Jacky Laulan

Bernard Fouquet

Camille Rodaix

Penelope Jauffret

Yves Roquelaure

Alexis Descatha
email: alexis.descatha@rpc.aphp.fr

Keywords: definition, aetiological factors, diagnosis, management and occupational impact definition, aetiological factors, diagnosis, management and occupational impact Thoracic outlet syndrome, rehabilitation, diagnosis, occupational disease

Introduction

Shoulder disorders, which include unspecific shoulder pain and specific disorders, are commonly diagnosed in primary care and often lead to prolonged disability. prevalence in the population of working age range between 7 to 47% for shoulder pain, depending on the population studied and the definition used [START_REF] Roquelaure | Epidemiologic surveillance of upperextremity musculoskeletal disorders in the working population[END_REF]. The impacts for workers are important in industry such as in office, especially for chronic shoulder pain [START_REF] Kuijpers | Costs of shoulder pain in primary care consulters: a prospective cohort study in The Netherlands[END_REF].

Although neck and arm pain is a frequent presenting complaint in the general population, an unusual and controversial cause must sometimes be considered [START_REF] Kieffer | Les syndromes de la traversée thoraco-brachiale[END_REF][START_REF] Riddell | Thoracic and vascular aspects of thoracic outlet syndrome[END_REF]: thoracic outlet syndrome (TOS), as this frequently complex disease is difficult to diagnose. A diagnosis of TOS can be rapidly considered by physicians with the clinical features suggestive of TOS and the risk factors and occupational situations associated with it. Considering multiple aspects of the outcome including pain, general physical function and work, rapid referral to specialized multidisciplinary units may then allow more effective management of this disease.

The purpose of this study is to review the definitions of TOS, the known risk factors, diagnostic criteria, and management. The links between TOS and the work environment will be described in particular detail on prevalence in the workforce, occupational risk factors, and work prognostic factors (including the key message for clinicians and rehabilitation professionals).

Definitions

Thoracic outlet syndrome covers a wide range of manifestations due to compression of nerves and vessels during their passage through the cervicothoracobrachial region. Various forms of TOS are distinguished: vascular forms (arterial or venous) which raise few diagnostic problems [START_REF] Kieffer | Les syndromes de la traversée thoraco-brachiale[END_REF], and "neurological" forms, which are by far the most frequent as they represent more than 95% of all cases of TOS [START_REF] Roos | Congenital anomalies associated with thoracic outlet syndrome[END_REF][START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF]. The "neurological forms" are classified in the "true" neurological form associated with neurological deficits (mostly muscular atrophy), and painful neurological forms (with no objective neurological deficit). These painful forms are very frequent, especially when patients are systematically screened for these symptoms. The existence of these forms of TOS remains controversial in part because muscular and neurological manifestations are strongly interrelated. Clinical experience suggests that the main triggering mechanism is more often a muscular dysfunction in the cervicoscapular region than primitive nerve compression. It is directly responsible for cervicoscapular symptoms (pain and discomfort) and sometimes for referred scapulobrachial and facial pain.

In parallel, shortened muscles (mainly scalene muscles) and cervicoscapular muscles imbalance may lead to intermittent nerve compression and/or tension on brachial plexus in the thoracic outlet resulting in proximal pain and producing pain and discomfort in the upper limb. The neurological involvement accounts for most of the distal symptoms, but the controversy concerning the reality of TOS is essentially due to the absence of objective criteria to confirm the diagnosis (no neurological weakness and normal neurophysiological examination). Despite considered as "debatable" for some authors, several arguments support the reality of this syndrome, such as the influence of TOS on the results of treatment of carpal tunnel and cubital tunnel syndromes [START_REF] Hérard | Devenir à long terme, clinique et électrique, des syndromes du canal carpien opérés. Facteurs pronostiques cliniques. 42 e congrès du GEM[END_REF][START_REF] Lascar | Cubital tunnel syndrome : a retrospective review of 53 anterior subcutaneous transpositions[END_REF].This problem is further complicated by the frequent concomitant presence of other neuromuscular diseases of the upper limb, which can be secondary to TOS or, on the contrary, may precede and predispose to the development of TOS [START_REF] Hérard | Devenir à long terme, clinique et électrique, des syndromes du canal carpien opérés. Facteurs pronostiques cliniques. 42 e congrès du GEM[END_REF][START_REF] Lascar | Cubital tunnel syndrome : a retrospective review of 53 anterior subcutaneous transpositions[END_REF], in which case TOS is often masked by the concomitant disease. "Neurological" forms of TOS can be subdivided into primary forms in which features of TOS may remain isolated or may be complicated by underlying neuromuscular disorders, and forms secondary to a more distal disease (neuromuscular or joint disease), always responsible for complex clinical features.

Aetiological forms

Painful forms of TOS can be due to four main causes, sometimes interrelated.

1/ Congenital abnormalities are often reported and can be associated with traumatic or functional causes. Bone anomalies (cervical rib, prolonged transverse process), fibrous anomalies (transversocostal, costocostal, etc.), or muscular anomalies (scalenus anticus muscle, sickle-shaped scalenus medius, etc.) are more frequent in patients who develop TOS [START_REF] Roos | Congenital anomalies associated with thoracic outlet syndrome[END_REF]. Bone anomalies are well known, but 2/3 of the abnormalities detected at operation are fibromuscular [START_REF] Roos | Congenital anomalies associated with thoracic outlet syndrome[END_REF] and the majority of bone anomalies do not cause TOS [START_REF] Adson | Surgical treatment for symptoms produced by cervical ribs and the scalenus anticus muscle[END_REF][START_REF]Les syndromes de la traversée cervico-thoraco-brachiale[END_REF]. These anomalies are part of a real local and regional "dysplasia" constituting only one of numerous predisposing factors, associated with a morphotype composed of narrow, drooping shoulders.

2/ Post-traumatic causes, either due to isolated trauma or repeated trauma, account for up to 2/3 of cases in some series [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF][START_REF] Ellison | Trauma-related thoracic outlet syndrome[END_REF]. Post-traumatic TOS due to soft tissue injury raises medicolegal and often management problems. These forms are related to neck and shoulder trauma, particularly "whiplash" injuries, or sometimes upper limb trauma. Injuries to scalene muscles and their subsequent fibrosis are implicated in this process [START_REF] Ellison | Trauma-related thoracic outlet syndrome[END_REF][START_REF] Sanders | Scalene muscle abnormalities in traumatic thoracic outlet syndrome[END_REF]. Diagnostic criteria of post-traumatic TOS are the pathogenic mechanism and the onset of symptoms within the first two years.

