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Choroid plexus (ChP) enlargement is an emerging radiological biomarker in multiple sclerosis (MS).This study aims to assess ChP volume in a large cohort of patients with radiologically isolated syndrome (RIS) versus healthy controls (HC) and explore its relationship with other brain volumes, disease activity, and biological markers.RIS individuals were included retrospectively and compared with HC. ChPs were automatically segmented using an in-house automated algorithm and manually corrected.A total of 124 patients fulfilled the 2023 RIS criteria, and 55 HCs were included. We confirmed that ChPs are enlarged in RIS versus HC (mean (±SD) normalized ChP volume: 17.24 (±4.95) and 11.61 (±3.58), respectively, p < 0.001). Larger ChPs were associated with more periventricular lesions (ρ = 0.26; r2 = 0.27; p = 0.005 for the correlation with lesion volume, and ρ = 0.2; r2 = 0.21; p = 0.002 for the correlation with lesion number) and lower thalamic volume (ρ = −0.38; r2 = 0.44; p < 0.001), but not with lesions in other brain regions. Conversely, ChP volume did not correlate with biological markers. No significant difference in ChP volume was observed between subjects who presented or did not have a clinical event or between those with or without imaging disease activity.This study provides evidence that ChP volume is higher in RIS and is associated with measures reflecting periventricular pathology but does not correlate with biological, radiological, or clinical markers of disease activity. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy.Methods: We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome.Results: We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response.Conclusions: We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. Objectives: Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. Methods: We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. Results: Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. Discussion: Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate. [ABSTRACT FROM AUTHOR]

Background and Objectives: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes., Methods: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method., Results: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%., Discussion: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk., Classification of Evidence: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Introduction: Over the past few years, anti-CD20 therapies like rituximab, ocrelizumab or ofatumumab have seen an increase in interest in the treatment of neurological autoimmune disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), or resistant forms of generalized myasthenia gravis (MG). They are generally well-tolerated, but recent reports have highlighted severe dental disorders in patients undergoing anti-CD20 therapies. The aim was to describe a series of cases and to compare with the available scientific literature., Methods: We reviewed 6 patient cases with dental disorders during anti-CD20 therapy that were reported to the pharmacovigilance center. A disproportionality analysis was also conducted on Vigibase® for each anti-CD20 and each adverse effect described in the cases., Results: Six cases of dental and gingival conditions in relatively young patients were reported (median age: 40.5 years old [min: 34; max: 79]). Oral conditions were developed in four patients with MS treated with ocrelizumab and in two patients receiving rituximab (one patient with MG and one with NMOSD). The onset of oral conditions ranged from 10 days to 2 years after treatment initiation. Notably, all patients treated with ocrelizumab experienced gingival recession. Various dental pathologies were observed, including tooth loss, dental pain, caries, brittle teeth, dental fractures, dental abscesses, and periodontitis. Analysis of Vigibase® revealed 284 worldwide cases of dental and gingival conditions under ocrelizumab, 386 cases under rituximab, and 80 under ofatumumab. Significant associations were found between these therapies and dental pathologies, particularly tooth abscesses and infections., Conclusion: To our knowledge, this is the first case series reporting dental conditions developed in patients long-term treated with anti-CD20 treatments. This issue, literature data, and Vigilyze® analysis might be considered a safety signal that necessitates being confirmed with more robust data, such as a retrospective study with a control group. Meanwhile, proactive measures are essential like frequent dental checkups and dental hygienic measures to prevent oral health problems associated with anti-CD20 therapies., (© 2024. The Author(s).)

