior year March and May 2009. Patient confidentiality was maintained as only the Stroke Coordinator viewed patient names. Results There were 35 Ischemic patients in the months of March and May 2010 combined. The average combined LOS in March and May 2010 is 4.66 days. There were 36 Ischemic patients in the month of March and May 2009 combined. The average combined LOS in March and May 2009 is 6.64 days. Conclusion: Initial research indicates that Multidisciplinary Stroke Grand Rounds benefits Ischemic Stroke patients by decreasing length of stays by an average of two days. Although this data set is small, a need for Multidisciplinary Stroke Grand Rounds on a regular basis is evident. A multihospital study is needed to obtain a larger data set, with collaborative efforts to offer Multidisciplinary Stroke Grand Rounds. Future studies might explore stroke awareness and use of best practices of participants. Author Disclosures: T. Hall: None. J. Quijano: None. C. Jastrzebski: None. Th P260 A Multidisciplinary Quality Improvement Project to Address Delays in CT Imaging and Thrombolytic Treatment in Acute Stroke Patients Janine M Mazabob, Gerard Brown, Patrick Stewart, Sarah Livesay, Suzanne Freeborg, St Luke's Episcopal Hosp, Houston, TX; Jose Suarez, Eric Bershad, Stelios Smirnakis; Baylor College of Medicine, Houston, TX

  Author Disclosures: M. Mazza: None. Z. Magdon-Ismail: None. S. Melluzzo: None. L. Coe: None. L. Schwamm: Consultant/Advisory Board; Modest; Massachusetts Department of Public Health;. T. Gropen: None.

  Author Disclosures: L. Hudson: None. N. Sanossian: None. A. Towfighi: None. E. Cheng: None. W. Cunningham: None. B.G. Vickrey: None.

  Author Disclosures: T.L. Imus: None. L. Williams: None. J.C. Hall-Barrow: None. T.L. Northcutt: None. D.M. Johnson: None.

  Emergency department nurses were required to activate the stroke team within 10 minutes of patient arrival. Other initiatives were put into action which helped us meet our objective. The emergency department collaborative established advanced nursing interventions and created an electronic computerized stroke order set. The emergency department worked in partnership with the lab creating specially labeled blood tubes and blood bags in conjunction with requiring blood to be hand delivered to laboratory personnel in order to improve turn around times. Later in the process we improved electrocardiogram (EKG) turn around times by ensuring the initiation of two IV's and an EKG upon patient arrival to the emergency department prior to going to CAT scan. CAT scans of the brain are also expedited by the radiology department and a Neuro-radiologist interprets the CAT scan immediately after completion with results being called to B.E.S.T. nurse and neurologist. Patients who are candidates for thrombolytic therapy are treated with pre-set doctor's orders to ensure administration of TPA (Tissue Plasminogen Activator) within 60 minutes of arrival. The order set includes consent for Alteplase administration and a medication dosing chart. The Stroke B.E.S.T. Call Review Committee started reviewing 100% of stroke calls in October 2009. The committee continued to monitor all B.E.S.T calls through June of 2010 with continued focus on improving stroke quality measures and turn around times. On June 10, 2010, Joint Commission surveyor for Stroke Accreditation conducted a site visit with full accreditation being recommended. Author Disclosures: G. Diaz: None. R. Burke: None. Th P273 Dysphagia Screening in the ER, How We Increased Compliance From 30 To 90؉% Peggy Ohnmacht, Jennifer Whitley, John Angrisani; WHITE PLAINS HOSPITAL, White plains, NY Background: White Plains Hospital Center has been a designated stroke center since July 2005.According to the Get with the Guidelines database one of the important core measures

  September 20, 2013 http://stroke.ahajournals.org/ Downloaded from conducted a retrospective analysis of all patients admitted to the UTHMS Stroke Service from January 2004 to October 2009 with discharge disposition of home, IR, SNF or Sub. Baseline demographics including age, gender, race and NIHSS were collected. Cerebrovascular disease risk factors [Age Ͼ 65, Cardiovascular Disease (CV), Diabetes Mellitus (DM), Hypertension (HTN), Hyperlipidemia (HLD) History of Stroke (CVA)] were used for independent risk assessment and risk stratification. Using multivariate logistic regression, the data was analyzed for differences in post-stroke disposition among patients with UI. Results: Home vs. Other Level of Care: Of 3744 patients, a total of 3260 were included in the analysis. Approximately 1593 were discharged home, 1667 to another level of care. Patients with UI are 4.44 times less likely to be discharged home. IR vs. SNF: Of 1497 patients, 953 patients were discharged to IR, 544 to SNF. Patients with UI are 3.65 times less likely to be discharged to IR. Conclusions: Acute stroke patients with UI are more 4.44 times less likely to be discharged home. If post-stroke care is necessary, rehabilitation is 3.65 times more likely to occur at a level reflective of worse functional status (SNF). This study is limited by its retrospective nature and the undetermined role of psychosocial factors related to discharge. Prospective studies addressing problems with urinary incontinence while the person is acutely hospitalized may augment long-term complications. Author Disclosures: N. Ifejika-Jones: None. N. Harun: None. N. Mohammed-Rajput: None. E. Noser: None. J. Grotta: None. Th P289 Urinary Tract Infections in Hospitalized Ischemic Stroke Patients: Source and Impact on Outcome Raymond Reichwein, Gayle Watson, Kathy Morrison, Kevin Cockroft; Penn State Hershey Med Cntr, Hershey, PA Introduction: Recent initiatives have focused on eliminating infections, such as urinary tract infections (UTI), in hospitalized ischemic stroke patients. However, many UTI may in fact be present on admission and little is known about the different factors that lead ischemic stroke patients to develop UTI and what affect the presence of UTI may have on overall outcome.

  Author Disclosures: R. Reichwein: None. G. Watson: None. K. Morrison: None. K. Cockroft: None. Th P290 Effect of Coronary Artery Disease on the Outcomes of the Patients with Ischemic Stroke in Taiwan JIU-HAW YIN, Robert J. Chen; Cheng-Hsin General Hosp, Taipei, Taiwan Background Patients with cerebral infarction may have an increased risk of death. Previous reports in Western countries showed their death were more often due to coronary artery disease (CAD) than recurrent cerebral infarction or other neurological diseases. However, there is no such evidence of data for Taiwanese patients. The present study would investigate CAD and the relevant outcomes for the patients with ischemic stroke in Taiwan. Methods and Results We conducted a prospective study of consecutive 615 hospitalized patients of the neurology service with a diagnosis of TIA or ischemic stroke from Sep. 2006 to Dec. 2008. All patients underwent brain CT on the day of admission, and repeated brain CT or MRI within one week.

  Author Disclosures: H. Fujii: None. T. Ohtsuki: None. S. Kubo: None. K. Sato: None. K. Takamatsu: None. A. Ota: None. T. Ota: None. M. Kuriyama: None. M. Matsumoto: None. , ROUDEBUSH VA MEDICAL CTR, Indianapolis, IN; Greg Arling, Regenstrief Institute, Inc., Indianapolis, IN; Xinli Li, Neale Chumbler, Arlene Schmid, ROUDEBUSH VA MEDICAL CTR, Indianapolis, IN; Diana Ordin, VHA Office of Quality and Performance, Washington, DC; Dawn Bravata; ROUDEBUSH VA MEDICAL CTR, Indianapolis, IN

  Author Disclosures: L.S. Williams: None. G. Arling: None. X. Li: None. N. Chumbler: None. A. Schmid: None. D. Ordin: None. D. Bravata: None. Th P294 Are Stroke Suvivors Getting the Rehabilitation Services they Need? Deborah A Willems, Southwestern Ontario Stroke Network, London, Canada; Dianne Bryant, Univ of Western Ontario, London, Canada; Christina O'Callaghan; Ontario Stroke System, Toronto, Canada

  Author Disclosures: F.B. Khan: None. R.E. Hall: None. M. Stamplecoski: None. A. Calzavara: None. J.A. Richards: None. M.K. Kapral: None. F.L. Silver: None.Th P302 Primary Stroke Center Designation is Associated with Increased Utilization of Intravenous Tissue Plasminogen Activator and Mechanical Embolectomy for Acute Ischemic Stroke in IllinoisMaggie McNulty, Bichun Ouyang, Maritza Barajas, Lauren N Macklis, Shyam Prabhakaran; Rush Univ Med Cntr, Chicago, IL

  , Laura J Fehrs, Georgia Dept of Community Health, Atlanta, GA; Kerrie A Krompf, Dept of Neurology, Emory Univ, Atlanta, GA; Katja G Bryant, Georgia Dept of Community Health, Atlanta, GA; Michael R Frankel; Dept of Neurology, Emory Univ, Atlanta, GA Background: The Georgia Coverdell Acute Stroke Registry (GCASR), part of the Centers for Disease Control and Prevention's Paul Coverdell National Stroke Registry, provides a platform for actively engaging hospitals in a continuous multi-faceted intervention to improve the quality of in-hospital stroke care. It is designed to track and improve the quality of in-hospital acute stroke care. Defect-free care is an accepted method for conservatively defining optimal quality care using multiple indicators for assessment. Objective: The purpose of this study is to assess trends in quality of care defined by defect-free care among hospitals participating in the GCASR. Methods: Hospitals were recruited during three phases in time. We analyzed 10 standard quality indicators of stroke care, including intravenous thrombolytic therapy within 3 hours, venous thromboembolism prophylaxis and antithrombotic therapy at discharge. We defined defect-free care at the patient level as 100% adherence to all of the indicators for which the patient was eligible, and compared the temporal relationship of participation in the registry among the three cohorts. Results: The three cohorts in the analysis were comprised of 23, 16, and 10 hospitals respectively. Cohort 1 started in November 2005, Cohort 2 in October 2006, and Cohort 3 in March 2008. Collectively, these hospitals represented approximately 35% of hospitals providing stroke care and 63% of stroke patients in Georgia. A positive trajectory of improving defect-free care was seen in each of the three cohorts (see Figure A). Some data elements and indicators were revised over time but analyses limited to time periods without revisions showed a similar pattern. Conclusions: Defect-free care improved steadily among hospitals participating in the GCASR. The consistent pattern of improvement seen within each cohort suggests that participation in a statewide registry can improve the quality of in-hospital acute stroke care. Author Disclosures: M.S. Ido: None. L.J. Fehrs: None. K.A. Krompf: None. K.G. Bryant: None. M.R. Frankel: None.Th P305 What Hospital Characteristics Are Associated With Better Quality Of Care? Results from The Michigan Coverdell Stroke Registry Mathew J Reeves, Michigan State Univ, East Lansing, MI; Adrienne Nickles, Rochelle Hurst, Stacey Roberts, Jay Fiedler; Michigan Dept of Community Health, Lansing, MI

  Author Disclosures: R.S. Jung: None. C. Sila: None. A.J. Furlan: None. C. Tatsuoka: None. L.A. McCartney: None. A. Gallan: None.

  Study of Acute Stroke Management and Outcome: Results from the Thai Stroke Registry (TSR) Yongchai Nilanont, Div of Neurology, Siriraj Hosp, Mahidol Univ, Bangkok, Thailand; Samart Nidhinandana, Div of Neurology, Phramongkutklao Hosp and College of Medicine, Bangkok, Thailand; Nijasri Suwanwela, Neurological Unit, Dept of Medicine, Chulalongkorn Univ, Bangkok, Thailand; Suchat Hanchaiphiboolkul, Dept of Neurology, Prasat Neurological Institute, Bangkok, Thailand; Pyatat Tatsanavivat, Div of Cardiovascular Disease and Internal Medicine, Khon Kaen Univ, Khon Kaen, Thailand; Niphon Poungvarin; Div of Neurology, Siriraj Hosp, Mahidol Univ, Bangkok, Thailand

  Author Disclosures: Y. Nilanont: None. S. Nidhinandana: None. N. Suwanwela: None. S. Hanchaiphiboolkul: None. P. Tatsanavivat: None. N. Poungvarin: None.Th P309 Predictors of the Use of Dysphagia Screening in Patients with Acute Ischemic Stroke Shihab Masrur, Berkshire Med Cntr, Pittsfield, MA; Eric E Smith, Univ of Calgary, Alberta, Canada; Jeffrey L Saver, UCLA Stroke Cntr, Los Angeles, CA; Mathew Reeves, Michigan State Univ, East Lansing, MI; Deepak L Bhatt, Brigham and Women hospital, Boston, MA; Xin Zhao, Duke Clinical Rsch Institute, Durham, NC; DaiWai Olson, Duke Univ Med Cntr, Durham, NC; Wenqin Pan, Adrian F Hernandez, Duke Clinical Rsch Institute, Durham, NC; Gregg C Fonarow, Ronald Reagan UCLA Med Cntr, LA, CA; Lee H Schwamm; Massachusetts General Hosp, Boston, MA

  stroke.ahajournals.org/ Downloaded from multiple comorbidities, at academic hospitals, or in certain regions are more likely to get DS. Further studies are needed to identify barriers and propose strategies to increase the routine use of dysphagia screening among all stroke patients. Author Disclosures: S. Masrur: None. E.E. Smith: None. J.L. Saver: None. M. Reeves: None. D.L. Bhatt: None. X. Zhao: None. D. Olson: None. W. Pan: None. A.F. Hernandez: None. G.C. Fonarow: None. L.H. Schwamm: None. Th P310 Association between Do Not Resuscitate Orders and the Quality of Acute Stroke Care in the Veterans Health Administration (VHA) Mathew J Reeves, Michigan State Univ, East Lansing, MI; Laura Myers, Veterans Health Administration (VHA) Stroke Quality Enhancement Rsch Initiative (QUERI) Program, Indianapolis, IN; Linda S Williams, Diana Ordin, Dawn M Bravata; Veterans Health Administration (VHA) Stroke Quality Enhancement Rsch Initiative (QUERI) Program, Indianaoplis, IN Background: Do Not Resuscitate (DNR) orders are common in patients hospitalized with acute ischemic stroke. Our objectives were to describe factors associated with DNR orders in hospitalized ischemic stroke patients, and to assess the relationship between DNR orders and quality of stroke care in the VHA. Methods:

  This research has received full or partial funding support from the American Heart Association, Pacific/Mountain Affiliate (Alaska, Arizona, Colorado, Hawaii, Idaho, Montana, Oregon, Washington & Wyoming).Author Disclosures: W. Hoover: None. T.J. Bernard: None. N.A. Goldenberg: None. M. Manco-Johnson: None. J.L. Armstrong-Wells: None.Th P313 Intraventricular Hemorrhage Score Applied to ChildrenJonathan T Kleinman, Stanford Sch of Medicine, Stanford, CA; Kyle Engelmann, Johns Hopkins Univ Sch of Medicine, Baltimore, MD; Sabrina E Smith, Lauren A Beslow, Daniel J Licht, Rebecca N Ichord, The Children's Hosp of Philadelphia, Philadelphia, PA; Argye E Hillis, Lori C Jordan; Johns Hopkins Univ Sch of Medicine, Baltimore, MD Objective: In pediatric intracerebral hemorrhage (ICH), there is little data other than ICH volume to help the clinician predict outcome. In adult ICH, the presence of intraventricular hemorrhage (IVH) is an independent predictor of outcome. We hypothesized that children with the most severe IVH would do poorly. Methods: Children, full term to 17 years, with spontaneous ICH and/or IVH on CT or MRI were prospectively enrolled from 2007-9. Exclusion: trauma; isolated SAH; ICH due to brain tumor; hemorrhagic conversion of stroke. Outcome analysis excluded children with pre-existing neurological deficits or death due to non-ICH causes. Measurements: Volumetric analysis of total brain volume (TBV), ICH, and IVH volume was performed by 2 raters using ImageJ. An IVH score was assigned independently by 4 raters using the Hallevi scheme to quantify IVH size in the right and left lateral ventricles, 3rd and 4th ventricles: 0, no blood; 1, posterior sedimentation of blood in the ventricle; 2, partly filled ventricle; 3, completely filled for each ventricle (range 0-12). Outcome assessment: Children were assessed at follow-up by a pediatric stroke neurologist with the King's Outcome Scale for Childhood Head Injury (KOSCHI) which ranges from 1 (death) to 5 (good recovery) at 3 and 12 months post-ICH. Functionally impairing deficits were KOSCHI Ͻ5 with KOSCHI Յ2 as poor outcome. Linear regression assessed the correlation of IVH score with volumetric measures. IVH score was added to a logistic regression model for prediction of functional impairment and poor outcome. Results: We enrolled 46 children, median age 2.73 years (0-17); 26 had pure ICH, 10 had pure IVH, and 10 had both. IVH scores ranged from 0-11, IVH volumes from 0.1-63.8cm3 and ventricles from 0.3-19% of TBV. Weighted Kappa statistic for IVH score agreement among raters was 0.84 (95%CI: 0.76 -0.91), 93.7% agreement. IVH score and manual IVH volume correlation was fair, R2ϭ0.52. At a median of 10 months (1-28 months), 25 children had KOSCHI Ͻ5. There were 2 deaths, both had ICH volume Ͼ4% of TBV, IVH scores Ն5, and herniation. Presence of hydrocephalus showed a trend for poorer outcome (pϭ0.09). Presence of IVH, high IVH score, or high IVH volume did not predict poor outcome or functional impairment in univariable or multivariable analyses. Conclusion: Only large ICH volume predicted poor outcome. Despite excellent agreement between raters, the IVH score and other measures of IVH did not predict outcome in this small pediatric sample. Hydrocephalus showed a trend toward poor outcome, and therefore may be important as a marker of clinically significant IVH. Author Disclosures: J.T. Kleinman: None. K. Engelmann: None. S.E. Smith: None. L.A. Beslow: None. D.J. Licht: None. R.N. Ichord: Other; Modest; Berlin Heart, Critical Event Committee for an FDA-monitored device trial. A.E. Hillis: None. L.C. Jordan: Other; Modest; Berlin Heart, Critical Event Committee for an FDA-monitored device trial.

  Author Disclosures: P. Ferrazzano: None. P. Cengiz: None. P. Kendigelen: None. K. Uluc: None. E. Akture: None. C. Song: None. L. Zhang: None. J. Lee: None. V. Chanana: None. B. Hutchinson: None. B. Meyerand: None. D. Sun: None.

  Author Disclosures: R. Garcia-Rinaldi: Research Grant; Modest; St. Jude Medical, Inc..Th P318 The Short-term Effect of Atorvastatin on Carotid Plaque Morphology Assessed by Computer-Assisted Gray Scale DensitometryDavid Della Morte, Dept of Neurology, Miller Sch of Medicine, Univ of Miami, Miami, FL; Issam Moussa, Endovascular Service, Cardiovascular Interventional Therapy, Dept of Cardiology, Cornell Univ, New York, NY; Mitchell S Elkind, Dept of Neurology, Columbia Univ, New York, NY; Ralph L Sacco, Tatjana Rundek; Dept of Neurology, Miller Sch of Medicine, Univ of Miami, Miami, FL

  Author Disclosures: F.D. Testai: None. V. Aiyagari: None. M. Hillmann: None. S. Amin-Hanjani: None. G. Dawson: None. P.B. Gorelick: None. Th P331 Hemodynamics are Altered in Patients with Aneurysm-related Vasospasm pre-& post-therapy: Serial Evaluation with Whole-brain CT Perfusion Cheemun Lum, Miguel Bussiere, Ejaz Ahmed, Matthew Hogan, Lawrie Garnett, John Hooper, John Sinclair, Mukul Sharma; The Ottawa Hosp, Ottawa, Canada Background & Purpose: Cerebral vasospasm from aneurysm-related SAH(aSAH) is a major cause of morbidity. Diagnosis & monitoring of vasospasm remains a challenge with limitations using TCD, cerebral angiography & CTA. In most settings decreased cerebral perfusion is inferred from changes in arterial diameter rather than by simultaneous measurement. Recent generation of 320-slice CT scanners now give whole brain CT perfusion(CTP) & CTA information with a single contrast bolus.

  Author Disclosures: S. Muehlschlegel: Research Grant; Significant; Worcester Research Foundation Grant 2010. B.A. Barton: None. M.A. Topcuoglu: None. J. Fok: None. A.B. Singhal: Other; Modest; medical-legal expert witness.

  Author Disclosures: H. Yao: None. Y. Miwa: None. Y. Takashima: None. T. Mori: None. A. Uchino: None. T. Yuzuriha: None. T. Sasaguri: None. M. Hashimoto: None.

Enzyme Inhibitors or Angiotensin Receptor Blockers Reduce Future Vascular Risk in Persons with a History of Stroke: A Meta-Analysis Meng

  Author Disclosures: Y. Shinohara for the CSPS II Group: Research Grant; Modest; The Japanese Ministry of Health, Labor and Welfare. Speakers; Modest; Diichi-Sankyo Co., Ltd.. Consultant/ Advisory Board; Modest; Pfizer Japan Inc.. Y. Huang for the CASISP cooperation investigators: None. Lee, Chang Gung Memorial Hosp, Chiayi, Taiwan; Jeffrey L Saver, UCLA STROKE CENTER, Los Angeles, CA; Keun-Sik Hong, Ilsan Paik Hosp, Inje Univ, Korea, Republic of; Qing Hao, UCLA STROKE CENTER, Los Angeles, CA; Jessica Chow, UCLA Sch of Public Health, Los Angeles, CA; Bruce Ovbiagele; UCLA STROKE CENTER, Los Angeles, CA

	Th MP76
	Angiotensin Converting

  Mei Li, Depts of Neurosurgery, Stanford Univ, Stanford, CA; Rong Xie, Depts of Neurosurgery,Stanford Univ, Stanford, CA; Michelle Cheng, Depts of Biological Sciences, Stanford Univ, Stanford, CA; Rona Giffard, Depts of Anesthesiology , Stanford Univ, Stanford, CA; Richard Roth, Depts of Chemical and Systems Biology, Stanford Univ, Stanford, CA; Robert Sapolsky, Depts of Neurosurgery, Biological Sciences, Stanford Univ, Stanford, CA; Heng Zhao; Depts of Neurosurgery,Stanford Stroke Cntr, Stanford Univ, Stanford, CA

Transplanted Adult Mouse Neural Stem/progenitor Cells Containing Arginine Decarboxylase Gene Promote Functional Repair And Plasticity After Experimental Stroke

	Jae Young Kim, Yu Mi Park, Kyung Ah Park, Won Taek Lee, Jong Eun Lee; Yonsei Univ,
	College of Medicine, Seoul, Korea, Republic of

W P83 Management of Acute Ischemic Stroke Associated with Acute Internal Carotid Artery Occlusion

	Author Disclosures: P.M. Riccio: None. F.R. Klein: None. C. Vigliano: None. P. Gonza ´lez: None.
	H. Raffaelli: None. L.A. Sposato: None.
	Manoj Mittal, Univ of Kansas Med Cntr, Kansas City, KS; Naveed Akhtar, Coleman Martin,
	William Holloway, Marilyn Rymer, Rebecca Sugg; Saint Luke's Brain & Stroke Institute,
	Kansas City, MO

e184 Stroke Vol 42, No 3 March 2011 by

  Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation.

guest on September 20, 2013 http://stroke.ahajournals.org/

Downloaded from W P86 Atorvastatin and Psychomotor Agitation after Carotid Endarterectomy Patricia

  M Riccio, Francisco R Klein, He ´ctor Raffaelli, Rafael Zamora, Luciano A Sposato; FAVALORO FOUNDATION, Buenos Aires, Argentina

W P98 Relationship of Site of Vertebral Stenosis to Early Recurrent Stroke Risk in Posterior Circulation Stroke and TIA Giosue

  `Gulli, St George's Univ of London, Cntr for Cinical Neuroscience, London, United Kingdom; Lars Marquardt, Peter M Rothwell, Univ of Oxford, Stroke Prevention Rsch Unit, Oxford, United Kingdom; Hugh S Markus; Univ of London, Cntr for Clinical Neuroscience, London, United Kingdom Background: In two recent studies, one Hospital based (St Georges Hospital: SGH) and the other population based

  Bedi: Consultant/Advisory Board; Modest; Panasonic Healthcare Co., Ltd.. K. Ishikawa: None. A. Yen: Consultant/Advisory Board; Modest; CardioNexus Corporation. H. Hassan: Consultant/Advisory Board; Modest; CardioNexus Corporation. D. Panthagani: Consultant/Advisory Board; Modest; CardioNexus Corporation. A. Bandekar: Consultant/ Advisory Board; Modest; CardioNexus Corporation. C. Hartley: Consultant/Advisory Board; Modest; CardioNexus Corporation.

  ,and 61 minutes (IQR 57) respectively, (pϭ0.019). Median door to needle times in group 1 [67 minutes(IQR 43)], and group 2 [62.5 minutes (IQR 52)] respectively (pϭ0.519), Median Onset to needle times in Group 1 (139 minutes (IQR 73)] and Group 2 (141.5 min(IQR109.5) (pϭ0.468). In multivariable analysis, age and baseline INR influenced onset to needle times and door to needle times in both the groups Older age resulted in marginally shorter times and elevated INR resulted in longer onset to needle times, presumedly due to the wait for confirmed laboratory measured INR. Conclusions: CTA based thrombolytic approach for acute ischemic stroke does not prolong door to needle time in routine clinical practice.Author Disclosures: S. Bal: None. B. Menon: None. N. Shobha: None. A.M. Demchuk: None. M.D. Hill: None.

  Tomohisa Nezu, Masatoshi Koga, Dept of Cerebrovascular Medicine, National Cerebral and Cardiovascular Cntr, Suita Osaka, Japan; Yoshiaki Shiokawa, Depts of Neurosurgery, Stroke Cntr, Kyorin Univ Sch of Medicine, Mitaka, Japan; Jyoji Nakagawara, Dept of Neurosurgery and Stroke Cntr, Nakamura Memorial Hosp, Sapporo, Japan; Eisuke Furui, Dept of Stroke Neurology, Kohnan Hosp, Sendai, Japan; Kazumi Kimura, Dept of Stroke Medicine, Kawasaki Med Sch, Kurashiki, Japan; Hiroshi Yamagami, Stroke Cntr, Kobe City Med Cntr General Hosp, Kobe, Japan; Yasushi Okada, Dept of Cerebrovascular Medicine, National Hosp Organization Kyushu Med Cntr, Fukuoka, Japan; Yasuhiro Hasegawa, Dept of Neurology, St Marianna Univ Sch of Medicine, Kawasaki, Japan; Kazuomi Kario, Div of Cardiovascular Medicine, Dept of Medicine, Jichi Med Univ Sch of Medicine, Shimotsuke, Japan; Satoshi Okuda, Dept of Neurology, National Hosp Organization Nagoya Med Cntr, Nagoya, Japan; Kouichirou Maeda, Kaoru Endo, Tetsuya Miyagi, Kazuo Minematsu, Kazunori Toyoda; Dept of Cerebrovascular Medicine, National Cerebral and Cardiovascular Cntr, Suita Osaka, Japan

P174 Frequency of Complete Resolution of Motor Symptoms among Stroke Patients Evaluated within 2 Hours of Symptom Onset Nerses

  Sanossian, May A Kim, Univ of Southern California, Los Angeles, CA; Scott Hamilton, Stanford Univ, Palo Alto, CA; Sidney Starkman, David S Liebeskind, UCLA Stroke Cntr, Los Angeles, CA; Marc Eckstein, Univ of Southern California, Los Angeles, CA; Samuel Stratton, Univ of California Los Angeles, Los Angeles, CA; Frank Pratt, Los Angeles County Fire Dept, Los Angeles, CA; Robin Conwit, National Institutes of Health, Bethesda, MD; Jeffrey L Saver, UCLA Stroke Cntr, Los Angeles, CA; FAST-MAG Investigators and Coordinators

Author Disclosures: W.G. Tekle: None. A.E. Hassan: None. G.J. Rodriguez: None. S.A. Chaudhry: None. G. Vazquez: None. A.I. Qureshi: None.

W

  Significant; Takeda Pharmaceutical Company Limited. M. Shimojo: Employment; Significant; Takeda Pharmaceutical Company Limited.

Author Disclosures: K. Murakami: Employment; Significant; Takeda Pharmaceutical Company Limited. M. Suzuki: Employment; Significant; Takeda Pharmaceutical Company Limited. N. Suzuki: Employment; Significant; Takeda Pharmaceutical Company Limited. K. Hamajo: Employment; Significant; Takeda Pharmaceutical Company Limited. T. Tsukamoto: Employ-ment;

  Disclosures: W.C. Culp: Research Grant; Significant; NIH R01 HL082481. R. Flores: Research Grant; Significant; NIH R01 HL082481. A.T. Brown: Research Grant; Significant; NIH R01 HL082481. L.J. Hennings: Research Grant; Significant; NIH R01 HL082481. P.K. Roberson: Research Grant; Significant; NIH R01 HL082481. S.D. Woods: Research Grant; Significant; NIH R01 HL082481. J.H. Hatton: None. R.D. Skinner: Research Grant; Significant; NIH R01 HL082481. M.J. Borrelli: None.

Blood Pressure Control with Clevidipine in Patients with Acute Intracerebral Hemorrhage is Rapid and Well Tolerated: The ACCELERATE Trial Carmelo

  Author Disclosures: H. xin: None. Y. Li: None. L.H. Shen: None. R. Zhang: None. L. Zhang: None. Z.G. Zhang: None. M. Chopp: None. Graffagnino, Duke Univ Med Cntr, Durham, NC; Sergio Bergese, Ohio State Univ, Columbus, OH; James Love, Moses H. Cone Health System, Greensboro, NC; Dietmar Schneider, Univ of Leipzig, Leipzig, Germany; Christos Lazaridis, Med Univ of South Carolina, Charleston, SC; Marc LaPointe, South Carolina College of Pharmacy, Charleston, SC; Kiwon Lee, Columbia Univ Med Cntr, New York, NY; Gwendolyn Lynch; Cleveland Clinic Hosps, Cleveland, OH

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	Aggressive

  blood pressure (Rϭ 0.2, pϭ0.29), age (Rϭ0.07, pϭ0.27) or PCC treatment (Rϭ -0. 5, pϭ 0.67) and significant hematoma expansion. Conclusion: Although PCC is associated with rapid reversal of INR, hematoma expansion remains frequent. Correction of the INR is necessary in AAICH treatment, but may not be sufficient to prevent expansion in all patients. A randomized controlled trial of PCC versus FFP/vitamin K in AAICH is warranted. Author Disclosures: N. Asdaghi: Research Grant; Significant; CIHR. C.C. Poon: None. T. Jeerakathil: None. K. Butcher: Research Grant; Significant; CIHR, AHFMR,HSFA.

  P. Broderick: Research Grant; Significant; IMS III PI. Consultant/Advisory Board; Modest; Genentech, Inc.. J.A. Spilker: None. T.A. Tomsick: Research Grant; Significant; IMS III Co-PI. M.D. Hill: Research Grant; Significant; IMS III Executive Committee. E.C. Jauch: Research Grant; Significant; IMS III Executive Committee. P. Mitchell: Research Grant; Modest; IMS III Executive Committee. B. Yan: Research Grant; Modest; IMS III EC. A. Abou-Chebl: None. K.M. Cockroft: None. D.M. Brown: None. P.D. Panagos: Research Grant; Significant; NIH SPOTRIAS. Speakers; Modest; Genentech, Inc. R.G. Nogueira: Consultant/Advisory Board; Modest; ev3 Neurovascular, Coaxia, Rapid Medical. Consultant/Advisory Board; Significant; Concentric Medical. P. Keller: None. P. Khatri: Research Grant; Significant; NIH K23; NIH IMS III Trial (IMM). Honoraria; Modest; AAN Acute Stroke Mgmt Seminar; Grand Rounds Lectures.

  Author Disclosures: E.I. Levy: Research Grant; Significant; BSX (SARIS). Other Research Support; Significant; MEND. Honoraria; Significant; BSX. Ownership Interest; Modest; Intratech Medical Ltd. Ownership Interest; Significant; Mynx/Access Closure. Consultant/Advisory Board; Significant; MEND. Other; Significant; Various medicolegal opinions as an expert witness. M. Rahman: None. A.A. Khalessi: None. P.T. Beyer: None. S.K. Natarajan: None. M.L. Hartney: None. D.J. Fiorella: Research Grant; Significant; NIH (SAMMPRIS). Speakers; Modest; MEND. Honoraria; Modest; MEND. Ownership Interest; Significant; MEND (Revasc). Consultant/Advisory Board; Modest; MEND. L.N. Hopkins: Research Grant; Significant; ev3(CREATE). Other Research Support; Significant; Toshiba. Speakers; Modest; ABT. Honoraria; Modest; SCAI. Ownership Interest; Significant; Valor Medical. Consultant/Advisory Board; Significant; MEND. Other; Significant; Conference Director Nurcon Conferences/Strategic Medical Seminars. A.H. Siddiqui: Research Grant; Modest; Univ at Buffalo. Research Grant; Significant; NIH NINDS. Speakers; Modest; Genentech. Honoraria; Modest; Emergency Medicine Conference. Consultant/Advisory Board; Modest; MEND. Other; Modest; Codman Neurovascular (for neurointerventionist training). J. Mocco: Other Research Support; Modest; Codman Neurovascular (institution receives). Consultant/Advisory Board; Modest; Lazarus Effect.

  Author Disclosures: H.M. Hefzy: None. E. Neil: None. P. Penstone: None. M. Mahan: None. P. Mitsias: Research Grant; Significant; Harris Stroke Fund. B. Silver: Honoraria; Modest; Chapters written for E-medicine and Medlink. Consultant/Advisory Board; Modest; abbott vascular. Other; Significant; Medical malpractice defense.

  , PϽ0.001] and CHADS2 score [ORϭ1.56 (95%CI: 1.16-2.09), pϭ0.003] were independently associated with poor outcome. After removing stroke severity from the model, CHADS2 score [ORϭ1.46 (95%CI: 1.15-1.85), pϭ0.002], male sex [ORϭ0.52 (95%CI: 0.32-0.85), pϭ0.009], previous anticoagulation with INR Ͼ2 [ORϭ0.33 (95%CI: 0.16-0.69), pϭ0.003] and IHD [ORϭ2.35 (95%CI: 1.24-4.44), pϭ0.009], were the variables associated with poor outcome. Conclusions: CHADS2 score is a strong predictor of poor outcome independent of stroke severity. Anticoagulation with INRϾ2 is associated with less severe strokes and better outcome.

of PFO Physiology on Circulatory Proteomic Profile in Ischemic Stroke Patients MingMing

  Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Ning, Ferdinando Buonanno, CardioNeurology Clinic, Clinical Proteomics Rsch Cntr, Dept of Neurology, Massachusetts General Hosp / Harvard Med Sch, Boston, MA; Michael Athenas, Dave Sarracino, Bryan Krastins, Clinical Proteomics Rsch Cntr, Dept of Neurology, Massachusetts General Hosp / Harvard Med Sch, Boston, MA; Zareh Demirjian, Dept of Hematology, Massachusetts General Hosp / Harvard Med Sch, Boston, MA; Ignacio Inglessis-Azuaje, Dept of Cardiology, Massachusetts General Hosp / Harvard Med Sch, Boston, MA; David McMullin, New York Univ, New York, NY; G William Dec, Igor Palacios, Dept of Cardiology, Massachusetts General Hosp / Harvard Med Sch, Boston, MA; Mary Lopez, Clinical Proteomics Rsch Cntr, Dept of Neurology, Massachusetts General Hosp / Harvard Med Sch, Boston, MA; Eng H Lo; Neuroprotection Rsch Laboratory, Dept of Radiology, and Clinical Proteomics Rsch Cntr, Dept of Neurology, Mass General Hosp / Harvard Med Sch, Boston, MA

	e254	Stroke Vol 42, No 3 March 2011
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  Author Disclosures: K.B. Barlinn: None. A.D. Barreto: Research Grant; Significant; National Institute of Neurological Disorders and Stroke (NINDS)/SPOTRIAS Program. A. Sisson: None. D.S. Liebeskind: Research Grant; Modest; National Institute of Neurological Disorders and Stroke (NINDS)/SPOTRIAS Program. L. Zhao: None. L.F. Cava: None. J.F. Rothrock: Other; Modest; Principal Investigator. M.E. Schafer: Employment; Significant; Sonic Tech, Inc., Philadelphia, PA, USA. J. Alleman: Employment; Significant; Cerevast Therapeutics, Inc., Redmond, WA, USA. J.C. Grotta: Research Grant; Significant; National Institute of Neurological Disorders and Stroke (NINDS)/SPOTRIAS Program. A.V. Alexandrov: Research Grant; Significant; National Institute of Neurological Disorders and Stroke (NINDS)/SPOTRIAS Program. Ownership Interest; Significant; Independent operator TCD device (Cerevast Therapeutics, Inc., Redmond, WA, USA). Consultant/Advisory Board; Significant; Cerevast Therapeutics, Inc., Redmond, WA, USA.

  Richard T Benson, Amie W Hsia, NIH Stroke Program, Washington, DC; Marieta Pehlivanova, MedStar Health Rsch Institute, Hyattsville, MD; Jose Merino, NIH Stroke Program, Suburban Hosp, Bethesda, MD; Lawrence Latour, Marie Luby, Shlee Song, John Lynch, Carsten H Ritter, NIH Stroke Program, Bethesda, MD; Alexander Katcheves, Anne Arundel Med Cntr, Annapolis, MD; Steve Warach; NIH Stroke Program, Bethesda, MD

  Nerses Sanossian, Univ of Southern California, Los Angeles, CA; Sidney Starkman, UCLA Stroke Cntr, Los Angeles, CA; Scott Hamilton, Stanford Univ, Palo Alto, CA; David S Liebeskind, UCLA Stroke Cntr, Los Angeles, CA; Marc Eckstein, Univ of Southern California, Los Angeles, CA; Samuel Stratton, Univ of California Los Angeles, Los Angeles, CA; Frank Pratt, Los Angeles County Fire Dept, Los Angeles, CA; Lucas Restrepo, Latisha K Ali, UCLA Stroke Cntr, Los Angeles, CA; Robin Conwit, National Institutes of Health, Bethesda, MD; Jeffrey L Saver, UCLA Stroke Cntr, Los Angeles, CA; FAST-MAG Investigators and Coordinators

  UTI, longer length of stay, and discharge to a facility other than home. Further research is needed to evaluate the appropriate indications for Foley catheter placement in stroke patients. Author Disclosures: S.N. Poisson: Research Grant; Modest; American Heart Association Western States Affiliate Clinical Research Program. S. Sidney: None. S. Johnston: None. M.N. Nguyen-Huynh: None.

  No evidence was available for 11/87 (13%) and only level C for 26/87 (30%) of variables in the 2007 guidance. After 2007, 6/11 (55%) criteria without evidence remained devoid of further data. Previous level C variables remained without more data in 24/26 (92%), yet level B was attained in 2 after 2007. Increased levels of evidence were established for 4 selection criteria, 1 baseline clinical measure, 1 imaging method, and 1 type of adverse event. At present, 42/87 (48%) of variables in the 2007 guidance have level A evidence, 11/87 (13%) level B, 28/87 (32%) level C, and 6/87 (7%) no evidence. Conclusions: Only limited evidence was available for 43% of variables stipulated in the 2007 guidance on neurothrombectomy. Trial design considerations that are limited in prior evidence or biased may erroneously alter data from subsequent studies. Evidence for interventional strategies is increasing but such emerging data should be used to continually revise regulatory guidance and future stroke trial design. Author Disclosures: D.S. Liebeskind: Research Grant; Significant; K23NS054084. Consultant/ Advisory Board; Modest; CoAxia, Inc.. M. Lee: None.

  The improved 90-day good outcome among patients undergoing mechanical thrombectomy combined with periprocedural heparin requires further study in a larger cohort. Author Disclosures: F. Nahab: None. G. Walker: Employment; Significant; Senior Director for Clinical Research at Concentric Medical, Inc.. J.E. Dion: None. W.S. Smith: Ownership Interest; Significant; Concentric Medical, Inc. Consultant/Advisory Board; Significant; Concentric Medical, Inc.

