Neuromuscular Disorders最新文献

{"title":"178PTwo-year stride-level evaluation of ambulatory function in ambulant DMD patients above 4 years old","authors":"M. Poleur ,&nbsp;G. Parinello ,&nbsp;E. Vrščaj ,&nbsp;A. Dolanska ,&nbsp;P. Nowakowski ,&nbsp;C. Anghelescu ,&nbsp;L. Szabo ,&nbsp;M. Leanca ,&nbsp;A. Mirea ,&nbsp;S. Kodsy ,&nbsp;A. Saleh ,&nbsp;D. Osredkar ,&nbsp;J. Haberlova ,&nbsp;A. Potulska-Chromik ,&nbsp;N. Butoianu ,&nbsp;P. Delmar ,&nbsp;P. Strijbos ,&nbsp;D. Eggenspieler ,&nbsp;L. Servais ,&nbsp;the ActiLiège-Next study group","doi":"10.1016/j.nmd.2025.105531","DOIUrl":"10.1016/j.nmd.2025.105531","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is characterized by severe and progressive muscle weakness. Assessing investigational drug efficacy in a reasonable timeframe is challenging due to a lack of objective, reliable, and sensitive outcome measures. The wearable sensor ActiMyo/Syde was developed to assess motor function accurately and precisely at the stride level during daily life. One variable derived from these sensor data, SV95C (measuring the 5% most rapid strides), was recently qualified as primary endpoint for ambulant DMD by the European Medicines Agency. To gather 3-year longitudinal functional data using this sensor, ambulant DMD patients and controls were enrolled in the ActiLiège-Next study. Patients were asked to wear sensors at both ankles daily during the first 3-12 months and for 1 month every 3 months afterwards, and controls were asked to wear them for 1 month every 12 months. Eighty-seven ambulant DMD patients aged 4 to 14 years (median: 8.0y) and 37 controls (9.8y) were enrolled. As of Jan 2025, &gt;95% of patients showed good adherence with sensor wear at baseline. SV95C reliability was excellent, with an intraclass correlation coefficient of 0.96 for patients and 0.87 for controls. The Spearman correlation with North Star ambulatory assessment, 6-minute walk test, 4-stair climbing test and time to rise from floor was 0.65, 0.54, -0.71 and -0.66, respectively (n=76-81; p&lt;0.001). For patients between 4 and 8 years old, mean SV95C improved from baseline at 6 months (0.08m/s, SRM [standardized response mean]=0.55, n=37), and then declined at 12 and 18 months (-0.06m/s, SRM=ns, n=27; and -0.13m/s, SRM=-0.52, n=18, respectively). Patients ≥8 years old experienced a marked decline at 6, 12 and 18 months: -0.09m/s (SRM=-0.51, n=30), -0.15m/s (SRM=-0.99, n=24) and -0.24m/s (SRM=-2.10, n=16), respectively. These data confirm the excellent reliability, external validity and responsiveness of SV95C in ambulant DMD above 4 years old. All available 18- and 24-month data will be shared at the congress.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105531"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"175PA prognostic score for time to loss of ability to rise from supine in Duchenne muscular dystrophy (DMD)","authors":"F. Muntoni ,&nbsp;J. Signorovitch ,&nbsp;J. Marden ,&nbsp;N. Done ,&nbsp;S. Wang ,&nbsp;H. Akbarnejad ,&nbsp;H. Kang ,&nbsp;T. Li ,&nbsp;S. Ward ,&nbsp;A. Manzur ,&nbsp;N. Goemans ,&nbsp;V. Straub ,&nbsp;E. Mercuri ,&nbsp;L. Servais","doi":"10.1016/j.nmd.2025.105528","DOIUrl":"10.1016/j.nmd.2025.105528","url":null,"abstract":"<div><div>Loss of ability to rise from supine (LoR) is an early milestone in DMD that reduces independence in daily living and marks the progression towards loss of ambulation. Previous research has identified single thresholds of rise from supine (RFS) time as prognostic for LoR (e.g., &gt;5s). We used machine learning to develop a prognostic score for time to LoR based on multiple data-driven thresholds and patient characteristics that are easily assessed in clinical practice and routinely included in clinical trials. Longitudinal data from 595 boys with DMD were drawn from UZ Leuven, PRO-DMD-01, North Star UK, iMDEX, and placebo arms from trials of tadalafil, ataluren, and drisapersen. LoR was defined as the first assessment with timed RFS ≥30s, graded RFS of 1, or NSAA rise score of 0. A Weibull survival classification and regression tree model was used to identify risk groups. Candidate predictors included age, height, weight, BMI, steroid regimen, type, and duration, RFS, 10-meter walk/run (10MWR), and NSAA items. Patients had a mean ±standard deviation baseline age of 8.3±2.1 years, with RFS time of 6.1±4.2s, and NSAA total score of 24.9±5.8. The fitted model identified 5 risk groups showing excellent risk stratification, with median times to LoR of 0.3, 0.7, 