Background: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk., Objective: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS)., Methods: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal., Results: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations., Conclusion: These recommendations propose a strategic approach to managing cancer risk in PwMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N. Collongues has received honoraria for consulting or presentation from Alexion, Biogen Idec, Bristol-Myers Squibb, Horizon Therapeutics, Merck Serono, Novartis, Roche, and Sanofi-Genzyme and is a member of the Editorial Board of the Journal de la Ligue Française contre la Sclérose en plaques and the Neurology and Therapy Journal. Françoise Durand-Dubief has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, BMS-Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Christine Lebrun Frenay has nothing to disclose. Géraldine Androdias has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Bertrand Audoin has nothing to disclose. Xavier Ayrignac has received consulting fees and lecturing fess, travel grants, and unconditional research support from Alexion, Biogen, Genzyme, Janssen, Merck Serono, Novartis, Roche, Sanofi Aventis, and Teva Pharma. Caroline Bensa has received consulting honoraria from Alexion, Sanofi, Merck, Biogen, BMS, and Novartis. Kevin Bigaut has received lecturing fees and travel grants from Biogen, Celgene-BMS, Novartis, Roche, and Sanofi-Genzyme. Julie Boucher has nothing to disclose. Bertrand Bourre serves on the scientific advisory board and has received funding for travel and honoraria from Alexion, Biogen, BMS, Horizon, Janssen, Merck, Novartis, Sanofi, and Roche. Clemence Boutiere has nothing to disclose. Pierre Branger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, and Sanofi-Genzyme. C. Carra-Dalliere has received travel grants and/or consulting fees from Alexion, Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Jonathan Ciron has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Novartis, Merck, Sanofi, Roche, Celgene-BMS, Alexion, and Horizon Therapeutics. Angelique Da Silva has received personal fees from Daichi and Leopharma. Gilles Defer has received personal fees from Biogen, Bristol-Myers Squibb, Merck Serono, Novartis, Sanofi-Genzyme, and Teva Pharmaceuticals. Sarah Demortière has nothing to disclose. Maxime Guillaume has received honoraria from Novartis, Merck, and Sanofi. Benjamin Hebant has nothing to disclose. Edouard Januel has nothing to disclose. Anne Kerbrat has nothing to disclose. Arnaud Kwiatkowski has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Roche, and Teva. Emmanuelle Leray has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, Merck, Novartis, Roche, and Sanofi-Genzyme. Elisabeth Maillart has received research support from Biogen and personal fees for lectures and serving on advisory boards from Biogen, Janssen, Merck, Novartis, Roche, Sanofi, and Teva. Guillaume Mathey has nothing to disclose. Xavier Moisset has received financial support from Allergan-Abbvie, Biogen, BMS, Grünenthal, Lilly, Lundbeck, Teva, Merck Serono, Novartis, Pfizer, Roche, and Sanofi-Genzyme and non-financial support from SOS Oxygène not related to the submitted work. Alexis Montcuquet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Alexison, Biogen, Merck Serono, Novartis, Sanofi-Genzyme, Roche, and Teva. Nathalie Morel has nothing to disclose. Romain Marignier has received personal fees from Horizon Therapeutics, Alexion, Roche, and UCB; and nonfinancial support from Horizon Therapeutics, Merck, Biogen, and Roche. Chloe Pierret has nothing to disclose. Julie Pique has received travel grants and personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Teva, Biogen, Novartis, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, and Alexion. Julien Poupart has nothing to disclose. Chloe Prunis has nothing to disclose. Eric Thouvenot has received personal fees from Actelion and Teva and grants from Biogen, Merck Serono, Novartis, and Roche. Thomas Roux has received personal compensation for consulting, speaking, or serving on a scientific advisory board from Alexion, Biogen, BMS-Celgene, Merck, Novartis, and Sanofi-Genzyme. Perrine Schmitt has nothing to disclose. Helene Zephir has nothing to disclose. Mikael Cohen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities from Ad Scientiam, Biogen, Merck, Sanofi-Genzyme, Roche, Celgene-BMS, Alexion, and Horizon Therapeutics.

Objective: The radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS., Methods: Patients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age-matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility-based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions., Results: 180 participants (45 RIS, 45 MS, 90 non-MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non-MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non-MS than MS from non-MS (p = 0.837). When a 6-lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis., Interpretation: This study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non-MS, with similar performances to those in MS., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Recent studies in adults suggested that extended-interval dosing of rituximab/ocrelizumab (RTX/OCR) larger than 12 months was safe and could improve safety. This was an observational cohort study of very active pediatric-onset multiple sclerosis (PoMS) (median (range) age, 16 (12-17) years) treated with RTX/OCR with 6 month standard-interval dosing ( n = 9) or early extended-interval dosing ( n = 12, median (range) interval 18 months (12-25)). Within a median (range) follow-up of 31 (12-63) months after RTX/OCR onset, one patient (standard-interval) experienced relapse and no patient showed disability worsening or new T2-weighted lesions. This study suggests that the effectiveness of RTX/OCR is maintained with a median extended-interval dosing of 18 months in patients with very active PoMS., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system., Objective: To determine the time to onset of symptoms consistent with MS., Design, Setting, and Participants: From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144., Interventions: Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred., Main Outcomes: Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs., Results: Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant., Conclusion and Relevance: Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum., Trial Registration: ClinicalTrials.gov Identifier: NCT03122652.

Introduction: The Expanded Disability Status Scale (EDSS) is the gold standard for evaluating clinical disability in multiple sclerosis (MS) in daily practice. However, more precise clinical assessment tools are needed. We assessed a new, automated rating of the neurological examination obtained with a mobile application (Quantified Neurological Examination - QNE)., Method: Consecutive MS patients were assessed for EDSS score and QNE application that calculates, from the description of the examination, a global score and subscores (qFSS) corresponding to the EDSS functional system scores (FSS). Brain MRI was analysed to obtain automatic measures of brain atrophy., Results: We performed 200 examinations and included 78 patients in the MRI analysis. The global QNE score was strongly correlated with the EDSS. qFSS was statistically different according to the corresponding FSS for each function, except for the visual FSS. EDSS was predominantly correlated to the pyramidal function of the lower limbs. QNE score and qFSS had at least equivalent correlation to MRI measures than EDSS, particularly regarding the gray matter and cortical volumes., Discussion: We propose an automated method to rate neurological disability in MS. While QNE strongly correlates with EDSS, it may allow a more precise way to monitor the evolution of disability., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: To evaluate whether the kappa free light chain index (K-index) can predict the occurrence of new T2-weighted MRI lesions (T2L) and clinical events in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS)., Methods: All consecutive patients presenting for the diagnostic workup, including CSF analysis, of clinical and/or MRI suspicion of multiple sclerosis (MS) since May 1, 2018, were evaluated. All patients diagnosed with CIS and RIS with at least 1-year follow-up were included. Clinical events and new T2L were collected during follow-up. The K-index performances in predicting new T2L and a clinical event were evaluated using time-dependent ROC analyses. The time to clinical event or new T2L was estimated using survival analysis according to the binarized K-index using an independent cutoff of 8.9, and the ability of each variable to predict outcomes was compared using the Harrell c-index., Results: One hundred and eighty two patients (146 CIS and 36 RIS, median age 39 [30; 48] y-o, 70% females) were included with a median follow-up of 21 [13, 33] months. One hundred five (58%) patients (85 CIS and 20 RIS) experienced new T2L, and 28 (15%; 21 CIS and 7 RIS) experienced a clinical event. The K-index could predict new T2L over time in CIS (area under the curve [AUC] ranging from 