Muscle & Nerve最新文献

{"title":"Chimeric Antigen Receptor T-Cells in Myasthenia Gravis: Advances, Safety Challenges, and Future Directions.","authors":"Tobias Hegelmaier, Alexander Duscha, Christiane Desel, Sarah Stassen, Tim Krzemien, Ann-Katrin Hennemann, Vaia Pappa, Aiden Haghikia","doi":"10.1002/mus.70222","DOIUrl":"10.1002/mus.70222","url":null,"abstract":"<p><p>This review examines the emerging application of chimeric antigen receptor (CAR) T-cell therapy in myasthenia gravis (MG), with emphasis on safety, efficacy signals, and future therapeutic potential in treatment-refractory disease. A comprehensive literature search was conducted across PubMed, medRxiv, bioRxiv, and Google Scholar for studies published between January 1, 2010 and July 1, 2025, using the terms \"CAR T-cell,\" \"chimeric antigen receptor,\" and \"myasthenia gravis.\" Eligible reports included clinical trials, case reports, case series, and mechanistic studies describing CAR T-cell therapy outcomes in MG. Across five independent case series, seven patients receiving CAR T-cells targeting CD19, BCMA, or bispecific antigens showed consistent clinical improvement. Peak expansion occurred 8-22 days postinfusion, with persistence of 28 to ~180 days. Despite small cohorts, safety in CAR T-cell therapy was favorable versus oncology, with mainly Grade 1-2 cytokine release syndrome, rare immune effector cell-associated neurotoxicity, and no severe or life-threatening events. Seven registered trials (> 260 patients) are expected to conclude between 2026 and 2029. Overall, CAR T-cell therapy shows substantial promise for treatment-refractory MG, potentially offering greater durability than existing therapies with an acceptable safety profile. Nevertheless, current evidence is restricted to small, uncontrolled studies, and long-term efficacy, durability, and optimal patient selection require validation in larger controlled trials.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"942-951"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Diagnostic Potential of Axon Excitability Is Consistent Across Hand Muscles in Amyotrophic Lateral Sclerosis.","authors":"Alana K O Hodgson, Christopher J McDermott, Pamela J Shaw, James J P Alix","doi":"10.1002/mus.70239","DOIUrl":"10.1002/mus.70239","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Recent work suggests that nerve excitability testing has diagnostic potential in amyotrophic lateral sclerosis (ALS). The diagnostic performance of nerve excitability across hand muscles is currently unknown. This study aimed to assess if muscles of the so-called split hand (abductor pollicis brevis [APB], first dorsal interosseous [FDI], and abductor digiti minimi [ADM]) manifest differences in diagnostic performance.</p><p><strong>Methods: </strong>We prospectively recruited 60 consecutive patients investigated for ALS. Nerve excitability, motor unit number and size (MScanFit), needle electromyography (EMG), and standard clinical data were collected. ALS and non-ALS groups were compared using t tests, area under receiver operating characteristic curves (AUROC), and multivariate modeling.</p><p><strong>Results: </strong>Forty-eight patients completed testing of all three muscles, 25 were diagnosed with ALS. The most prominent nerve excitability changes were in superexcitability (APB p = 0.001, FDI p = 0.0001, ADM p = 0.002). Diagnostic performance with superexcitability was similar across the three muscles (p > 0.05). Reductions in motor unit number were observed in ALS patients. Changes in excitability were evident without loss of motor units, most frequently in APB (40% of recordings). Improvements to the AUROC were obtained using combined excitability/motor unit parameters from APB/FDI (AUROC 0.97, p = 0.01 vs. FDI superexcitability alone). Combined excitability and motor unit modeling outperformed detection of EMG abnormalities.</p><p><strong>Discussion: </strong>Disturbances to nerve excitability are similar across the split hand muscles at the time of ALS diagnosis. These occurred prior to motor unit loss and traditional EMG changes. Combining excitability and motor unit parameters in the lateral hand can identify early pathology and potentially lead to earlier diagnosis.