[Awaji criteria: new diagnostic criteria for amyotrophic lateral sclerosis]. / Les critères d'Awaji: les nouveaux critères diagnostiques de la sclérose latérale amyotrophique.

Amyotrophic lateral sclerosis is the most common motor neuron disorder in adults. Although the diagnosis appears obvious in theory, clinical practice shows the contrary as diagnosis is delayed in many patients; the average time between symptom onset and diagnosis can reach 12 months. The delay can be explained by the variability of the clinical presentation and by the absence of diagnostic markers. In order to standardize diagnosis for enrollment in clinical research, diagnostic criteria for ALS were created and revisited during the last 20 years. In 2006, the Awaji criteria for the diagnosis of ALS were proposed, adding two major points to the diagnostic criteria: electromyography is considered equivalent to clinical examination for the identification of LMN signs and fasciculation potentials resume their prominent place in the diagnosis. Comparisons of the accuracy of the revisited El Escorial and Awaji criteria support improved diagnostic sensitivity without any effect on specificity with the new classification. The only weakness of the new classification involves patients with UMN signs in one region and LMN in two regions; these patients were previously classified as laboratory-supported probable ALS and currently as possible ALS, a lower level of diagnostic certainty. In all other instances the accuracy appears to be improved by the Awaji criteria. Nevertheless, there is a body of evidence suggesting the need for a revision of these new criteria, giving more weight to clinical and complementary findings of UMN involvement. The need to diagnose and treat ALS quickly could be facilitated by the inclusion of complementary investigations that detect UMN signs.

[Vascular leukoencephalopathy in patients without vascular risk factor or NOTCH3 mutation: clinical and radiological findings]. / Leucoencéphalopathies vasculaires chez des patients sans facteur de risque vasculaire ni mutation de NOTCH3: description clinique et radiologique.

INTRODUCTION: White matter lesions seen on MR scan reflect small vessel disease of the brain; increasing age and high blood pressure are the main risk factors. In young patients without vascular risk factors, screening for CADASIL mutation has to be done. Our aim was to describe clinical as well as radiological features of a series of patients without NOTCH3 mutation with severe vascular leukoencephalopathy not explained by the presence of vascular risk factors. MATERIAL AND METHODS: Inclusion criteria were grade 3 leukoencephalopathy according to the Fazekas scale, age<70years at onset, and negative screening for NOTCH3 gene. Patients with severe vascular risk factors or atherosclerosis were excluded. Clinical and MRI findings were analysed. RESULTS: Eight patients (four men) were included, five did not have any vascular risk factor. Mean age at onset was 59.5years. Initial symptoms were progressive in six cases of eight cases. They consisted of astasia-abasia and progressively worsened; of note one patient died 4years after disease onset. Cerebral MRI disclosed marked atrophy in five patients out of eight, temporal lobe (two out of eight) and external capsule (five out of eight) involvement was moderate. Four patients did not have any other atherosclerosis lesion. Seven out of eight had no retinal microangiopathy. High blood pressure was identified in two patients. CONCLUSION: The identification of vascular leukoencephalopathy in young patients without any vascular risk factors should lead the clinician to perform a complete work-up to search for treatable conditions including high blood pressure. Patients with vascular leukoencephalopathy usually present with astasia-abasia. In this context, cerebral MRI, cannot perfectly discriminate between patients with CADASIL from those with acquired small-vessel disease of the brain so that sequencing of NOTCH3 gene exons 2-24 is recommended.

Predictive value of motor evoked potentials in clinically isolated syndrome.

OBJECTIVES: To assess the predictive role of several measures obtained by transcranial magnetic stimulation (TMS) in patients with clinically isolated syndrome (CIS) for the risk of conversion to multiple sclerosis (MS) during the first 2 years. MATERIALS AND METHODS: We investigated 34 patients with CIS. After 2 years of follow-up and classification into two groups according to MS diagnosis, initial TMS measures were compared to determine their predictive values for conversion to MS. RESULTS: Sixteen patients developed MS. We observed a significant difference between the two groups for contralateral silent period and no significant difference for the central motor conduction time, amplitude ratio, motor threshold, ipsilateral silent period, and the transcallosal conduction time. CONCLUSIONS: Contralateral silent period (SP) seems to be a valuable parameter to early distinguish patients who will develop MS or not. This result about SP during CIS has never been described until now. An increased contralateral silent period would predict a conversion to MS with a positive predictive value of 75%, but this result needs to be confirmed in larger groups.