0.86 to 0.96) and in RIS (AUC ranging from 0.84 to 0.54) but also a clinical event in CIS (AUC ranging from 0.75 to 0.87). Compared with oligoclonal bands (OCBs), the K-index had a better sensitivity and a slight lower specificity in predicting new T2L and clinical events in both populations. In the predictive model, the K-index was the variable that best predict new T2L in both CIS and RIS but also clinical events in CIS (c-index ranging from 0.70 to 0.77), better than the other variables, including OCB., Discussion: This study provides evidence that the K-index predicts new T2L in CIS and RIS but also clinical attack in patients with CIS. We suggest adding the K-index in the further MS diagnosis criteria revisions as a dissemination-in-time biomarker., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised., Objectives: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS)., Methods: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients' history of COVID-19 infection., Results: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients., Conclusion: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

Background and Objectives: Exit strategies such as de-escalations have not been evaluated for rituximab in patients with neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that they are associated with disease reactivations and aimed to estimate this risk., Methods: We describe a case series of real-world de-escalations from the French NMOSD registry (NOMADMUS). All patients met the 2015 International Panel for NMO Diagnosis (IPND) diagnostic criteria for NMOSD. A computerized screening of the registry extracted patients with rituximab de-escalations and at least 12 months of subsequent follow-up. We searched for 7 de-escalation regimens: scheduled discontinuations or switches to an oral treatment after single infusion cycles, scheduled discontinuations or switches to an oral treatment after periodic infusions, de-escalations before pregnancies, de-escalations after tolerance issues, and increased infusion intervals. Rituximab discontinuations motivated by inefficacy or for unknown purposes were excluded. The primary outcome was the absolute risk of NMOSD reactivation (one or more relapses) at 12 months. AQP4+ and AQP4- serotypes were analyzed separately., Results: We identified 137 rituximab de-escalations between 2006 and 2019 that corresponded to a predefined group: 13 discontinuations after a single infusion cycle, 6 switches to an oral treatment after a single infusion cycle, 9 discontinuations after periodic infusions, 5 switches to an oral treatment after periodic infusions, 4 de-escalations before pregnancies, 9 de-escalations after tolerance issues, and 91 increased infusion intervals. No group remained relapse-free over the whole de-escalation follow-up (mean: 3.2 years; range: 0.79-9.5), except pregnancies in AQP+ patients. In all groups combined and within 12 months, reactivations occurred after 11/119 de-escalations in patients with AQP4+ NMOSD (9.2%, 95% CI [4.7-15.9]), from 0.69 to 10.0 months, and in 5/18 de-escalations in patients with AQP4- NMOSD (27.8%, 95% CI [9.7-53.5]), from 1.1 to 9.9 months., Discussion: There is a risk of NMOSD reactivation whatever the rituximab de-escalation regimen., Trial Registration Information: Registered on ClinicalTrials.gov: NCT02850705., Classification of Evidence: This study provides Class IV evidence that de-escalation of rituximab increases the probability of disease reactivation., (© 2023 American Academy of Neurology.)

Background: To characterise the response to treatment of inaugural optic neuritis (ON) in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD)., Methods: We searched the French MOGAD database for adults with inaugural ON with a detailed report of acute treatment modalities and measures of high-contrast best-corrected visual acuity (BCVA) at nadir and after 3 months. Predictors of visual outcomes were assessed by multivariable analysis., Results: Among 245 patients with at least one episode of ON, 82 fulfilled all criteria, and data on the peripapillary retinal nerve fibre layer (pRNFL) were available for 44. All patients received methylprednisolone (MP), combined with plasma exchange in 18. After 3 months, 75 of 82 (91%) patients retained full BCVA recovery, and median (range) pRNFL of the affected eye was 72 µm (40-102). Failure to regain 0.0 logarithmic minimum angle of resolution vision (Snellen 20/20) at 3 months was associated with time to first MP treatment ≥10 days (OR 16, 95% CI 1.14 to 213, p=0.01). pRNFL thickness after 3 months was related to better BCVA at nadir and time to first MP treatment <10 days (r2=19%, p=0.004 and r2=11%, p=0.03, respectively)., Conclusions: Time to MP affects functional but also structural visual outcomes of ON in MOGAD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Facial emotion recognition (FER) may be impaired in patients with multiple sclerosis (MS). Nevertheless, the literature is heterogeneous, with studies not highlighting this kind of impairment. Moreover, most studies have not explored differences between MS spectrum disorders (radiologically isolated syndrome (RIS), clinically-isolated syndrome (CIS), relapsing-remitting (RRMS), and progressive (primary - (PPMS) and secondary - (SPMS)). One hypothesis would be that FER impairment results from an alteration of eye-gaze strategies while observing emotional faces. Consequently, a FER deficit would be found in MS patients for whom these observation strategies would be disturbed and more frequent in the progressive forms., Methods: We prospectively enroled 52 patients (10 RIS, 10 CIS, 12RRMS, 10 SPMS, 10 PPMS) and 23 healthy controls (HC) to assess FER using Ekman Faces Test. Eye movements (number and duration of fixations) were recorded with an eye-tracking device., Results: 21% of the MS participants had significant FER impairment. This impairment was observed in all phenotypes. In progressive forms, FER impairment was more frequent, more severe, and associated with modified emotional face observation strategies. MS participants with significant FER impairment had significantly more modification of eye-gaze strategies during observation of expressive faces than MS participants without FER impairment., Conclusion: FER impairment seems to be linked to a deficit of attention orientation in MS. Remediation of eye-gaze strategies during observation of emotional faces could be beneficial, as observed in other neurological diseases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objectives: To evaluate the predictive value of serum neurofilament light chain (sNfL) and CSF NfL (cNfL) in patients with radiologically isolated syndrome (RIS) for evidence of disease activity (EDA) and clinical conversion (CC)., Methods: sNfL and cNfL were measured at RIS diagnosis by single-molecule array (Simoa). The risk of EDA and CC according to sNfL and cNfL was evaluated using the Kaplan-Meier analysis and multivariate Cox regression models including age, spinal cord (SC) or infratentorial lesions, oligoclonal bands, CSF chitinase 3-like protein 1, and CSF white blood cells., Results: Sixty-one patients with RIS were included. At diagnosis, sNfL and cNfL were correlated (Spearman r = 0.78, p < 0.001). During follow-up, 47 patients with RIS showed EDA and 36 patients showed CC (median time 12.6 months, 1-86). When compared with low levels, medium and high cNfL (>260 pg/mL) and sNfL (>5.0 pg/mL) levels were predictive of EDA (log rank, p < 0.01 and p = 0.02, respectively). Medium-high cNfL levels were predictive of CC (log rank, p < 0.01). In Cox regression models, cNfL and sNfL were independent factors of EDA, while SC lesions, cNfL, and sNfL were independent factors of CC., Discussion: cNfL >260 pg/mL and sNfL >5.0 pg/mL at diagnosis are independent predictive factors of EDA and CC in RIS. Although cNfL predicts disease activity better, sNfL is more accessible than cNfL and can be considered when a lumbar puncture is not performed., Classification of Evidence: This study provides Class II evidence that in people with radiologic isolated syndrome (RIS), initial serum and CSF NfL levels are associated with subsequent evidence of disease activity or clinical conversion., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Video-oculography (VOG) could be useful for monitoring neurodegenerative diseases and multiple sclerosis (MS), as a high prevalence of subclinical eye movements abnormalities (EMA) has been previously reported, with a potential prognostic value regarding disease evolution. However, access to VOG is limited in clinical practice., Objective: To evaluate the reliability of VOG recordings performed using eVOG, a mobile application developed on an iPad., Method: Patients with MS or related disease without clinically detectable EMA were enrolled in a cross-sectional study during which two VOG exams (classical VOG and eVOG) were performed on the same day. We examined reflex saccades, antisaccades, smooth pursuit and fixation. The total number of deficits, saccadic latencies and velocities, qualitative smooth pursuit were compared., Results: 30 patients were included. The mean number of EMA per patient on classical VOG was 4.1 and 2.3 on eVOG. We found a statistical association between the number of EMA for each exam (r = 0.66, p < 0.0001). Saccades latencies (r = 0.57, p < 0.0001) and velocities (r = 0.45, p < 0.0001) were also well correlated. Assessing eVOG accuracy, we found a sensitivity ranging from 44% to 100% and a specificity ranging from 71% to 88.9% depending on the considered abnormality., Conclusion: eVOG could be an easily accessible solution to screen MS patients for the presence of EMA. We plan to use eVOG on a larger cohort of patients, in a prospective study to assess the prognostic value of subclinical EMA in MS. We also plan to investigate the use of eVOG in other neurological conditions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Importance: Younger age, oligoclonal bands, and infratentorial and spinal cord lesions are factors associated with an increased 10-year risk of clinical conversion from radiologically isolated syndrome (RIS) to multiple sclerosis (MS). Whether disease-modifying therapy is beneficial for individuals with RIS is currently unknown., Objectives: To evaluate the 2-year risk of a clinical event (onset of clinical symptoms of MS) prospectively, identify factors associated with developing an early clinical event, and simulate the sample size needed for a phase III clinical trial of individuals with RIS meeting 2009 RIS criteria., Design, Setting, and Participants: This cohort study used data on prospectively followed-up individuals with RIS identified at 1 of 26 tertiary centers for MS care in France that collect data for the Observatoire Français de la Sclérose en Plaques database. Participants were aged 10 to 80 years with 2 or more magnetic resonance imaging (MRI) scans after study entry and an index scan after 2000. All diagnoses were validated by an expert group, whose review included a double centralized MRI reading. Data were analyzed from July 2020 to January 2021., Exposure: Diagnosis of RIS., Main Outcomes and Measures: Risk of clinical event and associated covariates at index scan were analyzed among all individuals with RIS. Time to the first clinical event was compared by covariates, and sample size estimates were modeled based on identified risk factors., Results: Among 372 individuals with RIS (mean [SD] age at index MRI scan, 38.6 [12.1] years), 354 individuals were included in the analysis (264 [74.6%] women). A clinical event was identified among 49 patients (13.8%) within 2 years, which was associated with an estimated risk of conversion of 19.2% (95% CI, 14.1%-24.0%). In multivariate analysis, age younger than 37 years (hazard ratio [HR], 4.04 [95% CI, 2.00-8.15]; P < .001), spinal cord lesions (HR, 5.11 [95% CI, 1.99-13.13]; P = .001), and gadolinium-enhancing lesions on index scan (HR, 2.09 [95% CI, 1.13-3.87]; P = .02) were independently associated with an increased risk of conversion to MS. Having 2 factors at the time of the index MRI scan was associated with a risk of 27.9% (95% CI, 13.5%-39.9%) of a seminal event within 2 years, increasing to 90.9% (95% CI, 41.1%-98.6%) for individuals with all 3 factors (3 risk factors vs none: HR, 23.34 [95% CI, 9.08-59.96]; P < .001). Overall, with 80% power to detect an effect size of 60% within 24 months, a total of 160 individuals with RIS were needed assuming an event rate of 20%., Conclusions and Relevance: This study found that age younger than age 37 years, spinal cord involvement, and gadolinium-enhancing lesions on index MRI scan were associated with earlier clinical disease and relevant to the number of enrolled patients needed to detect a potential treatment effect.

Objective: To explore the use of digital biomarkers to distinguish healthy controls (HC) from subjects with a radiologically isolated syndrome (RIS)., Methods: We developed a smartphone application called MS Screen Test (MSST) to explore several dimensions of the neurological exam such as finger tapping speed, agility, hand synchronization, low contrast vision and cognition during a short evaluation. This app was tested on a cohort of healthy volunteers including a subset of subjects who underwent two evaluations on the same day to assess reproducibility. In a second step, the app was tested on a cohort of RIS subjects. Performances of RIS subjects were compared with age and genre-matched HC., Results: HC underwent two consecutive evaluations on MSST. The analysis showed good reproducibility for all measures. Then 21 RIS subjects were compared to 32 matched HC. Compared to HC, we found that RIS subjects had a lower finger tapping speed on the dominant hand (5.6 versus 6.5 taps per second; p = 0.005), a longer inter hand interval during the hand synchronization task (14.4 versus 11.3 ms; p = 0.03) and significantly poorer scores on the low contrast vision and cognition tests., Conclusion: MSST only requires a smartphone to obtain digital biomarkers relative to several dimensions of the neurological examination. Our results highlighted subtle differences between HC and RIS subjects. We plan to evaluate this tool in MS patients, which will allow us to get a much larger sample of subjects, to determine whether digital biomarkers can predict disease course.

Myasthenia gravis can be efficiently treated with rituximab but there is no consensus regarding administration and dose schedules in this indication. No marker has yet been described to predict the clinical relapse of patients. Our objective was to identify the B cell subpopulations predicting clinical relapse in patients suffering from generalized myasthenia gravis and treated with rituximab. Clinical and biological data of 34 patients followed between 2016 and 2019 were prospectively collected every 3 months. Using multiparameter flow cytometry, we assessed the percentage in leucocytes of lymphocytes and several B cell subpopulations measured in residual disease conditions. CD19+ were also measured in non-residual disease conditions. Clinical examinations were performed by neurologists using the Osserman score. Clinical relapse occurred in 14 patients (41%). No patients required ICU or ventilatory assistance. The mean improvement of the Osserman score was 17.18 (3-45) after the first rituximab treatment (p < 0.0001). The mean delay between the first rituximab maintenance cycle and clinical relapse was 386.8 days. At the time of relapse, CD27+ increased (p = 0.0006) with AUC = 0.7654, while CD19+ did not. At a threshold of 0.01%, the sensitivity and specificity of CD19+CD27+ were 75.8% and 72.8%, respectively, and the positive and negative predictive values were 28.0% and 95.6%, respectively. The percentage of memory B cells in whole blood cells can accurately predict clinical relapse in myasthenia gravis patients treated with rituximab. This monitoring allows physicians to tailor rituximab administration and to decrease the number of infusions over time., (© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)

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., (© 2020 American Neurological Association.)

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities., Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity., Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020., Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms., Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes., Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01)., Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Background: The recent 2017 modification have increased the sensitivity of McDonald criteria for MS. Nevertheless, some MS patients with atypical MRI findings have been identified, leading to prolonged delay to diagnosis and high costs to look for alternative diagnoses., Objective: To describe a series of MS patients with atypical MRI presentation., Material and Methods: Patients with atypical MS were identified through a nationwide retrospective study. We established a five groups classification: tumefactive demyelinating lesion (TDL)-onset MS, acute disseminated encephalomyelitis (ADEM)-like MS, cavitary MS and leukodystrophy-like MS. All the patients meeting our radiological criteria for atypical MS were included., Results: A total of 57 patients met the inclusion criteria. 7 cases were classified in the TDL-onset group, 10 in the ADEM-like group, 26 in the cavitary group and 14 in the leukodystrophy-like group. Overall risk of conversion to MS after an isolated TDL was around 30% at five years. Patients in the TDL-onset and ADEM-like groups globally presented an acute onset and a relapsing-remitting evolution. Conversely, patients in the cavitary and leukodystrophy- groups largely evolved with a progressive and severe course., Conclusion: A significant number of MS patients can have a striking atypical presentation and may be misdiagnosed. This preliminary analysis helps to refine the spectrum of atypical MS patients., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: Neuromyelitis optica spectrum disorders (NMOSD) are identified as a spectrum of inflammatory demyelinating disorders involving the brain, spinal cord and optic nerves. These disorders require early diagnosis and highly active immunosuppressive treatment. Rituximab (RTX) has demonstrated efficacy in limiting relapse in NMOSD when using several administration schedules. We questioned if the CD19+ CD27+ memory B cell count was a more reliable marker to monitor RTX administration than the RTX plasma level and CD19+ B cell count., Methods: We analyzed 125 blood samples from 17 NMOSD patients treated with RTX and also measured the level of anti-aquaporine-4 antibodies (anti-AQP-4 Abs), human anti-chimeric antibodies to the murine fragment of RTX (HACA-RTX Abs), and the RTX concentration., Results: The mean follow-up time of the cohort was 7.4 (2-16) years. All patients improved with a mean EDSS going from 4 (1-8.5) to 2.7 (1-5.5). The mean interval between RTX infusions was 9.6 months with identification of prolonged responders. Total CD19+ B cell detection with the routine technique did not correlate to re-emergence of CD19+ CD27+ memory B cells. The RTX residual concentration did not correlate with the CD19+ CD27+ memory B cell count or with anti-RTX antibody production., Conclusion: In contrast to total CD19+ cell, detected with the routine technique, CD19+ CD27+ memory B cells are a reliable marker for biological relapse and allow a decrease in the frequency of infusions.