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"1138-1145"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of Nerve Conduction Demyelinating Parameters Between Baseline and Treatment Cessation May Not Be Predictive of Relapse in IVIg-Responsive CIDP Patients.","authors":"Marine Le Vavasseur, Capucine Blaise, Isabelle Cordelle, Pauline Reach, Sahar Chakroun, Nathalie Kubis, Pierre Lozeron","doi":"10.1002/mus.70199","DOIUrl":"10.1002/mus.70199","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Identifying factors associated with short-term relapse is essential for tailoring maintenance treatment on a case-by-case basis in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We sought to determine whether changes in demyelinating electrophysiological features during treatment could predict relapse after treatment discontinuation in a cohort of CIDP patients.</p><p><strong>Methods: </strong>We conducted a retrospective study of patients with CIDP treated with intravenous immunoglobulin (IVIg), all of whom had a first nerve conduction study (NCS) at treatment initiation or during treatment, while the disease was in a stable phase, followed by a second study at the time of treatment discontinuation. Demyelinating features and the degree of axonal loss were determined during each NCS and compared between the two examinations.</p><p><strong>Results: </strong>Thirty-one consecutive IVIg-responsive CIDP patients were included, with a mean age of 59.1 ± 14.6 years. Twenty (65%) were males. Sixteen patients (52%) relapsed after a mean of 6 months. Most patients demonstrated a reduced total number and type of demyelinating features between the two assessments, but overall, these changes were not different between the relapse and relapse-free groups. Similarly, axonal loss at our first assessment and the progression of axonal loss between our two assessments were not different in the relapse group compared to the relapse-free group.</p><p><strong>Discussion: </strong>In our population of IVIg responsive CIDP patients, we were unable to demonstrate the predictive value of follow-up nerve conduction studies alone for the risk of relapse. Looking at other biomarkers alone or in combination with NCS is necessary.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"984-989"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Serum Neurofilament Light Chain Into Amyotrophic Lateral Sclerosis Diagnostic Criteria.","authors":"Sean E Smith, Timothy M Miller, Andrew Atkinson, Alan Pestronk, Robert C Bucelli","doi":"10.1002/mus.70212","DOIUrl":"10.1002/mus.70212","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Serum neurofilament light chain (NfL) is a promising diagnostic biomarker for differentiating amyotrophic lateral sclerosis (ALS) from clinical mimics. This study assessed the utility of integrating serum NfL into current diagnostic criteria to enhance diagnostic certainty in patients with a provisional ALS diagnosis who were confirmed as having ALS at follow-up.</p><p><strong>Methods: </strong>We conducted a single-center, retrospective study of consecutive patients with a provisional ALS diagnosis at their initial visit at the WashU Medicine ALS Center. All underwent electrodiagnostic testing and serum NfL measurement via SIMOA using an HD-X analyzer (Quanterix). Elevated serum NfL was defined with a cutoff of 38 pg/mL.</p><p><strong>Results: </strong>The study included 43 patients with a provisional ALS diagnosis (29 men [67.4%]; median age, 63 years [range, 36-80 years]). At follow-up, 27/43 (62.8%) patients progressed to definite ALS. Serum NfL was elevated in 34/43 (79.1%) of the total cohort and 24/27 (88.9%) of those who progressed to definite ALS. Integrating serum NfL with Gold Coast Criteria (GCC) was associated with a tenfold increase in the odds of identifying patients likely to progress to definite ALS (OR 10 [1.39, 71.87], p = 0.02).</p><p><strong>Discussion: </strong>Our results suggest that serum NfL is a robust complement to current ALS diagnostic criteria and shows potential to improve early identification and diagnostic certainty of patients likely to progress to definite ALS. Integrating serum NfL with GCC provided the strongest predictive model. These findings warrant larger multicenter, prospective studies to confirm results.