Multiple sclerosis in 2020: un bon cru

The landscape of multiple sclerosis is changing, with new insights on prognosis, the emergence artificial intelligence in brain imaging, technological advances challenging knowledge disease pathogenesis, and identification novel therapeutic pathways. However, 2020 will certainly be remembered for spread COVID-19 pandemic. In this context, possibility an increased susceptibility to severe patients has rapidly become important question. Higher age, Expanded Disability Status Scale score 6 or more, obesity were identified as independent risk factors a French multicentre observational cohort.1Louapre C Collongues N Stankoff B et al.Clinical characteristics outcomes coronavirus 2019 sclerosis.JAMA Neurol. 2020; 77: 1079-1088Crossref PubMed Scopus (280) Google Scholar Whereas study, which included 347 patients, there was no significant association between disease-modifying treatment exposure severity, some evidence now emerging that therapies targeting CD20 might linked COVID-19, several studies aiming establish whether case are ongoing. How manage individuals radiologically isolated syndrome—people MRI scans compatible CNS inflammation but without neurological symptoms—remains because long-term outcome after diagnosis unknown. Radiologically Isolated Syndrome Consortium study,2Lebrun-Frenay Kantarci O Siva A al.Radiologically syndrome: 10-year estimate clinical event.Ann 88: 407-417Crossref (55) largest longest study date, 277 syndrome. cumulative probability event at 10 years 51·2%. Consistent previous publications, young age spinal cord lesions predictors first event. novelty here two additional factors—the presence oligoclonal bands elevated IgG index CSF infratentorial lesions—with stepwise increase associated number (probability ranging from 29% least one factor 87% those four factors). Nevertheless, absence results ongoing trials potential drugs (TERIS [NCT03122652] ARISE [NCT02739542]), recommendation treat Artificial opened avenues medical imaging general. sclerosis, example deep learning approach applying convolutional neural networks,4Wei W Poirion E Bodini al.Predicting PET-derived myelin content multisequence individual longitudinal analysis sclerosis.Neuroimage. 223117308Crossref (10) evaluating predicting lesion activity need contrast injection. conventional data 519 total 1390 enhancing used train test network performance. Participants classified 70% accuracy. Similarly, method proposed by Wei colleages4Wei could offer alternative PET scanning predict changes using quantitative MRI. Myelin 11C-PIB allows quantification vivo, invasive, injection radioactive tracer, poorly suited studies. colleagues4Wei allowed generation synthetic images sclerosis. By providing MRI-based algorithms, methods likely modify, near future, management well design With regard single-cell RNA-sequencing have revealed heterogeneity oligodendroglia, neurons, microglia healthy tissue. genetic epigenetic Wheeler colleagues5Wheeler MA Clark IC Tjon EC al.MAFG-driven astrocytes promote inflammation.Nature. 578: 593-599Crossref (172) investigated tissue experimental autoimmune encephalomyelitis (a rodent model sclerosis); they subpopulation characterised decreased expression antioxidant transcription NRF2 MAFG, leading repression anti-oxidant anti-inflammatory transcriptional programmes. Such pro-inflammatory detected within active white matter These results, identify how contribute damage, open perspectives candidates neurotoxic astrocytic activity. Promoting neuroprotection major challenge irreversible disability highly correlated accumulation neuronal damage. Several pro-remyelinating ongoing.6Lubetzki Zalc Williams Stadelmann Remyelination sclerosis: basic science translation.Lancet 19: 678-688Summary Full Text PDF (128) negative AFFINITY trial effect opicinumab relapsing released, ending development anti-LINGO-1 strategy. Bexarotene remyelination also been trialled (EudraCT 2014-003145-99) and, although primary efficacy reported drug tolerated, secondary suggest it repair.7Brown W, Cunnife N, Prados F, al. Phase 2 retinoid-X receptor agonist promotes people relapsing-remitting MSVirtual2020; virtual; Sept 11–13, (abstr LB01.02).Google direct neuroprotection, MS-SMART disappointing.8Chataway J De Angelis F Connick P al.Efficacy three neuroprotective progressive (MS-SMART): phase 2b, multiarm, double-blind, randomised placebo-controlled trial.Lancet 214-225Summary (61) This multi-arm, parallel-group, aimed evaluate (amiloride, fluoxetine, riluzole) selected searches research animal models trials. 393 none groups showed improvement (volumetric percentage volume change) baseline 96 weeks compared placebo. despite result, convincingly value feasibility multi-arm designed inform go no-go decision 3 neuroprotection. Finally, masitinib (NCT01433497) target innate immunity suggested positive versus placebo sclerosis.9Vermersch P, Hermine O. Masitinib (PPMS) non-active (nSPMS) AB07002. FC04.01).Google exciting behavioural interventions accumulating. published earlier year,10Bacmeister CM Barr HJ McClain CR al.Motor via surviving oligodendrocytes.Nat Neurosci. 23: 819-831Crossref (131) live follow oligodendrocytes sheaths murine demyelinated motor cortex assess task remyelination. Training led both oligodendrocytes—an result debate identity remyelinating cells adult CNS. not only strengthens role myelination, provides convincing demonstration timely intervention (after onset remyelination) accelerates functional recovery through enhanced EM reports grants personal fees Biogen, Novartis, Roche; Merck-Serono, Teva, Sanofi-Genzyme, Ad Scientiam outside submitted work. CL Biogen; Roche, Rewind, Ipsen