Multiple sclerosis (Houndmills, Basingstoke, England)最新文献

{"title":"Preventing frailty in multiple sclerosis is a realistic goal: No.","authors":"Antonio Scalfari, Alessia Bianchi","doi":"10.1177/13524585261466107","DOIUrl":"10.1177/13524585261466107","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1248-1250"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphocyte count polygenicity underlies dimethyl fumarate-associated lymphopenia in multiple sclerosis.","authors":"Kaarina Kowalec, Ali Manouchehrinia, Elaine Kingwell, Robert Carruthers, Ruth Ann Marrie, Charity Evans, Dalia Rotstein, Annie J Kuan, Wenzhuo Luo, Daniel Luo, Brianne Desrochers, Vilija G Jokubaitis, Jeannette Lechner-Scott, Vicki E Maltby, Kira Groen, Galen Eb Wright, Britt I Drögemöller, Sasha Bernatsky, Michael C Levin, Katherine Knox, Abdullah Al Maruf, Michael Zhong, Lars Alfredsson, Jan Hillert, Ingrid Kockum, Tomas Olsson, Pernilla Stridh, Klementy Shchetynsky, Kristy Dever, Julie MacIsaac, Michael S Kobor, Helen Tremlett","doi":"10.1177/13524585261471335","DOIUrl":"10.1177/13524585261471335","url":null,"abstract":"<p><strong>Purpose: </strong>One in 20 people using dimethyl fumarate (DMF), a commonly used disease-modifying therapy for multiple sclerosis (MS), develops severe lymphopenia. We aimed to identify genetic variation associated with DMF-related lymphopenia.</p><p><strong>Methods: </strong>Using a case-control design, we included cases that had either grade 2 (absolute lymphocyte count <0.8 × 10⁹/L) or 3 (<0.5 × 10⁹/L) lymphopenia during DMF. Controls had normal lymphocyte counts and ⩾1 year of DMF exposure. We generated a polygenic score for lymphocyte counts and evaluated its ability to predict DMF-associated lymphopenia in two cohorts, with adjustment for covariates. We also conducted a genome-wide association study (GWAS) and gene-based analyses.</p><p><strong>Findings: </strong>The discovery cohort comprised 238 PwMS of European genetic ancestry from Canada/Australia (<i>n</i> = 72 grade 2 cases, 34 grade 3 cases), and the replication cohort comprised 156 PwMS from Sweden (<i>n</i> = 34 grade 2, 14 grade 3). A higher polygenic score for lymphocyte counts predicted reduced risk of grade 2 lymphopenia (hazard ratio = 0.43, 95% confidence interval: 0.25-0.73). The GWAS identified one locus associated with the minimum lymphocyte count during DMF (rs17087205, beta = -0.63, SE = 0.11, <i>p</i> = 3.89e-8) but did not replicate (beta = -0.04, <i>p</i> = 0.47).</p><p><strong>Conclusion: </strong>Common polygenic variation of lymphocyte counts was significantly associated with moderate lymphopenia during DMF treatment.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1292-1301"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-dependent divergence in infection risks among patients with multiple sclerosis treated with fumarates versus anti-CD20 monoclonal antibodies.","authors":"Kyle Smoot, Erin E Longbrake, Mirla Avila, Sarah F Wesley, Afif Hentati, William Meador, John Scagnelli, Lynsey L Lakin, Mark Gudesblatt, Boyang Bian, Jason P Mendoza, Nicholas Belviso, James B Lewin, Sai L Shankar, Ahmed Z Obeidat","doi":"10.1177/13524585261475232","DOIUrl":"10.1177/13524585261475232","url":null,"abstract":"<p><strong>Background: </strong>People with multiple sclerosis (pwMS) treated with anti-CD20 monoclonal antibodies have an elevated infection risk, yet long-term comparative data with oral fumarates are limited.</p><p><strong>Objective: </strong>To compare infection incidence, healthcare resource utilization, and relapse outcomes among pwMS receiving fumarate or anti-CD20 therapy for ⩾2 years.</p><p><strong>Methods: </strong>This retrospective propensity-matched (1:2) analysis used US Komodo Health claims (1 January 2016-31 May 2022) for pwMS aged 18-64 years with ⩾2 years of continuous follow-up. Outcomes were assessed using Poisson generalized linear models.</p><p><strong>Results: </strong>A total of 1956 pwMS were matched (fumarates: <i>n</i> = 652; anti-CD20s: <i>n</i> = 1304), with mean follow-up ~3 years. By year 2, the fumarates group had a lower infection rate than anti-CD20s (rate ratio: 0.84; 95% CI: 0.73-0.97; <i>p</i> = 0.016), but the most substantial difference was observed in years 4+, where fumarate-treated patients had a 30% reduction versus anti-CD20s (rate ratio: 0.70; 95% CI: 0.52-0.95; <i>p</i> = 0.021).</p><p><strong>Conclusions: </strong>Fumarate therapy was associated with a lower infection risk versus anti-CD20s. The infection rate in the fumarates group remained relatively stable over time, but it progressively increased in the anti-CD20 group, with the most prominent differences observed at year 4 and beyond.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1302-1314"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gynecologic complications of disease-modifying therapy in women with multiple sclerosis.","authors":"Alexandra Balshi, John P Dempsey, Yanli Zhang-James, Riley Bove","doi":"10.1177/13524585261475100","DOIUrl":"10.1177/13524585261475100","url":null,"abstract":"<p><strong>Background/objectives: </strong>The long-term implications of multiple sclerosis (MS) disease-modifying therapies (DMTs) on gynecologic health remain understudied. We leverage a multicenter database to evaluate whether DMTs are associated with such complications.</p><p><strong>Methods: </strong>We propensity-score 1:1 matched women with MS on (1) any versus no or (2) moderate- to high- (vs low-) immunosuppressive DMT by age, marital status, race, ethnicity, tobacco use, body mass index, human papilloma virus (HPV) vaccination, and gynecologic examinations/screenings. We then compared matched cohorts with risk ratios (RRs) and 95% confidence intervals (CIs).</p><p><strong>Results: </strong>After matching, we analyzed 115,522 women with MS. The DMT (vs no DMT) group had increased risks of HPV positivity (RR: 1.52, 95% CI: 1.35-172), cervical dysplasia (RR: 1.40, 95% CI: 1.31-1.49), cervical cancer (RR: 1.23, 95% CI: 1.03-1.46), cervicitis (RR: 1.25, 95% CI: 1.10-1.41), herpes simplex virus positivity (RR: 1.29, 95% CI: 1.14-1.45), vulvovaginitis (RR: 1.30, 95% CI: 1.23-1.37), and Bartholin cysts/abscesses (RR: 1.37, 95% CI: 1.07-1.76). Moderate- to high- (vs low-) immunosuppressive.</p><p><strong>Discussion: </strong>MS DMTs, especially more immunosuppressive ones, are associated with increased risks of several gynecologic complications. Clinicians should recognize these potential sequelae of DMTs and integrate gynecological counseling/screening into MS care.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1315-1322"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should autologous HSCT be a first-line option in highly active MS? YES.","authors":"Alice Mariottini, Paolo A Muraro","doi":"10.1177/13524585261439669","DOIUrl":"10.1177/13524585261439669","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1139-1141"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing frailty in multiple sclerosis is a realistic goal: Commentary.","authors":"Lorena Lorefice, Robert Zivadinov","doi":"10.1177/13524585261466101","DOIUrl":"10.1177/13524585261466101","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1250-1251"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventing frailty in multiple sclerosis is a realistic goal: Yes.","authors":"Tobia Zanotto, Jacob J Sosnoff","doi":"10.1177/13524585261466113","DOIUrl":"10.1177/13524585261466113","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1246-1248"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ofatumumab and enteroviral encephalitis: a severe infectious complication as a class effect with anti-CD20 therapies.","authors":"Dalia L Rotstein, Sheliza Halani, Peter Vadas, James J Marriott","doi":"10.1177/13524585261444606","DOIUrl":"10.1177/13524585261444606","url":null,"abstract":"<p><strong>Background: </strong>Enteroviral encephalitis is a rare but potentially devastating infectious complication described under the anti-CD20 therapies rituximab and ocrelizumab.</p><p><strong>Case: </strong>A 37-year-old woman with multiple sclerosis (MS) on treatment with ofatumumab developed fever, confusion, seizures, and decreased level of consciousness. Magnetic resonance imaging (MRI) revealed bilateral, non-enhancing thalamic T2 hyperintensities, and cerebrospinal fluid showed pleocytosis with positive polymerase chain reaction (PCR) for enterovirus. The patient was treated with intravenous immunoglobulin and supportive care, and then pocapavir was given for ongoing neurologic deficits. She recovered over 6 weeks but continued to demonstrate neuropsychiatric symptoms.</p><p><strong>Conclusion: </strong>Enteroviral encephalitis is associated with anti-CD20 therapies for MS as a class effect including ofatumumab.