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

{"title":"Neuromyelitis optica spectrum disorder associated with Kabuki syndrome: First reported case and immunopathogenic considerations.","authors":"Marta Molina-Haro, José María Barrios-López, María Del Carmen Barrera-Aguilera","doi":"10.1177/13524585261490261","DOIUrl":"https://doi.org/10.1177/13524585261490261","url":null,"abstract":"<p><p>Kabuki syndrome, caused by <i>KMT2D</i> or <i>KDM6A</i> mutations, is a multisystem disorder with immune dysregulation. Its association with aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder has not been reported. A 17-year-old male with autoimmune hypothyroidism presented with acute visual loss and was diagnosed with AQP4-IgG-positive optic neuritis. He received corticosteroids, plasma exchange, and rituximab, achieving full recovery and remaining relapse-free during follow-up. Genetic testing showed a likely pathogenic <i>KMT2D</i> variant. This case documents the first association between these conditions, where immune dysregulation, including <i>FOXP3</i>-dependent regulatory T-cell dysfunction and Th17-skewed inflammation, suggests a mechanistic link with implications for diagnosis and management.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"13524585261490261"},"PeriodicalIF":5.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140402","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":"How patients with neuromyelitis optica spectrum disease accumulate disability.","authors":"Sifat Sharmin, Izanne Roos, Pakeeran Siriratnam, Serkan Ozakbas, Dana Horáková, Eva Kubala Havrdova, Petra Nytrová, Recai Turkoglu, Francesco Patti, Bassem Yamout, Samia J Khoury, Abdullah Al-Asmi, Guy Laureys, Raed Alroughani, Jeannette Lechner-Scott, Cavit Boz, Ayse Altintas, Aysun Soysal, Sara Eichau, Anneke van der Walt, Vilija Jokubaitis, Helmut Butzkueven, Mastura Monif, Tomas Kalincik","doi":"10.1177/13524585261489039","DOIUrl":"https://doi.org/10.1177/13524585261489039","url":null,"abstract":"<p><strong>Background: </strong>It is believed that patients with neuromyelitis optica spectrum disease acquire disability exclusively through relapses. However, the possibility of disability accumulation in the absence of relapses has also been suggested. We quantified irreversible disability accumulation in the presence and absence of relapses in neuromyelitis optica spectrum disease.</p><p><strong>Methods: </strong>We identified patients with neuromyelitis optica spectrum disease in the MSBase registry. Disability-worsening events were required to be sustained until the end of follow-up. Worsening in the absence of relapses was validated through primary record review.</p><p><strong>Results: </strong>Over 884 patient-years of follow-up, we identified 32 disability-worsening events in 31 patients. Notably, six events (18.7%) in five patients (1.9%) occurred in the absence of relapses. A positive association was identified between relapse trajectory and the hazard of disability worsening (hazard ratio (95% credible interval): 2.36 (1.61, 3.64)), and an inverse relationship with disability worsening occurring in the absence of relapses (0.41 (0.11, 1.47)).</p><p><strong>Conclusion: </strong>Irreversible disability worsening was rare in this proactively treated cohort of neuromyelitis optica spectrum disease patients (3.6 events per 100 patient-years). However, almost 19% of worsening occurred in the absence of relapses, reassuringly in only 2% of patients. Our findings support relapses as the principal driver of disability in neuromyelitis optica spectrum disease while also providing evidence of relapse-independent disability worsening beyond identifiable comorbidities.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"13524585261489039"},"PeriodicalIF":5.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140347","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":"Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis.","authors":"Alice Mariottini, Andrea Ginestroni, Edoardo Carlesi, Francesca Di Pasquale, Edoardo Simonetti, Linhsia Noferini, Antonella Gozzini, Gaia Costantini, Anna M Repice, Daniel S Reich, Enrico Fainardi, Chiara Nozzoli, Luca Massacesi","doi":"10.1177/13524585261489061","DOIUrl":"https://doi.org/10.1177/13524585261489061","url":null,"abstract":"<p><strong>Background: </strong>Available literature shows a marginal or no effect of disease-modifying therapies on paramagnetic rim lesions (PRLs), a promising magnetic resonance imaging marker of chronic inflammation in multiple sclerosis.