Neuromuscular Disorders最新文献

{"title":"45PGRO chemokines-induced neutrophil extracellular trap CITH3 as a new biomarker related to myasthenia gravis severity","authors":"H. Zhong,&nbsp;W. Zhang,&nbsp;D. He,&nbsp;R. Chen,&nbsp;L. Jin,&nbsp;J. Song,&nbsp;C. Yan,&nbsp;X. Huan,&nbsp;Y. Chen,&nbsp;X. Li,&nbsp;C. Zhao,&nbsp;S. Luo","doi":"10.1016/j.nmd.2025.105508","DOIUrl":"10.1016/j.nmd.2025.105508","url":null,"abstract":"<div><div>The role of innate immunity, particularly neutrophils, remains understudied in Myasthenia Gravis (MG) pathogenesis. To identify novel MG biomarkers through multi-omics screening. We performed eQTL GWAS analysis on 3273 proteins in Caucasian populations (3273 MG patients, 3301 controls), followed by validation in a Chinese Han population using ELISA and Luminex assays. Single-cell and bulk RNA sequencing analyses, flow cytometry, blood smear staining, and immunofluorescence were used to further investigate the ligand-receptor mechanism of candidate biomarkers. Genetically elevated plasma GRO chemokine levels significantly correlated with increased MG risk in Caucasians (p = 5.39e-06). ELISA and Luminex multiplex protein assays confirmed significantly higher plasma GRO chemokines in Chinese Han MG patients than controls (100 patients and 40 healthy controls, p &lt;0.0001). Hemogram analysis and flow cytometry revealed elevated neutrophil counts and CXCR2 (GRO receptor) expression in MG patients (50 patients and 50 controls, p &lt;0.0001). Neutrophil single-cell (n = 6) and whole blood bulk RNA-seq (n = 20) analyses demonstrated prominent CXCR2-induced neutrophil extracellular traps (NETs) in MG, confirmed by blood smear staining and immunofluorescence. ELISA measurements showed elevated plasma CITH3, a major NETs component, in MG patients (49 patients, 73 controls, p &lt;0.0001), which strongly correlated with MG severity scales and GRO levels (r&gt;0.4, p &lt;0.001). CITH3 derived from neutrophil death-induced NETS emerges as a novel potential biomarker for MG severity.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105508"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204187","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":"06OIn-depth examination of motor endplate pathology in AChR-Ab-positive myasthenia gravis","authors":"C. Preusse ,&nbsp;A. Meisel ,&nbsp;K. Brokamp ,&nbsp;A. Roos ,&nbsp;P. Doksani ,&nbsp;A. Hentschel ,&nbsp;M. Schuelke ,&nbsp;J. Rückert ,&nbsp;M. Pumberger ,&nbsp;F. Schömig ,&nbsp;W. Stenzel ,&nbsp;S. Hoffmann","doi":"10.1016/j.nmd.2025.105464","DOIUrl":"10.1016/j.nmd.2025.105464","url":null,"abstract":"<div><div>Since over 40 years it has been well established that complement deposition at the neuromuscular junction (NMJ) in AChR-antibody-positive myasthenia gravis (AChR-ab+ MG) contributes to the destruction of the motor endplate. However, despite these early findings, no comprehensive studies have been conducted to further investigate the underlying mechanisms or explore potential therapeutic strategies. Motivated by the rapid effects of novel therapies, which suggest that complete NMJ destruction is unlikely, we aim to re-examine the NMJ in AChR-ab+ MG using different techniques. In particular, using histology, electron microscopy (EM), transcript and proteomic analysis we investigated intercostal muscle (ICM) biopsies from 30 AChR-ab+ MG patients and compared these to non-myasthenic controls. Our histological analysis revealed clear C5b-9 deposition in all AChR-ab+ MG patients, with an average of 75% of investigated neuromuscular junctions (NMJs) showing complement positivity and an interindividual range of 33–100%, while no deposition was observed in control muscles. Moreover, electron microscopy (EM) studies showed postsynaptic simplification and shortened synaptic clefts, though not all NMJs exhibited these signs of endplate destruction. Notably, there was also considerable inter- and intraindividual variability in the extent of endplate damage, despite the overall high rate of complement deposition. Even though morphological changes in ICM