Dr Yusuf A Rajabally
email: yusuf.rajabally@uhl-tr.nhs.uk

Guillaume Nicolas

Françoise Piéret

Pierre Bouche

Peter Y K Van Den

Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study

Keywords: EFNS/PNS Guidelines, chronic inflammatory demyelinating polyneuropathy, electrophysiology, sensitivity, specificity

Abstract.

Background: Diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) have variable sensitivity and specificity. Newly published criteria by [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] combine clinical and electrophysiological components, either of which suffices to establish the diagnosis. European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria [2006], require mandatory electrophysiology, as do other sets of criteria.

Methods:

We assessed the value of the two above-mentioned sets of criteria, on 151 patients with CIDP, and 162 controls with axonal neuropathy, from four European centres. Results were compared with Van den Bergh and Piéret's criteria [2004], and those of the American Academy of Neurology (AAN) [1991]. The utility of more extensive nerve conduction studies was ascertained.

Results: Koski et al.'s criteria had a sensitivity of 63 % and specificity of 99.3 %.

With unilateral, right-sided, forearm/foreleg, four-nerve studies, EFNS/PNS criteria offered a sensitivity of 81.3% and specificity of 96.2% for "definite/probable" CIDP.

Van den Bergh and Piéret's criteria had a sensitivity of 79.5% and specificity of 96.9%. AAN criteria were poorly sensitive (45.7%) but highly specific (100%).

"Possible" electrophysiological CIDP as per EFNS/PNS criteria were poorly specific (69.2%). More extensive studies increased diagnostic sensitivity of EFNS/PNS criteria (96.7%) but reduced specificity (79.3%).

Conclusions: In our patient populations, the EFNS/PNS criteria were the most sensitive and allowed identifying a highly significantly greater number of patients than Koski et al.'s criteria. The latter were comparable in specificity to the "definite/probable" EFNS/PNS electrodiagnostic subcategories. More extensive nerve conduction studies improved diagnostic yield but resulted in loss of specificity.

Introduction.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a clinically heterogeneous disorder. In clinical practice, diagnosis relies heavily on electrophysiology, but electrodiagnostic criteria lack sensitivity [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF][START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF][START_REF] Rajabally | Optimizing the use of electrophysiology in the diagnosis of chronic inflammatory demyelinating polyneuropathy: a study of 20 cases[END_REF][START_REF] Magda | Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy[END_REF]. This may result in misdiagnosis, potentially denying patients effective treatment.

A new set of criteria comprising clinical and electrophysiological components has been reported and was validated in 48 patients by Koski et al. [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] These diagnostic criteria represent the only ones reported so far for which either clinical or electrophysiological requirements, are sufficient to establish a diagnosis of CIDP.

Their reliability has not so far been ascertained in other larger CIDP patient populations. Guidelines published in 2006 from the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) had also defined clinical and electrodiagnostic criteria. [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] The electrophysiological component within these criteria, essential for establishing the diagnosis, was based on a set originally described by Van den Bergh and Piéret. [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] Distal compound muscle action potential duration prolongation, found in one study to be a highly sensitive independent marker of CIDP, [START_REF] Thaisetthawatkul | Dispersion of the distal compound muscle action potential as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy[END_REF] was used as an additional criterion to those proposed by Van den Bergh and Piéret, to produce the EFNS/PNS electrodiagnostic criteria. A further electrodiagnostic subcategory ("possible CIDP") was also added, encompassing cases with demyelinating features in a single nerve instead of in 2 nerves. Subsequently, high diagnostic sensitivity and high negative and positive predictive values of the EFNS/PNS criteria were demonstrated in one population of CIDP patients. [START_REF] Tackenberg | Classifications and treatment responses in immune-mediated demyelinating polyneuropathy[END_REF] This has not been confirmed however more widely, in different populations. The American Academy of Neurology (AAN) criteria [START_REF]Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP)[END_REF] also require mandatory electrophysiology for the diagnosis.

We here evaluate the sensitivity and specificity of Koski et al.'s criteria [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] (Table 1) and the EFNS/PNS criteria [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] (Table 2), in a study involving four European Neurology/Neurophysiology centres. Direct evaluation of the electrophysiological part of these criteria was performed on patients meeting EFNS/PNS clinical requirements, as electrophysiology is mandatory for diagnosis with these criteria.

Comparison of nerve conduction studies of varying extensiveness was also made, as was comparison with the sensitivity and specificity of the electrophysiological part of the American Academy of Neurology (AAN) criteria, [START_REF]Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP)[END_REF] also essential for the diagnosis (Table 3). ). We also aimed to evaluate the diagnostic value of distal compound muscle action potential (CMAP) duration prolongation [START_REF] Thaisetthawatkul | Dispersion of the distal compound muscle action potential as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy[END_REF] by comparing the EFNS/PNS electrophysiological criteria with the original criteria of Van den Bergh and Piéret [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF], which did not include this parameter. (i) more than 50% of the motor nerves tested had an abnormal distal latency, 1 or (ii) more than 50% of the motor nerves tested had abnormal conduction velocity, 1 or (iii) more than 50% of the motor nerves tested had abnormal F-latency. 1

OR (clinical component):

b) (i) Symmetric onset or symmetric exam, and (ii) Weakness in all four limbs, and (iii) At least one limb with proximal weakness.

1: As per AAN criteria (see Table 3) F: Abnormal temporal dispersion (> 30 % duration increase between proximal and distal negative peak CMAP) in at least two nerves, or G. Distal CMAP duration (interval between onset of the first negative peak and return to baseline of last negative peak) of at least 9 ms in at least one nerve nerve + at least one other demyelinating parameter in at least one other nerve.

II. "Probable CIDP"

At least 30 % amplitude reduction of the proximal negative peak CMAP relative to distal, excluding the posterior tibial nerve,, if distal negative peak CMAP at least 20 % of lower limit of normal values in two nerves, or in one nerve nerve + at least one other demyelinating parameter in at least one other nerve.

III. "Possible CIDP"

As in "I" but in only one nerve.

Table 3: AAN electrodiagnostic criteria for CIDP [8]:

At least three of the following four to be fulfilled:

1. Significant reduction of motor nerve conduction velocity in 2 or more motor nerves:

a. <80% of LLN if CMAP >80% of LLN b. <70% of LLN if CMAP <80% of LLN 2.
Partial conduction block or abnormal temporal dispersion in 1 or more motor nerves: either peroneal nerve between ankle and below fibular head, median nerve between wrist and elbow, or ulnar nerve between wrist and below elbow.

Criteria suggestive of partial conduction block: < 15% change in duration between proximal and distal sites and > 20% drop in negative peak (-p) area or peak-to-peak (p-p) amplitude between proximal and distal sites.

Criteria for abnormal temporal dispersion and possible conduction block: > 15% change in duration between proximal and distal sites and > 20% drop in -p area or p-p amplitude between proximal and distal sites 3. Significant prolongation of distal motor latency in 2 or more motor nerves:

a. >125% of ULN if CMAP >80% of LLN b. >150% of ULN if CMAP <80% of LLN 4.
Significant prolongation or absence of F-waves in 2 or more motor nerves:

a. >120% of ULN if CMAP >80% of LLN b. >150% of ULN if CMAP <80% of LLN

Materials and Methods.

