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Resume Un depistage precoce et une prise en charge adaptee des troubles urinaires lies a la sclerose en plaques (SEP) doivent en reduire la morbidite. Une enquete transversale a ete conduite afin d’evaluer la frequence et la severite des troubles vesico-sphincteriens lies a la SEP dans une population non selectionnee et suivie en milieu neurologique aussi bien en ville qu’a l’hopital. Cent vingt-cinq patients SEP dont 44,7 % evoluaient depuis moins de 10 ans (77,6 % de femmes, âge moyen 44,4 ± 13,0 ans) ont repondu a un auto-questionnaire. Quatre-vingt-neuf patients (79,2 %) presentaient des troubles urinaires dont 42 (33,6 %) des troubles urinaires severes. Parmi les 99 patients presentant des troubles urinaires, 10,1 %, 24,2 % et 65,7 % se plaignaient respectivement de dysurie isolee, d’urgenturies/fuites isolees ou des 2 symptomes. 26,8 % des patients avec troubles urinaires ont eu des infections urinaires ayant necessite la prise d’antibiotiques (contre 4 % chez ceux sans trouble urinaire), avec un nombre moyen de 2,7 ± 2,7 infections urinaires au cours des 12 derniers mois. Seuls un quart (23,8 %) des patients ayant un trouble urinaire severe declaraient etre suivis par un specialiste, urologue ou medecin de medecine physique et de readaptation (MPR). Une majorite des patients (73,7 %) aurait aime connaitre le lien possible entre leurs troubles urinaires et leur pathologie (SEP). De nombreux patients (20,6 %) ont exprime le souhait d’avoir de l’aide pour gerer leurs problemes urinaires, notamment en cas de troubles severes (35,7 % des cas). Cette etude a permis de confirmer que les troubles urinaires sont frequents chez les patients SEP, sous-estimes et pas totalement pris en charge. Ces patients sont en demande d’information sur les symptomes et en recherche d’aide sur la prise en charge. En reponse, il nous a semble important d’informer les patients sur la frequence de la relation entre SEP et troubles urinaires, d’evaluer ces derniers regulierement avec un questionnaire specifique et de mettre en place une prise en charge adaptee selon un algorithme decisionnel bien defini en integrant le suivi par un specialiste en neuro-urologie.

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 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.

Resume Introduction Les pathologies du spectre des neuromyelites optiques (NMO-SD) ont emerge depuis une dizaine d’annee. Les entites paracliniques ont pu etre individualisees grâce aux biomarqueurs tels que les anticorps anti-aquaporines 4 (AQP4) et les anti-Myelin Oligodendrocyte Glycoprotein (MOG). Materiel et methode Une etude retrospective des patients du CHU de Strasbourg atteints de NMO-AQP4+, MOG+ et doubles seronegatifs a ete realisee pour comparer leurs caracteristiques cliniques, epidemiologiques et paracliniques. Resultats Trente-deux patients atteints de NMO ont ete inclus. Les NMO-AQP4+ avaient un âge median de 45 ans, etaient associees a une myelite dans 62,5 % des cas et a d’autres auto-anticorps dans 37,5 % des cas. Le nombre moyen de poussees dans l’histoire clinique etait de 3. L’acuite visuelle moyenne initiale sur les yeux en poussee etait de 0.3 LogMAR et l’acuite visuelle sequellaire des yeux ayant eu une poussee etait de 0.1 LogMAR. Les NMO-MOG+ avaient un âge median de 23 ans avec une acuite visuelle initiale severement touchee (0.6 LogMAR) mais une meilleure recuperation (0 LogMAR), un œdeme papillaire etait present dans 80 % des cas, le nombre moyen de poussees dans l’histoire clinique etait de 1. Les NMO-AQP4-/MOG- etaient plus frequentes chez les femmes (70 %) et etaient bilaterales dans 40 % des cas. Conclusion Les particularites semeiologiques des pathologies du spectre des NMO sont de mieux en mieux differenciees avec un impact sur le pronostic fonctionnel et evolutif pour les patients. D’autres biomarqueurs restent encore a identifier pour affiner le diagnostic et le traitement de ces atteintes.

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

Objectives Establish recommendations for the management of UTIs in MS patients. Background Urinary tract infections (UTIs) are common during multiple sclerosis (MS) and are one of the most common comorbidities potentially responsible for deaths from urinary sepsis. Methods The recommendations attempt to answer three main questions about UTIs and MS. The French Group for Recommendations in MS (France4MS) did a systematic review of articles from PubMed and universities databases (01/1980–12/2019). The RAND/UCLA appropriateness method, which has been developed to synthesize the scientific literature and expert opinions on health care topics, was used for reaching a formal agreement. 26 MS experts worked on the full-text review and a group of 70 multidisciplinary health care specialists validated the final evaluation of summarized evidences. Results UTIs are not associated with an increased risk of relapse and permanent worsening of disability. Only febrile UTIs worsen transient disability through the Uhthoff phenomenon. Some immunosuppressive treatments increase the risk of UTIs in MS patients and require special attention especially in case of hypogammaglobulinemia. Experts recommend to treat UTIs in patients with MS, according to recommendations of the general population. Prevention of recurrent UTIs requires stabilization of the neurogenic bladder. In some cases, weekly oral cycling antibiotics can be proposed after specialist advice. Asymptomatic bacteriuria should not be screened for or treated systematically except in special cases (pregnancy and invasive urological procedures). Conclusion Physicians and patients should be aware of the updated recommendations for UTis and MS.

Resume Les troubles cognitifs sont frequents chez les patients atteints de sclerose en plaques, avec des degres d’intensite divers. Ils peuvent impacter de maniere significative la vie quotidienne et professionnelle des patients, ainsi que leur qualite de vie. Le depistage de ces troubles est donc important et les neurologues doivent s’investir dans leur evaluation afin de proposer une prise en charge adaptee. Les liens entre cognition et comportement sont souvent intriques. Il peut etre utile de rappeler le vocabulaire neuropsychologique definissant les differents symptomes les plus souvent observes dans la sclerose en plaques. Ceci permet aussi de visiter clinique et anatomie. Nous proposons un lexique qui definit 118 termes susceptibles d’aider les neurologues dans la comprehension des troubles de la cognition et du comportement chez leurs patients, de faciliter leur ecoute dans un entretien, de prescrire quand il le faut une expertise de premiere ligne ou plus specialisee, de lire des travaux scientifiques ou ces donnees sont de plus en plus citees et de communiquer en utilisant un vocabulaire commun.

Pratique neurologique - FMC - Sous presse. Epreuves corrigees par l'auteur. Disponible en ligne depuis le mercredi 26 aout 2020

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.

Background Despite a recent interest in Real World Data, such studies are scarce in multiple sclerosis (MS) disease. The objective was to describe the patients, disease progression and use of DMDs in France and compare clinical effectiveness of first-line injectable DMDs. Methods We conducted a retrospective multicenter study in France, using data collected by 11 expert centers with the EDMUS software. Results Overall, 15,039 French MS patients were followed for a mean of 11.5 years. Mean age at start of disease was 32 years and 74% were women. After the disease onset, median time to reach EDSS 3 was 11 years and 51.8% of patients were relapse-free 2 years after the disease's onset. The mean delay between onset of disease and initiation of treatment was 5.7 ± 6.9 years. Over time, it decreased from 8.8 ± 7.8 to 0.7 ± 0.7 years for initiation of treatment before 2000 vs. after 2010, respectively. Two years after the initiation of treatment, the persistence rate of injectable disease modifying drugs (DMDs) was 60.7%. The effectiveness of these drugs were quite similar. Conclusion This study brings new insight on the natural history of MS and the use and effectiveness of injectable DMDs in this condition.

Mittels sogenannter zellbasierter Assays konnte in den vergangenen Jahren durch zahlreiche Arbeitsgruppen unabhangig eine robuste Assoziation von Immunglobulin-G-Autoantikorpern gegen menschliches Voll-Langen-Myelin-Oligodendrozyten-Glykoprotein (MOG-IgG) mit – meist rezidivierender – Optikusneuritis (ON), Myelitis und Hirnstammenzephalitis sowie mit Fallen akuter disseminierter Enzephalomyelitis (ADEM) gezeigt werden. Die MOG-IgG-positive Enzephalomyelitis (MOG-EM) gilt den meisten Experten inzwischen als eigenstandiges Krankheitsbild, das sich immunpathogenetisch sowohl von der klassischen multiplen Sklerose (MS) als auch von der Aquaporin-4(AQP4)-IgG-positiven Neuromyelitis-optica-Spektrum-Erkrankung (NMOSD) unterscheidet. Aufgrund erheblicher Ubereinstimmungen der beiden Erkrankungen in klinisch-radiologischer Hinsicht wurde die MOG-EM in der Vergangenheit oft unbeabsichtigt als MS fehldiagnostiziert. Daher werden derzeit viele Patienten mit vermuteter oder etablierter MS auf MOG-IgG getestet. Das Screening von grosen, nichtselektierten Kohorten auf seltene Biomarker kann jedoch den pradiktiven Wert eines Tests signifikant reduzieren. Um die damit verbundene Gefahr einer Uberdiagnostizierung der MOG-EM zu verringern, werden dringend selektivere Kriterien fur die Testung auf MOG-IgG benotigt. In der vorliegenden Arbeit schlagen wir, basierend auf Expertenkonsensus, Indikationen fur die MOG-IgG-Testung vor. Zusatzlich wird dem Leser eine Liste mit sogenannten „red flags“ an die Hand gegeben, d. h. klinischen und paraklinischen Befunden, die fur die MOG-EM eher atypisch sind und Anlass sein sollten, ein positives MOG-IgG-Laborergebnis kritisch zu hinterfragen. Zusatzlich geben wir Empfehlungen zur Testmethodik, zur Probenentnahme und zur Dateninterpretation und prasentieren erstmalig Diagnosekriterien fur die MOG-EM.

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

Introduction: While monophasic and relapsing forms of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) are increasingly diagnosed world-wide, consensus on management is yet to be developed. Objective: To survey the current global clinical practice of clinicians treating MOGAD. Method: Neurologists worldwide with expertise in treating MOGAD participated in an online survey (February–April 2019). Results: Fifty-two responses were received (response rate 60.5%) from 86 invited experts, comprising adult (78.8%, 41/52) and paediatric (21.2%, 11/52) neurologists in 22 countries. All treat acute attacks with high dose corticosteroids. If recovery is incomplete, 71.2% (37/52) proceed next to plasma exchange (PE). 45.5% (5/11) of paediatric neurologists use IV immunoglobulin (IVIg) in preference to PE. Following an acute attack, 55.8% (29/52) of respondents typically continue corticosteroids for ≥ 3 months; though less commonly when treating children. After an index event, 60% (31/51) usually start steroid-sparing maintenance therapy (MT); after ≥ 2 attacks 92.3% (48/52) would start MT. Repeat MOG antibody status is used by 52.9% (27/51) to help decide on MT initiation. Commonly used first line MTs in adults are azathioprine (30.8%, 16/52), mycophenolate mofetil (25.0%, 13/52) and rituximab (17.3%, 9/52). In children, IVIg is the preferred first line MT (54.5%; 6/11). Treatment response is monitored by MRI (53.8%; 28/52), optical coherence tomography (23.1%; 12/52) and MOG antibody titres (36.5%; 19/52). Regardless of monitoring results, 25.0% (13/52) would not stop MT. Conclusion: Current treatment of MOGAD is highly variable, indicating a need for consensus-based treatment guidelines, while awaiting definitive clinical trials.

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.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.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.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.

Objectives To establish recommendations on immunization for patients with multiple sclerosis (MS). Background Vaccines have been suspected in the past to trigger MS and relapses. With the extension of the immunoactive treatment arsenal, other concerns have been raised more recently about an increased risk of infection or a decreased effectiveness of immunization in immunosuppressed patients. Methods The French Group for Recommendations into Multiple Sclerosis (France4MS) performed a systematic search of papers in Medline and other university databases (January 1975–June 2018). The RAND/UCLA appropriateness method was chosen to review the scientific literature and to formalize the degree of agreement among experts on 5 clinical questions related to immunization and MS. Readers from the steering committee conducted a systematic analysis, wrote a critical synthesis and prepared a list of proposals that were evaluated by a rating group of 28 MS experts. The final version of the recommendations was finally reviewed by a reading group of 110 health care professionals and classified as appropriate, inappropriate or uncertain. Results Neurologists should verify the vaccination status as soon as MS is diagnosed and before disease-modifying treatments (DMTs) are introduced. The French vaccination schedule applies to MS patients and seasonal influenza vaccination is recommended. In the case of treatment-induced immunosuppression, MS patients should be informed about the risk of infection and the vaccination standards of the French High Council of Health should be applied. Live attenuated vaccines are contra-indicated in patients recently treated with immunosuppressive drugs, including corticosteroids; other vaccines can be proposed whatever the treatment, but their effectiveness may be partly reduced with some drugs. Conclusion Physicians and patients should be aware of the updated recommendations for immunizations of patients with MS.

BACKGROUND AND PURPOSE Assessing patients' disability in multiple sclerosis (MS) requires time-consuming batteries of hospital tests. MSCopilot is a software medical device for the self-assessment of patients with MS (PwMS), combining four tests: walking, dexterity, cognition and low contrast vision. The objective was to validate MSCopilot versus the Multiple Sclerosis Functional Composite (MSFC). METHODS This multicentre, open-label, randomized, controlled, crossover study enrolled 141 PwMS and 76 healthy controls (HCs). All participants performed MSCopilot and MSFC tests at day 0. To assess reproducibility, 46 PwMS performed the same tests at day 30 ± 3. The primary end-point was the validation of MSCopilot versus MSFC for the identification of PwMS against HCs, quantified using the area under the curve (AUC). The main secondary end-point was the correlation of MSCopilot z-scores with MSFC z-scores. RESULTS In all, 116 PwMS and 69 HCs were analysed. The primary end-point was achieved: MSCopilot performance was non-inferior to that of MSFC (AUC 0.92 and 0.89 respectively; P = 0.3). MSCopilot and MSFC discriminated PwMS and HCs with 81% and 76% sensitivity and 82% and 88% specificity respectively. Digital and standard test scores were highly correlated (r = 0.81; P