1.5, 2.7, and 4.5 years (log-rank p&lt;0.001). Risk groups differed by baseline RFS with thresholds at &lt;5s, &lt;10s, and &lt;21s, with further stratification by NSAA sit-to-stand score (0/1 vs 2). The model explained 42.2% of variation in time to LoR, comparable to more complex survival models with both continuous measures and age and 10MWR included as additional predictors (pseudo-R² 44.8%). This prognostic score, based on readily assessable functional measures, provides clinically meaningful differentiation of times to LoR. Upon validation in independent data, this model could inform the design of clinical trials seeking to enrich for levels of LoR risk and benchmark LoR outcomes for patients receiving novel therapies.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105528"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"41PTreatment outcomes in idiopathic inflammatory myopathies based on pathology and autoantibody profiles: a single-center study of 127 cases","authors":"N. Eura,&nbsp;Y. Nishimori,&nbsp;A. Yamanaka,&nbsp;T. Shiota,&nbsp;H. Tanaka,&nbsp;T. Ohashi,&nbsp;H. Shimizu,&nbsp;M. Yamaoka,&nbsp;N. Yamada,&nbsp;N. Iguchi,&nbsp;A. Tanaka,&nbsp;M. Sugata,&nbsp;H. Nanaura,&nbsp;T. Kiriyama,&nbsp;K. Sugie","doi":"10.1016/j.nmd.2025.105504","DOIUrl":"10.1016/j.nmd.2025.105504","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders affecting skeletal muscle and various organs. Although myositis-specific autoantibodies (MSAs) aid in diagnosis, treatment strategies remain suboptimal. Large-scale, subtype-specific outcome studies are limited. We retrospectively analyzed 127 IIM patients who underwent muscle biopsy at our institution between 2009 and 2023. Inclusion required pathological confirmation, excluding inclusion body myositis and secondary myositis related to collagen diseases or immune checkpoint inhibitors. MSAs were detected in 97 patients (76%). Among MSA-positive cases, dermatomyositis (DM: 27.1%) and immune-mediated necrotizing myopathy (IMNM: 27.1%) were most common, followed by antisynthetase syndrome (ASS: 14.4%) and polymyositis (PM: 2.7%). DM was linked to anti-TIF1-γ, MDA5, Mi-2, and NXP-2 antibodies (in that order); IMNM to SRP, HMGCR, and AMA-M2. HMGCR-positive patients had the highest CK levels. Interstitial lung disease (ILD) was seen in 90% of MDA5, 67% of Mi-2, and 50% of SRP cases. Malignancies occurred in all antibody subtypes except MDA5, NXP-2, and HMGCR, and originated from diverse organ systems. Seven of 13 traceable malignancy cases died within 3 years of IIM diagnosis. Notably, AMA-M2-positive patients showed a high frequency of respiratory failure unrelated to ILD (40%) and cardiac events such as arrhythmias or heart failure (89%). All patients received glucocorticoids. Immunosuppressants were used in 80% of MDA5, 60% of HMGCR, and 47% of ASS cases. The most frequently used immunosuppressant was tacrolimus, followed by methotrexate and azathioprine. IVIg was limited to four severe cases. At 3 years, the mean prednisolone dose was 8.4 ± 5.5 mg; only SRP-positive patients reached &lt;5 mg/day. Orthopedic complications such as fractures occurred in 9.2%. This study highlights clinical diversity and treatment challenges in IIM. Despite improved diagnostics, more effective, tailored therapies are urgently needed.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105504"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"04ODenervated human muscle fibers promote reinnervation via neurotrophic factor release in SMA and ALS","authors":"R. Gokul-Nath ,&nbsp;C. Collins ,&nbsp;L. Valverde ,&nbsp;C. Lleixa ,&nbsp;J. Verdú-Díaz ,&nbsp;A. Di Lorenzo ,&nbsp;P. Llarch ,&nbsp;L. Querol ,&nbsp;C. Marini-Bettolo ,&nbsp;R. Rojas-García ,&nbsp;J. Diaz-Manera","doi":"10.1016/j.nmd.2025.105462","DOIUrl":"10.1016/j.nmd.2025.105462","url":null,"abstract":"<div><div>Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neuromuscular disorders characterized by the progressive degeneration of motor neurons, leading to skeletal muscle denervation, weakness, and atrophy. However, the molecular pathways underlying the muscle response to denervation in human tissue remain poorly defined. We performed single-nucleus RNA sequencing (snRNA-seq) and ATAC-seq on muscle biopsies from patients with SMA type 3 (n = 7), ALS (n = 4), and age- and sex-matched healthy controls (n = 5). Data were analyzed using a custom bioinformatics pipeline based on Seurat and Harmony. Key findings were validated by immunofluorescence (IF) on additional