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Objective: To analyze the humoral response after COVID-19 vaccination in patients with multiple sclerosis (MS) according to disease-modifying treatments (DMTs) and in comparison with the humoral response after SARS-CoV-2 infection., Methods: We included 28 MS patients with serological results after COVID-19 vaccination (Pfizer-BioNTech or Moderna ARNm) and 61 MS patients with serological results after COVID-19 (COVID-19 group) among patients followed up at the MS Center of Strasbourg, France, between January and April 2021. The primary endpoint was the IgG index according to DMTs (anti-CD20 mAb, sphingosine 1-phosphate receptor [S1PR] modulator and other treatments) and COVID-19 vaccine or COVID-19 groups., Results: In the vaccinated MS patients, the median IgG index was lower in patients treated with anti-CD20 mAb and in patients treated with S1PR modulator compared to patients receiving other or no DMTs (4.80 [1.58-28.6], 16.5 [16.3-48.5], 1116 [434-1747] and 1272 [658-1886], respectively, P<0.001). Similar results were found for MS patients after COVID-19., Conclusions: Patients with MS and treated with S1PR modulators or anti-CD20 mAb had a reduced humoral response after COVID-19 vaccine., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: The spinal cord is one of the two main targets of neuromyelitis optica (NMO). The aim of this study was to highlight cervical spinal cord atrophy in NMO patients as compared to controls and to assess correlations between atrophy and clinical characteristics and cervical spinal cord MRI data., Methods: This prospective study investigated 15 patients with a diagnosis of NMOSD and 15 healthy controls. The whole cervical spinal cord was explored by MRI. The cross-sectional area (CSA) was estimate at every level of cup. This measurement was then averaged on the whole cervical spinal cord, providing a single measurement for every subject, denoted as mean CSA., Results: Mean CSA was 68.5 mm2 in the population of NMO patients and 72.8 mm2 in the population of healthy subjects. NMO patients had significantly smaller cervical spinal cord area than healthy controls (T test=0.009). Cervical spinal cord atrophy was associated with clinical signs of medullary involvement (T test=0.0006). There was a tendency toward a relation between cervical spinal cord atrophy and the Expanded Disability Status Scale (EDSS) (T test=0.07). This correlation seems statistically significant (T test<0.05) at the level of the upper cervical spinal cord (C2-C3) CONCLUSION: This study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Introduction: Neuromyelitis optica spectrum disorder (NMO-SD) has been recognized for the past decade. Biomarkers such as anti-Aquaporin 4 antibodies (AQP4) and anti-Myelin Oligodendrocyte Glycoprotein (MOG) have been able to classify NMO-SD into several groups., Methods: A retrospective study was performed in the Strasbourg University Medical Center among patients with AQP4+, MOG+ and double-seronegative NMO to compare their clinical, epidemiological and paraclinical features., Results: Thirty-two patients with NMO were included. The AQP4+ NMO patients had a median of age of 45 years, with associated myelitis in 62.5% of cases and other autoantibodies in 37.5% of cases. The mean number of relapses by clinical history was 3. The mean initial visual acuity during an exacerbation was 0.3 LogMAR, and the visual acuity after an exacerbation was 0.1 LogMAR. MOG+NMO patients had a median age of 23 years, with severely impaired initial visual acuity (0.6 LogMAR) but better recovery (0 LogMAR); optic disc edema was present in 80% of cases; the mean number of relapses on clinical history was 1. AQP4-/MOG- NMO's were more common in women (70%) and were bilateral in 40% of cases., Conclusion: The diagnostic characteristics of NMO-SD are becoming increasingly differentiated, with a positive impact on functional prognosis and long-term progression. Other biomarkers have yet to be identified to improve the diagnosis and treatment of these disorders., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

During the 20 past years, the management of multiple sclerosis (MS) has largely changed especially concerning therapeutical approach. Before 1996, treatments were restricted to corticosteroids for relapses, several symptomatic treatments and unselective immunosuppressive drugs (azathioprine, cyclophosphamide, methotrexate) with a low evidence of any efficacy. In the present review, we analyze the principal real-life cohorts of MS during several periods (before therapeutical modern area, first-generation treatment area and most recent period). Despite many methodological problems, we observe globally a delay of around 3-5 years between untreated cohorts and first-generation treatments for going to EDSS 6 which is probably the most robust score. This delay is clearly increase to at least 15 years with the most recent cohort treated first and second-line treatments confirming that early and more intensive treatment are necessary to have a long-term efficacy on disability progression and especially on severe disability represent by EDSS 