3/ "Functional" acquired causes are the most controversial, although probably the most frequent. In this group, upper limb dysfunction or a muscle imbalance of the neck and shoulder region is considered to be responsible [START_REF] Ellison | Trauma-related thoracic outlet syndrome[END_REF][START_REF] Barton | Occupational causes of disorders in the upper limb[END_REF][START_REF] Mackinnon | Clinical commentary : pathogenesis of cumulative trauma disorder[END_REF][START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF]. Two main features are mainly associated with "functional" acquired causes: "hypertrophic" muscle morphotype of the cervicoscapular region and "dropped" scapular morphotype (leading in some patients to a dysfunction of the normal scalenus anterior muscle). Muscles of the thoracic outlet are also accessory respiratory muscles capable of prolonged tonic contractions due to their high percentage of type I muscle fibres [START_REF] Machleder | The anterior scalene muscle in thoracic outlet compression syndrome. Histochemical and morphometric studies[END_REF]. Chronic stimulation of these muscles has also been shown to increase the percentage of type I fibres. Machleder showed that a normal scalenus anterior muscle contains 70% of type I fibres versus 85% in the case of TOS [START_REF] Machleder | The anterior scalene muscle in thoracic outlet compression syndrome. Histochemical and morphometric studies[END_REF]. The factors involved in the pathogenesis of these disorders include overuse and physical and mental stress phenomena, frequently associated with unfavourable psychosocial factors [START_REF] Fouquet | Facteurs psychiques et psychologiques des syndromes tunnellaires[END_REF].

Neck and shoulder symptoms are reported by 45% of subjects in certain occupations [START_REF] Sallstrom | Cervicobrachial disorders in certain occupations, with special reference to compression in the thoracic outlet[END_REF] and are related to repetitive movements and certain working positions, particularly in occupations requiring use of the arms in elevation (barbers, switchboard operators, assembly lines, etc.), with the head or shoulders flexed anteriorly (secretaries, computer operators, etc.) [START_REF] Mackinnon | Clinical commentary : pathogenesis of cumulative trauma disorder[END_REF][START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF][START_REF] Pascarelli | Understanding work-related upper extremity disorders : clinical findings in 485 computers users, musicians, and others[END_REF]. 4/ Other acquired causes are rare but must be systematically considered: tumours [START_REF] Rosset | Exostose ostéogénique de la première cote : une étiologie rare de syndrome de la traversée thoraco-brachiale[END_REF], hyperostosis, osteomyelitis, etc. The diagnosis is based on clinical examination and medical imaging (CT and MRI).

Diagnosis

Symptoms

Vascular forms of TOS can be either venous or arterial. Venous compression can be responsible for oedema or cyanosis of the upper limb. It can also present suddenly in the form of phlebitis occurring after varying degrees of effort. The patient may sometimes only present at the stage of sequelae with a thoracic collateral venous circulation. Arterial signs consist of either ischaemia on effort of the upper limb or positional vasomotor disorders. Signs of vertebrobasilar insufficiency, due to compression of the origin of the vertebral artery, or Raynaud's phenomenon may be observed [START_REF] Riddell | Thoracic and vascular aspects of thoracic outlet syndrome[END_REF]. The diagnosis of TOS is relatively simple in the presence of vascular symptoms in the upper limb when the arms are raised, but vascular forms are rare, as venous forms represent 2 to 3% of TOS and arterial forms represent about 1% [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF].

However, the presence of vascular signs may help to guide the diagnosis in the presence of a predominantly neurological form of TOS.

TOS with a muscular atrophy is exceptional and remains asymptomatic for a very long time. Very rarely, the patient may present with progressive atrophy of the intrinsic muscles of the hand, always starting with the thenar muscles and gradually spreading to the interosseous and hypothenar muscles [START_REF] Alexandre | Formes déficitaires du syndrome de la traversée thoraco-brachiale. A propos de 16 cas. 41 e congrès du GEM[END_REF]. In these forms of TOS associated with muscular atrophy, pain and paraesthesiae are often moderate or may even be absent. At an advanced stage, treatment may still be able to relieve pain, but the possibilities of motor recovery are very limited and sequelae are frequent [START_REF] Kieffer | Les syndromes de la traversée thoraco-brachiale[END_REF][START_REF]Les syndromes de la traversée cervico-thoraco-brachiale[END_REF][START_REF] Alexandre | Formes déficitaires du syndrome de la traversée thoraco-brachiale. A propos de 16 cas. 41 e congrès du GEM[END_REF][START_REF] Allieu | Les formes neurologiques du syndrome du hile du membre supérieur: le rôle du scalène moyen[END_REF].

Painful neurological forms of TOS account for 97% of all cases of TOS according to Roos [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF]. They are typically responsible for symptoms in the C8-T1 distribution (medial aspect of the arm, ulnar border of the forearm and hand), but the C7 nerve root and sometimes the superior trunk of the brachial plexus (C5-C6) may be responsible. Clearly systematized symptoms are rarely present. It has been reported that the 3 most disturbing preoperative symptoms are pain at rest (87% of cases), feeling of numbness (66% of cases) and decreased strength (55% of cases). In practice, the patient often reports vague, poorly defined, and inconsistent symptoms, but clinical interview often reveals difficulties during activities requiring elevation of the arms (hanging up the washing, brushing one's hair, etc.). Functional impairment and pain related to carrying heavy loads are frequent but less specific. Pain of the neck and shoulder region is at least partly due to muscle imbalance but can sometimes be due to a proximal form of TOS (C5-C6). Decompensation fairly frequently occurs after a change of job or in a context of carpal tunnel syndrome (double crush syndrome) [START_REF] Dahlin | The neurone and its response to peripheral nerve compression[END_REF][START_REF] Upton | The double crush in nerve entrapment syndromes[END_REF]. These patients present with complex upper limb pain [START_REF] Bontoux | Les syndromes douloureux chroniques du MS : place de la chirurgie. Table ronde sous la direction de J. Laulan et B. Fouquet[END_REF]. Carpal tunnel symptoms appear rapidly [START_REF] Narakas | The role of thoracic outlet syndrome in the double crush syndrome[END_REF] due to pre-existing irritation of the nerve fibres by TOS [START_REF] Dahlin | The neurone and its response to peripheral nerve compression[END_REF][START_REF] Upton | The double crush in nerve entrapment syndromes[END_REF][START_REF] Turner | Can the outcome of open carpal tunnel release be predicted?: a review of the literature[END_REF]. However, the pathophysiology of the association between upper-limb distal nerve entrapment and TOS is complex, and may not be only on irritation of nerve fibres. For instance, median nerve sensory fibres do not travel with the C8 fibres that are being hypothesized as the site of the double crush. Therefore, other mechanisms could be considered in relationship to increase median or ulnar nerve pressure and scalene muscle activity [START_REF] Monsivais | The scalene reflex : Relationship between increased median or ulnar nerve pressure and scalène muscle activity[END_REF], or a hypothesis of centralization of pain [START_REF] Latremoliere | Central sensitization: a generator of pain hypersensitivity by central neural plasticity[END_REF]. The associated TOS must be identified, as it can be responsible for persistent symptoms after treatment of carpal or ulnar tunnel syndrome [START_REF] Hérard | Devenir à long terme, clinique et électrique, des syndromes du canal carpien opérés. Facteurs pronostiques cliniques. 42 e congrès du GEM[END_REF][START_REF] Lascar | Cubital tunnel syndrome : a retrospective review of 53 anterior subcutaneous transpositions[END_REF][START_REF] Smith | The double crush syndrome: a commonoccurrence in cyclists with ulnar nerve neuropathy-a case-control study[END_REF].