From the four participating centres, Leicester (U.K.), Paris (France), Angers (France) and Brussels (Belgium), patients fulfilling clinical criteria defined by EFNS/PNS Guidelines for CIDP, were included, and their clinical and electrophysiological records were reviewed. Patients were selected on the basis of a clinical diagnosis of typical CIDP, as defined by the EFNS/PNS Guidelines. In addition, as per these Guidelines which define atypical forms, we included patients with Lewis-Sumner syndrome, predominantly distal weakness, focal involvement and those with associated concomitant diseases: diabetes mellitus, IgG and IgA monoclonal gammopathy, and IgM monoclonal gammopathy without anti-MAG activity. All exclusion criteria, as listed by EFNS/PNS Guidelines were otherwise met. [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] The patients from Brussels were those from which the Van den Bergh and Piéret criteria were originally derived. This did not affect the results for the EFNS/PNS criteria, as these patients were excluded from this analysis. The study was reviewed by our relevant Institutional Boards and did not require Ethics Commitee approval.

In view of the retrospective design, electrophysiological studies had been performed in a non-standardized manner, the number of nerves studied having varied from 4 to 8. Studies had been performed in the majority of patients pre-treatment, although in some cases, due to technical issues and lack of sufficiently extensive earlier evaluations (less than 4 motor nerves adequately tested), a subsequent, post-treatment study was considered for the current analysis. Extensiveness of the study of arm nerves varied from the distal forearm segment only, to a full length study up to Erb's point. The CMAPs were evoked from the median nerve (stimulating at wrist, elbow, and in some, axilla, Erb's point, and recording at the Abductor Pollicis Brevis muscle), ulnar nerve (stimulating at wrist, below elbow, and in some, above elbow, axilla, Erb's point, and recording at the Abductor Digiti Minimi muscle), common peroneal nerve (stimulating at ankle and fibular neck and recording at the Extensor Digitorum Brevis muscle) and tibial nerve (stimulating at ankle and popliteal fossa and recording at the Abductor Hallucis muscle). All nerve conductions were performed at ankle temperature ≥ 30º C and palm temperature ≥ 33 ºC. [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] Results were analyzed with each laboratory's range of normal values, and presence of demyelinating range values determined for each relevant parameter. Fulfillment of each set of electrodiagnostic criteria for CIDP was ascertained in each case. For consideration with proximal studies, the EFNS/PNS "probable CIDP" subcategory was modified, redefining conduction block as at least 50% amplitude reduction in all cases (rather than 30%), at Erb's point, for proximal upper limb studies, in accordance with previous evidence. [START_REF] Nicolas | Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy[END_REF][START_REF] Rajabally | Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy[END_REF] For the criteria described by Koski et al., patients with Lewis-Sumner Syndrome or monoclonal gammopathy were excluded from analysis, as per these authors' definitions. [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] Clinical records and histories were reviewed in detail to establish fulfillment of the clinical component of these criteria. Electrophysiological criteria fulfillment was established in each case, using available distal (foream and foreleg) studies with AAN criteria cut-offs. [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF][START_REF]Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP)[END_REF] Sensitivity and specificity were ascertained with 4 different nerve conduction study protocols ("PROTOCOLS I-IV") for EFNS/PNS criteria. "PROTOCOL I" corresponded to a unilateral right-sided distal segment 4 nerve-studies, including cases of "probable" and "definite" CIDP only. [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] "PROTOCOL II" considered the same unilateral 4-nerve study, but also included cases of "possible CIDP." [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] "PROTOCOL III" related to nerve conduction studies of 5 to 8 motor nerves, with proximal stimulations for at least 2, excluding the cases of "possible CIDP". Finally, "PROTOCOL IV" corresponded to similar more extensive nerve conductions, but including the cases of "possible CIDP". Fulfilment of Van den Bergh and Piéret's criteria [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] was ascertained using PROTOCOL I. AAN criteria [START_REF]Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP)[END_REF] were evaluated with all available nerve conduction results (irrespective of side of study).

To determine the specificity of the different criteria, we utilized the electrophysiological data from controls suffering from distal sensory or sensori-motor axonal neuropathy, from 3 of our 4 centres (Leicester, Paris and Brussels). None fulfilled EFNS/PNS clinical criteria for typical CIDP. All had been investigated with nerve conduction studies evaluating at least 4 motor nerves in the forearm and foreleg segments. A proportion had been investigated more extensively, with 5 to 8 nerves studied, and at least 2 upper limb nerves tested in their proximal segments.

The comparative diagnostic gain in sensitivity, achieved with the use of the more sensitive set of criteria, was calculated using a Mc Nemar's Test.

Results.

We included 54 patients from Leicester, U.K., 40 patients from Paris, France, 29 patients from Angers, France, and 28 patients from Brussels, Belgium, totalling 151 patients. Patients with CIDP had a mean age at onset of 52.5 years (mean for Leicester: 56.5; for Paris: 49.0; for Angers: 51.8; for Brussels: 50.4). There were 95 males and 56 females. Seven of our 151 patients had not been treated with immunomodulatory therapy, due to mild disease. Of the 144 who were treated, 136 (94.4%) had responded to treatment. Of the 108 CIDP patients who had a documented lumbar puncture result, 83 (76.9 %), had a raised cerebrospinal fluid protein level. We utilized a total of 162 controls with chronic distal sensori-motor axonal neuropathy.

Thirty-five were recruited from Paris, who had been investigated for 5-8 nerves with proximal stimulations for at least 2. Ninety-five controls were recruited from Leicester. Of those, 47 had been investigated for 5 to 8 nerves, with proximal stimulations for at least 2, and 48 had only undergone the basic unilateral right-sided 4-nerve distal segment study. Thirty-two controls were recruited from Brussels, all having undergone distal segment four-nerve studies. All controls were used to determine the specificity of AAN [START_REF]Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP)[END_REF] and Van den Bergh and Piéret's [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] criteria. Controls from Brussels were not included in the calculation of specificity of EFNS/PNS criteria, as their data did not include distal CMAP duration. Only 22 of the controls from Brussels were used to determine the specificity of Koski et al.'s criteria, as detailed clinical records were required for that purpose, and were unavailable for 10. Controls were older than CIDP patients (mean age: 61.2 years) and consisted of 93 males and 69 females.

The results for sensitivity are summarized in Table 3. Those relating to specifity are detailed in Table 4. Koski et al.'s criteria [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] offered a sensitivity of 63% and specificity of 99.3% versus controls. The total number of CIDP patients evaluated for these criteria was 127, excluding as per their definition, cases of Lewis-Sumner syndrome and those associated with monoclonal gammopathy. Of the cases meeting Koski et al.'s criteria, 30 fulfilled both clinical and electrophysiological components, 25 fulfilled only clinical criteria, and 25 met only the electrophysiological requirements. The criteria were highly specific (99.3%).

Only CIDP patients from Leicester, Paris and Angers were evaluated for distal CMAP duration prolongation, and had more extensive nerve conduction studies. Hence, the sensitivity of the EFNS/PNS electrophysiological criteria for CIDP [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] in those 3 centres combined was 81.3%, and specificity was 96.2% using PROTOCOL I. With PROTOCOL II, which also included the "possible CIDP" cases, sensitivity improved to 96.7%. However, this also resulted in increased misdiagnosis of controls as having CIDP, thereby reducing specificity to 69.2%. Sensitivity rose to 96.7% using PROTOCOL III, specificity being of 79.3%. Finally, PROTOCOL IV offered a sensitivity of 99.2%, but specificity was of only 61%. The sensitivity of the Van den Bergh and Piéret criteria [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] was of 79.5 % for the 4 centres combined. Combined specificity was 96.9 %. There were no significant differences in the sensitivity rates between Leicester, Paris and Angers for the EFNS/PNS criteria, with any protocol.