6. Larger cohorts with longer follow-up is necessary to confirm these tendencies and OFSEP observatory or MS base will probably provide us the possibility to conclude in a couple of years., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The ideal treatment for multiple sclerosis (MS) would target both the neuroinflammatory component of the disease (peripheral and central) and its neurodegenerative component, via modulation of a ubiquitous and pleiotropic common target. Sphingosine-1-phosphate (S1P), a product of sphingosine metabolism, regulates many biological functions (including cell proliferation and survival, cell migration, the immune response and cardiovascular function) via five subtypes of receptor. These receptors are expressed in all types of brain cells where they modulate a number of processes involved in neuronal plasticity, including myelination, neurogenesis and neuroprotection. This profile has aroused interest in modulation of S1P function as a therapeutic target in many brain diseases, particularly those in which the immune system plays a role in the development of brain lesions. Fingolimod, a S1P receptor modulator, exerts its beneficial effects in MS through its anti-inflammatory and anti-neurodegenerative effects. This review discusses recent evidence indicating that fingolimod may target both the inflammatory and neurodegenerative components of the disease process in MS., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Emotional disturbances in multiple sclerosis (MS) are often explored in terms of affect recognition, with controversial results that likely reflect the high lesional heterogeneity. Patients' emotional experience, however, has seldom been studied and has never been explored using fMRI., Objectives: To explore the emotional experience in MS and compare these data with fMRI measurements using for the first time real-life emotional scenes differing in valence and arousal., Methods: Twenty-five right-handed women with relapsing-remitting MS and 27 right-handed age-, sex-, and education-matched healthy controls visualized during an fMRI session, emotional scenes taken from the international affect picture system (IAPS) and differing in valence (positive, negative, neutral) and arousal (ranging from calm to excited). During a post-scanning debriefing, participants were asked to look again at each image and score it in terms of valence and arousal sensation on a scale of 1-9., Results: Cognitively well-preserved MS subjects presented a significantly more scattered emotional experience compared to controls in response to positive and negative pictures. In fMRI, MS patients also presented a higher variability of response when compared to controls in left inferior orbitofrontal cortex for positive stimulations. For negative condition, no significant results were observed between the two groups. However, a trend was detected in left amygdala, right fusiform gyrus, right caudate nucleus and right pallidum for negative stimulations., Conclusion: In response to emotional stimuli, MS subjects presented a scattered emotional experience subtended by a greater variability of brain response, highlighting an emotional pattern not previously reported in MS patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory disease of the central nervous system characterized, in particular, by disabling episodes of optic neuritis and longitudinal extensive transverse myelitis. Its main pathogenic characteristic is the presence of anti-aquaporin-4 antibodies (AQP4-Abs) in the serum of affected patients. However, a proportion of patients with the typical NMOSD phenotype are, in fact, negative (seronegative) for AQP4-Abs and, within this category of patients, a proportion of them instead express antibodies to myelin oligodendrocyte glycoprotein (MOG-Abs). The presence of MOG-Abs in the sera of seronegative NMOSD patients is more frequently associated with monophasic disease and moderate symptom severity, and also appears to predict a better outcome. The present report is a review of the clinical and immunological features of MOG-Ab-positive NMOSD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Aim: Multiple sclerosis (MS) is a disease of the central nervous system that affects young adults at a time when they launch into the workforce. The disease often has a great impact on working life. The objective of this survey was to identify the problems faced by people with multiple sclerosis in the context of their work., Methods: To describe the difficulties experienced at work by patients with multiple sclerosis, we carried out in 2010 a regional survey including neurology and functional rehabilitation centers., Results: Two hundred and seven MS patients of working age responded to the survey. The employment rate was 67.6%. Among difficulties expressed by patients, physical and mental fatigue appeared as the issues affecting work. For 41% of respondents, preventive measures at work could help maintain or resume employment., Conclusion: Problems of fatigability put forward by MS patients are elements that can predict a loss of employment., (Copyright © 2015. Published by Elsevier Masson SAS.)