Strokes with Large Vessel Occlusion

  Author Disclosures: K. Busl: None. R.G. Nogueira: Consultant/Advisory Board; Modest; ev3 Neurovascular, Inc; Coaxia, Inc; Rapid Medical, Inc. Consultant/Advisory Board; Significant; Concentric Medical, Inc. A.J. Yoo: Other Research Support; Significant; Penumbra, Inc. J.A. Hirsch: Ownership Interest; Modest; Intratech Medical. Consultant/Advisory Board; Modest; Intratech Medical. L.H. Schwamm: Consultant/Advisory Board; Modest; Lundbeck (International Steering Committee/DIAS-4 ). Consultant/Advisory Board; Significant; CoAxia, Inc. N.S. Rost: Research Grant; Significant; NIH-NINDS.

	Th P239
	Mild Manoj Mittal, Univ of Kansas Med Cntr, Kansas City, KS; Naveed Akhtar, Coleman Martin,
	William Holloway, Rebecca Sugg, Marilyn Rymer; Saint Luke's Brain & Stroke Institute,
	Kansas City, MO

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studies included 1843 patients, 428 of them (23%) were pre-treated with statins. Mortality at 3 months (1 study reported death at 1 month and was also included) was 37% in the SP group and 40.5% in the non-SP group (OR 0.84, 95%CI 0.67-1.06, pϭ0.13). Conclusions: In conclusion, prior treatment with statins was not associated with mortality neither in our study nor in a meta-analysis of reported studies.

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This research has received full or partial funding support from the American Heart Association, Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin). Author Disclosures: V. Prabhakaran: Research Grant; Significant; Supported by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health. D. Baniulis: Research Grant; Significant; Shapiro Research Grant. N. Kornder: Research Grant; Significant; Shapiro Research Grant. J. Voss: Research Grant; Significant; AHA undergraduate research award. V.A. Nair: Research Grant; Significant; Coulter Foundation. B. Kundu: None. J. Wood: None. A. Utter: None. T. Gallagher: None. A. Atassi: None. C. Moritz: None. E. Meyerand: None.

/ Advisory Board; Modest; Lundbeck. W. Hacke: Honoraria; Modest; Boehringer Ingelheim. M. Kaste: Honoraria; Modest; Boehringer Ingelheim. R. von Kummer: Honoraria; Modest; Boehringer Ingelheim. A. Shuaib: None. S. Senn: Consultant/Advisory Board; Modest; Vanda. D. Toni: Honoraria; Modest; Sanofi-Aventis. Research Support; Significant; Research contract founded by Spanish Ministry of Science (Carlos III Institut), Rı ´o

Th P41 Genome-wide Search for Ischemic Stroke Genes: The Siblings with Ischemic Stroke Study (SWISS) James F Meschia, Mayo Clinic, Dept of Neurology, Jacksonville, FL; Michael A. Nalls, Laboratory of Neurogenetics, Intramural Rsch Program, National Institute on Aging, Bethesda, MD; Stephen S. Rich, Cntr for Public Health Genomics, Univ of Virginia, Charlottesville, VA; Andrew Singleton, Laboratory of Neurogenetics, Intramural Rsch Program, National Institute on Aging, Bethesda, MD; John A. Hardy, Dept of Molecular Neuroscience, Institute of Neurology, Univ College London, London, United Kingdom; Thomas G. Brott, Mayo Clinic, Dept of Neurology, Jacksonville, FL; Robert D. Brown, Jr., Mayo Clinic, Dept of Neurology, Rochester, MN; Brett Kissela, Dept of Neurology, Univ of Cincinnati, Cincinnati, OH; Bradford B. Worrall, Depts of Neurology and Public Health Sciences, Univ of Virginia, Charlottesville, VA; for the SWISS Investigators.

W P208 Genome Wide Association Study of Intracerebral Hemorrhage

W. Mark Brown, Wake Forest Univ Health Sciences, Winston-Salem, NC; Alessandro Biffi, Massachusetts General Hosp, Boston, MA; Jeremiasz Jagiella, Jagiellonian Univ Botaniczna 3, Krakow, Poland; Mary Comeau, Wake Forest Univ Health Sciences, Winston-Salem, NC; Lynelle Cortellini, Massachusetts General Hosp, Boston, MA; Jessica G Woo, Lisa Martin, Cincinnati Children's Hosp Med Cntr, Cincinnati, OH; Matthew L Flaherty, Joseph P Broderick, Ranjan Deka, Univ of Cincinnati, Cincinnati, OH; Agnieszka Slowik, Jagiellonian Univ, Krakow, Poland; David Tirschwell, Univ of Washington, Seattle, WA; Magdy Selim, Harvard Med Sch, Boston, MA; Devin L Brown, Univ of Michigan Health System, Ann Arbor, MI; Scott Silliman Silliman, Univ of Florida college of Medicine, Jacksonville, FL; Bradford B Worrall, Univ of Virginia Health System, Charlottesville, VA; James F Meschia, Mayo Clinic, Jacksonville, FL; Kristin Schwab, Alison M Ayres, Steven M Greenberg, Massachusetts General Hosp, Boston, MA; Carl D Langefeld, Wake Forest Univ Health Services, Winston-Salem, NC; Daniel Woo, Univ of Cincinnati, Cincinnati, OH; Jonathan Rosand; Massachusetts General Hosp, Boston, MA A genetic predisposition to spontaneous intracerebral hemorrhage (ICH) is well established. Genome-wide association studies (GWAS) are underway in Caucasian ICH cases from population and multi-center based studies. We report the results of a GWAS meta-analysis for all, lobar and deep ICH. Methods: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study prospectively recruits cases of ICH in the Greater Cincinnati/Northern Kentucky area and identifies controls through random digit dialing. Cases and controls were collected by buccal swab and were genotyped using the Affymetrix 6.0 platform. The Genetics of Cerebral Hemorrhage on Anticoagulation (GOCHA) Study is a multi-center US-based study recruiting ICH cases from hospital-based cohorts and controls from the same institutions. ICH cases and community-dwelling controls were contributed by the Jagiellonian University (Krakow, Poland) ICH Study. Controls for all 3 groups were matched by age (ϩ/-5 yr), race and sex. The GOCHA and Jagiellonian cases and controls were genotyped using the Illumina 650 platform. Quality control analyses included batch effects, missing data, genetic outliners and HWE. Data were imputed using Impute 2.0 and HapMap 3 CEU data. The meta-analysis is based on an additive model using the inverse normal method weighted by respective sample size. All analyses were adjusted for admixture, age, sex, and high cholesterol. In addition, ICH was adjusted for hypertension (HTN), warfarin, and apolipoprotein E4 (APOE4); lobar was adjusted for APOE2 and APOE4; and deep was adjusted for HTN. Results: A total of 772 ICH cases and 872 controls including 326 lobar and 383 deep ICH cases were genotyped; 301/333 ICH cases/controls on Affymetrix 6.0 and 471/539 cases/controls on Illumina 1M. No regions reached genome-wide significance in meta-analysis or individual analyses. The Figure presents the -log 10 (p-value) for association with all ICH by genomic location. For a minor allele frequency of 0.2 and a type 1 error rate of 5x10E-7, our meta-analysis had 0.80 power to detect an ORϭ1.6 for ICH; ORϭ1.85 for lobar; and ORϭ1.80 for deep. Genomic control inflation factor was 1.01.

Conclusion:

In the largest GWAS of ICH reported to date, no association with a large effect size for ICH was identified after adjustment for multiple comparisons. This is consistent with ICH having a complex etiology with multiple smaller risk factors. The analysis demonstrates feasibility of collaboration between the study groups to enhance power to identify smaller effect sizes.

W P209 Spatial Trajectory of Hematoma Enlargement Predicts Clinical Deterioration and Mortality in Patients with Acute Intracerebral Haemorrhage

Jorge Pagola, David Rodrı ´guez-Luna, Marta Rubiera, Marc Ribo ´, Pilar Coscojuela, Socorro Pin ˜eiro, Olga Maisterra, Bernardo Ibarra, Francisco Romero, Jose ´A ´lvarez-Sabı ´n, Carlos A Molina; HOSPITAL VALL DЈHEBRO ´N, BARCELONA, Spain Background: Early hematoma growth (HG) has been shown to be an independent determinant of death and disability after intracerebral haemorrhage (ICH). Depending on ICH location, a predominant spatial growth direction may affect functionally critical and clinically eloquent structures leading to early clinical worsening. We aimed to investigate the spatial HG behaviour and the impact of the main HG trajectory on clinical course and outcome in patients with acute ICH. Methods: We prospectively studied patients with acute primary supratentorial ICH evaluated Ͻ 6 hours of symptom onset. Patients underwent baseline (Ͻ6h) and 24h CT scans, and a CTA (Ͻ6h) for the blinded detection of spot sign (SS). ICH volumes were measured at baseline (Ͻ6h) and follow-up (24h) CT scans. ICHs were classified as lobar, basal ganglia, thalamic, or multiple locations. The main 3-dimention ICH diameters were calculated at baseline and follow-up CTs, the largest longitudinal (L) and transversal (T) diameters in the axial plane and the largest altitudinal (A) diameter in the coronal. HG trajectory (mm) was calculated from each 3-D ICH diameter. Early neurological deterioration (END) was defined as increase Ն4 points in the NIHSS score or death at 24 hours. 90-day mortality was recorded. Results: A total of 138 acute primary supratentorial ICH were included in this study. 31.4% of them were lobar, 38% were located in basal ganglia, 17.5% in the thalamus, and 13.1% in multiple locations. Mean baseline ICH volume was 28.8 Ϯ 35.1 mL. HG occurred in 49 (35.3%) patients. The trajectory of HG was significantly larger in the L (2.89 Ϯ 0.49 mm) compared to T (1.8Ϯ 0.51 mm) and A (2.1Ϯ 0.56 ml) hematoma diameters (pϭ0.004, Krusskal-Wallis test). L trajectory of HG was significantly correlated with a higher degree of clinical worsening in lobar (rϭ0.59; pϭ0.002) and basal ganglia (rϭ0.61; pϭ0.001) hematomas, while T trajectory was associated with clinical worsening in thalamic hematomas (rϭ0.67; pϭ0.017). Only L growth Ͼ2.7mm (sensitivity 69%, specificity 71%) was significantly (pϽ0.001) associated with 3-month mortality. CTA SS was seen on 26 (19%) patients. CTA SS was internally and externally located in 8 (30%) and 18 (70%) patients, respectively. Distribution of CTA SS strongly predicted the main trajectory of HG. In 91% of patients, growth trajectory followed the location of CTA SS. Among patients with lobar and basal ganglia hematomas, CTA SS located along the L diameter was significantly (pϭ0.034) associated with early clinical deterioration. Conclusions: In patients with acute ICH, the spatial behaviour of HG may predict early clinical course. L trajectory of HG predicts clinical deterioration and mortality in lobar and basal ganglia ICHs. The presence and distribution of CTA SS heralds the main direction of HG and its longitudinal distribution predicts clinical worsening.

Author Disclosures: Z. Chen: None. Y. Hua: None. R.F. Keep: None. K. Muraszko: None. G. Xi: Research Grant; Significant; NS-052510.

W P220 Improvement in Functional Outcome after Isoflurane Preconditioning in a Murine Model of Intracerebral Hemorrhage Involves an Inducible Nitric Oxide Mechanism

Sarah E Keesecker, Paul R Gigante, Geoffrey Appelboom, Christopher P Kellner, Brian Y Hwang, Mason L Yeh, Justin Gorski, E S Connolly, Jr.; Columbia Univ, New York, NY Introduction: Isofluorane preconditioning in ischemic stroke has been shown to be inducible nitric oxide synthase (iNOS) dependent. Mounting evidence suggests that ischemic and hemorrhagic stroke share many molecular mechanisms of cellular injury and death. Therefore we sought to investigate the impact of isoflurane preconditioning on outcome and the role of iNOS as a potential mediator of neuroprotection in a murine model of ICH. Methods: Wild-type C57b mice underwent a 4-hour exposure to 1% isoflurane anesthetic 24 hours prior to ICH and control C57b mice were exposed to room air and underwent ICH. Subsequently, iNOS-/-mice were similarly preconditioned and underwent ICH for a total sample size of 44 mice. Intracerebral hemorrhage was performed using a double autologous blood injection into the right striatum. Neurologic function was evaluated at 24, 48, and 72 hours using the 28-point test, which quantifies function based on seven categories of sensory and motor testing with a possible score of 0 to 4 in each. Results: Neurological function testing demonstrated that WT mice preconditioned with isoflurane performed significantly better at 24 hours (8.7 ϩ 1.1 vs. 13.4 ϩ 0.7, PϽ.00001) 48 hours (6.3 ϩ 1.1 vs. 10.1 ϩ 0.9, PϽ.001), and 72 hours (4.5 ϩ 0.7 vs. 6.6 ϩ 0.9, PϽ.05) as compared to the WT controls. We subsequently reproduced the same preconditioning setting in our iNOS KO mice. We did not observe a significant difference in neurological function between the room air WT and room air iNOS-/-mice, the room air WT and isoflurane iNOS-/-mice, or the room air iNOS-/-and isoflurane iNOS-/-groups. Conclusions: Cerebral preconditioning with isoflurane leads to improved neurological function in WT mice. Mitigation of this preconditioning effect in iNOS-/-mice strongly implicates the iNOS gene in the isoflurane preconditioning pathway in ICH.

Author Disclosures: S. Amin-Hanjani: Research Grant; Significant; NINDS/NIH. Other Research Support; Modest; GE Healthcare. Consultant/Advisory Board; Modest; Micrus Corporation. X. Du: None. M. Zhao: Employment; Significant; VasSol, Inc.. Ownership Interest; Modest; VasSol, Inc. S. Ruland: Honoraria; Modest; Boehringer Ingelheim. Consultant/Advisory Board; Modest; Astra Zeneca. N. Mlinarevich: None. F.T. Charbel: Ownership Interest; Significant; VasSol, Inc..

W P237 Validation of 'Reversed Robin Hood Syndrome' by Acetazolamide-Challenged HMPA-SPECT in Patients with Severe Steno-occlusive Disease of Intracranial Carotid or Middle Cerebral Artery

Vijay K Sharma, National Univ Hosp, Singapore, Singapore; Georgios Tsivgoulis, Univ of Thrace, Alexandropoulis, Greece; Aftab Ahmad, Prakash R Paliwal, Hock L Teoh, Lily Y Wong, Su Jie, N Venketasubramanian, Michael T Wee, Hao Cheng, Philip A Ping, Vincent F Chong, Kay W Ng, Pei K Loh, Leonard L Yeo, Benjamin K Ong, Bernard P Chan, Arvind K Sinha; National Univ Hosp, Singapore, Singapore Author Disclosures: R. Leigh: None. A.E. Hillis: None. P.B. Barker: None.

W P241 Persistent contrast is a Predictor of Poor Clinical Outcome in Acute Stroke Patients Treated with Intrarterial Therapy

Jorge Pagola, Marta Rubiera, Pilar Coscojuela, David Rodriguez-Luna, Socorro Pin ˜eiro, Olga Maisterra, Jose ´A ´lvarez-Sabı ´n, Francisco Romero, Carlos. A. Molina, Marc Ribo ´; Hosp Vall dЈHebro ´n, Barcelona, Spain Background: The persistence of contrast sign (PCS) in the artery during an angiogram is a radiological sign that may be observed in some patients with an arterial occlusion. We aimed to evaluate if the presence of PCS in patients with acute stroke who underwent endovascular procedures may influence recanalization, clinical outcome and mortality as a surrogate marker of poor collateral circulation. Methods: Acute stroke patients (Ͻ8h) who underwent endovascular procedures were prospectively studied. Location of vascular occlusion was confirmed by angiography, and the presence of PCS was considered if after the complete angiography sequence (Ͼ8seconds) the contrast remained at the location of occlusion. Patients were evaluated using NIHSS and clinical improvement was considered if decrease Ն4 points from the baseline to discharge was observed. Results: 115 consecutive patients were included, mean age was 70.8 (Ϯ11.8), 42.7% were female (nϭ50) and median baseline NIHSS was 19 . Fifty-four patients (51.4%) showed recanalization after endovascular treatment (TIMI Ն2). Distribution of occlusion location was: ICA 39 (33.3 %), MCA 56 (48%), Basilar 14 (12 %). The PCS was observed in 40 patients (34.2%): ICA 30 (88.2%), MCA 4 (9%), Basilar 6 (66.7%). Patients with positive PCS had lower recanalization rate (41% vs 61.2%) (pϽ0.034), lower clinical improvement (23.8%vs 76.2%) (pϽ0.001) and a trend to a high mortality rate (43.2%vs24%) (pϭ0.058). Other clinical variables are included in table 1. A logistic regression model showed that only TICA occlusion .17) pϭ0.044)) and PCS ) (pϭ0.043)) were independent predictors of lack of clinical improvement after endovascular treatment. Conclusions: PCS is strongly associated to TICA occlusion; PCS is an independent predictor of lower clinical improvement after endovascular treatment in acute stroke patients.

Author Disclosures: A.E. Hassan: None. R. Husain: None. G. Vazquez: None. G.J. Rodriguez: None. M.K. Suri: None. R.P. Tummala: None. R.A. Taylor: None. M.A. Ezzeddine: None. A.I. Qureshi: None.

W P261 The Hyperdense Vessel Sign on CT is Predictive of Successful Recanalization Using the Merci Device in Acute Ischemic Stroke

Michael T Froehler, Satoshi Tateshima, Reza Jahan, Gary Duckwiler, Fernando Vinuela, Latisha K Ali, Sidney Starkman, David Liebeskind, Jeffrey Saver, Pablo Villablanca; UCLA, Los Angeles, CA Author Disclosures: M. Richardson: None. Conclusions: These results show that outcomes can be improved by utilizing AHA/ASA GWTG®-Stroke. This national registry provides support to improve outcomes by providing tools to impact performance measures based on best practice guidelines. It was an efficient tool to facilitate improved lipid management outcomes at LMC. Author Disclosures: V.S. Hicks, RN, BC: None.

W P295 Best Practice Guidelines Improve Lipid Management Outcomes

W P296 Let The Data Do The Driving: Informing Clinical Decision-making In The Community Hospital

Cindy Spencer, Nicole Connors; Wentworth Douglass Hosp, Dover, NH Background: In 2007, when our 124-bed community hospital collaborated with a major medical center for Telestroke support, analysis of current practice was required. Using AHA's Get With the Guidelines (GWTG) performance metrics, we reviewed all stroke cases during six weeks in 2007 (nϭ30). Compliance for Lipid Management was 71%, Smoking Cessation, 50%, and no eligible patients (nϭ 4) received t-PA. Our Defect-Free score (all patients receive all appropriate interventions) was only 29%. With substantial opportunities for improvement, we faced one challenge shared by all other community hospitals: with relatively low numbers of cases, one outlier significantly impacts compliance scores. Purpose: To design and implement a highly reliable, evidenced-based program for stroke management using quality metrics to inform and improve clinical practice, achieving and sustaining at least 85% compliance with GWTG's measures. Methodology: We established a quality subcommittee-our quality improvement (QI) staff joined clinical experts from nursing, radiology, and laboratory-to optimize processes. We review all patients discharged with stroke/TIA. Our quality coordinator extracts data from the electronic medical record, inputs it into a national stroke registry, and e-mails a preliminary report to the clinical experts for confirmation of each "not met." The quality subcommittee analyzes the validated results, identifies trends and outliers, creates action plans, and then reports at the Stroke Steering Committee for the critical final step: information delivery to physicians and therapists, nurses and technologists, managers and administrators. Each department shares the same irrefutable evidence of process and performance opportunities for improvement. Results: Our new stroke program went live in Nov. 2008. With analysis complete for the first five quarters (nϭ218), we exceeded goals on all GWTG metrics. Lipid Management reached 97%, Smoking Cessation, 97%, t-PA compliance improved to 89% (nϭ9), and our Defect-Free score achieved 96%. We earned AHA's Bronze award in 2009 and became the first NH hospital to achieve Silver Plus status. Conclusions: Through partnership with our QI colleagues and the launch of a highly reliable reporting structure, data now informs clinical practice. Three activities were crucial to success: collecting and analyzing reliable data, using metrics to identify areas for improvement and triage our activities, and exchanging information with key stakeholders. Our new goals include concurrent case reviews, shortening data turnaround times, securing budgeted hours for data collection, and engaging more clinicians as we optimize patient outcomes through evidenced-based practice and clinical excellence.

Author Disclosures: C. Spencer: None. N. Connors: None.

W P297 Subcortical Lesion Load And Not Inflammation Are Associated With Poor Cognition After Ischemic Stroke

Hen Hallevi, Einor Ben-Assayag, Shani Shenhar-Tsarfaty, Efrat Kliper, Ludmila Shopin, Sourasky medical center, Tel Aviv, Israel; Uri Goldbourt, Tel Aviv Univ, Tel Aviv, Israel; Nir Giladi, Sourasky medical center, Tel Aviv, Israel; Amos D Korczyn, Tel Aviv Univ, Tel Aviv, Israel; N Katz, Hebrew Univ, Jerusalem, Israel; Natan Bornstein; Sourasky medical center, Tel Aviv, Israel Introduction: Subcortical lesion load (SLL) refers to the quantity of hyperintenities present on FLAIR sequence in the white matter and basal ganglia on MRI. SLL is often present in stroke patients. Systemic inflammatory markers are also often elevated at stroke onset. Our study hypothesis was that patients with higher SLL are less likely to recover their cognitive function after a stroke or TIA and more likely to develop cognitive decline. In addition we sought to study the interaction between inflammation and SLL in terms of cognitive outcome. Methods: We hereby present preliminary results of mild ischemic stroke and transient ischemic attack (TIA) patients from the TABASCO (Tel Aviv Acute Ischemic Stroke Cohort) prospective consecutive cohort. All patients were cognitively intact before the stroke, had an MRI on admission along with cognitive assessment using the Montreal Cognitive Assessment (MoCA) test and the NEUROTRAX computerized assessment battery at baseline, 6 months and 1 year. Systemic inflammation was determined using WBC cound, CRP and fibrinogen levels drawn on admission. SLL was estimated semi-quantitavely using a simple 0 to 6 score for the white matter and basal ganglia. Results: 265 patients were available for assessment. Out of those 142 had complte Neurotrax data at 12 months and 74 had MoCA data at 12 months. On admission, the mean age was 65, median NIHSS was 2 and median MoCA was 25. Higher SLL (SLLϾ3) was associated with a decrease in executive and visual-spatial functions at one year (Rϭ0.25, pϭ0.006) while memory was less impaired. Higher SLL was also associated with a much higher proportion of patients with lower MoCA at one year (45% in patiens with SLLϾ3 vs 11% in SLL3; pϭ0.007). Systemic inflammation by itself had little influence on cognition. When cognition over time was assessed, cognitive decline was noted following a brief improvement in patients with high SLL as opposed to patients without it who showed steady improvement. See figure. Conclusions: In this preliminary cohort, we found correlation between higher SLL on MRI and greater cognitive decline with dysexecutive syndrome, at one year post first ever stroke or TIA. Systemic inflammation at stroke onset does not seem to contribute to this decline. White matter pathway disruption, neuronal death and acceleration Alzheimer-like pathology may all play a role in this phenomenon.

W P329 High Rate of Enrollment of Black Subjects in Genetic Substudy of Intracerebral Hemorrhage Natural History Study

Dorothy F Edwards, Univ of Wisconsin-Madison, Madison, WI; Ravi S Menon, Georgetown Univ, Washington, DC; M. C Gibbons, Johns Hopkins Univ, Baltimore, MD; Latoya Forrester, Georgetown Univ, Washington, DC; Jeffery Wing, Brisa Sanchez, Univ of Michigan, Ann Arbor, MI; Ali Fokar, Nawar Shara, Medstar Rsch Institute, Washington, DC; Chelsea S Kidwell; Georgetown Univ, Washington, DC Background: Historically, researchers have found that black patients have been significantly less likely than whites to participate in clinical research, particularly research involving genetic studies. Sociological factors such as distrust of the medical community, suspicion of genetic testing, and dislike of the general research process have all contributed to low recruitment rates of minorities including blacks. The purpose of this study is to examine recruitment rates by race in the overall DECIPHER intracerebral hemorrhage natural history project and in the genetic substudy. Methods: For all patients eligible for the DECIPHER study, we systematically record reasons for refusal for both the overall study and, if applicable, for the genetic substudy. Variables include whether patient or family was being approached and reasons for refusal. All recruiting coordinators for the DECIPHER project receive training in cultural competence and all materials have been culturally tailored. Results: Of 234 eligible patients, 135 (58%) agreed to participate in the DECIPHER project (62% of blacks vs. 49% of non-blacks, pϭ0.049). Of the 135 who consented, 44% were female, 72% were black, and 119 (88%) agreed to participate in the genetic substudy (87% of the black population vs. 91% of whites enrolled, pϭ0.76). The three most common reasons for refusal for the overall study were 1) distrust of research, 2) family refusal due to patient's poor prognosis, and 3) claustrophobia / dislike of MRI. The two most common reasons for refusal for the genetic substudy were 1) family refusal due to patient's poor prognosis (25%) and 2) family refusal due to discomfort with proxy consent process (25%). Conclusions: Despite previous studies showing lower rates of recruitment of blacks in clinical research, in our DECIPHER project, there was a statistically significant greater enrollment of blacks vs. non-blacks. For the genetic substudy, rates of recruitment were high for both populations and not significantly different. Coordinator training in cultural competence along with trial materials specifically designed to increase trust likely contributed in the overall success of recruitment of the black subjects in the DECIPHER project. Subjects willing to participate in clinical research in general appear to be more willing to participate in genetic research compared to the overall population. Supported by NIH NINDS grant U54 NS057405 (PI: Kidwell, CS ).

Author Disclosures: D.F. Edwards: Research Grant; Significant; NIH NINDS grant U54 NS057405. R.S. Menon: Research Grant; Significant; NIH NINDS grant U54 NS057405. M.C. Gibbons: Research Grant; Significant; NIH NINDS grant U54 NS057405. L. Forrester: Research Grant; Significant; NIH NINDS grant U54 NS057405. J. Wing: Research Grant; Significant; NIH NINDS grant U54 NS057405. B. Sanchez: Research Grant; Significant; NIH NINDS grant U54 NS057405. A. Fokar: Research Grant; Significant; NIH NINDS grant U54 NS057405. N. Shara: Research Grant; Significant; NIH NINDS grant U54 NS057405. C.S. Kidwell: Research Grant; Significant; NIH NINDS grant U54 NS057405.

W P330 UCLA ICH Grading System is a Better Prognostic Tool for Spontaneous Intracerebral Hemorrhage When Assessed at 24 hours After the Event

Mohammad Moussavi, Daniel Korya, Akash H Patel, Rola Mahmoud, Usama Siddique, Jit H Brahmbhatt, Spozhmy Panezai, Martin Gizzi, Jawad F Kirmani; New Jersey Neuroscience Institute, Edison, NJ Background and Purpose: Spontaneous intracerebral hemorrhage (ICH) comprises approximately a fifth of all strokes. UCLA validated a "simple, reliable grading scale" for prognostication of ICH patients. The grading system consists of five components including Glascow Coma Scale (GCS), patient's age, whether or not there is infratentorial involvement, and the presence or absence of intraventricular hemorrhage (IVH) at admission. About one-third of the patients experience growth of their hematoma in the first 24 hours. Our goal was to investigate if the ICH score (ICHs) at 24-hours is more accurate and reliable as a predictor of clinical outcome. Methods: -We conducted a retrospective analysis of prospectively collected data of consecutive patients who suffered a spontaneous ICH between 2006 and 2009. We excluded those who did not have a CT scan within the 16-32 hour window. Along with their medical records, all variables of ICHs at admission and 16-32 hours (mean 24 hours) were measured. We used the manual outlining method to measure hematoma on each slice of their head CT to calculate the total hematoma volume. Clinical outcomes were assessed using discharge modified Rankin Scale (dmRS). The data was compiled and was analyzed for strength of associations using SPSS software version 14.0. Results: -Of the 260 patients, 78 met the criteria (Mean ageϭ 69.21,SDϩ/-14.08; Maleϭ 44, 56%). Mean length of stay was 9.48 (SDϩ/-11.84) and mean dmRS was 4.21 (SDϩ/-1.55). Refer to table for association values. Conclusion: Based on our data ICHs at 24-hours after admission had the strongest positive correlation with dmRS amongst other variables such as admission ICHs, 24-hours hematoma volumes or GCS. This study suggest that assessing the ICHs at 24-hours may be a better prognostic indicator than the initial ICHs. A larger prospective study is warranted to further examine the relationship.

W P332 Is the Risk of Fatal Brain Edema Increased with Thrombolysis Among Patients with Acute Ischemic Stroke?

Haitham M Hussein, Saqib A Chaudhry, Ganesh Asaithambi, Ruth Thomson, Fahd Sultan, Robert A Taylor, Mustapha A Ezzeddine, M. Fareed K Suri, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: Anecdotal reports suggest that thrombolysis may increase the risk of fatal brain edema. The brain edema following thrombolysis may occur secondary to reperfusion or neurotoxic effect of thrombolytic agents. The aim of this study is to assess the association Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. between brain edema and intra-arterial (IA) or intravenous (IV) thrombolysis. Methods: A review of consecutive patients admitted with acute ischemic stroke to two academic institutions from 2006 to 2010 was performed. The study sample was dichotomized based on occurrence of in-hospital mortality and occurrence of fatal brain edema. Univariate analysis was conducted to compare these subgroups defined by occurrence of fatal edema or in-hospital mortality. A multivariate analysis was performed to adjust for age, sex and initial stroke severity as measured by National Institute of Health Stroke Scale (NIHSS) score. Results: There were 548 patients who suffered from ischemic stroke (mean age 66Ϯ16 years; 46% were women). Mean admission NIHSS score was 7Ϯ6 and Ͼ 10 in 112 patients (22%). 128 patients (23%) were treated with thrombolysis (IV, nϭ65 [51%]; IA, nϭ30 [23%]; IVϩIA, nϭ33 [26%]). In-hospital mortality was documented in 39 patients (7%). Of those, 27 patients (5%) died from brain edema. Other causes of death included cardiac arrest, respiratory failure, status epilepticus, and withdrawal of care. In univariate analysis, initial NIHSS score had the strongest association with both in-hospital mortality (median NIHSS 14 vs 4; PϽ0.0001) and fatal brain edema (median NIHSS 16 vs 4; PϽ0.0001). Age was only associated with in-hospital mortality (median age 71 vs 66; pϭ0.05) but not with fatal brain edema (pϭ0.5). Thrombolysis (any type) was not associated with in-hospital mortality (pϭ0.7) or fatal brain edema (pϭ0.5). There was no association between the type of IA thrombolysis (pharmacologic and/or mechanical) and the outcome variables. In multivariate analysis, only severe NIHSS (score Ͼ10) was associated with fatal brain edema (odds ratio [OR] 11.9, 95% confidence interval [CI] 4.8-32.9; PϽ0.0001) while age, IV, IA, and any thrombolysis were not associated with fatal brain edema.

Conclusion

W P333

Older Patients are at Higher Risk for Blood-Brain Barrier Disruption Following Treatment with IV-tPA, Independent of Impaired Kidney Function Ayush Batra, Shlee S Song, Jose G Merino, Amie W Hsia, John K Lynch, Marie Luby, Lawrence L Latour, Steven Warach; NINDS/NIH, Bethesda, MD Background: Disruption of the blood-brain barrier (BBB) can be characterized by the imaging marker Hyperintense Acute Reperfusion Marker (HARM). This marker has been defined as delayed gadolinium enhancement of the cerebrospinal fluid (CSF) space on fluid-attenuated inversion recovery (FLAIR) MRI. HARM has been associated with risk of hemorrhagic transformation, thrombolytic therapy, and worse clinical outcome. HARM has also been associated with increased age, but it is unknown whether this association is confounded by impaired gadolinium clearance due to age-related decreases in renal function. Methods: Patients (nϭ187) were selected from the LESION project of the NINDS Stroke Branch Registry, if they had the following features: treatment with IV-tPA, gadolinium enhanced MRI at baseline, and FLAIR MRI at 2 hr or 24 hr post tPA. HARM was defined as enhancement of sulcal spaces in 10 or more FLAIR slices. The estimated glomerular filtration rate (eGFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) using admission plasma creatinine values. The association between baseline renal function and HARM was examined through stepwise conditional logistical regression. Age, race, sex, NIHSS at presentation, hypertension history, diabetes history, plasma creatinine, eGFR, number of gadolinium doses and MRI field strength were entered into the model as potential covariates of HARM. Results: HARM was independently associated with age (p ϭ 0.003; odds ratio, 1.047; confidence interval, 1.016-1.079), after adjustment for eGRF, number of gadolinium doses, and MRI field strength. The other factors were not significant predictors of HARM. Conclusion: Age is an independent predictor of BBB disruption seen as HARM even after adjusting for the effects of the eGFR. These findings suggest that older patients are at higher risk for BBB disruption following treatment with IV-tPA, independent of their kidney function.

Author Disclosures: A. Batra: None. S.S. Song: None. J.G. Merino: None. A.W. Hsia: None. J.K. Lynch: None. M. Luby: None. L.L. Latour: None. S. Warach: None.

W P334 Gender Moderation in the Association between Mitochondrial Uncoupling Protein Genetic Variants and Carotid Plaque

Chuanhui Dong, David Della-Morte, Ashley Beecham, Mark S McClendon, Digna Cabral, Susan H Blanton, Ralph L Sacco, Tatjana Rundek; Univ of Miami, Miami, FL Background and Objective: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through controlling the production of reactive oxygen species. This study sought to investigate the association of SIRT and UCP genetic variants with the presence of carotid plaque and the potential gender moderation in their association. Methods: A total of 1,018 stroke-free subjects (61% female, mean ageϭ70Ϯ9 yrs) who underwent ultrasound measurement and genotyping were sampled from a multiethnic cohort of northern Manhattan. Multiple logistic regression were performed to investigate the association of genetic variants (SNPs and haplotypes) in SIRT and UCP genes (SIRT1-7, UCP1-5) with the presence of carotid plaque, after controlling for the significant sociodemographic and vascular covariates (age, gender, smoking, waist-hip ratio, diabetes and hypertension) as well as population stratification identified via principal component approach. SNP-by-sex interaction was examined and stratified analysis was followed if the interaction term in the model yielded an effect of p Ͻ 0.1. Multiple testing was adjusted with permutation. Results: After adjustment for covariates, UCP5 SNP rs5977238 showed the strongest association with carotid plaque with an additive effect of ORϭ0.5 (95%CIϭ0.3-0.7, pϭ0.0008, permutation adjusted pϭ0.03) and 4 other UCP5 SNPs were associated with plaque presence with a nominal PϽ0.05. A UCP5 haplotype (TTTCACATT) of 9 SNPs were also significantly associated with decreased risk for plaque (ORϭ0.5, pϭ0.0002, permutation adjusted pϭ0.01). Another significant association was found for SIRT6 SNP rs107251 (ORϭ1.7, 95%CIϭ1.2-2.4, pϭ0.001). Interaction analyses revealed a gender-specific effect for UCP3 SNPs (rs1685356, pϭ0.007; rs1726745, pϭ0.01) and UCP1 SNPs (rs7693034, pϭ0.06; rs6818140, pϭ0.06). Specifically, a significant increased risk was found for A-carrier women at rs1685356 or rs1726745 (ORϭ1.4, 95%CIϭ1.1-1.8, pϭ0.01) but not for men (p Ն 0.13). In contrast, a significant decreased risk was detected for C-carrier women at rs7693034 or rs6818140 (ORϭ0.7, 95%CIϭ0.5-0.9, p Յ 0.01) but not for men (pՆ 0.61). Conclusion: Our findings suggest that genetic variations in UCP1,3,5 and SIRT6 may be associated with subclinical atherosclerosis. Gender difference in the effect of UCP1,3 variants may indicate a gene-environmental interaction. Further fine mapping studies in larger populations are needed to validate the observed association and evaluate the gene-environmental interaction.

W P336

Lobar Tissue Loss in Cerebral Amyloid Angiopathy M.Ayaz Khan, Gregory A Dierksen, Amy Halpin, Mahmut E Gurol, Jonathan Rosand, Anand Viswanathan, David S Salat, Steven M Greenberg; Massachusetts General Hosp, Boston, MA Background: Brain atrophy occurs with aging, particularly in association with neurodegenerative processes. Recent studies suggest that cerebrovascular disease may also contribute to brain tissue loss. We investigated the possibility that advanced cerebrovascular ␤-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cortical tissue loss, particularly in the occipital brain regions most heavily affected by CAA. Methods: 24 nondemented CAA subjects (mean age Ϯ SD 73.4 Ϯ 9.9, 16 men/8 women) and 20 nondemented controls (68.7Ϯ 12.4, 12 men/8 women) were scanned on a 1.5 T (Seimens) scanner, using structural Multiecho MPRAGE (MEMPRAGE, 1 mm isotropic) scan, acquired twice and averaged. Images were processed and analyzed for volume in specified cortical (grey plus white matter, averaged across the two hemispheres) regions of interest (ROI) using FreeSurfer (www.nmr.mhg.harvard.edu). Damage related to prior hemorrhagic strokes was patched; regions patched more than 12% were excluded. Follow-up structural scans were collected for 13 of the CAA subjects after a mean stroke-free interval of 14.6Ϯ4.0 months. Serial scan processing was performed via a parcellation template based on both timepoints to minimize within-subject variation in parcellation. Results: In cross-sectional comparison, the CAA subjects showed nonsignificant reductions relative to the controls. In longitudinal analysis, we observed significant tissue loss in occipital lobe over the inter-scan interval (mean change between scans -1.8%, [95% confidence interval -3.4 to -0.2%], pϭ0.03), with greatest tissue loss in the lingual ROI (-3.4% [-5.3 to -1.4%], pϭ0.003). An example is shown in the Figure ,  with arrows pointing to ROIs (lateral occipital, lingual, cuneus) with evident atrophy on the follow-up scan. Parietal (-0.4%), frontal (ϩ0.4%), and temporal (-0.2%) lobes showed no detectable tissue loss (all pϾ0.5), suggesting that atrophy occurred preferentially in the occipital regions favored by CAA. Conclusions: These results indicate that advanced CAA is associated with tissue loss in the occipital lobe over a relatively short period of longitudinal follow-up. Cortical atrophy may thus be another manifestation of this small vessel disease of the brain.

Th P7 Thromboelastography (TEG) in Acute Ischemic Stroke

Jeremy S Wetzel, Andrea M Elliot, Cristina M Wallace, Son Duong, Evan G Pivalizza, Nusrat Harun, Mary Jane Hess, James C Grotta; Univ of Texas Med Sch at Houston, Houston, TX Background: TEG demonstrates the dynamics of coagulation (see figure 1). Rϭtime to clot initiation; Kϭspeed of clot buildup; Deltaϭtime to maximum rate of thrombus generation (intensity of thrombin burst); Gϭclot strength (increased in platelet-rich clots). There are limited data available about TEG and its utility in acute ischemic stroke (AIS). We studied TEG in patients with AIS to: 1. compare baseline TEG values in AIS vs controls; 2. distinguish clot subtype; 3. determine extent of fibrinolysis after tPA bolus. Methods: Consecutive patients with AIS who presented within 3 hours of onset were included. Venous blood was drawn upon arrival to the ED and 10 minutes after initiation of tPA. Results: A total of 32 AIS patients and 46 controls were evaluated; 15/32 AIS patients had both pre-and post-tPA TEG. Mean age was 67Ϯ18 years, 50% were female; of 32, 14 were of cardioembolic etiology, 3 were large artery atherosclerotic, 4 due to small artery occlusion, and 11 other/unknown. Baseline R was 5.8

Author Disclosures: J.J. Chang: None. J.P. Yang: None. Y. . Alderazi: None. M. Teleb: None. L. Restrepo: None.