Sensitivity and specificity of Van den Bergh and Piéret's criteria were also equivalent in all 4 centres, and comparable to those of the EFNS/PNS with PROTOCOL I, indicating that distal CMAP duration prolongation as an additional parameter to the electrophysiological criteria did not have much impact. American Academy of Neurology (AAN) electrophysiological criteria for CIDP [START_REF]Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP)[END_REF] showed a sensitivity of 45.7% in our 151 patients, and specificity of 100 % versus controls. Again, the figures were comparable in all 4 centres. The recommended unilateral distal segment 4 nerve study protocol allowed in our patients the identification of over 80% of cases with the EFNS/PNS criteria, with a very high specificity, comparable to that of the AAN criteria. Likely reasons for this high sensitivity are the need for abnormality of a single parameter to be present in 2 nerves, in contrast to the AAN criteria, which require abnormalities of three different parameters, notwithstanding the fact that the EFNS/PNS criteria set higher abnormality thresholds (e.g. for motor nerve conduction velocity, distal motor latency and conduction block), thereby allowing preservation of specificity. The usefulness of 8 nerve distal segment studies and proximal upper limb stimulations has been demonstrated previously with other electrodiagnostic criteria for CIDP [START_REF] Rajabally | Optimizing the use of electrophysiology in the diagnosis of chronic inflammatory demyelinating polyneuropathy: a study of 20 cases[END_REF][START_REF] Nicolas | Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy[END_REF]. High specificity of the proximal component of upper limb nerve conductions has also been shown [START_REF] Rajabally | Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy[END_REF], at previously advised cut-offs [START_REF] Nicolas | Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy[END_REF][START_REF] Oh | What is the best diagnostic index of conduction block and temporal dispersion ?[END_REF] . Our present study confirms the utility and reliability of these procedures with the EFNS/PNS criteria. Although reduced, specificity remains high at around 80% with such more extensive studies, using PROTOCOL III. One reason for this relative reduction in specificity despite improved sensitivity with increase in number of tested nerves, was the severity of axonal loss in some controls, accompanied by significant motor conduction velocity reduction, distal motor latency prolongation or temporal dispersion, these parameters having standardized cut-off values independent of CMAP. Furthermore, the specificity of temporal dispersion > 30 % at axilla and Erb's point, is suboptimal, as previously demonstrated, [START_REF] Rajabally | Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy[END_REF] and this also contributed to false positives.

To our knowledge, a single previous study demonstrated the high diagnostic value of the EFNS/PNS criteria, reporting a sensitivity of 97 %. [START_REF] Tackenberg | Classifications and treatment responses in immune-mediated demyelinating polyneuropathy[END_REF] The extensiveness of the electrophysiology was uncertain as described in this analysis, in particular regarding uni-or bilaterality of the studies. This could explain the higher sensitivity to that we have found with PROTOCOL I. Furthermore, only symmetrical presentations were included in that study, and this may also have have increased the sensitivity of the EFNS/PNS criteria, as the majority of patients with Lewis-Sumner syndrome do not have diffuse electrophysiological demyelination. [START_REF] Rajabally | Lewis-Sumner syndrome of pure upper-limb onset: diagnostic, prognostic and therapeutic features[END_REF] Finally, this study also excluded cases of CIDP with concurrent illnesses such as diabetes, which may have impacted on the results.

Van den Bergh and Piéret's original criteria [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] independently offered comparable sensitivity to those of the EFNS/PNS with PROTOCOL I, in our patients. These results suggest that use of distal CMAP duration prolongation may not contribute to substantially increasing diagnostic yield within the criteria. Considering only cases from Leicester, Paris and Angers, distal CMAP duration prolongation of > 9 milliseconds in any motor nerve, contributed to only one additional diagnosis (100 vs. 99) from a total of 123 patients, as all the other patients positive for this criterion also showed demyelinating range changes for other parameters. The high diagnostic sensitivity for Van den Bergh and Piéret's criteria was initially demonstrated in the original series (75%). [START_REF] Van Den Bergh | Electrodiagnostic criteria for acute and chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] This was also shown in a study of 32 patients from a single centre (71.8%), [START_REF] Cocito | Treatment response and electrophysiological criteria in chronic inflammatory demyelinating polyneuropathy[END_REF] which compared these criteria to those of the Inflammatory Neuropathy Cause and Treatment group criteria (sensitivity of 68.7%) [START_REF] Nicolas | Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] and those of the AAN (sensitivity of 48.6%). [START_REF] Thaisetthawatkul | Dispersion of the distal compound muscle action potential as a diagnostic criterion for chronic inflammatory demyelinating polyneuropathy[END_REF] The current findings are otherwise also in keeping with those of another previous analysis, from one of our 4 centres, which found distal CMAP duration prolongation in only 6 of 20 (30%) CIDP patients [START_REF] Rajabally | Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy[END_REF].

The comparative values of diagnostic criteria for CIDP have rarely been studied in a large number of patients from different centres. Previous studies have highlighted the poor sensitivity of older criteria such as those of the AAN. CIDP" electrodiagnostic subcategory found here, however suggests it should be used cautiously.

  The EFNS/PNS criteria, used with PROTOCOL I, offered significant improvement in diagnostic sensitivity compared toKoski et al.'s criteria. We evaluated both these criteria on 101 of our patients, excluding those with serum paraprotein and with a clinical diagnosis of Lewis-Sumner syndrome, which Koski et al. distinguished from CIDP, [5] and excluding the patients from Brussels, for whom distal CMAP duration data was not available. Considering these 101 patients, 65 (25/39 [64.1%] from Leicester, 26/40 [65%] from Paris and 14/22 [63.6%] from Angers) fulfilled Koski et al.'s criteria, in comparison to 85 (33/39 [84.6%] from Leicester, 33/40 [82.5%] from Paris and 19/22 [86.4%] from Angers), who met EFNS/PNS criteria with PROTOCOL I (Mc Nemar's Test; P = 0.000002). Forty-one of the 101 patients fulfilled Koski et al.'s clinical criteria, and 51 fulfilled the electrophysiological criteria. All 101 cases met EFNS/PNS clinical criteria for typical or atypical CIDP, and 85 fulfilled the electrodiagnostic requirements. The 20 additional diagnoses achieved with the EFNS/PNS criteria were those which did not meet either clinical or electrophysiological criteria described by Koski et al., but met the EFNS/PNS clinical criteria for atypical CIDP and its electrophysiological requirements. Compared to AAN criteria which only identified 56 of 123 cases from the abovementioned 3 centres, EFNS/PNS criteria allowed diagnosing 100 of 123 these patients (Mc Nemar's Test: P < 0.000001). With PROTOCOL I, EFNS/PNS criteria were of comparable specificity to those of Koski et al. (P = 0.11).

