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Background: Evidence on the impact of dimethyl fumarate (DMF) during pregnancy in women with multiple sclerosis (MS) is limited., Objectives: To investigate disease activity and pregnancy outcomes in a retrospective cohort of women exposed to DMF in early pregnancy., Methods: Women discontinuing DMF after pregnancy confirmation were identified from 29 Italian MS Centers. Disease activity 12 months before conception, during pregnancy, and 12 months postpartum were recorded, exploring reactivation predictors. Pregnancy and fetal outcomes were assessed., Results: The study analyzed 137 pregnancies (12 pregnancy losses, 125 live births) from 137 women (mean age 32.9 ± 4.7 years), discontinuing DMF within a median (interquartile range (IQR)) interval of 4.9 (3.7-5.7) weeks from conception. In live birth pregnancies, annualized relapse rate (ARR) significantly decreased during pregnancy (ARR = 0.07, 95% confidence interval (CI): 0.03-0.14, p = 0.021) compared to pre-conception (ARR = 0.21 (95% CI: 0.14-0.30)) and increased postpartum ((ARR = 0.22 (95% CI: 0.15-0.32), p = 0.006). Median time to first relapse (TTFR) was 3.16 (IQR: 1:87-5.42) months. Higher pre-conception relapse number (hazard ratio (HR) = 2.33, 95% CI: 1.08-5.02) and Expanded Disability Status Scale (EDSS; HR = 1.81, 95% CI: 1.17-2.74) were associated with shorter TTFR, while treatment resumption with longer TTFR (HR = 0.29, 95% CI: 0.11-0.74). Fetal outcomes were unaffected by DMF exposure., Conclusion: DMF discontinuation does not increase relapse risk during pregnancy. Early therapy restart prevents postpartum relapses. Early DMF exposure shows no adverse fetal outcomes., 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: D.L. received travel funding from Biogen, Merck-Serono, Sanofi-Genzyme, Teva, Bristol-Myers Squibb, Mylan, Novartis, Roche, Horizon, Alexion speaking or consultation fees from Sanofi-Genzyme, Merck-Serono, Teva, Biogen, Roche, Novartis, Bristol-Myers Squibb, Bayer-Schering. S.B. received travel funding from Biogen and Bristol-Myers Squibb. F.B. reported receiving teaching honoraria from Novartis and personal fees from Eisai, Biogen, and Chiesi outside the submitted work. M.P.A. has received research grants honoraria as a speaker and member of Advisory Boards from Biogen, Bayer, Novartis, Roche, Teva, Sanofi-Genzyme, Merck, Roche Celgene BMS, Janssen, Horizon. S.B. speaker honoraria and/or travel/congress grant from: Novartis, Merck-Serono, Alexion, BMS, Biogen, Roche, Janssen-Cilag. Research grant from Roche. G.B. received honoraria for speaking or consultation fee from Almirall, Biogen, Merck, Novartis, Sanofi, Teva, Roche. M.B. declares fees from Biogen, Sanofi-Genzyme, Roche, and Novartis. S.B. has been founded for advisory board, academic purposes and speech honoraria by Genzyme, Roche, Biogen, Merck-Serono, Novartis and Almirall. P.C. received honoraria for speaking and/or for consultancy and support for participation to scientific congresses from Almirall, Biogen, Merck-Serono, Novartis, Sanofi-Genzyme, Roche, Teva, Alexion, Celgene BMS, Janssen, Horizon. M.C. received personal compensations for public speaking from Novartis, Sanofi-Genzyme, Teva and consulting fees from Roche and Zambon. D.C. is an Advisory Board member of Almirall, Bayer-Schering, Biogen, GW Pharmaceutical, Merck-Serono, Novartis, Roche, Sanofi-Genzyme and Teva and received honoraria for speaking or consultation fee from Almirall, Bayer-Schering, Biogen, GW Pharmaceuticals, Merck-Serono, Novartis, Roche, Sanofi-Genzyme and Teva. He is also the principal investigator in clinical trials for Bayer-Schering, Biogen, Merck-Serono, Novartis, Roche, Sanofi-Genzyme. E.C. received travel grant, speaker fee and consultancy from Biogen Idec, Teva, Genzyme, Merck-Serono, Novartis, Roche and Admirall. A.C. has served on scientific advisory boards for Merck-Serono, Sanofi-Genzyme, Biogen, Novartis, Almirall. She has received institutional research support from Roche and Biogen. A.C. received speaker honoraria from Biogen, Sanofi-Genzyme, Teva and travel grants from Biogen, Merck, Sanofi-Genzyme, Teva; advisory boards member honoraria from Biogen, Merck, Novartis, Teva. E.D.A. received speaking honoraria from Biogen, Merck-Serono, Novartis, Sanofi-Genzyme, Bayer-Schering. M.D.F. participated on advisory boards and steering committees for and received speaker or writing honoraria, research support and