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"990-995"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Validation of the New PLS Diagnostic Criteria From PLS Natural History Study: EMG and Neurofilament Analyses.","authors":"Eric Sorenson, Daragh Heitzman, Ikjae Lee, Grace Jang, Lauren Elman, Ali A Habib, James Wymer, Ghazala Hayat, Stephen A Goutman, J Americo M Fernandes, Mary Kay Floeter, Senda Ajroud-Driss, Kelly Gwathmey, Edward Kasarskis, Yasushi Y Kisanuki, Catherine Lomen-Hoerth, David Walk, Wendy S Johnston, Frank Diaz, Nicholas J Maragakis, Sabrina Paganoni, Jaimin Shah, Bjorn Oskarsson, Lorne Zinman, Terry Heiman-Patterson, Omar Jawdat, Christina N Fournier, Michael T Pulley, Stephen N Scelsa, Christen Shoesmith, Zachary Simmons, Alexander V Sherman, Benjamin N Hoover, Rebecca Y Yun, Ken Cheung, Hiroshi Mitsumoto","doi":"10.1002/mus.70192","DOIUrl":"10.1002/mus.70192","url":null,"abstract":"<p><strong>Background: </strong>Primary lateral sclerosis (PLS) is an ultrarare upper motor neuron syndrome with a prognosis unique from classical ALS. The study of PLS is complicated by its rarity and the difficulty distinguishing PLS from ALS. We present data from a 1-year prospective follow-up study on PLS and efforts to distinguish it from ALS.</p><p><strong>Methods: </strong>Seventy-six PLS participants enrolled in this prospective natural history study. EMG studies, blood neurofilament light chain levels (NfLs), and demographic characteristics were obtained at baseline. At 1-year follow-up, repeat EMG studies were conducted to determine which participants fulfilled criteria for ALS. Baseline characteristics were then compared to determine features that predict reclassification.</p><p><strong>Results: </strong>Seventy participants completed 1-year follow-up. Five of the 70 were reclassified to ALS (7.1%). Those reclassified had higher trends in baseline blood NfL levels (91.4 vs. 34.0 pg/mL, p = 0.13) and shorter symptom duration (39 vs. 69 months in the PLS group, p = 0.15). Reclassification was noted in both probable and definite PLS participants. All cases with a symptomatic duration of less than 2 years retained the PLS phenotype (5 of 5). NfL levels over 90 pg/mL predicted reclassification with 94% specificity and 60% sensitivity. No other features predicted reclassification to ALS.</p><p><strong>Conclusions: </strong>In our population, reclassification of PLS to ALS occurred at a low frequency at 1 year follow-up (7.1%). Baseline NfL was the strongest predictor in differentiating UMN dominant ALS from PLS at 1-year follow-up. Based on our data, we propose EMG and NfL criteria for enrollment in future PLS trials.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"976-983"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risdiplam Add-On Therapy Following Onasemnogene Abeparvovec in Children With Spinal Muscular Atrophy and 2 SMN2 Copies: A Multi-Center Case Series.","authors":"Corinna Stoltenburg, Klaus Goldhahn, Arpad von Moers, Angela M Kaindl, Claudia Weiß","doi":"10.1002/mus.70246","DOIUrl":"10.1002/mus.70246","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Three disease-modifying therapies are approved for individuals with spinal muscular atrophy (SMA); however, data concerning the combination of these therapies remain limited. This study aimed to evaluate the safety and efficacy of add-on risdiplam in children who had experienced clinical deterioration despite gene therapy with onasemnogene abeparvovec.</p><p><strong>Methods: </strong>This is a retrospective case series study at two centers of children treated with risdiplam who had previously received onasemnogene abeparvovec. Therapy was evaluated by clinical examination, standardized physiotherapeutic assessments, and parent perspectives.