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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.)

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: 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: In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed., Objectives: To establish recommendations on pregnancy in women with NMOSD., Methods: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence., Results: A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments., Conclusion: Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices.

Objective: The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS)., Background: MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues., Methods: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence., Results: A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments., Conclusion: The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices.

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.)

Introduction: Many patients are referred to multiple sclerosis (MS) tertiary centers to manage brain white matter hyperintensities (WMH). Multiple diagnoses can match in such situations, and we lack proper tools to diagnose complex cases., Objective: This study aimed to prospectively analyze and correlate with the final diagnosis, cerebrospinal fluid (CSF) interleukin (IL)-1β, soluble IL-2 receptor (CD25), IL-6, IL-10, and kappa free light chains (KFLC) concentrations in patients presenting with brain WMH., Methods: All patients over 18 years addressed to our MS tertiary center for the diagnostic workup of brain WMH were included from June 1, 2020, to June 1, 2021. Patients were separated into three groups-MS and related disorder (MSARD), other inflammatory neurological disorder (OIND), and non-inflammatory neurological disorder (NIND) groups-according to clinical presentation, MRI characteristics, and biological workup., Results: A total of 176 patients (129 women, mean age 45.8 ± 14.7 years) were included. The diagnosis was MSARD ( n = 88), OIND ( n = 35), and NIND ( n = 53). Median CSF KFLC index and KFLC intrathecal fraction (IF) were higher in MSARD than in the OIND and NIND groups; p < 0.001 for all comparisons. CSF CD25 and IL-6 concentrations were higher in the OIND group than in both the MSARD and NIND groups; p < 0.001 for all comparisons. KFLC index could rule in MSARD when compared to NIND (sensitivity, 0.76; specificity, 0.91) or OIND (sensitivity, 0.73; specificity, 0.76). These results were similar to those with oligoclonal bands (sensitivity, 0.59; specificity, 0.98 compared to NIND; sensitivity, 0.59; specificity, 0.88 compared to OIND). In contrast, elevated CSF CD25 and IL-6 could rule out MSARD when compared to OIND (sensitivity, 0.58 and 0.88; specificity, 0.95 and 0.74, respectively)., Discussion: Our results show that, as OCBs, KFLC biomarkers are helpful tools to rule in MSARD, whereas elevated CSF CD25 and IL-6 rule out MSARD. Interestingly, CSF IL-6 concentration could help identify neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, and central nervous system (CNS) vasculitis. These results need to be confirmed within more extensive and multicentric studies. Still, they sustain that KFLC, CSF CD25, and CSF IL-6 could be reliable biomarkers in brain WMH diagnostic workup for differentiating MSARD from other brain inflammatory MS mimickers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Levraut, Landes, Mondot, Cohen, Bresch, Brglez, Seitz-Polski and Lebrun-Frenay.)

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., (© 2022. The Author(s).)

Background: A previous clinical study showed the high specificity, sensitivity and reliability of MSCopilot, a software medical device designed by Ad Scientiam for the self-assessment of people with Multiple Sclerosis (PwMS), compared to the traditional Multiple Sclerosis Functional Composite (MSFC). We conducted further analyses to assess MSCopilot's performance with respect to the Expanded Disability Status Scale (EDSS)., Methods: The data of 116 PwMS were analysed. We studied the correlations between MSCopilot scores and the EDSS, and their ability to distinguish PwMS with high and low EDSS through a study of the distribution of the digital test scores as well as logistic regression models. The same analyses were performed using the MSFC tests., Results: MSCopilot composite scores were as highly correlated to the EDSS (|r| = 0.65, p < 0.01) as their MSFC counterparts, confirming the known correlation of the MSFC with the EDSS. In a linear regression framework, the Walking digital tests have good explanatory power, especially for PwMS with EDSS > 3.5 (R² adj =0.47). The mean values of each MSCopilot subscore were significantly different between patients with an EDSS > 3.5 and others (p < 0.05), which could not be proved for the MSFC Cognition tests. MSCopilot4 was the best model to predict an EDSS score > 3.5 (AUC = 0.92)., Conclusion: These analyses confirm the reliability of MSCopilot and show interesting correlations with the EDSS (similar results obtained with the MSFC). MSCopilot was able to highlight nuances in the different stages of MS the MSFC could not capture., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

Background: Few studies assessed reliability and inter-rater variability of EDSS and functional parameters (FP) rating., Objective: To evaluate inter-rater variability and errors in EDSS and FP rating in junior (JN) and MS Neurologists (MSN)., Method: Patients with MS were examined by a JN and a MSN on the same day. Each assessor rated FP and EDSS, then used a smartphone app to get an automated calculation for each FP ("smartphone" FP, sFP) and for EDSS ("smartphone" EDSS, sEDSS) from the description of the neurological exam. Inter-rater variability was assessed comparing JN and MSN ratings for each method. Intra-rater variability was assessed comparing traditional and digital rating for a given assessor., Result: 103 patients were included. Perfect agreement between JN and MSN was met for 67% and 70% of patients regarding EDSS and sEDSS. Disagreement that could lead to a significant difference in terms of level of disability occurred in 17% for EDSS and 12% for sEDSS (p=0.07). Regarding intra-rater reliability, we found 38 rating discrepancies for JN and 14 for MSN (p=0.04)., Conclusion: We found a significant inter-rater variability as well as a substantial frequency of rating errors in JN. The use of less subjective, easier-to-rate scales should be encouraged., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS)., Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting MS., Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity., Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group ( p  = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p  = 0.029)., Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing-remitting MS. Our results suggest a superiority of NTZ over FTY.

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: Dalfampridine extended release (DAL) is a broad-spectrum voltage-gated potassium channel blocker that is indicated in multiple sclerosis to improve the nerve conduction of demyelinated axons. Seizures are a known side effect of DAL, which is contraindicated in patients with a history of epilepsy., Objective: Three cases of multiple sclerosis (MS) with de novo convulsive status epilepticus (CSE) probably related to dalfampridine administration are described., Methods: No patients had a history of seizures or renal impairment. Biological tests were normal. A brain magnetic resonance imaging (MRI) showed diffuse cortical and subcortical atrophy without active inflammatory lesions., Results: All three patients presented with CSE that was attributed to DAL and so was discontinued., Conclusion: These case reports illustrate that, aside from seizures, de novo CSE is a potential complication of MS patients treated with DAL.

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.)

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.)

Importance: The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge., Objective: To collect data from patients with MS switching from natalizumab to fingolimod., Design, Setting, and Participants: The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod., Main Outcomes and Measures: Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod., Results: Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05)., Conclusions and Relevance: In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.

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. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to develop evidence-based recommendations on pregnancy management for persons with multiple sclerosis (MS). Background: MS typically affects young women in their childbearing years. Increasing evidence is available to inform questions raised by MS patients and health professionals about pregnancy issues. Methods: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and university databases (January 1975 through June 2021). The RAND/UCLA appropriateness method was developed to synthesise the scientific literature and expert opinions on healthcare topics; it was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. Results: A strong agreement was reached for all 104 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, locoregional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses and disease-modifying treatments. Conclusion: The 2022 recommendations of the French MS society should be helpful to harmonise counselling and treatment practice for pregnancy in persons with MS, allowing for better and individualised choices. [ABSTRACT FROM AUTHOR]

Background: In 2020, the French Multiple Sclerosis (MS) Society (SFSEP) decided to develop a national evidence-based consensus on pregnancy in MS. As neuromyelitis optica spectrum disorders (NMOSD) shares a series of commonalities with MS, but also some significant differences, specific recommendations had to be developed. Objectives: To establish recommendations on pregnancy in women with NMOSD. Methods: The French Group for Recommendations in Multiple Sclerosis (France4MS) reviewed PubMed and universities databases (January 1975 through June 2021). The RAND/UCLA appropriateness method, which was developed to synthesise the scientific literature and expert opinions on health care topics, was used to reach a formal agreement. Fifty-six MS experts worked on the full-text review and initial wording of recommendations. A sub-group of nine NMOSD experts was dedicated to analysing available data on NMOSD. A group of 62 multidisciplinary healthcare specialists validated the final proposal of summarised evidence. Results: A strong agreement was reached for all 66 proposed recommendations. They cover diverse topics, such as pregnancy planning, follow-up during pregnancy and postpartum, delivery routes, loco-regional analgesia or anaesthesia, prevention of postpartum relapses, breastfeeding, vaccinations, reproductive assistance, management of relapses, and disease-modifying treatments. Conclusion: Physicians and patients should be aware of the new and specific evidence-based recommendations of the French MS Society for pregnancy in women with NMOSD. They should help harmonise counselling and treatment practise, allowing for better individualised choices. [ABSTRACT FROM AUTHOR]