Unlabelled: Following the publication practice guidelines for multiple sclerosis by a group of neurologists (multiple sclerosis study group [GRESEP]), the primary objective of this study was to compare the reality of practice to the guidelines according to the targeted clinical audit (TCA) method. The study was conducted at 17 neurology sites and was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). Two complementary surveys were done on the record keeping and the root causes of the deviations. The percentages of compliance ranged from 8 to 98% for the TCA-DIAG, and from 15 to 99% for the TCA-EVOL, with wide disparity between sites. The audits were able to identify causes of the flaws in traceability or accessibility. At the end of the study, despite its limitations, we think that the sharing of the results from different sites provided interesting approaches for the use of the assessment criteria defined by GRESEP in a complete audit cycle. This study is to our knowledge the first report of an experiment in which guidelines were created, and subsequently followed by the development of assessment criteria and then the performance of targeted clinical audits using them, all by the same participants., Context: Clinical practice guidelines (CPGs) are intended to help practitioners and patients make informed treatment choices, but their integration into actual practice remains problematic. This study was done immediately following the publication of CPGs for multiple sclerosis (MS) by the multiple sclerosis study group [GRESEP]. The primary objective was to generate quality criteria, to test them within the same group, and to analyze the observed deviations., Materials and Methods: The study was conducted in the 17 voluntary departments that had participated in the development of the CPGs. The targeted clinical audit method was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). All the files were evaluated by a clinical research technician using digital format, which ensured thoroughness of the collection. Two complementary surveys were done on the record keeping and the potential causes of the deviations., Results: The percentages of compliance to the criteria ranged from 8 to 98% (out of 240 files) for the TCA-DIAG, and from 15 to 99% (221 files) for the TCA-EVOL, with wide disparity between sites (interquartile distance ranges: TCA-DIAG between 0% and 55%; TCA-EVOL between 0% and 70%). The mean percentage of compliance with all the criteria as measured by the TCA-DIAG was 83.9% for the sites with digital files vs. 76.4% for those with only paper files (P<0.01). For the TCA-EVOL, the difference was not significant. Explanations for the observed deviations were suggested (1 to 9 according to the participants)., Discussion and Conclusion: The quantified results could not be compared to other studies given the unique nature of the experiment. The importance of the traceability of practices in the patient files was discussed and assessed with regard to continuity and safety of care, as well as the medical-legal perspectives. Causes of lack of compliance were suggested (particularly the absence of reminders, the lack of means and/or time). Despite the limitations of the study, we think it is advisable that when a group becomes involved in the development of CPGs that they follow with the development of assessment criteria in order to evaluate the validity as well as their character as intermediate indicators of the quality of practices., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Although radiologically isolated syndrome (RIS) is a newly defined entity, incidental findings of T2 hypersignals on brain MRI can lead to misdiagnosis or useless investigations. The detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a major indicator that helps in diagnosis of subclinical inflammatory disease of the central nervous system, but lumbar puncture still remains an invasive option., Methods: We have prospectively included patients with RIS, have compared the results of CSF and tear OCB detection by isoelectric focusing (IEF) and assessed concordance between OCB detection in tears and in CSF. Tears were collected using a Schirmer strip., Results: In 45 recruited RIS patients, OCBs were detected in CSF for 55% (25/45) and in tears for 50% (21/42) of samples., Conclusions: We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with RIS and be useful in follow-up., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid., Method: We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients., Results: The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died., Conclusion: Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The question of pregnancy in patients with multiple sclerosis is regularly raised due to the prevalence of the disease in middle age women. The multiple sclerosis think tank (Groupe de Réflexion sur la Sclérose en Plaques [GRESEP]) decided to develop recommendations on this issue, with consideration to both the impact of multiple sclerosis on pregnancy, and that of pregnancy on the disease. As with topics of previous works, the formal expert consensus method was used. The working group was composed of hospital-based and private practice neurologists. The reading group was composed of neurologists, anaesthetists and obstetricians. Each recommendation is presented with the relevant level of consensus., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Meningiomas are benign primary meningeal tumors. Their diagnosis may be incidental or in response to a work-up for neurological or ophthalmological symptoms., Patients and Methods: The clinical course of five patients with ophthalmological symptoms leading to the diagnosis of meningioma is described., Results: The case reports consist of five women (48 to 54 years old - mean 52 years at the onset of symptoms), all suffering from a progressive unilateral decrease in visual acuity with a normal initial fundus examination and ipsilateral visual field changes. Ancillary testing, in particular MRI and CT-scans, had to be repeated to make the diagnosis of meningioma, which was delayed from 18 months to 4 years., Discussion: The clinical presentation of these five cases was that of a retrobulbar optic neuropathy, which biased the work-up towards an inflammatory disease of the central nervous system such as multiple sclerosis. However, the atypical character of the neuropathy, which did not respond to intravenous steroids, caused the diagnosis to be questioned and radiological examinations repeated. The iso-intense appearance of meningiomas on T1 MR imaging and only