Apart from double crush syndrome, other secondary painful diseases may be associated, such as epicondylar pain secondary to medial or lateral insertion tendinitis. However, referred pain is not always easy to distinguish from a possible associated tendinitis (medial aspect of the elbow [START_REF] Pascarelli | Understanding work-related upper extremity disorders : clinical findings in 485 computers users, musicians, and others[END_REF][START_REF] Laulan | Chirurgie des lésions tendineuses du coude[END_REF]), which also raises the problem of the real (or at least the initial) cause of the pain [START_REF] Laulan | Chirurgie des lésions tendineuses du coude[END_REF]. Nevertheless, some of these forms of medial or lateral epicondylitis may resolve in response to rehabilitation for TOS.

Physical examination

At first sight, the physician may observe that the patient's upper limb is relatively immobile.

The shoulder can be lowered and protracted [START_REF] Mackinnon | Clinical commentary : pathogenesis of cumulative trauma disorder[END_REF]. Muscles of the scapular region and the scalene muscles may be contracted [START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF][START_REF] Laulan | Syndrome de la traversée thoraco-brachiale et activités professionnelles[END_REF]. The supraclavicular fossae may appear to be filled due to a cervical rib.

The physician must look for cyanosis or oedema of the upper limb or even a thoracic collateral venous circulation. The presence of a supraclavicular murmur is also an indication for complementary vascular investigations. Vascular tests (Adson, Wright, etc.) are of little value in neurological forms of TOS [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF]: the presence of dynamic compression is not synonymous with TOS, as it is detected in more than 50% of the general population [START_REF] Roos | Congenital anomalies associated with thoracic outlet syndrome[END_REF][START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF].

Positive vascular tests can only help to guide the diagnosis, but do not constitute formal diagnostic criteria per se.

Signs of neurological deficit, essentially motor weakness (intrinsic muscles), must be systematically investigated in the hand. We have seen several patients followed for many years for "cervicobrachial neuralgia", in whom the diagnosis of TOS was only proposed at the stage of atrophy of all intrinsic muscles of the hand, resembling an Aran-Duchenne hand [START_REF] Allieu | Les formes neurologiques du syndrome du hile du membre supérieur: le rôle du scalène moyen[END_REF]. However, objective clinical signs of muscularweakness are usually absent.

Stress tests are therefore particularly valuable. In the Roos stress test, the patient positions the shoulders in 90° of abduction with the elbows flexed to 90° and repeatedly opens and closes the hand [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF]. This test has a fundamental diagnostic value provided it triggers the symptoms spontaneously experienced by the patient in less than one minute [START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF]. Similarly, the presence of a supraclavicular positive Tinel sign has a major diagnostic value, but is less often present.

Elvey's test modified by Sanders (90° of abduction/external rotation of the upper limb, wrist in extension, then the head is tilted to the contralateral side [START_REF] Sanders | Thoracic outlet syndrome: a review[END_REF]), may also be useful. Finally, Morley's sign (tenderness in the supraclavicular fossa) may have a diagnostic value when it is clearly asymmetrical and especially when it triggers the patient's usual, more distal pain [START_REF] Morley | Brachial plexus neuritis due to a normal first thoracic rib : its diagnosis and treatment by excision of rib[END_REF].

These tests are quite sensitive but poorly specific. However, association of positive tests increased the probability of the TOS.

Complementary investigations

None of the various complementary investigations are truly useful for the diagnosis of painful forms of TOS. They are especially useful in rare vascular forms, in forms associated with neurological deficits, and prior to surgery. Standard radiographs, centered on the cervicothoracic spine, can demonstrate a cervical rib or a prolonged C7 transverse process.

Such an abnormality, on its own, is not sufficient to confirm the diagnosis of TOS, as only 5 to 10% of cervical ribs are associated with TOS [START_REF] Kieffer | Les syndromes de la traversée thoraco-brachiale[END_REF][START_REF] Adson | Surgical treatment for symptoms produced by cervical ribs and the scalenus anticus muscle[END_REF]. Some authors consider that CT scan can identify abnormalities in 30 to 60% of cases [START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF], but once again the presence of abnormalities is not synonymous with TOS [START_REF] Adson | Surgical treatment for symptoms produced by cervical ribs and the scalenus anticus muscle[END_REF]. MRI is of limited value for the diagnosis of TOS [START_REF] Narakas | The role of thoracic outlet syndrome in the double crush syndrome[END_REF]. However, these examinations are essential when a tumour is suspected.

Static and dynamic vascular examinations (Doppler ultrasound and angiography) are only useful in the presence of vascular clinical signs. The presence of arterial stenosis or even poststenotic aneurysm is a formal indication for surgery. Vascular examinations are of limited diagnostic value in isolated neurological forms [START_REF] Laulan | Défilé thoracobrachiaux : formes pures et formes complexes[END_REF]. It must be remembered that the presence of dynamic vascular compression is not synonymous with TOS.

Electroneuromyographic signs in favour of the diagnosis of TOS are: signs of chronic partial denervation in intrinsic muscles of the hand, decreased amplitude of sensory evoked potentials of the ulnar nerve and motor evoked potentials of the median nerve. Electroneuromyography (ENMG) only reveals abnormalities in severe cases and conduction velocities are only decreased in the case of permanent nerve compression. A reduction of the action potential in the territory of the cutaneous nerve of the forearm may be an earlier sign.

ENMG is usually normal. Many authors consider that the diagnosis of TOS can be raised before the appearance of signs of intrinsic muscle denervation [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF][START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF]. At an advanced stage, treatment may still be able to relieve pain, but the possibilities of motor recovery are very limited and sequelae are frequent [START_REF] Kieffer | Les syndromes de la traversée thoraco-brachiale[END_REF][START_REF]Les syndromes de la traversée cervico-thoraco-brachiale[END_REF][START_REF] Allieu | Les formes neurologiques du syndrome du hile du membre supérieur: le rôle du scalène moyen[END_REF][START_REF] Dahlin | The neurone and its response to peripheral nerve compression[END_REF]. The main role of ENMG is to detect an associated upper limb distal tunnel syndrome, like carpal tunnel syndrome or ulnar nerve at the elbow. Somatosensory evoked potentials are probably of no value for the diagnosis of TOS.

Thoracic outlet symptoms have generally been present for several years and are more or less well tolerated by the patient. Symptoms tend to be exacerbated by unusual activities or periods of stress.