muscle samples. To assess functional implications, rat spinal cord neurons were cultured in vitro with factors identified from muscle transcriptomic analyses. Fibro-adipogenic progenitor (FAP) cells were isolated from patient and control samples and subjected to single-cell RNA sequencing to identify transcriptionally distinct subpopulations. snRNA-seq revealed a significant increase in satellite and inflammatory cell populations, along with a reduction in myofiber and smooth muscle cell numbers in SMA and ALS muscle. Pseudobulk analysis showed that genes upregulated in SMA and ALS were enriched for pathways related to vascular development, cell projection organization, cell adhesion, synaptic remodelling, and neuronal development. A subpopulation of muscle fibers was identified in both SMA and ALS, characterized by elevated expression of genes involved in synaptic maintenance and axonal guidance, including MUSK, LRP4, COL19A1, EFNA5, and NTN1. ATAC-seq confirmed accessible chromatin regions at loci related to neuromuscular junction maintenance and neuronal growth, suggesting transcriptional readiness for protein expression. Immunofluorescence confirmed increased expression of these proteins in patient biopsies. Furthermore, rat spinal cord neurons cultured with muscle-derived neurotrophic factors such as EFNA, NTN1, and BDNF exhibited enhanced dendrite outgrowth. FAPs from patient muscle displayed upregulation of extracellular matrix components and neurotrophic factors implicated in neuronal support and synaptic repair. Our study reveals that denervated muscle fibers actively engage in a compensatory, pro-regenerative response by releasing neurotrophic factors aimed at restoring neuromuscular connectivity. These factors may serve as valuable biomarkers for disease progression and represent promising therapeutic targets for enhancing reinnervation in SMA and ALS. Future work should explore their potential in combination therapies aimed at modulating the muscle microenvironment to support motor neuron recovery.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105462"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to the 30th World Muscle Society Congress","authors":"","doi":"10.1016/j.nmd.2025.106211","DOIUrl":"10.1016/j.nmd.2025.106211","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 106211"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"169PComparison of western-blot, mass spectrometry and simple-western methods shows that simple-western is the most sensitive method to detect µ-dystrophin","authors":"L. Buscara ,&nbsp;S. Genries-Ferrand ,&nbsp;C. Varela Moreira ,&nbsp;N. Stiet ,&nbsp;G. Cedrone ,&nbsp;C. Sagrere ,&nbsp;F. Salsac ,&nbsp;R. El-Khoury ,&nbsp;E. Bertil-Froidevaux ,&nbsp;C. Georger ,&nbsp;S. Blaie ,&nbsp;L. Thibaut ,&nbsp;F. Cao ,&nbsp;S. Braun ,&nbsp;G. Perret ,&nbsp;M. Blatzer ,&nbsp;N. Daniele","doi":"10.1016/j.nmd.2025.105522","DOIUrl":"10.1016/j.nmd.2025.105522","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD), a rare X-linked genetic disorder affecting male children, leads to progressively severe muscle dysfunction often associated with respiratory and/or cardiac insufficiencies and premature death. The pathology is caused by out-of-frame mutations in the DMD gene, leading to absence of dystrophin, a large muscle protein. As the large size of dystrophin cDNA impedes its packaging in AAV vectors, various shorter micro-dystrophin (µDys) transgenes are used for clinical development. Different analytical methods may be used to measure the µDys levels from muscle biopsies. GNT-016, a clinical trial investigating an AAV-based µDYS, uses the simple-western (SW) method for quantifying the therapeutic product. In an effort to document the differences in methodologies, we performed a side-by-side comparison of 3 methods used in DMD clinical trials. Total proteins extracted from DMDmdx rats’ muscles sampled after intravenous treatment with an AAV8-spC5-12-µDYS were used for the quantification of µDYS in dose-response experiments performed by nano LC/MS mass spectrometry, western-blot and SW methodologies. SW is a capillary-based electrophoretic method allowing separation and detection of proteins in a single device. Both mass spectrometry and SW prove advantageous compared to western-blot in terms of reproducibility and repeatability (CV&lt;25% for SW and CV&lt;8% for mass spectrometry). However, SW is over 4,000 times more sensitive than the 2 other methods. Considering the limited amounts of patient’s tissue available to measure dystrophin quantities, sensitivity appears to be a key factor. SW variability is lower than the recommended guidelines and easier to set-up than mass spectrometry, which requires very specific equipment and technical expertise. This method, used for the quantification of µDYS expression in our clinical trial, was globally consistent with the immunohistological results performed on the same samples.