Search

International audience; Objective To assess the efficacy of tumour necrosis factor-α (TNF-α) inhibitors used as steroid-sparing monotherapy in central nervous system (CNS) parenchymal sarcoidosis. Methods The French Multiple Sclerosis and Neuroinflammation Centers retrospectively identified patients with definite or probable CNS sarcoidosis treated with TNF-α inhibitors as steroid-sparing monotherapy. Only patients with CNS parenchymal involvement demonstrated by MRI and imaging follow-up were included. The primary outcome was the minimum dose of steroids reached that was not associated with clinical or imaging worsening during a minimum of 3 months after dosing change. Results Of the identified 38 patients with CNS sarcoidosis treated with TNF-α inhibitors, 23 fulfilled all criteria (13 females). Treatments were infliximab (n=22) or adalimumab (n=1) for a median (IQR) of 24 (17–40) months. At treatment initiation, the mean (SD) age was 41.5 (10.5) years and median (IQR) disease duration 22 (14–49.5) months. Overall, 60% of patients received other immunosuppressive agents before a TNF-α inhibitor. The mean (SD) minimum dose of steroids was 31.5 (33) mg before TNF-α inhibitor initiation and 6.5 (5.5) mg after (p=0.001). In all, 65% of patients achieved steroids dosing

International audience; Introduction: Hepatitis E virus (HEV) infection has been reported to be associated with neurological disor-ders. However, the real prevalence of acute hepatitis E in those diseases is still unknown. We determinedthe prevalence of anti-HEV IgM antibody in a population with acute non-traumatic, non-metabolic,non-vascular neurological injury.Method: A registry was created in Grenoble Hospital University from 2014 to 2018 to collect data onpatients with acute (

Objectives. Central neurological manifestations of rheumatoid arthritis (RA) like rheumatoid meningitis (RM) are rare, little known and have a high rate of morbi-mortality. METHODS. We described six cases of RM that were directly related to RA activity after exhaustive assessment. RESULTS. They were mainly women, aged of 50 to 69. All were positive for anti-cyclic citrullinated peptide antibodies and half for rheumatoid factors. RA activity, duration, and treatments were heterogeneous including oral steroids, conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs. Symptoms were various, with acute or progressive beginning, main were: generalized or focal seizure (4/6), fever (3/6), headaches (3/6), and frontal syndrome (2/6). Imaging lesions were four leptomeningitis, one pachymeningitis, and one association of both. MRI usually showed hypersignal in various territories in T2-FLAIR (fluid attenuated inversion recovery) mode, and enhancement in T1-weighted mode after gadolinium injection. All patients had lumbar puncture that found sterile cerebrospinal fluid, no neoplasic cell, elevated cell count in 5/6 cases and elevated proteins concentration in 3/6 cases. Cerebral biopsy was possible for three patients, and definitively confirmed the diagnosis of aseptic lepto- or pachymenintis, excluding vasculitis and lymphoma. Different treatments were used like intravenous high dose steroids, immunoglobulins or biologic DMARDs, with variable clinical and imaging outcome: one death, one complete recovery, and four recoveries with sequelae. Conclusions. Clinical symptoms, imaging, lumbar puncture, and serological studies are often nonspecific, only histologic examination can confirm the diagnosis of RM. Any central neurological manifestation in RA patients, even in quiescent and ancient RA, should warn the physician.

International audience; Importance:Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated.Objective:To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013.Design, Setting, and Participants:This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018.Exposures:Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation.Main Outcomes and Measures:Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016).Results:In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016.Conclusions and Relevance:The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.