Th P11 The Role Of Sonolysis, Sonothrombolysis With And Without Microbubble In Acute Ischemic Stroke: A Systematic Review And Meta-analysis Of Randomized Control Trials And Case Control Studies

Maher Saqqur, Univ of Alberta, Edmonton, Canada; Georgios Tsivgoulis, Univ of Alexandroupolis, Alexandroupolis, Greece; Francois Nicoli, La Timone Univ Hosp Universitie de la Mediterranee, Marseille, France; David Skoloudik, Palacky Univ, Olomouc, Czech Republic; Christian , Squarcioni, Laurent Grimaud, La Timone Univ Hosp Universitie de la Mediterranee, Marseille, France; Vijay Sharma, Univ of Singapore, Singapore, Singapore; Marta Rubiera, Univ of Barcelona, Barcelona, Spain; Theodoros N. Sergentanis, Athens Univ Med Sch,, Athens, Greece; Vincent Larrue,, Universite de Toulouse III, ,, Toulouse, France; Ju ¨rgen Eggers, Asklepios Hosp North, Hamburg, Germany; Khurshid Khan, Univ of Alberta, Edmonton, Canada; Limin Zhao, Univ of Alabama, Birmingham, AL; Marc , Ribo, Hosp Universitari Vall d'Hebron,, Barcelona, Spain; Fabienne Perren, Neurosonology Unit, HUG, Univ Hosp and Med, Geneva, Switzerland; Dale Storie, Univ of Alberta, Edmonton, Canada; Carlos A. Molina, Hosp Universitari Vall d'Hebron,, Barcelona, Spain; Andrei V. Alexandrov; Univ of Alabama, Alabama, AL Background: Continuous monitoring with 2-MHz, single-element pulsed-wave ultrasonography had a biologic effect of diagnostic ultrasonography that aids systemic thrombolytic therapy in patients with acute ischemic stroke. Objectives: To describe and assess the evidence from case control studies (CCS) and randomized control trials (RCT) on the efficacy, tolerability and safety of sonolysis (TCD alone) sonothrombolysis (continous TCD monitoring with IV thrombolysis) with and without microbubble (MBs) in acute ischemic stroke patient. Search Methods: Several electronic databases and grey literature were searched under different Mesh terms from 1970 until now without any language limitation by one reviewer. Then, full article were retrieved for the relative subject. Selection criteria: RCT and CCS on sonolysis ,sonothrombolysis alone or with MBs in acute ischemic stroke patients, adult patient Ͼ 18 years old, with or without IV thrombolysis treatment. Outcome measures are: complete recanalization (CR) rate in 2 hours and 24 hours, modified rankin scale (mRS) and Barthel index (BI) at 3 months and symptomatic intracerebral hemorrhage (sICH). Data collection and analysis: Data will be extracted from the CCS and RCTs into the Rev Manger software. Meta-analysis was performed on the selected RCTs and CCS. Pooled and subgroup analysis were planned. Heterogeneity was assessed using Mantel Haenzel analysis method with random effect. Results: A total of 1287 titles were reviewed from electronic literatures. Thirty eight studies were retrieved and analyze carefully. Then, 28 articles were excluded and 10 studies (6 RCTs and 4 CCS) were included in our Meta-analysis. Sonolysis and Sonothrombolysis alone or with MBs are safe and carry the same risk of sICH as IV rtPA alone (OR of sICH: 1.17 (95 % CI: 0.56-2.41). (P ϭ 0.68). They are effective (OR of CR in 2 hours: 4.0, CI 95% :2.44-6.58, P Ͻ 0.00001 ) and have 2.80 times likelihood of good long term outcome (3 months mRS 0-1or 0-2) (ORϭ 2.31 (CI: 1.6-3.34) (P Ͻ 0.001). Further subgroup analysis based on the presence of MBs revealed that sonothrombolysis with MBs is safe (OR of sICH: 1, CI: 0.35 -2.87, Pϭ1)) and effective (OR of CR at 2 hours: 2.95, CI: 1.43-6.06) (Pϭ0.003) and OR of good long term outcome: 1.99, CI: 1.2-3.29, Pϭ0.007). Finally, subgroup analysis based on sonolysis alone versus none or ASA alone in acute ischemic stroke revealed that sonolysis alone is safe (OR of sICH: 0.57, CI: 0.07-4.92, Pϭ 0.61) and effective (OR of CR in 2 hours: 23.5, CI: 1-555, Pϭ0.05) and OR of good long term outcome: 2.78, CI: 1.10-7, Pϭ0.03). Conclusions: This type of novel treatment in acute ischemic stroke is safe and effective in enhancing recanalization rate and improving long term outcome. The evidence of safety and efficacy of MBs as an enhancing model of sonothrombolysis in acute ischemic stroke is evolving.

Background:

The earlier thrombolysis is given after ischemic stroke, the better outcome. The number needed to treat for favourable outcome is 3 for patients treated within first 90 minutes. A recent study has shown that ultraearly thrombolysis treatment (Յ 70 min) is associated with better outcome in patients with moderate to severe strokes. Our objective is to study this effect according to sex. Methods: multicenter prospective study of acute ischemic stroke patients treated with intravenous (IV) tPA in five stroke centres. Variables analysed: onset to treatment time (OTT), demographic data, vascular risk factors, baseline blood pressure and glycaemia, stroke etiology according with the International Classification of stroke, basal NIHSS and 3-months modified Rankin scale (mRS) score (worse outcome was defined as mRS Ͼ2). Using multivariate logistic regression, the association between OTT and 3-months favourable outcome (mRS 0-2) according sex was studied. Results: a total of 1147 patients were included, 53% men. Mean age (SD) was higher in women than in men (69.2 [14.2] vs. 66 [13.4], P thrombolysis (Յ 70 min) was associated with a better outcome only in severe strokes (NISHH Ͼ 16), both in women and men: OR 3.21 (1.11 to 9.23) and 9 (1.02 to 78.69) respectively. Early treatment (Ͻ90 min) was associated with better outcome in severe strokes, but it reached the statistic significance only in women: OR 2.76 (1.26 to 5.86) and 2.64 (0.95 to 7.29) respectively. Conclusion: Ultraearly thrombolysis (Յ 70 min) is associated with better outcome in severe strokes in both sexes. However, women could get great benefits than men from early treatment (Ͻ 90 min).

Th P13 Intra-venous Tissue Plasminogen Activator For Acute Central Retinal Artery Occlusion: A First Randomized Controlled Trial

Author Disclosures: P.M. Riccio: None. F. Klein: None. L.A. Sposato: None.

Th P49 Stroke Risk in Persons with Heart Failure: The REGARDS Study

Patrick Pullicino, Univ of Kent, Canterbury, United Kingdom; Leslie McClure, Univ of Birmingham, Birmingham, AL; Virginia Howard, Virginia G Wadley, Monica Safford, Univ of Alabama, Birmingham, AL; James Meschia, Mayo Clinic, Jacksonville, FL; Aaron Anderson, George Howard, Univ of Alabama, Birmingham, AL; Elsayed Soliman; Wake Forest Univ, Winston-Salem, NC Introduction: Heart failure (HF) is the second most frequent cause of cardioembolism after atrial fibrillation (AF) and affects 5 million US persons. In AF, risk factors for stroke are well established and this allows the use of risk stratification tools to help identify those most likely to benefit from warfarin. In HF, risk factors for stroke are not well known and no similar risk stratification tool exists, although up to 28% of persons with HF in sinus rhythm take warfarin. We examined demographic and clinical factors in HF, looking for predictors of high incident stroke risk. Methods: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study is a population based study of US adults aged Ն45 years. Participants were characterized as having HF (by digoxin use or both paroxysmal nocturnal dyspnea and orthopnea, excluding AF), AF (by self report or electrocardiogram and including participants with both HF and AF), or neither HF nor AF. Stroke incidence rates were computed following event adjudication, and a log-rank test used to show differences in time to stroke. Among participants with HF, age, sex, systolic blood pressure (SBP), hypertension, diabetes (DM) and history of prior stroke/transient ischemic attack (TIA) at baseline were compared between those with and without incident stroke using t-tests or chi-square tests. Cox models were used to compare the stroke risk among HF participants, for different levels of significant risk factors. Results: Of the 30,239 REGARDS participants, 1,397 were excluded because of missing essential variables. Of the remaining 28,842, 1,360 (5%) had HF, 2,538 (9%) had AF, and the remainder had neither. The stroke incidence rate was 0.69/100 patient years (95% CI 0.49,0.93) in participants with HF. After multivariable adjustment, participants with HF were 1.3 times (95% CI 0.92,1.9) more likely, to experience a stroke than those with neither HF nor AF. Among participants with HF, SBP (pϭ0.046), DM (pϭ0.03) and prior stroke/TIA (pϭ0.0004) increased the risk of stroke. HF participants with prior stroke/TIA and diabetes were more likely to have stroke than those with diabetes alone (table). Hazard ratio and stroke incidence among those with HF without AF Introduction: Recent studies have shown that intensive glycemic control failed to reduce cardiovascular risk in diabetic patients, while hyperglycemia in acute phase of stroke is detrimental to outcome. Hypothesis: We assessed the hypothesis that prestroke glycemic control (PSGC) may affect outcome in patients with acute ischemic stroke. Methods: FSR is a multicenter stroke registry of acute stroke patients admitted to seven stroke centers in Fukuoka, Japan. From June 1999 to March 2010, 6653 patients were enrolled. Among them, the patients who fulfilled the following criteria were included in this analysis: (1) first-ever stroke, (2) ischemic stroke, (3) hospitalization within 24 hours after onset, (4) HbA1c measured at admission, (5) no impairment of ADL before onset. PSGC state was categorized into four groups according to the Japan Diabetes Society guidelines, excellent (HbA1cϽ5.8%), good (5.8%ՅHbA1cϽ6.5%), fair (6.5%ՅHbA1cϽ8%) and poor (8%ՅHbA1c). Neurological severity was evaluated by NIHSS, which was divided into quartile. We defined "neurological worsening" when NIHSS at 3 weeks became worse than admission NIHSS, and "good recovery" when NIHSS improved more than 4 during 3 weeks in patients with admission NIHSSՆ5 or when NIHSS at 3 weeks was 0 in those with admission NIHSSՅ4. Functional outcome was assessed using modified Rankin Scale (mRS) and mRSՆ2 was defined as dependent. Results: A total of 3248 patients were studied. Admission NIHSS was not different among PSGC groups (Pϭ0.14), whereas NIHSS at 3 weeks was higher in poorer PSGC groups (Pϭ0.01). As PSGC became worse, the frequency of neurological deterioration was high (pϽ0.001) and that of good recovery was low (pϽ0.001). Functionally dependent patients were more prevalent in poorer PSGC groups (pϽ0.001). Multivariate-adjusted logistic regression analysis revealed that PSGC state was independently associated with functional outcome. Poor PSGC group showed increased risk of functional dependence at 3 months (Odds Ratio, 3.36; 95% CI, 1.91-5.94; PϽ0.001) compared with excellent PSGC group. Conclusions: The neurological improvement and functional outcome are significantly poor after ischemic stroke in patients with poor glycemic control before onset.

Conclusions

Author Disclosures: T. Matsuki: None. M. Kamouchi: None. S. Fujimoto: None. J. Jinnouchi: None. J. Hata: None. T. Ago: None. S. Sadoshima: None. T. Kitazono: None.

Th P58 Consciousness Impairment in a Consecutive Series of 1436 Acute Ischemic Strokes

Serban-George Puricel, Neurology Service, Cntr Hospier Universitaire Vaudois and Univ of Lausanne, Lausanne, Switzerland; Mohamed Faouzi, Institute of Social and Preventive Medicine, Cntr Hospier Universitaire Vaudois and Univ of Lausanne, Lausanne, Switzerland; Patrik Michel; Neurology Service, Cntr Hospier Universitaire Vaudois and Univ of Lausanne, Lausanne, Switzerland Background and objectives: Decreased level of consciousness (LOC) at ischemic stroke onset is infrequent and associated with a poor prognosis. Its causes and mechanisms are insufficiently understood. We aimed at finding predictors and topographic correlations for such strokes. Methods : In an acute hospital based registry of consecutive acute ischemic strokes admitted within 24 hours after last proof of wellbeing(Acute STroke Registry and Analysis of Lausanne, ASTRAL), decreased level of consciousness was defined as a value of Ն 1 on the corresponding NIHSS item on initial neurological assessment. Acute status epilepticus was excluded by EEG if suspected. Demographic, clinical, etiological, radiographic, arterial imaging and outcome factors were considered. Poor prognosis was defined as a modified Rankin Scale score of Ն 2 at 3 months. In a first multivariate logistic regression analysis of predictors of decreased LOC, we entered all significant variables except initial NIHSS. The second multivariate logistic regression analysis considered only significant variables concerning anatomical localisation and arterial territories. Results : In 1'436 acute ischemic strokes, 139 (9.7 %) had a decreased LOC on admission, of whom only one was attributable to early mass effect. These patients showed significantly poorer prognosis (OR 7.8,) and higher mortality rate at three months (OR 4.67,). On multivariate analysis, they had more frequently one or more previous strokes (OR 5.1, 95% CI 2.79-9.31), more frequently early ischemic changes on radiology (OR 1.74, 95% CI 1.10 -2.75) and a higher frequency of arterial stenosis or occlusion in the ischemic territory (OR 2.87, 95% CI 1.6 -4.91). Lacunar mechanism (OR 0.11, 95% CI 0.04 -0.36) and stroke with an uncertain cause (OR 0.37, 95% CI 0.18-0.71) were less frequent. Regarding localisation, patients with pure basilar strokes (OR 1.83, 95% CI 1.15-2.90), bilateral (OR 2.05, 95% CI 1.00-4.19), mixed supra-and infratentorial strokes (OR 6.11,, large hemispheric infarction, and involvement of midbrain simultaneous with at least one other posterior circulation structure (OR 4.99, 95% CI 2.13-11.65) showed decreased LOC. Limiting the multivariate analysis to stroke localization, LOC was more frequently normal in left sided infarctions (OR 0.56, 95% CI 0.36 -0.88) and in supratentorial strokes without cortical involvement (OR 0.23, 95% CI 0.10 -0.54). Conclusion: Decreased level of consciousness at ischemic stroke onset is related to the presence of previous strokes, current stroke mechanism, early ischemic changes on acute imaging and acute arterial occlusions. Lesions have to be distributed in specific patterns and widespread in infra-and supratentorial structures in order to decrease LOC, suggesting distributed networks for its maintenance. Clotilde Balucani, Virginia Howard, George Howard, Georgios Tsvigoulis, Karen Albright, Alexis Jernigan, April Sisson, Maruthi Kesani, Kristian Barlinn, Luis Cava, Paola Palazzo, Andrei Alexandrov, Anne Alexandrov; Univ of Alabama at Birmingham, Birmingham, AL Introduction: Few studies have looked at predictors of clinical outcomes of stroke in young adults residing in the Stroke Belt (Southeastern US). Subjects andMethods: We retrospectively abstracted baseline predictor and discharge data on all stroke patients aged 18-45 seen at a tertiary hospital in Alabama from October 2007-March 2010. Outcome was assessed by the discharge modified Rankin Score (mRS). Predictors of outcome were assessed using general linear models (regression), predicting the mean discharge mRS. Backwards stepwise regression was employed to develop a most parsimonious multivariable model. Results: Among 1453 consecutive stroke patients, 327 were young adults (22.5%). Ninety subarachnoid hemorrhages and 19 transient ischemic attacks were excluded from the analysis. Outcome data were available on 215 stroke patients -153 ischemic and 62 intracerebral hemorrhagic (ICH) infarcts (M:F 119:94) 52% White; with median admission NIH Stroke Scale (NIHSS) of 6 (interquartile range: 2 to 15) -who were relatively uniformly dispersed over the 0-to-6 range of mRS at discharge. Univariately, admission NIHSS was the most significant predictor of discharge mRS (pϽ0.0001). In addition, the discharge mRS was related to admission glucose, stroke subtype, use of illegal drugs, renal disease, history of coronary artery disease (CAD), current smoking and the presence of carotid artery plaques (Table ).The discharge mRS was not affected by age, sex, race, hypertension, diabetes, obesity, hypercholesterolemia, obesity, atrial fibrillation, congestive heart failure, systolic blood pressure, or admission creatinine (pϾ0.05). Only history of CAD persisted as a significant predictor after adjustment for baseline NIHSS. Discussion: These data suggest that after adjustment for stroke severity, history of CAD is the most potent predictor of functional outcome at discharge. We hypothesize that factors such as the use of illegal drugs or the presence of renal disease have their effect on stroke outcome though a pathway of presenting as a more severe stroke event. In contrast, CAD, which is often associated with left ventricular dysfunction with altered systemic perfusion, appears to have an effect on stroke outcome independent of the stroke severity.

Th P67 Baseline Smoking Level Increases the Long-Term Risk of Death or Non-Fatal Vascular Event in People with Stroke: a 10-Year Survival Analysis

Background: Stroke is the first-leading cause of death in Korea. With the rapid aging of our society, it is very important to reduce burden of stroke to us, and prevention is the most important strategy to accomplish this goal till now. However, we do not know how much each of major risk factors of stroke contributes to its incidence in our society. This study aimed to estimate the magnitude of major risk factors' association with ischemic stroke and the population attributable risk (PAR) for each risk factor. Methods: In this case-control study, a consecutive series of 3,629 patients who were hospitalized due to acute ischemic stroke within 7 days of onset between April 2008 and September 2009, were collected from 9 centers participating in the 'Clinical Research Center for Stroke' program sponsored and funded by the Korean government. Each case was age (ϩ-3 years) and sex-matched to each control. Control data were obtained from the Korean National Health & Nutrition Examination Survey (KNHANES), which was designed to represent the Korean population. We calculated adjusted odds ratios (ORs) with a conditional logistic regression model and PARs for the major risk factors of ischemic stroke. Results: The adjusted ORs (95% CI) were 2.11 (1.87ϳ2.37) for hypertension, 2.26 (1.97ϳ2.60) for diabetes mellitus, 1.25 (1.08ϳ1.44) for hyperlipidemia, 2.83 (2.46ϳ3.26) for current smoking, 4.63 (3.78ϳ5.68) for history of stroke, and 1.84 (1.46ϳ2.33) for history of ischemic heart disease. The PARs were 15.8ϳ22.8% for hypertension, 7.3ϳ11.4% for diabetes, 0.7ϳ3.9% for hyperlipidemia, 27.9ϳ37.5% for current smoking, 3.6ϳ6.0% for stroke history, and 0.8ϳ2.4% for ischemic heart disease. Both body mass index (BMI) or obesity (BMIՆ25kg/m 2 ) did not show significant association with ischemic stroke. Conclusion: This study is the first one to report the magnitude of relationships between major risk factors of stroke and ischemic stroke in the Korean population. With respect to prevention of stroke in the society level, the burden of smoking is relatively high in Korea compared to other well-known risk factors of stroke.

Author Disclosures: T. Park: None. K. Lee: None. Y. Ko: None. J. Park: None. S. Lee: None. K. Yu: None. J. Cha: None. J. Lee: None. M. Han: None. Y. Cho: None. J. Lee: None. J. Lee: None. H. Bae: None.

Th P69 Stroke Among The New Zealand Workforce: A Prospective Study Of Middle-aged Employees

Hope Buell, Patricia Metcalf, Daniel Exeter; Univ of Auckland, Auckland, New Zealand Aims: To examine the association between ethnicity and incident cerebrovascular disease among middle-aged employees. Methods andResults: Four thousand four hundred and eighty-five subjects from the New Zealand workforce (3239 men and 1246 women), aged 40-78 years who were free from stroke and worked full time at baseline (1989)(1990)(1991), were followed an average of 9 years. The outcome measure was incident fatal stroke or clinically verified non-fatal stroke (a total of 185 events). Kaplan-Meier analysis demonstrated that increased age, Pacific Islander ethnicity, current smoker, high blood pressure, increased waist measurement and diabetes were significant predictors of stroke (pϽ0.05). Cox proportional hazard models adjusted for sociodemographic and clinical risk factors measured did not reduce the estimate for Pacific Islander ethnicity (HR 1.77, 95% CI 1.16-2.81). Conclusion: In this population, Pacific Islander ethnicity is related to increased risk of stroke independent of demographic and clinical risk factors. Further research is needed to examine geographic variation and different stroke types (acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, transient ischemic attack) in this population.

Author Disclosures: H. Buell: None. P. Metcalf: None. D. Exeter: None. Patients in China were younger that those in Canada (MeanϮSD of age in years: 63.8Ϯ12.9 vs. 73.0Ϯ13.4, PϽ0.001) and were more likely to be male (61.2% vs. 48.8%, PϽ0.001).

Th P70 Comparison of baseline characteristics of strokes between China and Canada: results from the China National Stroke Registry and the Registry of the Canadian Stroke Network

Chinese patients presented at a younger age than Canadians. Intracerebral hemorrhage and ischemic strokes were more common in China (23.7% vs. 7.1%,PϽ0.001;66.3% vs. 46.0%, PϽ0.001), and TIA and undetermined strokes were more common in Canada (6.2% vs. 33.8%, PϽ0.0001; 0.6% vs. 9.8%, PϽ0.0001, respectively). There were no significant difference in subarachnoid hemorrhages between China and Canada (3.4% vs. 3.3%,pϭ0.74). Compared with Canadian patients, based on self-report disease histories, Chinese patients were more likely to smoke (38.9% vs. 14.1%, PϽ0.001) and more likely had hypertension (63.2% vs. 61.6%, pϭ0.04), but less likely had diabetes (17.7% vs. 23.7%, PϽ0.001), hyperlipidemia (9.7% vs. 30.2%, PϽ0.001), arterial fibrillation (5.5% vs. 13.9%, PϽ0.001) and previous stroke (30.9% vs. 34.1%, PϽ0.001). Conclusion: There are substantial differences in demographics, subtypes of stroke and risk factors between China and Canada. The proportion variation in stroke subtypes may be partly related to the ethnic differences between the two countries. Awareness of the key risk factors (e.g., smoking, hypertension) may be helpful in improving the stroke control and prevention strategies in China. The differences in treatments and outcomes after stroke remain to be determined in further analyses.

Th P71 Strokes and Tias in the Out-Of-Hospital Setting: Incidence and Temporal Trends

Simona Ferioli, Jane Khoury, Jane Eilerman, Dawn Kleindorfer, Kathleen Alwell, Charles J Moomaw, Daniel Woo, Matthew Flaherty, Pooja Khatri, Opeolu Adeoye, Joseph Broderick, Brett Kissela; Univ of Cincinnati, Cincinnati, OH Introduction: Stroke incidence in the US population has been typically addressed by population-based studies using data obtained predominantly through the inpatient setting. However, a substantial number of stroke cases are diagnosed in care facilities or outpatient clinics, as there has been a trend towards managing care in the outpatient setting. Ignoring these events can lead to a significant underestimate of incidence. We examined strokes and TIAs ascertained in the out-of-hospital setting, collected from three study periods of the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS). We hypothesized that the rate of out-of-hospital events has been increasing over time. Methods The events were ascertained during three one-year study periods (July1993-June1994, 1999, and 2005) among residents of the 5 counties that comprise the largely biracial study population of 1.3 million. We analyzed stroke events screened in all area hospital-based and health department clinics, as well as in a randomly selected sample of nursing homes and primary care physician settings. Cases were cross referenced with all events captured in the hospital setting in our study to prevent double counting. Events ascertained in physician offices and nursing homes were weighted to account for the sampling methodology. Results Incidence rates for out-of-hospital ascertained strokes and TIAs are shown in the table. Accounting for sampling methodology, using appropriate weighting, the out-of-hospital events accounted for 10.1% of stroke/TIA events within our population in 1993-94, and then increased to 24.5% in 1999 and 19.7% in 2005.

Conclusion:

The proportion of out-of-hospital cases in 1999 and 2005 was substantially higher than 1993-1994. We cannot rule out that the results may be related to subtle methodologic drift or random variability between periods. However, we speculate that the observed trend for more out-of-hospital management from the early 1990s to 2005 has been driven by the increasing financial pressures to manage medical issues in the outpatient setting, in order to reduce health care costs. Regardless, out-of-hospital ascertainment captures a substantial proportion of strokes and TIAs in our population, demonstrating that this methodology is crucial for understanding the true incidence of stroke. Table : CGNKSS Out-of-hospital Stroke/TIA Incidence rates (per 100,000; adjusted to 2000 US Census) -incidence rates include 95% confidence interval, n ϭ number of out-of-hospital cases ascertained, weighted n ϭ number of cases considered for incidence rate after adjusting for sampling methodology

Th P82 Combination of Neurovascular Imaging Modalities for Evaluation of Patients with Stroke

Ameer E Hassan, Saqib A Chaudhry, Fahd Sultan, Gabriella Vazquez, Shujaat Khalil, Muhammad Ansar, M. Fareed K Suri, Mustapha A Ezzeddine, Adnan I Qureshi; Zeenat Qureshi Stroke Res Ctr, Univ of Minnesota, Minneapolis, MN Background: A combination of two non-invasive tests, MR imaging/MR angiography (MRA) and CT/CT angiography (CTA), may reduce the need for conventional digitial subtraction angiography (DSA) for diagnosis of cerebrovascular disease among patients with stroke. Objective: To ascertain the effectiveness of a combination of two non-invasive tests in preventing the need for DSA in patients with stroke. Methods: All consecutive stroke patients from two comprehensive stroke centers from January 2008 to July 2010 were analyzed. Findings of CTA, MRA, and DSA were abstracted from chart review. We estimated the value of combination of two non-invasive tests to provide definitive diagnosis judged by the treating vascular neurologist either by definitely excluding or determining the need for surgical or endovascular treatment without any DSA. Results: A total of 700 patients (344 [49%] men) were studied in this cohort with a mean age of 63 years Ϯ 16. There were a total of 241 patients who had at least two imaging modalities, 81 patients with CTA /MRA combination, 69 patients with CTA/DSA combination, 65 patients with MRA/DSA combination, and 26 patients with all three modalities. Among the 107 patients who underwent a CTA and MRA, a DSA was still required for diagnostic purposes in 26 (24%) of the patients. Conclusion: In current practice, a combination of two vascular imaging studies is frequently used. In our experience, the findings derived from CTA and MRA combination still require confirmation with DSA in one-quarter of the patients.

Th P83 CT Assessment Of Blood Brain Barrier Permeability And Risk Of Haemorrhagic Transformation In Ischaemic Stroke

Adam J Couves, Ferghal McVerry, Niall J Macdougall, Krishna A Dani, Keith W Muir; Univ Of Glasgow, Glasgow, United Kingdom Introduction: Haemorrhagic Transformation (HT) is a potential complication of ischaemic stroke treatment associated with increased morbidity and mortality. CT perfusion (CTP) can be used to derive permeability maps which may reflect reduced blood brain barrier integrity. We investigated whether increased permeability could be predictive of HT in acute ischaemic stroke in addition to known predictors of HT. Methods Imaging and clinical data from patients with ischemic stroke who underwent plain computed tomography (CT) and CTP within 6hrs of symptom onset were reviewed. Non-contrast CT was assessed for the extent of early ischaemic changes using the Alberta Stroke Programme Early CT Score (ASPECTS). ASPECTS scores were evaluated on perfusion maps of cerebral blood volume (CBV), cerebral blood flow (CBF) and mean transit time (MTT), in addition to permeability maps of surface areas product (PS) and extraction ratio (E). Regions of interest (ROI) corresponding to ASPECTS were drawn on each map and mean values for each parameter were calculated. The same ROIs were assessed for HT according to the Safe Implementation of Treatments in Stroke (SITS) criteria, as well as infarction and normal /abnormal tissue on follow-up imaging at 24-72 hours. Binary logistic regression and ROC analysis were performed to identify predictors of HT. Results Imaging on 30 patients was reviewed, 9 of whom proceeded to HT. CBV and CBF were the only parameters able to predict an outcome of HT over infarction for a ROI (pϭ0.026 and pϭ0.002 respectively). ROC analysis revealed modest predictive values for HT with CBV and CBF with an area under the curve (AUC) of 0.67 for both. Extraction ratio was a more accurate predictor of infarction compared to conventional infarct markers CBF and CBV (AUCϭ 0.792, 0.692 and 0.627 respectively). Atrial Fibrillation was associated with HT ( pϭ0.01). Non significant associations included increased blood glucose (pϭ0.176), previous stroke (pϭ0.69), early ischemic change on baseline CT (pϭ0.121), and increasing extent of baseline permeability and perfusion abnormalities (pϭ.0.097 and 0.177) Conclusion: Permeability Surface Area Product and Extraction Ratio did not identify tissue destined to haemorrhage after stroke. CBF and CBV did predict HT, but predictive value was limited for both. Extraction Ratio may be useful in predicting extent of infarct core.

Th P84 Does Threshold Based Segmentation of MRI Correlate with Visual Reading of Ischemia and Perfusion Deficit in Acute Scans?

Marie Luby, Sundeep Boparai, John K Lynch, Jose ´G Merino, Lawrence L Latour, Shlee S Song, Amie W Hsia, Steven Warach; NINDS, Bethesda, MD Introduction: Threshold based segmentation (TBS) of MRI scans has the potential to automate the identification of ischemic and penumbral areas without lengthy processing and reader expertise. The objective of this study was to test specific Apparent Diffusion Coefficient (ADC) and perfusion Tmax thresholds for identification of ischemic and penumbral areas in acute stroke patients. Methods: LESION is a multicenter, prospective study of imaging in acute stroke. Patients were included in this TBS study if they had an acute MRI (1.5T or 3T scanners) with high quality DWI and PWI images based on visual inspection, had presented within 3 hours from onset, were scanned prior to acute intervention, had a diagnosis of definite acute ischemic cerebrovascular syndrome (AICS), and were enrolled between 2000-09. All MRI scans were reviewed by an experienced reader blinded to the qualitative reads to determine presence of ischemia, perfusion deficit, and evidence of mismatch. TBS of MRI scans were determined by generating the perfusion maps in Perfscape™ (Olea Medical) and then measuring the ADC and Tmax volumes in Neuroscape™ (Olea Medical) using an ADC value of 615 mm 2 /seconds and Tmax value of Ͼ 6 seconds. A mismatch definition of Tmax -ADC volume Ͼ 60 cc was used. The TBS decisions of ADC positive ϭ yes/no, Tmax positive ϭ yes/no, and mismatch ϭ yes

Th P86 MR Perfusion And Reperfusion As Predictors Of Hemorrhagic Transformation In Hyper-Acute Ischemic Stroke: A Voxel-Based Analysis

Andria L Ford, Washington Univ, St. Louis, MO; Hongyu An, Univ of North Carolina, Chapel Hill, NC; John J Lee, Rosana Ponisio, Washington Univ, St. Louis, MO; Hongtu Zhu, Univ of North Carolina, Chapel Hill, NC; Katie D Vo, Washington Univ, St. Louis, MO; William J Powers, Weili Lin, Univ of North Carolina, Chapel Hill, NC; Jin-Moo Lee; Washington Univ, St. Louis, MO Background: Studies examining MRI predictors of hemorrhagic transformation (HT) after ischemic stroke have demonstrated that severely decreased ADC is predictive. In this study, we hypothesized that in addition to severe ischemia, reperfusion may predict HT in ischemic stroke patients. Methods: Acute ischemic stroke patients underwent two MR scans: within 4.5 (tp1), at 6 (tp2), and at 24 hrs (tp3) after stroke onset. Susceptibility-weighted imaging (SWI) or gradient-echo (GRE), ADC, mean transit time (MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV) maps were obtained at all time-points. HT was delineated by a neuroradiologist (RP) on SWI or GRE at tp2 or tp3. Blood on tp1 was excluded from the analysis. To assess the effect of radiological variables (ADC, MTT, CBF, and CBV) in predicting HT, voxels from HT patients were pooled in a logistic regression (LR) model predicting the outcome of HT or no HT within the ischemic hemisphere. An equal number of voxels were randomly selected from the HT or non-HT regions to balance the influence of each patient on the final analysis. Each MRI parameter at tp1, tp2, or ⌬ (tp2-tp1) was individually assessed as an independent predictor of HT. Significant variables (pϽ0.05) were entered (forward selection) until additional variables no longer increased the model's goodness of fit [c-statistic/area under the curve (AUC)]. Results: Thirty-two ischemic stroke patients were imaged with MRI at 3.0Ϯ.8 hrs, 6.4Ϯ.4 hrs, and 24 hr after onset. Six patients with HT Ͼ 1 ml were included in the analysis (range 1-50.4 ml); only 1 HT was symptomatic. Cohort characteristics: 63 yrs-old; 1 female; NIHSS 15.3; 3 of 6 received IV tPA. In the pooled LR analysis, the overall model predicted HT ( 2 ϭ4188, dfϭ3, PϽ0.01) with the strongest predictor being MTT tp1 [␤ϭ0.145, Bϭ1.2, PϽ0.01, corresponding to a 20% increased HT risk with each 1 sec increase in MTT (increaseϭmore severe ischemia)], followed by ADC tp1 [a ˆϭ-0.06, Bϭ0.94, PϽ0.01, 6% increased HT risk for each 1 mm 2 /sec decrease in ADC (decreaseϭmore severe ischemia)], followed by ⌬MTT [␤ϭ-0.02, Bϭ.98, PϽ0.01, 2% increased HT risk for 1 sec decrease in ⌬MTT (decreaseϭreperfusion)]. While adding ADC tp1 to MTT tp1 in the model increased the AUC from 0.723 to 0.826, adding ⌬MTT increased the AUC to 0.827. In individual analyses of the 6 patients, significant predictors of HT were: MTT tp1 (5 pts), ADC tp1 (4 pts), and ⌬MTT (2 pts). ⌬MTT alone was most predictive in the 2 pts with largest HT volumes: pt with 50 ml HT (AUCϭ0.80); pt with 9.3 ml HT (AUCϭ0.76). Conclusion: This voxel-based analysis suggests that early MTT, an indicator of severe ischemia, may be as predictive as ADC for HT. While reperfusion was a weak predictor in the overall population, it was a strong predictor in two patients with the largest HTs. Further study is needed to confirm these findings in a larger cohort and determine if asymptomatic HT has a deleterious effect on outcome.

Author Disclosures: A.L. Ford: None. H. An: None. J.J. Lee: None. R. Ponisio: None. H. Zhu: None. K.D. Vo: None. W.J. Powers: None. W. Lin: None. J. Lee: None.

Th P87 Early Performance of MRI reduces the rate of Stroke Misdiagnosis in Young Adults

Pratik Bhattacharya, Nandakumar Nagaraja, Kumar Rajamani, Ramesh Madhavan, Sunitha Santhakumar, Seemant Chaturvedi; WAYNE STATE UNIVERSITY, Detroit, MI Introduction: The misdiagnosis of acute ischemic stroke in young adults is a significant problem since patients with stroke may have many decades of potential disability. Also, proven therapies for acute stroke may not be administered in misdiagnosed patients. In previous work, we found that stroke misdiagnosis occurs in 14% of young adults and that patients with posterior circulation strokes were more likely to be misdiagnosed (J Stroke Cerebrovasc Dis, in press). Hypothesis: We assessed the hypothesis that early use of MRI, arrival by ambulance, and presentation to a Primary Stroke Center (PSC) would be associated with a reduced rate of misdiagnosis. Methods: A prospective database of young adults (ages 16-49 years) with ischemic stroke (final diagnosis provided by vascular neurologists) was reviewed. We collected information on several variables, including age, gender, race, arrival by ambulance, whether brain MRI was performed within 48 hours, and initial presentation to a PSC. Ambulance arrival was determined by retrospective queries to patients. Variables were tested against emergency department (ED) misdiagnosis with chi square testing. Variables with a p value of able model. Results: 77 patients with a mean age of 37.9 years were reviewed. Women composed 57% of the group and race included White American (58.4%), African American (37.7%), and other groups (3.9%). 48.3% of patients arrived by ambulance, 53.2% had a brain MRI within 48 hours, and 23.4% initially presented to a PSC. The overall rate of ED misdiagnosis was 14.5%. Univariate testing for key variables and misdiagnosis was as follows:

In multivariable testing, performance of MRI within 48 hours (pϭ0.023) was associated with a lower rate of misdiagnosis and age Ͻ35 years was linked with greater likelihood of misdiagnosis (pϭ0.047). There was a trend for arrival by ambulance to be associated with a lower rate of misdiagnosis (pϭ0.06).

Th P95 Thrombus Hounsfield Units on Thin-Section Noncontrast CT Predicts Early Vascular Recanalization and Stroke Subtype After Thrombolysis

Josep Puig, Dept of Radiology (IDI), Girona Biomedical Rsch Institute, Hosp Universitari de Girona Dr Josep Trueta, Girona, Spain; Josep Daunis-i-Estadella, Dept of Informatics and Applied Mathematics, Univ of Girona, Girona, Spain; Helena Termes, Gerard Blasco, Sebastia Remollo, Santiago Mourelo, Sergi Juanpere, Dept of Radiology (IDI), Girona Biomedical Rsch Institute, Hosp Universitari de Girona Dr Josep Trueta, Girona, Spain; Anton Bardera, Imma Boada, Dept of Informatics and Applied Mathematics and Institute of Informatics and Applications, Univ of Girona, Girona, Spain; Maria Jimenez-Nieto, Mar Castellanos, Joaquin Serena, Dept of Neurology, Girona Biomedical Rsch Institute, Hosp Universitari de Girona Dr Josep Trueta, Girona, Spain; Salvador Pedraza; Dept of Radiology (IDI), Girona Biomedical Rsch Institute, Hosp Universitari de Girona Dr Josep Trueta, Girona, Spain Background and Purpose: Thin-section noncontrast CT (NCT) can detect thrombi in large arteries in acute stroke and provide a measure thrombus composition based on Hounsfield units (HU). Thromboembolic stroke can be caused by white, red, or mixed clots. White (platelet-rich) thrombus is resistant to thrombolytic drugs, but red (erythrocyte-rich) is not. HU are lower in white thrombi than in red. We investigated whether HU in thin-section NCT can differentiate subtypes of acute ischemic stroke and predict the lysability of thrombi. Methods: Two readers blinded to clinical data reviewed 1.25mm-section NCT studies obtained immediately before IV thrombolysis of middle cerebral artery (MCA) acute thrombi within 4.5 hours of stroke onset. Stroke subtype was assigned using TOAST criteria. HU values and ratios (rHU) were measured on thrombi and contralateral normal segments. We also evaluated the effected MCA segment, thrombus length, and time from onset. Recanalization was assessed by CT or MR angiography after IV thrombolysis. We found the cut-off value of thrombus HU for lysability by binary logistic regression. We sought associations between recanalization and stroke subtype, affected MCA segment, thrombus length, and time from onset with ANOVA, chi-square, and T-test. Results: We evaluated 39 patients (22 men, 17 women; aged 68.74Ϯ11.94 years). Breakdown of stroke subtype: 43.5% large artery atherosclerosis (LAA), 43.5% cardioembolism (CE), and 13% unknown/other. CT angiography detected thrombi in all patients. Recanalization occurred in 35.9% of patients. Mean rHU of recanalized and unrecanalized thrombus were 1.57Ϯ0.23 and 1.11Ϯ0.15, respectively (pϽ0.001). An rHU Ͼ 1.278 best predicted thrombus lysability (sensitivity 96.0%, specificity 92.9%, positive predictive value 96.0%, negative predictive value 92.9%). rHU values were 1.372Ϯ0.31 for CE, 1.101Ϯ1.17 for LLA, and 1.462Ϯ0.26 for unknown/other. rHU in LLA thrombi were lower than in CE and unknown/other stroke thrombi (pϭ0.004). Length, time from onset, and affected MCA segment did not correlate with early recanalization (pϭ0. 219, pϭ0.184, and pϭ0.168, respectively). Conclusion: Measuring thrombus HU can help determine stroke subtype and prognosis of IV thrombolytic therapy, enabling the best reperfusion strategy and early secondary prevention measures to be chosen for individual patients.