tissue is low, we identified transcript changes indicating an upregulation of immune cell markers, with particularly strong expression of IL1B and IL6. Interestingly, we also observed a significant increase in the B cell chemoattractant BAFF and its receptor CXCR5, despite the absence of detectable B cells in ICM. Furthermore, proteomic analysis identified an upregulation of DNM2 (Dynamin-2), which mediates endocytosis of synaptic vesicles and mutations of the DNM2 gene were found to be associated with centronuclear myopathies, neuropathies and other neuromuscular diseases. Moreover, we detected a downregulation of TARSH (Target of Nesh-SH3), which is especially interesting, as this protein is predicted to be involved in several processes, including extracellular matrix organization and was found in CHRNE-related congenital myasthenic syndrome. In summary, our findings demonstrate variability in complement deposition and NMJ destruction in AChR-ab+ MG, indicating that not all NMJs are equally affected. Histologic and transcriptomic analyses suggest a critical role of macrophages, which could promote future therapeutic strategies. Project supported by Janssen Pharmaceutica NV, a Johnson and Johnson company.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105464"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204247","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":"13PUlviprubart pharmacokinetics, pharmacodynamics (PK/PD), and safety: phase 1 study results in patients with inclusion body myositis (IBM)","authors":"M. Needham ,&nbsp;R. Henderson ,&nbsp;C. Liang ,&nbsp;D. Soler-Ferran ,&nbsp;J. Wilkins ,&nbsp;S. Greenberg","doi":"10.1016/j.nmd.2025.105477","DOIUrl":"10.1016/j.nmd.2025.105477","url":null,"abstract":"<div><div>IBM is a rare, progressive disease characterized by invasion of muscle by highly differentiated cytotoxic CD8+ T cells. Ulviprubart, a monoclonal antibody, selectively depletes cytotoxic CD8+ KLRG1+ T cells by targeting KLRG1 expressed on most IBM-muscle–infiltrating T cells. Here, we describe PK/PD and safety of ulviprubart in patients with IBM. In this phase 1, open-label study (NCT04659031), initial patients received subcutaneous ulviprubart (0.1, 0.5, or 2.0 mg/kg) as a single dose prior to dosing every 8 weeks (Q8W) ∼6−12 months later, while later patients received 2.0 mg/kg Q8W; patients received ulviprubart for up to 18 months. PK/PD and safety with ulviprubart were assessed. Nineteen patients (mean age, 66 years; 79% male) were enrolled (0.1 mg/kg: n=3; 0.5 mg/kg: n=3; 2.0 mg/kg: n=13). Ulviprubart displayed a long absorption phase, slow clearance, and 21-day half-life. Peripheral CD8+ KLRG1+ and CD4+ KLRG1+ T cell depletion was achieved, with mean CD8+ KLRG1+ T cell maximum depletions of 69%, 97%, and 98% after single doses of 0.1, 0.5, and 2.0 mg/kg, respectively. Effector CD8+ T cell populations (T-cell effector memory [TEM] and TEMs expressing CD45RA [TEMRA]) were depleted to the extent of their KLRG1 expression. Regulatory T cells and B cells were preserved. No treatment-related serious adverse events (AEs) or discontinuations due to AEs were reported. In patients with IBM, ulviprubart led to sustained selective depletion of peripheral blood CD8+ KLRG1+ T cells and had a favourable safety profile.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105477"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204296","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":"15PPrimary skeletal muscle peripheral T-cell lymphoma associated with HIV presenting with myopathic symptoms","authors":"G. Ji ,&nbsp;F. Sun ,&nbsp;X. Song","doi":"10.1016/j.nmd.2025.105479","DOIUrl":"10.1016/j.nmd.2025.105479","url":null,"abstract":"<div><div>Primary skeletal muscle lymphoma (PSML) is a rare form of non-Hodgkin lymphoma (NHL), predominantly of B-cell lineage. T-cell variants are exceedingly uncommon, with fewer than ten reported cases of primary skeletal muscle peripheral T-cell lymphoma, not otherwise specified (PSM-PTCL, NOS). We present a case of HIV-associated PSM-PTCL, NOS with