slightly hyperintense appearance on T2 may result in a diagnostic delay if the exam is not performed and interpreted by an experienced professional. Gadolinium contrast, fat suppression and centration on the anterior visual pathways are essential to a proper MRI examination., Conclusion: When confronted with a progressive, painless optic neuropathy unresponsive to steroid treatment, the diagnosis of meningioma of the anterior visual pathways must be considered. This diagnosis is enabled by a targeted MRI of the anterior visual pathways., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: Encephalitis is an inflammatory or infectious disease with an acute or subacute presentation. Immunological abnormalities in serum can be found but may be underdiagnosed. In several cases, a paraneoplastic origin with anti-neuron antibodies is noted. In all cases, other auto-antibodies can be found with or without any neoplastic mechanism., Objectives: The aim of our study was to describe a clinical, radiological and immunological cohort of patients with autoimmune encephalitis and suggest a diagnostic and therapeutic algorithm., Patients and Method: We performed a retrospective study in an immunological unit of neurology. All patients with autoimmune encephalitis between March 2000 and October 2009 were included. The clinical, imaging and immunological evaluations were recorded for each patient., Results: Our cohort included 16 patients (eight men and eight women), mean age 45.3±10years. All patients had acute or subacute neuropsychological or neuropsychiatric impairment and all patients but one had temporal lobe dysfunction confirmed by cerebral MRI, PET or SPECT. Epilepsy was observed in 56% of cases, extra-temporal lobe impairment in 50%, including sleep disturbances. A cancer was found in only 25% (two small-cell lung cancers, one testis seminoma, one non-small-cell lung cancer with Merckel cells cancer). Anti-neuron antibodies were noted in 56% of cases (two with anti-voltage gate potassium channel complex antibodies (ab), two with anti-NMDA-R ab, two with anti-glutamate acid decarboxylase ab, one with anti-Ma2, two with anti-Hu ab and two remained uncharacterized). Systemic antibodies were found in 50% (one anti-gangliosides, one anti-SSA and one anti-DNA and four antinuclear ab uncharacterized, two anti-TPO and two anti-phospholipids). All patients received immunomodulatory treatments, including intravenous immunoglobulins (IgIV) and cancer was treated. Five patients achieved complete recovery, partial improvement was observed in 10 patients and two patients died., Discussion: Despite clinical homogeneity at presentation, clinical outcome seems to be different between patients with antibodies against neuronal surface antigens and those with antibodies against intracellular antigens, which are more likely refractory to immunotherapy and paraneoplastic. The frequency of extra-temporal lobe impairment suggests that the term of limbic encephalitis should be changed to autoimmune encephalitis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Several practical questions useful for management of patients with multiple sclerosis remain unanswered in the current scientific literature. Decisions are often made individually, without the support of solid scientific evidence. In order to facilitate concurring practices, we present guidelines concerning useful serum exams for the diagnosis of multiple sclerosis. The methodology used was that of a formal expert consensus. A working group performed a systematic analysis of the literature, taking into account both previously existing recommendations and original articles, and then drafted guideline proposals. These proposals were subjected to the critical review of a rating group. Three written drafts, followed by rating of the guideline proposals culminated in a consensual document, which was submitted for review to a second independent reading group. The final resulting document provided the material for the present article, in which each recommendation is presented with its grade according to the level of proof or its degree of consensus in the absence of scientific proof., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Background: The role of thymectomy in myasthenia gravis remains controversial. The remission rate 5years after surgery varies from 13 to 51% in the literature. Sternotomy is the standard technique, though unacceptable by patients because of significant esthetic sequelae. Our objective was to demonstrate that the robot-assisted technique using the Da Vinci Surgical Robot II is at least as efficient and leaves fewer scars than the standard surgical technique., Methods: We retrospectively reviewed the data of 31 consecutive patients suffering from myasthenia gravis who underwent surgery in our center from January 1998 to March 2010. Ten patients with thymoma were excluded from this study. Two groups were formed: group 1 corresponding to patients treated with sternotomy, group 2 patients with robot-assisted technique. The duration of the hospital stay, the pain on D1, the degree of improvement at 1year according to Myasthenia Gravis Foundation of America (MGFA) classification, the frequency of relapses, and perioperative treatment were studied., Results: Our sample consisted of 14 women and seven men. The mean age was 31.3years. The mean delay before surgery was 24months. Group 1 included 15 patients and group 2 had six patients. The complete remission rate at 1year was 9.5% (n=2). Surgery decreased the frequency of relapses after surgery (P=0.08) equally in the two groups. The duration of hospital stay and the pain level on D1 in group 2 were significantly lower than those in group 1 (P=0.02 and P<0.001). The degree of postoperative improvement was not significantly different between the two groups (P=0.31)., Conclusion: The results at 1year are fully comparable for sternotomy and the robot-assisted technique. The robot provides additional benefits of minimally invasive techniques: minimal esthetic sequelae in often young patients, less parietal morbidity (including pain), shorter hospital stays. Our complete remission rate, lower than those in the literature, must be considered taking into account the early nature of these results. The surgical robot, because of its many advantages, appears to be a promising technique and should facilitate the early management of these patients., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objectives: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe attacks of optic neuritis and myelitis. Brain was classically, unlike in