</p><p><strong>Objective: </strong>To investigate longitudinal changes in PRL count in people with multiple sclerosis treated with autologous haematopoietic stem cell transplantation (AHSCT), exploring their potential as predictors of treatment response.</p><p><strong>Methods: </strong>Monocentric study including 30 AHSCT-treated people with multiple sclerosis who performed at least two brain magnetic resonance imaging scans with susceptibility-weighted imaging either (i) before and after AHSCT (pre/post-AHSCT group; n = 12) or (ii) after AHSCT only (post-AHSCT group; n = 18).</p><p><strong>Results: </strong>In the pre/post-AHSCT group, PRL count decreased in 2/5 (40%) PRL-positive cases over a median of 21 (7-74) months; 5/26 (19%) PRL s resolved. In the post-AHSCT group, PRL count decreased in 4/7 (57%) PRL -positive cases over a median of 51 (6-57) months; 10/20 (50%) PRL s resolved. The annualised paramagnetic rim lesion disappearance rate was -0.36 and -0.43 in the two groups, respectively. No new PRL appeared. Baseline PRL count correlated with disability in the pre/post-AHSCT group only (r = 0.741, p = 0.006).</p><p><strong>Conclusions: </strong>Given the reported long persistence of PRLs, these data indicate that AHSCT may accelerate their disappearance, suggesting an effect within the central nervous system on microglia/macrophages. PRLs could predict response to central nervous system-bioavailable treatments.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"13524585261489061"},"PeriodicalIF":5.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140331","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":"Myelin oligodendrocyte glycoprotein antibody-associated disease in a patient with AIRE gene dominant-negative mutation.","authors":"Linling Wang, Ruiwen Hu, Lei Chen, Jingqi Wang, Jiahao Lin, Rui Li, Xueqiang Hu, Wei Qiu, Xiaonan Zhong, Tingting Lu","doi":"10.1177/13524585261490277","DOIUrl":"https://doi.org/10.1177/13524585261490277","url":null,"abstract":"<p><p>Myelin oligodendrocyte glycoprotein antibody-associated disease is a demyelinating disorder affecting the central nervous system. Autoimmune regulator mutations disrupt central tolerance and cause immunodeficiency and autoimmune manifestations. We report the case of a 49-year-old Asian male with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease and a heterozygous dominant-negative autoimmune regulator mutation (c.901G > A, p.Val301Met), alongside vitiligo, cryptococcal disease and nasopharyngeal carcinoma. This case raises a potential link between negative selection failure and myelin oligodendrocyte glycoprotein antibody-associated disease and suggests that autoreactive T cells may be primary pathogenetic drivers, implying that restoring immune tolerance could inform future therapeutic approaches.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"13524585261490277"},"PeriodicalIF":5.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140414","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":"Should autologous HSCT be a first-line option in highly active MS? No.","authors":"Karlo Toljan, Anu Jacob","doi":"10.1177/13524585261439664","DOIUrl":"10.1177/13524585261439664","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1141-1143"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147795652","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":"Induced pluripotent stem cell treatment for microglia replacement in progressive MS.","authors":"Agastya Reddy Malladi, Naghmeh Abbasi Kasbi, Jeffrey A Cohen, Olaf Stuve","doi":"10.1177/13524585261459847","DOIUrl":"10.1177/13524585261459847","url":null,"abstract":"<p><strong>Background: </strong>Induced pluripotent stem cells (iPSCs) offer a novel approach to target microglia, key drivers of multiple sclerosis (MS) pathology. A promising therapeutic strategy involves depleting resident microglia using colony-stimulating factor 1 receptor (CSF-1R) inhibitors, followed by differentiating iPSCs into microglia in vitro and transplanting them into the central nervous system (CNS). However, no studies have yet specifically examined iPSC-derived microglial replacement in MS.