Table 4 :Table 5 :

 45 Sensitivity of Koski et al.'s criteria [5], EFNS/PNS electrodiagnostic criteria [1], Van den Bergh and Piéret electrodiagnostic criteria [2], AAN electrodiagnostic criteria [8] in patients with a clinical diagnosis of CIDP Specificity of Koski et al.'s criteria, EFNS/PNS criteria with various diagnostic subcategories, Van den Bergh and Piéret's criteria and AAN criteria: Controls with a clinical diagnosis of chronic distal sensory or sensori-

[ 1 - 4 , 8 ]

 148 Our findings are limited by the difficulties in comparing a set of criteria requiring fulfilment of either clinical or electrophysiological components (Koski et al.'s),[START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] and of another requiring mandatory electrophysiology (EFNS/PNS).[START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] The methodology was further complicated by the different clinical definitions for "CIDP" as used within the 2 different sets. However, comparison of the 101 patients from our study, acceptable for evaluation according to the definitions of both sets (excluding cases of Lewis-Sumner syndrome and with associated monoclonal gammopathy), suggests the EFNS/PNS criteria are more sensitive than those of Koski et al. while offering similar high specificity. In our current analysis, only 51 of the 101 patients met Koski et al.'s electrophysiological criteria while 85 met those of the EFNS/PNS. Koski et al.'s clinical criteria fail to pick up atypical cases such as those with distal or asymmetrical involvement or patients without four limb motor weakness. Considering that diagnostic difficulty may precisely arise in such patients in practice, this is a limitation to their utility. Illustrating this point, only 41 of the 101 patients met Koski et al.'s clinical criteria, while they all fulfilled EFNS/PNS criteria for typical or atypical CIDP. In addition, Koski et al.'s electrophysiological criteria require at least75 % of excitable motor nerves and > 50 % of these exhibiting either abnormal distal latency, conduction velocity, or F latency. This can be problematic in cases with severe secondary axonal degeneration, or in patients tested for an even number of nerves. Furthermore, we here compared EFNS/PNS criteria with PROTOCOL I, i.e. using 4 studied nerves, with Koski et al.'s criteria, using all available nerves, which artificially increased the sensitivity of the latter, as all our patients were evaluated for 4 nerves or more. Also, as proximal weakness in at least one limb was mandatory for fulfilment of Koski et al.'s clinical criteria, use of controls with distal sensory or sensori-motor neuropathy clearly increased the specificity of these criteria. Finally, the present results also demonstrate the possibility of usefully and reliably utilizing the EFNS/PNS criteria with more extensive nerve conduction studies, including proximal stimulations for upper limb nerves. The poor specificity of the "possible

Table 1 : Koski et al.'s criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) [5]:

 1

	Patients with a chronic polyneuropathy, progressive for at least 8 weeks, would be classified as having
	CIDP if they had:
	No serum paraprotein and
	No documented genetic abnormality
	AND EITHER (electrophysiological component):
	a) at least 75 % of motor nerves tested has a recordable response AND one of the following conditions
	is satisfied:

Table 2 : EFNS/PNS electrodiagnostic criteria for CIDP [1]: I: "Definite CIDP": at

 2 least one of the following: A. At least 50 % prolongation of the motor distal latency above the upper limit of normal values in two

	nerves, or
	B. At least 30 % reduction of motor conduction velocity below the lower limit of normal values in two
	nerves, or
	C. At least 20 % prolongation of F-wave latency above the upper limit of normal values in two nerves
	(> 50 % if amplitude of negative peak compound muscle action potential (CMAP) < 80 % of lower
	limit of normal values), or
	D. Absence of F waves in two nerves if these nerves have amplitudes of distal negative peak at least 20
	% of lower limit of normal values + at least one other demyelinating parameter in at least one other
	nerve, or
	E. Partial motor conduction block: at least 50 % amplitude reduction of the proximal negative peak
	CMAP relative to distal, if distal negative peak CMAP at least 20 % of lower limit of normal values, in
	two nerves, or in one nerve + at least one other demyelinating parameter in at least one other nerve, or

Patients from Brussels all underwent only unilateral right-sided distal studies and were not evaluated for distal CMAP duration. PROTOCOL I = unilateral right-sided distal study of 4 motor nerves {"definite CIDP" + "probable CIDP"} PROTOCOL II = unilateral right-sided distal study of 4 motor nerves {"definite CIDP" + "probable CIDP" + "possible CIDP"} PROTOCOL III = proximal and distal study of 5 to 8 motor nerves, with proximal studies for at least 2 arm nerves {"definite CIDP" + "probable CIDP"} PROTOCOL IV= proximal and distal study of 5 to 8 motor nerves, with proximal studies for at least 2 arm nerves {"definite CIDP" + probable CIDP" + "possible CIDP"}

  EFNS/PNS criteria allowed a significant additional number of patients to be diagnosed (Mc Nemar's Test; p < 0.00001, for both PROTOCOLS I and III).

	100% [0] 100% [0] 95.5% [1] 99.3% [1] diagnostic sensitivity from 80.6% to 98.7%. However, this was achieved with decline 96.8% [3] 69.5 % [29] 80.9% [9] 59.6% [19] 96.8% [3] 100% [0] 35 94.3% [2] 68.6% [11] 77.1% [8] 62.9% [13] 94.3% [2] 100% [0] Brussels, Paris, France. Belgium. 32 (only 22 for Koski et al.'s criteria) ----100% [0] 100% [0] TOTAL 162 (82 with more extensive studies) 96.1% [5] 71.5% [37] 79.3% [17] 61% [32] 96.9% [5] 100% [0] in specificity from 96.1% to 79.3%. Use of the "possible CIDP" subcategory improved the sensitivity of unilateral 4-nerve distal studies (PROTOCOL II) by 15.4% but unacceptably worsened specificity by 24.6%. With more extensive nerve conductions and inclusion of cases of "possible CIDP" (PROTOCOL IV), additional gain in sensitivity was minimal (2.5%), but loss of specificity considerable (further N.B. We found that more extensive nerve conduction studies (PROTOCOL III) improved decline by 18.3%).

Discussion.

The diagnostic criteria by Koski et al. [START_REF] Koski | Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy[END_REF] offer the potential convenience and advantage of combining clinical and electrophysiological components, either of which suffices for a positive diagnosis of CIDP. These criteria were derived from classification, performed through generation of an expert consensus diagnosis (the "gold standard") and regression tree analysis of 150 patients, amongst which 58 had CIDP, and later validated in 48 other CIDP subjects. However, they exclude patients with Lewis-Sumner syndrome, as well as those with associated monoclonal gammopathy.

Although shown to be of high sensitivity and specificity in one CIDP patient population , [START_REF] Tackenberg | Classifications and treatment responses in immune-mediated demyelinating polyneuropathy[END_REF] the electrophysiological criteria for CIDP defined by the EFNS/PNS Guidelines [START_REF] Hughes | European Federation of Neurological societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society[END_REF] have not been evaluated more widely in different patient populations.