clinical features mimicking inflammatory myopathy. A 44-year-old man with a 5-year history of HIV presented with a 2-month history of intermittent fever and progressive limb weakness. Physical examination showed proximal-dominant muscle weakness and generalized edema. Laboratory tests revealed leukocytosis, anemia, elevated creatine kinase, metabolic acidosis, and negative myositis-specific autoantibodies. Electromyography showed a myopathic pattern. Due to rapidly worsening symptoms and lack of autoimmune markers, a muscle biopsy was performed. Histopathology showed diffuse infiltration of atypical lymphoid cells between muscle fibers. Immunohistochemistry revealed strong CD3 positivity and CD20 negativity, with high Ki-67 proliferation index (∼90%). Tumor cells were negative for CD10, CD117, CD34, CD68, CD99, pan-CK, MyoD1, MPO, TDT, and desmin, ruling out myogenic, myeloid, and epithelial malignancies. PET/CT revealed diffuse FDG uptake across multiple skeletal muscles with only minimal lymph node involvement. Bone marrow examination showed no infiltration. These findings confirmed the diagnosis of PSM-PTCL, NOS. Despite initiation of corticosteroids and chemotherapy, the disease progressed rapidly due to heavy tumor burden. The patient developed systemic complications and died shortly after discharge. This case underscores the diagnostic challenge in distinguishing aggressive lymphoma from inflammatory myopathies, particularly in immunocompromised individuals. Although HIV increases the risk of NHL, primary skeletal muscle involvement is rare and often misdiagnosed. Early biopsy is critical in patients with muscle-dominant symptoms and inconclusive autoimmune workup. This report emphasizes the need to consider lymphoma in the differential diagnosis of unexplained myopathic symptoms in HIV-positive patients.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105479"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204298","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":"34PCharacterization of inflammatory infiltrate in inclusion body myositis and its comparison with other IIMs","authors":"N. Rajput","doi":"10.1016/j.nmd.2025.105497","DOIUrl":"10.1016/j.nmd.2025.105497","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Inclusion body myositis (IBM) is an inflammatory autoimmune disorder of skeletal muscle affecting patients over the age of 40, with distinctive clinical and histopathological features. A direct cause of&lt;/div&gt;&lt;div&gt;IBM muscle damage is T cell–mediated cytotoxicity of IBM myofibers. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. This ambispective observational study included 26 patients biopsy proven IIMs cases over a period of six years. Both retrospective and prospective data were collected, including detailed clinical profiles, laboratory parameters, and histopathological features. To further characterize the nature of the inflammatory infiltrate, confocal microscopy was performed using a panel of nine inflammatory cell markers: CD3, CD4, CD8, CD16, CD56, CD68, CD86, CD163 and KLRG1. These markers were analyzed in dual combinations. Twenty-six biopsy proven patients of IIMs (16 IBM + 8 DM + 1OM + 1IMNM) were included in this study. The baseline demographics included age 36-72 years, (Male:Female;16:10). Clinically differential diagnosis included inflammatory and metabolic myopathies, LGMD, SLE with myopathy. Histopathological features in inclusion body myositis included loss of fascicular architecture (12/16 cases), rimmed vacuoles (8/16 cases), variation in fibre size (all 16 cases) and inflammatory infiltrate in all 16 cases with CD3 and CD8 positivity in 14/16 cases, and two cases with CD3 and CD4 positivity. Dermatomyositis features included loss of fascicular architecture (6/8 cases), Perifascicular atrophy (5/8 cases), variation in fiber size (8/8 cases), chronic inflammatory infiltrate (6/8 cases; with CD3 and CD8 positive cells in 4/8 cases, CD3, CD4 and CD8 positive cells in 2/8 cases). Single case of IMNM showed maintained fascicular architecture with mild