Secondary TOS can also be observed in combination with any painful disease of the upper limb, especially when symptoms are longstanding and/or disabling, or when they occur in an unfavourable socioeconomic context [START_REF] Fouquet | Facteurs psychiques et psychologiques des syndromes tunnellaires[END_REF][START_REF] Mackinnon | Clinical commentary : pathogenesis of cumulative trauma disorder[END_REF]. The patient develops more or less adapted compensations with secondary dysfunction of the whole upper limb. In this case, the secondary imbalance of neck and shoulder muscles is responsible for TOS, which in turn exacerbates the symptoms and can be responsible for chronic disorders. Epicondylar pain associated with TOS shows a poorer response to treatment [START_REF] Narakas | The role of thoracic outlet syndrome in the double crush syndrome[END_REF].

Differential diagnosis

The absence of clinical signs of muscular weakness and usually ENMG signs requires a very rigorous diagnostic approach. At this stage, TOS must be a diagnosis of exclusion.

The diagnosis of vascular forms is usually fairly straightforward, as most of the symptoms and signs are suggestive of TOS. On the other hand, Raynaud's phenomenon is rarely related to TOS (3 to 5% of cases) and other aetiologies should be investigated. Of the various tunnel syndromes, ulnar nerve compression at the elbow raises the most difficult problems of differential diagnosis. Although both diseases can cause paraesthesiae on the ulnar border of the hand, ulnar nerve compression is associated with more clearly systematized disorders (little finger and ulnar hemi-pulp of the ring finger). ENMG can eliminate this diagnosis. Carpal tunnel syndrome only raises diagnostic difficulties in atypical forms. Most importantly, carpal tunnel syndrome is so common that the diagnostic work-up should be continued in the presence of atypical symptoms, even when ENMG is suggestive of carpal tunnel syndrome. Note that Phalen's test can be positive in the presence of isolated TOS [START_REF] Narakas | The role of thoracic outlet syndrome in the double crush syndrome[END_REF].

Rotator cuff syndrome can usually be easily distinguished from TOS on clinical examination.

The diagnosis may be more difficult in the presence of degenerative disease in the same upper limb. In diffuse idiopathic pain syndrome or fibromyalgia, pain is both peripheral and axial, but some authors consider "disputable TOS" to be a particular form of fibromyalgia.

Finally, certain clinical forms or early stages of central nervous system diseases can be responsible for upper limb pain, paraesthesiae or distal muscle atrophy (syringomyelia, multiple sclerosis, amyotrophic lateral sclerosis). Cervical spondylotic myelopathy and certain peripheral neuropathies can present with atrophy of the intrinsic muscles of the hand, systematically requiring a complete neurological examination and ENMG.

All causes of upper limb pain can therefore be considered, but these causes can be simply concomitant diseases (tunnel syndrome or tendinitis) rather than true differential diagnoses.

Recognition of this syndrome can avoid a number of unnecessary examinations or operations.

However, evaluation of the psychosocial setting is essential, as these patients are known to frequently present an "unusual" psychological profile. Gockel showed that patients with TOS presented sympathetic hyperreactivity compared to a control population [START_REF] Gockel | Cardiovascular functional disorder and distress among patients with thoracic outlet syndrome[END_REF]. Socioeconomic or affective situations likely to lower pain tolerance or promote the emergence of "reactive" disorders must also be detected. As in all upper limb pain syndromes, stress, a certain individual susceptibility and poor motivation can be involved [START_REF] Miller | Chronic upper limb pain syndrome (repetitive strain injury) in the Australian workforce : a systematic cross sectional rheumatological study of 229 patients[END_REF]. The individual perception of symptoms clearly differs as a function of the context in which they occur [START_REF] Mackinnon | Clinical commentary : pathogenesis of cumulative trauma disorder[END_REF].

Treatment

Three types of treatment can be proposed: preventive measures, rehabilitation and surgery.

1/ Preventive measures are essential to correct or eliminate any risk factors identified, particularly in the workplace, as discussed below [START_REF] Novak | Evaluation of patients with thoracic outlet syndrome[END_REF]. The use of orthoses has also provided useful results on distal symptoms in some patients [START_REF] Nakatsuchi | Conservative treatment of thoracic outlet syndrome using an orthosis[END_REF].

2/ Rehabilitation was performed for many years according to Peet's protocol [START_REF] Peet | Thoracic-outlet syndrome : evaluation of a therapeutic exercise program[END_REF], but a slightly modified protocol has often been used over recent years, comprising an initial analgesic and muscle relaxant phase that appears to give better results (especially in painful neurological from). Correctly conducted rehabilitation can provide prolonged relief of symptoms in about 2/3 of patients [START_REF] Aligne | La rééducation des syndromes de la traversée thoraco-brachiale[END_REF][START_REF] Revel | Rééducation des syndromes de la traversée cervico-thoracobrachiale (à propos de 26 cas)[END_REF]. It is especially effective on proximal pain [START_REF] Smith | The double crush syndrome: a commonoccurrence in cyclists with ulnar nerve neuropathy-a case-control study[END_REF]. In refractory forms, multidisciplinary management is essential with evaluation of the various factors participating in maintenance of chronic pain and a retraining programme like those proposed in chronic low back pain [START_REF] Fouquet | Stratégie de prise en charge des troubles musculo-squelettiques en médecine physique et réadaptation[END_REF].

3/ Surgery remains very controversial, even in relation to the various techniques [START_REF] Riddell | Thoracic and vascular aspects of thoracic outlet syndrome[END_REF].

Schematically, some authors are in favour of supraclavicular scalenectomy, while others are in favour of transaxillary resection of the first rib [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF][START_REF] Allieu | Les formes neurologiques du syndrome du hile du membre supérieur: le rôle du scalène moyen[END_REF][START_REF] Laulan | Défilé thoracobrachiaux : formes pures et formes complexes[END_REF]. Scalenectomy appears to be associated with a lower success rate, and the results obtained also tend to wane with time [START_REF] Gockel | Long-term results of primary scalenectomy in the treatment of thoracic outlet syndrome[END_REF].

It can be responsible for certain vascular and neurological complications and appears to be associated with a higher incidence of postoperative reflex sympathetic dystrophy. A cervical approach is especially indicated for resection of a superficial cervical rib, otherwise we consider transaxillary resection of the first rib to be the most appropriate method [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF], as it is an effective procedure provided all nervous and vascular structures are completely released.

However, this surgery is difficult and not devoid of certain risks with a high morbidity. A combination of the two techniques can sometimes be necessary [START_REF] Roos | Thoracic outlet syndromes : Update 1987[END_REF].