Th P96 The Value of CT Perfusion (CTP) Prognostic Maps in Predicting Reversible and Irreversible Neurological Dysfunction Following Reperfusion Therapies

Limin Zhao, Kristian B Barlinn, Karen C Albright, Maruthi Kesani, Kara A Sands, Michael J Lyerly, Luis F Cava, Clotilde Balucani, Anne W Alexandrov, Comprehensive Stroke Cntr, Univ of Alabama Hosp, Birmingham, AL; Mark R Harrigan, Dept of Neurosurgery, Univ of Alabama Hosp, Birmingham, AL; Joseph A Horton, Dept of Radiology, Univ of Alabama Hosp, Birmingham, AL; Damon E Patterson, Andrei V Alexandrov; Comprehensive Stroke Cntr, Univ of Alabama Hosp, Birmingham, AL Background&Purpose: We aimed to evaluate the ability of a commercially available CTP prognostic maps software to identify reversibly and irreversibly damaged brain functions in the best case scenario: patients who achieved early and complete tissue reperfusion. Subjects&Methods: Consecutive ischemic stroke patients who received reperfusion therapies, those with early (Ͻ 2 hours from treatment initiation) and complete (TIMI III-or equivalent) reperfusion were included in the analysis. CTP prognostic maps (Phillips Brilliance CT) were assigned as "red", or irreversible if CBV fell below 2 ml/100g and "green", or recoverable if the affected/un-affected MTT ratio was Ͼ1.4. Only patients with MCA territory affected were included and subcomponents of the NIHSS scale pre-and post-treatment were analyzed based on anatomical correlation of the affected CTP areas and corresponding neurological functions. ASPECT scores and early ischemic changes in the corresponding vascular territories were also obtained from a non-contrast pre-treatment CT scans independent of CTP and clinical findings. Results: Among 109 consecutive patients who had intra-arterial reperfusion procedures (age 60Ϯ15 years, 55% men, median NIHSS 15, interquartile range 9.5-21), 18 had pre-treatment CTP and had early complete reperfusion. We identified 50 affected areas on CTP [red 13 (26%), green 37 (74%)] with corresponding measurable neurological deficits including aphasia, arm, face weakness, and inattention. The lowest follow-up NIHSS subcomponent scores were obtained after treatment until discharge. Red areas correctly identified 11/13 (85%) of functions that did not recover despite early reperfusion. Red portions Ͼ30% of the total affected area correctly predicted 92% of irreversibly lost function, while red portions Ͻ30% of the total area identified 40% of lost functions (OR 7.2,pϭ.006). "Green" correctly identified 17/37 (46%) of functions that recover after early reperfusion (OR 4.7,pϭ0.095). ASPECTS Ͻ7 for irreversible loss were correct in 34/44 (77%), while ASPECTS Ͼ7 predicted 11/28 (39%) of recoverable functions (OR 2.2, 95% CI 0.8 -6.1, pϭ0.184.)Conclusions: In patients achieving early and complete reperfusion, pre-treatment CTP prognostic maps had the highest predictive value for irreversibly lost neurologic functions with CBVϽ2ml/100g particularly when red areas extended to over 30% of the total affected area. Prediction of recoverable functions on CTP had a modest value similar to that of the ASPECT score from a non-contrast CT. Background: Cerebral perfusion imaging in acute stroke could improve patient selection for reperfusion therapies. CT perfusion and MR perfusion are competitively used to image core/penumbra mismatch in acute stroke. We sought to assess the agreement of these two techniques on qualitative assessment of mismatchMethods: Patients with acute ischemic stroke from 2 major academic hospitals who had undergone both CT and MRI perfusion at baseline were included in the analysis. All perfusion images were independently interpreted in a blinded fashion and random order by two experienced vascular neurologists who were unaware of the clinical presentation. For each patient, readers scored the presence or absence of a clinically significant CBV/Tmax mismatch on CT, and a DWI/Tmax mismatch on MRI. Interreader and intermodality agreement analysis was then performed using kappa statistics. Results: A total of 19 patients were included in the analysis. Time interval between obtaining CT and MR images ranged from 33 to 185 minutes. 12/19 patients were treated with intravenous rt-PA. Interreader agreement on mismatch was perfect with kappaϭ1.00 for both CBV/Tmax (19/19; mismatch present in 15 cases, absent in 4), and DWI/Tmax (17/17; 12 present, 5 absent, 2 uninterpretable due to poor bolus). Intermodality agreement was present in 13/17 cases (kappaϭ0.36, pϭ0.12). Of the remaining four cases, three had a mismatch based on CT perfusion (CBV/Tmax) but not on MRI and one patient had a mismatch on MRI (DWI/Tmax) but not on CT perfusion. All four of these patients were treated with intravenous rt-PA. A review of corresponding CTAs and MRAs revealed no evidence for interval recanalization. Conclusion: Our results demonstrate an excellent interreader agreement on mismatch classification for both CTP and MRI. The agreement between two techniques was modest. Potential causes for this difference may include the impact of intravenous thrombolytic therapy, time interval between the two studies, and suboptimal CTP coverage.

Author Disclosures: M. Grigoryan: None. G.W. Albers: None. R. Bammer: None. M. Straka: None. M. Mlynash: None. S. Kemp: None. L. Wechsler: None. D. Thai: None. M. Lansberg: None.

Th P98 Clot Or Not: Using The Sigmoid Plate Sign On Head CT to Differentiate Transverse Sinus Thrombosis from a Congenitally Atretic Cerebral Transverse Sinus

Yolanda Chik, JOHNS HOPKINS HOSPITAL, Baltimore, MD; Rebecca F Gottesman, JOHNS HOPKINS BAYVIEW MED CTR, Baltimore, MD; Steven Zeiler, JOHNS HOPKINS HOSPITAL, Baltimore, MD; Jason Rosenberg, Rafael H Llinas; JOHNS HOPKINS BAYVIEW MED CTR, Baltimore, MD Background: Transverse sinus venous thrombosis can be a difficult diagnosis given its non-specific clinical signs and lack of specificity on MR venograms. We hypothesize that comparison of the sigmoid plates on non-contrast brain CT can differentiate transverse sinus clot from a congenitally atretic sinus when dropout of transverse sinus flow is seen on MRV. Methods: We collected 53 subjects with MRV dropout of a transverse sinus. A retrospective review of all available brain imaging and medical records on each subject (our gold standard) determined 11 had thrombosis and 42 had an atretic transverse sinus. De-identified non-contrast brain CTs, marked with side of MRV dropout, were sent to 2 blinded neurologists for adjudication of the presence or absence of the sigmoid plate sign. A positive sigmoid plate sign was defined as an asymmetrically smaller sigmoid plate, hypothesized as consistent with an atretic sinus, in the presence of MRV dropout on that side. A mutual answer was provided by the reviewers when they disagreed. Sensitivity, specificity, a Fisher's exact test, and odds ratio for the distribution of the sign in subjects with clot and subjects with sinus atresia were calculated. Results: Each blinded neurologist had a sensitivity of 91% (detecting 10/11 clots based on absence of the sigmoid plate sign) and specificity of 71-81% (detecting atretic sinuses based on presence of the sign), compared to the gold standard diagnosis. Cohen's kappa was 0.60. The composite sensitivity was 91% and specificity was 86%. 9% of individuals (1/11) with clot had a positive sigmoid plate sign, compared with 86% of individuals with an atretic sinus (pϽ0.001). An absent sigmoid plate sign in the presence of MRV dropout was associated with a 60-fold higher odds (95% CI 6.45, 558) of having clot, compared to subjects with a positive sigmoid plate sign. Sensitivity and specificity improved to 100% and 92%, respectively, in the 19 cases where MRV dropout was on the right side. Conclusion: Asymmetries of the sigmoid plates on non-contrast brain CT are a very sensitive and specific measure of differentiating transverse sinus thrombosis from an atretic transverse sinus when dropout of MRV flow is visualized. Background: Approximately 25% of stroke patients have unwitnessed strokes. These patients are often ineligible for IV thrombolysis because the last known well time (LKW) was Ͼ4.5 h before ED arrival, even if their true onset time was within 3 h. Recent studies suggest that negative FLAIR MRI can be used to identify patients with LKW Ͻ 3 h. Controversy exists on the reproducibility of this technique in a clinical setting. One study reported mean kappa () agreement values regarding FLAIR negativity to be only 0.29 among 4 readers. It has been suggested that combining qualitative review of DWI and FLAIR MRI with region of interest (ROI) analysis can improve time prediction reliability. We sought to investigate interrater and intersite agreement using this approach. Methods: MRI from patients with witnessed left anterior circulation strokes within 24 h of LKW were analyzed. Two readers at 2 sites first qualitatively classified FLAIR lesions as negative or positive based on a brief description and 3 representative FLAIR images: 1 negative, 2 positive (1 subtle, 1 obvious). The signal intensity ratio (SIR) of the mean signal intensity (SI) of an ROI on the lesion to the mean SI of an ROI on the opposite side was measured. For ROI placement, readers were instructed to: (1) choose the slice with the greatest FLAIR SI that corresponds to the acute DWI lesion; (2) select the slice that matches the largest DWI lesion if FLAIR is negative; (3) select the brightest lesion in cases of multiple areas of infarct. A decision tree was created using recursive partitioning with cross-validation where the inputs were the 4 qualitative assessments and 4 SIR reads. Results: MRI from 85 patients were analyzed: 56 with LKW Ͻ 3.5 h (Early) and 29 with LKW Ͼ 3.5 h (Late). The derived tree model resulted in the rules: (1) if SIRՆ1.26, the pattern was Late. (2) Otherwise, if the patient was visually deemed FLAIR negative, the pattern was Early. (3) If the patient was visually FLAIR positive but had SIRϽ1.13, the pattern was Early. (4) Patterns not meeting any of these criteria were Late. For qualitative FLAIR reads, Fleiss' ϭ0.36, sensitivity (sens)ϭ41%, specificity (spec)ϭ80%. Intraclass correlation coefficient for SIR was 0.66. Using SIRϽ1.26 for Early or Late classification resulted in a ϭ0.45, sensϭ87%, and specϭ57%. Using the combined visual inspection and SIR, Fleiss' ϭ0.47, sensϭ66%, specϭ68% across 4 readers. Site 1 interrater ϭ0.50. Site 2 interrater ϭ0.55. Comparing the best readers at each site, intersite ϭ0.59. Conclusion: Combined FLAIR and ROI analysis produced improved agreement in classifications of Early and Late stroke patterns while maintaining good sensitivity and specificity. We obtained moderate interrater and intersite agreement using simple rules that can be easily and rapidly performed at MR consoles. With formal rigorous training on a representative dataset, agreement will likely increase substantially.

Th P100 Value of Computed Tomography Perfusion Imaging in Evaluation of Patients withTransient Ischemic Attack

Haralabos Zacharatos, Ameer E Hassan, Saqib A Chaudhry, Mushtaq Qureshi, Rizwan Husain, M. Fareed K Suri, Mustapha A Ezzeddine, Adnan I Qureshi; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: The presence of tissue at risk can be identified on computed tomography perfusion (CT-P) imaging using a combination of increased mean transit time (MTT), decreased

Introduction:

In routine clinical practice, relative cerebral blood flow (rCBF) is estimated using gadolinium-based contrast (dynamic susceptibility contrast (DSC)) magnetic resonance imaging (MRI), which is sensitive to arrival and transit delay time. Arterial spin labeling (ASL), a technique that magnetically labels blood flowing to the brain, is a non-invasive alternative that can be used to quantify cerebral blood flow. Our goal was to test whether ASL could be used to quantify rCBF values in the core, mismatch and reverse mismatch in acute ischemic stroke patients. Methods: Acute stroke patients were imaged with a 3T-Philips MRI to identify diffusion (DWI) and perfusion (ASL and DSC) deficits. Following DWI, DSC and ASL image coregistration, the acute diffusion and perfusion deficits were segmented on DWI and DSC time to peak (TTP), blinded to ASL (Figure 1a,1b). TTP was estimated using DSC. Three regions were defined: core (DWIϩ, TTPϩ), mismatch (DWI-, TTPϩ), and reverse mismatch (DWIϩ, TTP-). Resulting volumes of interest (VOIs) were mirrored across midline into the contralateral hemisphere. All VOIs were copied to the ASL images; and rCBF was calculated as the ratio of the mean signal intensity measured on the side of the lesion to that of the homologous region in the contralateral hemisphere (Figure 1c). Mismatch, reverse mismatch and core VOIs Ͼ 2cc were used for paired comparison Wilcoxon ranks test between regions. Results: Thirty patients (66.4Ϯ16.8 years) were included in the study. Patients had a median NIHSS of 9 (IQR 4-19.5). Median time from onset to MRI was 5.8 (IQR 2.6-17.3) hours. Median volumes were: DWI, 11.3 cc; TTP, 53.5 cc; core, 8.1 cc; mismatch, 41.9 cc; and reverse mismatch, 2.8 cc. The average rCBF ratios were significantly higher in the mismatch (0.51Ϯ0.23, pϽ0.05) versus the core (0.36Ϯ0.33) and reverse mismatch (0.65Ϯ0.47, pϽ0.01) versus the core (0.35Ϯ0.34).

Conclusion:

We have shown that rCBF calculated using ASL was greater in the mismatch (DWI-, TTPϩ) versus the core, suggesting relatively higher blood flow in the mismatch and supporting the concept of salvageable tissue. By using DSC for detection (of a perfusion deficit) and ASL for an independent measure of rCBF values, the strengths of each technique can be used synergistically.

Th P102 A Regional Model of Collateral Perfusion Accurately Predicts Tissue Fate in Acute Ischemic Stroke

David S Liebeskind, Fabien Scalzo, Qing Hao, Jeffry R Alger, Xiao Hu, UCLA, Los Angeles, CA; for the UCLA Collateral Investigators Background: A reliable method for prediction of tissue fate during the acute phase of ischemic stroke may be used to tailor therapeutic decisions and prognostication. Predictive models have primarily focused on numerical simulations to improve accuracy without consideration of the underlying pathophysiology of collateral perfusion. As in the pulmonary circulation, regional perfusion in the brain may vary depending on compartmental pressure differentials. We developed a regional model of collateral perfusion that incorporates such cerebrovascular physiology to predict infarct evolution from core to surrounding tissue. Methods: Consecutive cases of acute middle cerebral artery occlusion (MCAO) with serial MRI at baseline and day 5 were analyzed. Measures of cerebral perfusion pressure, tissue pressure and venous pressure were extracted from diffusion-weighted and dynamic susceptibility contrast enhanced perfusion imaging. Based on pressure differentials validated in blood flow models, we identified 3 distinct zones corresponding to core, penumbra, and benign hyperemia. Following coregistration with day 5 images, a nonlinear statistical model was used to quantify the predictive capacity of the regional maps and accuracy was compared with Tmax. Results: 42 cases (mean age 66.7Ϯ18.5 years; 26 women, 16 men) of acute MCAO with serial MRI were analyzed. Distinct zones reflecting pressure differentials between the arterial, tissue and venous compartments were constructed and displayed as parametric images. Regional zones comparable to core, penumbra, and benign hyperemia were identified. The regional model was able to accurately classify voxel outcome defined as infarction on day 5 fluid attenuation inversion recovery sequences across various grades of reperfusion. Voxel classification results revealed accuracies of 93.8Ϯ2.05% for the regional model compared with 92.2Ϯ3.25% using Tmax. Using two distinct models based on dichotomized reperfusion status, accuracies of the regional model improved to 95.7Ϯ1.9% for the regional model versus 94.4Ϯ2.5% using Tmax (no reperfusion) and 94.4Ϯ2.5% for the regional model versus 93.0Ϯ4.3% using Tmax (reperfusion). Unlike Tmax prediction, poor quality images and noise on multiparametric images limited the regional model in isolated cases. Conclusions: A regional model of collateral perfusion can reliably predict tissue fate for infarction with accuracy that exceeds Tmax prediction. Incorporation of reperfusion status and other angiographic variables can be used to maximize performance of this novel prediction algorithm derived from underlying vascular pathophysiology.

Th P110 Secondary Signal Changes And Apparent Diffusion Coefficient Decrease Of The Substantia Nigra Following Striatal Infarction

Th P115 Does Intracerebral Hemorrhage Mimic Benign Dizziness Presentations? A Population Based Study

Kevin A Kerber, James Burke, Devin Brown, William Meurer, Melinda Smith, Lynda Lisabeth, Lewis Morgenstern, Darin Zahuranec; Univ of Michigan, Ann Arbor, MI Objective: Uncertainty exists about the use of neuroimaging studies in dizziness presentations. Screening for intracerebral hemorrhage (ICH) with head computerized tomography (CT) is common even when the presentation suggests a benign dizziness disorder. As an early step in informing decisions, we used a population-based stroke database to assess the frequency with which ICH might mimic a benign dizziness presentation. Methods: The Brain Attack Surveillance in Corpus Christi (BASIC) project was used to identify cases of ICH from January 1, 2000, to December 26, 2007. The hospital records of ICH cases with a National Institutes of Health Stroke Scale (NIHSS) of Ͻ 2 were abstracted for more detailed information. Cases were classified as benign dizziness presentations when isolated dizziness and a normal general neurological examination were documented. Results were summarized using descriptive statistics. Results: Of 595 ICH cases, only 2.2% (13 of 595) had dizziness as the primary presenting symptom and an NIHSS Ͻ 2. No case mimicked a benign dizziness presentation. Only one case had isolated dizziness symptoms but this patient had dysmetria documented on the exam. All other cases had either focal or global neurological symptoms or exam abnormalities. Conclusions: No case of ICH mimicking a benign dizziness presentation was identified in this population-based stroke surveillance study. This finding raises the possibility that screening for ICH may not be necessary when dizziness is an isolated symptom and the exam is normal, but more research is required.

Th P116 Practice Variation in the Use of Neuroimaging Studies to Evaluate Emergency Department (ED) Patients with a Chief Complaint of Dizziness

Anthony Kim, UCSF, San Francisco, CA; Steve Sidney, Kaiser Permanente Div of Rsch, Oakland, CA; Jeffery G Klingman, Kaiser Permanente Med Cntr, Walnut Creek, CA; S. Claiborne Johnston; UCSF, San Francisco, CA Background: Stroke is an important consideration when evaluating ED patients with dizziness symptoms. However, head CTs are relatively insensitive to posterior circulation stroke and involve radiation exposure, whereas more-sensitive brain MRI studies are costly and must be targeted to the most appropriate patients. Despite these challenges, practice variation in the use of neuroimaging studies the impact of this variation on stroke diagnoses has not been well described. Methods: We reviewed comprehensive electronic medical records for all adults with a chief complaint of dizziness who were evaluated at the 20 EDs of a large Northern California integrated health care program in 2008. Patient demographics, vascular risk factors, and subsequent diagnoses of stroke were abstracted from medical records. The primary outcome was a head CT or brain MRI within two days of the initial ED presentation. We used a random-effects logistic model to account for patient-level differences in demographics and vascular risk factors at each facility. Results: Of 378,992 adult patients seen in 2008, dizziness was listed as a chief complaint in 20,795 (5.5%) patients, varying from between 3.3% and 8.5% of all patients at each site. Overall, 5,585 (26.9%) patients had a head CT and 652 (3.1%) had a brain MRI. The proportion of patients who had any neuroimaging varied from a low of 21.8% to a high of 32.8%, which represents a 1.5-fold difference in centers with the lowest and highest rates of neuroimaging (pϽ0.001, Figure ). Differences in patient-level factors_including age, sex, and vascular risk factors (hypertension, hyperlipidemia, diabetes, and atrial fibrillation) as well as differences in site-level factors such the proportion of patients with dizziness and the proportion of patients with dizziness who were admitted to hospital_did not account for the variation in neuroimaging rates. Higher neuroimaging rates by site was not associated with a greater number of strokes diagnoses (Figure ), with an incidence of stroke diagnosis of 2.4% overall and a range of 1.7% to 3.4% by site. Conclusion: There is substantial variation in the use of neuroimaging for ED patients with dizziness without an associated improvement in detection of stroke. This suggests that standardized methods for targeting imaging to the most appropriate patients have the potential to reduce low-yield neuroimaging without sacrificing diagnostic accuracy. This research has received full or partial funding support from the American Heart Association, National Center.

Author Disclosures: A. Kim: None. S. Sidney: None. J.G. Klingman: None. S. Johnston: None.

Th P117 Transient Isolated Dysphasia is Associated With a High Rate of Potential Cardiac Sources for Embolism

Jason K Wasserman, Univ of Ottawa, Ottawa Hosp Rsch Institute, Ottawa, Canada; Jeff J Perry, Dar Dowlatshahi, Grant Stotts, The Ottawa Hosp, Ottawa Hosp Rsch Institute, Ottawa, Canada; Marco Sivilotti, Queens Univ Dept. Emergency Medicine, Kingston, Canada; Andrew Worster, McMaster Univ, Dept. Emergency Medicine, Hamilton, Canada; Marcel Emond, Laval Univ, Dept. Emergency Medicine, Quebec, Canada; Jane Sutherland, Ottawa Hosp Rsch Institute, Ottawa, Canada; Ian Stiell, Mukul Sharma; The Ottawa Hosp, Ottawa Hosp Rsch Institute, Ottawa, Canada Background: A cardiac source is often implicated in strokes in which the deficit includes aphasia. However, much less is known about the etiology of isolated dysphasia after transient ischemic attack (TIA). Objective: To determine if patients with transient ischemic attack, presenting with isolated dysphasia are more likely to have a potential cardiac source for embolism than those with other forms of transient ischemic attack. Methods: We prospectively identified and followed a cohort of patients receiving a final diagnosis of TIA in eight Author Disclosures: J.R. Romero: Other Research Support; Significant; GlaxoSmithKline, support research project cerebral microhemorrhages. H. Lau: None. A. Pikula: None. H. Artinian: None. T. Nguyen: None. M. Ogrodnik: None. F. Koyfman: None. C.S. Kase: None. V.L. Babikian: None.

Th P125 TeleStroke 2010: A Survey of Currently Active Stroke Telemedicine Programs in the US

Gisele S Silva, Universidade Federal de Sa ˜o Paulo, Sa ˜o Paulo, Brazil; Anand Viswanathan, Emma Shandra, Lee H Schwamm; Massachusetts General Hosp, Boston, MA Introduction: Little is known about adoption or success of telestroke networks outside of federally funded programs or those reported in the literature. Our objective was to conduct an environmental scan of telemedicine-based (telestroke) stroke programs in the United States. Hypothesis: We hypothesized that US telestroke programs have diverse structures but face similar obstacles. Methods: We conducted Google and Pubmed searches to find any potential telestroke programs operating since 2000. A dedicated project analyst contacted all identified programs, interviewed respondents in-depth and collected online survey data using a tool developed to assess various structural and functional aspects of the programs. Results: In total, 100 possible programs in 43 states with active telestroke programs were identified and 38 programs agreed to participate. The programs that did not participate were similar to the ones that did, in terms of county level data (total population, % population age Ն25 yr, % of individuals below poverty line), annual hub hospital admissions, number of beds and annual emergency department (ED) visits. The top 3 clinical needs met by the telestroke programs were: ED consultation (100%), patient triage (83.8%), and inpatient teleconsultation (46.0%). The median telestroke program length was 891 days [495.5, 1256]. Most of the programs (94.6 %) used two-way, real-time interactive video plus teleradiology to support the consultation process. Dedicated telemedicine software was used by 44.44% of the programs to document and store consults. The mean number of spokes per hub increased from 2007 to 2009 (3.78 vs. 7.60; PϽ0.05; range 0-28). In 65.5% of hubs, more than 80% of spoke sites were rural and in 51.7% of hubs, more than 80% of spokes were small hospitals (0-99 beds). Background&Purpose: Telemedicine aids selection of stroke patients who may require an emergency transfer to a comprehensive stroke center to receive additional therapies other than intravenous (IV) thrombolysis. We report our experience on emergency transfers within the telemedicine Stroke East Saxony Network (SOS-NET) of 14 cooperating hospitals covering a population of 1.7 million people in eastern Saxony, Germany. Subjects&Methods: We reviewed consecutive acute stroke patients who were transferred emergently from remote spoke sites to our comprehensive stroke center. Teleconsultations were performed 24-hours/day by certified stroke neurologists with access to high-speed videoconferencing and transfer of neuroimages. Recommendation for emergent transfers was given by the stroke neurologist on service. Clinical data including National Institutes of Health Stroke Scale (NIHSS) score at baseline and the modified Rankin Scale (mRS) score at discharge were prospectively documented in the databank of the telestroke service. Favourable outcome at discharge was defined as mRS scores 0-2. Results: In 2009, we conducted 550 teleconsultations and recommended transfer in 139 (25%) patients (mean age 64Ϯ14 years, 55% men, median NIHSS score 6 [interquartile range 3-16.5]). The mean time from teleconsultation to arrival at our stroke center was 1.8Ϯ0.9 hours. Twenty-nine (21%) emergent transfers had a non-stroke diagnosis (brain tumours, 9 [6%]; seizures, 5 [4%]; other etiologies, 15 [11%]). The remaining 110 tranferred patients had stroke diagnoses (ischemic strokes, 47 [34%]; transient ischemic attacks, 5 [4%]; intracranial hemorrhages [ICH], 58 [42%]). Of the 47 ischemic stroke patients, 12 (26%) received IV tPA at spokes ("drip&ship"). Intra-arterial reperfusion procedures were performed in 6 (13%) and decompressive hemicraniectomy was done in 6 (13%) ischemic stroke patients. In ICH patients, acute interventions were: endovascular procedures, 3 (5%); neurosurgical hematoma evacuation, 19 (33%); aneurysm clipping, 3 (5%); and additional or isolated external ventricular drainage, 13 (22%). At discharge, 37 (34%) stroke patients had a favourable outcome while mortality rate was 9%. Conclusions: Telemedicine based selection of candidates for transfer to a comprehensive stroke center can be a beneficial concept for stroke patients by delivering interventional stroke therapies that require advanced multispecialty experts. Objective: To study the perceived quality of informed consent for thrombolysis in acute ischemic stroke (AIS) patients receiving IV-tPA. Methods: Videotapes of 14 randomly selected telestroke cases with IV tPA administered were independently reviewed for adequacy of informed consent by 5 independent raters: a neurologist and emergency physician who routinely treat stroke, a medical risk management paralegal, a bioethicist, and a lay person. A 4 point Likert scale (insufficient (0), poor (1), adequate (2), exceeds expectations (3)) was used to assess the quality of the informed consent presentation by the treating physician (MD) and the degree of understanding demonstrated by the patient or family (Pt-Fam) authorizing consent. Factors associated with adequacy of consent (age, sex, education level, duration of consent, NIHSS, Pt vs. family) were analyzed by t-test or Wilcoxon, inter-rater reliability by kappa. Results: All patients were English speaking with a mean age of 69 Ϯ 15.8 and median NIHSS score 11.5. Family members gave primary consent in 50% of cases after a mean duration of consent lasting 2.7 Ϯ 1.3 min. Consent was rated adequately understood by Pt-Fam in 78.6% cases. There were no significant differences between the two groups (Table ). Distribution of scores varied between raters (Figure). The inter-rater reliability between all 5 raters, the 2 MD or the 3 non-MD raters was (kϭ0.07 vs. 0.24 vs. -0.06) for quality of MD consent and (kϭ 0.12 vs. -0.06 vs. 0.17) for Pt-Fam understanding, respectively. Median Pt-Fam understanding ratings did not differ from MD consent ratings (Pt-Fam ϭ 2 [IQR 2-2] vs. MD rating ϭ 2 [2-3]). Consent interactions rated unacceptable (insufficient or poor) with regards to Pt-Fam understanding also had (non-significantly) lower ratings for MD consent performance when compared to cases with higher Pt-Fam ratings (1.67 vs 2.45; pϭ0.21). Conclusion: Despite high variability in the perceived quality of informed consent in this time-sensitive clinical situation, almost 80% of patients were rated by all reviewers as having adequate understanding of risks and benefits of tPA. The telestroke consent scenario likely reflects in-person practice. This study suggests the need for a standardized but brief tPA consent process that includes patient/family demonstration of understanding. Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Introduction: Organized systems of acute stroke care improve delivery. The hospitals of Orange County, CA, the 5th most populous US county (3.1 million over 789 sq miles), met over 5 years in a grass roots effort with Emergency Medical Services to establish Stroke Neurology Receiving Centers (SNRC), which would receive patients from 911 calls for suspected stroke Ͻ5 hr old. The system became policy May, 2009, with 9 hospitals designated as SNRC agreeing to provide acute stroke care compliant with AHA guidelines; note that 8/9 were JCAHO stroke center or AHA-GWTG at system inception. The current report describes the first year experience. Methods: Each SNRC completed a form for each patient admitted under this system. Missing data were not imputed. Results: From April 2009-April 2010, 1,364 patients with suspected stroke Ͻ 5 hr old were evaluated at the 9 SNRCs. Primary discharge diagnosis (nϭ1,110) included ischemic stroke (49%) and hemorrhagic stroke (19%). Mean age was 74 yrs (range 8-103). Time of arrival was unevenly distributed, e.g., 23% of arrivals were between 11am -2pm. Median NIHSS score was 7 on admit (nϭ932) and 3 on discharge (nϭ683). Gender was 55% F / 45% M, with F having higher baseline NIHSS than M (8 vs 7, p Ͻ 0.04). Patients were 74% Caucasian, 12% Asian, 9% Hispanic, 1% Black, 4% other; baseline NIHSS differed by ethnicity (pϽ0.001), being higher in Asian and Hispanic patients. Acute therapy was IV tPA in 110 (20.2% of ischemic strokes) and IA procedure in 42 (7.7%); for both, baseline NIHSS was higher (pϽ0.0001) among those so treated, e.g., NIHSSϭ12 with IV tPA therapy vs. 7 no IV tPA. Change in NIHSS score from admit to discharge was larger among those who did, vs. did not, receive IV tPA (6 vs. 1 point, p Ͻ 0.0001). Time from door to IV tPA averaged 86 minutes. Death occurred in 11%, and did not vary in relation to IV tPA. There was no significant change over the 12 months in baseline NIHSS, use of IV tPA or IA therapy, death, or time from door to treatment. Conclusions: In the first year of this system, we found that women, minorities, and patients receiving acute therapy had more severe strokes. IV tPA, given in Ͼ20% of ischemic strokes, significantly reduced impairment with no effect on survival. Important aspects of the program include spoke hospital transfer to SNRC without option of diversion; and SNRC requirements for community outreach, neurosurgical capabilities, and stroke specific rehabilitation programs. A countywide stroke response system, organized among hospitals most of which were organized stroke centers at the start, can provide effective stroke care. Results: Three different data sharing methodologies have been developed. M1, in three unique attempts, yielded successful match rates of 47%, 50%, and 53%. This method may be inadequate as suggested by the low match rates. The success rate of M2 was close to 100%. This model proved successful from a data perspective but requires considerable human resources. The process for M3 is undergoing refinement and the results will be forthcoming. M3 appears promising and plans are underway to develop a secure web-based portal for use by the LEMSAs and the CSR to facilitate data sharing and report generation. Discussion: As Stroke Systems of Care are developed and implemented throughout California, it is imperative that data inform the process. In particular, data should be used to optimize decision-making regarding the treatment, transport, and destination of suspected stroke patients and to support continuous quality improvement efforts. In California, the CSR and the LEMSAs are working to make this happen.

Th P135 Recruitment of Ischemic Stroke Patients in Clinical trials in General Practice and Implications for Generalizability of Results

M. Fareed K Suri, Adnan I Qureshi, Mustapha A Ezzeddine; Zeenat Qureshi Stroke Rsch Cntr, Univ of Minnesota, Minneapolis, MN Background: While results of clinical trials are used to impact practice among patients with ischemic stroke, very little information is available regarding proportion and characteristics of patients recruited in clinical trials in general practice. Methods: We performed this analysis to provide an audit of recruitment in clinical trials among patients with acute ischemic stroke using data from University Healthsystems Consortium (UHC) benchmarking project. A review of 40 consecutive ischemic stroke cases meeting inclusion criteria and discharge within a 6 month period was conducted in 32 hospitals. We performed a multivariate analysis to identify demographic and clinical factors associated with recruitment of patients with ischemic stroke into clinical trials. Results: A total of 1256 patients (mean age 67 years, range 18-99 years) were included. Most presented through the emergency department (nϭ1035). A total of 77 (6%) patients were recruited in clinical trials; 33 and 14 patients recruited in drug or device trials, respectively. In the multivariate analysis, age under 80 years (odd ratio [OR] 2.3, 95% confidence interval [CI] 1.1 -5.1), white or African-American race as compared with others (OR 2.6, 95% CI 1.0 -6.9), evaluation by a neurologist or stroke team (OR 15, 95% CI 2.0 -108), and the use of intravenous thrombolysis (OR 7.2, 95% CI 4.1 -13) were associated with recruitment in clinical trials. There was no relationship between patient's gender and recruitment in clinical trials. The rate of intracranial hemorrhage (6% vs 2%, PϽ0.05) and progression of stroke (12% vs 3%, PϽ0.05) were higher among those recruited in clinical trials. Conclusions: Only a minority of patients with ischemic stroke in practice are recruited into clinical trials. Patients recruited in clinical trials appear to have different characteristics from those who are not recruited limiting the generalizability of results from current trials.

Author Disclosures: M.K. Suri: None. A.I. Qureshi: None. M.A. Ezzeddine: None.

Th P136 Un-witnessed Stroke: Impact of Different Onset Times on Eligibility into Stroke Trials

Matthew B Maas, Aneesh B Singhal; Massachusetts General Hosp, Boston, MA Background: In patients with un-witnessed stroke the actual onset time is variable; e.g. for 'wake-up' strokes the onset may be closer to the time first seen abnormal (FSA). Trials enrolling patients with un-witnessed stroke onset (over 25% of all strokes) have conservatively used 'last seen well' (LSW) as the time of stroke onset, which is appropriate given time-sensitive risks. While this LSW approach is appropriate to minimize risk with thrombolysis, it limits patient recruitment. In a NINDS funded phase II acute stroke trial of normobaric oxygen (NBO) therapy, we used the mid-point between LSW and FSA. The rationale was to assess the safety of hyperoxia at delayed timeframes. Here we explored the impact of alternative methods of determining onset time, on trial eligibility. Methods: We analyzed 641 consecutive patients with suspected stroke presenting to our hospital from Jan 2007 to July 2008. Time of onset was calculated by threeMethods: (1) LSW, (2) FSA, (3) midpoint between LSW and FSA. Subjects with incomplete data or a non-ischemic stroke final diagnosis were excluded. Rates of NBO trial eligibility based on different onset times were compared, with 9 hours being the inclusion time window. Results: Onset time was known in 440 subjects (69%). Of the remaining 201 patients with un-witnessed onset, 114 (57%) were 'wake-up' strokes. Among un-witnessed stroke subjects (Figure 1), eligibility increased from 42.2% using LSW, 63.2% using the midpoint, and 80.6% using FSA (Chi square PϽ0.001). The impact on overall enrollment for the full cohort (Figure 2) was still significant with an increase from 61% to 67% to 73% (pϽ0.001). Conclusion: Given potential advantages in safety evaluation and inadequate enrollment rates in acute stroke trials, alternative onset time definitions, perhaps in combination with advanced neuroimaging methods of onset time estimation (e.g. FLAIR-DWI mismatch), should be considered for early phase trials. Background Federal research guidelines mandate that health researchers obtain accurate, complete, timely data and monitor study subjects for serious adverse events. Barriers to accessing medical records to fulfill these requirements are growing, including misinterpretation of HIPAA regulations and increasing use of electronic medical records (EMRs) that are not readily available to research coordinators and monitors. The NIH Field Administration of Stroke Therapy -Magnesium (FAST-MAG) study is a large stroke trial in Los Angeles. Research staff at a centralized research center coordinates the study at 50 hospitals and multiple other care facilities. This design allows for significant information sharing regarding the process of obtaining data. Purpose To describe the challenges for researchers in accessing study subjects' medical record data, in light of HIPAA and the transition from paper-based medical records to EMRs. Methods A survey and focus group discussion with 8 FAST-MAG research staff was performed for a descriptive analysis of the challenges faced in obtaining study data. Results Among the 50 participating hospitals, 8 now employ solely EMRs, 11 remain completely paper-based, and 31 use a combination of both. We identified 13 reported challenges in the overall process of obtaining research data. The most frequently encountered barriers to obtaining data were 1) limited local nursing staff knowledge regarding how to print EMRs, and 2) delays in obtaining medical records after discharge. Also frequent, and particularly distressing to the research nurses, were: 3) local nursing staffs' ambivalence or lack of knowledge regarding the appropriate use of HIPAA for research, and 4) the burdensome task of becoming familiar with an immense variety of documentation systems. Conclusions: Hospital staff and systems need to focus on accuracy of research data and ease of obtaining study pertinent data, all the while increasing the privacy of patients' records. Based on the experiences of study nurses, a number of proactive solutions are available to facilitate obtaining medical records. It is invaluable to develop rapport by having one dedicated research RN assigned to each site to identify key personnel, and maintain successful working relationships. It is beneficial to credential research staff as authorized users of site EMRs and to work with site IT staff to create study-specific printing instructions for the staff nurses to use. Ideally, a study specific print option can and should be generated specifically for the study purposes and be made accessible to staff nurses when presented with a signed research HIPAA. This would minimize staff's time, increase accuracy of data, and assure that only study data is transferred, thereby increasing patient privacy.

Th P138 P2Y12 Receptors In Ischemic Inflammation: A New Role For Clopidogrel?

Carla Webster, Genentech, South San Francisco, CA; April McManus, Masaaki Hokari, Xian Nan Tang, Midori A Yenari; UCSF, San Francisco, CA Background: Microglia are among the first immune cells to respond to ischemic insults. Triggering of this inflammatory response is not precisely known, but may involve extracellular release of nucleotides from necrotic cells which bind microglial purinergic receptors. One such receptor, P2Y12, implicated in chemotaxis, is the receptor to which clopidogrel binds and inhibits. Methods: Primary murine enriched neuronal cultures were prepared with or without the addition of microglia (BV2 cell line), them subjected to oxygen glucose deprivation. siRNA was used to knockdown P2Y12 or NFkB in BV2 cells. Mice deficient in P2Y12, or wildtype littermates (nϭ6/group), were subjected to 12 min forebrain ischemia and hippocampal CA1 counts were assessed 72 h later. Results: The addition of microglia to enriched-neuron cultures increased neuron damage following OGD (oxygen glucose deprivation). Microglia formed clusters around these neurons following OGD. P2Y12-deficient microglia prevented increased neuron injury (pϽ0.05) and prevented microglial clustering (pϽ0.05). Deficiency of NF-kappaB, a major immune transcription factor in microglia led to similar observations (pϽ0.05). To delineate a link between P2Y12 and NF-kappaB activation, added ATP (P2Y12 agonist) increased NF-kappaB activation at potentially pathologic concentrations. Migration assays showed that OGD-conditioned media from neurons, but not astrocytes, led to microglial migration. P2Y12 deficient mice subjected to forebrain ischemia also suffered little hippocampal injury compared to wildtype mice (pϽ0.05), suggesting a toxic potential of the P2Y12 receptor. Conclusions: P2Y12 signaling through NF-kappaB appears to play a role in microglial activation and neurotoxocity under ischemic/ischemia-like conditions. We demonstrate a role of P2Y12 in ischemia in terms of microglia-mediated neurotoxicity, and suggests a potential additional benefit of clopidogrel.

This research has received full or partial funding support from the American Heart Association, National Center.

Th P139 Effect of Normobaric Oxygen Therapy in a Rat Model of Intracerebral Hemorrhage

Aneesh B Singhal, Norio Fujiwara, Emiri T Mandeville, Ken Arai, Eng H Lo; Massachusetts General Hosp, Boston, MA Background: Recent studies suggest that early normobaric oxygen (NBO) therapy is neuroprotective in acute ischemic stroke. Since NBO may be most effective as a pre-hospital therapy (before a definite diagnosis of ischemic versus hemorrhagic stroke can be established), it is important to understand the effects of NBO on intracerebral hemorrhage (ICH). In this study, we tested the effects of NBO in a rat model of striatal ICH. Methods: ICH was induced by stereotactic injection of collagenase type VII (0.5U) into the right striatum of anesthetised male Sprague-Dawley rats. One hour later, rats were randomized into Controls (nϭ13) vs NBO treatment (nϭ13). NBO was applied for two hours. Hemorrhagic blood volume and brain water content were quantified at 72 hours after injection. Neurological outcomes (forelimb placement test, forelimb asymmetry, neuroscore) were assessed at 72 hours post-ICH. Results: NBO did not worsen hemorrhage severity or brain edema (Figure). There were no significant differences in hemorrhagic blood volumes (Control, 6.4Ϯ0.9l versus NBO, 7.0Ϯ2.1l, pϭ0.18) or brain water content (Control, 81.9Ϯ1.1% versus NBO, 81.6Ϯ0.5%, pϭ0.58). NBO did not affect any of the neurological outcome tests. Forelimb placement was significantly affected by ICH (NBO contralateral, 21.5Ϯ11% vs ipsilateral, 88.5Ϯ13%, PϽ0.01, Controls; contralateral, 14.6Ϯ9% vs ipsilateral, 86.1Ϯ10%, PϽ0.01), however there was no significant difference between NBO and Controls. NBO also had no significant effect on the forelimb asymmetry test (NBO, 26.0Ϯ39% vs Controls, 31.1Ϯ33%). Finally, according to the 5-point neuroscore scale, NBO did not affect mortality and neurologic outcomes.

Th P140 BNIP3 Mediates Autophagic Neuronal Death in Stroke Through a Mechanism Involving Beclin 1

Ruoyang Shi, Jiequn Weng, Ling Zhao, Jiming Kong; Univ of Manitoba, Winnipeg, Canada Excessive autophagy has been implicated in delayed neuronal death in stroke. The aim of the present study is to determine the role of BNIP3 in autophagic neuronal death. We performed immunohistochemistry, quantitative western blot, immunoprecipitation, cell transfection, RNA interference and electron microscopy to analyze the expression and localization of BNIP3 and autophagy markers in degenerating primary neurons in an oxygen and glucose deprivation (OGD) model of stroke, and in a neonatal cerebral ischemia/hypoxia (I/H) animal model. In primary neuronal cultures exposed to OGD for 6 hours followed by reperfusion (RP) for 24, 48 and 72 hours, respectively, an increase of autophagy was observed as determined by the ratio of LC3-II to LC3-I, an autophagy marker protein. Using Fluoro-Jade C and MDC double-staining, and electron microscopy we found that the increment in autophagy after OGD and RP injury was accompanied by increased autophagic cell death rates, while this increase could be attenuated by the specific autophagy inhibitor, 3-Methyladenine (3-MA). The death-inducing gene BNIP3 was highly expressed in neurons exposed to OGD. We proved that the time course and expression levels of Beclin 1 (BECN1), an autophagy-regulating protein, correlated with the expression of BNIP3. Knockdown of BNIP3 by miRNA reduced OGD-induced Beclin 1 expression Author Disclosures: Y. Yagita: None. T. Sasaki: None. N. Oyama: None. Y. Sugiyama: None. Y. Terasaki: None. E. Omura-Matsuoka: None. K. Kitagawa: None. The MRI signal obtained is however not specific for the SPIO labeled stem cells and experimental paradigms rely on histological verification using Prussian Blue staining. Here we explored synchrotron X-ray fluorescence imaging using a hard X-ray microprobe in continous rapid scanning mode to detect iron in SPIO labeled stem cells after intravascular transplantation in an experimental stroke model. XRF allows element-specific quantitative mapping of metals both in an entire brain section and of individual cells at 3 micron resolution with greater speed than traditional microprobes. Methods: Stroke was induced in NodScid mice using a hypoxia-ischemia model. Animals underwent unilateral temporary common carotid artery (CCA) occlusion followed by exposure to 8% O2 for 20 minutes and subsequent reperfusion. On day 3 after stroke 5x105 SPIO labeled human derived embryonic neural progenitor cells (hNPC) expressing a luciferase reporter gene were injected into the ipsilateral CCA. Control animals received either stereotactic intraparenchymal injection of 5x105 SPIO labeled hNPC or saline. Bioluminescence imaging and MRI using a FIESTA sequence were performed 24 hours after cell injection. After transcardial perfusion and slicing at 30m, whole brain sections were scanned at the Stanford Synchrotron Radiation Lightsource on beamline 2-3 with specific subregions imaged with 3m spot size and at 200 ms per point. Sections were then stained with Prussian Blue and human specific antibodies. Results: Bioluminescence imaging and MRI demonstrated significant homing of hNPC to the ischemic hemisphere but not to the contralateral hemisphere (pϽ0.01). Typical areas of susceptibility artifact were seen in the cortex, the hippocampus and to a lesser extent in the striatum. RS-XRF depicted distinct areas of Fe signal distributed in the ischemic hemisphere correlating with MRI findings. High-resolution scans depicted single cells in clusters with an average iron content of 7.0632pg. Intraparenchymal cell grafts appeared as focal signal on MRI and RS-XRF. Saline controls produced a needle shaped artifact on MRI, which correlated to a Fe signal on RS-XRF very distinct from the cellular morphology of SPIO labeled hNPC. Prussian blue staining correlated with RS-XRF imaging. Conclusions: The synchrotron X-ray microprobe in rapid-scanning mode allows high-resolution quantitative Fe specific imaging of single cells. Here we demonstrate its application in a multimodality imaging paradigm to track SPIO labeled hNPC in a stroke model. We found excellent correlation between Bioluminescence imaging, MRI, RS-XRF and histology. This research has received full or partial funding support from the American Heart Association, National Center.

Th P145 High Resolution Rapid Scanning X-ray Fluorescence Imaging To Track SPIO Labeled Neural Stem Cells In An Experimental Stroke Model

Author Disclosures: J.Y. Chua: None. Z. Tymchak: None. W. Zheng: None. H. Nichol: None. M. Kelly: None. R. Guzman: None.

Th P146 Tissue Plasminogen Activator Induces Vasoconstriction in Acute Ischemic Stroke Rat Model

Author Disclosures: S.D. Woods: Research Grant; Significant; NIH R01 HL082481. R. Flores: Research Grant; Significant; NIH R01 HL082481. J.D. Lowery: Research Grant; Significant; NIH R01 HL082481. W.C. Culp: Research Grant; Significant; NIH R01 HL082481.

Th P148 Neuroprotective Effect of TAK-937, a Novel Cannabinoid Receptor Agonist, in a Nonhuman Primate Thromboembolic Stroke Model

Motohisa Suzuki, Kazuhiro Hamajo, Noriko Suzuki, Koji Murakami, Tetsuya Tsukamoto, Masato Shimojo; Takeda Pharmaceutical Company Limited, Osaka, Japan Introduction: TAK-937 is a novel, highly potent and selective cannabinoid (CB1/CB2) receptor agonist. In the previous studies, TAK-937 has demonstrated neuroprotective effects in rat transient and permanent middle cerebral artery (MCA) occlusion models. In this study, the effect of TAK-937 was examined in a non-human primate (cynomolgus monkey) thromboembolic stroke model to determine if these effects translate phylogenetically across species. Methods: Thromboembolic stroke in male cynomolgus monkeys was induced by injection of an autologous blood clot into the left internal carotid artery to occlude the MCA. Intravenous Author Disclosures: M. Suzuki: Employment; Significant; Takeda Pharmaceutical Company Limited. K. Hamajo: Employment; Significant; Takeda Pharmaceutical Company Limited. N. Suzuki: Employment; Significant; Takeda Pharmaceutical Company Limited. K. Murakami: Employment; Significant; Takeda Pharmaceutical Company Limited. T. Tsukamoto: Employment; Significant; Takeda Pharmaceutical Company Limited. M. Shimojo: Employment; Significant; Takeda Pharmaceutical Company Limited.

Th P149 Granulocyte Colony-Stimulating Factor Enhances Arteriogenesis and Ameliorates Cerebral Damage in a Mouse Model of Ischemic Stroke

Yukio Sugiyama, Yoshiki Yagita, Naoki Oyama, Yasukazu Terasaki, Emi Omura-Matsuoka, Tsutomu Sasaki, Kazuo Kitagawa; Osaka Univ Graduate Sch of Medicine, Osaka, Japan

Table of Contents

• Abstract Abstract Background and Purpose: Enhancing collateral artery growth is a potent therapeutic approach to treat ischemic cerebrovascular disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has gained attention for its ability to promote arteriogenesis, ameliorating brain damage, by the mechanisms involving monocyte up-regulation. However, the recent clinical study testing its efficacy in myocardial ischemia has raised the question about its safety. It may increase vulnerability of atherosclerotic plaque to rupture. Here we tested alternative colony stimulating factors for their effects on collateral artery growth and brain protection. Methods: Brain hypoperfusion was produced by occluding left common carotid artery (CCA) in C57/BL6 mice. Following the surgery, G(granulocyte)-CSF, M(macrophage)-CSF, GM-CSF (100 g/kg/day), or vehicle (normal saline) was administered subcutaneously for 5 consecutive days. The angio-architecture for leptomeningeal anastomoses was visualized by latex perfusion 2 days after the CSF treatment (nϭ5, each group). A set of animals underwent subsequent permanent ipsilateral middle cerebral artery (MCA) occlusion and infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining (nϭ6, each group). Circulating blood monocytes were counted by the hematology analyzer and blood smear examination (nϭ5, each group). Mac-2 positive cells in the dorsal surface of the brain were determined by immunohistochemistry (nϭ7, each group). Results: G-CSF as well as GM-CSF promoted leptomeningeal collateral growth after CCA occlusion (G-CSF, 27.5Ϯ1.3 m, 61 vessels, GM-CSF, 28.0Ϯ1.8 m, 59 vessels vs vehicle, 22.5Ϯ0.9 m, 60 vessels, PϽ0.01, respectively). Infarct volume following MCA occlusion was reduced by G-CSF, similarly to GM-CSF (G-CSF, 35.4Ϯ4.7 mm 3 , GM-CSF, 38.0Ϯ4.1 mm 3 vs vehicle, 53.1Ϯ5.2 mm 3 , PϽ0.05, respectively). Both G-CSF and GM-CSF increased circulating blood monocytes (G-CSF, 547.8Ϯ/114.1l, GM-CSF, 536.8Ϯ138.0/l vs vehicle, 101.0Ϯ34.4/l, PϽ0.01, respectively) and Mac-2 positive cells in the brain dorsal surface (G-CSF, 107.4Ϯ14.6, GM-CSF, 104.6Ϯ10.1 vs vehicle, 51.4Ϯ4.9, PϽ0.01, respectively), suggesting the mechanisms coupled to monocyte up-regulation might be shared. M-CSF showed none of theses effects. Conclusion: G-CSF enhances collateral artery growth and reduces infarct volume in a mouse model of brain ischemia, similarly to GM-CSF.

Author Disclosures: Y. Sugiyama: None. Y. Yagita: None. N. Oyama: None. Y. Terasaki: None. E. Omura-Matsuoka: None. T. Sasaki: None. K. Kitagawa: None.

Th P150 AMPK Regulates Ischemic Cell Death through GSK3-Beta

Sharon Benashski, Jun Li, Louise McCullough; Univ of Connnecticut Health Cntr, Farmington, CT Introduction: Cerebral ischemia can lead to energy failure and thus cell death. AMP-activated protein kinase (AMPK) is involved in an array of cellular cascades activated to deal with changing cellular energy status during cerebral ischemia. Acute activation of AMPK via phosphorylation occurs after stroke and leads to an exacerbation of ischemic injury. Metformin is an AMP-activated protein kinase (AMPK) activator. Although acute AMPK activation is detrimental in stroke, chronic metformin treatment improves stroke outcome by downregulating AMPK. Glycogen synthase kinase 3-␤ (GSK3␤) is a downstream effecter of AMPK. It has been reported that GSK3␤ inhibition in stroke is protective by preserving a cellular survival factor ␤-catenin. In this study, we evaluated the hypothesis that inhibition of AMPK by chronic metformin is neuroprotective by inhibiting GSK3␤. Methods: Focal stroke was induced by reversible middle cerebral artery occlusion (MCAO-90 minutes) in male wild-type (WT) mice treated with vehicle or 50 mg kg -1 (i.p.) Metformin for 3 weeks prior to MCAO. Stroke outcome was determined with CV staining at 24 hrs following MCAO. Phosphorylated GSK 3␤ (inactivated form), ␤-catenin and AMPK phosphorylation were determined by Western blot at 4 hours following MCAO. Protein levels were normalized to total GSK3␤. Data were presented as meanϮsem PϽ0.05. Results: Chronic treatment with Metformin reduced infarct size 24 hours after stroke both in the striatum and total hemisphere (Cortex: 48.3Ϯ2.1% vs. 32.1Ϯ6.6%; Striatum: 53.6Ϯ4.0% vs. 45.3Ϯ2.9% PϽ0.05, Total: 45.3Ϯ2.9% vs. 29.3Ϯ4.9%, PϽ0.05). Western blots demonstrated chronic metformin reduced pAMPK levels. Stroke induced an increase in pGSK3␤ 4 hours after stroke (0.4Ϯ0.4 Vehicle Sham vs 2.1Ϯ 0.4 Vehicle Stroke). Chronic metformin treatment further enhanced the stroke-induced increase in pGSK3␤ (1.9Ϯ 0.1 Sham vs 7.4Ϯ 3.6 Stroke). In addition stroke induced a decrease in ␤-catenin 4 hours after stroke and this decrease was eliminated by chronic metformin treatment. Conclusion: Chronic metformin treatment increased pGSK3␤ (inactivated form) that in turn ameliorated the decrease of ␤-catenin seen in vehicle treated animals. Our data demonstrated that in the ischemic brain, inhibition of AMPK inactivates pGSK3␤ and increases ␤-catenin activity. Our study suggested that GSK3␤ may contribute to the effect of AMPK in stroke by regulating beta-catenin.

Th P168 Nationwide Survey of Expert Opinions about Resuming Anticoagulant Therapy After Intracerebral Hemorrhage for Patients with Nonvalvular Atrial Fibrillation

Koichiro Maeda, Masatoshi Koga, National Cerebral and Cardiovascular Cntr, Osaka, Japan; Yasushi Okada, National Hosp Organization Kyushu Med Cntr, Fukuoka, Japan; Kazumi Kimura, Kawasaki Med Sch, Kurashiki, Japan; Hiroshi Yamagami, Kobe City Med Cntr General Hosp, Kobe, Japan; Satoshi Okuda, National Hosp Organization Nagoya Med Cntr, Nagoya, Japan; Yasuhiro Hasegawa, St Marianna Univ Sch of Medicine, Kawasaki, Japan; Yoshiaki Shiokawa, Kyorin Univ Sch of Medicine, Mitaka, Japan; Eisuke Furui, Kohnan Hosp, Sendai, Japan; Jyoji Nakagawara, Nakamura Memorial Hosp, Sapporo, Japan; Kazuomi Kario, Jichi Med Univ, Shimotsuke, Japan; Tomohisa Nezu, Kaoru Endo, Tetsuya Miyagi, Kazuo Minematsu, Kazunori Toyoda, National Cerebral and Cardiovascular Cntr, Osaka, Japan; the Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) Study Inve Background and Purpose: Warfarin-related intrecerebral hemorrhage (ICH) in patients with atrial fibrillation (AF) is associated with high incidence of subsequential hematoma enlargement and high mortality. Conversely, withholding of warfarin has a potential risk to develop thromboembolic complications such as embolic stroke. There is a considerable dilemma concerning when to resume anticoagulant therapy following ICH, because there is no established guideline for appropriate antithrombotic therapy in acute ICH patients with AF. We conducted a nationwide survey regarding resumption of anticoagulant therapy in patients with acute ICH on warfarin with nonvalvular AF. [Methods] A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with nonvalvular AF was mailed to physicians responsible for ICH management at 416 hospitals in October 2009. [Results] Of those mailed, 329 physicians (79%) responded with a filled-in questionnaire. On admission, all respondents stopped oral warfarin intake and 94% of them normalized prothrombin time (PT-INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrations (10%). Regarding the further prevention of thromboembolism, 91% resumed anticoagulant, 3% used antiplatelets instead of warfarin, and 6% disagreed with resuming any antithrombotic therapy. Of those who agreed to resume anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The key findings on follow-up CT to restart anticoagulation were absorption tendency of hematoma in 47%, followed by discontinuation of hematoma growth in 28%, and complete absorption of hematoma in 17%. To resume anticoagulation, warfarin alone was used in 76% and unfractionated heparin alone or combined with warfarin in 20%. Major contraindications for resuming anticoagulation were recurrent ICH and poor functional status corresponding to the modified Rankin Scale score of 4 or 5 (170 respondents, 59.4% for each), followed by dementia or frequent falls (139, 48.6%), suspected cerebral amyloid angiopathy (107, 37.4%), multiple brain microbleeds on T2*-weighted MRI (85, 29.7%), advanced age (80 years old, 71, 24.8%), and so on. Conclusions: For acute ICH patients with nonvalvular AF, a large majority of Japanese physicians stopped oral warfarin intake and normalized PT-INR on admission, but resumed anticoagulation several days to months later. However the strategies to normalize PT-INR and to resume anticoagulant therapy enormously varied and depended on physicians decisions.

Author Disclosures: K. Maeda: None. M. Koga: None. Y. Okada: None. K. Kimura: None. H. Yamagami: None. S. Okuda: None. Y. Hasegawa: None. Y. Shiokawa: None. E. Furui: None. J. Nakagawara: None. K. Kario: None. T. Nezu: None. K. Endo: None. T. Miyagi: None. K. Minematsu: None. K. Toyoda: None.

Th P169 Tamoxifen Treatment For Intracerebral Hemorrhage

Qing Xie, Jian Guan, Guohua Hua, Richard F Keep, Ya Hua; Univ of Michigan, Ann Arbor, MI Introduction: Tamoxifen is a selective estrogen receptor modulator. In this study we investigated whether or not tamoxifen reduces intracerebral hemorrhage (ICH)-induced brain injury in rats. Methods: In all experiments, adult male Sprague-Dawley rats received an injection of 100 l autologous whole blood into the right basal ganglia. In the first set of experiments, rats were treated with tamoxifen (2.5 mg/kg or 5 mg/kg, i.p.) or vehicle 2 and 24 hours after ICH and were killed at day 3 for brain edema measurement. In the second set of experiments, rats were treated with tamoxifen (5 mg/kg) or vehicle and magnetic resonance imaging (MRI) and behavior tests were performed at days 1, 7, 14 and 28. Rats were killed at day 28 for brain histology. Results: ICH causes brain edema in rats. Tamoxifen treatment at the dose 5 mg/kg significantly reduced brain water content (82.2 Ϯ 0.7% vs. 83.4 Ϯ 1.1% in vehicle treated group, p0.05). Brain histology showed that tamoxifen reduces caudate atrophy at day 28. The brain tissue loss in ipsilateral caudate at day 28 was significantly less in tamoxifen-treated rats (21.9 Ϯ 4.3% vs. 30.3 Ϯ 1.8% in vehicle-treated group, PϽ0.05). Tamoxifen also improved functional outcome (pϽ0.05). MRI demonstrated a tendency of smaller T2* lesions in tamoxifen-treated rats (28.5 Ϯ 4.7 vs. 34.3 Ϯ 6.1 mm3 in the vehicle-treated group, pϭ0.14). However, 2 out of 5 rats treated with tamoxifen developed hydrocephalus. Conclusions: These results suggest that tamoxifen has neuroprotective effects in ICH, but the cause of hydrocephalus development following tamoxifen treatment needs to be examined further.

Author Disclosures: Q. Xie: None. J. Guan: None. G. Hua: None. R.F. Keep: None. Y. Hua: Research Grant; Significant; NS-057539.

Th P170 Prior Antiplatelet Use is Associated With Hematoma Growth in Patients With Spontaneous Intracerebral Hemorrhage

Ozlem Kayim Yildiz, Ethem M Arsava, Mehmet A Topcuoglu, Erhan Akpinar; Hacettepe Univ Sch of Medicine, Ankara, Turkey Objective: Patients presenting with intracerebral hemorrhage (ICH) often report use of antiplatelet medications, even more common than anticoagulants. Recent studies have yielded conflicting results regarding the effects of antiplatelet usage on ICH course. In this study, our aim was to determine the effect of prior antiplatelet medication use on admission hematoma volume and hematoma growth in patients with spontaneous ICH. Methods: A consecutive series of patients with cranial computed tomography (CT) within 12 hours of symptom onset and a follow-up imaging within 72 hours were included into the study. Patients using anticoagulants at the time of stroke onset were excluded. Hematoma volume on admission and follow-up CT images were calculated by using the ABC/2 method. In addition to hematoma volume, clinical (age, gender, stroke risk factors, admission stroke severity, admission blood pressure, admission glucose level, antiplatelet usage) and imaging (time of imaging, hematoma location, intraventricular hemorrhage) data were collected in all patients. Univariate and multivariate analyses were performed to determine variables associated with admission hematoma volume and hematoma growth. Results: A total of 153 patients (59 female, 94 male) were included into the study. The mean (Ϯstandard deviation) age of the study population was 66Ϯ12 years. Fifty-two (34%) patients were on antiplatelet medication. The median (interquartile range) admission hematoma volume was 23.7 (9.3-71.3) mL. Overall, 64.1% of the patients exhibited some degree of hematoma growth and 27.2% of the patients had significant hematoma growth (defined as an increase of Ն33% or 12.5 mL expansion from baseline). Patients on antiplatelet medications tended to have larger admission hematoma volumes [35.0 (11.5-82.3) mL vs. 20.8 (8.0-64.3) mL; pϭ0.17]. Anti-platelet usage was associated with significant hematoma growth in both univariate (pϭ0.008) and multivariate (pϭ0.029) analyses. Conclusion: Antiplatelet medication usage at the time of stroke is an independent predictor of hematoma growth. These findings, together with reports on prior literature, suggest a promising role for therapies aiming restoration of thrombocyte function in preventing hematoma expansion during the acute stages of ICH.

Author Disclosures: O. Kayim Yildiz: None. E.M. Arsava: None. M.A. Topcuoglu: None. E. Akpinar: None.

Th P171 The Rate of Contrast Extravasation in Patients with Intracerebral Hemorrhage

Christopher D d'Esterre, Ting Yim Lee, Univ of Western Ontario, London, Canada; Richard Aviv; Sunnybrook Health Sciences Cntr, Toronto, Canada Objective: CT perfusion (CTP)-derived permeability surface area product (PS) is a novel method of measuring the rate of contrast extravasation from the intra-to extravascular compartment. Knowing the rate of contrast extravasation may provide insight into the pathophysiology of hematoma expansion by identifying the target abnormality most likely to contribute to hematoma growth. This study assessed whether CTP derived permeability (PS) measures can distinguish between different rates of contrast extravasation for patients with and without CTA Spot Sign or post contrast CT contrast leakage (PCL). Methods: We report CT perfusion (CTP)-derived blood brain barrier (BBB) permeability findings of 16 consecutively screened ICH patients with and without confirmed contrast extravasation within 3 hours of symptom onset. CTP-derived parametric maps of permeability surface area product (PS) were analyzed using custom software (IDL v6.1,RSI Inc, Boulder, Colo. USA). Three regions of interest were placed on perfusion weighted average images: 1) Extravasation positive regions (CT angiographic Spot Sign and post contrast leakage (PCL)), 2) mirrored contralateral hematoma volumes and 3) background hematoma remote from ROI 1. Baseline and follow up hemorrhage volumes were measured. Results: Mean PS was 3.8 Ϯ 2.9 ml-1x min-1x(100g)-1, 0.12 Ϯ 0.39 ml(min-1)(100g-1) and 0.10 Ϯ 0.26 ml(min-1)(100g-1), in the extravasation positive, background hematoma and contralateral mirror regions respectively (p Ͻ 0.05 each). Within the extravasation positive group, mean PS of CTA Spot sign and PCL was 6.5 Ϯ 1.6 ml(min-1)(100g-1) and 0.95 Ϯ 0.39 ml(min-1)(100g-1) respectively (p Ͻ 0.05). Mean hematoma volume increased from 34.1 Ϯ 41.0 ml to 40.2 Ϯ 46.1 ml in extravasation positive patients and decreased from 19.8 Ϯ 31.8 ml to 17.4 Ϯ 27.3 ml in the absence of extravasation (p Ͻ 0.05). Conclusion: A clinical technique that quantifies the rate of extravasation provides objective assessment of hematoma expansion risk rather than the qualitative approach currently used. Such information may become increasingly important as novel ICH treatments are developed that will target specific lesions. We report a gradation of PS values in CTA and post contrast CT detected lesions and patients without extravasation.

Author Disclosures: C.D. d'Esterre: None. T. Lee: Consultant/Advisory Board; Modest; Consultant for GE. R. Aviv: None.

Th P172 Contrast Extravasation is a More Sensitive Predictor of Intraparenchymal Hemorrhage Growth than Spot Sign

Sweta Goel, Marisa S Gallo, Claire J Creutzfeldt, Jonathan R Weinstein, Rebecca R Masters, Sandeep P Khot, Kyra J Becker, W T Longstreth, David L Tirschwell; Harborview Med Cntr,Univ of Washington, Seattle, WA Background and Objective: Intraparenchymal hemorrhage (IPH) growth is associated with poor outcome. Our objective was to describe the prevalence of a spot sign(SpS), contrast extravasation (CEx) and IPH growth in patients presenting to hospital at various times after symptom onset and to evaluate the performance of SpS and CEx in predicting IPH growth.Methods: We abstracted demographics, clinical data and radiological findings of 284 IPH patients admitted to a tertiary hospital from 2005 to 2008 who had CT angiography (CTA) and follow-up imaging (closest to 24 hours after first scan). We calculated IPH volumes from first and follow up scans using the ABC/2 method; SpS from CTA source images; and CEx from post-contrast images. The proportion of patients with SpS or CEx, and those showing significant IPH growth (Ͼ30% or Ͼ6cc) are presented for 5 time epochs based on the interval between symptom onset and 1 st CT scan (0-6, 6-12, 12-24, Ͼ24 hrs and unknown). Results: Mean age was 64 years (SD 15), 44% were females, and 72% had hypertension. Mean GCS ϭ 9.8 (SD 4.6) and CT IPH volume ϭ 34cc (SD 35) at presentation. Median time (interquartile range) from onset to first CT ϭ 6.5 hrs (3.2-23), between CT and CTA ϭ 2.9 hrs (0-5.3), and between first and follow-up CT ϭ 12 hrs (5.3-19). Of the 284 patients, 9% had SpS, 23% had CEx and IPH growth was present in 29%. Almost half of the 284 patients (46%) had their first CT from 0-6 hrs from onset, 21% 6-12 hrs, 9% 12-24 hrs, 18% Ͼ24 hrs and 6% an unknown time of onset. Ignoring the unknown times, significant decreases over the 4 known time epochs were observed for SpS (13%, 8%, 0%, 2%, Pϭ0.006), CEx (36%, 15%, 4%, 6%, PϽ0.001) and IPH growth (39%, 20%, 12%, 18%, Pϭ0.001). For unknown time cases, SpSϭ11%, CExϭ22% and IPH growthϭ33%. IPH growth was significantly associated with SpS (RR 2.3, 95% CI 1.6-3.4) and CEx (RR 2.9, 2.1-4.0). SpS sensitivity for detecting IPH growth was 19% (95% CI 11-29), specificityϭ95% (91-98) and area under the ROC curve (C) ϭ .57; for CEx sensitivityϭ46% (35-57), specificityϭ87% (81-91) and Cϭ.66 (C for CEx Ͼ C for SpS, Pϭ.0005). Conclusions: Consistent with the literature, SpS, CEx and IPH growth are more common in patients seen earlier after symptom onset. Confirming results of smaller studies, CEx is a more sensitive screening tool than SpS for identifying patients who go on to have IPH growth. All CTA protocols should include post-contrast CT, and CEx should be used for clinical decision making once an effective treatment becomes available. Many IPH patients present without known timing of symptom onset and still have significant rates of CEx and IPH growth. IPH trials focused on reducing IPH growth may benefit from greater patient eligibility and statistical power if inclusion criteria focus on presence of CEx rather than time since onset.

Author Disclosures: S. Goel: None. M.S. Gallo: None. C.J. Creutzfeldt: None. J.R. Weinstein: None. R.R. Masters: None. S.P. Khot: None. K.J. Becker: None. W.T. Longstreth: None. D.L. Tirschwell: Research Grant; Significant; Novo Nordisk Inc.

Th P173 Validation Of A Computerized Planimetric Tool For Quantifying Intraventricular Hemorrhage Volumes.

Dar Dowlatshahi, Univ of Ottawa, Ottawa Hosp Rsch Institute, Ottawa, Canada; Jayme Kosior, Sherif Idris, Muneer Eesa, Peter Dickhoff, Manish Joshi, Suresh Subramaniam, Sarah Tymchuk, Michael D Hill, Univ of Calgary, Calgary, Canada; Richard Aviv, Sunnybrook Health Sciences Cntr, Toronto, Canada; Richard Frayne, Andrew M Demchuk, Univ of Calgary, Calgary, Canada; for the PREDICT/Sunnybrook study Investigators Background: Intracerebral hemorrhage (ICH) volume and intraventricular hemorrhage (IVH) extension are independent predictors of outcome following hemorrhagic stroke. Early ventricular rupture and subsequent auto-decompression of parenchymal hematoma is common in ICH. Ventricular decompression decreases ICH volumes, but also results in IVH expansion and increased IVH volume, both of which are associated with poor outcome. Given volume and expansion are common surrogate outcomes for ICH studies, easy and accurate measurement of IVH and volume dynamics following ventricular rupture is relevant to hemostatic trials.

Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Amytis Towfighi, Waimei Tai, Univ of Southern California, Los Angeles, CA; Daniela Markovic, Bruce Ovbiagele; Univ of California at Los Angeles, Los Angeles, CA Background: Recent nationwide prevalence studies in the United States (US) demonstrated an increasing prevalence of self-reported stroke in middle-aged women compared to similarly aged men, particularly amongst those aged 45-54 years. It is unclear, however, whether this trend is due to an actual rise in stroke incidence or improved stroke survival amongst young/middle-aged women. Studies of sex differences in stroke case fatality have had variable results and few have focused specifically on individuals younger than age 65 years. We therefore assessed temporal trends in sex-specific mortality amongst US adults aged 35 to 64 years hospitalized with stroke. Methods: Data were obtained from all US states that contributed to the Nationwide Inpatient Sample. All individuals aged 35-64 years hospitalized between 1997 and 2006 with a primary discharge diagnosis of stroke (nϭ2,537,097) were identified using International Classification of Diseases, Ninth Revision procedure codes. We determined temporal trends in sex-specific hospital mortality after stroke. Both unadjusted and adjusted mortality rates were analyzed for men and women between the ages of 35-44, 45-54, and 55-64 years (controlling for sociodemographic factors, comorbidities, stroke type, tissue plasminogen activator, in-hospital complications, and length of stay). Results: From 1997 to 2006, mortality after stroke amongst individuals aged 35-64 years decreased in both men (6.06% to 5.15%) and women (6.02% to 4.88%). In the 35-44 year age group, mortality after stroke was lower in 2005-2006 compared to 1997-1998 (OR 0.59, 95% CI 0.51-0.69 in men and OR 0.60, 95% CI 0.51-0.71 in women). Mortality after stroke also decreased amongst those aged 45-54 years and 54-64 years, but to a lesser extent. While unadjusted analysis revealed that women aged 35-44 years had lower mortality after stroke compared to men (OR 0.89, 95% CI 0.83-0.95), this difference became insignificant after controlling for stroke type. On the other hand, comparison of mortality after stroke between men and women aged 45-64 years revealed that mortality was lower for women than men in both the 45-54 year age group (OR 0.94, 95% CI 0.90-0.98) and 55-64 year age group (OR 0.96, 95% CI 0.93-1.00) after controlling for confounders. Conclusion: : This study of sex-specific stroke mortality rates amongst individuals aged 35-64 years revealed a decline in mortality rates from 1997 to 2006 amongst both men and women. The most prominent decline in mortality rates has been amongst those aged 35-44 years. The slightly lower mortality in women vs. men aged 45-54 years may in part be contributing to the recently reported rising stroke prevalence observed in midlife women; however, prospective studies are warranted.

Th P182 Primary Stroke Centers Achieve High Compliance with Disease Performance Measures

Mark J Alberts, Northwestern Univ Med Sch, Chicago, IL; Jerod M Loeb, Jean Range, Ann Watt, Karen Kolbusz, M J Hampel, Vicki Cantwell, Jospeh Troy; The Joint Commission, Oakbrook Terrace, IL Background: Primary Stroke Centers (PSCs) can achieve improved patient outcomes using a variety of processes. We analyzed standardized stroke disease performance measure data (DPMs) for PSCs to determine if duration of certification correlated with improved compliance with various DPMs. Our hypothesis was that institutions that achieved repeated certification as a PSC would also realize higher rates of compliance with the DPMs. Methods: We analyzed data on PSCs certified by The Joint Commission from 2008 through 2010. Characteristics of the PSC and compliance with the eight DPMs were analyzed as a function of the number of certification cycles and teaching statusResults: Data were available from 745 PSCs (428 teaching, 317 non-teaching) and 361,512 eligible patients. The number of PSCs going through 1, 2, and 3 cycles of certification was 253, 255, and 243 respectively. When comparing PSCs after 1 and 3 cycles of certification, significant improvements were seen in the following DPMs: IV-TPA administration to eligible patients within 3 hours of stroke onset (73.7% vs 84.0%, p ϭ 0.004); anticoagulation for atrial fibrillation (93.3% vs 97.1%, p ϭ 0.03); stroke education (74.6% vs 82.8%, p ϭ 0.02); discharge on statin therapy (86.1% vs 91.0%, p ϭ 0.05); DVT prophylaxis (90.6% vs 95.2%, p ϭ 0.06). Other measures such as antithrombotics by day 2 (96% vs 97%, p ϭ 0.15), consideration for rehabilitation (96% vs 97.3%, p ϭ 0.36), and discharge on antithrombotics (98% vs 99%, pϭ0.28) were at high levels after one cycle with little room for improvement in compliance by cycle 3. Hospital teaching status did not correlate with compliance for any DPM. Conclusions: PSCs that complete multiple certification cycles are more likely to be compliant with several DPMs, especially IV-TPA administration. Teaching and non-teaching institutions achieve equal rates of compliance with all current DPMs.

Author Disclosures: M.J. Alberts: Speakers; Significant; Genentech. Consultant/Advisory Board; Modest; Genentech. Other; Modest; Uncompensated consultant to The Joint Commission. J.M. Loeb: Employment; Significant; The Joint Commission. J. Range: Employment; Significant; The Joint Commission. A. Watt: Employment; Significant; The Joint Commission. K. Kolbusz: Employment; Significant; The Joint Commission. M.J. Hampel: Employment; Significant; The Joint Commission. V. Cantwell: Employment; Significant; The Joint Commission. J. Troy: Employment; Significant; The Joint Commission.

Th P183 University of Colorado Hospital In-Hospital Stroke Alert Improvement Project

Alex Graves, Rebekah Zaemisch, William Jones, Kerry Brega, Ethan Cumbler; Univ of Colorado Hosp, Aurora, CO Background: Between 4-17% of all stroke patients have onset of symptoms while hospitalized. Delays in recognition and assessment are common. Research suggests in-hospital stroke alerts have greater delays compared to those in the ED. At University of Colorado Hospital (UCH), median time from in-hospital stroke alert to brain imaging was found to be 2-3 times longer than those in the ED and exceeded the benchmark of 25 minutes suggesting need for process improvement. Purpose: The In-Hospital Stroke Alert Improvement Project was designed to identify and rectify delays in recognition and assessment of new neurologic deficits developing in hospitalized patients. Methods: The In-Hospital Stroke Alert Improvement Project consisted of 6 core elements: Mapping of existing process, system re-design to address unreliable or slow steps, standardization of communication, in-hospital stroke alert checklists, rigorous measurement, and real time feedback. Root cause analysis during the pre-intervention phase (9/2008 -2/2009) was performed using interviews with stroke team members, staff, and direct observation of alerts. Bottlenecks identified included IV access, transportation, correct test ordering, and CT notification. An interdisciplinary team developed and implemented solutions to identified barriers during the intervention phase (3/2009 -5/2009). Checklist cards were created for both the stroke team and nursing clearly defining roles and how to execute each step in the in-hospital stroke alert. CT technicians were provided stroke alert notification pages, the stroke team assumed responsibility for transportation, a thrombolytic kit was assembled in pharmacy, and rapid response nurses were made available to respond anywhere tPA was to be given. Real time measurement and feedback was implemented. Change in stroke alert response times were tracked for 6 months ( 6

Th P184 Foley Catheterization and Urinary Tract Infections in Patients Hospitalized with Stroke

Sharon N Poisson, UCSF, San Francisco, CA; Steven Sidney, Kaiser Permanente Div of Rsch, Oakland, CA; S. Claiborne Johnston, Mai N Nguyen-Huynh; UCSF, San Francisco, CA Introduction: In conditions other than stroke, most hospital-acquired UTIs are related to bladder catheterizations, which occur in 15-25% of all hospitalized patients. The frequency of catheterization and catheter-associated UTI in patients hospitalized with stroke are not well documented. Methods: We utilized data on 105 randomly selected patients with ischemic stroke in QUISP, a randomized quality improvement trial focused on secondary stroke prevention, conducted between January 2004 and September 2006 in 14 hospitals in a Northern California managed care plan. Charts were abstracted for dates of Foley catheterization, days with fever (Ͼ38.4°C), laboratory and prescription information. We examined the association between Foley catheterization and UTI and between UTI and outcome (hospital length of stay, discharge disposition, recurrent stroke, or re-hospitalization). Definite UTI was defined by the CDC criteria for public reporting of hospital-acquired symptomatic UTI, including a positive culture and fever. Because records of other UTI symptoms were not available, likely UTI was defined as fever plus any of the following: urinalysis with positive nitrites, leukocyte esterase or pyuria, physician diagnosis of UTI, or appropriate treatment of UTI with antibiotics. Adjustments were made for age, gender, race, and cardiovascular risk factors. All analyses were conducted using generalized estimating equations to adjust for within and between hospital variances. Results: Of 105 patients, 40 (38%) had Foley catheters placed during their hospital admission. The mean duration of catheterization was 3.6 days (range 1-9 days). Women were more likely than men to have catheters placed (46% vs. 24%, pϭ0.02), but demographics and past medical history did not differ significantly. Eleven patients with (28%) and 4 patients without (6%) catheters had positive cultures (pϭ0.002). Catheterized patients were more likely to have a definite UTI (10% vs. 2%, pϭ0.05) or a probable UTI (20% vs. 6%, pϭ0.003). In multivariable analysis, there remained a trend toward prediction of definite UTI (OR 5.40, 95% CI 0.61-48.0) as well as probable UTI (OR 3.20, 95% CI 0.83-12.36) in catheterized patients. Foley catheterization was independently associated with an increase in length of stay (OR 1.45 95%CI 1.10-1.91) and increased likelihood of discharge to a facility other than home (OR 2.55, 95% CI 1.02-6.37). Conclusions: Compared to general medical patients, stroke patients are more likely to have Foley catheters placed during hospital admission, and catheters are associated with a trend toward greater likelihood of symptomatic Author Disclosures: R. Figari: None. R. Salazar: None. M. Lu: None. P. Penstone: None. P. Mitsias: Research Grant; Significant; NINDS-1R01NS070922-01, Mort and Brigitte Harris Foundation.