Introduction Les formes progressives de scleroses en plaques (SEP) resultent de mecanismes a predominance metabolique, aboutissant a une hypoxie relative du systeme nerveux central. La biotine semble offrir des resultats encourageants. Objectifs Evaluer l’impact fonctionnel en vie reelle d’un traitement par biotine durant un an chez des patients presentant une SEP progressive au CHU de Grenoble. Patients et Methodes Nous avons realise une evaluation prospective sur 12 mois chez des patients presentant une SEP progressive, avec score EDSS superieur ou egal a 4, pour lesquels un traitement par biotine etait initie. Nous avons evalue la marche (TWF25), le handicap (EDSS), d’autres parametres fonctionnels et des auto-questionnaires a l’inclusion et a 12 mois (M12). Les patients etaient consideres comme repondeurs si l’EDSS etait ameliore de 0,5 a 1 point selon le score initial ou si le TWF25 diminuait d’au moins 20 %. Resultats Trente patients ont ete inclus. Quatre patients (13,3 %) ont rempli le critere de jugement : 1 sur l’EDSS et 3 sur le TWF25. Seize patients se sont aggraves sur l’un de ces parametres. Le score de fatigue a M12 etait significativement plus faible qu’a l’inclusion, mais sans passer sous le seuil pathologique. Huit patients sur les 22 reevalues rapportaient une amelioration subjective, et 6 se decrivaient comme aggraves. La tolerance etait correcte, il n’y a pas eu de poussee. Discussion Nous avons observe les memes resultats que ceux de la litterature. L’evaluation fonctionnelle s’est revelee complexe, parfois discordante avec le ressenti des patients et difficilement extrapolable a la consultation de routine. Du fait de l’evolution naturelle des SEP progressives, il se discute de considerer comme repondeurs au traitement egalement ceux stables. Conclusion La biotine permet une amelioration fonctionnelle de 13 %, ainsi qu’une reduction du score de fatigue, chez nos patients presentant une SEP progressive. Des etudes de phase III restent a realiser.

Objective. To evaluate the efficacy of resistance exercises in RA patients. Methods. A systematic literature search was done using Pubmed, Embase and Cochrane databases through November 2009 and in abstracts presented at rheumatology scientific meetings over the past 3 years. Randomized controlled trials (RCTs) comparing resistance exercise based therapy with interventions without resistance exercise for the treatment of RA patients were included. Outcomes studied were post-intervention disability on the HAQ, functional capacity assessed by walking speed, pain on the visual analogue scale (VAS), joint count, isometric, isokinetic and grip strength. Efficacy was assessed by weighted mean differences (WMDs) and tolerance was assessed by relative risk (RR). Data were pooled using the inverse of variance model, and heterogeneity was tested. Results. Ten RCTs, including 547 patients, met the study inclusion criteria. The mean (S.D.) Jadad score was 2.3 (0.6). Resistance exercises significantly improved isokinetic strength (WMD = 23.7%, P < 0.001), isometric strength (WMD = 35.8%, P < 0.001), grip strength (WMD = 26.4%, P < 0.001) and HAQ (WMD =0.22, P < 0.001). Exercise also had a positive impact on the 50-foot walking test (WMD =1.90 s, P < 0.001) and ESR (WMD =5.17, P = 0.005). Withdrawals [RR = 0.95, 95% confidence interval (CI) 0.61, 1.48] and adverse events (RR = 1.08, 95% CI 0.72, 1.63) were well balanced in both groups. Patient and exercise characteristics did not influence the results. Subgroup analysis revealed a trend towards higher efficacy associated with high-intensity programmes. Conclusion. Resistance exercise in RA is safe, and the improvement in most outcomes was statistically significant and possibly clinically relevant for RA disability.