Progressive solitary sclerosis is characterized by an isolated central nervous system demyelinating lesion arising in the spinal cord and brainstem, responsible for progressive motor impairment. We describe the case of a 40-year-old patient treated for more than 2 years with high doses of biotin (CERENDAY ® ) for progressive symptoms of solitary sclerosis, who presented asymptomatic new T2 white matter lesions on brain magnetic resonance imaging (MRI). As there is no treatment option for solitary sclerosis, high doses of biotin were proposed, but had no impact on the progression of motor deficit. As the brain MRI showed no evidence of T2 lesions during the 10 years before the introduction of biotin, the demonstration of dissemination over time with this treatment raises questions. High doses of biotin have shown efficacy in some patients with spinal progressive MS, but could reveal a latent inflammatory condition.

Cognition and health-related quality of life (HRQoL) are early involved in multiple sclerosis (MS). The aim of QUALICIS study was to monitor cognition and HRQoL prospectively in a cohort of clinically isolated syndrome (CIS) patients starting a treatment with subcutaneous beta-1b interferon as a first disease modifying treatment (DMT), and to assess their correlation with the clinical outcome 6years later. Relapse history, EDSS and yearly standardized brain MRI data were also collected. 37 patients were included. Cognition and HRQoL remained stable over treatment period. At baseline, we found that SDMT was moderately correlated to T2 lesion load (r=-0.47, p=0.04). Baseline SDMT was predictive of HRQoL at year 2 (r=0.53, p=0.02). Regarding 6-year outcome, the most specific predictive factor of favorable outcome was achieving "No Evidence of Disease Activity" (NEDA) status at year 1. In this group, all the patients had a stable EDSS score and none switched to a second line therapy. In the "non-NEDA" group, 44% of patients experienced EDSS worsening and 38.9% switched to a second line therapy. The number of gadolinium enhancing lesions on baseline scan was the only predictive factor of poor outcome in this subgroup of patients (2 vs. 0.13, p=0.03). Our results suggest that NEDA at 1year could be used to predict long term outcome after initiation of DMT in CIS. For non-NEDA patients, monitoring SDMT and brain atrophy could be potentially relevant, but this should be confirmed on a larger sample., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Neuromyelitis optica spectrum disorders (NMOSD) represent a differential diagnosis of multiple sclerosis (MS). Detection of anti-aquaporin-4 antibodies (AQP4-Ab) is the strongest argument to confirm NMOSD. Diagnosing NMOSD is a major concern because specific MS disease modifying drugs can lead to neurological worsening., Objective: To report the case of two natalizumab (NTZ) treated patients who presented a false positive result for AQP4-Ab., Methods: A retrospective analysis of NTZ-treated patients who were tested positive for AQP4-Ab in our MS center., Results: Two patients treated by NTZ presented a false positive result., Conclusions: Clinicians should be aware of potential technical issues in detecting AQP4-Ab in NTZ-treated patients leading to false positive results., (© The Author(s), 2016.)