The relationship between neuromyelitis optica (NMO) and multiple sclerosis (MS) has long been controversial. NMO was previously considered a form of MS involving predominantly the spinal cord and optic nerve. However, since the discovery of NMO-IgG/aquaporin-4 (AQP4) antibody, an NMO-specific autoantibody to AQP4, some unique clinical features, and magnetic resonance imaging (MRI) and other laboratory findings in NMO, have been further clarified. AQP4 antibody is now the most important laboratory finding for the diagnosis of NMO. Besides typical NMO, some patients with recurrent optic neuritis or recurrent longitudinally extensive transverse myelitis alone are also often positive for AQP4 antibody. Moreover, studies of AQP4 antibody-positive patients have revealed that brain and brainstem lesions are not uncommon in NMO, and some patterns appear to be unique to NMO. All these findings have expanded the NMO concept into 'NMO spectrum disorder' (NMOSD), and new criteria have recently been published. A new antigenic target, myelin oligodendrocyte glycoprotein (MOG), has also been discovered recently. This new antibody seems to correspond to around 20% of seronegative patients, but its specificity needs to be evaluated more precisely, especially in pediatric populations. These recent findings may also have therapeutic impact, as it has been demonstrated that many MS drugs can exacerbate NMO. This report provides an overview of the clinical and neuroimaging features of NMOSD, followed by its treatment.

International audience

Tumefactive demyelinating lesions of the central nervous system can be the initial presentation in various pathological entities [multiple sclerosis (the most common), Balo’s concentric sclerosis, Schilder’s disease and acute disseminated encephalomyelitis] with overlapping clinical presentation. The aim of our study was to better characterize these patients. Eighty-seven patients (62 women and 25 men) from different MS centers in France were studied retrospectively. Inclusion criteria were (1) a first clinical event (2) MRI showing one or more large demyelinating lesions (20 mm or more in diameter) with mass-like features. Patients with a previous demyelinating event (i.e. confirmed multiple sclerosis) were excluded. Mean age at onset was 26 years. The most common initial symptoms (67% of the patients) were hemiparesis or hemiplegia. Aphasia, headache and cognitive disturbances (i.e. atypical symptoms for demyelinating diseases) were observed in 15, 18 and 15% of patients, respectively. The mean largest diameter of the tumefactive lesions was 26.9 mm, with gadolinium enhancement in 66 patients (81%). Twenty-one patients (24%) had a single tumefactive lesion. During follow-up (median time 5.7 years) 4 patients died, 70 patients improved or remained stable and 12 worsened. 86% of patients received initial corticosteroid treatment, and 73% received disease-modifying therapy subsequently. EDSS at the end of the follow-up was 2.4 ± 2.6 (mean ± SD). This study provides further evidence that the clinical course of MS presenting with large focal tumor-like lesions does not differ from that of classical relapsing-remitting MS, once the noisy first relapsing occurred.

International audience; Objectifs Décrire l’utilisation des traitements de fond chez les patients ayant une sclérose en plaques (SEP) rémittente en France entre 1990 et 2017 : quels traitements ? À quel moment ? Combien de temps ? Quels changements ? Méthodes Tous les patients de l’Observatoire français de la SEP (OFSEP), ayant une SEP rémittente (évoluant par poussées), vivants au 1er janvier 1996 ont été inclus, soit au total 41 305 patients. Tous les traitements de fond, y compris utilisés hors Autorisation de mise sur le marché (AMM), ont été pris en compte, sans durée minimale considérée. Les interférons sont les premiers traitements à avoir été approuvés, en 1996, et depuis, l’arsenal thérapeutique à disposition des neurologues pour la prise en charge des patients a fortement changé (12 traitements disponibles à ce jour), notamment avec l’arrivée du natalizumab en 2007 et des formes orales de première ligne en 2014. Les données ont été analysées globalement et via plusieurs cohortes longitudinales définies selon la période de début de la SEP et suivies dans les quatre périodes suivantes

Background Early manifestations of Multiple Sclerosis (MS) can be atypical and misleading, and several case report studies have highlighted that MS onset sometimes takes the form of a psychotic or manic episode. Methods All neurologists belonging to the French Multiple Sclerosis Observatory network were contacted by email and were asked to find patients with MS who presented with a history of psychiatric episode(s) near MS onset. Results Seventeen patients were selected that met the criteria of presenting with psychotic or manic symptoms either before the diagnosis of MS ( N =8), or at the time of the first neurological episode or shortly after ( N =9). Patients with a history of a psychiatric episode occurring before the first neurological episode were diagnosed on average 7 years later than patients with either a first neurological or a mixed (both neurological and psychiatric) episode. However, psychiatric symptoms in the first group and the first neurological symptoms of MS in the second group occurred at a similar age. Conclusion Based on this multiple case study, we question whether past psychotic or manic episode should be considered equivalent to a first manifestation of MS.