Background: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS) Objective: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing–remitting MS Method: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. Results: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group (p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). Conclusion: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing–remitting MS. Our results suggest a superiority of NTZ over FTY. [ABSTRACT FROM AUTHOR]

Objective: We have previously identified male sex, younger age, and the presence of spinal cord lesions as independent factors that increase the 5-year risk for evolution from radiologically isolated syndrome (RIS) to multiple sclerosis. Here, we investigate risk factors for the development of a clinical event using a 10-year, multinational, retrospectively identified RIS dataset.Methods: RIS subjects were identified according to 2009 RIS criteria and followed longitudinally as part of a worldwide cohort study. We analyzed data from 21 individual databases from 5 different countries. Associations between clinical and magnetic resonance imaging (MRI) characteristics and the risk of developing a first clinical event were determined using multivariate Cox regression models.Results: Additional follow-up data were available in 277 of 451 RIS subjects (86% female). The mean age at RIS diagnosis was 37.2 years (range, 11-74 years), with a median clinical follow-up of 6.7 years. The cumulative probability of a first clinical event at 10 years was 51.2%. Age, positive cerebrospinal fluid for oligoclonal bands, infratentorial lesions on MRI, and spinal cord lesions, were baseline independent predictors associated with a subsequent clinical event. The presence of gadolinium-enhanced lesions during follow-up was also associated with the risk of a seminal event. The reason for MRI and gadolinium-enhancing lesions at baseline did not influence the risk of a subsequent clinical event.Interpretation: Approximately half of all individuals with RIS experience a first clinical event within 10 years of the index MRI. The identification of independent predictors of risk for symptom onset may guide education and clinical management of individuals with RIS. ANN NEUROL 2020;88:407-417. [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: Dalfampridine extended release (DAL) is a broad-spectrum voltage-gated potassium channel blocker that is indicated in multiple sclerosis to improve the nerve conduction of demyelinated axons. Seizures are a known side effect of DAL, which is contraindicated in patients with a history of epilepsy. Objective: Three cases of multiple sclerosis (MS) with de novo convulsive status epilepticus (CSE) probably related to dalfampridine administration are described. Methods: No patients had a history of seizures or renal impairment. Biological tests were normal. A brain magnetic resonance imaging (MRI) showed diffuse cortical and subcortical atrophy without active inflammatory lesions. Results: All three patients presented with CSE that was attributed to DAL and so was discontinued. Conclusion: These case reports illustrate that, aside from seizures, de novo CSE is a potential complication of MS patients treated with DAL. [ABSTRACT FROM AUTHOR]

Background: Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far. Objective: To compare CPM to methylprednisolone (MP) in SPMS. Methods: Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area—MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model. Results: Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31–1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14–4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17–0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected. Conclusion: Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability. Trial Registration: Clinicaltrials.gov [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Radiologically isolated syndrome (RIS) is a sub clinical demyelinating neurological disorder and to date no biomarker that triggers the seminal event has been identified. As for multiple sclerosis (MS), disease activity and clinical course are unpredictable. In MS, exploratory studies reported increased IL-17 levels in CSF but results in detecting IL-17 in serum at different stage of the disease are controversial. Objectives We investigate levels of IL-17 in serum and CSF in patients diagnosed at different stages of demyelinating diseases (RIS, CIS, relapsing remitting (RR) or active multiple sclerosis patients:AMS) as a marker of inflammatory condition. Methods 1417 sera has been tested for IL-17A (1177 from active MS, 80 RRMS, 35 RIS, 35 CIS, 10 IIH: idiopathic intracranial hypertension, and 80 controls) and 240 CSF from RIS, CIS, IIH and controls. Results No difference has been found between RIS who early clinically converted and CIS patients who rapidly evolve in McDonald or clinically definite MS, nor active MS. No correlation was found with usual MRI or CSF criteria. Conclusion Our results do not confirm that IL-17 can be considerate as a reliable marker of inflammation in the demyelinating spectrum disorders, either in blood or CSF. [ABSTRACT FROM AUTHOR]

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease.Methods: This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment.Results: Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab.Conclusion: In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding eight cases of patients with a solitary demyelinating lesion in the cervico-medullary junction by S. Lattanzi and colleagues in the 2014 issue.

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]