Analyse de la période des relais thérapeutiques vers un traitement de haute efficacité chez les patients atteints d'une sclérose en plaques de forme récurrente-rémittente : une étude rétrospective strasbourgeoise/thèse présentée pour le diplôm

Médecine (neurologie)Introduction : La période des relais thérapeutiques dans la sclérose en plaques est à risque de poussées et d'effets indésirables, mais est encore trop peu étudiée. L'objectif de l'étude était d'analyser la survenue de poussées et d'effets indésirables durant cette période. Méthodes : Nous avons analysé de façon rétrospective les relais thérapeutiques vers un traitement de haute efficacité, réalisés entre 2007 et 2021, chez des patients âgés de plus de 18 ans, atteints de sclérose en plaques de forme récurrente-rémittente, suivis au CHU de Strasbourg. La survenue d'une poussée ou d'un effet indésirable était recueillie pour la période de washout et les 6 mois après le relais. Résultats : 448 relais thérapeutiques issus de dossiers de 340 patients ont été analysés, dont 207 vers le fingolimod (FTY), 164 vers le natalizumab (NTZ) et 77 vers les anticorps monoclonaux anti-CD20 (rituximab, et ocrelizumab). Les patients avec au moins une poussée durant le washout avaient significativement une durée de traitement antérieur plus courte, une durée de washout plus longue et plus souvent des prises de contraste sur l'IRM cérébrale avant le relais. Aucun effet indésirable n'a été constaté durant cette période. Les facteurs de risque significatifs de poussée(s) après le relais étaient en analyse multivariée : la survenue de poussée(s) durant l'année précédant le relais ou durant la période de washout, le sexe féminin, le nombre de traitements avant le relais thérapeutique. Il existait une tendance à une augmentation de la survenue de poussée(s) après le relais pour les relais FTY vers anti-CD20 et NTZ vers le FTY. Les types de relais ne semblaient pas influencer la survenue d'effets indésirables après les relais. Durant les 6 mois suivant le relais, les effets indésirables étaient rares. La durée de washout n'était pas clairement corrélée à la survenue d'un effet indésirable. Conclusion : La période de relais thérapeutique reste une période à risque de poussées, mais peu à risque d'effets indésirables. Raccourcir la période de washout pourrait minimiser ce risque de poussées sans pour autant augmenter celui des effets indésirables.Introduction: The switch period in multiple sclerosis is at risk of flare-ups and adverse effects, but is still too little studied. The aim of the study was to analyze the occurrence of relapses and adverse effects during this period. Methods: We retrospectively analyzed the switchs towards a high efficacy treatment, carried out between 2007 and 2021, in patients over the age of 18, suffering from relapsing-remitting multiple sclerosis, followed at the University Hospital of Strasbourg. The occurrence of a relapse or an adverse effect was collected for the washout period and the 6 months after the switch. Results: 448 therapeutic switch from 340 patients were analysed, including 207 towards fingolimod (FTY), 164 towards natalizumab (NTZ) and 77 towards anti-CD20 monoclonal antibodies (rituximab and ocrelizumab). Patients with at least one relapse during the washout had a significantly shorter duration of previous treatment, a longer washout duration and more often contrast enhancement on brain MRI before the swtich. No adverse effects were observed during this period. The significant risk factors for relapses after the switch were in multivariate analysis: occurrence of relapse during the year preceding the switch or during the washout period, female sex, number of treatments before the relay therapeutic. There was a trend for an increase in the occurrence of relapse(s) after the switch for the FTY to anti-CD20 and switch NTZ to FTY. The types of switch did not seem to influence the occurrence of adverse effects after the switch. During the 6 months following the switch, adverse effects were rare. Washout duration was not clearly correlated with the occurrence of an adverse effect. Conclusion: The switch period remains a period at risk of relapses, but with little risk of adverse effects. Shortening the washout period could minimize this risk of relapses without increasing the risk of adverse effects.Thèses et écrits académique

A rise in cases of nitrous oxide abuse: neurological complications and biological findings

BACKGROUND: The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. METHODS: We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. RESULTS: Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. CONCLUSION: We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study

BACKGROUND: Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. METHODS: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. RESULTS: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). CONCLUSION: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA