Search

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.

Background: Epidemiologic studies on coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (pwMS) have focused on the first waves of the pandemic until early 2021., Objectives: We aimed to extend these data from the onset of the pandemic to the global coverage by vaccination in summer 2022., Methods: This retrospective, multicenter observational study analyzed COVISEP registry data on reported COVID-19 cases in pwMS between January 2020 and July 2022. Severe COVID-19 was defined as hospitalization or higher severity., Results: Among 2584 pwMS with confirmed/highly suspected COVID-19, severe infection rates declined from 14.6% preomicron wave to 5.7% during omicron wave ( p  < 0.001). Multivariate analysis identified age (odds ratio (OR) = 1.43, 95% confidence interval (CI) = [1.25-1.64] per 10 years), male sex (OR = 2.01, 95% CI = [1.51-2.67]), obesity (OR = 2.36, 95% CI = [1.52-3.68]), cardiac comorbidities (OR = 2.36, 95% CI = [1.46-3.83]), higher Expanded Disability Status Scale (EDSS) scores (OR = 2.09, 95% CI = [1.43-3.06] for EDSS 3-5.5 and OR = 4.53, 95% CI = [3.04-6.75] for EDSS ⩾6), and anti-CD20 therapies (OR = 2.67, 95% CI = [1.85-3.87]) as risk factors for COVID-19 severity. Vaccinated individuals experienced less severe COVID-19, whether on (risk ratio (RR) = 0.64, 95% CI = [0.60-0.69]) or off (RR = 0.32, 95% CI = [0.30-0.33]) anti-CD20., Discussion: In pwMS, consistent risk factors were anti-CD20 therapies and neurological disability, emerging as vital drivers of COVID-19 severity regardless of wave, period, or vaccination status., 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: L.J. reports no disclosure. E.J. reports no disclosure. P.L. reports no disclosure. E.M. has received research support from Fondation ARSEP and Biogen Idec, travel funding and/or consulting fees from Alexion, Biogen Idec, BMS, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. J.D.S. reports no disclosure. H.Z. has no disclosure related to this manuscript. Unrelated to this manuscript H.Z. received consulting fees from Biogen Idec, Sanofi, Merck, Novartis, Roche, Horizon Therpaeutics, Alexion, BMS, and Grant Research Support from ROCHE. J.P. reports no disclosure. P.K. reports no disclosure. D.B. reports no disclosure. O.H. has received consulting and lecture fees from Bayer Schering, Merck, Teva, Genzyme, Novartis, Almirall, and Biogen Idec, travel grants from Novartis, Teva, Genzyme, Merck Serono, and Biogen Idec, and research support from Roche, Merck, and Novartis. L.G. has received consulting and/or lecture fees and/or travel funding from Novartis, Merck, Sanofi, BMS, and Biogen. C.B. has received consulting honoraria from Alexion, Sanofi, Merck, Biogen, BMS, Novartis, Roche, and Teva. M.T. reports receiving consulting and lecture fees from Merck, Novartis, and Biogen Idec, travel grants from Sanofi, Merck Serono, and Biogen Idec. S.V. has received lecturing fees, travel grants, and research support from Biogen, BMS-Celgene, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. O.C. reports receiving personal fees from Biogen, Roche, Merck, Novartis, Janssen, and Sanofi and nonfinancial support from Roche, Merck, and Novartis outside the submitted work. A.M. reports no disclosure. D.L. reports receiving grants from Roche, Sanofi, the ARSEP Foundation, the EDMUS Foundation, and the National Agency of Research and receiving personal fees from Biogen, Novartis, Alexion, Merck, and MSD outside the submitted work. E.B. has received honoraria and consulting fees from Alexion, Novartis, Sanofi Aventis, Biogen Idec, Genzyme, Merck, Roche, and Teva. C.L-F. reports no disclosure. B.B. serves on scientific advisory board, has received funding for travel and honoraria from Alexion, Biogen, BMS, Janssen, Merck, Novartis, Sanofi, Roche, and Teva. P.B. reports receiving personal fees from Novartis, Biogen, Merck, BMS, Alexion, and Sanofi outside the submitted work. B.S. reports research support from Roche, Sanofi, and Merck and personal fees for lectures or advisory boards from Novartis, Sanofi, Biogen, Janssen, and Merck. P.C. reports receiving personal fees for board participation from Janssen and Novartis and for board participation and travel from Sanofi and Merck outside the submitted work. E.T. reports receiving personal fees from Biogen, BMS, Janssen, Horizon, Merck, Novartis, and Sanofi outside the submitted work. E.M. reports no disclosure. T.M. reports receiving travel grants and fees for advisory boards from Biogen, Roche, Novartis, Sanofi, and Teva outside the submitted work. F.S. reports receiving consulting and/or lecture fees and/or travel funding from Novartis-Pharma, Biogen, Roche, Sanofi, Linde, and LVL. M.Z. reports receiving expert testimony from Alexion and Novartis, and travel grants from Merck, Roche, and Sanofi Aventis France. C.P. reports receiving honoraria and consulting fees from Alexion, Biogen, Merck, Horizon, and Roche outside the submitted work and serving as president of the Francophone Multiple Sclerosis Society from 2021 to 2024. C.L. has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, and research grant from Biogen.