Resume Introduction La sclerose en plaques (SEP) est une maladie du systeme nerveux central qui affecte le jeune adulte a une periode ou il se lance dans la vie active. Le retentissement de la maladie sur la vie professionnelle est souvent majeur. L’objectif de cette enquete etait de recenser les problemes que rencontrent les personnes atteintes de sclerose en plaques dans le cadre de leur travail. Methodes Il s’agit d’une enquete regionale realisee en 2010 par des praticiens neurologues et de medecine physique et de readaptation (MPR) d’Alsace sur une periode de 4 mois. Resultats Deux cent sept patients SEP en âges de travailler ont repondu a cette enquete. Le taux d’emploi etait de 67,6 %. Parmi les difficultes exprimees par les patients, la fatigabilite physique et intellectuelle apparaissent comme les principales difficultes ressenties au travail. Discussion Les problemes de fatigabilite mis en avant par les patients sont des elements pouvant presager d’une perte d’emploi, et qui necessite la mise en place de maniere precoce de mesures de sauvegarde, en favorisant une prise en charge pluridisciplinaire.

Resume Introduction La xanthomatose cerebrotendineuse, leucodystrophie metabolique de transmission autosomique recessive, est secondaire a un deficit en 27-sterol-hydroxylase, enzyme intervenant dans le catabolisme du cholesterol. Les symptomes classiquement revelateurs sont des xanthomes cutanes et tendineux (cliniques ou infracliniques), une cataracte precoce, une atteinte neurologique complexe et une diarrhee. L’imagerie cerebrale met en evidence une atteinte symetrique de la substance blanche et des noyaux denteles. Le diagnostic, suspecte sur une augmentation du cholestanol serique, est confirme par la presence d’une mutation dans le gene CYP27A1. Le traitement repose sur l’acide chenodesoxycholique. Methode Nous rapportons une serie multicentrique retrospective de 15 cas de xanthomatose cerebrotendineuse diagnostiques a l’âge adulte. Les donnees cliniques, moleculaires et IRM ont ete analysees pour chaque patient inclus. Resultats L’âge moyen de diagnostic etait de 39 ans (extremes : 27–65). Soixante-treize pour cent des patients debuterent leur maladie dans l’enfance et 27 % a l’âge adulte. Toutes les formes a debut pediatrique ont eu un diagnostic a l’âge adulte (âge moyen du diagnostic : 40 ans [extremes : 28–65]). Les symptomes cliniques associaient de maniere variable un syndrome cerebelleux, pyramidal, des troubles cognitifs, une epilepsie, une neuropathie (recherchee chez 10 de nos malades, presente chez 8 et de profil variable), des troubles psychiatriques, une cataracte et des xanthomes. Un patient avait une presentation atypique a savoir, une monoparesie associee a des xanthomes. L’IRM cerebrale, anormale chez tous nos malades, pouvait montrer une atteinte des noyaux denteles (47 %), une leucopathie periventriculaire (73 %) predominant dans les regions posterieures (60 %), une atteinte de la substance blanche de mecanisme vasculaire (7 %), une atteinte des faisceaux cortico-spinaux (53 %), des pallidums, du corps calleux ou une atrophie cortico-sous-corticale (33 %). Quatre-vingt-treize pour cent des patients avaient un taux de cholestanol serique eleve. La mutation la plus frequente etait 1183C>T, retrouvee chez 5 de nos 15 malades. Un traitement par acide chenodesoxycholique a permis une amelioration initiale chez 8 malades, suivie d’une stabilisation chez cinq d’entre eux, et d’une aggravation chez les trois autres. Quatre patients sont decedes des complications de la maladie. Conclusion Cette serie est la plus importante serie francaise rapportee a ce jour. Une xanthomatose cerebrotendineuse doit etre recherchee devant l’association de xanthomes (cliniques ou radiologiques) a un trouble neurologique. La maladie debute frequemment dans l’enfance mais de maniere aspecifique rendant compte du retard diagnostique. L’atteinte des noyaux denteles est tres evocatrice mais peu sensible. La leucopathie sus-tentorielle a souvent un gradient antero-posterieur. Une distribution vasculaire et une atteinte du corps calleux ne doivent pas faire exclure le diagnostic. Le dosage du cholestanol est tres fiable, son elevation permet de retenir le diagnostic, neanmoins celui-ci doit etre confirme par la biologie moleculaire.

Background and purpose Anti-β2-glycoprotein I (anti-β2-GPI) antibodies are part of the heterogeneous family of antiphospholipid antibodies and seem to be present in various neurological manifestations in addition to antiphospholipid syndrome (APS). Our objective was to analyse the clinical, radiological and therapeutic characteristics of neurological patients with positive anti-β2-GPI antibodies and without the Sapporo criteria for APS. Methods The medical records were retrospectively reviewed of 28 consecutive patients hospitalized in the Neurology Department of Strasbourg University Hospital, France, in whom anti-β2-GPI antibodies (immunoglobulin G and/or immunoglobulin M) were positive and other antiphospholipid antibodies negative, from November 2005 to July 2011. Clinical, radiological, biological and therapeutic data and clinical course were studied. Results Positive anti-β2-GPI antibodies were present in 28 patients. The predominant physiopathological process was mainly inflammatory (25% with myelitis, 14.3% with optic neuritis) or vascular (14.3% with cerebral ischaemia, 7.1% with cerebral vasculitis). Brain magnetic resonance imaging was performed in 89.3% of patients: atypical lesions were observed in 44% and typical inflammatory and vascular lesions in 16% and 12%, respectively. Conclusion The anti-β2-GPI antibody seems to be involved in two types of neurological disease: vascular or inflammatory ‘multiple sclerosis-like’ disease. These two types of patients frequently develop an autoimmune disease (multiple sclerosis, systemic lupus erythematosus, APS). However, a large proportion of the patients had an undefined profile with aspecific cerebral lesions and required monitoring. This study raises questions about a separate entity at the border between APS and multiple sclerosis which remains to be better defined in a larger cohort.