Importantly, the issue of their specificity, when including cases of "possible CIDP" has remained uncertain. Furthermore, although utilized within other criteria, [START_REF] Nicolas | Proposed revised electrophysiological criteria for chronic inflammatory demyelinating polyradiculoneuropathy[END_REF][START_REF] Hughes | Inflammatory Neuropathy Cause and Treatment (INCAT) Group. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy[END_REF] and shown to be reliable with appropriate cut-offs for conduction block and temporal dispersion, [START_REF] Rajabally | Proximal nerve conduction studies in chronic inflammatory demyelinating polyneuropathy[END_REF] The specificity was high overall with PROTOCOL I, and individually in the two centres where controls were recruited. As compared to the AAN criteria, the Competing interests: none declared.


Khalil El Karoui

Frédéric Méchaï

Florence Ribadeau-Dumas

Jean-Paul Viard

Marc Lecuit

Bertille De Barbeyrac

Olivier Lortholary
email: olivier.lortholary@nck.aphp.fr

Prof O Lortholary

Reactive arthritis associated with L2b lymphogranuloma venereum proctitis

Keywords: Chlamydia trachomatis, lymphogranuloma venereum, reactive arthritis, HIV infection

An ongoing outbreak of lymphogranuloma venereum (LGV) L2b proctitis, predominantly in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) has been reported in industrialized countries. We describe a case of reactive arthritis after L2b proctitis. This case expands the spectrum of severe complications related to LGV L2b proctitis. Since this infection may be asymptomatic, this organism should be screened for in HIV positive MSM with symptoms consistent with reactive arthritis.

INTRODUCTION

Chlamydia trachomatis (CT) is the etiological agent of major human infections including trachoma (classically serovars A-C), urogenital infections (serovars D-K) and lymphogranuloma venereum (LGV) (serovars L1-L3).

Since 2003, an ongoing LGV proctitis outbreak has been reported in industrialized countries, including France (mainly in Paris). [START_REF] Ward | Lymphogranuloma venereum in the United kingdom[END_REF] To date, most LGV isolates of the recent outbreak have been identified as L2b. [START_REF] Spaargaren | New lymphogranuloma venereum Chlamydia trachomatis variant, Amsterdam[END_REF] We report a case of a sexually acquired reactive arthritis (SARA) associated with a CT serovar L2b proctitis in an HIV-infected man.

CASE REPORT

A 41-year-old Caucasian homosexual man was admitted in our infectious diseases department for oligoarthritis. HIV-1 infection had been diagnosed 4 years earlier, when he presented with cutaneous secondary syphilis. Antiretroviral therapy had not yet been commenced as he had remained well.

One month after an episode of unprotected anal receptive intercourse, he presented with weight loss, fever, purulent rectal discharge, and tenesmus. Proctitis was clinically diagnosed, and he was successfully treated with oral doxycycline (100 mg twice/day). Polymerase chain reaction (PCR) for Chlamydia trachomatis (CT) was positive on taken blind anal sample. The

LGV variant L2b was detected by genotyping (PCR-RFLP) of the omp1 gene encoding the major outer membrane protein (MOMP) and sequencing the variable domain 2 of omp1 gene.

[3]Seven days after the diagnosis of proctitis, he presented with bilateral serous conjunctivitis.

A few days later, the patient was hospitalized for investigation of oligoarthritis of the right wrist, right knee and both ankles. Physical examination revealed pain and swelling of right wrist, right knee, both ankles and left metatarso-phalangeal joints, with sausaging of second and third left toes. Laboratory tests were as follows: CD4 lymphocyte count 252/µL (21%), HIV-1 viral load 6200 genome copies/mL (Log 3.8), negative serological tests for Yersinia, Salmonella, and Campylobacter, negative stool culture. HLA B27 testing was positive while search for rheumatoid factor, antinuclear antibodies and anti-cyclic citrullinated peptide antibodies was negative. Analysis of right knee synovial fluid revealed a raised white blood cells of 4900/mL (90% neutrophils) and negative bacterial culture. 16S rRNA gene PCR amplification and CT-specific PCR on synovial fluid were both negative. Cultures for N. gonorrhoeae, and Mycoplasma species from urethral swab were negative, as well as CTspecific PCR on first void urine sample. X-ray examinations of all involved joints revealed no abnormality.

A diagnosis of SARA complicating CT L2b proctitis was proposed. Oral doxycycline was continued for a total of 30 days (200mg/day). Oral ketoprofen (150mg/day) allowed complete clinical recovery after 2 months, and no relapse occurred after one year of follow-up.

DISCUSSION

Our patient presented with a SARA, 2 weeks after a CT serovar L2b infectious proctitis. Of note, conjunctivis was bilateral and resolved spontaneously, which argues against a direct conjunctive CT infection. Other classic features of SARA, such as balanitis, or sacro-ileitis were absent. However, our patient fulfilled the currently proposed criteria for reactive arthritis (ReA). [START_REF] Rihl | Infection and musculoskeletal conditions: Reactive arthritis[END_REF] The association of urogenital CT (serovars D-K) with SARA is well described. [START_REF] Keat | Chlamydia trachomatis and reactive arthritis: the missing link[END_REF][START_REF] Butrimiene | Potential triggering infections of reactive arthritis[END_REF] This association, and the strong temporal relationship between SARA and proctitis in our patient argues for a SARA related to CT L2b proctitis. Cases of ReA associated proctitis and CT infection have already been published, but direct evidence of CT infection was not available, co-infection with other ReA associated-microorganisms was not ruled out, and serovar was not determined. [START_REF] Keat | Chlamydial infection in the aetiology of arthritis[END_REF][START_REF] Neumann | Reiter's syndrome as a manifestation of an immune reconstitution syndrome in an HIV-infected patient: successful treatment with doxycycline[END_REF] Differential diagnoses, including (i) infection with other ReA triggering microorganisms and (ii) gonococcal arthritis, were ruled out with (i) serological tests, cultures of urethral swab, and (ii) 16S rRNA gene PCR on synovial fluid. ReA has been reported to occur in up to 10% patients with HIV infection. However, there is no direct correlation between ReA and HIV infection per se, and this association is thought to be related to the co-infections occurring in HIV-infected patients, as shown in our case. [START_REF] Reveille | Infection and musculoskeletal conditions: Rheumatologic complications of HIV infection[END_REF] In the recent outbreak, LGV predominantly caused proctitis or proctocolitis, primarily through unprotected anal receptive or insertive intercourse, [START_REF] Ward | Lymphogranuloma venereum in the United kingdom[END_REF] a substantial proportion of patients even being asymptomatic. [START_REF] Van Der Bij | Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study[END_REF] Diagnosis is essential as prolonged treatment (3 weeks) with doxycycline or macrolides is required in LGV (CT serovar L1-3) proctitis, in contrast to infection with other serovars for which short term treatment is possible. [START_REF] Van Der Bij | Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study[END_REF] Given the recent outbreak, CT L2b proctitis associated SARA appears to be rare, and less frequent than SARA related to other CT serovars (incidence estimated around 1-3% in CT D-K serovars). [START_REF] Rihl | Infection and musculoskeletal conditions: Reactive arthritis[END_REF] Strong local immune response in proctitis could prevent dissemination of infection and subsequent ReA. [START_REF] Rihl | Infection and musculoskeletal conditions: Reactive arthritis[END_REF] In conclusion, SARA may be triggered by epidemic LGV L2b isolate responsible for proctitis in HIV-infected MSM.

Word count : 750

Abstract word count: 73

Authors contributions:

K.E.K, F.M., and O.L. were in charge of the patient, and wrote the manuscript. F.R.D, J.P.V, and M.L. were in charge of the patient, and carefully revised the manuscript. B.de B. performed the strain serovar identification and carefully revised the manuscript.

