Therapeutic Advances in Neurological Disorders最新文献

{"title":"Psoriasis under B-cell depleting therapies in multiple sclerosis: a retrospective multicenter analysis.","authors":"Patricia Kirschner, Franz F Konen, Franziska Axhausen, Ulas Ceylan, Erda Bucak, Romy Baumgart, Lars Masanneck, Stefan Gingele, Kerstin Steinbrink, Sven G Meuth, Ralf Gold, Stephanie Wolff, Simon Faissner, Thomas Skripuletz, Steffen Pfeuffer, Marc Pawlitzki","doi":"10.1177/17562864261427169","DOIUrl":"10.1177/17562864261427169","url":null,"abstract":"<p><strong>Background: </strong>B-cell depleting therapies (BCDT), including ocrelizumab, ofatumumab, and ublituximab, are highly effective disease-modifying therapies for multiple sclerosis (MS). Several case reports have raised concerns about new-onset or exacerbation of psoriasis under BCDT.</p><p><strong>Objectives: </strong>This article aims to analyze clinical characteristics, treatment courses, and outcomes of MS patients who developed or experienced worsening of psoriasis during BCDT.</p><p><strong>Design: </strong>This retrospective, multicenter analysis included patients from four German university hospitals (Düsseldorf, Hannover, Bochum, Giessen).</p><p><strong>Methods: </strong>We retrospectively screened 3228 MS patients under BCDT between 2020 and 2024 for development of psoriasis or an exacerbation of a known psoriasis. Clinical data, including Expanded Disability Status Scale, Psoriasis Area and Severity Index scores, treatment regimens, and comorbidities, were analyzed.</p><p><strong>Results: </strong>Among 3228 patients treated with BCDT, 7 developed new-onset psoriasis and 10 showed exacerbation of preexisting psoriasis. The median time to psoriasis onset or worsening was 13 months (3-83 months) under continuous treatment with BCDT. Topical therapies were effective in most cases, but a change of MS treatment or initiation of psoriasis-specific immunotherapies, including the interleukin-17A-antibody secukinumab, was required in four patients.</p><p><strong>Conclusion: </strong>Psoriasis onset or worsening during BCDT is rare. While most cases are manageable with standard psoriasis treatments, severe cases may necessitate therapy adjustments. The potential immunological interplay between MS and psoriasis treatment warrants further investigation.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261427169"},"PeriodicalIF":4.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prospects of CAR T-cell therapies in changing the therapeutic algorithm of neurologic autoimmunities.","authors":"Marinos C Dalakas","doi":"10.1177/17562864261429570","DOIUrl":"10.1177/17562864261429570","url":null,"abstract":"<p><p>T cells, genetically modified to express chimeric antigen receptors (CAR T), successfully used in hemato-oncologic malignancies, are showing promising and sustained benefits in refractory autoimmune neurological diseases, including Myasthenia Gravis, stiff-person syndrome, neuromyelitis optica, myositis, autoimmune neuropathies, and multiple sclerosis. Several reported patients with a steadily progressive disease and evolving disability unresponsive to available therapies, including rituximab and new biologics, after 2-3 months of treatment with CARs targeting CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts exhibit impressive, long-lasting, and drug-free clinical improvements with the potential for immune reset shifting immunity to a healthy state without the need for continuing more immunotherapy cycles. The review discusses what the unmet needs are with the present neuroimmunotherapeutics pointing out the disease stage and patient subsets for which CAR T-therapy is most suitable highlighting that CAR T should be applied in the early stages of disability development when patients reach early-active/refractory status rather than waiting for very late disease progression when neurological deficits might be irreversible. The future trajectory of CAR T cells is also described as a promising means destined to change the present therapeutic algorithm in all neuro-autoimmunites, even