funding for traveling from Alexion, BMS, Bayer, Biogen Idec, Genzyme, Horizon, Merck, Mylan, Novartis, Roche, Siemens Healthineers, Teva and Viatris. R.D. received honoraria as a speaker and member of advisory boards by: Merck-Serono, Roche, Novartis and travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme, Roche, Merck-Serono. R.F. has received consulting fees and honoraria for advisory boards from Biogen Idec, Merck-Serono, Novartis, Roche, and TEVA. E.F. has received travel grants from Biogen, Merck, Sanofi-Genzyme, Novartis, and Roche. M.F. is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Associate Editor of Radiology, and Associate Editor of Neurological Sciences; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and Teva; participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme; he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and Fondazione Italiana di Ricerca per la SLA. M.F. published opinions in a medical journal on other pharmaceuticals and received financial support for travel and meeting attendance from Biogen, Merck, Roche, Sanofi-Genzyme and Novartis. A.G. received honoraria for speaking and travel grants from Merck, Genzyme, Teva, Mylan, Roche and Novartis. F.G. received research funding from Sanofi-Genzyme and Biogen, fees for advisory boards and speaking honoraria from Biogen, Novartis, Sanofi-Genzyme, Merck-Serono and Roche, travel funding from Biogen, Sanofi-Genzyme, Merck-Serono, and Roche. A.I. received consulting fees from Janssen. R.L. received personal compensations for speaking or consultancy from Biogen, BMS, Sanofi, Merck, Novartis, Roche and Alexion. L.L. received travel grant, speaker fee and consultancy from Biogen Idec, Teva, Sanofi-Genzyme, Merck-Serono, Novartis, Roche and Almirall. M.L. has served on advisory boards and/or has received travel grants and/or speaker honoraria from Merck, Biogen, Almirall, Novartis, and Sanofi-Genzyme. G.L. received speaker honoraria and/or consultancy from Biogen, Teva, Genzyme, Merck, Novartis, Almirall, Roche. G.M. received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme, Bristol-Myers Squibb, Horizon, Roche, Merck-Serono. M.M. received compensation for consulting services, speaking activities, and participation in advisory board from Alexion, Almirall, Bayer, Biogen, Bristol-Myers Squibb, Celgene, CSL Behring, Novartis, Roche, Sanofi-Genzyme, Janssen, Merck-Serono, and Viatris; he received research support from Biogen, Merck-Serono, Novartis, and Roche. L.M. received honoraria for speaking activity at scientific meetings and/or advisory boards from Biogen, Merck-Serono, Sanofi-Genzyme, Novartis, Roche, Alexion, Celgene, Almirall. G.N. received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme, Horizon, Roche, Merck-Serono. F.P. reports grants from Biogen, grants from Merck, grants from FISM, grants from Onlus association, grants from University of Catania, personal fees from Almirall, personal fees from Bayer, personal fees from Biogen, personal fees from Merck, personal fees from Roche, personal fees from Sanofi, personal fees from TEVA, outside the submitted work. P.R. received travel expenses or honoraria for speaking or participating to advisory board by: Biogen idec, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi. S.R. has received travel expenses or honoraria for speaking or participating to advisory boardby: Biogen idec, Merck, Sanofi-Genzyme, Novartis, Teva, Roche, Bristol-Myers squibb. G.S. received travel expenses by Roche and Novartis. E.S. received speaker honoraria and/or consultancy from Biogen, Teva, Genzyme, Merck, Novartis, Almirall, and Roche. L.S. received congress grants from Merck-Serono, Biogen and board grants from Norvartis, Merck-Serono. M.P.S. has received consulting fees from Biogen, GeNeuro, MedDay, Merck, Novartis, Roche, Sanofi and Teva. V.T. has received honoraria, travel grants and research grant support from FISM, Italian Ministry of Health, Alexion, Roche, Merck, Biogen, Novartis, Viatris, Bristol-Myers Squibb, Almirall, Horizon, Lundbeck, Sanofi, Janssen. D.V. has received travel grants and honoraria for Advisory Boards from Novartis, Roche, Teva, Sanofi-Genzyme, Merck-Serono, and Almirall. G.A.M. received ravel funding, speaking or consultation fees from Almirall, Bayer-Schering, Biogen, Sanofi-Genzyme, Merck-Serono, Novartis, Teva, Mylan, Bristol Mayers Squibb and research grants from Roche and Biogen. The remaining authors have nothing to disclose.

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach., Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses., Methods: Observational retrospective multi-centers Italian cohort study., Results: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion ( p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU ( p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively)., Conclusions: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment., 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: C. Lapucci has received honoraria for speaking, travel grants, and for participating in the advisory board from Merck, Sanofi, Novartis, Roche, Alexion. J. Frau served on scientific advisory boards for Biogen and Genzyme, and has received honoraria as a speaker from Merck Serono, Genzyme, Biogen, and Teva. E. Cocco reported grants, personal fees, and non-financial support from Biogen and Merck; personal fees and non-financial support from Novartis; grants from Roche; and personal fees from Genzyme. G. Coghe received honoraria for consultancy or speaking from Biogen, Novartis, Sanofi, Genzyme, Serono, Teva, and Almirall. M. Petracca has received travel/meeting expenses from Novartis, Janssen, Roche, and Merck; speaking honoraria from HEALTH&LIFE S.r.l., AIM Education S.r.l., Biogen, Novartis, and FARECOMUNICAZIONE E20; honoraria for consulting services and advisory board participation from Biogen; research grants from Baroni Foundation and the Italian Ministry of University and Research. R. Lanzillo has received honoraria from Biogen, Merck, Novartis, Roche, and Teva. V. Brescia Morra has received research grants from the Italian MS Society and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme, and Teva. C.G. Nicoletti received travel funding from Biogen, Merck Serono, Sanofi-Genzyme, Roche, Teva, Novartis, Bristol Mayer Squibb, Janssen, Almirall and consultation fees from Sanofi, Almirall, Merck- Serono, Roche, Novartis, and Biogen. She is a sub-investigator in clinical trials being conducted for Biogen, Merck Serono, Roche, Biogen, Sanofi, Novartis, Teva, Bristol Mayer Squibb. D. Landi has received travel funding from Biogen, Merck Serono, Sanofi, Teva, Bristol Myers Squibb, Mylan; speaking or consultations fees from Sanofi, Merck Serono, Teva, Biogen, Roche, Novartis, Bristol Myers Squibb, BayerSchering. G. Marfia has received travel funding, speaking or consultation fees from Almirall, Bayer-Schering, Biogen, Sanofi, Merck Serono, Novartis, Teva, Mylan, Bristol Mayers Squibb and research grants from Roche and Biogen. M. Vercellino has received congress grants, speaker fees and advisory board fees from Merck-Serono, Novartis, Roche, Biogen, Sanofi Genzyme. P. Cavalla has received honoraria as speaker or travel grants to attend national and international conferences or consultation for advisory boards from Alexion, Almirall, Bayer Schering, Biogen, Cellgene-BMS, Merck-Serono, Teva, Roche, Novartis, Sanof-Genzyme, and Janssen. A. Bianco has received honoraria for speaking, advisory board/consulting from Biogen, Novartis, Merck Serono, Roche, Sanofi Genzyme. M. Mirabella has received honoraria for speaking, advisory board/consulting from Biogen, Novartis, Merck Serono, Roche, Almirall, Sanofi Genzyme, Janssen, Bristol-Myers Squibb, Viatris, Alexion. He is principal investigator in clinical trials for Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, CSL Behring, Ultragenix, Argenx. V. Torri Clerici acted as an Advisory Board member of Biogen Idec, Novartis, Merck Serono, Roche, Sanofi Genzyme, Almirall, Lundbeck and Bristol Myers Squibb; she received funding for traveling and honoraria for speaking or writing from Novartis, Sanofi Genzyme, Horizon, Merck Serono, Roche, Bristol Myers Squibb, Janssen and Almirall. She received support for research project by Almirall. E. Tomas received funding for work contract from Roche. M.T. Ferrò has received consultancy fees or speaker compensation from Sanofi, Bristol, Biogen Idec, and Novartis. L. Moiola has received honoraria for speaking and for participating in advisory board from Merck, Celgene, Biogen, Sanofi, Novartis, Roche, Alexion. M. Zaffaroni has received advisory board membership, speakers honoraria, travel support, research grants, consulting fees or clinical trial support from Actelion, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Merck, Novartis, Sanofi, Roche, Teva. M. Ronzoni has received travel grants for congresses participation from Biogen, Genzyme, Novartis e Merck. G. Novi has received speaker honoraria from Merck, Novartis, Roche, Alexion. M. Cellerino has received consulting fees from Novartis, Genzyme, Teva and Zambon. A. Uccelli has received grants (to his institution) from FISM, Biogen, Roche, Alexion, and Merck Serono and has participated on a data safety monitoring board or advisory board (to his institution) for BD, Biogen, Iqvia, Sanofi, Roche, Alexion, and Bristol Myers Squibb. M. Inglese received grants from NIH, NMSS, and FISM; received fees for consultation from BMS, Janssen, Roche, Genzyme, Merck, Biogen and Novartis. P. Grossi, A. Nozzolillo, and F. Pinardi have nothing to disclose.

Background: In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with multiple sclerosis (MS), but there are no data about maternal and fetal outcomes., Objectives: In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection., Methods: We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020-2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score-based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders., Results: In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32-3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations., Conclusion: Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes., 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: S.S. has received honoraria or consultancy fees for participating to advisory boards, giving educational lectures and/or travel and registration coverage for attending scientific congresses or symposia from F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck Serono, Novartis, Teva, and Biogen Idec/Gen Pharma. R.K. has received honoraria for giving educational lectures, consultancy fees for participating advisory boards, and travel grants for attending scientific congresses or symposia from Roche, Sanofi-Genzyme, Merck Serono, Novartis, Teva, Biogen Idec/Gen Pharma of Turkey, Abdi İbrahim İlac, Deva, and ARIS. A.S. has received honoraria or consultancy fees for participating to advisory boards, giving educational lectures and/or travel and registration coverage for attending scientific congresses or symposia from F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck Serono, Novartis, Teva, Biogen Idec/Gen Pharma of Turkey, and Abdi İbrahim İlac. E.P. received compensation for travel grants, participation in advisory board and/or speaking activities from Biogen, Merck Serono, Sanofi, Teva, and Novartis and serves on the editorial board of Frontiers in Neurology and Brain Sciences. M.P.A. served on scientific advisory boards for and has received speaker honoraria and research support from Biogen Idec, Merck Serono, Bayer Schering Pharma, and Sanofi Aventis and serves on the editorial board of Multiple Sclerosis Journal and BMC Neurology. M.P.S. received consulting fees from Roche, Biogen, Merck, Novartis, Sanofi, Celgene, Immunic, Geneuro, GSK, and MedDay; received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Roche, Biogen Merck, Novartis, Sanofi, and Celgene; and participated on a Data Safety Monitoring Board or Advisory Board for Roche, Sanofi, Novartis, and Merck. I.S. received consulting fees from Hippocrates Research, NovaNeuro, Sakura Italia, ADL Farmaceutici, and Associazione Commissione Difesa Vista Onlus. C.C. received grants or contracts from Roche, Novartis, Merck Serono, Biogen, and Celgene and received consulting fees from Biogen. L.M. received compensation for consulting services, travel grants, and/or speaking activities from Biogen, Serono, Sanofi, Teva, Roche, and Novartis. E.S. received personal compensation from Almirall, Biogen, Sanofi, Novartis, Roche, Horizon, Alexion, Merck, Mylan, and Teva for traveling and advisory boards. S.D.B. received personal compensation from Alexion, Almirall, Biogen, Merck Novartis, Roche, and Sanofi for traveling and advisory boards. M.B. received honoraria for speaking, advisory board, consulting from Teva, Genzyme, Biogen, Bristol MS, Merck, and Novartis. M.C. received personal compensations from Novartis, Genzyme, and Teva and consulting fees from Zambon. R.F. received honoraria for advisory boards and consulting from Bristol MS, Roche, Merck, and Novartis. P.C. received honoraria as speaker or travel grants to attend national and international conferences or consultation for advisory boards from Alexion, Almirall, Bayer Schering, Biogen, Cellgene-BMS, Janssen, Merck Serono, Teva, Roche, Novartis, Sandoz, and Sanofi-Genzyme. S.T. received travel grants or personal compensations from Biogen, Novartis, Sanofi-Genzyme, Roche, Janssen, Teva, and Almirall. The remaining authors have nothing to report.

