Neuromuscular Disorders最新文献

{"title":"188PBilateral analysis of upper limb endpoints in ambulant and non-ambulant DMD patients.","authors":"M. Michaëls ,&nbsp;A. Prins ,&nbsp;E. Fleerakkers ,&nbsp;M. van der Holst ,&nbsp;E. van Zwet ,&nbsp;H. Kan ,&nbsp;E. Niks","doi":"10.1016/j.nmd.2025.105541","DOIUrl":"10.1016/j.nmd.2025.105541","url":null,"abstract":"<div><div>In Duchenne muscular dystrophy (DMD), systemic therapeutical approaches face challenges in tissue exposure. Intramuscular (IM) dosing may increase tissue concentrations, limit systemic adverse effects, and be relevant to more advanced stages of the disease, especially when targeting the upper limb. We compared disease progression between the dominant and non-dominant arm in DMD to explore the possibilities of clinical trials using a self-controlled design in IM interventions. PUL2.0 total score, isometric strength for shoulder abduction, elbow flexion, elbow extension and wrist dorsiflexion using MicroFET2, isokinetic strength for elbow flexion and extension using Biodex pro 4 and handgrip strength using MyoGrip were assessed in the dominant and non-dominant upper limb at baseline and 12 months. Upper arm extensor and flexor muscle fat fractions were assessed with quantitative MRI. Wilcoxon signed rank test for PUL2.0 and paired t-tests for other endpoints were used to assess differences at baseline and for deltas over time. Twenty-two patients were assessed at baseline, median age 9.2y, range 6.0 – 17.0 and ten for the 12-month follow-up visit, with fifteen expected to do so by October 2025. At baseline, only PUL2.0 total score and handgrip were higher in the dominant arm compared to non-dominant (36.5 vs 35.0, p=0.003 and 8.0 vs 7.2Kg, p=0.033). No significant dominant – non-dominant difference for delta over time was seen for any of the endpoints, including PUL2.0 total score, –2.0 (4.3) vs. –1.0 (3.3), shoulder abduction, –7.6 (14.3) vs. –6.5N (20.6), elbow isometric flexion, – 1.9 (6.1) vs. – 3.9N (10.9) and handgrip –0.2 (1.8) vs. –0.4Kg (2.0). Ongoing analyses include quantitative MRI results. Our results strengthen clinical observations that differences in DMD progression between dominant and non-dominant upper limbs are limited. This paves the way for clinical trials using unilateral and/or local IM interventions with a patient as his own control design.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105541"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204499","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":"191PComprehensive analysis of longitudinal SV95C measurements, an e-digital mobility assessment in a real-life DMD population in the GNT-014-MDYF natural history study","authors":"T. Montier ,&nbsp;S. De Lucia ,&nbsp;J. Davion ,&nbsp;C. Espil ,&nbsp;M. Guglieri ,&nbsp;B. Chabrol ,&nbsp;L. Le Goff ,&nbsp;A. Seferian ,&nbsp;G. Perret ,&nbsp;E. Guemas ,&nbsp;A. Valent ,&nbsp;F. Cao ,&nbsp;V. Laugel ,&nbsp;F. Muntoni","doi":"10.1016/j.nmd.2025.105544","DOIUrl":"10.1016/j.nmd.2025.105544","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease characterized by variable age of loss of ambulation. Hospital based physiotherapist-assisted (PA) functional assessments are commonly used for monitoring clinical progression. Stride Velocity at the 95th Centile (SV95C) captures daily ability using a wearable device in a real-life setting and therefore relies less on patient collaboration with assessment or inter-evaluator variability. The European Medicines Agency (EMA) qualified SV95C as a primary endpoint in DMD. This analysis aims to explore its validity and normative data in a prospective natural history (NH) study (GNT-014-MDYF). DMD boys, aged 5-9 years, receiving steroids and achieving an NSAA ≥18 were enrolled. The SV95C and other clinical functional outcomes (e.g., NSAA) were measured every 6 months. Data (n=77) were described for age subgroups (5-8Y and &gt;8Y). SV95C reliability was analyzed by intra-class correlation coefficient (ICC) with SV95C separated by 2 half recording periods. Spearman’s correlation and regression methods were employed to assess the relationship between SV95C and other functional outcomes. The sensibility to change by Standardized response mean (SRM) was assessed. Patients showed good compliance with the use of device (eg 96% at baseline). SV95C was highly reliable overtime (ICC 0.96- 0.98 over two years), with clear separation from the healthy controls. Good correlations were observed between SV95C and other PA outcomes (Correlation coefficient from 0.56 to 0.83).