multiple sclerosis (MS), spared. Nevertheless recent studies showed that brain lesions can be seen with MRI. We studied the diffusion characteristics of normal-appearing white matter (NAWM) and abnormal white matter in NMO patients compared with NAWM in healthy subjects., Patients and Methods: Diffusion tensor imaging (DTI) scans of the brain and spinal cord were obtained from 25 patients with NMO and 20 age- and gender-matched healthy subjects. Region of interest (ROI) analysis of the apparent diffusivity coefficient (ADC) and fractional anisotropy (FA) was performed in brain NAWM (optic radiations, corpus callosum [CC] and anterior and posterior limbs of the internal capsule [IC]) and in spinal cord NAWM and in lesions., Results: ADC was increased and FA decreased in NMO patients in the posterior limb of the IC in the optic radiations and in spinal cord NAWM. FA was lower in spinal cord lesions. In contrast, there was no difference between the two groups in the anterior limb of the IC nor in the CC., Conclusion: These results suggest that DTI abnormalities are very severe in NMO spinal cord lesions. In our study, DTI abnormalities in NAWM were restricted to optic radiations and cortico-spinal tracts, suggesting secondary Wallerian degeneration. In contrast, NAWM outside these tracts (CC and anterior IC) remained normal suggesting that, unlike what is observed in MS, there is no infra-lesional abnormality in NMO., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The aim of the Multiple Sclerosis Think Tank (Groupe de réflexion sur la sclérose en plaques [GRESEP]) is to prescribe recommendations following a systematic literature search and using a Rand Corporation and California University (RAND/UCLA) appropriateness derived method, in response to practical questions that are raised in the management of patients with multiple sclerosis (MS). The topics of this working program were chosen because they were not addressed in the French recommendations and because of the few data in the literature that enabled practices to be based on validated data. Following the theme on useful serum testing with suspected multiple sclerosis, the subjects of the present work concern the detection and management of cognitive impairment in the beginning stages of the disease course. Two clinical questions were asked: which complementary exams (besides physical examination and neuropsychological tests) would help in the screening of cognitive impairment at the beginning of the disease? What care management should the person with MS and cognitive impairment be offered (treatments and neurocognitive rehabilitation)? The recommendations are the result of a consensus amongst a working group, a rating group and a reading group comprised of hospital neurologists involved in the management of patients with multiple sclerosis. Each recommendation is presented with the degree of consensus that it was accorded., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Inflammatory optic neuritis (ON) represents a frequent clinical situation in neurology and ophthalmology. The most current etiology is multiple sclerosis (MS) but, when MRI and Cerebrospinal fluid (CSF) analyses are normal, ON is usually considered as "idiopathic" with a suspected viral etiology. In rare cases, a systemic disease such as sarcoidosis, lupus or Sjögren syndrome may be diagnosed. In several cases either a recurrence or a myelitis may occur without any argument for MS. In the first case, it corresponds to relapsing inflammatory optic neuritis (RION) and in the second case to neuromyelitis optica (NMO). In the present paper, the author successively presents the various clinical situations and complementary findings (infectious, vasculitis, NMO or idiopathic) that can lead to a differential diagnosis of MS in a context of ON., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The aim of the Multiple Sclerosis Think Tank (Groupe de Réflexion sur la Sclérose en Plaques [GRESEP]), composed of hospital neurologists involved in the management of patients with multiple sclerosis, is to provide recommendations in response to clinical questions that are raised when managing these patients. After work done on the themes of useful serum testing with suspected multiple sclerosis, detection and management of cognitive disorders early in the course of the disease, and definition and early management of the disease, GRESEP wanted to develop recommendations on the management of multiple sclerosis (MS) relapse. Following a systematic analysis of the literature, the procedure of formal expert consensus enabled consensual recommendations among a working group, a rating group and a reading group to be written. Each recommendation is presented with its grade or the degree of consensus that it was accorded., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The aim of the Multiple Sclerosis Think Tank (Groupe de Réflexion sur la Sclérose en Plaques: GRESEP), composed of hospital neurologists involved in the management of patients with multiple sclerosis, is to provide recommendations in response to clinical questions that are raised when managing these patients. After work done on the themes on useful serum testing with suspected multiple sclerosis, as well as the detection and management of cognitive disorders early in the course of the disease, the subject of the present work is the early definition and early treatment of the disease. Following a systematic literature review, a RAND/UCLA appropriateness-derived method enabled consensual recommendations among a working group, a rating group and a reading group to be developed and formulated. Each recommendation is presented with the degree of consensus that it was accorded., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: First treatment protocols for multiple sclerosis (MS) have been established in France for over 15 years. Presently, a large majority of patients are treated, or has been treated in the past years, with one or more disease modifying drugs. However, despite a long-term follow-up, a certain patients remain untreated., Objective: The aim of this study was to determine in a large cohort the proportion of patients who never received any medication for MS and to analyze their profiles and reasons for no treatment., Patients and Methods: We studied a cohort of 1187 MS patients followed in a French (Alsace) cohort, all included in the EDMUS (European database for Multiple Sclerosis). We then performed a retrospective study on patients followed from at least 5 years (724 patients) and retained those who had never received MS medication., Results: Seventy patients (9.8% of the whole cohort) corresponded to the inclusion criteria. They were 57 women and 13 men, mean age 54.9 years (range 33-81). The mean duration of the disease was 20.6 years (range 5-56). MS was of relapsing remitting type in 46 patients (65.7%), primary progressive in 11 patients (15.7%) and secondary progressive in 13 patients (18.6%). In patients with relapsing remitting disease, the annualized relapse rate was 0.33 (range 0.08-1). Mean EDSS was 3.4 after a mean follow-up of 20.6 years. Progression index was 0.16 without any differences between progressive and relapsing remitting forms (0.15 and 0.16 respectively). Reasons for not treating were: lack of disease activity (65.8%), very slow disease progression (10%), patient's initial decision followed by very slow progression (14.2%), contraindication for treatment in patients with longstanding progressive disease (10%). There were also patients (4.3%) whose initially well-stabilized disease recently became active again, leading to reconsideration about starting treatment., Conclusion: After a mean follow-up of 20 years, the proportion of treatment-free patients was around 10%. Most of these patients had a relapsing remitting form with a low rate of relapse or a progressive form with very slow progression., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Charcot first described emotional deficits in multiple sclerosis (MS) in the XIXth century. Despite this early description, there are very few studies about emotions and MS., Objectives: This study aimed at better understanding the emotional process in MS and more specifically recognition of facial emotions and emotional experience., Methods: Thirteen women with remittent MS (R-MS), with a mean EDSS score of 2, were compared with thirteen healthy control subjects, matched for age (mean age of 42±2), sex and educational level. The Beck Depression Inventory (BDI), the Hamilton Anxiety Scale and the brief repeatable battery of neuropsychological tests for MS (BCcogSEP) were administered. Recognition of faces and facial expression of emotion were assessed by the Benton facial recognition test and recognition of facial emotions was assessed by Ekman's facial expression test. We have also presented 12 different sounds and pictures from the International Affective Digitized Sounds and Picture System (IADS and IAPS) in order to study the emotional experience by using criteria of valence and arousal., Results: No deficit of facial emotion recognition was found in MS in this small population. Nevertheless, patients who had difficulty recognizing faces were the least able to recognize facial expressions. No significant difference was observed between the patient and control group for the experience of emotional valence. However, independently of their mood and cognitive status, the self-assessment of the MS patient population suggested that the patients were less reactive to negative sounds (P=0.005) and negative pictures (P=0.002) as compared with the control group, pointing to lesser sensitivity towards aversive stimuli., Conclusion: These data suggest disorders in emotional processes in R-MS, mainly a poor reactivity to negative stimuli which may have an impact on everyday life. A larger population should be studied to confirm these modifications of emotion., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Love is a complex emotional state which is difficult to define. Considering anthropological studies, this feeling can now be divided into three distinct behaviors: lust, attraction for a specific partner and conjugal or filial attachment., State of Art: For each, recent findings have contributed to identify specific neuronal networks which are interconnected as shown by common activation of limbic and paralimbic systems. A major role of arginine/vasopressin and oxytocin has also been pointed out for mate choice and attachment promotion. In the field of neurology, studies about pathologies of love are sparse and mainly focused on sexual disorders. Pathologies of attachment like autism and borderline personality are beginning to be identified., Perspectives: Future investigations would yield a better understanding of this complex emotional state and a better detection of new pathologies related to a major affective disability., Conclusion: Neurosciences have contributed to highlight mechanisms involved in love., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Oculomotor deficiencies in multiple sclerosis (MS) are frequently characterized by internuclear ophthalmpoplegia or isolated abduction or adduction palsies. Complete unilateral conjugate gaze paralysis and the "one and a half" syndrome are rare. Complete bilateral horizontal gaze paralysis has been exceptionally reported., Observation: Here, we describe an unusual oculomotor paralysis as a suspected first event of MS. A 24-year-old woman with an uneventful medical history presented for sudden onset of binocular diplopia. On examination, abduction and adduction saccades were impossible, whereas vertical eye saccades and convergence were normal. Oculocephalic reflex failed to improve horizontal eye movement. No nystagmus and no other sign of brainstem dysfunction were observed. Visual acuity was 4/10 in the right eye and 6/10 in the left eye. A sign of Marcus Gunn was noted in the right eye. Blood samples and cerebrospinal fluid were normal, no oligoclonal bands were detected. Visual evoked potentials were significantly impaired in both eyes and argued for bilateral optic neuritis. Brain MRI scans showed white matter T2-hypersignal abnormalities, which fulfill Barkhof criteria for MS. A small symmetric lesion was noted in the posterior part of the medial pontine tegmentum. As a first episode of MS was suspected, treatment with methylprednisolone 1000 mg/d for 3 days was started, and was followed by complete recovery of eye movements and visual acuity after 3 weeks., Discussion: To our knowledge, only two cases of complete horizontal bilateral ophthalmoplegia have been reported in the literature. Both were associated with peripheral facial nerve palsy as a first event in MS. In our case report, we describe for the first time a complete bilateral horizontal ophthalmoplegia with no other brainstem dysfunction. By analogy with the "one and a half" syndrome, such complete horizontal gaze paralysis could be named a "one and one" syndrome and seems to be specifically related to a first event of MS., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The association of visual and auditory impairments, simultaneously or consecutively, is