Background: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients., Objective: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis., Methods: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022. A control group of 1354 women was extracted from the database of the Multiple Sclerosis and COVID-19 (MuSC-19). Univariate and subsequent logistic regression models were fitted to search for risk factors associated with severe COVID-19 course (at least one outcome among hospitalization, intensive care unit [ICU] admission and death)., Results: In the multivariable analysis, independent predictors of severe COVID-19 were age, body mass index ⩾ 30, treatment with anti-CD20 and recent use of methylprednisolone. Vaccination before infection was a protective factor. Vaccination before infection was a protective factor. Pregnancy was not a risk nor a protective factor for severe COVID-19 course., Conclusion: Our data show no significant increase of severe COVID-19 outcomes in patients with multiple sclerosis who contracted the infection during pregnancy.

Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available., Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test., Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model., Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p  = 0.002)., Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity., Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models., Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse., Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

Background: Cognitive dysfunction affects 40%-65% of multiple sclerosis (MS) patients, most often affecting information processing speed and working memory, mediated by the pre-frontal cortex (PFC)., Objective: Our study aimed to investigate PFC functioning through a task-switching protocol in relapsing-remitting multiple sclerosis (RRMS) patients without cognitive impairment., Methods: A total of 24 RRMS patients and 25 controls were enrolled. Two different tasks were performed in rapid and random succession, so that the task was either changed from one trial to the next one (switch trials) or repeated (repetition trials). Switch trials are usually slower than repetitions, causing a so-called switch cost (SC)., Results: Patients had worse performance than controls only in the switch trials, as indicated by increased SC and reaction times. Moreover, patients showed a reduced ability to reconfigure the task-set for the execution of a new task and to disengage from the previous one., Conclusion: Our results showed a primary deficit in executive control processes involved in the task-switching performance in RRMS patients without cognitive impairment. This deficit may depend on the functional impairment of the PFC, which is essential to adjust behaviour rapidly and flexibly in response to environmental changes, representing one of the most sophisticated human abilities.

Background: Highly common in multiple sclerosis (MS), fatigue severely impacts patients' daily lives. Previous findings of altered connectivity patterns led to the hypothesis that the distortion of functional connections within the brain-muscle circuit plays a crucial pathogenic role., Objective: The objective of this paper is to identify markers sensitive to fatigue in multiple sclerosis., Methods: Structural (magnetic resonance imaging with assessment of thalamic volume and cortical thickness of the primary sensorimotor areas) and functional (cortico-muscular coherence (CMC) from simultaneous electroencephalo- and surface electromyographic recordings during a weak handgrip task) measures were used on 20 mildly disabled MS patients (relapsing-remitting course, Expanded Disability Status Scale score ≤ 2) who were recruited in two fatigue-dependent groups according to the Modified Fatigue Index Scale (MFIS) score., Results: The two groups were similar in terms of demographic, clinical and imaging features, as well as task execution accuracy and weariness. In the absence of any fatigue-dependent brain and muscular oscillatory activity alterations, CMC worked at higher frequencies as fatigue increased, explaining 67% of MFIS variance (p=.002)., Conclusion: Brain-muscle functional connectivity emerged as a sensitive marker of phenomena related to the origin of MS fatigue, impacting central-peripheral communication well before the appearance of any impairment in the communicating nodes.

Background: Gender effects are strong in multiple sclerosis (MS), with male patients showing a worse clinical outcome than female patients. Functional reorganization of neural activity may contribute to limit disability, and possible gender differences in this process may have important clinical implications., Objectives: The aim of this study was to explore gender-related changes in functional connectivity and network efficiency in MS patients. Additionally, we explored the association of functional changes with cognitive function., Methods: Sixty subjects were included in the study, matched for age, education level and intelligence quotient (IQ). Male and female patients were matched for disability, disease duration and white matter lesion load. Two cognitive domains often impaired in MS, i.e. visuospatial memory and information processing speed, were evaluated in all subjects. Functional connectivity between brain regions and network efficiency was explored using resting-state functional magnetic resonance imaging and graph analysis. Differences in cognitive and functional characteristics between groups, and correlations with cognitive performance, were examined., Results: Male patients showed worse performance on cognitive tests than female and male controls, while female patients were cognitively normal. Decreases in functional connectivity and network efficiency, observed in male patients, correlated with reduced visuospatial memory (r = -0.6 and r = -0.5, respectively). In the control group, no cognitive differences were found between genders, despite differences in functional connectivity between healthy men and women., Conclusions: Functional connectivity differences were found in male patients only and were related to impaired visuospatial memory. These results underline the importance of gender in MS and require further investigation in larger and longitudinal studies.