</div><div>At 1 and 2 years, SRM were -0.47 and -0.80 in SV95C with mean declines from baseline of 0.097m/s and 0.162m/s for 5-8Y and 0.298m/s and 0.363m/s for &gt;8Y groups. This analysis demonstrated the validity of SV95C in a NH study with standardized follow-up and its consistency with published data. SV95C was sensitive to detect clinical change and correlated well with other clinical measures. The predictability and clinical meaningful thresholds are to be explored.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105544"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204502","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":"31PClinico-sero-pathological and transcriptomic features of inclusion body myositis with T-cell large granular lymphocytic leukemia","authors":"P. Soontrapa ,&nbsp;I. Pinal-Fernandez ,&nbsp;P. Paul ,&nbsp;M. Skolka ,&nbsp;M. Milone ,&nbsp;M. Shi ,&nbsp;M. Shah ,&nbsp;A. Mammen ,&nbsp;T. Liewluck","doi":"10.1016/j.nmd.2025.105494","DOIUrl":"10.1016/j.nmd.2025.105494","url":null,"abstract":"<div><div>T-cell large granular lymphocytic leukemia (T-LGLL) is a rare indolent cytotoxic lymphocyte leukemia reported in 40–58% of inclusion body myositis (IBM) patients. We investigated the spectrum of myopathies in T-LGLL patients and compared clinicopathologic, laboratory, and transcriptomic features between IBM patients with and without T-LGLL. We retrospectively reviewed two Mayo Clinic cohorts: T-LGLL patients (2003–2018) evaluated for myopathies, and IBM patients (2016–2022) tested for T-LGLL by T-cell receptor gene rearrangement or flow cytometry. Among 447 T-LGLL patients, 13 (2.9%) had myopathies; IBM (n=7, 1.6%) was most common, followed by nonspecific inflammatory myopathy (n=3), nonspecific myopathy (n=2), and radiation-induced myopathy (n=1). Among 43 IBM patients, 9 (20.9%) had T-LGLL, with 5 diagnosed prior to the onset of weakness. Seven patients from the IBM cohort overlapped with the T-LGLL cohort. Clinical, pathological, and laboratory features were similar between IBM patients with and without T-LGLL, except for milder finger flexor weakness (median summated MRC 8.0 vs 6.0; p=0.01) and more frequent neutropenia (55.6% vs 0%; p&lt;0.001) in the T-LGLL group. Two patients received immunotherapy for T-LGLL without improvement in myopathy. Transcriptomic analysis of IBM muscle biopsies showed that patients with T-LGLL had a more active immune profile, with upregulation of T-cell and macrophage markers, elevated levels of IFN-γ and IFN-γ–inducible genes, heightened cytokine activity, and enhanced immunoglobulin production. T-LGLL occurred in a minority of IBM patients in our cohort, less than previously reported. Despite similar clinicopathological features, transcriptomic data suggest IBM with T-LGLL reflects a more immunologically active disease subtype, which could have important implications for the development of future therapies.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105494"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204099","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":"44PHigh-resolution spatial transcriptomics reveals myofiber-immune cell interactions in inclusion body myositis","authors":"S. de Haan,&nbsp;L. Heezen,&nbsp;A. Mahfouz,&nbsp;H. Kan,&nbsp;U. Badrising,&nbsp;P. Spitali","doi":"10.1016/j.nmd.2025.105507","DOIUrl":"10.1016/j.nmd.2025.105507","url":null,"abstract":"<div><div>Inclusion Body Myositis (IBM) is the most common inflammatory muscle disease in older adults with no effective treatment available. Unlike other inflammatory myopathies, IBM follows a slowly progressing, chronic disease course characterized by intracellular inflammation, including T-cell infiltration, and degenerative myofiber pathology including protein aggregates, centralized nuclei and rimmed vacuoles - together resulting in muscle damage. To understand the interplay between immune cells and myofiber pathology in IBM, we performed high-resolution Spatial Transcriptomics on human IBM and healthy control muscle biopsies (n=3). This approach allows