Background: The kappa free light chains index (κ-index) is increasing in importance as a fast, easy, cost-effective, and quantitative biomarker in multiple sclerosis (MS), which can replace cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) detection. In previous studies, controls often included mixed patients with several inflammatory central nervous system disorders. The aim of the present study was to assess the κ-index in patients with serum aquaporin-4 (AQP4)-IgG or myelin-oligodendrocyte-glycoprotein (MOG)-IgG., Methods: We analyzed CSF/serum samples of patients with AQP4-IgG or MOG-Ig and evaluated distinct κ-index cut-offs. We described clinical and magnetic resonance imaging (MRI) features of patients with the highest κ-index values., Results: In 11 patients with AQP4-IgG, median κ-index was 16.8 (range 0.2; 63) and 6/11 (54.5%) had κ-index >12. Among 42 patients with MOG-IgG, 2 had low positive MOG-IgG titers, were ultimately diagnosed with MS, and had a markedly increased κ-index (54.1 and 102.5 respectively). For the remaining 40 MOG-IgG-positive patients the median κ-index was 0.3 (range 0.1; 15.5). Some 6/40 (15%) and 1/40 (2.5%) patients had a κ-index >6 and >12, respectively. None fulfilled MRI dissemination in space and dissemination in time (DIS/DIT) criteria and the final diagnosis was MOG-IgG-associated disease (MOGAD) for these 40 patients. Four of the 40 (10%) MOG-IgG-positive patients had OCB., Conclusion: While a marked increase in κ-index could discriminate MS from MOGAD, a low κ-index threshold could lead to confusion between MS and MOGAD or AQP4 antibody-positive neuromyelitis optica spectrum disorder., (© 2023 European Academy of Neurology.)

Background: Previous cross-sectional studies have reported distinct clinical and radiological features among the different acute optic neuritis (ON) aetiologies. Nevertheless, these reports often included the same number of patients in each group, not taking into account the disparity in frequencies of ON aetiologies in a real-life setting and thus, it remains unclear what are the truly useful features for distinguishing the different ON causes. To determine whether clinical evaluation, ophthalmological assessment including the optical coherence tomography (OCT), CSF analysis, and MRI imaging may help to discriminate the different causes of acute ON in a real-life cohort., Methods: In this prospective monocentric study, adult patients with recent acute ON (<1 month) underwent evaluation at baseline and 1 and 12 months, including, high- and low-contrast visual acuity, visual field assessment and OCT measurements, baseline CSF analysis and MRI., Results: Among 108 patients, 71 (65.7%) had multiple sclerosis (MS), 19 (17.6%) had idiopathic ON, 13 (12.0%) and 5 (4.6%) had myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, at last follow up respectively.At baseline, the distribution of bilateral ON, CSF-restricted oligoclonal bands, optic perineuritis, optic nerve length lesions and positive dissemination in space and dissemination in time criteria on MRI were significantly different between the four groups (p <0.001). No significant difference in visual acuity nor inner retinal layer thickness was found between the different ON aetiologies., Conclusions: In this large prospective study, bilateral visual involvement, CSF and MRI results are the most useful clues in distinguishing the different aetiologies of acute ON, whereas ophthalmological assessments including OCT measurements revealed no significant difference between the aetiologies., Competing Interests: Declaration of Competing Interest No disclosure relevant to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.

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: Natalizumab is a high-efficacy therapy for recurrent multiple sclerosis (RMS) with a four-week administration interval. Controlled trials have shown that extending this interval to six weeks led to better safety without increasing the risk of relapse. We aimed to analyze the safety of extending the natalizumab interdose interval from 4 to 6 weeks in a real-life setting., Methods: This monocentric retrospective self-controlled study included adult patients with RMS treated with natalizumab with a four-week interval between infusions for a minimum of six months, before switching to a six-week interval. The main outcomes were the incidence of MS relapse, new MRI lesions, and MRI activity signs during the two periods, with patients being their own controls., Results: Fifty-seven patients were included in the analysis. The mean (95%CI) annualized relapse rate (AAR) before natalizumab introduction was 1.03 (0.52; 1.55). During the four-week interval dosing period, no patient presented with an MS relapse, and seven (13.5%) patients had new MRI lesions. During the six-week interval dosing period, no relapse was observed and two (3.6%) patients had new MRI lesions., Conclusion: We did not observe more relapses or signs of MRI activity when extending the interval between natalizumab infusions from four to six weeks., Competing Interests: Conflicts of interest LJ, RD, OG, AL, AG, CP: nothing to disclose. MBM received personal compensation for consulting and travel fees from Biogen and Merck. CB received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Biogen, BMS-Celgene, Merck, Novartis, Teva, and Sanofi-Genzyme., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: In patients with multiple sclerosis (MS), factors associated with severe COVID-19 include anti-CD20 therapies and neurologic disability, but it is still unclear whether these 2 variables are independently associated with severe COVID-19 or whether the association depends on MS clinical course., Objective: To assess the association between anti-CD20 therapies and COVID-19 severity in patients with relapsing-remitting MS (RRMS) and progressive MS (PMS)., Design, Setting, and Participants: This multicenter, retrospective cohort study used data from the COVISEP study, which included patients with MS and COVID-19 from February 1, 2020, to June 30, 2022, at 46 French MS expert centers, general hospitals, and private neurology practices. Eligible patients with RRMS were those treated with high-efficacy MS therapy (ie, anti-CD20, fingolimod, or natalizumab), and eligible patients with PMS were those younger than 70 years with an Expanded Disability Status Scale (EDSS) score of 8 or lower. Patients were monitored from COVID-19 symptom onset until recovery or death., Exposures: Current anti-CD20 therapy (ocrelizumab or rituximab)., Main Outcomes and Measures: The main outcome was severe COVID-19 (ie, hospitalization with any mode of oxygenation or death). All analyses were conducted separately in patients with RRMS and PMS using propensity score-weighted logistic regression. Subgroup analyses were performed according to COVID-19 vaccine status, sex, EDSS score, and age., Results: A total of 1400 patients, 971 with RRMS (median age, 39.14 years [IQR, 31.38-46.80 years]; 737 [76.1%] female) and 429 with PMS (median age, 54.21 years [IQR, 48.42-60.14 years]; 250 [58.3%] female) were included in the study. A total of 418 patients with RRMS (43.0%) and 226 with PMS (52.7%) were treated with anti-CD20 therapies. In weighted analysis, 13.4% and 2.9% of patients with RRMS treated and not treated with anti-CD20 had severe COVID-19, respectively, and anti-CD20 treatment was associated with increased risk of severe COVID-19 (odds ratio [OR], 5.20; 95% CI, 2.78-9.71); this association persisted among vaccinated patients (7.0% vs 0.9%; OR, 8.85; 95% CI, 1.26-62.12). Among patients with PMS, 19.0% and 15.5% of patients treated and not treated with anti-CD20 had severe COVID-19, respectively, and there was no association between anti-CD20 treatment and severe COVID-19 (OR, 1.28; 95% CI, 0.76-2.16). In PMS subgroup analysis, anti-CD20 exposure interacted negatively with EDSS score (P = .009 for interaction) and age (P = .03 for interaction); anti-CD20 therapies were associated with risk of severe COVID-19 only in patients with less neurologic disability and younger patients with PMS., Conclusions and Relevance: In this cohort study, risk of severe COVID-19 was higher in patients with PMS than in those with RRMS. Use of anti-CD20 therapies was associated with an increased risk of severe COVID-19 among patients with RRMS. In patients with PMS, there was no association between anti-CD20 therapies and risk of severe COVID-19.

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 and Purpose: This study was undertaken to determine the role of optical coherence tomography (OCT) in predicting the final visual and structural outcome, and to evaluate the correlation between functional eye outcome and retinal changes, in patients with a first episode of optic neuritis (ON)., Methods: In this prospective study, consecutive adult patients with acute ON underwent ophthalmological evaluation at baseline and at 1 and 12 months, including OCT measurements of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell and inner plexiform layer, and inner nuclear layer thicknesses; high- and low-contrast visual acuity; visual field assessment; and baseline brain magnetic resonance imaging. Univariate and multivariate linear regressions were used to assess predictive factors of outcome. Correlations between 12-month visual function and retinal structure were estimated by Spearman coefficients. Two groups of patients were analyzed, with or without multiple sclerosis (MS)., Results: Among 116 patients, 79 (68.1%) had MS, and 37 (31.9%) had ON not related to MS (including 19 idiopathic [i.e., isolated] ON, and 13 and five with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies, respectively). We found no independent predictive factor of visual and retinal outcome. Analysis of the relationship between the visual field test (mean deviation) and pRNFL thickness demonstrated a threshold of 75.4 μm and 66.4 μm, below which the mean deviation was worse, for patients with MS (p = 0.007) and without MS (p &lt; 0.001), respectively., Conclusions: We found that inner retinal layer measurements during the first month are not predictive of final outcome. The critical threshold of axonal integrity, below which visual function is damaged, is different between patients with and without MS., (© 2022 European Academy of Neurology.)

Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry., Case Series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild., Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

Background: The perception of diagnosis announcement, the social support and the coping strategies seem to be determining factors for the quality of life of multiple sclerosis (MS) patients, with possible transcultural variations. This study explores these psychosocial dimensions in Lebanese and French MS patients., Methods: For this cross-sectional multi-center study, 8 questionnaires were used to assess quality of life, family support, coping strategies, mood, fatigue, stress, and hopelessness in MS patients. 7 were translated into Arabic and then back translated into French. These were administered to a group of Lebanese MS patients and compared to an MS sample from France. The data was collected for both populations and analyzed., Results: A total of 107 patients were included, 46 Lebanese and 61 French. The majority of MS patients were young females with a high level of education, relapsing remitting form of MS and a low level of disability. Both populations exhibited comparable quality of life and answers on the questionnaires regarding mood disorders, hopelessness, and perceived stress. However, the French patients had significantly more fatigue. Perceived social support given by family was considered greater in the French group compared to the Lebanese one. Also, maladaptive coping strategies (such as self-distraction, denial, behavioral disengagement, substance use, self-blame, venting) were used more frequently by the French population compared to the Lebanese, and this correlated with higher anxiety scores. Diagnosis communication was overall brief, informative, and satisfying in both populations., Conclusion: This study highlighted transcultural differences between French and Lebanese MS patients mainly in social support and coping strategies., (Copyright © 2022. Published by Elsevier B.V.)

Background: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses., Objective: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV., Methods: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS., Results: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) ( p  = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53-3.30, p = 0.54)., Conclusion: These results suggest that YFV does not worsen the course of RR-MS.

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.

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of 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: Launched in the US in 2012, Choosing Wisely ® is a campaign promoted by the American Board of Internal Medicine (ABIM) Foundation with the goal of improving healthcare effectiveness by avoiding wasteful or unnecessary medical tests, treatments and procedures. It uses concise recommendations produced by national medical societies to start discussions between physicians and patients on the relevance of these services as part of a shared decision-making process. The Multiple Sclerosis Focus Group (Groupe de Reflexion Autour de la Sclérose en Plaques; GRESEP) undertook a pilot study to assess the relevance and feasibility of this approach in the management of multiple sclerosis (MS) in France., Methods: Recommendations were developed using the formal consensus method from the guidelines of the French National Health Authority (HAS). A steering committee selected the themes and drafted concise evidence reviews. An independent rating group then assessed these recommendations for clarity, relevance and feasibility., Results: Seven recommendations were accepted: (1) avoid systematic ordering of multimodal evoked potential studies for diagnosing MS; (2) do not treat MS relapses with low-dose oral corticosteroids; (3) when treating MS relapse with high-dose corticosteroids, the systematic use of the intravenous route is unnecessary if the oral route can be used; (4) systematic hospitalization is not necessary for treating MS relapse with high-dose corticosteroid therapy, particularly if the oral route is used, except for the first treated relapse and the presence of exclusion or non-eligibility criteria; (5) in the absence of clinical signs or symptoms of urinary infection, avoid systematic screening with urine microscopy and culture before the administration of corticosteroid therapy for MS relapse in patients using intermittent self-catheterization; (6) avoid antibiotic treatment of clinically asymptomatic MS patients using intermittent self-catheterization, even if urine microscopy and culture reveal the presence of microorganisms; and (7) avoid introducing symptomatic drug treatment for MS-related fatigue., Conclusion: This pilot study, the first of its kind in France, has demonstrated the relevance and feasibility of adapting the Choosing Wisely ® model to MS by practitioners specializing in the disorder. However, the acceptability of these recommendations by other practitioners in other specialist fields as well as their impact on everyday clinical practices now need to be studied., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Competing Interests: C. Bensa déclare avoir participé à des interventions ponctuelles rémunérées d’expertise scientifique, de conseil ou à des conférences pour les sociétés Biogen Idec, Teva Pharma, Novartis, Genzyme ; et avoir été prise en charge à l’occasion de congrès par les sociétés Biogen Idec, Teva Pharma, Novartis, Genzyme, Merck Serono.

Unlabelled: Following the publication practice guidelines for multiple sclerosis by a group of neurologists (multiple sclerosis study group [GRESEP]), the primary objective of this study was to compare the reality of practice to the guidelines according to the targeted clinical audit (TCA) method. The study was conducted at 17 neurology sites and was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). Two complementary surveys were done on the record keeping and the root causes of the deviations. The percentages of compliance ranged from 8 to 98% for the TCA-DIAG, and from 15 to 99% for the TCA-EVOL, with wide disparity between sites. The audits were able to identify causes of the flaws in traceability or accessibility. At the end of the study, despite its limitations, we think that the sharing of the results from different sites provided interesting approaches for the use of the assessment criteria defined by GRESEP in a complete audit cycle. This study is to our knowledge the first report of an experiment in which guidelines were created, and subsequently followed by the development of assessment criteria and then the performance of targeted clinical audits using them, all by the same participants., Context: Clinical practice guidelines (CPGs) are intended to help practitioners and patients make informed treatment choices, but their integration into actual practice remains problematic. This study was done immediately following the publication of CPGs for multiple sclerosis (MS) by the multiple sclerosis study group [GRESEP]. The primary objective was to generate quality criteria, to test them within the same group, and to analyze the observed deviations., Materials and Methods: The study was conducted in the 17 voluntary departments that had participated in the development of the CPGs. The targeted clinical audit method was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). All the files were evaluated by a clinical research technician using digital format, which ensured thoroughness of the collection. Two complementary surveys were done on the record keeping and the potential causes of the deviations., Results: The percentages of compliance to the criteria ranged from 8 to 98% (out of 240 files) for the TCA-DIAG, and from 15 to 99% (221 files) for the TCA-EVOL, with wide disparity between sites (interquartile distance ranges: TCA-DIAG between 0% and 55%; TCA-EVOL between 0% and 70%). The mean percentage of compliance with all the criteria as measured by the TCA-DIAG was 83.9% for the sites with digital files vs. 76.4% for those with only paper files (P<0.01). For the TCA-EVOL, the difference was not significant. Explanations for the observed deviations were suggested (1 to 9 according to the participants)., Discussion and Conclusion: The quantified results could not be compared to other studies given the unique nature of the experiment. The importance of the traceability of practices in the patient files was discussed and assessed with regard to continuity and safety of care, as well as the medical-legal perspectives. Causes of lack of compliance were suggested (particularly the absence of reminders, the lack of means and/or time). Despite the limitations of the study, we think it is advisable that when a group becomes involved in the development of CPGs that they follow with the development of assessment criteria in order to evaluate the validity as well as their character as intermediate indicators of the quality of practices., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To characterise recurrence of multiple sclerosis (MS) inflammatory activity during the year following natalizumab (NTZ) cessation., Methods: Thirty-two patients with MS were included in a monocentric cohort study. Data were collected prospectively during and after NTZ, with serial clinical and MRI evaluations. The first relapse occurring after interrupting NTZ was the primary outcome measure. The numbers of gadolinium-enhancing lesions before, during and after NTZ treatment, were compared., Results: During the year following NTZ cessation, the cumulative probability of relapses was estimated at 52.9% and an unusually high MRI inflammation was noticed. It was defined by a number of gadolinium-enhancing lesions >5 and exceeding the gadolinium lesions existing before NTZ initiation. Rebound of MS activity after NTZ cessation was characterised by association of relapses and unusual MRI inflammation. Cumulative probability of rebound was estimated at 39% and mostly occurring between 3 months and 9months after interrupting NTZ. Risk of rebound appears related with a higher annualised relapse rate and a lower Expanded Disability Status Scale score before NTZ initiation. Rebound was associated with severe recurring relapses in 9% of the patients., Conclusions: This study identifies rebound after NTZ cessation as an association of relapses and high MRI activity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The question of pregnancy in patients with multiple sclerosis is regularly raised due to the prevalence of the disease in middle age women. The multiple sclerosis think tank (Groupe de Réflexion sur la Sclérose en Plaques [GRESEP]) decided to develop recommendations on this issue, with consideration to both the impact of multiple sclerosis on pregnancy, and that of pregnancy on the disease. As with topics of previous works, the formal expert consensus method was used. The working group was composed of hospital-based and private practice neurologists. The reading group was composed of neurologists, anaesthetists and obstetricians. Each recommendation is presented with the relevant level of consensus., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Several practical questions useful for management of patients with multiple sclerosis remain unanswered in the current scientific literature. Decisions are often made individually, without the support of solid scientific evidence. In order to facilitate concurring practices, we present guidelines concerning useful serum exams for the diagnosis of multiple sclerosis. The methodology used was that of a formal expert consensus. A working group performed a systematic analysis of the literature, taking into account both previously existing recommendations and original articles, and then drafted guideline proposals. These proposals were subjected to the critical review of a rating group. Three written drafts, followed by rating of the guideline proposals culminated in a consensual document, which was submitted for review to a second independent reading group. The final resulting document provided the material for the present article, in which each recommendation is presented with its grade according to the level of proof or its degree of consensus in the absence of scientific proof., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The aim of the Multiple Sclerosis Think Tank (Groupe de réflexion sur la sclérose en plaques [GRESEP]) is to prescribe recommendations following a systematic literature search and using a Rand Corporation and California University (RAND/UCLA) appropriateness derived method, in response to practical questions that are raised in the management of patients with multiple sclerosis (MS). The topics of this working program were chosen because they were not addressed in the French recommendations and because of the few data in the literature that enabled practices to be based on validated data. Following the theme on useful serum testing with suspected multiple sclerosis, the subjects of the present work concern the detection and management of cognitive impairment in the beginning stages of the disease course. Two clinical questions were asked: which complementary exams (besides physical examination and neuropsychological tests) would help in the screening of cognitive impairment at the beginning of the disease? What care management should the person with MS and cognitive impairment be offered (treatments and neurocognitive rehabilitation)? The recommendations are the result of a consensus amongst a working group, a rating group and a reading group comprised of hospital neurologists involved in the management of patients with multiple sclerosis. Each recommendation is presented with the degree of consensus that it was accorded., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The aim of the Multiple Sclerosis Think Tank (Groupe de Réflexion sur la Sclérose en Plaques [GRESEP]), composed of hospital neurologists involved in the management of patients with multiple sclerosis, is to provide recommendations in response to clinical questions that are raised when managing these patients. After work done on the themes of useful serum testing with suspected multiple sclerosis, detection and management of cognitive disorders early in the course of the disease, and definition and early management of the disease, GRESEP wanted to develop recommendations on the management of multiple sclerosis (MS) relapse. Following a systematic analysis of the literature, the procedure of formal expert consensus enabled consensual recommendations among a working group, a rating group and a reading group to be written. Each recommendation is presented with its grade or the degree of consensus that it was accorded., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The aim of the Multiple Sclerosis Think Tank (Groupe de Réflexion sur la Sclérose en Plaques: GRESEP), composed of hospital neurologists involved in the management of patients with multiple sclerosis, is to provide recommendations in response to clinical questions that are raised when managing these patients. After work done on the themes on useful serum testing with suspected multiple sclerosis, as well as the detection and management of cognitive disorders early in the course of the disease, the subject of the present work is the early definition and early treatment of the disease. Following a systematic literature review, a RAND/UCLA appropriateness-derived method enabled consensual recommendations among a working group, a rating group and a reading group to be developed and formulated. Each recommendation is presented with the degree of consensus that it was accorded., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Since commercialisation of the first immunomodulatory drug (IMD) for multiple sclerosis (subcutaneous interferon beta-1b) in 1995, three new IMD have been on the market: two interferons (intramuscular interferon beta-1a and subcutaneous interferon beta-1a) and glatiramer acetate. These four immunomodulatory drugs have a similar efficiency: they reduce by about 30% the relapse rate of treated patients compared to untreated patients. Their effect on disability is moderate mainly due to the reduced relapse rate. Lately, in 2002, mitoxantrone was approved for aggressive relapsing-remitting MS and in 2007 the first monoclonal antibody (natalizumab) was approved for active relapsing-remitting MS., (Copyright (c) 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: Subclinical demyelinating lesions may occur in the brains of asymptomatic individuals., Objective: To describe the clinical and magnetic resonance imaging (MRI) follow-up of patients with subclinical demyelinating lesions that fulfill the Barkhof/Tintoré criteria., Design: Prospective study., Setting: University-affiliated teaching hospitals., Patients: Fifty-three women and 17 men with subclinical demyelinating lesions (mean age, 35.63 years)., Main Outcome Measures: Cerebrospinal fluid, MRI, and visual evoked potential measurements., Methods: All patients underwent their first brain MRI for various medical problems that were not suggestive of multiple sclerosis (MS). The patients' physicians proposed that they undergo paraclinical studies (blood, cerebrospinal fluid, and visual evoked potential analysis) and follow-up with MRI., Results: Twenty-three patients (33%) had clinical conversion: 6 to optic neuritis, 6 to myelitis, 5 to brainstem symptoms, 4 to sensitive symptoms, 1 to cerebellar symptoms, and 1 to cognitive deterioration. The mean time between the first brain MRI and the first clinically isolated syndrome was 2.3 years (range, 0.8-5.0 years). Twelve patients had been treated with immunomodulators after a clinically isolated syndrome. Examination of pejorative markers for clinical conversion showed that sex, number of T2 lesions, presence of oligoclonal bands, and IgG index were not statistically different in patients with MS determined by MRI compared with clinically definite MS. Visual evoked potential abnormalities, young age, and gadolinium enhancement on follow-up MRI were more frequent in clinically definite MS than in MS determined by MRI., Conclusions: In this cohort, we determined the rate of clinical conversion (33%) during a mean follow-up of 5.2 years. To our knowledge, this is the first clinically isolated syndrome cohort with preclinical follow-up. Early treatment of these patients with MS determined by MRI should be discussed.

The concept of preclinical multiple sclerosis is now well recognised, and a diagnosis of silent brain T2 lesions is frequent because of the ease of performing MRI. Nevertheless, patients with incidental brain MRI fulfilling Barkhof- Tintoré criteria are more rare. We report a descriptive retrospective study of clinical and 5 year MRI follow-up in patients with subclinical demyelinating lesions fulfilling MRI Barkhof-Tintoré criteria with a normal neurological examination. 30 patients were identified and the first brain MRI was performed for various medical events: headaches (n = 14), migraine with (n = 2) or without (n = 4) aura, craniocerebral trauma (n = 3), depression (n = 3), dysmenorrhoea (n = 2), epilepsy (n = 1) and cognitive changes (n = 1). Mean time for the second brain MRI was 6 months (range 3-30). 23 patients had temporospatial dissemination (eight with gadolinium enhancement). 11 patients had clinical conversion: optic neuritis (n = 5), brainstem (n = 3), sensitive symptoms (n = 2) and cognitive deterioration (n = 1). Eight (72%) already had criteria of dissemination to space and time before the clinical event. Mean time between the first brain MRI and clinically isolated syndrome (CIS) was 2.3 years. To our knowledge, this is the first cohort of CIS with preclinical follow-up. Early treatment should be discussed in view of the predictive value on conversion of the MRI burden of the disease.

In Multiple Sclerosis (MS), one of the most frequent neurological diseases in young adults, cognitive dysfunctions have been under considered whereas their evolution may produce a fronto-sous-cortical deterioration and more than half of the MS patients present such dysfunctions. Nevertheless sensory evoked-potentials are classically used in this disease, event-related potentials (ERP) are not included in the clinical exploration of MS. Two studies are presented aimed at further tracking the usefulness of ERP for detecting early cognitive dysfunctions in MS. All of the patients presented a relapsing remitting MS for less than 5 years with a moderate physical handicap and complained from their memory. They performed a neuropsychological set and ERP were elicited using the oddball paradigm in both modalities, visual and auditory. In the first study, 10 patients without cognitive dysfunction at the neuropsychological evaluation and 10 patients with an attention deficit participated with 10 age-matched controls. In the second study, 10 patients with memory impairment at the neuropsychological evaluation and 10 age-matched controls were included. Our data argue for an earlier modification of ERP parameters in the visual modality than in the auditory one, even before the modification of cognitive scores. In both studies, P300 parameters were correlated to neuropsychological performances (and especially to the attention examination in the first study and to memory tests in the second study) in both modalities. Taking into account the clinical usefulness of ERPs, it is nowadays important to include this electrophysiological method in evaluation and follow-up of MS, and not only using the auditory modality but also the visual presentation in order to detect earlier cognitive dysfunctions even before modification of neuropsychological performances.