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105522"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"54VPDistinct histopathological features of juvenile idiopathic inflammatory myopathies: a quantitative comparative study","authors":"F. Hakim ,&nbsp;S. Sakka ,&nbsp;M. Snoussi ,&nbsp;O. Boudawara ,&nbsp;K. Moalla ,&nbsp;N. Bouattour ,&nbsp;S. Daoud ,&nbsp;N. Charfi ,&nbsp;L. Sellami ,&nbsp;S. Marzouk ,&nbsp;T. Boudawara ,&nbsp;M. Damak","doi":"10.1016/j.nmd.2025.105517","DOIUrl":"10.1016/j.nmd.2025.105517","url":null,"abstract":"<div><div>Juvenile idiopathic inflammatory myopathies (JIIM), defined by onset before 18 years of age, are rare autoimmune disorders that can present with distinct clinical and serological profiles. However, specific histopathological features in JIIM remain underexplored. This study aims to identify histological characteristics distinct to JIIM through a quantitative comparative analysis. We conducted a retrospective study on patients diagnosed with IIM at a Tunisian neurology center, following the 2017 ACR-EULAR criteria. Histopathological features were analysed through a review of available slides, including fiber atrophy, necrosis, ischemia, regeneration, fibrosis, and inflammatory infiltrates, graded with a predefined scoring system. Available muscle samples were collected and examined for immunohistochemical markers (CD4, CD8, CD20, CD31, CD68, anti-MxA). Histological findings in juvenile patients were collected compared to those in adults. We included 13 juvenile cases from 100 IIM patients (13%). The mean age of JIIM was 12± 5,2 years (range: 3–17). Sex ratio: 0.18. JIIM included 10 dermatomyositis patients (2 anti-Mi2, 1 anti-NXP-2, 1 seronegative) and 3 overlap myositis (1 scleromyositis, 1 lupus-associated myositis, 1 anti-Jo-1 anti-synthetase syndrome). Juvenile onset was correlated with severe fiber atrophy (38.4%, p=0.024) with a perifascicular atrophy extended into the endomysium (53.8%, p=0.01). It was also associated with severe inflammatory infiltrates (46%, p=0.02), primarily in the perivascular region (84.6%, p=0.23). However, inflammatory cell types, vascular injury, and MXA staining did not show a specific pattern related to juvenile onset. JIIM is characterized by distinct histopathological features, including pronounced inflammatory infiltrates and perifascicular atrophy. These findings highlight the age-specific mechanisms in JMII, which may be associated with more severe outcomes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105517"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on ‘Levels of exercise exposure among people living with neuromuscular disorders: lessons learned from real-world data’","authors":"Eric Lukas Voorn","doi":"10.1016/j.nmd.2025.105453","DOIUrl":"10.1016/j.nmd.2025.105453","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"54 ","pages":"Article 105453"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"302PWhole-body fat-referenced MRI measures disease progression in patients with spinal and bulbar muscular atrophy","authors":"M. Karlsson ,&nbsp;P. Widholm ,&nbsp;A. Ahlgren ,&nbsp;P. Hatsis ,&nbsp;C. Gentry ,&nbsp;C. Grunseich ,&nbsp;A. Gharib ,&nbsp;A. Kokkinis ,&nbsp;A. AlQahtani ,&nbsp;P. Fratta ,&nbsp;L. Zampedri ,&nbsp;D. Jayaseelan ,&nbsp;H. McKenzie ,&nbsp;S. Wastling ,&nbsp;M. Katsuno ,&nbsp;S. Yamada ,&nbsp;Y. Kishimoto ,&nbsp;T. Kawase ,&nbsp;T. Taoka ,&nbsp;V. Vigiletta","doi":"10.1016/j.nmd.2025.105550","DOIUrl":"10.1016/j.nmd.2025.105550","url":null,"abstract":"<div><div>More sensitive outcome measures in spinal bulbar muscular atrophy (SBMA) clinical trials are needed. Fat-referenced MRI has been successful in characterizing muscle atrophy and fat replacement in other neuromuscular diseases. We aimed to investigate the ability of fat-referenced MRI to assess changes in muscle composition and track disease progression in SBMA and the association to clinical outcomes. Whole-body Dixon MRI of 25 SBMA patients with mild-to-moderate disease severity were analyzed using AMRA Researcher, quantifying lean muscle volume (LMV), muscle fat fraction (MFF), and muscle fat infiltration (MFI) in 38 muscle groups. Muscles were classified as Normal Appearing, Intermediate, or End-Stage based on baseline fat content. Muscle measurements were combined into composites. Responsiveness was assessed using standardized response mean (SRM). Composites were correlated to SBMA functional rating scale (SBMAFRS), modified SBMAFRS (leg and trunk), and 2-minute-walk-test (2MWT) at baseline. The mean±SD age was 57.6±7.1 years, SBMAFRS 40.6±3.9, CAG Repeats 45.3±3.7, BMI 26.3±3.8 kg/m2. Patients had median (min,max) 5 (0,30) Normal Appearing, 26 (8,34) Intermediate, and 2 (0,13) End-Stage muscles. 