CONFLICT OF INTEREST. None

ACKNOWLEDGEMENTS. The authors thank Maithe Clerc for genotyping analysis and

Nicolas Dupin for his careful review of the manuscript.

KEY MESSAGES

1-LGV L2b, as well as other CT serovars, may trigger SARA in HLAB27-positive HIVinfected men who have sex with men.

2-Given the recent outbreak,

LGV L2b infection should be systematically screened for in MSM with reactive arthritis, even though no proctitis symptoms are present.

3-This case adds reactive arthritis to the severe complications of LGV L2b proctitis, and underscores the importance of rapidly diagnose and treat this infection.


Saïd Assar
email: said.assar@it-sudparis.eu

Imed Boughzala
email: imed.boughzala@it-sudparis.eu

Isabelle Boydens
email: iboydens@ulb.ac.be

Back to practice, a decade of research in e-government

published or not. The documents may come

E-government definition and evolution

Information and communication technologies (ICT) have been used in governmental organizations since the beginning of the computer era. For example, one of the first large scale applications of computers was during the presidential election in the US in 1954. Since then, governmental information systems have evolved in parallel with those of organizations in the private sector. When internet technologies and the e-business phenomena hit the market a decade ago, the terms "e-government" and "digital government" were introduced and many definitions have emerged in the research literature [START_REF] Grönlund | Introducing e-Gov: History, Definitions and Issues[END_REF][START_REF] Yildiz | E-government research: Reviewing the literature, limitations and ways forward[END_REF]. For the sake of this chapter, we retain the following characteristics: (1) the usage of internet technologies to deliver services online and to rationalize, redesign and significantly improve public administrative processes; (2) the reorganization of public institutions so that to reduce cost and to enhance the quality and the efficiency of services offered to citizens, companies and other governmental partners; (3) the development of a new democratic spaces in which relations between public institutions, citizens and enterprises are redefined according to a participatory perspective. The ultimate goal is to leverage technology for creating a new generation of cost efficient, transparent, interactive and ubiquitous ICT-enabled public services. E-government is constantly evolving all around the world. This evolution is regularly measured and tracked by public institutions, private agencies and researchers alike. At the European level, the European Commission has conducted since 2001 a benchmarking project that measures the availability and sophistication of 20 basic public services for citizens and businesses. This benchmark establishes the foundations for the progressive and planned modernization of pan-EU egovernment comparison. For businesses, the services being monitored include social security contributions for employees, corporate tax and VAT (Value Added Taxes) declaration and payment, and public procurement. For citizens, the services being tracked include income tax declaration and payment, change of address notification, job search and requests for car registration and building permits. The development of e-services is measured with two indicators: the degree of 'sophistication' of the public services that are offered online, and the number of services that are fully available online ([EUC09]). Figure 1.1 presents the five-stage maturity model for benchmarking e-services sophistication. Stages 1 to 3 correspond to the increasing levels of sophistication which are 'one-way interaction' and 'two-way interaction'. Stage 4 corresponds to the 'transactional' stage -also called full electronic case handling -where the user applies for and receives the service online, without any additional paper work. The fifth level, 'targetisation' (or 'personalization'), provides an indication of the extent by which front-and back-offices are integrated, data is reused and services are delivered proactively (users do not have to submit a request to take advantage of the service).

. At the international level, the United Nations department of Economic and Social Affairs (UNDESA) has regularly published reports which rank the member states of the UN according to a quantitative composite index of e-readiness based initially on website assessment, telecommunication infrastructure and human resource endowment ([UN05], (UN08])1 . In its 2010 edition, significant changes to the survey instrument were introduced, focusing more on how governments are using websites and Web portals to deliver public services and expand opportunities for citizens to participate in decision-making ([UN10]). According to this latest report, table 1.1 presents top 20 countries in e-government development. For the E-Participation Index, Republic of Korea, Australia and Spain hold the 3 first positions in the top 20 countries. At the academic level as well, many models have been proposed to understand the maturity of e-government and to capture different stages of e-services development. While initial stages in these models are very similar concentrating on the availability of governmental information, on the possibility of downloading forms for initiating an administrative process (e.g. identity card renewal), and on the possibility of handling this process partly or fully online in a transactional bidirectional mode, later stages differ slightly. In [START_REF] Layne | Developing fully functional E-government: A four stage model[END_REF], later stages concentrate on the vertical integration (local systems linked to higher level systems within similar functions) and horizontal integration (systems integrated across different functions, real one-stop function for citizens and enterprises). In [START_REF] Siau | Factors Impacting E-Government Development[END_REF], later stages concentrate on public services transformation through their integration in a homogenous network of governmental services. This last stage is characterized by political transformations as it requires the reorganization of public agencies. In [START_REF] Ebrahim | A Strategic Framework for E-government Adoption in Public Sector Organisations[END_REF] and [START_REF] St-Amant | E-Gouvernement : cadre d'évolution de l'administration électronique[END_REF], the integration of public services (with each other and with private sector services and systems) is also the main issue for the latest stages of the maturity proposed frameworks. Finally, in [START_REF] Andersen | E-government maturity models: Extension of the Layne and Lee model[END_REF], an extension to the initial model of [START_REF] Layne | Developing fully functional E-government: A four stage model[END_REF] is proposed based on an empirical investigation in Denmark. The latest stage of this extended model is called 'Revolution' and highlights fundamental change in governmental practices and processes characterized by data mobility and sharing across public and private organizations, application mobility across public employees and services, and ownership to data transferred to final users. The authors recognize however that there are cases where direct application of their model is less appealing and where specific contextual element should be taken into account (e.g. back-office intelligence units, homicide investigations in police departments).

To conclude this first section, the question of measuring e-government performance and evolution is an important issue for all stakeholders. Although significant and relevant data is gathered annually about the subject by international institutions (United Nations, European Commission), and although many research models have been proposed to characterize the underlying evolution process, the subject is still investigated by the research community (e.g. [START_REF] Koh | Measuring e-government readiness[END_REF], [SHA08], [START_REF] Berntzen | Benchmarking e-government: A comparative review of three international benchmarking studies[END_REF]).

E-government as a field of research

E-government started as a practitioner field of investigation, basically convening practitioners trying to meet the new challenges of the internet medium by implementing new systems and offering new services creatively [START_REF] Grönlund | Introducing e-Gov: History, Definitions and Issues[END_REF]. Based initially on empirical insights from practice, first e-government conferences were practitioner-oriented with some academic invited keynotes. Rapidly, more academia-oriented conferences emerged, and the body of e-government related knowledge grew rapidly. The maturity of the emerging research field was questioned already in 2004 [START_REF] Grönlund | State of the Art in e-Gov Research -A Survey[END_REF]. It was criticized then as lacking theoretical foundation with insufficient levels of rigor and relevance in applying investigation method, in establishing results and in claiming their applicability to more general cases.

Significant efforts have been made since then to improve e-government research quality [START_REF] Grönlund | e-Gov Research Quality Improvements Since 2003: More Rigor, but Research (Perhaps) Redefined[END_REF], and to define more rigorously e-government as a domain of investigation and as a field of research [START_REF] Heeks | Analyzing e-government research: Perspectives, philosophies, theories, methods, and practice[END_REF][START_REF] Hovy | Chapter 3: An outline for the foundations of digital government research[END_REF]. In these studies, a large number of research papers published in prominent conferences and journals were analyzed according to multiple criteria's:

-Research type: descriptive, theoretical, theory testing, theory generating, philosophical.

