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Background: Outcomes of coronavirus disease 2019 (COVID‐19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. Methods: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID‐19 between 1 March 2020 and 30 June 2020. Main outcome was COVID‐19 severity score assessed on a seven‐point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). Results: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24‐year‐old patient with positive aquaporine‐4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti‐CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0–4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0–6.5]). Conclusions: COVID‐19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID‐19; however, we recommend personal protective measures to reduce risk of SARS‐CoV‐2 infection in this immunocompromised population. [ABSTRACT FROM AUTHOR]

Background: The kappa free light chains index (κ‐index) is increasing in importance as a fast, easy, cost‐effective, and quantitative biomarker in multiple sclerosis (MS), which can replace cerebrospinal fluid (CSF)‐restricted oligoclonal bands (OCB) detection. In previous studies, controls often included mixed patients with several inflammatory central nervous system disorders. The aim of the present study was to assess the κ‐index in patients with serum aquaporin‐4 (AQP4)‐IgG or myelin‐oligodendrocyte‐glycoprotein (MOG)‐IgG. Methods: We analyzed CSF/serum samples of patients with AQP4‐IgG or MOG‐Ig and evaluated distinct κ‐index cut‐offs. We described clinical and magnetic resonance imaging (MRI) features of patients with the highest κ‐index values. Results: In 11 patients with AQP4‐IgG, median κ‐index was 16.8 (range 0.2; 63) and 6/11 (54.5%) had κ‐index >12. Among 42 patients with MOG‐IgG, 2 had low positive MOG‐IgG titers, were ultimately diagnosed with MS, and had a markedly increased κ‐index (54.1 and 102.5 respectively). For the remaining 40 MOG‐IgG‐positive patients the median κ‐index was 0.3 (range 0.1; 15.5). Some 6/40 (15%) and 1/40 (2.5%) patients had a κ‐index >6 and >12, respectively. None fulfilled MRI dissemination in space and dissemination in time (DIS/DIT) criteria and the final diagnosis was MOG‐IgG‐associated disease (MOGAD) for these 40 patients. Four of the 40 (10%) MOG‐IgG‐positive patients had OCB. Conclusion: While a marked increase in κ‐index could discriminate MS from MOGAD, a low κ‐index threshold could lead to confusion between MS and MOGAD or AQP4 antibody‐positive neuromyelitis optica spectrum disorder. [ABSTRACT FROM AUTHOR]

Background and purpose: Lesion remyelination preserves axonal integrity in animal models of multiple sclerosis (MS), but an in vivo demonstration of its protective effect on surrounding tissues in humans is lacking. Methods: Nineteen persons with MS were enrolled in a cohort study and underwent two positron emission tomography (PET)/magnetic resonance imaging (MRI) scans 1–4 months apart. Voxelwise maps of Pittsburgh compound B distribution volume ratio, reflecting myelin content, were used to calculate an index of baseline demyelination, and of dynamic demyelination and remyelination over the follow‐up in 549 single white matter lesions. Changes in fractional anisotropy and mean diffusivity, reflecting microstructural damage, were calculated in the proximal and distal 3‐mm‐thick rings surrounding each lesion, and used to classify perilesional microstructure as "preserved" or "worsening" over the follow‐up. Mixed‐effect linear models and logistic regressions were employed to investigate whether PET‐derived lesional indices were associated with changes in MRI metrics in perilesions, and to identify which of them best predicted the microstructural evolution of perilesions over time. Results: A higher index of remyelination, and a lower index of baseline and dynamic demyelination in lesions were associated with a less severe microstructural deterioration of the corresponding proximal and distal perilesions over time (p‐value range: <0.001–0.012), but the index of remyelination was the best predicting variable of perilesional fate. For every extra 1% of remyelination within each lesion, the probability of the corresponding perilesional microstructure remaining preserved over time increased by 39% (odds ratio = 6.62, 95% confidence interval = 2.16–20.32, p < 0.001). Conclusions: Intralesional remyelination is associated with the microstructural preservation of surrounding tissues, possibly preventing neuroaxonal damage resulting from Wallerian degeneration. [ABSTRACT FROM AUTHOR]

Aims: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real‐life setting. Methods: A population‐based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1–3.5 years of follow‐up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively. Results: Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF‐IMM patients, 1679 DMF‐TERI patients, and 376 DMF‐FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61–0.86]) and TERI (0.81 [0.68–0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS‐specific disability was not significantly different for any matched cohorts. Conclusion: DMF is associated with lower risk of treated relapse for patients with RRMS than other first‐line RRMS agents (TERI and IIM). [ABSTRACT FROM AUTHOR]

Objective: As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta‐analysis compares the efficacy of first‐line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used. Methods: Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first‐line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first‐line immunosuppression had to be available, calculable, or provided by the authors. Results: We gathered data from 919 NMO patients (232 RTX‐, 294 MMF‐, and 393 AZA‐treated patients). The risk of first relapse after first‐line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA. Interpretation: The findings suggest that RTX is more efficient than MMF as a first‐line therapy. Even if the results of our meta‐analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX. [ABSTRACT FROM AUTHOR]

Objective: The main objective was to compare clinical features, disease course, and myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) dynamics between children and adults with MOG‐Ab–associated disease (MOGAD). Methods: This retrospective multicentric, national study included 98 children and 268 adults with MOGAD between January 2014 and September 2019. Cox regression model for recurrent time‐to‐event data and Kaplan–Meier curves for time to antibody negativity were performed for the objectives. Results: Isolated optic neuritis was the most frequent clinical presentation in both children (40.8%) and adults (55.9%, p = 0.013), and acute disseminated encephalomyelitis syndrome was more frequent in children (36.7% vs 5.6%, p < 0.001). Compared to adults, children displayed better recovery (Expanded Disability Status Scale ≥ 3.0 at last follow‐up reached only by 10 of 97 [10.3%] vs 66/247 [26.7%], p < 0.001). In the multivariate analysis, adults were at higher risk of relapse than children (hazard ratio = 1.41, 95% confidence interval [CI] = 1.12–1.78, p = 0.003). At 2 years, 64.2% (95% CI = 40.9–86.5) of nonrelapsing children became MOG‐Ab negative compared to 14.1% (95% CI = 4.7–38.3) of relapsing children (log‐rank p < 0.001), with no differences observed in adults (log‐rank p = 0.280). Interpretation: MOGAD patients differ in the clinical presentation at onset, showing an age‐related shift in the clinical features across age groups. Compared to children, adults have a higher risk of relapse and worse functional recovery. Finally, children with monophasic disease become MOG‐Ab negative earlier than relapsing children, but this is not true in adults. Considering these differences, management and treatment guidelines should be considered independently in children and adults. ANN NEUROL 2021;89:30–41 [ABSTRACT FROM AUTHOR]