offering a promising path toward a cure, pointing out that, in contrast to currently approved biologics that selectively target one immunoregulatory factor, CD19 CAR T cells exert effects even beyond B cells, cross the blood-brain barrier and lymphoid tissues, and expand as \"living cells\" to memory cells ensuring sustained long-term benefits. Key therapeutic uncertainties and practicalities are however highlighted, including the exact duration of CAR T-cell therapy-induced drug-free remissions, logistical challenges, economic limitations, and the need for extensive collaborative efforts with experts in specialized clinical centers.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261429570"},"PeriodicalIF":4.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testing for neural antibodies in autoimmune encephalitis: who, what, where, when, why, and how.","authors":"Shaza Almweisheer, Kamala Sangam, Ola Ismail, Adrian Budhram","doi":"10.1177/17562864261429181","DOIUrl":"10.1177/17562864261429181","url":null,"abstract":"<p><p>In recent decades, neural antibody testing has emerged as a cornerstone of autoimmune encephalitis (AE) diagnosis. Commercially available assays to detect these antibodies are now in widespread use, resulting in dramatically increased test accessibility and reduced turnaround times. However, there remains heterogeneity in testing approach and pitfalls related to test ordering as well as diagnostic test performance, which may vary across laboratories depending on their testing methodologies or algorithms. This creates the potential for both false-negative and false-positive results, which can lead to patient misdiagnosis if clinicians are not familiar with both the strengths and limitations of this testing in practice. In this narrative review, we discuss the approach to patient selection for antibody testing, importance of serum and cerebrospinal fluid testing using appropriately handled specimens, potential limitations of local versus reference laboratory testing, optimal timing of testing, benefit of testing to patient management, and diagnostic performance of different test methodologies and algorithms ( the \"who, what, where, when, why, and how\" of neural antibody testing in AE), with the aim of providing a practically useful framework for clinicians who order this testing.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261429181"},"PeriodicalIF":4.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12988283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative treatments for migraine: a new era.","authors":"Francesca Pistoia","doi":"10.1177/17562864261428244","DOIUrl":"10.1177/17562864261428244","url":null,"abstract":"","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261428244"},"PeriodicalIF":4.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CT perfusion ischemic core predicts PH-2 hemorrhagic transformation following intravenous alteplase bridging treatment prior to endovascular thrombectomy.","authors":"Asaf Honig, Aviva Alpernas, Yoel Schwartzmann, Hen Hallevi, Issa Metanis, Einor Ben-Assayag, Tali Jonas-Kimchi, Udi Sadeh, Hamza Jubran, Oz Haim, Jose Cohen, Ronen R Leker, Jeremy Molad","doi":"10.1177/17562864261425623","DOIUrl":"10.1177/17562864261425623","url":null,"abstract":"<p><strong>Background: </strong>Intravenous thrombolysis (IVT) administered as a bridging therapy prior to endovascular thrombectomy (EVT) for acute ischemic stroke may increase the risk of hemorrhagic-transformation (HT). CT-perfusion (CTP) imaging enables quantitative assessment of ischemic core and penumbral tissue and may support individualized hemorrhagic risk stratification.</p><p><strong>Objectives: </strong>To assess whether baseline CTP-defined ischemic core parameters are associated with parenchymal-hematoma type 2 (PH-2) following bridging IVT before EVT.</p><p><strong>Design: </strong>Observational-cohort-study.</p><p><strong>Data sources and methods: </strong>Consecutive patients with large-vessel occlusion treated within 4 h of symptom onset at two tertiary stroke centers between 2017 and 2023 were analyzed. All patients underwent baseline CTP imaging. Outcomes were compared between patients treated with IVT plus EVT and those treated with direct-EVT. HT was assessed on 24-h follow-up noncontrast-CT using ECASS-2 criteria. Multivariable logistic regression was performed to identify independent predictors of PH-2.</p><p><strong>Results: </strong>Among 398 patients (50.6% male), 180 received IVT + EVT (mean age 70.2 ± 15.0 years) and 218 underwent direct-EVT (69.5 ± 14.5 years). Baseline characteristics, workflow times, thrombectomy passes, and reperfusion rates were comparable. PH-2 was associated with higher mortality (43.8% vs 11.7%, <i>p</i> < 0.001) and worse 90-day functional outcome (median modified Rankin Score 4 (2-6) vs 3 (1-4), <i>p</i> = 0.002). Bridging-IVT was associated with higher PH-2 rates compared with direct EVT (6.1% vs 2.0%, <i>p</i> = 0.036), without increased symptomatic intracranial-hemorrhage. In sensitivity analyses, bridging-IVT was associated with higher PH-2 rates only in patients with any ischemic core (7.8% vs 1.5%, <i>p</i> = 0.014), core volume >10 mL (8.8% vs 0.8%, <i>p</i> = 0.004), and >20 mL (8.7% vs 1.3%, <i>p</i> = 0.03). Penumbral volume was not associated with PH-2. In multivariable analysis, any ischemic core (odds ratio (OR) 12.67, <i>p</i> = 0.02) and core volume >10 mL (OR 11.12, <i>p</i> = 0.034) independently predicted PH-2.</p><p><strong>Conclusion: </strong>Baseline CTP-defined ischemic core volume is strongly associated with severe HT following bridging intravenous alteplase prior to EVT and may inform individualized risk-benefit assessment of bridging therapy.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261425623"},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positioning siponimod and the post-treatment gap: the unmet needs of SPMS patients in Italian real-world practice.","authors":"Aurora Zanghì, Giovanna Borriello, Matteo Foschi, Assunta Bianco, Elisabetta Signoriello, Maria Cellerino, Paola Sofia Di Filippo, Francesco Baldisseri, Giuseppe Romano, Alessandra Cicia, Giacomo Lus, Matilde Inglese, Massimiliano Mirabella, Carlo Avolio, Emanuele D'Amico","doi":"10.1177/17562864251399560","DOIUrl":"10.1177/17562864251399560","url":null,"abstract":"<p><strong>Background: </strong>Siponimod, a selective sphingosine-1-phosphate receptor modulator was approved for patients with Secondary progressive Multiple Sclerosis (SPMS) with ongoing disease activity. However, its real-world positioning and management after discontinuation remain challenging.</p><p><strong>Objectives: </strong>To evaluate the real-world use of siponimod in Italian real world setting, focusing on discontinuation rates, possible predictors, and post-treatment management.</p><p><strong>Methods: </strong>A retrospective, multicenter study on patients treated with siponimod across six Italian MS centers. Demographics, prior disease modifying therapy (DMTs), reasons for discontinuation, adverse events, and subsequent therapies were collected. Statistical analyses included propensity-adjusted Cox model.</p><p><strong>Results: </strong>A total cohort of 188 patients (63.8% female, median age 52 years) was enrolled, out of them 76(40.4%) discontinued siponimod, with a median treatment duration of 26 months. The main reason for discontinuation was safety concerns (72.4%), particularly persistent lymphopenia (43.6%) and recurrent infections (27.3%). Disease activity accounted for 27.6% of discontinuations. No significant demographic or clinical predictors of discontinuation were identified. After discontinuation, 49 patients (64%) started a new DMT, most commonly ocrelizumab (<i>n</i> = 22) or cladribine (<i>n</i> = 15), while 25 (32.9%) received no further therapy.</p><p><strong>Conclusion: </strong>High discontinuation rates, mainly due to safety, and frequent post-treatment gaps highlight the need for improved, individualized management strategies for SPMS after siponimod.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864251399560"},"PeriodicalIF":4.