DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Le diabète :une bonne compréhension de cette affection en améliore le contrôle.

info:eu-repo/semantics/publishe

Efficacy and Safety of Fingolimod in Daily Practice: Experience of an Academic MS French Center

International audienceIntroduction: Fingolimod (Fg), a sphingosine 1-phosphate receptor modulator, decreases the annual relapse rate (ARR) in relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to assess the efficacy and safety of Fg in daily practice in patients with RRMS, previously treated with natalizumab (Nz) or not, and systematically followed during at least 1 year.Methods: Data were collected from the patient files. Primary endpoint was the comparison between the ARR the year before Fg onset and after 1 and 2 years of Fg treatment. The secondary endpoints were the difference between Expanded Disability Status Scale (EDSS) at Fg onset and after 1 and 2 years of treatment, and safety.Results: In the whole sample, we confirmed Fg efficacy on the ARR (0.895 before vs. 0.364 1 year after, p < 0.0001). Between our two groups (with or without Nz before Fg), the ARR was higher in the Nz group during the first year but similar during the second year. The EDSS was stable during the first year of Fg but significantly higher after 2 years (3.33 vs. 3.72, p = 0.02). Concerning safety, only three patients had to discontinue Fg because of tolerance issues.Conclusion: Our study showed that Fg is safe in RRMS and can be used either after first-line treatments or after Nz. However we observed a mild disability progression after 2 years

The Xenopus tadpole: an in vivo model to screen drugs favoring remyelination

International audienceBackground:In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely.Objective:A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules.Methods:In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced demyelinating responses. As tadpoles are transparent, these events can be monitored in vivo and quantified. At the end of metronidazole-induced demyelination, tadpoles were screened in water containing the compounds tested. After 72 h, remyelination was assayed by counting numbers of oligodendrocytes per optic nerve.Results:Among a battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring remyelination. Crispr/cas9 gene editing showed that the promyelinating effect of siponimod involves the sphingosine-1-phosphate receptor 5.Conclusion:This Xenopus transgenic line constitutes a simple in vivo screening platform for myelin repair therapeutics. We validated several known promyelinating compounds and demonstrated that the strong remyelinating efficacy of siponimod implicates the sphingosine-1-phosphate receptor 5

Cerebellar encephalitis and peripheral neuropathy with an atypical clinical and neuroimaging signature following Covid-19 vaccine: a report of two cases Authors

International audienceBackground. Immune-mediated neurological syndromes may occur following SARS-CoV-2 infection or vaccination. Their presentation can be extremely heterogeneous and there are no established guidelines for treatment.Methods. We report the clinical and instrumental features of two patients presenting neurological syndromes started two weeks after Covid-19 vaccine, with infection co-occurring in one case, describe their common neuroimaging profile and illustrate their response to immunosuppressive treatment.Results. Both patients displayed simultaneous central and peripheral nervous system involvement. Cerebellar ataxia and predominantly sensory neuropathy/neuronopathy were present in one case, whereas rapidly evolving quadriparesis, sensory level, bulbar deficits and altered vigilance characterized the other. Electrophysiological studies were in favor of both central and peripheral conduction deficits. Brain MRI displayed inflammatory changes with contrast enhancement in superior cerebellar peduncles in both cases. Intrathecal IgG synthesis was present, but no known autoantibodies were found in plasma and CSF. Immunosuppressive treatments, namely plasma exchanges and high-dose corticosteroids, had a partially favorable impact, at least on central involvement.Conclusions. We report two cases of cerebellar encephalitis following Covid-19 exposure with an atypical neuroimaging signature involving superior cerebellar peduncles. This neuroinflammatory pattern, already identified in patients exposed to SARS-CoV-2 vaccine, suggests that cerebellar encephalitis may be considered a rare but severe adverse event of RNA vaccine against Covid-19. We also provide evidence concerning the potential benefit of intensive immunosuppressive strategies in such cases