Th P189 Early Neurological Deterioration And Capillary Glucose Levels In Acute Stroke

Author Disclosures: N.S. Sangha: None. R. Pandurengan: None. M. Kasam: None. T. Wu: None. N. Gonzales: None. V. Misra: None. J. Grotta: None. S. Savitz: None.

Th P198 Acute Stroke Causes Changes in Spleen Size Over Time

Preeti sahota, James P Hovis, Thanh-Tung Bui, Nusrat Harun, James Grotta, Sean Savitz; Univ of Texas, Houston, TX Introduction: Animal studies have demonstrated that the spleen contracts after stroke and promotes secondary inflammatory response that enhances neurodegeneration. There are no known studies on splenic changes in patients with acute stroke (AS). We conducted a prospective pilot study to evaluate changes in spleen size over time following AS. The following hypotheses were tested: • Whether the spleen undergoes demonstrable size changes over time following AS? • Is there clinical correlation of splenic contraction with severity of stroke? Methods Patients with AS, 18 years or older and presenting within 6 hours of onset, in absence of concomitant MI, trauma, autoimmune disease, fever, hypoxemia or hemodynamic instability were enrolled. We collected demographics, vitals and NIHSS; first splenic ultrasound (SUG) was performed within 6 hours of onset using Philips CX50 S5 MHz transducer. Splenic length, width and thickness were measured with hilum as reference point. SUG was repeated once within 24 hours of onset and then daily along with NIHSS until day 7 or discharge, whichever was earlier. Splenic volume was calculated and corrected for height, weight and gender using a published formula by Geraghty et al to determine the relative degree of splenic size changes (atrophy versus enlargement) compared to the expected normal range. Based on 5 consecutive daily SUGs in 8 healthy volunteers, splenic volume variation below 15% was considered normal. Results The clinical and SUG characteristics of 19 patients are summarized in the table. A significant increase in mean splenic volume was seen over the week (p-0.037), indicating rapid contraction and then gradual increase towards normalcy in most patients. Three patients had below 15% splenic volume change, two of whom had significant recovery (NIHSS Ͻ1) within a day. Rest of patients showed splenic contraction at first SUG or within next 6-24 hours, followed by varying degree of recovery in individual patients (figure). Most patients with severely contracted spleens (Ͻ1 percentile) initially had moderate to severe stroke. Conclusions: The spleen undergoes dynamic changes in size after AS. Stroke severity and outcome may correlate with extent of splenic contraction and recovery over time. Further studies are needed to determine the clinical significance of these findings.

Th P203 Neural Stem Cell Engraftment Peaks at 3 Days After Intraarterial Delivery in a Mouse Hypoxic-Ischemic Stroke Model

Sahar Rosenblum, Nancy Wang, Josh Y Chua, Raymond Choi, Hotaik Sung, Jay K Nathan, Harjus Birk, Raphael Guzman; Stanford Univ, Palo Alto, CA Intro: With its minimal invasiveness and ability to target a wide area of the brain, intra-arterial (IA) neural progenitor cell (NPC) transplantation has emerged as a potent therapeutic avenue for stroke. However, the effects of timing of transplantation on cell delivery efficiency remain unknown. In this study, we transplanted NPCs at specific time points after stroke to evaluate cell engraftment and viability with in-vivo bioluminescent imaging. Methods: Mouse NPC's (5x105 in 5l saline) harboring a reporter gene construct containing renilla luciferase were delivered to the brain via the ipsilateral carotid artery at 6 hours, 24 hours, 3, 7 and 14 days after hypoxic-ischemic stroke in Bl6 mice (Nϭ10 per group), using a microneedle. Cell engraftment was monitored by in-vivo bioluminescence imaging (BLI) for luciferase activity, performed immediately and 4 days after IA injection. Stroked brain homogenates were analyzed using quantitative RT-PCR for the chemokine CCL2 and adhesion molecule VCAM1 to investigate the mechanism of cell recruitment. Western blotting was performed to corroborate RNA expression data. Results: Cell engraftment was significantly higher when NPCs were injected at 3 days after stroke (1.86 x 10 6 photons/s/cm 2/sr) as compared to 6 hours (3.87 x 10 5 photons/s/cm 2/sr) and 14 days (5.51 x 10 5 photons/s/cm 2/sr) (pϽ0.01). NPCs transplanted at three days post-stroke also demonstrated greatest survival when imaged at 4 days after IA injection (pϽ0.01). Quantitative RT-PCR showed that CCL2 expression in the ipsilateral brain as compared to naı ¨ve brains was significantly upregulated at 3 days (520.9 fold regulation) after stroke as compared to 6 hours (32.5 fold regulation), 5 days (422.1) and 14 days (323.8) after stroke. VCAM-1 expression in the ipsilateral brain was significantly upregulated at 24 hours (4.055 fold regulation) after stroke compared to 6 hour (0.245 fold regulation) after stroke. Western blotting data revealed a peak in VCAM expression at 3 days post stroked with bands having a relative intensity of 1.14 as compared to 6 hours (0.95), 5 days (0.36), and 14 days (0.88). Preliminary cell counts revealed a significant peak in cell homing to the injured brain (pϽ0.05) compared to 6 hour and 14 day time points. Conclusion: Intravascular transplantation of NPCs 3 days after stroke resulted in significantly higher delivery of NPCs to the area of injury and highest degree of cell survival at 4 and 7 days after injection. The observed differences in cell engraftment may be attributed to a favorable environment for NPC migration as evident by the secretion pattern of chemoattractant factors and adhesion molecules such as CCL2 and VCAM-1 in the injured brain.

This research has received full or partial funding support from the American Heart Association, Western States Affiliate (California, Nevada & Utah).

Author Disclosures: S. Rosenblum: None. N. Wang: None. J.Y. Chua: None. R. Choi: None. H. Sung: None. J.K. Nathan: None. H. Birk: None. R. Guzman: None.

Th P204 Mechanical Thrombectomy by the Penumbra System has the Potential to Improve Neurological and Functional Outcomes in Japanese Patient with Acute Ischemic Stroke

Nobuyuki Sakai, Kobe City General Hosp, Kobe, Japan; Kazunori Toyoda, National Cerebral and cardiovascular Cntr, Suita, Japan; JR-NET2 and SAMURAI study Investigators, Penumbra System Pivotal and POST Investigators Introduction: Mortality from acute ischemic stroke in Japan is known to be much lower than that reported in the West. In Japan, IV rt-PA therapy has been approved since 2005, and endovascular intervention is indicated in patients who are either contraindicated to, or failed IV rt-PA therapy. However, mechanical thrombectomy devices, such as the Merci Retriever or Penumbra System are not approved, and it remains controversial if mechanical thrombectomy has a role for acute stroke intervention in Japan. Methods: This study was a retrospective review of 1176 acute stroke patients from 13 hospitals in the JR-NET2 and SAMURAI registry group. The goal was to select those who would qualify for mechanical thrombectomy therapy but were never treated. These patients (Nϭ334) had large vessel occlusions who presented within 8 hours from symptom onset with a NIHSS score of at least 8 and not eligible for IV rt-PA therapy. Their outcomes were then compared with matched patients pooled from the Penumbra Pivotal and POST trials* who were treated by the Penumbra System (Nϭ143). The primary endpoints were all cause mortality, poor functional outcome as defined by a modified Rankin Scale (mRS) score of Ͼ5 and good functional outcome as defined by a mRS score of Ͻ2 at 90 day post-procedure. Results: Table Conclusion: These results suggest that patients with large vessel occlusion, eligible for mechanical thrombectomy in Japan, who present within 8 hours from symptom onset and with a NIHSS score of at least 8 could potentially get benefits from treatment by the Penumbra System.

Author Disclosures: N. Sakai: None. K. Toyoda: None.

Th P205 Long-term Clinical Outcome Following Endovascular Reperfusion Therapy In Severe Ischemic Stroke Patients

MASAHITO NAKAZAKI, Takahisa Mori, Hiroyuki Tajiri, Tomonori Iwata, Yuichi Miyazaki; Shonan Kamakura General Hosp, kamakura, Japan Object The purpose of our study was to investigate long-term clinical outcome following endovascular reperfusion therapy in severe ischemic stroke patients with occlusions of the internal carotid artery (ICA) or the middle cerebral artery (MCA), and to find predictors of favorable clinical outcome. Methods We retrospectively analyzed the acute stroke patients 1) who were admitted to our institution from 2004 to 2009, 2) with serious neurological symptoms of GCS of 12 or less or NIHSS score of 10 or more, 3) who had total occlusion of the ICA or MCA displayed by MRA, and 4) who underwent emergency reperfusion endovascular therapy within 6hours from stroke onset. We investigated patient's baseline features, emergency MRI finding, stroke subtypes, successful recanalization defined as TIMI2 or 3, onset-to-treatment time (OTTT), NIHSS score on admission (AD-NIHSS),and the 7th day (7D-NIHSS), and mRS at 3 months (3M-mRS). We defined favorable clinical outcome as mRS of 0-2, and assessed predictors for favorable clinical outcome by using logistic regression analysis. We evaluated factors for long-term survival with cox proportional hazard model. Results Fifty nine patients were analyzed. Their median age was 77, women were 26 patients, median follow-up period was 6 months (range: 1-72 months), median AD-NIHSS was 18, median DWI-ASPECT score was 7, median OTTT was 2.67 hours, fifty two patients had cadiogenic stroke, successful recanalization was achieved in 33 patients (56.0%), median 7D-NIHSS was 10, and median 3M-mRS was 3. Logistic regression analysis demonstrated that successful recanalization (OR11.9, 95%CI 2.08-67.93, Pϭ0.005) was the independent predictor of favorable clinical outcome (3M-mRS of 0-2) . Successful recanalization following endovascular reperfusion therapy (OR9.57 95%CI1.47-62.10 Pϭ0.018 ) was the independent significant predictor for long-term survival free from any death. In patients with and without successful recanalization, cumulative survival probability at 1 year free from any death was 83.1% and 60.4% (pϭ 0.002), respectively. Conclusion: In severe ischemic stroke patients who underwent endovascular reperfusion therapy for the ICA or MCA occlusion within 6hours from onset, successful recanalization was the significant predictor for favorable 3M-mRS of 0-2 and long-term survival.

Author Disclosures: M. Nakazaki: None. T. Mori: None. H. Tajiri: None. T. Iwata: None. Y. Miyazaki: None.

Th P206 Endovascular Treatment Outcomes in Acute Stroke Patients with Distal MCA lesions: A single center experience

Jitendra Sharma, Sonal Mehta, Shakeel Chowdhry, Neelima Tummala, Ashish Nanda, Kristine Blackham; Univ Hosps Case Med Cntr, Cleveland, OH Objectives: To assess the safety and efficacy of endovascular treatment modalities in acute ischemic stroke patients with distal MCA lesionsBackground: Endovascular treatment modalities have been shown to be efficacious in acute ischemic strokes resulting from proximal middle cerebral artery (MCA) lesions. Data regarding their utility in treating distal MCA clots such as M2 and M3 branches is limited. Methods: Retrospective chart review was performed in 190 consecutive patients who underwent endovascular treatments for acute ischemic stroke at our center between 2005 and 2009, nϭ39 patients had distal MCA (M2 and M3) branches occlusion. This study included 22 males and 17 females with mean age of 69.25Ϯ12.75). In our study group, 84.6% (nϭ33) were hypertensive, 35.9% (nϭ14) were diabetic, 61.5% (nϭ24) had hyperlipidemia and 30.7 % (nϭ12) had atrial fibrillation. The mean NIHSS on admission was 14.64 and that on discharge was 8.71. The primary outcome measures following the intervention were intracranial hemorrhage (ICH) rate, mortality and recanalization rate. Results: In our study group 73.1% (nϭ30) patients had lesions in the M2 branches, 23% (nϭ9) in M3 and 3.9% (nϭ2) in M4 branches. 92.3% (nϭ36) of these patients were treated with IA tPA. In addition, one patient received mechanical thrombectomy using Penumbra device. Of the other 3 patients, one had recanalization with mechanical clot disruption, one had spontaneous improvement of symptoms during the procedure and one had attempted mechanical thrombectomy with penumbra device. None of the patients had MERCI clot retrieval, angioplasty or stenting. Partial-to-complete recanalization (TIMI 2-3) was achieved in 64% (nϭ25) patients. Post procedure symptomatic hemorrhages were found in 9.7% (nϭ4) patients. The mortality rate was 19.5 % (nϭ8) in our study group. Conclusions: Emergent Author Disclosures: K. Hong: None. M. Lee: None. S. Lee: None. Q. Hao: None. D. Liebeskind: None. J. Saver: None.

Th P208 Ascertaining the Impact of Distal Embolization in Recanalization Therapies for Acute Ischemic Stroke

Matthew S Tenser, Univ of Southern California, Los Angeles, CA; Jeffrey L Saver, Latisha K Ali, Doojin Kim, Bruce Ovbiagele, Sidney Starkman, Michael T Froehler, Sarah Song, Radoslav Raychev, Reza Jahan, Satoshi Tateshima, Nestor Gonzalez, Gary R Duckwiler, Fernando Vinuela, David S Liebeskind; Univ of California, Los Angeles, Los Angeles, CA Background: Endovascular recanalization therapies (ERT) are evolving to expand options for treatment of acute ischemic stroke. While these procedures have higher rates of recanalization than IV tPA, they are associated with higher rates of symptomatic hemorrhage and mortality. Another possible complication of recanalization therapy, either intravenous or intra-arterial, is distal embolization (DE). We investigated the clinical impact of DE in patients treated with various methods of recanalization therapy. Methods: Ischemic stroke patients from 2005 to 2010, treated with either IV tPA alone or ERT with or without IV tPA, were identified in a prospectively maintained database. Post-treatment MR imaging for all patients was evaluated for changes consistent with DE. Catheter angiograms for ERT patients were evaluated for evidence of DE. Successful recanalization (SR) for ERT patients was defined as TICI 2b or 3, and recanalization for IV tPA patients was determined using post-treatment MRA. Variables analyzed included demographics, clinical history, laboratory and imaging findings, method of recanalization, initial NIHSS, and discharge modified Rankin Score (mRS). Results: Among 18 patients treated with IV tPA only, the mean age was 67.2 (range 41-97), 55.6% were female, and median initial NIHSS was 11.5. Among 50 ERT patients, mean age was 67.4 (range 29-95), 62% were female, and median initial NIHSS was 18.5. For ERT patients, affected vessels were: ICA -26%, M1 MCA -62%, and other -12%. For IV patients, vessels were: ICA -11%, M1 MCA -28%, and other -61%. Therapies for ERT patients were Merci retriever alone in 50%, Merci retriever plus IV or IA tPA in 27%, IA tPA alone in 6%, and other in 17%. SR was achieved in 32% of ERT. Recanalization was seen on post-treatment MRA in 40% of those receiving IV tPA. SR was seen in 70% of ERT patients with final mRS 0-2, and 23% of those with final mRS 3-6 (Pϭ0.012). DE was seen in 46% of ERT patients and 13% of IV tPA patients. DE was not more common among ERT patients who achieved SR than those who did not, 36% vs 28% (Pϭ0.76). DE after recanalization was seen in 50% of IV tPA patients. For ERT patients, new DWI lesions consistent with DE were seen in 60% of those with final mRS 0-2, and 32.5% of those with mRS 3-6 (Pϭ0.22). For IV tPA patients, new DWI lesions were seen in 0% of those with discharge mRS 0-2 and 37.5% of those with discharge mRS 3-6 (Pϭ0.24). The mean discharge mRS of ERT patients was lower in those with DE, 3.2 vs 4.1 (Pϭ0.03). DE was more common in ERT patients with non-disabled (mRS 0-2) than disabled outcomes, 80% vs 37.5% (Pϭ0.04). For ERT patients who had both DE and SR, 60% had final mRS 0-2 and 7.5% had final mRS 3-6 (pϽ0.001) Background: Acute ischemic stroke treatment is guided by therapeutic windows. These windows are decided upon the moment of witnessing the stroke onset or when the patient was last seen normal. However, "last seen normal" principle is likely to overestimate the time interval between symptom onset and treatment. Objective: To compare outcomes between eligibility determination by "witnessed onset" and "last seen normal" principle among acute ischemic stroke patients undergoing endovascular treatment. Methods: Consecutive patients with acute ischemic stroke who underwent emergent endovascular treatment over five years were included. A univariate analysis was performed comparing patients who had a "witnessed onset" of stroke symptoms and patients in whom the moment they were "last seen normal" was considered the time of onset. Patient characteristics and outcomes were compared between the two groups including age, admission National Institutes of Health Stroke Scale score (NIHSSS), discharge NIHSSS, discharge modified Rankin scale (mRS), and in-hospital mortality. Results: A total of 172 patients, mean age Ϯ standard deviation (SD) 67Ϯ15.3 years and mean National Institutes of Health Stroke Scale Score (NIHSSS) ϮSD of 15.4Ϯ6.3 had a witnessed stroke time of onset (Group A). 41 patients, mean age ϮSD 61.1Ϯ15.5 and mean NIHSSS ϮSD 14.1Ϯ6.4 underwent endovascular treatment based on the time the patient was last seen normal (Group B). There were no significant differences in baseline characteristics, admission NIHSSS, proportion of patients in whom the NIHSSS improved Ն4 points or returned to 0 (Aϭ64.5%, Bϭ78.1%; pϭ0.098), and in whom discharge modified Rankin Scale was 0-2 (Aϭ 32.9%, Bϭ 36.6%; pϭ0.66). There was a significant difference in the median time interval between symptom onset or last seen normal and microcatheter placement in the cerebral circulation (Aϭ 299 minutes, Bϭ 563 minutes; pϭϽ0.001). The rate of symptomatic intracerebral hemorrhage was lower in group B (7% vs 0%; pϭ0.08) and there was a trend to a significantly higher in hospital mortality in patients with witnessed acute ischemic stroke symptom onset (Aϭ 23.3%, Bϭ9.8%; pϭ0.051). Conclusion: There appears to be differences in outcomes between patients treated based on eligibility determination using witnessed stroke symptom onset or last seen normal symptom principles. Future guidelines must consider these two patient populations in a separate context. Background: Epidemiologic studies have shown that patients admitted on weekends are less likely to undergo necessary invasive cardiac procedures, contributing to the higher mortality rate seen in weekend admissions. Little is known about how this "weekend effect" influences intra-arterial therapy (IAT). The purpose of this study was to investigate time to treatment and outcome in patients receiving IAT on weekends as compared to weekdays. Methods: Data from UT Houston and UAB IAT databases were examined. Patients lacking time of admission data were excluded. The remaining patients were divided into those arriving on a weekend (17:01 Friday to 08:59 Monday) and those arriving on a weekday. Demographics, NIHSS, admission glucose, and time to treatment were examined. Primary outcomes including mortality, favorable discharge disposition (home or inpatient rehab), and length of stay, symptom onset to IAT treatment times, recanalization rates and sICH were compared between weekend and weekday admissions. Results: A total of 392 consecutive patients were screened (299 UT, 93 UAB). 392 patients met inclusion criteria. 33% percent (129/392) arrived on a weekend. Demographics and outcomes are shown in Table 1. After adjusting for age, baseline NIHSS and admission glucose, weekend admission was not a significant independent predictor of sICH (ORϭ0.91, 95% CIϭ0. pϭ.80),favorable disposition (ORϭ1.11,pϭ.70), favorable mRS at discharge (ORϭ1.12, 95% CIϭ0.61-2.07, pϭ.71), or death (ORϭ0.89, 95% CIϭ0.48-1.63, pϭ.70). Conclusions: Our study found no weekend effect on intra-arterial therapy. Our results may not be generalizable, however, as our experience reflects centers with

Th P214 Successful Endovascular Acute Stroke Intervention Prevents Infarct Core Growth

Vincent Truong, Rori Spray, Kerri Remmel, Alex Abou-Chebl; Univ of Louisville Sch of Medicine, Louisville, KY Objective: CT perfusion (CTP) imaging has been widely applied in patients with acute ischemic stroke for assessing penumbral tissue aiding in decision-making on whether or not endovascular therapy (ET) should be initiated. However, there is a paucity of data showing that successful recanalization prevents infarct growth in those with baseline penumbra. We sought to determine if successful ET can prevent lesion growth. Methods: Using an IRB-approved prospectively collected interventional registry, we identified consecutive patients with anterior circulation strokes during a 2year period treated with ET who also had interpretable CTP and 24-48hour post-ET follow-up CT (patients with follow-up MRI were excluded). Data collected included demographics, admission NIHSS, glucose, and blood pressure, IV-lytic and ET technique, time from stroke onset to ET, and final recanalization (TIMI) grade. Only patients with CBF lesion 20% larger than CBV lesion and ischemic core (defined as CBV Ͻ50% of contralateral normal side) 1/3 MCA territory were offered ET. For outcome assessment, ABC/2 volume calculation was obtained from CBV slices and compared with the corresponding follow-up CT slices showing the final infarct. Results: Twenty patients (65% women) with a mean age of 63Ϯ19years were identified. Mean admission NIHSS, glucose, and blood pressure were 18Ϯ4, 146Ϯ47mg/dl, and 152/79Ϯ25/18mmHg respectively. The mean time to ET was 6.9Ϯ4.2hours. All received endovascular embolectomy in addition to IV-tPA in 5(20%) or IA-tPA and/or GPIIb/IIIa antagonist in 8(40%) patients. There was no statistically significant difference in baseline demographics and endovascular techniques between 14 patients (70%) who achieved recanalization (TIMI 2-3) and 6(30%) who did not (TIMI 0-1). No statistically significant infarct growth existed in patients with recanalization (13.5Ϯ8.5cm 3 CBV vs. 11.4Ϯ8.1cm 3 follow-up CT, pϭ0.54). However, in patients who did not recanalize (TIMI 0-1) there was a significant increase in final infarct volume (15Ϯ5.73cm 3 vs. 28.4Ϯ10.3cm 3 , pϭ0.034), which was similar to the initial CBF volume (21.7Ϯ8.7cm 3 vs. 28.4Ϯ10.3cm 3 , pϭ0.30). Conclusion: In our experience, successful ET was associated with tissue salvage in patients with acute ischemic stroke. CTP data can be used to predict the final infarct size in patients with ischemic stroke and may be helpful in therapeutic decision making. These results need to be validated in future studies.

Author Disclosures: V. Truong: None. R. Spray: None. K. Remmel: None. A. Abou-Chebl: None.

Th P215 The Internal Maxillary Artery is the Key External to Internal Carotid Collateral in Carotid Occlusion

Ritesh Kaushal, Randall C Edgell, Nirav Vora, Richard Callison, Eliahu Feen, Paisith Piriyawat, Aninda Acharya, Salvador Cruz-Flores; SAINT LOUIS UNIVERSITY, Saint Louis, MO

Th P221 Anterior Circulation Large Vessel Occlusion Stroke Presenting With Mild Symptoms. Clinical Outcomes And Safety Of Intravenous Thrombolysis And Endovascular Treatment

Aitziber Aleu, Hosp Universitari Germans Trias i Pujol, Badalona. Barcelona, Spain; Ridwan Lin, UPMC stroke Institute., Pittsburgh, PA; Monica Millan, Hosp Universitari Germans Trias i Pujol, Badalona. Barcelona, Spain; Syed F Zaidi, UPMC stroke Institute., Pittsburgh, PA; Natalia Perez de la Ossa, Hosp Universitari Germans Trias i Pujol, Badalona. Barcelona, Spain; Mouhammad A Jumaa, UPMC stroke Institute., Pittsburgh, PA; Sira Domenech, Hosp Universitari Germans Trias i Pujol, Badalona. Barcelona, Spain; Amer Malik, UPMC stroke Institute., Pittsburgh, PA; Carlos Castan ˜o, Cristina Guerrero, Hosp Universitari Germans Trias i Pujol, Badalona. Barcelona, Spain; Jaume Roquer, Hosp Del Mar, Barcelona, Spain; Joaquin Serena, Hosp Universitari Dr. Josep Trueta, Girona, Spain; Antoni Davalos, Hosp Universitari Germans Trias i Pujol, Badalona. Barcelona, Spain; Tudor Jovin; UPMC stroke Institute., Pittsburgh, PA Background: While intravenous thrombolysis (IVT) for stroke presenting with mild symptoms (SPMS) is an accepted paradigm in most centers, there is considerable heterogeneity in practice regarding endovascular treatment (EVT) for SPMS not responding to or ineligible for IVT. We sought to assess IVT and EVT for SPMS due to anterior circulation large vessel occlusion (ACLVO) with regard to safety and clinical outcomes. Methods: Retrospective analysis of thrombolysis databases in two university hospitals. Patients with ACLVO confirmed by transcranial Duplex or angiography and NIHSS score Ͻ8 treated either with IVT only or with EVT were selected. Successful recanalization was defined as TIMI 2 or 3 in the EVT group and as TIBI 4, 5 or improvement of 1 or more in the TIBI scale in the IVT group. Symptomatic intracerebral hemorrhage (SICH) was defined as PH2 with neurologic deterioration, and favorable outcome as modified Rankin score of Ͻ3 at 3 monthsResults: Thirty-seven patients were treated with IVT only and 23 patients were treated with EVT (in 8 cases EVT followed IVT due to lack of recanalization). Median [quartiles] age was 73 [60,77] in the IVT group and 62 [52,66] in the EVT group (pϭ0.021), and median NIHSS score before treatment was 6 [4,7] and 4.5 [2,6] (pϭ0.068), respectively. Distribution of the site of occlusion in IVT/EVT groups was M1 30%/43%, M2 67%/13%, terminus ICA 3%/17% and tandem ICA-MCA 0%/26% (pϭ0.001). Recanalization at 2 hours after treatment occurred in 64.3% of the IVT and in 90.5% of the EVT group (pϭ0.047). SICH appeared in 10.8% and 5.3% (pϭ0.491), favorable outcome was recorded in 70.3% and 73.3% (pϭ0.789) and mortality in 10.8% and 15.8% (pϭ0.444). After exclusion of M2 occlusions in each group similar results were obtained. Conclusions: Patients with stroke presenting with mild symptoms and anterior circulation large vessel occlusion show high rate of favorable outcome and low mortality whether treated with IVT or EVT. Successful recanalization was more frequent with endovascular therapy. In these selected patients, treatment with EVT appears to have similar safety profile and outcomes than IVT only. Larger, prospective studies are needed to confirm these preliminary findings.

Th P222 Early Ischemic Lesion Recurrence Pattern In The Borderzone Region After Thrombolysis

Sam Yeol Ha, Chung-Ang Univ College of Medicine, Seoul, Korea, Republic of; Oh Young Bang, Gyeong-Moon Kim, Chin-Sang Chung, Kwang Ho Lee; Samsung Med Cntr, Sungkyunkwan Univ, Seoul, Korea, Republic of Background : The ischemic penumbra is defined as ischemic tissue which is functionally impaired and is at risk of infarction and has the potential to be salvaged by reperfusion. The possibility of penumbral region would be highest in the borderzone territory in ischemic stroke, and this be continued after thrombolysis. Methods: From Samsung Acute Stroke Registry, 35 patients with middle cerebral artery stroke were included, who were treated by combined intravenous and intra-arterial thrombolysis or intra-arterial thrombolysis within 6 hours of symptom onset and they underwent brain MRI including diffusion-weighted and perfusionweighted imaging and follow up MRI at 1 st and 7 th day. We analysed the early ischemic lesion recurrence pattern in the borderzone region in the good recanalization group (TIMI 2 or 3) and divided these lesions into cortical borderzone and deep subcortical borderzone infarction. Results : Ischemic lesion recurrence in the borderzone region developed in the 14 patients of the 21 patients shown good recanalization. All these patients except one showed clinical improvement on NIHSS scores (improvement range 1 to 14). Cortical borderzone (CBZ) recurrence lesions were seen in patients with slow antegrade/retrograde collateral flow(Nϭ8) and isolated deep subcortical borderzone (IDSBZ) recurrence lesion in patients with fast collateral flow(Nϭ6). These patients with borderzone lesion recurrence in the good recanalization group showed residual stenosis in occlused vessel or focal incomplete recanalization after thrombolysis on angiography, and the recurrence lesion developed around dark vessels on T2*-weighted gradient echo imaging. The patients with CBZ recurrence lesion showed larger diffusion-perfusion (TmaxՆ8 sec) mismatch (69.5Ϯ46.5 vs 46.7Ϯ40.2, pϭ0.014) and initial NIHSS scores (13.8Ϯ4.4 vs 11.8Ϯ3.9, pϭ0.217) than the patients with IDSBZ recurrence lesion. Conclusion: Early ischemic lesion recurrence pattern in the borderzone region represents temporal and spatial progression of the penumbra even though good recanalization and vessel flow status before and after thrombolysis.

Th P223 Early Benefit of Thrombolysis is Limited to Strokes of Minor and Moderate Severity

George Ntaios, Mohamed Faouzi, Neurology Service, CHUV, Lausanne, Switzerland; Patrik Michel; CHUV, Lausanne, Switzerland Introduction: A large number of parameters have been identified as predictors of early outcome in patients with acute ischemic stroke. The present work analyzes a wide range of demographic, metabolic, physiological, clinical, laboratory and neuroimaging parameters in a large population of consecutive patients with acute ischemic stroke and aims to identify independent predictors of early clinical course. Subjects andMethods: We used prospectively collected data from the Acute STroke Registry and Analysis of Lausanne (ASTRAL). All consecutive patients between 01/2003 and 12/2008 admitted to our stroke unit and/or intensive care unit with ischemic stroke within 24 hours after onset of symptoms were analyzed. Univariate and multivariate analysis was performed to identify significant association with NIHSS score at admission and 24 hours. We also sought for any interactions between identified predictors. Results: 1446 patients were included in the analysis. In multivariate analysis, NIHSS at 24 hours was associated with NIHSS at admission (␤ϭ1, PϽ0.001), initial glucose (␤ϭ0.05, PϽ0.002) and thrombolytic intervention (␤ϭ-2.91, PϽ0.001). There was a significant interaction between thrombolysis and NIHSS at admission (pϽ0.001), indicating that the latter does not improve early clinical course in patients with severe stroke. Conclusions: Thrombolytic treatment, lower initial glucose and lower initial stroke severity predict favourable early clinical course. However, the effect of thrombolysis was limited to minor and moderate stroke, and was absent in patients with severe stroke.

Author Disclosures: G. Ntaios: None. M. Faouzi: None. P. Michel: None.

Th P224 Facilitated Recanalization

Background:

The optimal treatment method for tandem occlusions (TO) of the extracranial internal carotid artery (ICA) and intracranial arteries is not well established. One approach consists of proximal followed by distal recanalization, during which the process of facilitated recanalization (FR) may be observed. FR involves spontaneous intracranial recanalization immediately following proximal revascularization, thereby obviating the need for intracranial intervention. We aimed to evaluate the incidence of this phenomenon in a cohort of TO patients treated via endovascular means at our center. Methods: Consecutive patients with TO of the ICA origin and an intracranial artery (i.e. ICA terminus, M1 middle cerebral artery [MCA], or M2 MCA) were identified in the UPMC endovascular acute stroke database. In all cases, treatment approach consisted of proximal revascularization with angioplasty and stenting followed by, if necessary, intracranial recanalization. The incidence of FR and clinical outcomes in the FR versus non-FR group was analyzed. Endpoints were successful recanalization (TIMI Ն 2), parenchymal hematoma (PH), and good clinical outcome (mRS Յ 2) at 3 months. Results: Of Author Disclosures: J. Sharma: None. S. Mehta: None. S. Chowdhry: None. A. Nanda: None. N. Tummala: None. K. Blackham: None.

Th P231 Initial Assessment of CT Perfusion Parameters to Determine Thresholds for Infarct Core, Ischemic Penumbra, and Benign Oligemia in Patients undergoing Endovascular Revascularization Therapy (ERT)

Sundeep Mangla, Zhenteng Li, Brandon Smoller, Alan Cherney; SUNY Downstate Health Science Cntr, Brooklyn, NY Background and Purpose: CT Brain Perfusion (CTP) is emerging as a powerful tool in guiding stroke therapy. Limited studies have shown CTP parameter (MTT, CBF, CBV) thresholds that differentiate ischemic penumbra from infarct core. The purpose of this study is to determine CTP parameter thresholds (MTT, CBF, CBV) that differentiate infarct core, penumbra, and benign oligemia in patients undergoing ERT. Methods: A retrospective review of a prospective clinical database for patients receiving ERT was performed from 05/01/07 through 12/31/09. Among 14 patients found, five patients were excluded secondary to absence of perfusion imaging. The remaining 9 who underwent CTA and CTP on presentation, and delayed noncontrast CT (NCT) or MRI, Ͼ24 hrs after stroke were divided into either the persistently occluded group or the revascularized group, based on results from catheter angiography immediately post-intervention. CTP source images were processed by Philips Extended Brilliance Workshop 3.5.0.2254 with anterior cerebral artery as the Arterial Input Function and superior sagittal sinus as the Venous Output Function. A MATLAB graphic user interface developed by our research team was used to co-register perfusion maps with delayed final infarct NCT or MRI. For both groups, the final infarct was outlined as region of interest (ROI) on the NCT or MRI. For the occluded group, the region that survived (n ROI ϭ32) was defined as benign oligemia (BO) while the region that infarcted (n ROI ϭ35) represented the original penumbra (P) and infarct core (IC). In contrast, for the revascularized group, the region that survived (n ROI ϭ35) encompassed the original benign oligemia and penumbra while the final infarct (n ROI ϭ22) was defined as the infarct core. In addition, contralateral regions with normal perfusion were used for normalization. Results: In the occluded group, ROI's that demonstrated absolute CBV Ͼ 3.5 (ml/100g) and CBF Ͼ 30 (ml/min/100g) trended towards survival in absence of revascularization (benign oligemia). Relative values did not appear to demonstrate any predictive trends. For the revascularized group, ROI's with absolute CBV Ͼ 3.0 and CBF Ͼ 20 were potentially salvagable (penumbra). Relative CBV Ͻ .7 and CBF Ͻ .3 were also potentially salvageable following successful ERT. (Figure 1)

Th P236 Comparison of Ultrasonography and MR Images to High Risked Plaques for Carotid Artery Stenting; with a Pathological Diagnosis

Manabu Inoue, Showa Univ Northern Yokohama Hosp, Yokohama, Japan; Takehiko Nagao, Yubuhito Mochizuki, Masahiro Ida, Manabu Takahashi, Tokyo Metropolitan HMTC Ebara Hosp, Tokyo, Japan; Mitsuru Kawamura, Showa Univ Hosp, Tokyo, Japan; Masayuki Yokochi, Hideki Takubo; Tokyo Metropolitan HMTC Ebara Hosp, Tokyo, Japan

[Background] Carotid ultrasonography (CUS) has been the first choice for the indication of carotid artery stenting (CAS) for a long time, though the examination alone was difficult to fully predict the risk of complications such as re-stenosis and distal embolism. Plaque findings such as fibrous caps and intramural hemorrhages are the particularly valuable information. We used the MRI plaque imaging together to evaluate the plaque findings for comparison and the accuracy was decided by the pathological results. [Methods] We retrospectively studied consecutively 18 carotid plaque specimens from 18 patients with carotid endarterectomy and compared their findings between MRI plaque imaging and CUS. The study focused fibrous caps and intramural hemorrhage findings inside the plaques. Conventional method was used for CUS. The 1.5T MAGNETOM Avanto MRI performed PROPELLER (Periodically Rotated Overlapping Parallel Lines with Enhanced Reconstruction) sequence for plaque imaging to avoid motion artifacts and also Gd-enhancement images were performed at the plaque portions. Distinguished signal of the plaque was sub-quantitatively analyzed. The pathological diagnosis was given by an independent pathologist unaware of clinical information. [Results] The sensitivity and specificity of CUS in detection of fibrous caps were both 100%, respectively. In the other hand, the sensitivity and specificity of Gd-enhanced PROPELLER-ed MR plaque imaging were 40% and 100%, respectively. Strikingly, the sensitivity and specificity of CUS in the detection of intramural hemorrhages were only 22.2% and 100%, respectively, when the sensitivity and specificity of Gd-enhanced PROPELLER-ed MR plaque imaging were 77.8% and 100%. The accuracy of the Gd-enhanced PROPELLER-ed MR plaque imaging in the detection of intramural hemorrhage was significantly higher in comparison to that obtained using CUS. Also from the pathological results, Gd-enhanced MR images could detect the inflammation inside the vulnerable plaques meanwhile the CUS could not detect well enough numbers in contrary. Conclusions: Plaques accompanied with fibrous caps, CUS showed higher detection than MR plaque images, but with intramural hemorrhages seen in vulnerable plaques, which most complications might occur, the enhanced MR plaque images with PROPELLER sequence showed higher accuracy for diagnosis. This concludes that plaques with inflammation are only detected by the MRI, and even with Doppler CUS, the resolution of intramural hemorrhages has its limits. We suggest to use the MR plaque imaging with Gd-enhanced PROPELLER sequence together with the CUS to prevent the complications for high risk CAS cases.

Th P237 Thrombolysis In Cerebral Ischemia/tici Vs. Thrombolysis In Myocardial Ischemia/ Timi Scores As Assessment Tool For Recanalization In Endovascular Therapy For Acute Stroke Due To M1 Mca Occlusion

Oana Spataru, Syed Zaidi, Mouhammad Jumaa, Ridwan Lin, Lawrence Wechsler, Michael Horowitz, Brian Jankowitz, Amin Aghaebrahim, Maxim Hammer, Vivek Reddy, Tudor Jovin; UPMC, Pittsburgh, PA Introduction: There is considerable debate whether TIMI scores vs. TICI scores should be used as recanalization outcome mesurement for endovascular acute stroke trials. We sought to compare these two scoring methods with respect to clinical outcomes and final infarct volumes in a homogenous patient population with M1 MCA occlusion who underwent follow-up MRI imaging. Methods: Retrospective review of a prospectively acquired endovascular stroke database was performed. Patients with M1 MCA occlusion and available DWI MRI on follow-up were selected. Collected data included baseline risk factors, clinical and imaging characteristics. Prospectively collected TIMI scores were obtained at the time of the procedure by the treating interventionalist. TICI scores were obtained subsequently by blinded investigators. Post treatment DWI volumes obtained by a blinded investigator using a semiautomated method, and 90 day modified Rankin scores (mRS) were reviewed. Successful recanalization was defined as TIMI grade 2 & 3, TICI grade 2a, 2b or 3 or altenatively as TICI 2b or 3 only. Clinical outcome was considered favorable if 90 day mRS was Յ 2. Results: Between November 2002 and April 2010, we identified 178 patients. TIMI grade 2 & 3 recanalization was achieved in 144 (80.9%) patients. Overall 76 (45.8%) patients had favorable outcomes. A high correlation between TIMI and TICI scores was noted (spearman 0.79, PϽ0.0001). By TIMI scores, succsesfull recanalization was achieved in 144/178(81%) of patients. By TICI with 2a as cutoff in 150/178(84.27%) and with 2b as cutoff in 98/178 (55%) of patients. In univariate and multivariate analyses all recanalization cutoffs were found to be significantly associated with outcomes (for TIMI23 OR 12.65, 95% CI 2.08-76.72, pϭ0.006, for TICI2a OR 11.75, 95% CI 1.8-75.6, pϭ0.009, for TICI 2b OR 9.08, 95% CI 2.7 -30.5, PϽ0.0001) A strong corelation between both TICI and TIMI scores and final infarct volumes was found (see graphs).