</p><p><strong>Results: </strong>Five patients with SMA (four male and one female), diagnosed between 0 and 8 months, were included in the study. All had 2 SMN2 copies and were started on risdiplam between five and 48 months after onasemnogene abeparvovec. Risdiplam was added due to motor regression, dysphagia, new onset of respiratory insufficiency, and/or recurrent pneumonias. Four children showed improvements in motor development, swallowing, and respiratory function. One child remained stable. Parents perceived a significant improvement in general impression, motor, and respiratory function. The add-on therapy was well tolerated without adverse events.</p><p><strong>Discussion: </strong>Our results indicate an improvement in most children in a case series through add-on risdiplam. Evaluating clinical outcome parameters in clinical practice may prove challenging and should be complemented by the parental perspective. The decision regarding the use of add-on therapy in children with SMA who receive one line of treatment but show a clinical deterioration should be considered on an individual level, and assessments of predefined therapeutic goals are recommended.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"1164-1171"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experience Using Efgartigimod to Treat Juvenile Myasthenia Gravis in China: A Multicenter Retrospective Study.","authors":"Jing Lin, Guoyan Qi, Susan Luo, Qilong Jiang, Bitao Bu, Min Liu, Yuzhen Wei, Meigui Han, Junhong Yang, Zhilan Zhao, Lili Zhang, Yifan Zhang, Haoyou Xu, Xingjie Hao, Zhijun Li","doi":"10.1002/mus.70202","DOIUrl":"10.1002/mus.70202","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Current therapeutic management of juvenile myasthenia gravis (JMG) predominantly relies on conventional immunosuppressive therapies and expert consensus extrapolated from adult data, creating a critical gap in high-quality, pediatric-specific clinical evidence. The aim of this study was to assess the efficacy and safety of efgartigimod in the pediatric population.</p><p><strong>Methods: </strong>This multicenter retrospective study enrolled JMG patients (under 18 years), from 12 Chinese centers, who received at least one dose of efgartigimod. Efgartigimod was administered as weekly intravenous infusions. Study visits included W0 (baseline: pretreatment) and W1-W4 (weekly posttreatment follow-ups). Efficacy was assessed via MG-related Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis (QMG) score, and the MG Composite (MGC) scale.</p><p><strong>Results: </strong>Seventeen JMG patients (3 males, 14 females) with a median disease duration of 23 months were included. At W0, 88.2% of patients were classified as Myasthenia Gravis Foundation of America (MGFA) class II-V and were anti-acetylcholine receptor (anti-AchR) antibody positive. After efgartigimod treatment, clinically meaningful improvement (CMI) was observed in 70.6% (W1), 73% (W2), and 91.7% (W4); 66.7% achieved minimal symptom expression by W4. MG-ADL and QMG scores decreased by 30% and 30.1% (W1) and by 87.6% and 71.8% (W4) compared to W0. No treatment-related adverse events occurred.</p><p><strong>Discussion: </strong>Our study suggests efgartigimod is an effective therapeutic option for JMG, with favorable efficacy and safety profiles. Further studies are necessary to validate the efficacy and safety of efgartigimod in the pediatric population.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"1025-1031"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Thymectomy on the Incidence of Extrathymic Cancers and Autoimmune Diseases in Patients With Non-Thymomatous Myasthenia Gravis.","authors":"Mohamed Khateb, Adnan Almasri, Carolina Barnett-Tapia, Vera Bril","doi":"10.1002/mus.70218","DOIUrl":"10.1002/mus.70218","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Thymectomy is associated with positive effects on myasthenia gravis (MG), but there is conflicting evidence regarding potential deleterious long-term outcomes, such as increased cancer and autoimmune disease risk. We aimed to assess these outcomes in thymectomized versus non-thymectomized MG patients.