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.

Resume Introduction L’induction therapeutique dans les formes tres inflammatoires de sclerose en plaques remittente recurrente (SEP-RR) est une strategie interessante, jusqu’a maintenant limitee a la mitoxantrone. Observations Nous rapportons l’evolution clinico-radiologique rapidement favorable de trois patientes ayant une forme tres active de SEP-RR, des le premier mois apres l’initiation du traitement par natalizumab. Discussion Chez les trois patientes decrites, le natalizumab a montre une efficacite precoce, avec disparition du rehaussement des lesions par le gadolinium sur l’IRM realisee un mois apres l’initiation du traitement. Une strategie d’induction par natalizumab pourrait etre une option interessante chez les patients ayant une forme agressive de SEP-RR.

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS), two inflammatory demyelinating diseases, are characterized by different therapeutic strategies. Currently, the only biological diagnostic tool available to distinguish NMO from MS is the specific serum autoantibody that targets aquaporin 4, but its sensitivity is low.Objective:To assess the diagnostic accuracy of metabolomic biomarker profiles in these two neurological conditions, compared to control patients.Methods:We acquired serum spectra (47 MS, 44 NMO and 42 controls) using proton nuclear magnetic resonance (1H-NMR) spectroscopy. We used multivariate pattern recognition analysis to identify disease-specific metabolic profiles.Results:The1H-NMR spectroscopic analysis evidenced two metabolites, originating probably from astrocytes, scyllo-inositol and acetate, as promising serum biomarkers of MS and NMO, respectively. In 87.8% of MS patients, scyllo-inositol increased 0.15 to 3-fold, compared to controls and in 74.3% of NMO patients, acetate increased 0.4 to 7-fold, compared to controls. Using these two metabolites simultaneously, we can discriminate MS versus NMO patients (sensitivity, 94.3%; specificity, 90.2%).Conclusion:This study demonstrates the potential of1H-NMR spectroscopy of serum as a novel, promising analytical tool to discriminate populations of patients affected by NMO or MS.

Background and purpose BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing−remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. Methods Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y). Results NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. Conclusions The efficacy of NTZ therapy on relapsing−remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

International audience; BACKGROUND: Launched in the US in 2012, Choosing Wisely® is a campaign promoted by the American Board of Internal Medicine (ABIM) Foundation with the goal of improving healthcare effectiveness by avoiding wasteful or unnecessary medical tests, treatments and procedures. It uses concise recommendations produced by national medical societies to start discussions between physicians and patients on the relevance of these services as part of a shared decision-making process. The Multiple Sclerosis Focus Group (Groupe de Reflexion Autour de la Sclérose en Plaques; GRESEP) undertook a pilot study to assess the relevance and feasibility of this approach in the management of multiple sclerosis (MS) in France.METHODS: Recommendations were developed using the formal consensus method from the guidelines of the French National Health Authority (HAS). A steering committee selected the themes and drafted concise evidence reviews. An independent rating group then assessed these recommendations for clarity, relevance and feasibility.RESULTS: Seven recommendations were accepted: (1) avoid systematic ordering of multimodal evoked potential studies for diagnosing MS; (2) do not treat MS relapses with low-dose oral corticosteroids; (3) when treating MS relapse with high-dose corticosteroids, the systematic use of the intravenous route is unnecessary if the oral route can be used; (4) systematic hospitalization is not necessary for treating MS relapse with high-dose corticosteroid therapy, particularly if the oral route is used, except for the first treated relapse and the presence of exclusion or non-eligibility criteria; (5) in the absence of clinical signs or symptoms of urinary infection, avoid systematic screening with urine microscopy and culture before the administration of corticosteroid therapy for MS relapse in patients using intermittent self-catheterization; (6) avoid antibiotic treatment of clinically asymptomatic MS patients using intermittent self-catheterization, even if urine microscopy and culture reveal the presence of microorganisms; and (7) avoid introducing symptomatic drug treatment for MS-related fatigue.CONCLUSION: This pilot study, the first of its kind in France, has demonstrated the relevance and feasibility of adapting the Choosing Wisely® model to MS by practitioners specializing in the disorder. However, the acceptability of these recommendations by other practitioners in other specialist fields as well as their impact on everyday clinical practices now need to be studied.