[Natural history of adult-onset eIF2B-related disorders: a multicentric survey of 24 cases]. / Histoire naturelle des leucodystrophies avec mutation EIF2B: étude rétrospective multicentrique de 24 cas adultes.

INTRODUCTION: The childhood ataxia with central nervous system hypomyelination-vanishing white matter syndrome (CACH-VWM) was first characterized in children (2-5 years) on clinical and MRI criteria: cerebellospastic signs associated with episodes of rapid deterioration following stress and extensive cavitatingleucoencephalopathy. Causative mutations were found in the five genes encoding the subunits of the eukaryotic initiation factor 2B (eIF2B), involved in protein synthesis and its regulation under cellular stresses. A broad clinical spectrum has been subsequently described from congenital to adult-onset forms leading to the concept of eIF2B-related disorders. Our aim was to describe clinical and brain magnetic resonance imaging characteristics, genetic findings and natural history of patients with adult-onset eIF2B-related disorders. METHODS: The inclusion criteria were based on the presence of EIF2B mutations and a disease onset after the age of 16 years. One patient with an asymptomatic diagnosis was also included. Clinical and MRI findings were retrospectively recorded in all patients. This multicentric study included 24 patients from 22 families. RESULTS: A sex-ratio imbalance was noted (male/female=5/19). The mean age of onset was 30 years (range 12-62). Initial symptoms were neurologic (n=20), psychiatric (n=3) and ovarian failure (n=6). During follow-up (mean: 11 years, range 2-35 years), two patients died. Of the 22 survivors, 67% showed a decline in their cognitive functions and mean EDSS was 5.6 (range=0-9.5). One case remained asymptomatic. Stress worsened clinical symptoms in 33% of the patients. Magnetic resonance imaging findings consisted of cerebral atrophy (92%), extensive cystic leucoencephalopathy (83%), corpus callosum involvement (92%) and cerebellar (37%) T2-weighted hyperintensities. Most patients (83%) showed mutations in the EIF2B5 gene. The recurrent p.Arg113His-eIF2Be mutation was found at a homozygous state in 58% of the 24 eIF2B-mutated patients. CONCLUSION: eIF2B-related disorder is probably underestimated as an adult-onset inherited leucoencephalopathy. Cerebral atrophy is constant, whereas the typical vanishing of the white matter can be absent. Functional and cognitive prognosis remains severe. Molecular diagnosis is facilitated for these forms by screening for the recurrent p.Arg113His-eIF2Be mutation.

Bilateral hand amyotrophy with PMP-22 gene deletion.

Hereditary neuropathy with liability to pressure palsies (HNPP) phenotypes are heterogeneous. We report the case of a 52-year-old woman without medical history, who complained of bilateral hand weakness suggestive first of a motor neuron disorder. The presence of a diffuse predominant distal demyelinating neuropathy suggested a deletion of PMP-22 gene, which was confirmed by genetic analysis. This case report underlines a novel phenotype related to the deletion of PMP-22 gene.

[Thoracic outlet syndrome: an unusual postoperative complication]. / Le syndrome du défilé thoraco-brachial: une complication post-opératoire inhabituelle.

UNLABELLED: Introduction. Neurogenic Thoracic Outlet Syndrome (NTOS) is a chronic lower trunk brachial plexus entrapment caused by a cervical rib or a fibrous band. True NTOS is rare and progresses usually slowly. Case report. A 12-year-old girl complained of numbness and weakness of the right upper limb immediately after an orthopedic surgical procedure for scoliosis. Neurological and neurophysiological features were both consistent with a neurogenic thoracic outlet syndrome (NTOS). CONCLUSION: This observation illustrates the risk of NTOS after certain surgical procedures, especially when a prolonged prone position with abducted shoulders is required.

[Cyclosporin-induced toxic neuromyopathy]. / Neuromyopathie toxique induite par la ciclosporine.