a rare condition at the onset of neurological diseases. To determine whether audiovisual impairment can be associated with a specific group of neurological disorders at onset, we performed a prospective study of 307 patients over 6 months in a specialized neurological unit in inflammatory diseases. Six patients (2%) experienced inaugural audiovisual impairments. The mean age of patients at onset was 39.5 ± 14.7 years, with a male:female ratio of 1:2. Both deficiencies were reported in three cases, including loss of visual acuity with tinnitus (two cases) or hearing loss (one case). Initial visual dysfunction, characterised by loss of visual acuity, was noted in one patient. Initial auditory impairment, characterised by dizziness and hearing loss, was noted in two patients. The mean interval between the occurrence of visual and auditory impairments was 3.8 ± 4.3 months. A neurological diagnosis was made in four cases (67%) at a mean time of 4.6 ± 4.6 months after disease onset. Visual impairments were optic neuritis for multiple sclerosis, serous retinal detachment for Vogt-Koyanagi-Harada's disease, a central retinal artery occlusion for Susac's syndrome and a retinal vasculitis for Cogan's syndrome. The systematic investigation of inaugural audiovisual impairment in young patients could help shorten the time to a specific neurological diagnosis., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Epidemiological studies of Alzheimer disease have shown a higher prevalence of women. Some data argue for a link between Alzheimer disease and the decrease of estrogen in post-menopausal women. Animal studies have shown a beneficial effect of estrogen on memory with a decrease of amyloid deposition in models of AD, whereas estrogen has a positive effect on BDNF. Six studies have shown a positive effect of estrogen therapy on memory and studies on structural and functional imaging have shown a beneficial effect of estrogens but the largest study on prevention of dementia with estrogens (WHI) showed a deleterious effect. To better understand this paradoxical situation, we reviewed the literature on estrogens, memory and Alzheimer disease. We first discuss the promnesic effect of estrogen on mice and rats, second the neuroprotector effect of estrogen on animal models of Alzheimer disease, and third the available human studies. We hypothesize a link with the time of instauration of the estrogen treatment. Nevertheless this hypothesis remains to be demonstrated., (2009 Elsevier Masson SAS. All rights reserved.)

Introduction: Psychotic symptoms are not readily recognized in multiple sclerosis, especially at the beginning of the disease., Methods: We report the cases of four patients who developed psychotic symptoms that led to the diagnosis of multiple sclerosis. We describe the psychiatric and neurological features, MRI findings, clinical outcome and treatment., Results: Two patients developed persecutory delusions, one presented a manic episode and the fourth melancholia with catatonia. Mean age was 39 years (range 20-49 years). Two patients had a personal history, but none a familial history of psychiatric disease. Examination of the cerebrospinal fluid revealed an oligoclonal pattern in all patients. All patients fulfilled Barkhof's MRI criteria. Three have had brain MRI with injection during psychotic symptoms. In these three cases, a frontal lesion appeared. The patient with catatonia also had a new lesion in the cerebellum and in the brainstem. All patients needed a "psychiatric" treatment, including antipsychotics. The psychiatric event lasted three months for two patients and the two others experienced relapse., Conclusion: Acute psychiatric symptom may reveal multiple sclerosis at the beginning of the disease. Frontal lobe localization is suggested. We propose that a psychotic event may correspond to a multiple sclerosis event., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Introduction: In small-fiber neuropathy, skin biopsy reveals a reduction of intraepidermal nerve fiber density (IENFD), a feature often necessary for diagnosis. In France, this technique has not been widely used for this purpose., Patient and Method: To validate this method, we studied 13 patients with suspected small-fiber neuropathy, analyzed their nervous intra- and subepidermal network with a punch skin biopsy and compared our data with those of literature., Results: Ten patients had pure small-fiber neuropathy and three an axonal polyneuropathy involving large-caliber nerve fibers. In the group of patients with pure small-fiber neuropathy, we found medium IENFD (11.6 +/- 4.46 fibers per millimeter in the proximal thigh and 7.15 +/- 3.59 fibers per millimeter in distal leg), well correlated with the electron microscopy quantitative and qualitative analysis of the unmyelinated subepidermal fibers., Conclusion: This work demonstrated the good reproducibility of skin biopsy for analyzing the small-fibers in our cohort. These results require further confirmation in a larger cohort and validation in comparison with controls analyzed on a local level. Nevertheless, these techniques seem to be useful to assess the difficult diagnosis of small-fiber neuropathy.

Introduction: Acute myelitis accounts for 4 to 5 percent of all cases of neuroborreliosis. In the literature, simultaneous spinal MRI and cerebrospinal fluid (CSF) investigations are presented for only 8 cases. We describe here 3 cases of acute Lyme myelitis., Method: In a cohort of 45 patients with neuroborreliosis, diagnosed between January 1998 and January 2005, 3 had acute myelitis. Clinical, biological and radiological data were studied., Case Reports: The three patients had motor, sensorial and sphincter involvement. Extra-spinal involvement, such as fever and headache for one, facial nerve palsy for the second and subarachnoid hemorrhage for the third, was also noted. Pleocytosis varied from 10 to 520 white cells per mm3. Lyme serology was positive in CSF for all. Intrathecal anti-Borrelia antibody index was positive or intermediate for all three patients. Spinal cord MRI revealed a large hyperintense zone involving more than 3 vertebral segments. Myelitis was central, posterior or transverse in the axial plane. The clinical course was favorable after a three-week course of appropriate antibiotics., Conclusion: These 3 cases and the others from the literature show the diversity of the clinical and radiological features of acute myelitis: transverse, central or posterior myelitis. Thus, Lyme serology in CSF in indicated for patients presenting acute myelitis, particularly in endemic areas.