variation in size, along with few degenerating fibers. On confocal microscopy 6/16 IBM cases showed inflammatory cells with dual positivity for CD3 and CD8, 5/16 IBM cases showed KLRG1 positive cells out of which single case showed dual positivity for CD8 and KLRG1, 3/16 IBM cases showed CD68 positive cells while all IBM cases were negative for CD16, CD56, CD86, and CD163 inflammatory markers. On confocal 3/8 dermatomyositis cases showed dual positivity for CD3 and CD8 markers, and single cases showed cells positive for CD16, CD68, and KLRG1, respectively. While all dermatomyositis cases were negative for CD86, CD163, and CD56 inflammatory markers. The IMNM case exhibited a complete absence of inflammatory cells. In comparison, the overlap myositis case showed selective infiltration by CD3-positive cells, with all remaining markers remained negative. In our analysis, inclusion body myositis showed prominent infiltration by CD8+ and KLRG1+ highly differentiated T cells, a pattern not observed in dermatomyositis or other IIMs. Given the limited response to steroid treatment in IBM, these ce","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105497"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204341","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":"22PProteomic profiling in juvenile dermatomyositis toward the elucidation of protein signatures correlating with severity of myopathology","authors":"A. Roos ,&nbsp;M. Pauper ,&nbsp;E. Holla ,&nbsp;A. Hentschel ,&nbsp;C. Nelke ,&nbsp;S. Beltran ,&nbsp;H. Kölbel ,&nbsp;C. Tucht ,&nbsp;T. Ruck ,&nbsp;U. Schara-Schmidt ,&nbsp;A. Della-Marina","doi":"10.1016/j.nmd.2025.105485","DOIUrl":"10.1016/j.nmd.2025.105485","url":null,"abstract":"<div><div>Juvenile dermatomyositis (JDM) is an idiopathic, pediatric-onset inflammatory myopathy, primarily manifested via muscle inflammation and skin rash. Specific biological processes such as the interferon signaling pathway are known to play a role in the disease, but the precise molecular pathology is still incompletely understood. With muscle biopsies being invasive, molecular studies to understand protein dysregulations driving disease onset and severity of muscle pathology are limited. Here, we used a myopathological scoring system enabling to systematically stratify JDM patients into severity groups. Untargeted proteomics on muscle tissue was applied to measure protein levels and assess the differential abundance in each group and in healthy controls and to identify biological processes correlating with the severity of myopathology, and thus disease activity. Our analyses revealed a number of differentially abundant proteins that positively correlated with disease severity. Notably, interferon-induced GTP-binding protein Mx1 (MX1) consistently emerged as the most statistically significant protein. upregulated proteins were predominantly associated with immune system functions, while downregulated proteins were linked to mitochondrial processes. Clustering of proteins based on their expression identified four distinct protein groups with unique expression patterns across controls and severity groups. Each expression pattern cluster was enriched for specific biological processes or cellular components relevant to JDM pathology. Immunofluorescence imaging validated proteomics results and confirmed the increase in MX1 and a role of periostin in fibrotic remodeling. Our combined findings provide critical insights into the molecular mechanisms driving disease onset and severity in muscle tissue, advancing our understanding of JDM's underlying pathophysiology.