for in situ, subcellular molecular analyses of myofibers, fiber-immune cell interactions, and the discovery of antigens presented on myofibers involved in immune cell infiltration. Our dataset includes 5000 pre-configured genes encoding signaling components, and 480 in-house selected genes specific to muscle tissue and neuromuscular diseases. To define individual myofibers, image-based fiber segmentation was performed by developing a customized muscle-specific segmentation pipeline using Cellpose within the SPArrOW spatial library, resulting in the recovery of over 8,000 and 2,000 IBM and healthy control myofibers, respectively. Preliminary data analysis indicates an increase in number and diversity of mononuclear inflammatory cells, including an expansion of T-cells and a distinct B-cell population in IBM. Unsupervised myofiber clustering indicates a population of damaged myofibers and a reduction in Type 2 myofibers in IBM. Additionally, IBM biopsies show a specific myofiber population surrounded by immune infiltrates enriched for transcripts encoding known protein aggregates, HLA-proteins, and genes potentially involved in protein aggregation and/or antigen presentation. Our data presents a valuable resource to investigate molecular changes in IBM, enhancing our understanding of immune-myofiber crosstalk, antigen presentation, and disease progression of IBM.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105507"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204186","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":"174PHow can we analyze natural history across multiple sites without moving the data? - a feasibility study and early pilot using PUL 2.0","authors":"F. Muntoni ,&nbsp;E. Niks ,&nbsp;M. Michaëls ,&nbsp;M. Brooke ,&nbsp;Y. Meijer-Krom ,&nbsp;B. Wong ,&nbsp;L. Servais ,&nbsp;W. Franke ,&nbsp;J. Kurps ,&nbsp;J. Freimark ,&nbsp;E. Billmyer ,&nbsp;J. Marden ,&nbsp;J. Signorovitch ,&nbsp;S. Ward","doi":"10.1016/j.nmd.2025.105527","DOIUrl":"10.1016/j.nmd.2025.105527","url":null,"abstract":"<div><div>Analysis of Real-World Data from patients with DMD has proven pivotal in advancing understanding of natural history, which in turn has led to better clinical trial design and analysis. However, natural history can evolve. With both care standards and the availability of new therapies evolving differently across centers and geographies, it is imperative that comparisons of outcomes are understood in the context in which they were observed. To address these concerns, cTAP engaged The Hyve, a knowledge engineering consultancy, to investigate collaboration via federated analyses, an approach that enables analyses of data without moving data outside organizations and geographies. A feasibility study was conducted through semi-structured interviews with four geographies assessing interoperability along three axes: data, technology, and governance. Feasibility was ranked as Low, Medium, or High based on a qualitative assessment of the extent of changes required to processes, technologies or data. A pilot study adapted analytical code to the data model used at LUMC which was then run against patient data at that center. A federated framework is feasible. For data, sites collect similar data and use the same functional assessments. For technology, there is no existing end-to-end solution, but there are components available that can be assembled. For governance, sites are fully compliant and require no change. cTAP will need to formalize current manual processes for securing iterative site approval of analyses to ensure an auditable governance. Execution of the code in the pilot study generated a prognostic model for PUL 2.0 in a single run with no errors. Enabling important scientific analyses requiring multi-institutional collaboration to be addressed is feasible. A decade of successful multi-institutional collaboration with cTAP lowers the barrier to execution.