Introduction : la neurosarcoïdose (NS) est une atteinte peu fréquente du système nerveux central dans le cadre d’une sarcoïdose systémique, associée à une morbidité importante. Son diagnostic est difficile : l’atteinte neurologique peut parfois être isolée, les présentations cliniques, biologiques et radiologiques ne sont pas spécifiques. A ce jour aucun biomarqueur n’a fait la preuve de son efficacité pour le diagnostic de la NS. Le dosage de l’enzyme de conversion de l’angiotensine dans le liquide céphalorachidien (ECA-LCR) est un examen disponible en routine mais controversé pour le diagnostic de la NS avec peu de données dans la littérature quant à ses performances. Matériel et méthode : nous avons conduit une étude multicentrique rétrospective incluant tous les patients ayant eu un dosage de l’ECA-LCR au CHU de Grenoble Alpes entre 2012 et 2020 et ceux pour lesquels un diagnostic de NS était évoqué au CHU de Genève entre 2006 et 2012. Nous avons évalué les paramètres diagnostiques de l’ECA-LCR, la corrélation avec l’ECA plasmatique et l’impact d’un traitement par un inhibiteur de l’enzyme de conversion (IEC) sur l’ECA-LCR. Résultats : 18 des 578 patients inclus avaient un diagnostic de NS probable (16) ou confirmée (2) selon les critères proposés par le Neurosacroidosis Consortium Consensus Group. Pour un seuil de 2UI/L la spécificité du test était de 91,7% et la sensibilité de 38,9%. Pour une prévalence estimée à 0,76 / 100 000 hospitalisations au CHU de Grenoble (95% IC [2,64 ; 12,58]), la valeur prédictive négative (VPN) du test est de 99% et la valeur prédictive positive de 0,0004%. Il n’existait pas de corrélation entre l’ECA sérique et l’ECA-LCR (R = 0,21 ; p = 0,42). Au contraire de l’ECA sérique, il n’y avait pas de différence entre les patients traités ou non par inhibiteur de l’enzyme de conversion pour le dosage de l’ECA-LCR (1,2 vs 1,5 ; p=0,15). Conclusion : cette étude préliminaire va dans le sens d’autres travaux qui retrouvaient également une bonne spécificité de l’ECA-LCR pour le diagnostic de la NS. L’analyse d’un plus large échantillon devrait permettre de confirmer ces résultats et proposer d’inclure l’ECA-LCR dans la stratégie diagnostique de la NS.

Introduction: cognitive impairement is an usual infectious and non infectious encephalitis complication, but is not assessed in clinical practice. Objective: describe neuropsychological outcomes following encephalitis or meningo encephalitis, according to the etiology or the evaluation period. Methods : all the patients hospitalised in the CHUGA between the 1st of january 2013 and the 31st of december 2018 for an encephalitis or meningoencephalitis were included. All the standardized neuropsychological assessments were analized. The abilities were classified between normal, poor and pathological range. We conducted a descriptive analysis depending on the etiology et the delay of testing from the onset. Results: 131 patients were admited for an encephalitis, 33 recieved a neuropsychological assessment (19 men ; median age = 57,9 [23-86] years) whose 20 infectious encephalitis, 5 immune and 8 undetermined. Fivetee percent of patients had amnesic symptoms, with verbal memory storage default and active reserch in visual memory trouble. They also had executive dysfunctions as speed processing slow-down (61%), perseverations (42,6%) and mental flexibility defect (32,2%). Most of them (75%) were able to get back to their previous activities. Discussion: in the absence of invalids symptoms, cognitive aftermath are under retrieved in clinical practice, However, assessing that kind of impairement is usefull for socio-professional rehabilitation.; Introduction : les encéphalites infectieuses et non infectieuses sont fréquemment compliquées de troubles cognitifs, peu explorés de façon exhaustive en pratique clinique quotidienne. Objectif: décrire l'évolution neuropsychologique observée au décours d'une encéphalite ou méningo-encéphalite, selon l'étiologie et le délai d'évaluation. Méthodes : nous avons inclus l'ensemble des patients hospitalisés au CHUGA entre le 1er janvier 2013 et le 31 décembre 2018 pour une encéphalite ou méningo-encéphalite. L'ensemble des bilans neuropsychologiques réalisés a été analysé et les performances ont été classées selon que les résultats étaient dans les normes, affaiblis ou pathologiques. Nous avons réalisé une analyse descriptive en fonction de l'étiologie impliquée et selon le délai d'évaluation. Résultats : 131 patients ont été hospitalisés pour une encéphalite, 33 ont bénéficié d'un examen neuropsychologique (19 hommes; âge moyen=57,9 [23-85] ans) dont 20 encéphalites d'origine infectieuse, 5 dysimmunes et 8 d'étiologie non déterminée. On retrouve une majorité de troubles mnésiques par défaut de stockage en modalité verbale et défaut d'accès sur matériel visuel pour 50% des patients ; ainsi que des troubles dysexécutifs dominés par un ralentissement du traitement de l'information (61%), des persévérations (42,6%) et un défaut de flexibilité mentale (32,3%). La majorité (75%) reprenait ses activités antérieures au décours. Discussion : les séquelles cognitives d'encéphalites sont peu explorées en pratique quotidienne en l'absence de symptômes invalidants. Leur évaluation est néanmoins utile à la réadaptation socio-professionnelle.