Conclusion:

Our results indicate that TIMI and TICI scores are highly correlated both with respect to clinical outcomes and with respect to final infarct volumes. The concern that TIMI scores do not adequately reflect tissue reperfusion status post endovascular therapy for acute stroke could not be substantiated by our findings.

Th P244 Severity, Age, and Leukoaraiosis affect Rehabilitation Outcomes of Inpatients with Different Types of Ischemic Stroke

Joe Senda, Yasuaki Mizutani, Kazuhiro Hara, Ryoichi Nakamura, Shigenori Kato, Mizuki Ito, Naoki Atsuta, Hirohisa Watanabe, Gen Sobue, Dept of Neurology, Nagoya Univ Graduate Sch of Medicine, Nagoya, Japan; Keiichi Ito, Kensuke Hamada, Yushi Oshima, Motomu Terasawa, Tomoteru Kotake, Hideo Kishimoto, Kozo Fukuda; Kami-iida Rehabilitation Hosp, Nagoya, Japan Background and Purpose: We investigated the clinical factors affecting rehabilitation outcomes of inpatients with ischemic strokes of different etiologies. Methods: Subjects were 314 ischemic stroke patients (196 males, 118 females; age 71.7Ϯ12.4 years; length of hospitalization 84.6Ϯ26.3 days) transferred from stroke units or emergency units for inpatient rehabilitation at Kami-iida Rehabilitation Hospital (January 2007-December 2009). National Institutes of Health Stroke Scale (NIHSS) scores and head-MRI/MRA were assessed for all patients on admission. Functional Independence Measure (FIM) scores were measured both on admission and discharge. Results: Stroke etiologies were as follows: lacunar (LI) in 27 patients; atherothrombosis (AT) in 49; branch-atheromatousdisease (BAD) in 90; artery to artery embolism (A to A) in 33; cardiogenic embolism (CE) in 64; undetermined embolism (unable to differentiate between A to A and CE) in 40; the 11 remaining patients were not categorized. The NIHSS scores for patients with a definite diagnosis on admission were: 5.07Ϯ3.28 in LI; 11.41Ϯ6.24 in AT; 8.74Ϯ4.12 in BAD; 9.06Ϯ5.04 in A to A; and 9.65Ϯ5.98 in CE. The FIM scores at discharge were: 97.19Ϯ18.78 in LI; 83.57Ϯ23.85 in AT; 98.38Ϯ18.33 in BAD; 90.09Ϯ23.41 in A to A; and 83.91Ϯ27.98 in CE. MRI demonstrated high periventricular hyperintensity (PVH) scores in the LI and A to A patients (LI; 2.19Ϯ0.60, AT; 1.46Ϯ0.78, BAD; 1.45Ϯ0.73, A to A; 1.63Ϯ0.69, CE; 1.16Ϯ0.68). MRA demonstrated high rates of stenosis (Ն50%) or occlusion with intracranial arteries in the AT and A to A patients (LI; 9/27 [33.3%], AT; 38/49 [77.5%], BAD; 18/90 [20.0%], A to A; 28/33 [84.8%], CE; 27/64 [42.2%]). A multiple linear regression over all disease types revealed that NIHSS scores on admission (␤ϭ-0.653, Bϭ-2.813, PϽ0.001), age (␤ϭ-0.292, Bϭ-0.788, PϽ0.001) and PVH scores (␤ϭ-0.126, Bϭ-3.861, pϭ0.003) (R 2 ϭ0.565) clearly affected rehabilitation outcome (FIM scores at discharge), especially in A to A patients [NIHSS scores (␤ϭ-0.708, Bϭ-3.095, PϽ0.001); PVH scores (␤ϭ-0.256, Bϭ-9.065, pϭ0.015) (R 2 ϭ0.728)]. A multiple linear regression on the data from A to A patients also showed that, based on large-vessel arteriosclerosis, ischemic stroke rehabilitation outcome appeared to be influenced by leukoaraiosis. Conclusion: Our study revealed that severity, age, and leukoaraiosis at the start period of rehabilitation affect inpatient rehabilitation outcomes with ischemic stroke patients.

Author Disclosures: P.R.A. Cavalcanti: None. T.F. Campos: None. L.S. Berk: None. J.F. Araujo: None.

Th P246 Dysphagic Pattern According to Stroke Location

Ju Kang Lee, Hwan Tae Lee, Jeom Sun Jeong, Ki Deok Park, Jeong Man Kim, Yeong-Bae Lee; Gachon Univ, Sch of Medicine, Incheon, Korea, Republic of Author Disclosures: T. Kagiyama: None. T. Soeda: None. Y. Yokoyama: None. N. Hagiwara: None. Y. Watanabe: None. Y. Ishimatsu: None. N. Yokoyama: None. K. Kusuda: None. T. Kurokawa: None. K. Onoyama: None. S. Ibayashi: None.

Th P252 Use of Intelligently Controlled Assistive Rehabilitation Elliptical Trainer to Improve Walking and Fitness during Acute Stroke Rehabilitation

Judith M Burnfield, Adam P Taylor, Thad W Buster, Yu Shu, Amy J Goldman, Carl A Nelson; Madonna Rehabilitation Hosp, Lincoln, NE Introduction: During stroke rehabilitation, patients often seek to improve walking. While sophisticated devices exist to enable the mass repetition of a gait-like movement pattern thought to be important for promoting neuroplastic changes, many patients lack access due to the expense (e.g., robotic gait trainers) or need for multiple clinicians (e.g., partial body weight support treadmill training). ICARE, an Intelligently Controlled Assistive Rehabilitation Elliptical trainer, is an affordable training device developed to address these barriers. The current study explored the feasibility of incorporating ICARE training into an inpatient stroke rehabilitation program. Methods: Ten acute stroke rehabilitation inpatients were enrolled in the ICARE study within 96 hours of admission (ages 39-88 years; mean admission FIM locomotion scoreϭ2). Participants ICARE trained 3 to 5 times/week as an adjunct to physical therapy (mean total sessionsϭ10; rangeϭ3-25). Initial velocity (VEL), step length (SL), and body weight support (BWS) settings were customized to each participant. Total duration of exercise per session (DUR) and subsequent setting adjustments were determined based on participant's fatigue and cardiovascular response. Paired t-tests evaluated significant changes in training parameters (i.e., VEL, SL, total strides/session, DUR, and BWS) and participants' responses (i.e., HR; rating perceived exertion, RPE) between training's beginning (first two sessions averaged) and end (last two sessions averaged), as well as self-selected overground walking velocity pre and post ICARE training. Results: ICARE function improved from beginning to end of training as evidenced by significant increases in VEL (31 vs. 39 RPM; PϽ0.001), SL (20 vs. 25"; PϽ0.001), number of strides/session (426 vs. 778; pϭ0.002) and DUR (12.5 vs. 20.5 min; pϭ0.002), and decreases in external BWS (26 vs. 21% BW; pϭ0.023). HR (87 vs. 93 bpm) and RPE (12.4 vs. 12.6) did not change significantly between beginning and end. Overground walking velocity also improved (preϭ19 vs. postϭ37 m/min; pϭ0.007). Conclusions: ICARE enabled mass practice of a simulated gait activity, as evidenced by the large number of strides/session. The augmentation of traditional therapy with ICARE was tolerated well. Important gains were noted in endurance and speed (both overground walking and ICARE training).

Th P253 Muscle Demands of Device Assisted versus Clinician Assisted Sit-to-stand Transfers: Implications for Stroke Rehabilitation

Amy J Goldman, Thad W Buster, Adam P Taylor, Mitchell J Ediger, Yu Shu, Judith M Burnfield; Madonna Rehabilitation Hosp, Lincoln, NE Introduction: Back injuries are a serious problem in the rehabilitation setting. Frequent lifting of patients during transfers increases the risk of injury. Although mechanical sit-to-stand devices are readily available in most rehabilitation settings, some team members prefer manual transfers due to perceptions that they can more effectively facilitate activation of weakened muscles. The purpose of the current study was to compare hemiparetic muscle demands during device-assisted and clinician-assisted transfers in individuals recovering from a stroke. Methods: Ten adults (50-82 years) engaged in acute inpatient stroke rehabilitation participated. A Vancare VeraLift 350 (V) was used for device-assisted trials. Surface electromyography (EMG) recorded activity of the hemiparetic limb's gluteus maximus, lateral hamstring, vastus lateralis, gastrocnemius, and tibialis anterior. Participants performed three deviceassisted sit-to-stand conditions: 1) giving best effort (V-BE); 2) giving no effort (V-NE); and 3) physical therapist guided motions using physical and verbal assistance (V-PT). A fourth trial, with only the physical therapist's assistance (PT), was performed. The same physical therapist (36 years old, 10 year stroke rehabilitation experience) provided assistance for trials. Peak EMG was expressed as a percentage of each muscle's maximum voluntary contraction (% MVC). Duration was expressed as a percentage of the movement trial. One-way ANOVA's with repeated measures identified significant differences in EMG peak and duration across conditions (PT, V-PT, V-BE, and V-NE). When assumptions of normality were violated, Friedman's ANOVA on Ranks was performed. Bonferroni adjustments accounted for multiple comparisons. Statistical significance was defined as PϽ 0.010. Results: Figure 1 summarizes significant findings for the five hemiparetic limb muscles. Conclusions: Hemiparetic muscle Abstracts and presentations are embargoed for release at date and time of presentation or time of AHA/ASA news event. Information may not be released before then.

Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. by guest on September 20, 2013 http://stroke.ahajournals.org/ Downloaded from activation increased when effort was encouraged (verbally and/or manually). Ankle muscles, in general, were less active when strapped into the mechanical device than when mobile with the PT.

Author Disclosures: A.J. Goldman: None. T.W. Buster: None. A.P. Taylor: None. M.J. Ediger: None. Y. Shu: None. J.M. Burnfield: None.

Th P254 Serum Uric Acid and Outcome after Ischemic Stroke. Results from the Mexican Multicenter Ischemic Stroke Registry (The PREMIER Study)

Erwin Chiquete, Hosp Civil de Guadalajara 'Fray Antonio Alcalde', Guadalajara, Mexico; Jose Ĺ Ruiz-Sandoval, Hosp Civil de Guadalajara, Guadalajara, Mexico; Carolina Leo ´n-Jime ´nez, ISSSTE, Guadalajara, Mexico; Ana Teresa Ochoa-Guzma ´n, Hosp Civil de Guadalajara, Guadalajara, Mexico; Luis M Murillo-Bonilla, Universidad Auto ´noma de Guadalajara, Guadalajara, Mexico; Antonio Arauz-Go ´ngora, Instituto Nacional de Neurologı ´a y Neurocirugı ´a, Mexico City, Mexico; Fernando Barinagarrementeria, Hosp Angeles de Quere ´taro, Quere ´taro, Mexico; Alma Ramos-Moreno, INNOVAL, Mexico City, Mexico; Carlos Cantu ´, Instituto Nacional de Ciencias Me ´dicas y Nutricio ´n, Mexico City, Mexico; PREMIER Investigators Background: The relationship between serum uric acid (SUA) and stroke remains controversial and it is not clear whether the association is either circumstantial or causal. Some recent evidence supports that this routinely measured cardiovascular marker is a risk factor independently related with stroke outcome. Therefore, we aimed to examine the relationship of SUA with ischemic stroke subtypes and the clinical outcome. Methods: We analyzed data of patients for whom SUA was measured at hospital admittance from different geographic regions of Mexico, included in the PREMIER study (Primer Registro Mexicano de Isquemia Cerebral) from October 2004 to August 2006. We considered for the analyses the personal risk factors, National Institutes of Health Stroke Scale (NIHSS) at hospital arrival, comorbidities treatment, and final outcome as assessed by the modified Rankin scale (mRS) at 30-day, 3-, 6-and 12-month follow-up. Results: A total of 463 patients were included (52% men, mean age 68 years; range 21 to 104 years). Mean SUA at hospital admittance was 6.1 Ϯ 3.7 mg/dl (0.36 Ϯ 0.22 mmol/l); higher for men, as compared with women [6.6 Ϯ 3.9 vs. 5.5 Ϯ 3.5 (0.39 Ϯ 0.28 vs. 0.32 Ϯ 0.20 mmol/l); pϭ0.002 ]. A SUA of Յ4.5 mg/dl (Յ0.26 mmol/l; the lowest tertile of the sample) was associated with functional independence at 30 days post-infarction in univariate analysis (mRS 0 to 1: 47.7% vs. 32.7%, for the lowest vs. higher tertiles, respectively; pϭ0.005), but not with stroke mortality or functional independence at 3-, 6-and 12-month follow-up. In a multivariate analysis controlled for age, gender, hypertension, diabetes, body mass index, statin, anti-hypertensive and anti-platelet therapy, previous stroke and smoking habit; a SUA of Յ4.5 mg/dl (Յ0.26 mmol/l) was independently associated with 30-day functional independence (OR: 1.94, 95% CI: 1.21-3.10). Moreover, a lower SUA was also associated with a minor stroke (NIHSS of Ͻ5 points at hospital admittance: 47.3% vs. 33.4%, for the lowest vs. higher tertiles, respectively; pϭ0.02). We observed a trend towards higher SUA values among strokes due to large and small vessels disease, as compared with other stroke mechanisms [6.4 Ϯ 4.1 vs. 5.5 Ϯ 3.5 (0.38 Ϯ 0.24 vs. 0.34 Ϯ 0.19 mmol/l); pϭ0.08 ]. Conclusions: A SUA of Յ4.5 mg/dl (Յ0.26 mmol/l) is independently associated with a higher chance of being functionally independent at 30 days post-stroke, possibly due through a reciprocal relationship with minor strokes. Higher SUA levels tend to be found among small-and large-vessels disease, underlying the participation of uric acid in atherotrombosis pathogenesis.

Author Disclosures: E. Chiquete: None. J.L. Ruiz-Sandoval: None. C. Leo ´n-Jime ´nez: None. A. Ochoa-Guzma ´n: None. L.M. Murillo-Bonilla: None. A. Arauz-Go ´ngora: None. F. Barinagarrementeria: None. A. Ramos-Moreno: None. C. Cantu ´: None.

Th P255 Caregivers Solutions to Problems Experienced in Caring for Stroke Survivors

Victoria Steiner, Joan Bick, Sandra Krzysiak, Beth Runner, Linda L Pierce; The Univ of Toledo, Toledo, OH Background and Purpose: Stroke is a leading cause of long-term disability. Many stroke survivors return home to be cared for by untrained and unprepared new caregivers and problems surface. The research on these caregivers' successes in finding solutions to problems is limited. The purpose of this secondary analysis of data project was to identify solutions to problems that family caregivers used while caring for stroke survivors. Methods: These data came from a larger stroke study where biweekly interview data for 73 adult caregivers over a 1-year period were collected. Eighteen men and 55 women from northern Ohio and southern Michigan participated. These caregivers were asked about problems /challenges that they had experienced while caring for the stroke survivor. When problems were identified, the caregivers were asked what solutions they had tried to solve them. These data were analyzed using Colaizi's rigorous content analysis method. Results: Six themes for the caregivers' solutions to problems in caring for the stroke survivor emerged from these data and were drawn to the process dimensions in Friedemann's framework of systemic organization. Themes included: 1) getting life in order through changing behaviors or altering the environment (system maintenance in Friedemann's terms); 2) seeking medical advice and treatment (system maintenance and individuation); 3) reaching out to family, friends or community resources (coherence); 4) psychologically accepting the new normal (system maintenance and individuation); 5) hanging on to what they had (coherence); and 6) taking time for self (individuation). No differences appeared among these themes for male versus female caregivers. Conclusions: These caregivers of stroke survivors were doing everything in their power to preserve their lives and family system. Knowing caregivers' solutions to problems in caring for the stroke survivor can help nurses, and others, to provide them with education and problem solving strategies which assist them in adapting to their new caregiver role. Yeon Hwan Park, HeeKyung Chang; Seoul National Univ, Seoul, Korea, Republic of Background: While adult daycare is considered a culturally acceptable model of long-term care in countries with a tradition of family-oriented caregiving, South Korea is struggling as soaring needs for developing qualified daycare services based on the needs of older adults and family caregivers. Purpose: The aim of this study was to examine the effectiveness of Adult Daycare Service (ADS) based on partnership for older adults with stroke and their family caregivers. Methods: A quasi-experimental intervention study. Older adults with stroke from two ADS centers in Korea were separately allocated to either an experimental (nϭ16) or a control group (nϭ13). Experimental group received health education and tailored rehabilitation program with their family caregivers based on partnership by trained ADS center nurses for 12 weeks. Results: The mean ages were 76.6 years (experimental) and 77.0 years (control). There were no significant differences in socio-demographic and clinical characteristics between two groups. Intervention participants had improved changes in diastolic blood pressure (pϭ.019), cognitive function (PϽ.001), performance of activities of daily living (PϽ.001), and nutritional status (PϽ.001). Three of the quality-of-life domains showed trends toward increased in the experimental group: physical functioning (PϽ.001), role physical (pϭ.001), and role emotional (PϽ.001). Conclusion: The ADS based on partnership had significant effects on blood pressure control and improving cognitive function, performance of activities of daily living, and nutritional status of older adults with stroke. Further research is needed to develop nursing intervention for older adults with stroke at long term care facilities as well as at home and evaluate the long Author Disclosures: P. Ohnmacht: None. J. Whitley: None. J. Angrisani: None.

Th P274 Dysphagia Screening: A Nurse Driven Process

Joan A Mesler, Melanie Wallace, Arvind Vasudevan, Paula McClean, Angela Reid, Marjorie Wiley, Andrea Eudy, Barbara Fox, Joey Campbell; CMC-NORTHEAST, CONCORD, NC Project Selection: Stroke continues to be the third leading cause of death in the United States and the number one cause of adult disability. North Carolina is one of three states that make up the "Stroke Buckle" where the stroke death rates are two times greater than the rest of the nation (Rosamond et al., 2008). According to the North Carolina Stroke Care Collaborative, Cabarrus county stroke death rates fall slightly below that of the US at 48.9% per 100,000 populations. A frequent, yet preventable complication of stroke is aspiration pneumonia. In order to help prevent this, patients must receive nothing by mouth until they are determined to be safe to take food or liquid without signs and symptoms of aspiration. This determination is completed by performing a dysphagia screen. With a shared passion and goal for improving stroke care and outcomes, the Stroke Program and the Neuroscience Department at Carolinas Medical Center-NorthEast were committed to exploring potential solutions to this problem. Goal: The American Stroke Association had set goals for core measures associated with stroke. Our immediate goal was the 85th percentile with a stretch goal of the 95th percentile. Our goal was not only to improve performance in this area but provide quality care to our patients based on evidenced base practice. Improvement Process: After review of current policies, baseline data, and future external regulations, the team performed a literature review of published evidence and networked with other national health agencies and facilities to consider established approaches that were being utilized. Criteria for screening this population was established and the team began constructing a tool for utilization by the bedside nurse for dysphagia screenings. Compliance monitoring of the tool occurred concurrent and recommendations were reported back to the team. Results/Outcomes: The dysphagia screen compliance rate in the stroke population for year to date 2010 is 98%. Innovation, Sharing Knowledge: Staff ownership paved the way to improving this measure and ultimately ensuring better patient outcomes. By sharing ownership in the process and providing input it remained on the dashboard of bedside nurses. The patient and family/caregiver were included in the process to increase education and understanding of dysphagia and steps to prevent development of pneumonia.

Author

Background:

The diagnosis and treatment of stroke is time-sensitive. Patient outcomes are directly affected by the amount of time that the healthcare team uses to make the stroke diagnosis and start treatment. Appropriately administering the clot-busting drug alteplase (tissue plasminogen activator) (t-PA) (thrombolytic) (lytic) during the "golden hour" following stroke diagnosis greatly increases the chance of a positive outcome. The stimulus for stroke system re-design is apparent with stroke as the third leading cause of death in the United States and this healthcare organization's location in the heart of the stroke buckle. Purpose: Eligible patients treated with t-PA have shorter lengths of stay, more discharges to home, decreased rehabilitation and nursing home costs, and improved quality-adjusted life-years (QALY) saved (NINDS, 1995). Given the time urgency of stroke care and deficits when stroke is untreated (Saver JL Stroke 2005), our stroke team established a goal to decrease the average emergency department door to lytic time by 15%. Methods: Administrative support, strong leadership, collaboration, clinical champions and continuing education are important elements of success for stroke centers. An algorithmic approach, standardization, process improvement, and high reliability principles were used for implementation of evidenced based interventions, including thrombolytic administration. Concurrent and retrospective analysis of the Code Stroke process and regional thrombolytic utilization and referral was performed. Staff interviews, flowcharting, and concurrent quality clinician feedback and analysis were used and a Stroke Clinical Efficiency Group was developed with diverse membership. This enhanced our stroke continued readiness and to obtain input for an integrated approach. Post thrombolytic administration team analysis was employed to "drill-down" on the barriers and challenges to meeting door to lytic benchmarks. Results: Improvements have positively impacted code stroke response targets. Augmentation of code stroke processes has resulted in improved door to lytic times, improved quality of life for patients and families, and reduced costs. Response time data has indicated that we are below the benchmark for several response times. The average door to lytic time decreased per data point 20% from 95 (July-December 2009) to 76 (January-May 2010), and by 30% per monthly comparison, from 97.6 to 68, respectively. Conclusions: Collaboration, use of best practice guidelines, and high reliability principles resulted in improvements in the rapid assessment and treatment of stroke patients. Next steps are to establish stretch goals for all code stroke response times and promote best practice in stroke care throughout the region. Introduction/Hypothesis: A positive relationship between hospital patient-volume (HV) and outcomes is widely acknowledged. We asked whether this relationship holds between the HV for ischemic stroke and variables such as the likelihood, promptness, and risks of IV tissue plasminogen activator treatment (tPA). Methods: We used the Colorado Stroke Registry, a prospective database shared by 38 hospitals, to identify patients meeting these criteria: ischemic stroke with onset in a community setting and arrival to hospital from the scene by EMS or private means within 180 minutes. Transfers between hospitals were excluded. We explored the relationship of HV (the # of included records from each hospital) with the hospital-specific relative risks for: receiving tPA, receiving tPA within one hour, having a listed contraindication to tPA, and having symptomatic intracerebral hemorrhage (SICH) after tPA. We also compared HV to median arrival-to-CT and median arrival-to-tPA times. Statistical comparisons were made by linear regression, Chi-Square, t-test, and Kruskal-Wallis, as appropriate. Results: From Ͼ8,700 ischemic strokes we identified 2,136 patients meeting inclusion criteria. HV ranged from 1 to 289 patients across 32 hospitals with data. The median HV was 31, with an interquartile range of 4.5-127. HV was not significantly correlated with: median age, gender, median NIHSS, median onset-to-arrival-time, or mode of arrival. HV was strongly correlated with the likelihood of receiving tPA, which was 3 times more likely in hospitals above the HV median as compared to those below (24% vs. 8%, p ϭ 0.0002). HV was not correlated with: tPA-in-1-hour, median arrival-to-CT-time, median arrival-to-tPA-time, listed contraindications to tPA, or SICH. Conclusions:Our data show that the number of ischemic strokes recorded by hospitals correlates positively with the likelihood of receiving tPA. It does not, however, correlate with the promptness of either CT scanning or tPA administration. Neither does it correlate with the risk of SICH following tPA. As a caveat, we acknowledge limitations in ourConclusions: our data are observational in nature and based on self-reporting from hospitals. Nevertheless, this analysis suggests that "practice does not make perfect" for tPA use in ischemic stroke. This is surprising since a positive correlation between volume and outcome is seen in skill-dependent procedures such as heart surgery. In comparison, administration of tPA is a relatively low skill procedure (although one requiring considerable clinical judgment). Lower volume hospitals appear to be capable of giving tPA as quickly and as safely as higher volume hospitals, but they are significantly less likely to use tPA at all. These findings, if confirmed by other investigators, may have relevance in planning and improving stroke systems of care.

Author Disclosures: D.B. Smith: None. P. Murphy: None. W. Jones: None.

Th P278 The impact of the European Cooperative Acute Stroke Study (ECASS) III on clinical practice

Jens Minnerup, E. Bernd Ringelstein, Dep of Neurology Muenster, Muenster, Germany; Klaus Berger, Heike Wersching; Institute of Epidemiology and Social Medicine, Muenster, Germany Introduction: ECASS III extended the thrombolysis time window for stroke patients from 3 to 4.5 hours after symptom onset. Since a large proportion of stroke patients arrive at hospital later than 3 hours ECASS III raised hope that more patients will be treated with rt-PA. To investigate the effect of the extended thrombolysis time window on routine stroke care we studied the proportion of stroke patients that received thrombolysis before and after the publication of ECASS III in September 2008. Additionally we determined whether the time window extension led to delay of treatment initiation. Methods: Data were collected prospectively within the regional Stroke Register of Northwestern Germany between January 2007 and December 2009. The onset-to-door (OTD) time was categorized into 6 hours. The door-to-needle (DTN) time was categorized into 180 minutes. To compare thrombolysis rates before and after publication of ECASS III we used a logistic regression analysis. Results: A total of 91805 ischemic stroke patients were included in the analysis. Overall, 9262 patients (10.1 %) were treated with rt-PA. The proportion of patients treated with rt-PA significantly increased over time. The strongest increase was observed for patients admitted between 3 and 6 hours after symptom onset between the third and the fourth quarter of 2008 (88.9% relative increase in IV 2008 compared to the first half year of 2007, PϽ0. 05,Figure). During the study period the proportion of patients with a DTN time Ͻ 30 minutes continuously increased and the proportion of patients with DTN times of Ͼ 60 minutes decreased. Conclusions: The results of ECASS III were rapidly incorporated in clinical practice. The overall proportion of rt-PA treated stroke patients and in particular those with OTD times of 3 to 6 hours increased after ECASS III publication. Previous concerns regarding an increase in DTN time were not confirmed.

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Th P279 Physicians Delay Thrombolysis if There Is More Time to The End of The Thrombolytic Window

Robert Mikulı ´k, International Clinical Rsch Cntr, St.Anne's Univ Hosp, Brno, Czech Republic; Petr S ˇevc ˇı ´k, Neurology department, Univ Hosp, Plzen, Czech Republic; Daniel S ˇan ˇa ´k, Neurology department,Univ Hosp, Olomouc, Czech Republic; Michal Bar, Neurology department, Univ Hosp, Ostrava, Czech Republic; Daniel Va ´clavı ´k; Neurology department, Ostrava Vı ´tkovici, Czech Republic Background: The earlier that thrombolysis is initiated, the greater the benefits of the treatment. We assess the hypothesis that the initiation of thrombolytic treatment is delayed if physicians have more time before the end of the thrombolytic time window. Methods: Prospectively collected data from the SITS register on all patients treated with thrombolysis between Jan/2004 and Feb/2010 in the Czech Republic were analyzed. A multiple regression analysis was used to assess the correlation between onset-to-door time and door-to-needle time. Also, patients were stratified according to onset-to-door time into 3 groups (0-60, 61-120, and 121-180 minutes), and inter-group differences were assessed with ANOVA and Chi-square tests. Results: Altogether, 2958 patients arrived within 3 hours of symptom onset in 51 stroke centers in the Czech Republic (78% of all hospital-based neurology departments). Of these, 2644 (89%) were treated with thrombolysis within 3 hours, and 314 (11%) after 3 hours. The number of patients arriving at 0-60, 61-120, and 121-180 minutes after symptom onset was 1453 (49%), 1206 (41%), and 299 (10%), respectively. Door-to-needle time was negatively correlated with onset-to-door time (rϭ -0.32, PϽ0.001) and significance did not change after adjustments for age, sex, baseline NIHSS, and year of treatment(rϭ -0.32, PϽ0.001). Door-to-needle time was 85Ϯ42, 70Ϯ31, and 48Ϯ23 min (pϽ0.001) in patients arriving 0-60, 61-120, and 121-180 minutes after symptom onset, respectively. Also, door-to-needle time Յ60 minutes was achieved in 31, 45, and 79% (pϽ0.001) of patients arriving 0-60, 61-120, and 121-180 minutes after symptom onset, respectively. Conclusions: Although half of thrombolytic candidates arrive at the hospital within 60 minutes of symptom onset, the benefit of thrombolysis is diminished for these patients because physicians delay the treatment. It is necessary to improve adherence to guidelines and to treat patients within 60 minutes of arrival at the hospital regardless of the amount of time left to the end of thrombolytic window. This study was supported by a grant from IGA MH CR NS10106-4/2008.

Author Disclosures: R. Mikulı ´k: None. P. S ˇevc ˇı ´k: None. D. S ˇan ˇa ´k: None. M. Bar: None. D. Va ´clavı ´k: None.

Th P280 Patient Refusal of Tissue Plasminogen Activator for Acute Stroke

Farhaan S Vahidy, UTH -Med Sch, Houston, TX; Nusrat Harun, UT Health, Houston, TX; James C Grotta, UTH -Med Sch, Houston, TX; Mohammad H Rahbar, UT Health, Houston, TX; Nneka L Ifejika-Jones, Sean I Savitz; UTH -Med Sch, Houston, TX Introduction: Intravenous t-PA (IV t-PA/t-PA) has been established as a cornerstone therapy for eligible patients with acute ischemic stroke (AIS). There is paucity of data on AIS patients who refuse IV t-PA. We characterized the incidence, demographics, severity, and outcome of AIS patients who were eligible yet refused IV t-PA. We hypothesized that demographic markers, clinical presentation, and outcome of AIS patients who refuse t-PA would differ from those patients who receive it. Methods A retrospective analysis of our stroke registry was conducted from July 1, 2004 to June 30, 2010. Patients presenting after the 3-hour window were excluded. We collected demographics, baseline NIH Stroke Scale (NIHSS) scores and discharge outcomes on patients who refused IV t-PA, and those who were treated with IV t-PA within 3 hours of symptom onset. A written consent for t-PA administration is usually not obtained from patients presenting within the 3-hour window. Results A total of 687 patients were treated with t-PA. Twenty six (3.7%) patients refused, translating into an incidence of one t-PA refusal for every 26 eligible patients. There has been a gradual decline in refusal with maximum number of cases (24/26 -92.3%) occurring from 2004 to 2007. A small fraction (11.5%) of patients also refused other treatments and diagnostic work-up. The mean onset to arrival time for t-PA refusals was not statistically different from those who received t-PA. Most refusals (61.5%) were either completely or in part insured via Medicare while 15.3% were uninsured. There were a significantly higher percentage (73%) of female patients who refused t-PA as compared to 49.3% who got treated (pϭ0.018). Age and ethnicity were not significantly different between the two groups. Admission NIHSS score, discharge mRS and the length of hospital stay were all significantly lower for t-PA refusals. After controlling for baseline NIHSS, refusal patients had a 2.5 times odds of improved outcome compared to t-PA treated patients (pϭ0.02).

Conclusion:

Over the period of investigation, there has been a low and gradually declining incidence of t-PA refusal. Female gender stood out as a significant indicator for refusal. No additional clear-cut demographic characteristics came forth as refusal predictors. The refusal patients had milder strokes, shorter hospital stays, and consequently better outcomes compared with treated patients. Further research would benefit understanding of patient refusal of standard of care treatment for acute stroke.

Th P281 Prognostic Modeling For An Efficacy And A Safety Of Thrombolysis In Acute Ischemic Stroke Patients

JiSung Lee, Korea Univ, Seoul, Korea, Republic of; Hee-Joon Bae, Seoul National Univ Bundang Hosp, Seongnam, Korea, Republic of; Youngchai Ko, Chungbuk National Univ College of Medicine, Cheongju, Korea, Republic of; Myung Suk Jang, Seoul National Univ Bundang Hosp, Seongnam, Korea, Republic of; Jong-Moo Park, Eulji General Hosp, Seoul, Korea, Republic of; Tai Hwan Park, Seoul Med Cntr, Seoul, Korea, Republic of; Kyung Bok Lee, Soonchunhyang Univ Hosp, Seoul, Korea, Republic of; Soo Joo Lee, Eulji Univ Hosp, Daejeon, Korea, Republic of; Yong-Jin Cho, Ilsan Paik Hosp, Goyang, Korea, Republic of; Moon-Ku Han, Seoul National Univ Bundang Hosp, Seongnam, Korea, Republic of; Juneyoung Lee; Korea Univ, Seoul, Korea, Republic of Background: Thrombolysis is the only proven treatment against acute ischemic stroke till now, but has limitations such as uncertainty of recanalization and risk of hemorrhagic complication. In order to overcome these, new approaches are emerging such as combination therapies, development of new thrombolytic drugs, and use of prognostic models to identify patients who can benefit from thrombolysis. This study aimed at developing and validating a prognostic model on efficacy and safety for Korean patients who are eligible for thrombolysis. Method: Data from a consecutive series of patients with acute ischemic stroke, who were hospitalized to Seoul National University Bundang Hospital within 12 hours from onset between 2004/1 and 2008/3, were used to develop the prognostic model. For external validation, data collected from 6 hospitals between April 2008 and September 2009 were used. The prognostic models for efficacy (modified Rankin scale (mRS) at 3 month Յ2) and safety (symptomatic hemorrhagic transformation) outcomes were constructed with multivariable logistic regression models, and bootstrap procedures were used for internal validation. External validation was evaluated for applicability of the developed model. Model performance was assessed for discrimination with receiver operator characteristic (ROC) curves and for calibration with calibration plot. To improve the prediction, recalibration was conducted by updating intercept and calibration slope. Results: In the efficacy model, age, history of diabetes, history of stroke, prior use of antiplatelets, initial NIHSS, thrombolysis, previous mRS, and stroke subtypes were included. Internal and external validation showed excellent discrimination (AUCϭ0.87 and 0.84, respectively). But the calibration for the external dataset was not so good. Therefore, updating of models through recalibration method was performed with evident improvement in calibration. The safety model considered predictors of age, gender, history of diabetes, stroke, hypertension, and hyperlipidemia, prior use of antiplatelets, statin, and anticoagulants, initial NIHSS, thrombolysis, interval from onset to arrival, initial systolic BP, initial glucose, and stroke subtypes. External validation showed excellent discrimination (AUCϭ0.82) and its calibration using the external dataset was satisfactory. Updated models through recalibration method showed good calibration towards the external dataset. Conclusion: This study demonstrated the successful development of the externally validated prognostic models for thrombolysis candidates using basic clinical predictors. We hope these models are used by clinicians in emergency settings in identifying patients that would be more benefited and less harmed from thrombolysis.

Author Disclosures: J.

Th P282 The Risk of Thrombolysis in Demented Population: A Case Control Study

Amer Alshekhlee, Jacob Kitchner, Sushant Kale, Eli Feen, Paisith Piriyawat, Charlie Callison, Randall Edgell, Nirav Vora, Salvador Cruz-flores; St. Louis Univ, St. Louis, MO Background: Thrombolysis for acute ischemic stroke (AIS) in elderly population is associated with higher mortality and intracerebral hemorrhage (ICH) rates. In this study, we assess impact of dementia on these outcomes. Methods: A cohort of patients with AIS was identified from the National Inpatient Sample database for the years 2000 to 2007. We selected patients with dementia that was identified by the ICD-9-CM codes including Alzheimer disease, senile, presenile, vascular, fronto-temporal, and Lewy body dementia. In addition, we compared the outcomes of demented patients treated with thrombolysis with a matched random sample of non-demented individuals that was selected from a pool of those with AIS and treated with thrombolysis (3 controls per case). Multivariate logistic regression analyses were used to assess covariates associated with hospital mortality and ICH. Results: In this analysis, 35557 patients were admitted with the diagnosis of AIS and superimposed dementia; only 207 (0.56%) had received thrombolysis treatment. In-hospital mortality (17.48% vs. 8.63%) and ICH (5.80% vs. 0.38%) were higher in the thrombolysis group (P Ͻ 0.0001) compared to those who did not receive thrombolysis. Multivariate analysis for hospital mortality showed association with thrombolysis (odds ratio 'OR' 16.15;95% confidence interval 'CI' 8.54,30.53) and ICH (OR 2.80;95% CI,1.82,4.32). Compared to a matched population (non-demented and treated with thrombolysis, nϭ 621), those demented and treated had a slight but insignificant increase in ICH (5.80% vs. 4.51%; P ϭ 0.45) and mortality (17.39% vs. 14.49%; P ϭ 0.31) rates. Among all treated patients, ICH remained predictor of mortality (OR 2.25;95% CI 1.02,4.99).

Conclusion:

The use of thrombolysis in elderly demented population harbor the same risks compared to the non-demented counterparts. The presence of ICH remains predictor of a higher mortality rate in elderly demented patients.

Author Disclosures: A. Alshekhlee: None. J. Kitchner: None. S. Kale: None. E. Feen: None. P. Piriyawat: None. C. Callison: None. R. Edgell: None. N. Vora: None. S. Cruz-flores: None.

Th P283 Symptomatic Intracerebral Hemorrhage Following Stroke Thrombolysis. What Is The Impact Of Different Criteria On Patient Long-term Outcome?

Daniel Strbian, Helsinki Univ Hosp, Helsinki, Finland; Tiina Sairanen, Helsinki Univ Central Hosp, Helsinki, Finland; Atte Meretoja, Helsinki Univ Hosp, Helsinki, Finland; Janne Pitka ¨niemi, Helsinki Univ, Helsinki, Finland; Jukka Putaala, Oili Salonen, Heli Silvennoinen, Markku Kaste, Turgut Tatlisumak, Helsinki Univ Hosp, Helsinki, Finland; Helsinki Stroke Thrombolysis Registry Group Objectives Symptomatic intracerebral hemorrhage (sICH) worsens outcome of ischemic stroke patients following thrombolysis. Dissimilar definitions of sICH were used in randomized trials and registries. We studied the magnitude of impact of sICH according to various definitions on patients' long-term outcome. Methods Our study cohort included 985 ischemic stroke patients treated with intravenous thrombolysis within 4.5 hours from the symptom onset according to the institutional guidelines at the Helsinki University Central Hospital between 1995 and 2008. Using univariate methods we analyzed differences in baseline demographic, clinical, and radiological characteristics of patients with versus without sICH (according to SITS, ECASS, and NINDS/Cochrane definitions). For each definition, we assessed association with 3-month outcome (modified Rankin Scale, mRS) in a multivariate model adjusted for possible confounders. Implementing receiver operating characteristic (ROC) curve and integrated discrimination improvement (IDI), we further studied impact of each definition on outcome. IDI analysis is, very briefly, a measure of improvement in model performance (increase in sensitivity and specificity) after adding a new parameter into the model (model M2 vs. M1). For both AUC-ROC and IDI analyses, two models were used. Patients' outcome (3-month mRS 3-6, 4-6, 5-6, or mortality) was used as a dependent variable in both models. As independent variables, model 1 (M1) included age, baseline NIHSS score, baseline glucose level, OTT, and presence of hyperdense artery sign or artery occlusion in any cerebral artery on baseline imaging. Model 2 (M2) included the same variables as M1 plus information on presence/lack of sICH (separately for each definition). Findings The frequency of sICH was 2.1% (SITS), 7.0% (ECASS), 9.4% (NINDS/Cochrane), whereas 19.8% of patients had any ICH. Of all sICH cases, 96% occurred within 36 hours after thrombolysis. Multivariate analysis showed independent association of sICH according to all definitions with poor outcome and mortality. Based on prediction modeling with AUC-ROC curve and IDI analyses, unwanted outcomes were largely explained by such parameters as age, baseline NIHSS and blood glucose, OTT, and signs of artery occlusion on baseline imaging. Compared with these parameters, the presence or lack of sICH had smaller additional predictive effect. This was especially true for minor impact of SITS-defined sICH, whereas ECASS-and NINDS/Cochrane-defined sICH had 2 to 3 times larger impact on outcome prediction. ECASS-defined sICH had somewhat bigger impact on predicting mRS 5 to 6 and mortality than NINDS/Cochrane. Conclusions: sICH according to the ECASS definition had largest impact on patients' outcome.