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105527"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204213","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":"01PKnowledge of Indonesian neurologists in the diagnosis and management of patients with idiopathic inflammatory myopathy","authors":"M. Abdan Syakuron ,&nbsp;M. Hakim ,&nbsp;A. Budikayanti ,&nbsp;W. Wiratman ,&nbsp;A Yanuar. Safri ,&nbsp;N. Fadli ,&nbsp;A Ridski. Harsono ,&nbsp;F. Octaviana ,&nbsp;L. Ari Indrawati","doi":"10.1016/j.nmd.2025.105465","DOIUrl":"10.1016/j.nmd.2025.105465","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIM) should be managed in a multidisciplinary manner, including neurologists. Prior IIM study at Dr Cipto Mangunkusumo Hospital (CMH) showed 7 months as the median time delay from specialist to IIM diagnosis. We aimed to assess the knowledge of Indonesian neurologists using an anonymised e-survey (32 questions) in six domains (etiology, classification, clinical manifestation, supporting examination, management, and prognosis) which was developed by the medical staff of neuromuscular diseases of CMH. The number of subjects who participated in this study were 198/2750 members of the Indonesian Neurological Association members. The subjects' working distribution was divided into three regions (86,3% works in western part as the most densely populated area in Indonesia) The median of knowledge questions scores was 16(0-66)/100. Majority of subjects had good knowledge in the etiology aspect but quite poor in other domains especially classification. Overlap myositis and Antisynthetase syndrome (ASS) were the least known IIM spectrum (22.2 and 14.14%, respectively). Only half of subjects recognized neck flexor muscle weakness as a IIM symptom. Ptosis was misinterpreted as IIM sign in 24.74% subjects. Although most subjects (74.7%) recognized gottron papule, only 8.6% of subjects knew all dermatomyositis skin lesions. Aldolase was only recognized as one supporting data for IIM in 27.27% subjects. Only 1.5% of subjects knew all MSA. Furthermore, autoantibodies specific to ASS were the least known MSA (9.09%). Knowledge about the use of steroid-sparing agents still required improvement. Only one third of the subjects answered correctly about the highest time frame for malignancy. Only 3% answered malignancy's risk factor for IIM correctly. Overall, knowledge of the etiology of IIM was relatively good, but knowledge of the other five domains should be improved. Competency to manage IIM should be sharpened through continuing medical education.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105465"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204258","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":"172PClinical and genetic characteristics of adult patients with Duchenne muscular dystrophy","authors":"L. Leonardis ,&nbsp;N. Matajurc ,&nbsp;N. Teran","doi":"10.1016/j.nmd.2025.105525","DOIUrl":"10.1016/j.nmd.2025.105525","url":null,"abstract":"<div><div>Duchenne muscular dystrophy (DMD) is a severe rare X linked progressive inherited muscular disorder, leading to a premature loss of ambulation and mortality. The aim of this study was to examine the clinical and genetic characteristics of adult patients with DMD, followed at the national tertiary neuromuscular centre. Seventeen patients, aged 27 (1st – 3rd quartile: 20-32, range: 19-37) years had genetically confirmed DMD, mostly caused by deletions (53%), followed by point mutations (35%), and duplications (11%) in DMD. All patients were wheelchair-bound. They got the first wheelchair at the age of 10 (SD 3) years. The median of vital capacity was 11 % of predicted values (1st – 3rd quartile: 8-34). 15/17 (88%) patients used mechanical ventilation, the mean age at the start of non-invasive ventilation usage was 21 (SD 5) years. 16/17 (94%) used cough-machine. Body mass index was 22,9 (SD 6,8, range: 9,9 – 37,5). Most of the patients (59%) were unable to feed themselves, they lost their ability to feed themselves at the age of 20 (SD 8, range 10-36) years. One patient had from 23 years of age radiologically inserted gastrostomy. Four patients (24%) had dilatative cardiomyopathy and arrhythmia. Four patients (24%) were still on daily oral prednisolone. Eight (47%) of them had operation of Achill tendons. 13/17 (76%) were unemployed, 4/17 (24%) were students. On Satisfaction with life scale they reached 24 (SD 6, range: 12-33) points. In conclusion, this analysis of adults living with DMD highlights the significant clinical burden and complex care needs associated with advanced disease stages, emphasizing the importance of multidisciplinary management and ongoing support in this population.