INTRODUCTION: Cyclosporine is an immunosuppressive treatment whose side effects limit its usefulness. Among neurological side effects, neuropathies or myopathies have been reported, specially inpatients given combinations of cyclosporine with co-enzyme A reductase inhibitors. CASE REPORT: We report here the case of a 67-year-old woman who developed few months after a kidney graft sensorimotor disorders which progressed rapidly. Since all etiologies of such a disorder were ruled out, the hypothesis of toxicity exclusively induced by cyclosporine was suggested and confirmed by the improvement observed after its withdrawal. CONCLUSION: This observation highlights the fact that cyclosporine may induce neuromyopathies even when given alone at the therapeutic dosage.

[Primary lateral sclerosis with breast cancer, a potential paraneoplastic neurological syndrome]. / Sclérose latérale primitive et cancer du sein: syndrome neurologique paranéoplasique ou association fortuite?

Few reports indicate that motor neuron diseases may have paraneoplastic origin. A 70 year-old woman suffering from progressive upper motor neuron disease is presented. Laboratory, radiological and neurophysiologic studies were compatible with primary lateral sclerosis. Six years later a routine screening led to the discovery of a breast cancer, suggesting that the upper motor neuron syndrome could be paraneoplastic. So, in female patients with primary lateral sclerosis, a mammography should be recommended to search for breast cancer.

[Acute motor axonal neuropathy, enterovirus and Amyotrophic lateral sclerosis: can there be a link?]. / Syndrome de Guillain Barré axonal, entérovirus et sclérose latérale amyotrophique: peut-il y avoir une relation?

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of both upper and lower motor neurons. Acute motor axonal neuropathy (AMAN) affects only the lower motor neuron and occurs, in the majority of cases, after an infection. To date, the etiology of ALS remains unknown but seems multifactorial. A 60 year-old man with a past medical history of AMAN developed ALS 9 years later. At that time, genomic sequences of enterovirus (echovirus 6 and 7) were detected in cerebrospinal fluid by RT-PCR. This particular succession led to discuss a possible link between theses two disorders and consequently the involvement of enterovirus in the development of ALS.

[Demyelinating neuropathy and Sjögren's syndrome: a diagnostic pitfall]. / Neuropathie démyélinisante et syndrome de Gougerot-Sjögren: un piège diagnostique.

INTRODUCTION: Neuropathies induced by Sjögren's syndrome (SS) are usually axonal. Nevertheless some demyelinating neuropathies have been described in patients with SS. To date, the relationship between demyelinating neuropathies and SS remains imprecise. CASE REPORT: A 75 year-old man presented with a chronic history of sensory disturbances linked to demyelinating neuropathy. Electroneuromyography revealed a demyelinating neuropathy and complementary tests revealed both Sjögren's syndrome (SS) and HMSN IA. CONCLUSION: We suggested that an inherited affection might be researched before considering that demyelinating neuropathy might be a form of peripheral nervous system involvement in SS.

[Acute demyelinating motor neuropathy: an atypical form of the Guillain-Barre syndrome?]. / Neuropathie motrice aiguë démyélinisante secondaire à une gastro-entérite: une forme atypique de syndrome de Guillain-Barré?

A 33-year-old man presented an acute motor demyelinating neuropathy following Campylobacter jejuni enteritis. The patient was improved with an IgIV treatment. Clinical features and course time were compatible with the diagnosis of a Guillain-Barré syndrome. The electrophysiologic studies were in favor of multifocal motor neuropathy with conduction blocks. We discuss the nosologic group of this neuropathy.

Absence of the OPTN mutation in a patient with ALS and familial primary open angle glaucoma.

The optineurin (OPTN) gene, known to be implicated in primary open-angle glaucoma (POAG), is the more recent genetic factor linked to ALS. We report the case of a 75year-old man who developed ALS and whose medical history was dominated by a familial POAG. The absence of OPTN gene mutation in a patient who suffered from two conditions linked to mutations of this gene does not support involvement of OPTN in ALS.

Improvement of a CIDP associated with hepatitis C virus infection using antiviral therapy.

A 57-year-old man with chronic inflammatory demyelinating polyneuropathy associated with hepatitis C virus infection was treated successfully with the combination of peginterferon-alpha-2b and ribavirin. Viral eradication was confirmed during the 4th week of treatment and was followed 3 weeks later by neurologic improvement. The patient resumed normal activity 1 year after the therapy was completed.