Thoracic outlet syndrome and the workplace

Certain physical factors, especially dynamic factors, can predispose to TOS, particularly its painful forms. Many jobs involve repetitive movements and certain postural constraints such as jobs requiring use of the arms in elevation (hairdressers, switchboard operators, assembly lines, etc.). Repetitive movements with the upper limb raised, in antepulsion or abduction, carrying heavy loads on the shoulder or with the arm outstretched can induce compressions due to closure of the thoracic outlet and intermittent pressure on the brachial plexus (industrial workers, cashiers). Postural factors incriminated in sedentary jobs are mainly prolonged cervical flexion (protraction of the head), and abduction and internal rotation of the shoulders (computer workers, musicians). These types of working position can induce an imbalance of muscles or the peripheral nervous system (tunnel syndromes). Use of the hand to move loads requires balanced control of all muscles of the upper limb and shoulder girdle. Many workrelated overuse syndromes can therefore be associated with secondary TOS.

A review of the epidemiological literature, based on the Pubmed and Embase databases and using "thoracic outlet syndrome" and "occupational" as key words, limited to the human adult population and articles in French and English, looking for demonstrated occupational risk factors associated with thoracic outlet syndrome gave disappointing results. Fifty five articles were identified on the basis of these criteria. The second step consisted of reading the titles, abstracts, or articles according to their relevance in order to only include epidemiological studies (excluding case reports and editorials). Cross-references also identified several other articles. Ten articles were finally selected. Most of these articles concerned painful neurological forms of TOS with no neurological deficits, apart from the study by Sällström [START_REF] Sallstrom | Cervicobrachial disorders in certain occupations, with special reference to compression in the thoracic outlet[END_REF]. Diagnostic criteria, when they were defined, were very diverse, ranging from nonspecific tests (pain and limitation of neck and upper limb movements for Ohlsson [START_REF] Revel | Rééducation des syndromes de la traversée cervico-thoracobrachiale (à propos de 26 cas)[END_REF], pain or paraesthesia of the upper limb for at least one week or once a month during the last 12 months for Battavi [START_REF] Battevi | The occurrence of musculoskeletal alterations in worker populations not exposed to repetitive tasks of the upper limbs[END_REF]), or a combination of symptoms and a clinical examination including specific stress tests [START_REF] Pascarelli | Understanding work-related upper extremity disorders : clinical findings in 485 computers users, musicians, and others[END_REF][START_REF] Lederman | Neuromuscular problems in musicians[END_REF][START_REF] Hagberg | Prevalence rates and odds ratios of shoulder-neck diseases in different occupational groups[END_REF].

The first result is the important prevalence in the workforce in these selected papers. In a sample including 191 workers (industry and service workers) with symptoms from the cervicobrachial region, 18% had TOS symptoms (27% of women and 11% of men) [START_REF] Sallstrom | Cervicobrachial disorders in certain occupations, with special reference to compression in the thoracic outlet[END_REF].

Pascarelli and Hsu found a 70% prevalence in a population workers with upper-limb complaints of computer users and musicians (70% and 28 % respectively [START_REF] Pascarelli | Understanding work-related upper extremity disorders : clinical findings in 485 computers users, musicians, and others[END_REF]), with a diagnosis including stress tests.

Postural constraints specific to certain occupations appeared to be possible risk factors according to these studies, especially the use of music instruments or video display screens (cashiers, secretarial work using a computer). Pascarelli and Hsu suggested that TOS related to postural constraints could predispose to other musculoskeletal disorders via a cascade compression mechanism (double crush syndrome) [START_REF] Pascarelli | Understanding work-related upper extremity disorders : clinical findings in 485 computers users, musicians, and others[END_REF]. The role of this postural component in the pathogenesis of TOS must be considered not only in people working with their hands raised above the horizontal plane, such as painters, masons or forestry workers, but also people with jobs requiring retropulsion of the shoulders and rotation of the neck or working with the upper suspended, such as dentists, physiotherapists, hairdressers or musicians [START_REF] Kahn | Problèmes rhumatismaux spécifiques des musiciens[END_REF][START_REF] Fiorentini | Occupational relevance of subclavian vein thrombosis in association with thoracic outlet syndrome[END_REF]. Sällström and Schmidt [START_REF] Sallstrom | Cervicobrachial disorders in certain occupations, with special reference to compression in the thoracic outlet[END_REF] reported, in addition of a high prevalence of TOS, 2% of forms with severe symptoms. Prevalence rates according to job category could not be studied due to methodological limitations of the study. Hagberg and Wegman [START_REF] Hagberg | Prevalence rates and odds ratios of shoulder-neck diseases in different occupational groups[END_REF], in their review on musculoskeletal disorders of the shoulder, reported an excess risk of TOS in construction workers exposed to vibrations.

Overall, these studies presented many methodological limitations and no conclusion can be drawn concerning a significant association between TOS and occupational exposure (and therefore possible worker's compensation, except in particular cases).

The management of work-related TOS presents a number of specificities that should be known by physicians and occupational therapists. Key message is a multidisciplinary approach with medical care (as previously discussed) and workplace prevention. Preventive measures must be applied to correct or eliminate risk factors such as carrying heavy loads, correction of certain postures (arm in abduction-antepulsion), regular rest breaks, etc. Global management of workplace aspects is essential in view of the importance of mental health determinants involved in the pathogenesis of musculoskeletal disorders, mediation of pain processes and consequences of the pain in terms of work incapacity and disability [START_REF] Fouquet | Syndromes de la traversée thoraco-brachiale : sont-ils d'origine professionnelle ? Cervicoscapulagies professionnelles[END_REF].

Prognostic factors also depend on the social context of multidisciplinary management: a surgical series in the USA showed that the main factor preventing return to work was related more to psychosocial working conditions than to the operation itself [START_REF] Fouquet | Syndromes de la traversée thoraco-brachiale : sont-ils d'origine professionnelle ? Cervicoscapulagies professionnelles[END_REF]. Other associated overuse syndromes must also be managed after analysing the risk factors involved.

Conclusion

Apart from vascular and objective neurological deficit forms, TOS is a complex disease in terms of its aetiologies, pathophysiology, diagnosis and management. However, even functional, painful forms can be suspected by clinical examination and identification of risk factors. When in doubt, a multidisciplinary approach by specialized teams can allow early diagnosis and management of these patients including work rehabilitation taking into account prevalence in the workforce. Despite the low level of evidence, there is a possible link between the workplace and the individual in the pathogenesis and course of this disease.

Further studies with clear definition, standardized exposure assessment should be conducted to study the role of occupational factor in the thoracic outlet syndrome.

  The differential diagnosis of upper limb pain includes: other causes of brachial plexus pain, cervical pain, tunnel syndromes, degenerative disease of the upper limb, and non-compressive central and peripheral neurological disease. The other causes of brachial plexus pain to be systematically considered are: Pancoast syndrome, radiation-induced brachial plexopathy and Parsonage-Turner syndrome. The clinical context and clinical interview can generally guide the diagnosis which must be confirmed by clinical examination and complementary investigations (ENMG and/or MRI). Although typical forms of nerve root pain do not raise any major diagnostic problems, some cases limited to distal paraesthesiae can be mistaken for TOS. The examination of the cervical spine, testing of deep tendon reflexes, Spurling manoeuvre and ENMG generally clarify the diagnosis. The possibility of referred pain from posterior joint or myofascial disorders of the anterior scalenus or of the sterno-cleido-mastoid muscles must also be considered. Finally, cervical spondylotic myelopathy can initially present with distal upper limb symptoms. The diagnosis can be corrected by a history of cervicobrachial neuralgia and symptoms below the level of the lesion.