Background: Polymyositis with cranial neuropathy has been rarely reported., Case Reports: We describe here three cases of polymyositis with trigeminal or facial neuropathy. Patients had muscular weakness, myalgia, rhabdomyolysis, endomysial infiltration with necrosis and regeneration at biopsy of muscle and, for two of them, a myopathic pattern at electromyogram. Two patients had also a Sjögren's syndrome and anti-nuclear antibodies. Anti-JO1 antibodies were presents in only one case. The outcome for one patient was good with corticosteroids alone. One other improved with the adjunction of immunoglobulin. The third one had a macrocheilia, a facial diplegia, antibodies against voltage-gated potassium channels and a neuromyotonia secondary to a paraneoplastic syndrome. He died after one year despite a treatment by corticosteroids and immunoglobulin. Patients fulfilled the diagnosis of polymyositis according to clinical, electromyographic, biological and histopathologic criteria. For the two patients with Sjögren's syndrome, the question of a primitive or a secondary Sjögren's syndrome remains unknown., Conclusion: The occurrence of a cranial neuropathy in polymyositis should make us looking for an association with paraneoplastic syndrome or connective tissue disease.

Multiple sclerosis (MS) has been described for more than a century, but its cause remains unknown. Numerous reports were written concerning borderline forms of the disease. In the present review we present MS related disorders such as neuromyelitis optica and acute demyelinating encephalomyelitis.

Controversial results have been published on potential link between cancer and multiple sclerosis. Multiple sclerosis has been linked to reduced rates of cancer prior to the era of immunomodulating or immunosuppressive treatments and until today, only 9 studies can be found in the literature. New strategies and early use of IM or IS drugs in MS justify to study and follow patients to detect a potential increase of cancer's incidence in treated patients. It is important to follow and collect prospectively in MS centers, patients with history of cancer, to document histologies, and potential relations with repeated IM or IS treatments. A prospective study is in progress in French MS centers on behalf the Club Francophone de la SEP (CARIMS Project).

Objectives: To study influences of pregnancy on the time-course of myasthenia gravis (MG) and of MG on pregnancy, delivery, postpartum and newborn., Methods: We retrospectively collected data from 100 women affected with MG, hospitalized between 1994 and 2003 in departments of Neurology of Lille University Hospital., Results: Eighteen patients had a total of 36 pregnancies, occurring 7.2 years on average after MG onset. MG exacerbation occurred in 7 patients (26 percent) during pregnancy and in 4 (14.8 percent) during postpartum. One patient died of acute respiratory failure during postpartum. Delay between the onset of MG and pregnancy was the only variable significantly associated with MG exacerbation: 5.8 years when exacerbation and 9.5 years when no exacerbation (p=0.03). Seven miscarriages, two therapeutic abortions and no death at birth were reported. Levels of anti-acetylcholine receptor antibodies were abnormal in 3 of 27 newborns (11 percent), but only one (3.7 percent) developed seronegative transient neonatal myasthenia gravis., Discussion: During pregnancy, the clinical course of MG is variable but exacerbations were associated with a shorter delay between MG diagnosis and pregnancy. The risk of transient neonatal myasthenia gravis is relatively small but exists even when the parturient has stable MG without elevated levels of anti-acetylcholine receptor antibodies., Conclusion: Our study confirms pregnancy is more difficult to manage at the beginning of MG. Given the unpredictable course of MG during pregnancy, we recommend women affected with MG to begin a pregnancy when the disease is stable.

Introduction: Guillain-Barré syndrome can occur at any time of pregnancy with the same incidence as in the general population. Observations. We report two cases of patients who developed a progressive ascending paralysis during the second trimester of pregnancy. The worsening of the respiratory insufficiency for one of them required a transfer to an intensive care unit for artificial ventilation lasting 102 days. In the two cases, cerebrospinal fluid examination revealed albumin-cytological dissociation and repeated electrophysiological studies showed typical features of demyelinating neuropathy with conduction blocks. Biological investigations, especially CMV and Campylobacter jejuni serologies, were all negative. Intravenous immunoglobulin infusions, in one case associated with high doses of corticosteroïds, were ineffective. Rapid improvement was observed in the two patients after delivery., Conclusion: These cases raise the question of the relationships between the Guillain-Barré syndrome and pregnancy. The occurrence of the disease, as well as the rapid recovery in post-partum, could be consecutive to a partial failure of the maternal immunological tolerance toward the fetus.

Multiple sclerosis (MS) has been described for more than a century, but its cause remains unknown. Numerous reports have been written concerning borderline types of the disease. In the present paper we present the pseudo-tumoral variants of MS (so called Balo's, Marburg's and Schilder's forms), demographic variants (young and elderly onset of MS), related disorders (neuromyelitis optica and acute demyelinating encephalomyelitis). We also discuss the differential diagnosis with other auto-immune diseases.