12-month change in whole-body composite LMV/MFF/MFI was mean±SD (SRM) -4.38±2.48% (-1.76), 2.49±1.38 p.p. (1.81), and 0.79±0.51 p.p. (1.55) respectively (p&lt;0.001). Change in thigh composite was -4.97±3.50% (-1.42), 2.81±1.65 p.p. (1.70), and 1.05±0.76 p.p. (1.38) (p&lt;0.001). There were moderate correlations to SBMAFRS (r: 0.46/-0.41/-0.51), modified SBMAFRS (r: 0.50/-0.63/-0.67), and 2MWT (r: 0.73/-0.53/-0.55). Whole-body MRI captures muscle composition in SBMA patients and shows good responsiveness in describing 12-month natural progression. Baseline MRI assessments reflect disease severity as measured by SBMAFRS and 2MWT.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105550"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"301PPatterns of volume and fat infiltration in skeletal muscle of adults with spinal muscular atrophy","authors":"T. Duong,&nbsp;M. Anna Yao,&nbsp;R. Yoseph Hailu,&nbsp;S. Vogt-Domke,&nbsp;J. Day,&nbsp;N. Hageman","doi":"10.1016/j.nmd.2025.105549","DOIUrl":"10.1016/j.nmd.2025.105549","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) is a genetic disorder characterized by protein deficiency affecting lower motor neurons and the neuromuscular junction, leading to muscle weakness and fatigue. Pathologically, muscles exhibit progressive fat infiltration and atrophy. Whole-body MRI is a valuable tool for assessing these changes in vivo. Structural T1 MRI sequences can quantitatively measure fat replacement in skeletal muscle, while fluid-sensitive T2 sequences, such as short tau inversion recovery (STIR), can detect inflammatory changes that precede clinical symptoms and fat infiltration. These imaging techniques can serve as diagnostic biomarkers and monitor disease progression. Recent advancements in artificial intelligence (AI) have enabled reliable automated methods for masking and identifying individual muscles in whole-body MRI, facilitating group-level analysis of muscle volume and fat fraction. Previous studies have highlighted distinct patterns of muscle involvement across different SMA types. This study aims to characterize the neuromuscular pathway structures affected in adults with SMA type 3. We conducted whole-body 3T MRI on six subjects with SMA type 3 (five ambulatory, one non-ambulatory; ages 26-67). Imaging sequences included T1 (2-point) DIXON, T2 STIR, and structural T1/T2 of the brain. An AI-based masking approach (Springbok) was employed to isolate and assess 71 individual muscles across 36 functional groups for muscle volume, fat fraction, and left-right asymmetry. Group-level analysis revealed reduced volumes in hip flexors, hip adductors, knee extensors, and proximal upper extremity muscles, with significant fat infiltration in these areas. Asymmetry levels varied among subjects, with individual muscles exhibiting localized fat infiltration patterns. Notably, atrophy and fat fraction were most pronounced in the hip and knee extensors in the lower extremities, while axial muscles of the trunk and proximal limbs were predominantly affected in the upper extremities. These findings align with previous studies and clinical presentations, suggesting a targeted pathological process affecting specific motor units. This study supports the hypothesis that SMN protein deficiency in SMA selectively impacts certain neuromuscular motor groups, correlating with segmental lower motor neuron weakness observed clinically and in post-mortem analyses. Limitations include the small cohort size and absence of additional imaging modalities. Future research will aim to enhance statistical power and explore central effects on higher structures within the neuromuscular pathway, potentially identifying specific biomarkers or therapeutic targets.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105549"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}