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105525"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204264","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":"185PChanges in timed items in DMD patients amenable to skipping exons 44, 45, 51 and 53: a 24-month collaborative study","authors":"G. Cicala ,&nbsp;G. Coratti ,&nbsp;S. Paolucci ,&nbsp;G. Baranello ,&nbsp;J. Exposito Escudero ,&nbsp;A. Wolfe ,&nbsp;M. Brooke ,&nbsp;S. Messina ,&nbsp;F. Ricci ,&nbsp;A. D'Amico ,&nbsp;L. Bello ,&nbsp;C. Bruno ,&nbsp;V. Sansone ,&nbsp;R. Masson ,&nbsp;V. Nigro ,&nbsp;M. Pane ,&nbsp;A. Nascimento ,&nbsp;F. Muntoni ,&nbsp;E. Mercuri ,&nbsp;on behalf of the Italian DMD network","doi":"10.1016/j.nmd.2025.105538","DOIUrl":"10.1016/j.nmd.2025.105538","url":null,"abstract":"<div><div>This study explored 24-month changes in motor function among 458 ambulant boys with genetically confirmed Duchenne muscular dystrophy (DMD), using two timed items: 10-meter walk/run (10MWR) and time to rise from floor (TRF). Participants were recruited from Italian, UK, and Spanish networks and assessed at baseline, 12, 18, and 24 months. When exon-skipping subgroups were examined the 10MWR were overall stable, with minimal differences across skipping subtypes. In boys ≥7, all exon categories showed functional decline, with exon 51 showing the greatest deterioration. The TRF in contrast showed an increase in TRF, indicating a functional deterioration in both age groups across all exon categories with a more severe increase in boys ≥7, particularly for exons 51 and 53. Overall, the results show a different trend in the two-timed items. On one hand, the 10WR showed a profile consistent with previous reports in NSAA and 6MWT with overall stable results below the age of 7 years and little differences across skipping subgroups. On the other hand, in the TRF the deterioration could already be observed in the younger group and became more marked in the older ones. These findings emphasize the variability in early disease progression in boys with DMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105538"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204354","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":"39PThe effects of myositis-specific autoantibodies in immune-mediated necrotizing myopathy on muscle fiber contractility","authors":"T. Kerkhoff ,&nbsp;S. Luijcx ,&nbsp;B. Ardiç ,&nbsp;P. Stachurska ,&nbsp;A. van der Kooi ,&nbsp;E. Aronica ,&nbsp;J. Raaphorst ,&nbsp;C. Ottenheijm","doi":"10.1016/j.nmd.2025.105502","DOIUrl":"10.1016/j.nmd.2025.105502","url":null,"abstract":"<div><div>Immune-mediated necrotizing myopathy (IMNM) is the most severe myositis subtype in terms of muscle weakness. Immunosuppressive therapies are still insufficient and there is a need for better and personalized therapies. IMNM is associated with myositis-specific autoantibodies (MSAs) against signal recognition protein-54 (SRP) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), which have been suggested to play a pathogenic role. We have previously shown that the force generating capacity of muscle fibers from IMNM patients is impaired, however we do not know the cause of this impairment. Since these patients have elevated MSAs (up to 1000x fold), this raises the question whether it is caused by the MSAs. Either anti-SRP+, anti-HMGCR+ or seronegative serum was drawn from IMNM patients and healthy controls and stored in our biobank. Subsequently, healthy murine intact muscle fibers from the Flexor Digitorum Brevis (FDB) muscle were isolated for our ex-vivo culture model. After 1 day of culture (to allow the muscle fibers to recover from isolation), the fibers are exposed to the serum for 2 hours. Then the fibers were assessed for contractility in two different set-ups. The first set-up is an innovative high throughput set-up, in which muscle contractility and calcium handling was measured during electrical stimulation. In the second set-up we permeabilized the muscle fibers and mounted them between a force transducer and length motor. Fibers were exposed to solutions with incremental Ca2+-concentrations and the force was measured (without potential confounding effects of Ca2+ cycling by the sarcoplasmic reticulum). Afterwards, the fiber was