Author Disclosures: M.J. Wilder: None. M.M. Cortez: None. P.P. Ng: None. J.J. Majersik: None.

Th P287 Stroke Care and Outcomes in Patients With Pre-existing Dementia

Gustavo Saposnik, Univ of Toronto, Toronto, Canada; Roula Raptis, Applied Health Rsch Cntr, Toronto, Canada; Paula Rochon, Univ of Toronto, Toronto, Canada; Ying Liu, Institute for Clinical Evaluative Sciences, Toronto, Canada; Moira K Kapral, Muhammad Mamdani, Univ of Toronto, Toronto, Canada; Robert Cote, Mc Gill Univ, Montreal, Canada; Sandra Black, Univ of Toronto, Toronto, Canada; on behalf of the Investigators of the Registry ofthe Canadian Stroke Network, Stroke Outcomes Rsch Canada (SORCan) Working group Background: Stroke can be a devastating medical condition for patients and their families. With an aging population, patients are increasingly likely to present with stroke and pre-existing dementia. Little is known about how pre-existing dementia influences care processes and outcomes after stroke. Objective: To compare processes of care and short and long-term outcomes in patients with an acute ischemic stroke with and without pre-existing dementia. Methods: We conducted a retrospective cohort study using the Registry of the Canadian Stroke Network (RCSN) to identify patients presenting to 12 participating institutions with an acute first ischemic stroke between 2003-2008. Pre-existing dementia was defined as any type of dementia that was present prior to the stroke case index. Palliative patients were excluded. Logistic regression analysis and Cox-proportional Hazard models were developed to compare the outcomes of interest. Outcome Measures: 1°) Mortality at discharge, 30-days, and 1-year; 2°) Performance measures, disability at discharge (mRS Ն3), disposition. Results: Among 9304 eligible patients with an acute ischemic stroke, 702 (9.1%) had a history of dementia. Patients with dementia were older (mean age 81 vs. 70 years; PϽ0.001) and had more severe strokes (as per the Canadian Neurological Scale Ͻ4, 20.7% vs. 10.5%; PϽ0.001) than those without dementia. Stroke patients with dementia had also a higher prevalence of diabetes and atrial fibrillation. There was a minor difference in admission to stroke unit (63% vs 67.6%; OR 0.82, 95%CI 0.70-0.96) and those with dementia were less likely to receive thrombolysis (10.5% vs 15.7%; OR 0.63, 95%CI 0.49-0.81). There were no differences in other performance measures (glucose on admission, swallowing assessment, time from stroke onset to ER, discharge on antithrombotics or warfarin for AF). Patients with pre-existing dementia had higher disability at discharge (80.6% vs. 56.6%; OR 3.20, 95%CI 2.64-3.87) and were less likely discharged to place of residence prior to stroke (24% vs. 45%; PϽ0.001). Stroke fatality was dramatically higher in those with dementia, but this was explained by age, sex, stroke severity and co-morbid illness (Table ). Conclusions: Stroke patients with pre-existing dementia have twice the mortality rates as those without, but, the increased rates may be attributable to older age, greater stroke severity and comorbid illness rather than dementia itself. Still, two-thirds survive one year with greater disability and institutionalization, representing an increasing stroke care challenge, given population aging. Although UI has been used to predict functional outcome, there is limited data on the direct role of UI as an independent predictor of post-stroke disposition. Hypothesis: Low NIHSS is an established predictor of higher functional status. We assessed the hypothesis that absence of UI predicts post-stroke disposition to a functional level similar to low NIHSS.

Th P296 Patients with Stroke in Northeastern Brazil are Infrequently Treated with Thrombolysis and Evaluated for Stroke Etiology

Joa ˜o Jose ´Freitas de Carvalho, Hosp Geral de Fortaleza, Ceara, Brazil; Cicera Borges Machado, Secretaria de Saude do Estado do Ceara, Ceara, Brazil; Georgiana Alvares Andrade Viana, Hosp Geral de Fortaleza, Ceara, Brazil; Monique Bueno Alves, Bento Cardoso dos Santos, Gisele S Silva; Hosp Israelita Albert Einstein, Sa ˜o Paulo, Brazil Introduction: Little information exists on the epidemiology of patients admitted to Brazilian emergency departments (EDs) with stroke. Fortaleza is the state capital of Ceara ´(Northeastern Brazil), has a population of over 2.5 million, and is the 5th largest city in Brazil. Hypothesis: We hypothesized that patients admitted with stroke in Fortaleza are infrequently treated with thrombolysis and that investigation of stroke etiology is not routinely performed. Methods: Data were prospectively collected from patients admitted to the EDs of 19 hospitals in Fortaleza with a diagnosis of stroke or transient ischemic attack (TIA) by trained research coordinators from June-2009 to May-2010. In 2008, 90% of the patients admitted with stroke in Fortaleza were evaluated in either one of the 19 hospitals studied. Daily visits to EDs of the selected hospital were performed and all patients admitted with a diagnosis of stroke or TIA were prospectively evaluated. A dedicated nurse coordinator reviewed all the patients. Controversies were discussed with two stroke neurologists. Results: We evaluated 1510 patients. Mean age was 67.9 Ϯ 14.5 yo (50.2% males). Ischemic stroke was the most frequent subtype (71.8%), followed by parenchymal hemorrhage (20%), subarachnoid hemorrhage (5.4%) and TIA (2.7%). The prevalence of stroke risk factors was: hypertension (81.8%), diabetes (39.1%), hyperlipidemia (22.6%), obesity (10.1%), smoking (22%), alcohol use (18.8%), previous stroke (32.4%) and previous myocardial infarction (8.4%). Head computerized tomography was performed in 90.3% of the patients, carotid-ultrasonography in 18.5%, cerebral angiography in 4.7%, electrocardiogram in 68.6% and echocardiogram in 24.8%. One hundred thirty seven patients (9.1%) were admitted to stroke units. Mortality in patients admitted to stroke units was lower when compared to patients admitted to regular wards (11.8% versus 24.7%, PϽ0.01). Eleven patients (1% of the patients with ischemic stroke) were treated with thrombolysis. Twenty three percent of the patients died during hospital admission. Age, history of hypertension, diabetes and having depressed level of consciousness (pϽ0.01) were univariate predictors of in hospital mortality. After multivariate logistic regression analysis, admission to regular wards was an independent predictor of in hospital mortality. Conclusion: The prevalence of stroke risk factors and clinical presentation in our cohort was similar to previously reported series. Evaluation of stroke etiology and treatment with thrombolysis were infrequent. Less of 25% of the patients with ischemic stroke were properly evaluated to exclude cardioembolic or large artery atherosclerotic sources. Although less than 10% of the patients were treated in specialized stroke units, a difference in in hospital mortality favoring stroke unit care could be observed. Background: Get with the Guidelines (GWTG)-Stroke is a widely used quality improvement registry but questions remain about its representativeness. We used national fee-for-service Medicare (FFS CMS) claims data to compare patient characteristics of ischemic stroke cases enrolled in GWTG-Stroke to those not enrolled in the registry. Methods: All 926,756 FFS CMS claims for ischemic stroke (primary ICD-9 discharge code 434 or 436) for the period 4/2003 and 12/2007 were matched to 228,815 subjects who had a clinical diagnosis of ischemic stroke in the GWTG-Stroke registry during the same time period. Data on patient characteristics were obtained from CMS claims. Comparisons between the FFS CMS cases that were matched to GWTG-Stroke registry and the remaining unmatched FFS CMS cases were performed using unadjusted analyses. Because of the sample size, all differences, regardless of magnitude, were statistically significant. Results: Among 926,756 FFS CMS claims, 144,344 were successfully matched to the GWTG-Stroke registry, leaving 782,412 unmatched FFS CMS claims. Demographic differences between the two groups were relatively minor (Table ). GWTG-Stroke cases had a higher prevalence of a past medical history of carotid stenosis. Patients enrolled in GWTG-Stroke were more likely to be admitted to larger, teaching hospitals in urban areas. The geographic distribution was similar, except for modestly fewer patients in the Midwest. (Table ) Discussion Background: There are few data on temporal trends in the time from ischemic stroke symptom onset to hospital presentation. Recent trials have expanded the time window for acute treatment but there are few data on the number of patients arriving in later time windows. Methods: Characteristics of ischemic stroke patients enrolled in GWTG-Stroke between 2004-2009 were determined across different epochs of symptom onset to arrival time. Patients were divided into specific time epochs ranging from 24h. Logistic regression was used to identify independent predictors of early arrival, defined as 2h, among all patients with documented time of onset 24h. Results: Of 414,540 ischemic stroke patients, 182,691 (44%) had a recorded time of onset 24 hours, and 49,986 (11.3%) were missing both onset time and date. There was a small but significant decrease in the percentage of patients presenting 2h (20.9% in 2004 vs. 18.5% in 2009), and a small but significant increase in those arriving between 2-3.5h after onset (6.61% vs. 5.83%), and 3.5-8h (10.6% vs. 7.9%). Independent factors associated with presentation 2h after symptom onset included younger age, arrival by EMS and stroke onset during weekday regular hours (9 am -5 pm) (Table ). Factors associated with lower likelihood of presentation 2h included increasing calendar year, diabetes, and smoking. Similar results, including the same relationship between increasing calendar year and lower likelihood of 2h presentation, were seen when the model was re-run in all patients including those with missing onset times; the sole exception was that previous stroke or TIA was no longer associated with Ͻϭ2h presentation. Conclusions: Arrival times of acute ischemic stroke showed no improvement from 2004 to 2009, and may have slightly lengthened. Further efforts are needed to improve stroke recognition and response. Nevertheless, around 20% of ischemic stroke patients arrive Ͻϭ2h , 25% Ͻϭ3.5h, and 35% Ͻϭ8h, suggesting that a substantial proportion of patients could potentially be eligible for acute stroke interventional therapies. Background: With the advent of effective treatment for acute stroke, including thrombolytic therapy and organized supportive care in certified stroke centers, states and counties through the US medical system began implementing regional systems of acute stroke care in the first decade of the 21st century. In these systems, laws or regulations direct that emergency medical services (EMS) systems preferentially route acute stroke patients directly to Primary Stroke Centers (PSCs) certified as capable of reliably delivering proven therapies. The pace, geographic range, and population reach of regional stroke system implementation has not previously been delineated. Methods: We identified the occurrence and year of implementation of regional stroke systems of care by review of legislative archives, internet and media reports, consultation with the American Heart Association/American Stroke Association and the Centers for Disease Control, and phone interviews with state public health and emergency medical service officials from each of the fifty states. U.S. census population databases were researched. Results: The first counties to pass regional stroke system of care regulations were in Alabama in 2000 and the first states to pass laws for EMS to route patients directly to PSCs were Florida and Massachusetts in 2004. By 2010, a total of 16 states had state-level legislation or regulations requiring EMS routing to PSCs, as did individual counties in an additional 3 states. The geographic spread of systems is shown in the figure below. The US population covered residing in jurisdictions with regional stroke systems of care increased substantially in the latter half of the decade, from 0.4% in 2000; through 9% in 2004; 24% in 2005; 25% in 2006; 27% in 2007; 32% in 2008; and 50% in 2009. By mid-2010, 52% of the U.S. population was being serviced by EMS preferential PSC routing protocols. Conclusions: The first decade of the 21st century witnessed a remarkable structural transformation in acute stroke care, with over half of all Americans now living in states/counties that ensure patients are brought to stroke-capable facilities. However, additional efforts are needed to extend regional stroke systems of care to more states and counties and the nearly half of US citizens currently not assured of emergency access to best care practices. This research has received full or partial funding support from the American Heart Association, National Center. We report the results of the 2010 survey on stroke service structures. Methods: All participating hospitals completed a web based form providing information on the structure of stroke services as of 1 st April 2010 providing data on number of patients managed, staffing levels and expertise, imaging resources, thrombolysis services treatment ratesResults: 100% of hospitals providing acute stroke care participated in the audit (159 hospital organisations with 201 sites. The proportion of hospitals offering thrombolysis on site has increased from 42% in 2008 to 74% with the median number of patients treated over the previous year increasing from 6 (IQR 2-14) to 14 (IQR 6-27). Nationally 3.8% of unselected stroke admissions were thrombolysed and 37% of centres treated more than 20 patients over the previous year. 10.7% of hospitals thrombolysed more than 10% of their stroke admissions. The quality of thrombolysis services appears to be high with all services under the supervision of specialist stroke physicians. All sites now have a stroke unit and the number of stroke beds has increased from a national ratio of 1 bed per patient to 1.07. TIA services have improved with the proportion of hospitals with a neurovascular clinic increasing from 95% to 98% and with reduced waiting times for an appointment from 7 days (IQR 5-12) to 3 days (IQR 2-7) over the last two years. Conclusions: Hyperacute stroke care and access to thrombolysis in the UK have improved substantially in the last two years with treatment rates matching those of other European and North American health care systems. Background: The benefit of intravenous (IV) tissue-Plasminogen Activator (t-PA) in patients with acute ischemic stroke is dependent on early administration in eligible patients. It has been estimated that 2 million neurons are lost for every minute the brain is deprived of blood flow. The Georgia Coverdell Acute Stroke Registry (GCASR), funded by the Centers for Disease Control and Prevention, provides a platform for actively engaging hospitals in a continuous multi-faceted interventional strategy to improve the quality of in-hospital stroke care. Stroke registries are used to track and improve the process of care, including identifying factors that predict earlier treatment and recommending methods to shorten treatment delay. Such information would assist hospitals in improving their quality of stroke care. Objective: The purpose of this analysis is to determine factors associated with the time from hospital arrival to the initiation of intravenous t-PA (door-to-needle time) in patients with acute ischemic stroke. Methods: We examined predictors of door-to-needle time including demographic (age, gender, race, time of presentation), clinical (stroke severity, past medical history), and administrative (duration in registry, hospital size) variables. Duration of hospital participation in the registry varied depending on when hospitals were recruited. A multivariate analysis was performed using the generalized linear MIXED method. Results: We analyzed data collected on 798 patients admitted with acute ischemic stroke who were treated with IV t-PA at 22 hospitals over a four year period (2005 -2009). The average door-to-needle time was 84.1 minutes. After adjusting for baseline differences, the mean door-to-needle time in patients with atrial fibrillation was 11 minutes longer than that for other patients (95% CI: 3.6-18.5, pϭ0.004). In patients admitted to hospitals participating in the registry for more than 1 year, the mean door-to-needle time was 11.6 minutes shorter (95% CI: 3.1-20.0, pϭ0.0086). Conclusion: Quality improvement efforts are effective in reducing delays in treatment with IV t-PA. Longer duration of participation in the GCASR shortened the time to treatment with IV t-PA by reducing the door-to-needle time. Other patient variables, such as atrial fibrillation, may be helpful in Author Disclosures: D. Della Morte: None. I. Moussa: None. M.S.V. Elkind: None. R.L. Sacco: None. T. Rundek: Research Grant; Significant; TR received investigator initiated research grant from Pfizer, Inc for these results.

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Failure to honor embargo policies will result in the abstract being withdrawn and barred from presentation. Background: One forth of stroke patients with a high-grade intracranial stenosis had recurrence within 2 years. The morphology and progression of acute symptomatic intracranial plaques are poorly understood. Methods: In this on-going study, patients with acute strokes attributed to a Ͼ70% intracranial stenosis were recruited to receive an intensive control of atherosclerotic risks. Patients with non-atherosclerosis stroke etiology were excluded. In addition to aspirin (80mg/day), pre-specified therapeutic targets were low-density lipoprotein (LDL) Յ70 mg/dL, HbA1c Յ6.5%, systolic blood pressure Յ140mmHg, and abstinence from smoking. Clinical progress and risk factor profile were serially monitored. 3D-rotational and digital subtraction angiograms were obtained at baseline (within 2 weeks from the index stroke) and in 12 months. An independent radiologist masked to the sequence of the angiograms rated the plaque vulnerability based on surface irregularity, presence of ulcer and maximal luminal diameter loss. Plaque regression was defined as a diameter gain Ͼ15% and healing of ulcer, if any, in 12-month angiogram. Results: Of the 30 patients enrolled, 15 completed the 12-month angiogram. Mean age was 65.0 years and 11 were males. Distributed in middle cerebral arteries (nϭ13) and distal internal carotid artery (nϭ2), the baseline stenosis (mean) was (78.33Ϯ8.6%). Surface irregularity and ulcers were found in 9 (60%) lesions. Overall, mean LDL (mg/dL) was reduced from baseline 136 (IQR 117-159) to 61 (IQR 51-70) (pϽ0.01); HbA1c (%) from 6.7 (IQR 5.9-7.5) to 5.7 (IQR 5.3-6.3) (pϽ0.05); systolic blood pressure (mmHg) from 132 (IQR 120-140) to 123 (IQR 120-132) (pϽ0.05). In 12 months, no recurrence of stroke was reported. Plaque regression was evident in 9 lesions (60%). One lesion (6.7%) progressed and 5 stenoses (33.3%) remained static. Conclusion: Morphological evaluation of intracranial plaque is feasible with 3D-rotational angiography. Intensive control of cardiovascular risks may halt progression of symptomatic intracranial plaques.

Th P320 Analysis of baseline data on the Cilostazol-Aspirin Therapy Against Recurrent Stroke with Intracranial Artery Stenosis (CATHARSIS)

Shinichiro Uchiyama, Dept of Neurology, Tokyo Women's Med Univ, Tokyo, Japan; Nobuyuki Sakai, Dept of Neurosurgery and KCGH Stroke Cntr, Kobe City Med Cntr General Hosp, Kobe, Japan; Makoto Takagi, Tokyo Saiseikai Central Hosp, Tokyo, Japan; Kazuo Minematsu, Dept of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Cntr, Suita, Japan; Masayuki Ezura, Dept of Neurosurgery, Sendai Med Cntr, Sendai, Japan; Yasushi Okada, Clinical Rsch Institute and Dept of Cerebrovascular Medicine, Cerebrovascular Cntr, National Hosp Organization Kyushu Med Cntr, Fukuoka, Japan; Yoji Nagai; Translational Rsch Informatics Cntr, Foundation for Biomedical Rsch and Innovation, Kobe, Japan Intracranial arterial stenosis (IAS) is more common in Asian than in Caucasian. Based on the results of the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID), warfarin is not recommended because of the concern of safety, whereas the efficacy of aspirin is not enough for stroke prevention in these high-risk patients. Recent results of Cilostazol Stroke Prevention Study II (CSPS II) showed that ciloztazol was more effective than aspirin for stroke prevention in Japanese patients with non-cardioembolic ischemic stroke without increasing bleeding risk. The CATHARSIS (ClinicalTrials.gov Identifier; NCT00333164) was a randomized controlled trial to compare the effect of aspirin plus cilostazol with that of aspirin alone on the progression of IAS as well as ischemic and hemorrhagic events in patients with symptomatic IAS. Inclusion criteria were (1) ischemic stroke after two weeks to six months from onset, (2) responsible lesions identified on MRI, (3) IAS Ͼ50% on MRA in the territory of responsible lesion, (4) IAS in the supraclinoid internal carotid artery (ICA), M1 portion of the middle cerebral artery, or basilar artery (BA), (5) age of 45-85 years, (6) out-patients, and (7) a written informed consent from the patient or family. A total of 165 patients (109 males, average 68 years) were enrolled from 60 stroke centers across Japan. Median duration from onset of stroke to the study entry was 30 days. An infarct with more than 1.5 cm in diameter was identified in 70 (42.4%) patients. The responsible lesions in the cortex, white matter, basal ganglia, and brainstem were observed in 57 (34.5%), 57 (34.5%), 33 (20.2%), and 13 (7.9%) patients, respectively. The stenosis of M1, supraclinoid ICA, and BA was seen in 127 (77.0%), 20 (12.1%), and 18 (10.9%) patients, respectively. Hypertension, hypercholesterolemia, diabetes, obesity (BMIՆ25), CKD (eGFRϽ60 mL/min/1.73m 2 ), and current cigarette smoking were associated in 72.1%, 51.5%, 35.8%, 32.1%, 26.1%, and 20.0% of the patients, respectively. Non-medication rates of diabetes, hypercholesterolemia, and hypertension were 33.9%, 21.2%, and 15.1%. In conclusion, M1 was the most predominant site of stenosis in our patients with symptomatic IAS, who had metabolic risk factors including hypercholesterolemia, diabetes, and obesity as compared with general Japanese patients with ischemic stroke, that are not well recognized or controlled.

Author Disclosures: S. Uchiyama: None. N. Sakai: None. M. Takagi: None. K. Minematsu: None. M. Ezura: None. Y. Okada: None. Y. Nagai: None.

Th P321 Antiplatelet Resistance in Patients with Recent Cerebral Ischemic Events

Oliver Blanchard, Eric Ehrensperger, Jeffrey Minuk, Susan Solymoss, Robert Co ˆte ´; McGill Univ, Montreal, Canada Background: Antiplatelet agents reduce the risk of vascular events by about 25% in high-risk individuals. A substantial proportion of patients continue to experience vascular events while on antiplatelet therapy. Antiplatelet resistance or non-response could partially explain this limited efficacy. Furthermore, antiplatelet resistance in patients with previous ischemic stroke or TIA could increase the risk of recurrent ischemic events. The purpose of this study, therefore, was to determine if antiplatelet responsiveness, as measured by the PFA-100, is associated with recurrent ischemic events. Methods: Patients with a recent TIA or ischemic stroke (IS) within the previous 3 months on antiplatelet therapy were recruited. Demographic data were collected including type and dose of antiplatelet agent (ASA, dipyridamole, clopidogrel, or combination). All subjects underwent complete neurological evaluations, routine blood tests, as well as measurement of platelet function using the PFA-100 technique (Col/Epi and Col/ADP) at baseline and every 4 months during their follow up. Patients were followed prospectively for a period of 2 years for the occurrence of ischemic events (defined as either TIA, IS, MI, angina, or vascular death). Investigators were blinded to the patients' antiplatelet response status at all times. Antiplatelet resistance was correlated with the occurrence of ischemic events. Results: Eighty one patients were recruited in the study from the McGill University Cerebrovascular Clinic from 2002 to 2009. The mean age is 69 years and 67% are male. Eleven patients were lost to follow up and 8 patients were followed for less than 12 months. Analysis of data was done for all patients who were followed for a minimum period of 12 months. Consequently, 19 patients were excluded from analysis leaving us with sixty two patients followed over an average of 22.8 months. Amongst these patients, a little more than 60% were taking ASA, either alone or in combination. At baseline, 42% were non-responders / resistant to antiplatelet agents (defined as PFA-100 Col/Epi Յ 170 sec). Recurrent ischemic events were slightly more common in responders compared to non-responders (22% vs. 19%,pϭNS). Conclusions: A significant proportion of patients with cerebrovascular disease exhibit antiplatelet resistance. Our study shows that antiplatelet resistance as determined by PFA-100 is not correlated with a higher risk of recurrent ischemic events.

Author Disclosures: O. Blanchard: None. E. Ehrensperger: None. J. Minuk: None. S. Solymoss: None. R. Co ˆte ´: None.

Th P323 Underuse of Antithrombotic Therapy and Clinical Outcome in Patients with Acute Ischemic Stroke and Atrial Fibrillation in a Hispanic Population

Carlos Cantu, Instituto Nacional de Ciencias Me ´dicas y, Mexico City, Mexico; Antonio Arauz, Instituto Nacional de Neurologı ´a y Neurocirugı ´a MVS, Mexico City, Mexico; Jose L Ruiz-Sandoval, Hosp Civil de Guadalajara, Guadalajara, Mexico; Luis Murillo-Bonilla, Universidad Auto ´noma de Guadalajara, Guadalajara, Mexico; Erwing Chiquete, Hosp Civil de Guadalajara, Guadalajara, Mexico; Jorge Villarreal, Hosp General de Culiacan, Culiacan, Mexico; Ricardo Rangel, Hosp Universitario de Nuevo Leo ´n, Monterrey, Mexico; Fernando Barinagarrementeria; Hosp Angeles de Quere ´taro, Quere ´taro, Mexico Background and Purpose: Guidelines strongly recommend oral anticoagulants (OAC) for stroke prevention for high-risk individuals with atrial fibrillation, yet it is often underused in developed countries. Moreover, stroke patients taking OAC at stroke onset have less disabling strokes than individuals taking aspirin or no antithrombotic therapy. This study examined the magnitude of this problem in a developing country using a large prospective stroke registry in a Hispanic population. Methods: We analyzed data from patients who presented with a recent ischemic stroke (IS) or TIA that were enrolled in three Mexican stroke registries; databases were merged into a common stroke registry (nϭ3194: ISϭ2837, TIA ϭ357). We selected patients with a known history of atrial fibrillation (AF). Cerebrovascular events were categorized as first-ever stroke/TIA or recurrent strokes. Primary end points were (1) the use of prestroke antithrombotic medications and admission international normalized ratio (INR), and (2) short-term outcome regarding prestroke antithrombotic medication. Results: There were 385 patients with known AF for a prevalence of 12.5% in IS and 8.1% in TIA patients. In patients with a history of AF and a previous TIA/IS (nϭ145), only 13.1% were taking oral anticoagulants (OAC) with therapeutic INR at the time of stroke onset, 22.8% were taking OAC with subtherapeutic INR (Ͻ2), 32.4% were on antiplatelets, and 31.7% were on no antithrombotics. Among patients with a history of AF and a first-ever IS/TIA (nϭ240), preadmission medications were OAC in 24% (subtherapeutic INRϽ2.0 in 20%), antiplatelets in 25%, and no antithrombotics in 51%. There were significant differences in disability (Rankin 2-5) and case fatality rate regarding the use of prestroke antithrombotic medication as shown in the Figure : patients using OAC in therapeutic range at the time of ischemic stroke had a better outcome when compared with individuals taking aspirin or no antithrombotic therapy (Pϭ0.01). Conclusions: In this Hispanic population most of the patients with atrial fibrillation admitted with an acute stroke, and who were candidates for oral anticoagulation, were on no antithrombotic therapy or were either not taking OAC or were subtherapeutic at the time of ischemic stroke. Patients taking OAC in therapeutic range at stroke onset had less disability and mortality on short-term outcome.

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Th P324 PROTEGE-ACV Program: Achieving Long-term Adherence To Secondary Stroke Prevention Goals

Claudia Alonzo, Laura Brescacı ´n, Marı ´a C Zurru ´, Fabiana Ortega, Silvina Brienza, Julieta Montecchia, Daniela Gil, Marcelina Carretero, Luis Ca ´mera, Edgardo Cristiano, Gabriel Waisman, Hosp Italiano de Buenos Aires, Buenos Aires, Argentina; Bruce Ovbiagele; UCLA Stroke Cntr, Los Angeles, CA Background: Long-term compliance is a huge challenge in stroke secondary prevention. We assessed the effectiveness of a quality-of-care stroke program on achieving long-term adherence in a Latin American university hospital. Methods: ischemic stroke patients were included in PROTEGE-ACV, a multidisciplinary program adapted from UCLA PROTECT Program, aimed to meet secondary prevention goals. Patients with severe functional impairment (Rankin Ն4), severe dementia or life expectancy less than three years after stroke were excluded. Results: In March 2010, 171 of 413 patients (41%) included in PROTEGE-ACV had two or more years of follow-up. Mean age was 74.9Ϯ11 years, with 50.3% females. Vascular RF profile was: HT (87%), dyslipidemia (88%), metabolic syndrome (50%); obesity (50%); type 2 DBT (17%); smokers and former smokers (46%); history of stroke or TIA (26%), CHD (15%), peripheral artery disease (12%); AF (15%); and CRF (10%). There was high level of compliance to ambulatory visits to their primary care physician (10.2Ϯ7) and neurologists (6.5Ϯ6) during this period. Most patients achieved optimal vascular RF control as well as very high adherence to drug therapy after one and two years of follow-up (table). Kaplan-Meier analysis showed a two-year recurrence probability and all-cause mortality rate of 9.3% and 20%, respectively. Conclusion: A multidisciplinary approach, with special focus on vascular RF control and patient education, significantly improves adherence to treatment and narrows the gap between evidence-based guidelines and clinical practice. A team-work strategy, patients close supervision and electronic records follow-up with frequent reminders to primary care physicians, could be key factors to improve compliance over long follow-up, with high impact on decreasing mortality and recurrence rates. We found a predominance of females (68%; nϭ2,647)and mean age was 45 years (18-90). When we associated level of education with awareness of the disease we found a statistically signficant positive association (Chi value 461.4 and Cϭ0.33) previous to and after the campaign. 60% (nϭ2343) believed that stroke is infrequent; of the 10 risk factors mentioned in the survey, the most recognized was Arterial Hypertension. 37% (nϭ605) before the campaign did not recognize any of the symptoms, while this percentage fell by 10% (nϭ90) in the post-campaign period. 35.5% in the pre-campaign period was unaware of the appropriate actions to take during a stroke, while at the three-month post-campaign period 65.4% responded with the correct option. 40% in the pre-campagin period recognized the specific treatment, a figure that increased to 83.4% three months later. Conclusions: This study reveals the lack of knowledge in this population and the positive impact of education created by the campaign. We should continue to carry out population studies, as this is the appropriate tool for delineating and improving the objectives for new strategies.

Author Disclosures: G. Bruera: None. A. Arca: None. L. Sposato: None. S. Ameriso: None. M.C. Zurru ´: None.

Th P326 High Factor Xl Is a Common, Ubiquitous Thromobophilic Abnaormality for both Arterial and Venous Thrombosis.

Naseer A Khan, Abir Ahmad, Waqas Ahmed, Charles Glueck, Ping Wang; Jewish Hosp, Cincinnati, OH Background: We assessed associations between high factor XI and arterial and venous thrombosis.The patients with high Factor XI included a broad mixture of disorders which can lead to Deep venous thrombosis (DVT), Pulmonary embolism (PE), Idiopathic intracranial hypertension (IIH), central retinal vein occlusion and recurrent pregnancy loss. Routine measurement of Factor XI in these high risk patients may open new doors to prevent and treat the above mentioned thromboembolic complications. Methods : Of 661 patients referred for evaluation for atherothrombosis-cerebrovascular disease (ATCVD) or venous thrombosis, of whom 50 (7.6%) had high factor XI (Ͼorϭ150%), we assessed associations between high factor XI and arterial and venous thrombosis. The 50 patients included 30 women, 20 men, 45 Caucasians, 2 African American and 3 others with a mean Ϯ SD age of 50 Ϯ 11. High Factor XI was the only coagulation disorder in 5 patients (10%), and was accompanied by 1,2,3,4, and Ͼor ϭ 5 other thrombophilic-hypofibrinolytic disorders in 13(26%), 9(18%), 11(22%), 6(12%) and 6(12%) patients, respectively. The patients with high Factor XI included a broad mixture of disorders where arterial and venous thrombi are a major pathoetiology. Results : Of the 50 patients, 16 (32%) had ATCVD, 12(25%) deep venous thrombosis/pulmonary embolism (DVT/PE), 7(14%) idiopathic intracranial hypertension (IIH), 5(10%) osteonecrosis of the hip, 3 (6%) central retinal vein thrombosis, 3 (6%) amourosis fugax, 3 (6%) recurrent pregnancy loss and 1 (2%) ischemic stroke. MeanϮ SD age in the 16 patients with high Factor XI and ATCVD was 51 Ϯ 10 years (range 32-74), with mean total cholesterol 212 Ϯ 66 mg/dl, triglycerides 399 Ϯ 40 mg/dl, and HDL cholesterol 39 Ϯ 11 mg/dl. Triglycerides levels were Ͼ 150 mg/dl in 11 of the 16 patients with ATCVD and high Factor XI. In the 661 patients in our center having Factor XI and triglycerides measures, Factor XI correlated with triglycerides (rϭ .19), PϽ.0001). We have found high Factor XI (Ͼor ϭ150%) in 12 of 20 (60%) patients with DVT/PE, 5/25 (20%) with osteonecrosis of the hip, 3/16 (18%) recurrent pregnancy loss, 16/102 (16%) premature ATCVD, 3/24 (13%) amaurosis fugax, 3/32 (9%) central retinal vein thrombosis, 7/190 (3.7%) IIH, and 6/29 (21%) ischemic stroke (5 of these 6 also had premature ATCVD. Conclusion: High Factor XI is a common, Ubiquitous thrombophilic abnormality for both venous and arterial thrombosis, and should be included in the panel of coagulation measurements made in arterial and venous thrombosis. Jesse Dawson, Terence J Quinn, Matthew R Walters, Kennedy R Lees; Institute of Cardiovascular and Med Sciences,Univ of Glasgow, Glasgow, United Kingdom Introduction: Subclinical disorders of thyroid function may be associated with increased vascular risk. We explored the relationship between biochemical thyroid status and subsequent cardiovascular events in a cohort of patients referred with suspected TIA. Methods -Data from consecutive referrals attending our clinic from August 1992 onwards were used. Subjects were followed up by record linkage to death and hospital discharge records. The primary endpoint was the occurrence of a cardiovascular (CV) event defined as death or hospital discharge following stroke, myocardial infarction or other vascular cause. Patients had serum thyroid stimulating hormone (TSH) and thyroxine (T4) measured at first clinic attendance. Based on these results, patients were classed as: euthyroid (TSH 0.45 to 4.5mU/L); treated hypothyroidism (taking thyroid replacement); overt hypothyroidism; overt hyperthyroidism; subclinical hypothyroidism or subclinical hyperthyroidism. Those with untreated overt disease were excluded from the main analysis. A Cox proportional hazard model was generated to compare the CV event rate between the thyroid groups. Results: Thyroid function tests were available for 2306 of 3522 (65%) individuals; 1023 (44.4%) were male and mean age was 65.4 years (SD 13.2). The majority of individuals (1924, 83.4%) were euthyroid, 173 (7.5%) had treated hypothyroidism, 128 (5.6%) had subclinical hypothyroidism, 56 (2.4%) had subclinical hyperthyroidism, leaving 3 (0.1%) individuals with overt hyperthyroidism and 22 (1%) with overt hypothyroidism. Of the total, 817 (35.4%) experienced a primary endpoint event and 400 (17.3%) died from vascular causes. Following exclusion of overt thyroid disorders, those with subclinical hyperthyroidism had lowest serum total cholesterol (pϭϽ0.001, one-way ANOVA), while euthyroid subjects were youngest (pϭ0.003, one-way ANOVA) and had the lowest proportion of females. On univariate analysis, greater age, male gender, previous hypertension, previous stroke, diabetes, cerebrovascular disease and greater serum creatinine linked with the primary outcome. There was no relationship between thyroid status and occurrence of the primary outcome. This remained after adjustment for the above variables (HR for CV event on multivariate analysis (relative to euthyroid individuals) for treated hypothyroidism 0.89 (95% CI 0.66 to 1.2), subclinical hypothyroidism 1.16 (95% CI 0.86 to 1.56) and subclinical hyperthyroidism 1.10, (95% CI 0.72 to 1.69)).

Conclusion:

We found no evidence of a relationship between subclinical disorders of thyroid function and occurrence of subsequent cardiovascular events in those referred to a cerebrovascular clinic.

Author Disclosures: J. Dawson: None. T.J. Quinn: None. M.R. Walters: None. K.R. Lees: None.

Th P328 Antihypertensive Class And Stroke Recurrence: An Analysis Of The VISP Trial

Guillermo Solorzano, Fang Chen, Josyf C Mychaleckyj, Wei-Min Chen, Univ of Virginia, Charlottesville, VA; Fang-Chi Hsu, Wake Forest Univ Sch of Medicine, Winston-Salem, NC; Michele Sale, Bradford B Worrall; Univ of Virginia, Charlottesville, VA Background: Hypertension is a major modifiable risk in stroke recurrence, but the optimal antihypertensive class for reducing future risk is uncertain. Agents that increase levels of angiotensin II (e.g. thiazide diuretics) may be more effective at reducing recurrent stroke compared to agents that lower angiotensin II levels (e.g. ACE inhibitors (ACE-I)) independent of antihypertensive effects. The Vitamin In Stroke Prevention Study (VISP) was a multi-center trial of high-versus low-dose vitamin therapy in individuals with non-disabling ischemic stroke and elevated homocysteine. We investigated recurrent stroke among those taking thiazides vs. ACE-I in the VISP study and hypothesized a lower risk of recurrent stroke in patients taking thiazides compared to those on ACE-I. Methods: Retrospective analysis of stroke recurrence in participants enrolled in VISP. To reduce potential confounding due to medication changes over the course of the two year trial or any effect due to the interaction between vitamins and antihypertensive agents, we used medication status at the randomization visit. We classified participants as; 1) thiazides but not ACE-I; 2) ACE-I but not thiazides and 3) neither agent. We excluded 242 individuals on both thiazides and ACE-I. Because of low recurrent stroke rates in the entire population, analysis by other antihypertensive classes was not possible. Results: Demographic data are summarized in the table. More of those taking only ACE-I at randomization had recurrent stroke compared to those taking only thiazides (OR ϭ 1.92, 95% CI ϭ 1.09, 3.40). Fewer recurrent strokes occurred in those taking thiazides compared to patients on antihypertensives other than ACE-I or thiazides (OR ϭ 0.49, 95% ϭ CI 0.28-0.85). Excluding the 1,258 not on any antihypertensive agent, the association between reduced stroke recurrence in patients taking thiazides vs. any other agent remained (ORϭ 0.39, 95% CI ϭ 0.22-0.69). Conclusion: Based on this post hoc analysis, thiazides are associated with a lower risk of recurrent stroke compared to the use of ACE-I in patients with hyperhomocystenemia. Conversely, ACE-I use is associated with a higher risk of stroke recurrence when compared to the use of thiazides. In future studies, we plan to explore possible genetic determinants of these associations through the use of genomic techniques. The unaware risk factors were defined as newly-diagnosed hypertension, diabetes, hyperlipidemia, and atrial fibrillation. We also analyzed socio-demographic data such as an age, sex, region, education level. Results: At the time of stroke/TIA, individual unawareness regarding hypertension, diabetes, hyperlipidemia, and atrial fibrillation was 7.8%, 15.3%, 36.5%, and 47.3% respectively. Global unawareness, if any unawareness of 4 risk factors above, was observed in 26.5% of patients (nϭ1136). The global unawareness was not related with age and gender in the univariate analysis. The unaware risk factors were more often found in metropolitan residents compared with the residents at small cities and rural areas (31.4% vs. 22.3, pϭ0.01). Level of education was associated with the unawareness (education years: Ͼ6 vs. Յ6; 33.9% vs. 28.8%, pϭ0.002). In multivariate analysis, including other confounders such as history of stroke or coronary artery disease, smoking, and obesity, the global unawareness were associated with education years (OR 0.86; 95%CI, 0.78-0.95) and living in the metropolitan area (OR 1.74; 95% CI 1.49-2.04). Conclusion: A considerable portion of stroke patients is unaware of their own risk factors, especially hyperlipidemia and atrial fibrillation, before the stroke. The difference in living region and education level may influence the awareness which is the first step for prevention and control of stroke.

Th P330 Soluble Endoglin and Vasospasm in Subarachnoid Hemorrhage.

Fernando D Testai, Venkatesh Aiyagari, Maureen Hillmann, Sepideh Amin-Hanjani, Univ of Illinois at Chicago, Chicago, IL; Glyn Dawson, Univ of Chicago, Chicago, IL; Philip B Gorelick; Univ of Illinois at Chicago, Chicago, IL Cerebral vasospasm (VS) is a frequently encountered complication of SAH that is associated with delayed brain ischemia and poor neurological outcome. Approximately 60-70% of SAH patients have angiographic evidence of VS, half of them being symptomatic (sVS). The pathogenesis of VS is multifactorial and not completely understood. Soluble endoglin (sEng) is an antiangiogenic protein that has been associated with pre-eclampsia which, as is the case of SAH, is characterized by endothelial dysfunction and VS. Here we examined whether the