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergency use of eculizumab in impending and manifest myasthenic crisis: a retrospective case series.","authors":"Ying Huang, Yihan Xiong, Hui Zhan, Futian Wu, Yichun Jiang, Yaqing Zhang, Jiaxun Chen, Silin Zeng, Ting Zhang, Xiaofeng Xiong, Zhuomin Chen, Fang Yang, Gang Li, Qianhui Xu","doi":"10.1177/17562864261425088","DOIUrl":"10.1177/17562864261425088","url":null,"abstract":"<p><p>Impending and manifest myasthenic crisis (MC) represent life-threatening neurological emergencies that require immediate intervention. Although eculizumab, a terminal complement C5 inhibitor, has established efficacy in generalized myasthenia gravis, most studies have focused on long-term outcomes, and its potential for rapid onset of effect in acute exacerbations has not been well evaluated. We retrospectively analyzed four acetylcholine receptor (AChR) antibody-positive patients (five acute episodes) who received eculizumab as emergency therapy between January 2024 and July 2025. All patients presented with impending or manifest MC; none had received intravenous immunoglobulin, plasma exchange, or neonatal Fc receptor (FcRn) inhibition within the preceding month. According to the Myasthenia Gravis Foundation of America classification, three patients had class IVb and one had class V. Triggers for exacerbation included COVID-19 infection (<i>n</i> = 2), puerperium (<i>n</i> = 1), PD-1 inhibitor exposure (<i>n</i> = 1), and common infection (<i>n</i> = 1). Within 48 h of eculizumab administration, Quantitative Myasthenia Gravis scores improved from 28.2 ± 4.8 to 15.0 ± 4.1, while Myasthenia Gravis Activities of Daily Living scores decreased from 16.8 ± 2.8 to 6.0 ± 4.3. Notable milestones achieved included arterial blood gas improvement within 7.5 h (one patient), nasogastric tube removal within 48 h (three patients), and successful extubation at 17 h (one patient). No treatment-related adverse events were observed. These preliminary findings suggest that eculizumab may be associated with rapid, temporally related clinical improvement within 48 h with a favorable short-term safety profile in AChR antibody-positive patients with impending or manifest MC, particularly those with complement activation triggers. Larger prospective studies with standardized short-term assessment protocols, including frequent neurological evaluations during the first 48 h, are warranted to further validate its efficacy and define its role as an emergency therapy in the acute management of myasthenic exacerbations.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261425088"},"PeriodicalIF":4.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plain Language Summary of a Phase 2b Randomized Controlled Trial of Ecopipam and Its 12-Month Open-Label Extension in Children and Adolescents With Tourette Syndrome.","authors":"Donald L Gilbert, David J B Kim, Meredith M Miller, Sarah D Atkinson, George B Karkanias, Frederick E Munschauer, Stephen P Wanaski, Timothy M Cunniff","doi":"10.1177/17562864261424987","DOIUrl":"https://doi.org/10.1177/17562864261424987","url":null,"abstract":"<p><p>What is this summary about? The purpose of this summary is to explain the results from two studies that looked at the safety and effects of an investigational drug called ecopipam. \"Investigational\" means that the drug has not been approved by the United States Food and Drug Administration (FDA) yet. The studies tested if ecopipam could safely improve symptoms and quality of life in children and adolescents with Tourette syndrome. Please note that ecopipam is not currently approved to treat Tourette syndrome.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261424987"},"PeriodicalIF":4.1,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vedolizumab and the gut-CNS axis in multiple sclerosis: considering T cell licensing pathways.","authors":"Afsaneh Shirani, Olaf Stuve","doi":"10.1177/17562864261423751","DOIUrl":"10.1177/17562864261423751","url":null,"abstract":"<p><strong>Background: </strong>The role of gut-mediated T cell licensing in multiple sclerosis (MS) remains incompletely understood.