</p><p><strong>Objectives: </strong>This review evaluates the feasibility of replacing pathogenic microglia in MS with iPSC-derived microglia.</p><p><strong>Methods: </strong>A systematic literature search identified studies on microglial depletion, iPSC differentiation into microglia, and transplantation, as well as reports involving other MS-relevant neural cell types.</p><p><strong>Results: </strong>Direct studies on iPSC-derived microglia transplantation in MS are currently lacking; however, several preclinical investigations using iPSC-derived neural stem cells and oligodendrocyte precursor cells in animal models demonstrate robust engraftment, targeted migration to demyelinated lesions, reduced inflammation, enhanced remyelination, and significant functional recovery in vivo. These findings, besides microglia-specific transplantation, depletion, and repopulation studies in other disease contexts, support the biological plausibility of iPSC-based CNS cell replacement and inform future microglial transplantation research.</p><p><strong>Conclusion: </strong>Replacing pathogenic microglia with iPSC-derived counterparts represents an emerging therapeutic avenue for progressive MS. Rigorous preclinical studies are needed to confirm safety, optimize transplantation, and evaluate long-term efficacy.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1129-1138"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148552115","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":"Impact of multiple sclerosis disease-modifying therapies on chronic lesion tissue expansion.","authors":"Daniel Guilfoyle, Kayla Ward, Samuel Klistorner, Nathaniel Lizak, Heidi N Beadnall, Robert Zivadinov, Bianca Weinstock-Guttman, Izanne Roos, Helmut Butzkueven, Anneke van der Walt, Katherine Buzzard, Olga Skibina, Mike G Dwyer, Yael Barnett, Elaine Lui, Meng Law, Andy Shieh, Alexander Klistorner, Chenyu Wang, Tomas Kalincik, Michael Barnett","doi":"10.1177/13524585261459228","DOIUrl":"10.1177/13524585261459228","url":null,"abstract":"<p><strong>Background: </strong>Chronic lesion tissue expansion (CLTE) reflects slow, concentric growth of established multiple sclerosis (MS) lesions and is linked to central brain atrophy and disability progression. Whether existing MS disease-modifying therapies (DMTs) differentially influence this aspect of progressive MS biology remains unclear.</p><p><strong>Objectives: </strong>To compare the effect of current DMTs on CLTE in a multicentre, real-world MS cohort.</p><p><strong>Methods: </strong>We conducted a retrospective, observational study using linked clinical data from MSBase and the MSBase Imaging Repository. Data from patients aged ⩾18 years with ⩾3 longitudinal MRI scans, and 7 therapies with ⩾100 stable treatment epochs were included. Therapy effects on CLTE, new T2 lesions, and brain atrophy were assessed using epoch-based covariate-adjusted generalised estimating equation models, with fingolimod as a comparator.</p><p><strong>Result: </strong>The cohort included 564 patients contributing 1648 stable treatment epochs. After adjustment for demographic, clinical, and imaging covariates, B-cell depleting therapy was the only DMT associated with significantly lower CLTE (β = -4.03, <i>p</i> = 0.017) relative to fingolimod. CLTE was independently associated with age, baseline lesion volume, and centre effects.</p><p><strong>Conclusions: </strong>B-cell depletion is associated with reduced CLTE, a promising biomarker of progressive MS biology.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1145-1154"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364844","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":"Longitudinal magnetic resonance spectroscopy study of metabolite changes over 2 years in relapsing and primary progressive multiple sclerosis treated with ocrelizumab.","authors":"Erin L MacMillan, Bretta Russell-Schulz, Glaynel Alejo, Christopher Harp, Briana Cameron, Ryan Winger, Sherman Jia, Ann Herman, Jasmyne Kassam, Michael Waine, Irene M Vavasour, Helen Cross, Roger Tam, Anthony L Traboulsee, Robert Carruthers, Shannon H Kolind","doi":"10.1177/13524585261456964","DOIUrl":"10.1177/13524585261456964","url":null,"abstract":"<p><strong>Background: </strong>Magnetic resonance spectroscopy (MRS) offers non-invasive assessments of neuron-oligodendrocyte coupling and neuroinflammation to monitor treatment response in multiple sclerosis (MS).