-Research method: product description, survey, questionnaire, experiment, ethnography, grounded theory, document analysis, reflection on project experiment, web content evaluation, literature review.

-Researcher's home department: business, computer science, political science, information systems, library and information studies, government agency, non academic research institution.

-Literature used: public administration, management, computer science, egovernment, information systems, e-business, political science.

Findings confirm what other researchers have suggested [SCH07].

Egovernment is an emergent multidisciplinary field of research in which focus on practice and on practical recommendations is a prominent characteristic. Although theoretical ground is still under construction, it certainly qualifies as a legitimate emerging scientific discipline.

Presentation of the book

The material presented in this book is a collective contribution to the egovernment domain. Contributors come from 9 different countries and are either practitioners in e-government or researchers which have been directly or indirectly implicated in e-government projects. Each chapter is a specific field study in which different investigation methods have been applied and combined according to the case study methodological approach [YIN03]. The primary audience of this book is scholars and practitioners in the area of e-government. It is also of interest to MSc level students in curriculums related to ICT in public administration, information systems and e-business, and who seek practical cases in online services design, implementation and evaluation.

To present the research topics that are covered by the book chapters, we rely on future research themes identified by the road mapping e-government research project eGovRTD 2020 [COL07]. This project, funded by the European Community within the 6 th framework program FP6, aims to identify and characterize the key research challenges, required constituencies and possible implementation models for holistic and dynamic governments in Europe and around the world in 2020 and beyond. This project identified 13 interrelated research themes, out of which 11 are of concern for the research work presented here. A mapping between these research themes and the chapters of this book is presented in table 1.2, together with a mapping to the investigation methods used in the chapter's case study.

Chapter 2, entitled "E-procurement, from project to practice: Empirical evidence from the French public sector" by Godefroy Beauvallet, Younès Boughzala and Saïd Assar, is an analysis of public e-procurement adoption in France. Electronic platforms for supporting public transactions are an important application of egovernment. In France, new regulations since 2005 are pushing public and private actors to adopt electronic means for handling all steps of purchase process in public organizations. Based on two different quantitative surveys made in 2005 and in 2008, the authors analyze the public and private users' perception of the virtualization of the procurement process. Between 2005 and 2008, a significant progress is noticed in adopting electronic means for public agencies to publish a call for tender, for enterprises to upload a proposal using an electronic signature, and to a much less extent, for public managers to process the submitted proposals and taking a decision concerning the choice of the product and of the provider. Many enterprises are still reluctant to submit proposals online because there is a lack of confidence in the digital system. And, unfortunately, there is a visible digital divide between public agencies (e.g. ministries, main governmental institutions) that have enough resources to master the technology; and those, mainly local authorities in rural parts of the country that are struggling to digitalize their procurement processes.

Table 1.2: Mapping between chapters' content (columns), investigation methods and research themes (lines).

In chapter 3, Lizbeth Herrera and J. Ramon Gil-Garcia analyze a successful strategy involving three ICT projects through a case study of a Mexican federal agency. Entitled "Implementation of E-Government in Mexico: The Case of INFONAVIT", this chapter uses a technology enactment framework composed of institutional, organizational, and managerial factors. Overall, the results of this study show that having a strategic plan that aligns the ICT project objectives with the overarching organizational goals leads to successful implementation because the technical, organizational, and institutional resources are managed in an integrated fashion. The chapter also reports specific factors that had an impact on the characteristics and success of the three ICT projects.

The context of the case study analyzed in chapter 4 is the US army services. In the chapter entitled "The Casualty Assistance Readiness Enhancement System (CARES) -A Case Study in Rapid Prototyping and Design for Flexibility", Simon R. Goerger, Ernest Y. Wong, Dale L. Henderson, Brian K. Sperling and William Bland describe and evaluate a system implemented to help in processing the benefits that are due to the surviving family of fallen U.S. military service members. Most of these entitlements require a considerable amount of paperwork and necessitate a great deal of patience, attention to detail, and composure from families at a time when their grief is raw. Even though the U.S. Army appoints a Casualty Assistance Officer (CAO) to help surviving family members through this process, the soldiers serving as CAOs tend to be inexperienced and oftentimes find themselves challenged to provide accurate and thorough assistance. Consequently, some families do not receive all benefits in a timely manner, and some entitlements may be overlooked entirely. The Casualty Assistance Readiness Enhancement System (CARES) is an information system designed to improve how the Department of the Army cares for military families. The tool and associated process reduced the time required to complete forms, reduced the potential for errors on repetitive information, assisted CAOs through the process and provided electronic copies of completed forms. The approach in the design of CARES (the process) demonstrates a viable methodology for the rapid development of a software solution to support an administrative process that is often performed by inexperienced users under the guidance and review of mid level managers.

Chapter 5 is dedicated to electronic identification. As online services are now widely used, and as the exchanges of personal data become more and more widespread, electronic identification is becoming a key function for the security of the process and for the protection of privacy. In France and throughout Europe, egovernment services, as well as private services, already use different means of electronic identification. Fabrice Mattatia, in his chapter entitled "An overview of some electronic identification use cases in Europe" presents problems concerning identification in the digital space, and reviews the different technical solutions that are actually implemented in Europe for issuing electronic identity cards (e-ID). He discusses as well the question of e-ID interoperability, which is the main issue when it comes to give access to all European citizens to e-services of any Member State.

Chapter 6, by Rowena Cullen, is entitled "Privacy and personal information held by government: a comparative study, Japan and New Zealand". This chapter reports on the concepts of information privacy and trust in government among citizens in Japan and New Zealand in a trans-national, cross-cultural study. Data from both countries is presented, and cultural and other factors are sought which might explain differences in attitudes shown. Hofstede's dimensions of culture are used as the theoretical background for the analysis of cultural differences. In both countries, citizens display a range of views, not related to age or gender. New Zealand citizens express concern about information privacy in relation to information held by government, but show a higher level of trust in government overall. Japanese citizens interviewed also indicated that they had major concerns about information privacy, and had considerably less trust in government than New Zealand respondents showed. They were more inclined to attribute breaches of privacy to lax behavior in individuals than government systems. In both countries citizens showed an awareness of the trade-offs necessary between personal privacy and the needs of the state to hold information for the benefits of all citizens, but knew little about the protection offered by privacy legislation, and expressed overall concern about privacy practices in the modern state.

The main theme of chapter 7 is information quality. Data quality is a strategic matter in the context of e-government as the integration of services requires authentic, coherent and reliable data. However, establishing databases that are devoid of duplication, redundancy or ambiguity isn't simple neither in theory nor in practice, although administrative databases are often regarded wrongly as 'simple'. In its chapter entitled "Strategic issues relating to data quality for e-government: learning from an approach adopted in Belgium", Isabelle Boydens demonstrates that this is not the case, in particular because of the questions of interpretation that they raise. This chapter is based on case studies stemming from the Belgian federal administration (social security, business directories, federal authentic sources, etc.). Contrary to the assertions of common theories postulating a permanent bijective relationship between data and the corresponding reality, she argues that an empirical information system evolves over time along with the interpretation of the values that it allows to determine. To address data quality, she proposes a temporal framework that provides new operational strategies to improve administrative data quality (mainly, new ways to define quality indicators for continuous monitoring and reengineering strategies). This framework demonstrates how the approach is generally applicable in the context of empirical information systems.