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1339-1342"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling the long-term risk of severe adverse events in a cohort of multiple sclerosis patients treated with different treatment sequences: Results from the Italian Multiple Sclerosis and Related Disorders Registry (I-MS&RD) (ProSA study).","authors":"Damiano Paolicelli, Giuseppe Lucisano, Alessia Manni, Pietro Iaffaldano, Marta Simone, Antonio Iaffaldano, Tommaso Guerra, Vincenzo Mangialardi, Francesco Patti, Eleonora Cocco, Giovanna De Luca, Pietro Annovazzi, Paolo Ragonese, Carlo Pozzilli, Matilde Inglese, Paola Perini, Claudio Gasperini, Carla Tortorella, Girolama Alessandra Marfia, Diana Ferraro, Giacomo Lus, Marika Vianello, Maria Assunta Rocca, Antonella Conte, Silvia Romano, Vincenzo Brescia Morra, Alessandra Lugaresi, Alessia Di Sapio, Clara Grazia Chisari, Raffaella Cerqua, Umberto Aguglia, Ilaria Pesci, Carlo Avolio, Emanuele D'Amico, Roberto Bergamaschi, Rocco Totaro, Marco Rovaris, Sebastiano Crisafulli, Massimiliano Mirabella, Paola Cavalla, Roberta Fantozzi, Antonio Gallo, Maria Pia Amato, Massimo Filippi, Maria Trojano","doi":"10.1177/13524585261457317","DOIUrl":"10.1177/13524585261457317","url":null,"abstract":"<p><strong>Background: </strong>In multiple sclerosis (MS), real-world evidence supports early intensive treatment (EIT) with high-efficacy therapies (HET) over escalation (ESC), although comparative data on long-term safety across sequences remain limited.</p><p><strong>Objective: </strong>To compare the incidence of infections and neoplasms in patients treated with different treatment sequences.</p><p><strong>Methods: </strong>Data were extracted from the Italian MS and Related Disorders Register. DMTs were classified as moderate-efficacy treatment (MET), continuous HET (C-HET) or pulsed HET (P-HET). Six therapeutic sequences were reconstructed: MET-only, C-HET-only, P-HET-only, MET→C-HET, MET→P-HET and P-HET→MET. Incidence rates (IRs; per 1000 person-years) and incidence rate ratios (IRRs) were estimated using multivariable Poisson regression, adjusting for age, sex, Expanded Disability Status Scale (EDSS), disease duration, MS phenotype and prior relapse activity.</p><p><strong>Results: </strong>A total of 37,375 patients were included in the analysis, with a median duration of treatment exposure of 8.8 years. Infection risk was significantly higher with C-HET-only (IR, 24.82; IRR, 3.12), P-HET-only (IR, 13.43; IRR, 1.69), MET→C-HET (IR, 10.46; IRR, 1.32) and MET→P-HET (IR, 12.30; IRR, 1.55) versus MET-only (IR, 7.94), while P-HET→MET showed no significant difference from MET-only (IR, 7.67; IRR, 0.97). Regarding neoplasm incidence, P-HET-only showed the lowest rates (IR, 0.18; IRR, 0.24), whereas it was significantly higher in C-HET-only (IR, 1.33; IRR, 1.79) and MET→C-HET (IR, 1.01; IRR, 1.36) versus MET-only (IR, 0.74).</p><p><strong>Conclusions: </strong>This is the first real-world study to compare the safety of different sequences in a national registry. ESC strategies did not confer a long-term safety advantage over EIT. Among HET regimens, C-HET was associated with the greatest risk of both serious infections and neoplasms, whereas P-HET showed the lowest neoplasm incidence.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1278-1291"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequent early cognitive impairment in both pediatric MS and MOGAD.","authors":"Michiel Simon Jan Buijze, Sandy Molenaar, Rosa Verkerk, Maud Alida Quist, Willemijn Marije Carolien van der Vlugt, Rinze Frederik Neuteboom","doi":"10.1177/13524585261465586","DOIUrl":"10.1177/13524585261465586","url":null,"abstract":"<p><strong>Background: </strong>Studies on early cognitive impairment (CI) in pediatric multiple sclerosis (MS) are heterogeneous and data on pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are scarce.</p><p><strong>Objectives: </strong>To evaluate early cognitive dysfunction in both diseases and delineate disease-specific neurocognitive profiles.</p><p><strong>Methods: </strong>A cross-sectional study of children with MS and MOGAD assessed neurocognition within 2 years after disease onset using a comprehensive test battery. Test results were converted to <i>Z</i>-scores. CI was defined as <i>Z</i>-scores below -1.5 in ⩾2 domains. Children were compared by CI status and domain deficits quantified with composite <i>Z</i>-scores.</p><p><strong>Results: </strong>Sixty-seven participants were analyzed (MS <i>n</i> = 36, MOGAD <i>n</i> = 31). Despite normal full-scale intelligence quotient, 47% of MS children and 43% of MOGAD children (acute disseminated encephalomyelitis excluded) met criteria for CI. Domain-specific impairments were prominent in complex attention, with significantly reduced composite <i>Z</i>-scores (MS: -1.24, <i>p</i> < 0.001; MOGAD: -1.12, <i>p</i> = 0.019). MS children additionally showed lower scores on tasks of visuospatial processing and visual memory. Only fatigue was significantly associated with the presence of CI (PedsQL fatigue <i>Z</i>-score: -2.61 vs -0.75, <i>p</i> = 0.005).</p><p><strong>Conclusion: </strong>In both pediatric MS and MOGAD, early CI is prevalent with difficulties in complex attention. Visuospatial cognition appears to be an additional vulnerable area for children with MS.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1168-1181"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}