</p><p><strong>Objective: </strong>To track changes in N-acetylaspartate and myo-inositol in relapsing MS (RMS) and primary progressive MS (PPMS) patients treated with ocrelizumab over 2 years.</p><p><strong>Methods: </strong>Single-voxel MRS at 3T was acquired at baseline in 10 healthy controls (HCs), and weeks 0, 12, 24, 52, and 96 in MS participants at a single center.</p><p><strong>Results: </strong>Baseline myo-inositol was higher in PPMS than RMS (<i>p</i> = 0.047) and HC (<i>p</i> = 0.001), and correlated with disability across both MS groups (<i>r</i> = 0.57, <i>p</i> = 0.0006). Following treatment with ocrelizumab, both RMS and PPMS demonstrated declines in myo-inositol over time, returning toward HC levels (RMS <i>p</i> = 0.016; PPMS <i>p</i> = 0.004). Conversely, N-acetylaspartate was not different between groups and remained stable over time.</p><p><strong>Conclusion: </strong>Ocrelizumab treatment is associated with declining myo-inositol levels measured by MRS in both RMS and PPMS. Myo-inositol offers a unique biomarker to track resolution of gliosis and reactive microglia with treatment. Furthermore, the relationship between a higher concentration of myo-inositol and greater disability across both MS subtypes at baseline supports the presence of \"smouldering inflammation\" as a disease process across the spectrum of MS.</p><p><strong>Clinical trial: </strong>Sub-study of the Ocrelizumab Biomarker Outcome Evaluation (OBOE; ML29966) trial: https://clinicaltrials.gov/study/NCT02688985.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1155-1167"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13646435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355526","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":"TSPO-PET-measurable neuroinflammation associates with information processing speed decline in multiple sclerosis.","authors":"Maija Saraste, Taru Nikkilä, Markus Matilainen, Päivi Hämäläinen, Saara Wahlroos, Johan Rajander, Anniina Snellman, Juha Rinne, Laura Airas","doi":"10.1177/13524585261446839","DOIUrl":"10.1177/13524585261446839","url":null,"abstract":"<p><strong>Background: </strong>Impaired information processing speed (IPS) is a common and disabling cognitive deficit in multiple sclerosis (MS).</p><p><strong>Objectives: </strong>To assess whether glial activation measured using translocator protein-positron emission tomography (TSPO-PET) predicts performance and long-term change on the Symbol Digit Modalities Test (SDMT).</p><p><strong>Methods: </strong>Forty-eight people with MS underwent [¹¹C]PK11195 TSPO-PET, magnetic resonance imaging (MRI), diffusion tensor imaging and SDMT at baseline; 34 repeated SDMT a median (first to third quartile) 4.9 (3.7-5.2) years later. Glial activation was quantified using the distribution volume ratio (DVR). Multivariable regression models were used to identify predictors of baseline SDMT and subsequent change.</p><p><strong>Results: </strong>Normal-appearing white matter (NAWM) radial diffusivity (estimate [95% confidence interval (CI)] -129 [-214, -44]), thalamic DVR (-52.5 [-94.8, -10.2]) and age (-0.57 [-1.07, -0.06]) explained 41% of baseline SDMT variance. NAWM DVR was the strongest predictor of SDMT change, explaining 53% of variance when adjusted for baseline SDMT (-6.23 [-8.55, -3.91]). A model including lesion rim DVR (odds ratio 1.36 [1.06, 1.73]) and baseline SDMT (1.18 [1.01, 1.37]) predicted SDMT decline with 73% sensitivity and 83% specificity (area under the curve [AUC] = 0.85).</p><p><strong>Conclusion: </strong>Diffuse neuroinflammation in the NAWM is associated with future SDMT change, suggesting a potential role for chronic glial activation in IPS deterioration in MS.</p>","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1193-1204"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148102505","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":"Enteroviral infections with antiCD20 therapies-A class effect?","authors":"Jakob Stögbauer, Mathias Fousse","doi":"10.1177/13524585261444588","DOIUrl":"10.1177/13524585261444588","url":null,"abstract":"","PeriodicalId":520714,"journal":{"name":"Multiple sclerosis (Houndmills, Basingstoke, England)","volume":" ","pages":"1342-1343"},"PeriodicalIF":5.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877205","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}