Jean Pera
email: jean.pera@insa-lyon.fr

Sophie Husson

Bernard Guilhot

Keywords: Calcium carbonate, Calorimetry, Carbosilicate, Cement, Hydration, Infrared spectroscopy, Microstructure, Strength

Some work has been carried out on the effect of calcium carbonate on cement paste, but there is no general agreement on the relative effects of different amounts of calcium carbonate on cement paste properties. The objective of the present work is to assess the effect of various amounts of calcium carbonate on the hydration of tricalcium silicate in order to explain the physico-chemical changes occurring during Portland cement hydration. It is shown that calcium carbonate has an accelerating effect on C 3 S and cement hydration and leads to the precipitation of some calcium carbosilicate hydrate. K Ke ey yw

I. Introduction

For a long time, ground limestone has been considered as an inert filler. However, recent studies carried out in the 1980s have pointed out the following phenomena: calcium carboaluminate hydrates precipitate during the hydration of cements containing ground limestone [START_REF] Bachiorrini | Interactions physico-chimiques entre l'aluminate monocalcique et différents carbonates au cours de l'hydratation[END_REF][START_REF] Bachiorrini | Influence de la calcite sur l'hydratation de l'aluminate monocalcique -Corrélation entre les résultats expérimentaux et la thermodynamique du système[END_REF][START_REF] Vs Ramachandran | Thermal analysis of cement components hydrated in the presence of calcium carbonate[END_REF][START_REF] Bushnell-Watson | The detection of the carboaluminate phase in hydrated high alumina cements by differential thermal analysis[END_REF][START_REF] Bachiorrini | Hydratation du ciment alumineux en présence d'agrégats calcaires[END_REF][START_REF] Henning | Einfluss von Calcit auf die Hydratation von Portland-Zement[END_REF][START_REF] Henning | Einfluss von Dolomit auf die Hydratation von Portland-Zement[END_REF],

during the formation of ettringite, sulfate ions can be replaced by carbonate ions without modifying the sequences of the reaction [START_REF] Vernet | Séquences cinétiques des réactions d'hydratation de l'aluminate tricalcique en présence de gypse, de chaux et de fillers calcaires[END_REF][START_REF] Negro | Sur l'emploi du filler calcaire comme régulateur de prise[END_REF][START_REF] Bensted | Further hydration investigation involving Portland cement and the substitution of limestone for gypsum[END_REF][START_REF] Bonnin | Système aluminate de calcium gypse-chaux et eau. 7 e Congrès International de la Chimie des Ciments[END_REF],

there is an interaction between calcium silicate (alite) and calcium carbonate; the latter accelerates the hydration of C3S and modifies the Ca/Si ratio of C-S-H [START_REF] Vs Ramachandran | Influenza del CaCO 3 sulla idratazione e sulle caracteristiche microstrutturali del silicato tricalcio[END_REF][START_REF] Vs Ramachandran | Dependence of the fineness of carbonate on the hydration behaviour of tricalcium silicate[END_REF][START_REF] Vs Ramachandran | Cement with calcium carbonate addition[END_REF].

As the interactions of ground limestone and C 3 A are well documented, we have, in the present paper, focused our attention on the reactions which occur during the hydration of C 3 S in the presence of calcium carbonate. The behaviour of blended Portland cements containing up to 50% ground limestone has also been investigated.

II. Experimental

I II I. .1 1. . M Ma at te er ri ia al ls s II.1.1. Calcium carbonate (CaCO 3 ) The calcite studied was derived from marble and was very pure (98.6% CaCO 3 ). Its specific gravity was 2.75. It was ground to get the following characteristics: 100% particle below 20 µm, average diameter D s O = 2.5 µm, 35% particles below 1 µm.

For this product, the Blaine specific surface area was 680m 2 kg -1 and the BET specific surface area was 3600 m 2 kg -1 Calcium silicate (C 3 S) Calcium silicate was synthesized by reacting a well mixed stoichiometric blend mixture of pure calcium carbonate and reactive silica. The blend was wetted and pellets prepared. The temperature program was as follows: 20-700°C: 20°C min -1 700-1000°C: 15°C min -1 temperature maintained at 1000°C for 40 min. 1000-1450°C: 8°C min -1 1450-1600°C: 5°C min -1 temperature maintained at 1600°C for 120 min. The residual lime (CaO) was measured by hydrochloric acid titration of a solution containing 250 mg C 3 S and 100 mL ethyleneglycol, shaken at 70°C for 30 min. The calcination was considered good as the free CaO content was less than 2%. A well-crystallized triclinic C 3 S was then obtained and ground in a laboratory ball-mill. Its particle size distribution was characterized by: 100% particles below 80 µm D 50 = 15 µm 30% particles below 10 µm

II.1.2. Ordinary Portland Cement (OPC)

The cement used in the present study was a CPA CEM I 52.5 according to the European prestandard ENV 197-1 for common cements. Its Bogue potential composition was C 3 S = 67.9%; C 2 S = 4.8%; C 3 A = 10.4%; C 4 AF = 9.3%. Its Blaine and BET specific surface areas were 364 m 2 kg -1 and 1400 m 2 kg -1 , respectively. The average value of the particle size distribution was D 50 = 16 µm. I II I. .2 2. . M Me et th ho od ds s u us se ed d f fo or r i in nv ve es st ti ig ga at ti io on n Isothermal calorimetry was used to study the interactions between C 3 S (or OPC) and CaCO 3 . C 3 S (or OPC) was mixed with CaCO 3 in the weight ratio 1:1. The mixture (300 mg) was then hydrated in presence of the same quantity of water (300 mg). The total heat developed during the reaction was recorded. The length of the experiment was 15 h. The morphology of these hardened pastes was investigated by means of scanning electron microscopy (SEM), and the hydrates formed were identified, using infrared spectrometry (IRS), X-ray diffraction (XRD) and differential thermal analysis (DTA). Pastes of pure C 3 S (or OPC) and CaCO 3 were prepared at equivalent consistency. The water to solid ratios are shown in Table 1.

From Table 1, it is clear that the presence of CaCO 3 has a plasticizing effect on the paste: the higher the CaCO 3 content, the lower the amount of mixing water. Minicylinders of paste were cast (φ = 20 mm, h = 40 mm), demoulded after 2 days of hydration, and kept at 20°C and relative humidity 95% until mechanical testing, which occurred after 7, 28 and 60 days of age.