Resume Introduction Les meningiomes sont des tumeurs meningees primitives benignes. Leur decouverte peut etre fortuite ou secondaire a l’exploration de symptomes neurologiques, voire ophtalmologiques. Patients et methodes Nous rapportons les histoires cliniques et paracliniques de cinq patientes ayant presente des symptomes ophtalmologiques qui ont conduit au diagnostic de meningiomes. Resultats Il s’agissait de cinq femmes, âgees de 52 ans en moyenne au moment du debut des symptomes. Elles presentaient toutes une baisse de l’acuite visuelle unilaterale progressive avec un fond d’œil initialement normal, associee a une alteration du champ visuel ipsilateral. Les differents examens complementaires et notamment radiologiques ont du etre repetes pour mener au diagnostic de meningiome dans un delai allant de 18 mois a quatre ans. Discussion Le tableau clinique de ces cinq cas est celui d’une neuropathie optique retrobulbaire ayant oriente le bilan vers la recherche d’une maladie inflammatoire du systeme nerveux central. Mais le caractere atypique de la neuropathie a fait reconsiderer le diagnostic et repeter les examens d’imagerie. Le caractere iso-intense des meningiomes en T1 et peu hyperintense en T2 en imagerie par resonance magnetique (IRM) peut conduire a un retard diagnostique et therapeutique si l’examen n’est pas fait et interprete par un professionnel experimente. L’injection de Gadolinium, les sequences avec suppression de graisse et le centrage sur les voies optiques anterieures sont des elements indispensables lors de l’IRM. Conclusion Devant une neuropathie optique indolore, d’evolution progressive, et resistante a la corticotherapie, le diagnostic de meningiome des voies optiques anterieures doit etre envisage. Celui-ci est facilite par une IRM adaptee aux voies optiques.

Resume Introduction Les encephalites sont des tableaux aigus inflammatoires ou infectieux pour lesquels des anticorps (Ac) sont rarement mis en evidence. Objectifs Evaluer le profil clinique, biologique et radiologique des patient atteints d’encephalites auto-immunes et degager des conduites a tenir diagnostiques et therapeutiques en fonction des sous-groupes de patients. Patients et methode Nous avons mene une enquete retrospective au sein des services de neurologie du CHU de Strasbourg. Tous les patients ayant presente un tableau d’encephalite dysimmunitaire entre mars 2000 et mai 2011 ont ete inclus. Resultats Notre cohorte se compose de 16 patients âges en moyenne de 45,3 ans et presentant tous une atteinte neuropsychologique ou neuropsychiatrique. Une atteinte epileptique est retrouvee dans 75 % des cas, une atteinte extralimbique dans 50 %. Seul 25 % des patients ont presente un cancer. L’imagerie a mis en evidence une souffrance temporale dans 94 % des cas. Des Ac antineuronaux sont retrouves dans 56 % des cas. Tous les patients ont recu un traitement immunomodulateur. L’amelioration a ete significative dans 63,3 % des cas, complete dans 31 %. Discussion Une specificite syndromique est complexe a etablir et la frequence des atteintes extralimbiques doit faire reconsiderer le concept d’encephalite limbique isolee au profit de celui d’encephalites dysimmunitaires. La recherche d’un cancer doit etre systematique mais n’aboutie que dans 25 % des cas. Il semble exister une meilleure reponse au traitement immunomodulateur lorsque la cible antigenique est membranaire.

Background: Few data are available for patients with a late onset (≥ 50 years) of neuromyelitis optica (LONMO) or neuromyelitis optica spectrum disease (LONMOSD), defined by an optic neuritis/longitudinally extensive transverse myelitis with aquaporin-4 antibodies (AQP4-Ab). Objective: To characterize LONMO and LONMOSD, and to analyze their predictive factors of disability and death. Methods: We identified 430 patients from four cohorts of NMO/NMOSD in France, Germany, Turkey and UK. We extracted the late onset patients and analyzed them for predictive factors of disability and death, using the Cox proportional model. Results: We followed up on 63 patients with LONMO and 45 with LONMOSD during a mean of 4.6 years. This LONMO/LONMOSD cohort was mainly of Caucasian origin (93%), women (80%), seropositive for AQP4-Ab (85%) and from 50 to 82.5 years of age at onset. No progressive course was noted. At last follow-up, the median Expanded Disability Status Scale (EDSS) scores were 5.5 and 6 in the LONMO and LONMOSD groups, respectively. Outcome was mainly characterized by motor disability and relatively good visual function. At last follow-up, 14 patients had died, including seven (50%) due to acute myelitis and six (43%) because of opportunistic infections. The EDSS 4 score was independently predicted by an older age at onset, as a continuous variable after 50 years of age. Death was predicted by two independent factors: an older age at onset and a high annualized relapse rate. Conclusion: LONMO/LONMOSD is particularly severe, with a high rate of motor impairment and death.