Introduction: Magnetic resonance imaging (MRI) has transformed management of patients with multiple sclerosis. The exact contribution of brain MRI remains a subject of debate, but it is generally considered to provide a more specific and more sensitive outcome measure for monitoring purposes and for testing new therapies. The choice of MRI techniques, and measurement reproducibility for multiple sclerosis brain lesions are not defined with precision for routine practice. There are many sources of error when comparing successive images which can be overcome to some extent with repositioning and image processing techniques., Methods: We evaluated the impact of image repositioning on treatment decision-making for twelve relapsing remitting patients. Brain MRIs were performed every three months for a one-year period. Two neurologists interpreted the non-repositioned and repositioned images giving their analysis of changes in the lesions visualized on the T2 sequences and their therapeutic decisions., Results: For the first neurologist, analysis of the non-repositioned images yielded six patients whose lesions had worsened while for the repositioned images there were only three. For the second neurologist, four patients had more lesions with the non-repositioned images and only three with repositioning. The subjective interpretations were the same for the two neurologists when they used repositioned images., Conclusions: Comparison by two neurologists of non-repositioned and repositioned MRI, with no other image processing, affected the analysis and in certain cases propositions for treatment.

Background and purpose New criteria for the diagnosis of multiple sclerosis ( MS) and discovery of myelin oligodendrocyte glycoprotein ( MOG) or aquaporin-4 ( AQP4) antibodies (Abs) have changed the management of optic neuritis ( ON). Our aim was to specify, in view of these recent advances, the etiologies of acute demyelinating ON for consecutive patients. Methods Retrospective database analysis was undertaken of consecutive adult patients with acute ON admitted from 1 December 2014 to 31 January 2016. Diagnosis of MS was made according to the 2010 McDonald criteria. Patients with Abs to AQP4 or MOG were classified as ON- AQP4 and ON- MOG, respectively. Patients who did not fulfill the diagnostic criteria and were negative for AQP4 and MOG Ab tests were classified as having idiopathic ON. Results Of 110 patients assessed, 78 had ON related to MS (70.9%). All patients without MS were tested for AQP4 and MOG Abs: 11 had MOG Ab (10%), 5 had AQP4 Ab (4.5%) and 16 were considered as having idiopathic ON (14.5%). Presence of intrathecal IgG oligoclonal bands was strongly associated with MS (mean, 88.4% vs. 34.4% in patients without MS; after Bonferroni correction, P < 0.0001). Conclusions Optic neuritis related to MOG Ab was the second cause identified of demyelinating ON in our center. Idiopathic ON was as frequent as both ON- AQP4 and ON- MOG combined. [ABSTRACT FROM AUTHOR]

Abstract: Since commercialisation of the first immunomodulatory drug (IMD) for multiple sclerosis (subcutaneous interféron beta-1b) in 1995, three new IMD have been on the market: two interferons (intramuscular interferon beta-1a and subcutaneous interferon beta-1a) and glatiramer acetate. These four immunomodulatory drugs have a similar efficiency: they reduce by about 30% the relapse rate of treated patients compared to untreated patients. Their effect on disability is moderate mainly due to the reduced relapse rate. Lately, in 2002, mitoxantrone was approved for aggressive relapsing-remitting MS and in 2007 the first monoclonal antibody (natalizumab) was approved for active relapsing-remitting MS. [ABSTRACT FROM AUTHOR]