III. Results and discussion

. Isothermal calorimetry

The isothermal calorimetry curves showing the rate of heat development of 300 mg C 3 S and (150 mg C 3 S+150 mg CaCO 3 ) during hydration, up to 15 h, are given in Figure 1. The values recorded for the blend (C 3 S+CaCO 3 ) were always higher than those of hydrated C 3 S. The total heat resulting from pure C 3 S hydration was 145 joules, whilst that of the mixture (50% C 3 S+50% CaCO 3 ) reached 260 joules. These results are in good agreement with those obtained by Ramachandran [START_REF] Vs Ramachandran | Cement with calcium carbonate addition[END_REF]. They indicate that CaCO 3 cannot be considered as an inert addition towards C 3 S hydration.

III.1.2. SEM examination

As shown in Figure 2, the pastes presented about the same texture after 7 days of hydration; namely platlets of calcium hydroxide and fibrils of C-S-H. After 60 days of hydration, the morphology of the pastes is different, as presented in Figure 3. In pure C 3 S, platlets of calcium hydroxide and C-S-H type II are present according to Taylor [START_REF] Hfw Taylor | The hydration of tricalcium silicate[END_REF]. In 'C 3 S+CaCO 3 ' paste, granules of C-S-H are formed.

III.1.2. Infrared spectrometry

The IR spectra of hydrated C 3 S at different ages are shown in Figure 4. Those of the 'C 3 S+CaCO 3 ' paste are shown in Figure 5. The wavenumbers present in each product hydrated either for one day or 28 days are reported in Table 2. The vibrations associated with each wavenumber are also presented in Table 2. In hydrated C 3 S, all the Si-O-Si stretching bands were reorganized between 1 and 28 days. The structure of tobermorite gel was reached [START_REF] Vc | The Infrared Spectra of Minerals[END_REF], as shown by the emboldened wavenumbers. In the blend 'C 3 S+CaCO 3 ,' the characteristic bands of the CO 3 ion appeared. Some SiO 4 bands were shifted after one day of hydration, demonstrating the accelerating effect of CaCO 3 on C 3 S hydration. Those results were also obtained using the diffuse reflectance method, as shown in Figure 6. The results of XRD investigations are given in Figure 7, after 60 days of hydration. The following conclusions can be drawn from these analyses: calcium hydroxide is present in all compositions; the intensity of the C 3 S peak decreases when the amount of CaCO 3 increases such that in the blend containing 50% CaCO 3 , these peaks have almost disappeared; the intensity of the peak at 2θ = 14.9° increases with the CaCO 3 content and is due to the formation of some hydrated carbosilicate.

The consumption of CaCO 3 was studied by means of DTA. The area of the decomposition peak of CaCO 3 decreased with the hydration time and the temperature corresponding to the maximum of this peak shifted towards smaller values as shown in Figure 8. Such results were previously observed by Henning [START_REF] Henning | Einfluss von Calcit auf die Hydratation von Portland-Zement[END_REF] in the case of precipitation of carbonate hydrates.

III.1.4. Compressive strength of pastes

The compressive strength of the different pastes is presented in Figure 9. The presence of CaCO 3 at levels higher than 30% has a beneficial effect on the strength, whatever the hydration time may be. It is possible to compute the K(t) value for each paste using Feret's formula: 2 where R(t) is the strength after t days of hydration, K(t) is the coefficient of reactivity of the binder, Vs, is the volume of binder, and Vt, the sum of the following three volumes: binder, water and entrained air. In the present study, the volume of air was measured at 1.5-1.6%. Table 3 shows the K [START_REF] Henning | Einfluss von Dolomit auf die Hydratation von Portland-Zement[END_REF] and K(60) values obtained for the different pastes. After 7 days hydration, all blended pastes develop higher K [START_REF] Henning | Einfluss von Dolomit auf die Hydratation von Portland-Zement[END_REF] 10 shows that the same type of curve is observed with OPC and pure C 3 S. The heat produced by the reaction between 50% OPC and 50% CaCO 3 is about double that issued from plain OPC hydration.

R(t) = K(t)(V s/ V t)

III.2.2. Hydrates formed

As shown by XRD (Figure 11) carboaluminate and carbosilicate have been precipitated after 60 days of hydration. The presence of calcium carboaluminate hydrate was also observed by infrared spectrometry (bands at 3670 and 3530 cm -1 ). IR spectroscopy also pointed out differences in AF m and AF t phases (Figure 12). In the paste containing pure OPC, both monosulphate (bands at 100 and 1170 cm -1 ) and ettringite (band at 1120 cm -1 ) are present. In the paste containing 50% CaCO 3 , monosulphate almost disappeared and the band at 1120 cm -1 was reinforced, so some SO 4 ions in ettringite were probably replaced by CO 3 ions. The band assigned to the ν 3 SiO 4 , vibration at 970 cm -1 was also slightly modified and that of carbonate at 875 cm -1 amplified.

III.2.3. Compressive strength of pastes

The compressive strength of pastes is presented in Figure 13. The strength is maintained or even increased in pastes containing 10% CaCO 3 . Lower strengths are obtained with higher CaCO 3 levels. These results mean that the development of strength is not similar in C 3 S and OPC pastes containing CaCO 3 . In OPC, interactions occur between C 3 A and CaCO 3 , leading to the production of calcium carboaluminate hydrate and the modification of ettringite, whereas in blended C 3 S pastes, only calcium carbosilicate hydrate is obtained. Nevertheless, the level of strength remains acceptable for a 50% level of OPC substitution: it is 81% that of OPC alone. This result proves that chemical reactions occur, but in a smaller extent than in C 3 S pastes and more CaCO 3 , remains as an inert filler.

IV. Conclusion

As shown by isothermal calorimetry, more total heat is developed in C 3 S or cement containing up to 50% calcium carbonate than in the absence of CaCO 3 under comparable conditions signifying the accelerating effect of CaCO 3 . Hydration of C 3 S in the presence of CaCO 3 , results in the production of some calcium carbosilicate hydrate and good mechanical performance for amounts of CaCO 3 higher than 30%. In cement paste, calcium carbonate modifies the AF m and AF t phases, and produces calcium carbosilicate and carboaluminate hydrates but does not lead to the same strength development as in C 3 S paste.

I

  II II I. .1 1. . R Re ea ac ct ti io on ns s b be et tw we ee en n

Figures 6 F

 6 Figures

  values than pure C 3 S which proves that CaCO 3 reacts chemically. After 60 days hydration, only pastes containing more than 30% CaCO 3 , develop higher K(60) values.

	I II II I. .2 2. . R Re ea ac ct ti io on ns s b be et tw we ee en n O OP PC C a an nd d C Ca aC CO O 3 3
	III.2.1. Isothermal calorimetry
	Figure

  . .