</p><p><strong>Objective: </strong>We hypothesized that T cell licensing in the gut contributes to MS pathogenesis and evaluated whether vedolizumab-an anti-α4β7 integrin, gut-selective monoclonal antibody approved for inflammatory bowel disease (IBD)-is associated with MS prevalence.</p><p><strong>Design: </strong>Retrospective observational study.</p><p><strong>Methods: </strong>Using Epic Cosmos, a large deidentified U.S. electronic health record platform, we identified individuals with Crohn's disease (CD) or ulcerative colitis (UC) and a concomitant MS diagnosis between August 2010 and August 2025.</p><p><strong>Results: </strong>Among 1,027,704 CD and 1,294,362 UC patients, 8,098 (0.79%; 95%CI:0.77%-0.81%) and 9,564 (0.74%; 95%CI:0.73%-0.76%) had MS, respectively. In contrast, among vedolizumab-treated patients, only 125 with CD (0.22%; 95%CI:0.18%-0.26%) and 109 with UC (0.17%; 95%CI:0.14%-0.20%) developed MS within five years of treatment.</p><p><strong>Conclusion: </strong>While causality cannot be inferred, our findings highlight an opportunity to further explore whether vedolizumab-associated differences in MS prevalence may relate to gut-associated immune processes.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261423751"},"PeriodicalIF":4.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12923930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential response to ofatumumab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study.","authors":"Qian Zhou, Yuzhen Ouyang, Fei Jiang, Qiuming Zeng, Ting He, Zeyi Wen, Guanzhong Shi, Xiaohua Dong, Haobing Cai, Wei Xiang, Miao Su, Kailin Li, Huan Yang","doi":"10.1177/17562864261421717","DOIUrl":"10.1177/17562864261421717","url":null,"abstract":"<p><strong>Background: </strong>Ofatumumab (OFA), a humanized anti-CD20 monoclonal antibody, shows potential in myasthenia gravis (MG) with antibody against acetylcholine receptor (AChR-Ab), but comparative efficacy across AChR and muscle-specific kinase (MuSK) subtypes remains uncharacterized.</p><p><strong>Objectives: </strong>To evaluate OFA's clinical and immunological effects in AChR-MG versus MuSK-MG, identify predictors of minimal symptom expression (MSE), and explore the dynamics of B-cell repopulation.</p><p><strong>Design: </strong>A retrospective study in a single center.</p><p><strong>Methods: </strong>Twenty-one refractory MG patients (13 MuSK+, 8 AChR+) received individualized OFA induction (Regimen 1: two 20 mg doses ⩾2 weeks apart; Regimen 2: single 20 mg dose) and maintenance (20 mg upon CD19 + B counts ⩾5 cells/μL repopulation or clinical exacerbation). Outcomes included time-to-MSE, Quantitative Myasthenia Gravis Score (QMGS) dynamics, prednisone reduction, and serial immunophenotyping (B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L (sCD40L), microphage migration inhibitory factor (MIF), and immunoglobulin).</p><p><strong>Results: </strong>MuSK-MG achieved faster MSE (median time: 6 vs 15 months, log-rank <i>p</i> = 0.164, age-adjusted Cox <i>p</i> = 0.027), and a higher 3-month improvement (92.3% vs 50.0%; <i>p</i> = 0.047). Earlier achievement of MSE was associated with shorter disease duration (<i>p</i> = 0.038) and concomitant corticosteroid therapy (<i>p</i> = 0.030). Prednisone doses decreased significantly over 6 months (<i>p</i> = 0.029) without difference between groups (<i>p</i> = 0.109). MuSK-MG showed synchronized BAFF/APRIL declines while AChR-MG presents transient BAFF elevation and sustained APRIL. BAFF levels showed a significant positive correlation with QMGS in MuSK-MG, while IgM/IgG positively correlated with QMGS in both subtypes. Median B cell-repopulation time was 47.7 days.</p><p><strong>Conclusion: </strong>OFA demonstrates superior efficacy in MuSK-MG with distinct immunological modulation. AChR-MG requires combinatorial strategies targeting compensatory pathways.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"19 ","pages":"17562864261421717"},"PeriodicalIF":4.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}