Chapter 8, by Lucie Langer and entitled "Long-term verifiability of remote electronic elections" is directly related to the e-participation theme of research. Retention of election documents is essential for verifying the proper conduct of an election ex post. The documents retained provide for later review in case an election contest is filed. In the context of the German Basic Law, the principle of public elections laid implies the need for public verifiability. This applies to remote electronic voting in particular as physical observation is not achievable in this case. While the retention obligations on paper-based elections are governed by electoral law, according specifications for e-voting are still an open issue. The chapter therefore addresses the following questions: Which existing legal obligations on retention of election data have to be complied with? How can they be transferred to the scenario of remote electronic elections? Based on an analysis of the retention obligations specified in German electoral law, the author identifies the conditions which must be documented and are thus subject to long-term verifiability. She investigates then how they can be adapted to the scenario of remote electronic elections. Her work contributes to establishing the basis for legally binding e-voting in Germany. As electoral law in Europe is rather consistent, this contribution might be useful to other countries as well.

Chapter 9 is entitled "Laws-based ontology for e-Government services construction -Case study: the specification of services in relationship with the venture creation in Switzerland", and is written by Abdelaziz Khadraoui, Wanda Opprecht, Michel Léonard, Christine Aïdonidis. The compliance of e-Government services with legal aspects is a crucial issue for administrations. This issue becomes more difficult with the fast-evolving dynam-ics of laws. This chapter presents an approach to describe and establish the link between e-Government services and legal sources. This link is established by an ontology which is called "Laws based ontology". This ontology is used as means to define and to construct e-Government services. It may not be exhaustive, but it is nonetheless based upon an unquestionable source of information, the laws themselves. The proposed approach is illustrated with one case study: the specification of services in relationship with the venture creation in Switzerland and in the State of Geneva. The authors have selected the Commercial Register area which mainly encompasses the registration of a new company and the modification of its registration.

The theme of chapter 10 by Anne Fleur Van Veenstra and Marijn Janssen is service integration and interoperation on the web, and it is entitled "Architectural principles for orchestration of cross-organizational service delivery -Case studies from the Netherlands". Realizing integrated service delivery (ISD) requires government agencies to collaborate across their organizational boundaries. Orchestration of services is one way of achieving coordination of processes across multiple organizations. In this chapter, authors identify architectural principles for orchestration by looking at three case studies of cross-organizational service delivery chain formation in the Netherlands (preparation module for joint permit requests, information system for import of veterinary products, and information system supporting the asbestos removal process). In total, six generic principles were formulated and were subsequently validated in two workshops with experts: (i) build an intelligent front office, (ii) give processes a clear starting point and end, (iii) build a central workflow application keeping track of the process, (iv) differentiate between simple and complex processes, (v) ensure that the decision making responsibility and the overview of the process are not performed by the same process role, and (vi) create a central point where risk profiles are maintained.

Chapter 11 is entitled "Achieving Interoperability Through Base Registries for Governmental Services and Documents Management", and it is written by Yannis Charalabidis, Fenareti Lampathaki and Dimitris Askounis. As digital infrastructures increase their presence worldwide and citizens and businesses are provided with high quality one-stop services, there is a growing need for the systematic management of those newly defined and constantly transforming processes and electronic documents. An Interoperability Registry is a system devoted to the formal description, composition and publishing of traditional or electronic services, together with the relevant document and process descriptions in an integrated schema. Through such a repository, the discovery of services by users or systems can be automated, resulting in an important tool for achieving interoperability. This chapter describes the architecture, components, underlying ontology of an interoperability registry platform that has been developed in Greece, the context of the new Greek Digital Strategy plan. The chapter illustrates the applicability of the approach through experimentations with the VAT process, which is by nature, a process spanning multiple organizations.

The theme of chapter 12 is Human-Computer Interface. Entitled "Envisioning Advanced User Interfaces for e-Government Applications: a Case Study", it is written by Gaëlle Calvary, Audrey Serna, Joëlle Coutaz, Dominique Scapin, Florence Pontico, and Marco Winckler. The adoption of e-government services provided to citizens depends upon how such applications comply with the users needs. Unfortunately, building e-government web site doesn't guarantee that all citizens who come to use it can access its contents. These services need to be accessible to all citizens/customers equally to ensure wider reach and subsequent adoption of the e-government services. User disabilities, computer or language illiteracy (e.g. foreign language), flexibility on information access (e.g. user remotely located in rural areas, homeless, mobile users), ensure user privacy on sensible data are some of the barriers that must be taken into account when designing the User Interface (UI) of e-government applications. Whilst several initiatives (such as the W3C WAI) focus on how to promote usability and accessibility of content provided via e-government, many governments are enhancing their technology to make their services compatible with new communication channels available through multiple devices including interactive digital TVs (iTV), personal digital assistants (PDAs), and mobile phones. In this chapter, the authors focus on this latter issue, which means the development of multi-target government services available across several platforms. They discuss the major constraints underlining the importance of investment on the UI's design of e-Government applications. They propose a framework for envisioning advanced UIs where the adaptation to the user's capabilities, available devices as well as physical and social environment will play a major role. This approach is illustrated through an experimental system developed for handling scholarship requests in a regional French administration.

Chapter 13 is entitled "Practices to develop Spatial Data Infrastructures: Exploring the contribution to E-government" and is written by Joep Crompvoets, Glenn Vancauwenberghe, Geert Bouckaert, and Danny Vandenbroucke. The main objectives of this chapter are to introduce Spatial Data Infrastructures (SDIs), and to explore their potential contribution to e-government. In order to understand the possible strengths of SDIs for e-government, the concept, components, governance and the cost -benefit analyses regarding the implementation of these infrastructures are first explained and presented followed by a short presentation of four existing SDIs in practice (Europe, Catalonia, Flanders and Leiedal). These practices show clearly the dynamic, integrated and multiple natures of SDIs. The main reason to invest in SDIs is that they facilitate the sharing of spatial data in a way that the management and use of these spatial resources happens more efficiently and effectively. While sharing resources from multiple sources is still not common practice in e-government implementation, it will be very likely that ICTs will play a key role in improving the sharing of public resources. Lessons learnt from the existing SDI-practices and understanding of the nature of SDIs could therefore be useful support to develop efficient and high quality e-governments systems.

Figure 1

 1 Figure 1.1: E-government evolution framework (extracted from [EUC09]) According to the 2009 edition of the European Commission benchmark ([EUC09]), the leading six nations on the full online availability of the basic 20 services are: Austria, Malta, Portugal, the United Kingdom, Sweden and Slovenia. With regard to the online sophistication of the 20 basic services, the leading six nations are Malta, Portugal, Sweden, Austria, Slovenia and Estonia.

Table 1 .

 1

1: Top 20 countries in e-government development (extracted from [UN10])

All survey data since

has been compiled by the UNDESA into an 'E-Government Readiness Knowledge Base' available online at http://www.unpan.org/egovkb/.