	T Ta ab bl le e 3 3: : R Re ea ac ct ti iv vi it ty y o of f t th he e d di if ff fe er re en nt t b bi in nd de er rs s
	C C3 3S S	1 10 00 0 9 90 0	8 80 0	7 70 0	6 60 0	5 50 0
	C Ca aC CO O3 3 ( (w wt t% %) ) 0 0	1 10 0	2 20 0	3 30 0	4 40 0	5 50 0
	K K( (7 7) )	1 10 00 0 1 10 07 7 1 12 29 9 1 17 79 9	1 16 64 4 1 15 57 7
	K K( (6 60 0) )	2 22 25 5 1 12 25 5 1 13 30 0 3 30 00 0 3 37 75 5 4 41 10 0
	F Fi ig gu ur re e 1 13 3: : C Co om mp pr re es ss si iv ve e s st tr re en ng gt th h o of f c ce em me en nt t p pa as st te es s c co on nt ta ai in ni in ng g d di if ff fe er re en nt t a am mo ou un nt ts s o of f C Ca aC CO O3 3. .
	Tables
	T Ta ab bl le e 1 1: : W Wa at te er r t to o s so ol li id d r ra at ti io os s o of f p pa as st te es s
	C C3 3S S ( (w wt t% %) )		1 10 00 0	9 90 0	8 80 0	7 70 0	6 60 0	5 50 0
	C Ca aC CO O3 3 ( (w wt t% %) )		0 0		1 10 0	2 20 0	3 30 0	4 40 0	5 50 0
	W W/ /S S S S= = C C3 3S S + + C Ca aC CO O3 3	0 0. .3 35 5 0 0. .3 34 4 0 0. .3 33 3 0 0. .3 32 2 0 0. .3 31 1 0 0. .3 3
	O OP PC C ( (w wt t% %) )		1 10 00 0	9 90 0	8 80 0	7 70 0	6 60 0	5 50 0
	C Ca aC CO O3 3 ( (w wt t% %) )		0 0		1 10 0	2 20 0	3 30 0	4 40 0	5 50 0
	W W/ /S S S S= = O OP PC C + + C Ca aC CO O3 3 0 0. .2 28 8 0 0. .2 28 8 0 0. .2 27 7 0 0. .2 26 6 0 0. .2 25 5 0 0. .2 24 4
	T Ta ab bl le e 2 2: : I In nf fr ra ar re ed d r re es su ul lt ts s o of f h hy yd dr ra at te ed d C C3 3S S a an nd d ( (C C3 3S S+ +C Ca aC CO O3 3) )
			C C3 3S S				C C3 3S S + + C Ca aC CO O3 3
	W Wa av ve en nu um mb be er r ( (c cm m -1 -1 ) )			V Vi ib br ra at ti io on n	W Wa av ve en nu um mb be er r ( (c cm m -1 -1 ) )	V Vi ib br ra at ti io on n
	1 1 d da ay y		2 28 8 d da ay ys s				1 1 d da ay y	2 28 8 d da ay ys s
	1 16 63 35 5		1 16 63 30 0		ν ν2 2 H H2 2O O	1 16 63 35 5	1 16 63 35 5	ν ν2 2 H H2 2O O
	1 14 48 80 0		1 14 45 50 0		ν ν3 3 C CO O3 3	1 14 43 37 7	1 14 43 37 7	ν ν3 3 C CO O3 3
	9 93 38 8		9 96 60 0		ν ν3 3 S Si iO O4 4	1 11 16 61 1	1 11 16 61 1	ν ν1 1 C CO O3 3
	9 90 05 5					ν ν3 3 S Si iO O4 4	9 95 54 4	9 96 63 3	ν ν3 3 S Si iO O4 4
	8 88 82 2		8 88 82 2		ν ν3 3 S Si iO O4 4	8 87 76 6	8 87 76 6	ν ν2 2 C CO O3 3
	F Fi ig gu ur re e 1 12 2: : M Mo od di if fi ic ca at ti io on n o of f A AF Fm m a an nd d A Af ft t p ph ha as se es s i in n t th he e p pa as st te e c co on nt ta ai in ni in ng g 5 50 0% % O OP PC C a an nd d 5 50 0% % C Ca aC C0 03 3 a af ft te er r 6 60 0 d da ay ys s o of f 8 85 55 5 8 85 55 5 ν ν3 3 S Si iO O4 4 8 84 49 9 ν ν3 3 S Si iO O4 4
	h hy yd dr ra at ti io on n. . 6 66 60 0		6 66 65 5		ν ν4 4 S Si iO O4 4	7 71 12 2	7 71 12 2	ν ν4 4 C CO O3 3
			6 64 40 0		ν ν4 4 S Si iO O4 4	6 66 60 0	6 66 60 0	ν ν4 4 S Si iO O4 4
	5 51 18 8					ν ν4 4 S Si iO O4 4	5 50 06 6	4 48 86 6	ν ν4 4 S Si iO O4 4
	4 45 50 0		4 45 50 0		ν ν2 2 S Si iO O4 4	4 45 52 2	4 46 62 2	ν ν2 2 S Si iO O4 4


MD Alexis Descatha
email: alexis.descatha@rpc.aphp.fr

MD Laure Huard

MD Sarah Duval

The sensitivity and specificity of ultrasound for the diagnosis of carpal tunnel syndrome. A meta-analysis

published or not. The documents may come

Sir,

We read with a particular interest de meta-analysis entitled "The Sensitivity and Specificity of Ultrasound for the Diagnosis of Carpal Tunnel Syndrome" by Fowler, Gaughan and Ilyas [START_REF] Fowler | The Sensitivity and Specificity of Ultrasound for the Diagnosis of Carpal Tunnel Syndrome: A Meta-analysis[END_REF] . It is true ultrasound has garnered interest in the last decade for diagnosis of carpal tunnel syndrome considering its low costs, noninvasiveness and short examination times, especially with the improvement of the transducers in the last five years. Therefore, a systematic review of available data and meta-analysis on validity of ultrasound for the diagnosis of carpal tunnel syndrome seemed to be particularly important. However, although the authors apparently rigorously selected papers by following PRISMA or MOOSE guidelines 2;3 , their metaanalysis is problematic. Actually, as the authors themselves stated in their discussion, they combined results of different threshold of cross-sectional area of median nerve, which could lead to artificial variation of sensitivity or specificity or, at the opposite, hide real variation of these parameters. We are also concerned about the reference used in the selected studies, such as the transducers used: more details are needed on what is clinical reference standard (what clinical testing used, who performed it), what is considered by authors as a positive electrodiagnostic testing, what ultrasound machine and transducers used? This is particularly important to understand the heterogeneity of the results found by authors. The authors detailed why likelihood ratio are better than sensitivity and specificity in the method section but unfortunately did not give any results about them.

In conclusion, the authors gave probably a fair review of what information about validity in diagnosis of carpal tunnel syndrome by ultrasound but their meta-analysis should be interpreted with caution, and need further work. We feel authors could be detailed more about references and materials used (including the year of publication) to study the sensitivity of change without including subgroup. Likelihood ratio would give better results than only sensitivity and specificity. Finally, we think, even though it is probably not feasible to pool raw data by contacting authors, perform separate analyses at different thresholds are mandatory to obtain reliable accuracy for clinicians.