Background: Non infectious encephalitis are becoming better understood thanks to improvement in the neuroimmunology. Methods : We retrospectively examined the neurological and psychiatric symptoms, the paraclinic investigations, the treatment and the future of 19 patients with a diagnosis of non infectious encephalitis in Grenoble University Hospital from 2006 to 2012. Results: Out of 19 patients with a diagnosis of non infectious encephalitis, 14 were women. The population had a mean age of 49.5 years (range, 4-87), with a bimodal distribution, 2 major periods seem at risk : young adults and patients over 60 years old. From their past history, 5 patients had immune diseases, 3 had gynecological tumors. From the clinical markers, two major symptoms were characterized: either patients had confusional symptoms or they suffered from epileptic seizures with or without psychiatric symptoms. From that population, 5 patients had antineuronal antibodies : 2 anti-NMDA-R antibodies, 1 anti-VGKC antibodies, 1 anti-CV2 antibodies and 1 uncharacterized antibody. A gynecological tumor was diagnosed in 2 patients with antineuronal antibodies. Prognosis of that type of encephalitis is variable from death to complete recovery or partial recovery with persistant cognitive or psychiatric impairment. Discussion: These non infectious encephalitis are fairly described and are often a diagnosis of exclusion. Clinical and laboratory data with neuroimmunological improvement should help to better define these encephalitis in order to improve their treatment.; La recherche étiologique des encéphalites non infectieuses se précise grâce à l'identification de nouvelles cibles antigéniques au niveau du système nerveux central. L'objectif est de mieux caractériser ces encéphalites souvent étiquetées idiopathiques en colligeant leurs caractéristiques cliniques et paracliniques, leur évolution et l'attitude thérapeutique instaurée. Il s'agit d'un travail rétrospectif (de 2006 à mars 2011), avec inclusion prospective depuis mars 2011, sur le CHU de Grenoble. 19 patients, dont 14 femmes, ont été inclus dans ce registre avec une répartition bimodale, le jeune adulte et la personne de plus de 60 ans. Deux tableaux cliniques ont été caractérisés, d'une part une séméiologie confusionnelle "plus" et d'autre part une séméiologie épilepto-psychiatrique. 2 cas d'Ac anti-NMDAr, 1 cas d'Ac anti-VGKC, 1 marquage membranaire fort et 1 cas d'anti-CV2 sont retrouvés. Une tumeur a été retrouvée chez 2 patientes. Un traitement immunoactif a été utilisé chez 13 patients. L'évolution est variable. Ces encéphalites d'étiologie indéterminée sont assez peu décrites et restent souvent un diagnostic d'élimination. La confrontation de données séméiologiques aux avancées immunologiques concernant les cibles antigéniques des encéphalites dysimmunes devrait permettre de mieux définir le cadre de leur prise en charge diagnostique et thérapeutique.