Background Neuromyelitis optica (NMO) is an inflammatory disease involving predominantly the spinal cord and optic nerves. Whether patients with NMO have a loss in white or grey matter (GM) volumes remains to be determined. Methods Thirty patients with NMO, 30 healthy subjects matched for age and gender, 21 patients with multiple sclerosis (MS) and 20 patients with a clinically isolated syndrome (CIS) were studied. We applied a SIENAX post-treatment software. We compared white matter (WM) and GM volumes between groups and explored correlations of changes in NMO patients with age, gender, duration, disease severity, visual acuity and T2 hyperintensities. We also performed a voxel-based morphometry (VBM) analysis to identify the regions affected by loss of volume. Results White matter volume was significantly reduced in patients with NMO (764.4 ± 58.3 cm3) compared to healthy subjects (843.1 ± 49.3 cm3) (P

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.

Resume Introduction Les premiers traitements de fond de la sclerose en plaques (SEP) ont obtenu une autorisation de mise sur le marche (AMM) en France a la fin des annees 1990. Actuellement, la majorite des patients atteints de SEP sont traites ou ont ete traites dans les annees passees par un ou plusieurs traitements de fond. Cependant, un certain nombre de patients restent sans traitement malgre un suivi prolonge. Objectifs L’objectif de notre etude a ete d’evaluer au sein d’une cohorte regionale, le nombre de patients qui n’ont jamais recu de traitement de fond, de determiner leur profil et d’etablir les raisons de cette absence de traitement. Patients et methodes Sur une cohorte Alsacienne de 1187 patients SEP recenses dans la base de donnees informatisee EDMUS (European database for Multiple Sclerosis), nous avons mene une etude retrospective concernant les patients suivis regulierement pour SEP depuis au moins cinq annees ( n = 724) et n’ayant jamais recu de traitement de fond ( n = 70). Resultats Soixante-dix patients (9,8 % de la cohorte etudiee) repondaient a nos criteres d’inclusion. On denombrait 57 femmes et 13 hommes d’un âge moyen de 54,9 annees (33–81). La duree moyenne d’evolution de la maladie etait de 20,6 ans (5–56). La SEP etait de type remittente chez 46 patients (65,8 %), primitivement progressive chez 11 patients (15,7 %) et secondairement progressive chez 13 patients (18,5 %). Dans les formes remittentes le taux annualise de poussee etait de 0,33 (0,08–1). L’Expanded Disability Status Scale (EDSS) moyen etait de 3,4 apres 20,6 ans d’evolution moyenne. L’indice de progression (IP) correspondant au score EDSS/nombre d’annees de suivi etait donc de 0,16, sans difference significative entre les formes progressives et les formes remittentes (0,15 et 0,16 respectivement). Les motifs de non traitement etaient representes par une absence d’activite importante de la maladie depuis le debut chez 65,8 %, une progression tres lente chez 10 %, un refus initial du traitement suivi d’une progression lente de la maladie chez 14,2 %, et une contre-indication au traitement dans 10 % des cas ayant une forme progressive ancienne evoluee. Enfin trois patients (4,3 % des cas) avaient initialement une stabilite de la maladie mais avec une reactivation recente pour laquelle un traitement de fond etait en instance d’instauration. Conclusion Apres un suivi moyen de 20 ans, la proportion de patients ne relevant pas d’un traitement de fond est de l’ordre de 10 %. Il s’agit essentiellement de forme remittente avec une frequence de poussee tres basse ou de patients ayant une forme progressive a progression tres lente.

Objective: The purpose of our study was to assess the influence of pregnancy on the course of neuromyelitis optica (NMO) and the impact of epidural analgesia and breastfeeding on its activity in the postpartum period. Methods: We performed a retrospective study of patients with NMO diagnosed according to Wingerchuk criteria. We noted the number of relapses during the year before pregnancy (BP), during pregnancy (first trimester, second trimester, third trimester), and the year after (Y + 1: first trimester, second trimester [PP2], and third and fourth trimesters postpartum). Epidural analgesia and breastfeeding were recorded. Disability was evaluated with the Kurtzke Expanded Disability Status Scale (EDSS). The annualized relapse rate (ARR) was calculated. Results: We identified 124 patients (85 female) in the French NOMADMUS cohort on November 1, 2010. A total of 20 women (including 25 pregnancies) were informative with complete files. Comparisons between the ARR of each period and BP (1.0 ± 0.09) only showed an increased tendency for PP2 (0.8 ± 0.06, p = 0.07). Epidural analgesia and breastfeeding had no influence on the course of NMO. The EDSS score increased from 1.5 ± 1.7 BP to 2.6 ± 1.9 Y + 1 ( p = 0.027). Conclusion: This study shows that pregnancy influences the activity of NMO, a finding that justifies close medical monitoring. We found no evidence to suggest that either epidural analgesia or breastfeeding has an aggravating effect on NMO.