</p><p><strong>Methods: </strong>We retrospectively reviewed the medical records of patients with acquired, autoimmune MG followed at the Prosserman Neuromuscular Clinic, University Health Network (UHN), between January 2000 and July 2025. We excluded patients with malignancy or other autoimmune diseases before MG. We created matched datasets (thymectomy vs. no-thymectomy) and built Cox models to assess the rate of new malignancy or autoimmune disease. We also used inverse probability of treatment weights (IPTW) to balance relevant covariates (age at MG onset, sex, disease duration, medications) in the full sample, and tested Cox models in the weighted dataset for each outcome.</p><p><strong>Results: </strong>Of 566 patients, 106 had a thymoma and were excluded. Of the 460 patients included, 161 had a thymectomy. There was no difference in the hazard ratio (HR) for a new malignancy in the matched cohort (HR: 0.94, CI 0.83-1.07) nor in the IPTW model. The incidence of autoimmune disease was slightly higher in the thymectomy group in the matched cohort (HR 1.33 [1.15-1.52]), but there was no difference in the IPTW analyses (HR 1.55, CI [0.40-5.9]).</p><p><strong>Discussion: </strong>In this cohort of patients with non-thymomatous MG, thymectomy was not associated with an increased risk of malignancy. Different models for a second autoimmune disease had conflicting findings, requiring further research.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"1065-1072"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMNR7 as a Neuromyopathy-A Novel VWA1 Variant With Minipolymyoclonus, Fasciculations, and Scapular Winging.","authors":"Riya Sharma, Siddharth Chand, Sandeep Singh, Mahesh Prakash, Manoj Kumar Goyal, Ritu Shree","doi":"10.1002/mus.70102","DOIUrl":"10.1002/mus.70102","url":null,"abstract":"","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"1190-1193"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Nusinersen Monotherapy Versus Combination Therapy With Nusinersen and Onasemnogene Abeparvovec in Spinal Muscular Atrophy Type 1 Patients With Two SMN2 Copies: A Multicenter Study From Türkiye.","authors":"Hulya Maras Genc, Fulya Kurekci, Gulten Ozturk, Ayfer Sakarya Gunes, Sema Saltik, Mehmet Akif Kilic, Gokce Cirdi, Olcay Unver, Mustafa Komur, Ismail Hakki Akbeyaz, Yılmaz Zindar, Leman Tekin Orgun, Cisem Duman Kayar, Serhat Guler, Ezgi Caglar, Esma Sengec, Edibe Pembegul Yildiz, Bulent Kara, Dilsad Turkdogan","doi":"10.1002/mus.70191","DOIUrl":"10.1002/mus.70191","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Data comparing nusinersen monotherapy with combination therapy using nusinersen and onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) type 1 patients are limited. This study aimed to compare the clinical outcomes of nusinersen monotherapy versus combination therapy (nusinersen and OA) in SMA type 1 patients with two SMN2 copies.</p><p><strong>Methods: </strong>This retrospective multicenter study included 82 patients divided into nusinersen monotherapy (n = 42) and combination therapy (n = 40) groups. Outcomes included motor milestones, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) scores, respiratory and nutritional status, and survival. Patients were stratified by age at treatment initiation (≤ 3, 3-6, and > 6 months). An age-matched subgroup analysis was performed.</p><p><strong>Results: </strong>Age at treatment initiation, total administered nusinersen doses, and follow-up duration were comparable between groups. All deaths (n = 8) occurred in the monotherapy group among patients who initiated treatment after 3 months of age (p = 0.005). There was no significant difference between groups in the age at achieving unsupported sitting. In the age-matched subgroup analysis (n = 44, 22 per group), no significant differences were found between monotherapy and combination therapy in terms of motor function, CHOP-INTEND progression, respiratory and feeding status. Earlier treatment was associated with better feeding outcomes (OR: 0.740, p = 0.024). Pre-treatment respiratory and feeding status were also predictive of corresponding outcomes.</p><p><strong>Discussion: </strong>Early treatment is the main determinant of outcomes, while combination therapy shows no clear advantage over monotherapy. Larger prospective studies are needed to clarify the role and timing of combination therapy.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"966-975"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}