stored in a buffer for gel electrophoresis to fiber type. Our data suggest that muscle contractility is altered after 2h exposure to serum of IMNM patients compared to healthy controls: during electrical stimulation, sarcomere shortening was higher after exposure to anti-SRP+, anti-HMGCR+ and seronegative serum, indicating altered contractility. Preliminary data suggest that exposure to anti-HMGCR+ serum lowers the maximum force of healthy muscle fibers, but Ca2+-sensitivity of force was not altered. Serum of IMNM patients has a direct impact on muscle contractility. It remains unclear which serum component causes the impact. Therefore, experiments are ongoing with the IgG and IgG-depleted serum of these patients to further investigate the role of the MSAs.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105502"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204393","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":"40PClinical features of cardiac complications and restrictive ventilatory impairment in AMA-positive myositis: findings from a nationwide cross-sectional study","authors":"M. Maeda ,&nbsp;T. Kawahara ,&nbsp;A. Kubota ,&nbsp;J. Shimizu ,&nbsp;T. Toda","doi":"10.1016/j.nmd.2025.105503","DOIUrl":"10.1016/j.nmd.2025.105503","url":null,"abstract":"<div><div>Serum anti-mitochondrial antibodies (AMA) are detected in approximately 5–20% of patients with idiopathic inflammatory muscle diseases, representing a distinct subtype designated as AMA-positive myositis. The clinical features of AMA-positive myositis typically include a chronic disease course, muscle atrophy, frequent cardiac involvement, and restrictive ventilatory impairment. We conducted a detailed subanalysis of cardiac complications and restrictive ventilatory impairment using data from a nationwide questionnaire survey. Between February and August in 2021, we sent an initial questionnaire (first survey) to the heads of neurology departments at 811 facilities certified by the Japanese Society of Neurology. A follow-up survey (second survey) was then conducted to collect detailed clinical data from respondents to the first survey. Among the 85 patients for whom detailed information was obtained from the second survey, 75% had cardiac complications and 49% had restrictive ventilatory impairment. Regarding cardiac complications, 65% of patients had arrhythmias, 44% had heart failure, and 24% had conduction blocks. Echocardiographic findings revealed that 16% of patients had an ejection fraction &lt;50% with diffuse hypokinesis. Holter electrocardiography showed ventricular arrhythmias in 61%, supraventricular arrhythmias in 58%, conduction defects in 9%, and sick sinus syndrome in 2% of patients. Cardiac devices were implanted in 32% of patients. Specifically, catheter ablation, pacemaker implantation, Implantable cardioverter defibrillator implantation, and HeartWare ventricular assist device implantation were performed in 21%, 12%, 8%, and 1% of patients, respectively. Electroencephalographic abnormalities were observed in 27% of patients. With regard to restrictive ventilatory impairment, 12% of patients showed a vital capacity &lt;50% on pulmonary function tests, and 22% had pCO₂ &gt;45 mmHg in arterial blood gas analysis. Ventilatory support was provided to 22% of patients. Among them, 50% received invasive positive pressure ventilation, while the remaining 50% received noninvasive positive pressure ventilation. Previous case reviews have highlighted the presence of both cardiac and respiratory involvement in patients with AMA-positive myositis; however, considerable variability in the reported frequencies across institutions has been noted. In contrast, the present cross-sectional study clarified the prevalence of both cardiac and restrictive ventilatory involvement in Japan and further demonstrated their clinical severity by revealing the frequencies of cardiac device implantation and the use of ventilatory support. These findings emphasize the need for comprehensive monitoring and multidisciplinary management of both cardiac and respiratory involvement in patients with AMA-positive myositis.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105503"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204394","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}