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105485"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204345","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":"53VPNeutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic markers in idiopathic inflammatory myopathies","authors":"F. Hakim ,&nbsp;S. Sakka ,&nbsp;M. Snoussi ,&nbsp;N. Bouattour ,&nbsp;K. Moalla ,&nbsp;S. Daoud ,&nbsp;N. Charfi ,&nbsp;S. Marzouk ,&nbsp;M. Damak","doi":"10.1016/j.nmd.2025.105516","DOIUrl":"10.1016/j.nmd.2025.105516","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases characterized by muscle weakness and muscle inflammatory infiltrates. Systemic inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with mortality, but their direct correlation with disease severity markers remains poorly understood. This study evaluates the relationship between NLR, PLR, and clinical severity markers to determine their prognostic value in IIM. A retrospective study was conducted at the adult neurology Dept Sfax, Tunisia, spanning 23 years (2001–2024). It included 101 patients diagnosed with IIM according to the 2017 ACR-EULAR criteria. Hematological parameters, including complete blood count, neutrophil, lymphocyte counts, NLR, and PLR, were analysed. Correlations were assessed between these markers and prognostic factors, including muscle weakness (Medical Research Council [MRC] scale), respiratory or pharyngeal involvement, the need for methylprednisolone (MP) or second-line immunosuppression, treatment response, and severity scores (Modified Rankin Scale [mRS] and Modified Gardner-Medwin-Walton Scale [mGMWS] at baseline, one year, and three years). A total of 101 patients were included (mean age: 44.9 years, 71% female). Mean NLR was 3.69 ± 4.97, and mean PLR was 188.5 ± 151.6. PLR correlated with lower MRC scores in the pelvic region (p=0.041), initial mRS (p&lt;0.001) and mGMWS scores (p=0.036). NLR correlated with lower MRC scores in the hip region (p=0.017) and initial and three-year mGMWS scores (p=0.047, p=0.044). NLR was associated with the necessity of MP use (p=0.043), while PLR was linked to relapse risk despite appropriate treatment (p=0.001). These findings highlight NLR and PLR as accessible prognostic markers in IIM, predictive of initial muscle weakness severity, therapeutic requirements (MP use), and long disease outcomes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105516"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204447","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":"189PElectrical impedance myography as a tool for monitoring disease progression in mouse models of Duchenne muscular dystrophy: a longitudinal, multisite study","authors":"P. Mantuano ,&nbsp;M. van Putten ,&nbsp;B. Sonbas Cobb ,&nbsp;K. Putker ,&nbsp;B. Boccanegra ,&nbsp;C. Tanganyika-de Winter ,&nbsp;L. Tulimiero ,&nbsp;A. Schneider ,&nbsp;O. Cappellari ,&nbsp;D. Van De Vijver ,&nbsp;S. Engelbeen ,&nbsp;S. Pandeya ,&nbsp;J. Nagy ,&nbsp;S. Rutkove","doi":"10.1016/j.nmd.2025.105542","DOIUrl":"10.1016/j.nmd.2025.105542","url":null,"abstract":"<div><div>Establishing reliable readouts to monitor disease status and response to therapy in preclinical studies is vital, especially for rare neuromuscular disorders such as Duchenne muscular dystrophy (DMD). Electrical impedance myography (EIM) is a non-invasive technique where a weak, high-frequency electrical current is applied to muscle surface and the resulting voltage patterns measured. Changes in EIM components (i.e., resistance, reactance, phase) reflect muscle status. In recent years, EIM has shown promise as a tool to longitudinally assess disease-induced changes and effects of therapies in DMD patients and animal models. However, preclinical findings have been limited to single-site studies and narrow age ranges. As part of the 'Of Mice and Measures' (OMAM) study, aimed at obtaining comparative data on DMD murine models’ natural history, we carried out a multicenter study to validate EIM as a translatable preclinical-to-clinical tool in dystrophic settings. Monthly in vivo EIM measurements were performed at two independent sites (UniBa and LUMC), on the gastrocnemius of male mdx mice on different genetic backgrounds (classic, mildly affected BL10-mdx mice and hyper-fibrotic, more severely affected D2-mdx mice, vs. strain-matched wild types), from 8 to 52 weeks of age. First EIM training and data analysis were conducted at BIDMC. EIM data sets were largely comparable across study sites, with longitudinal phase values at a selected frequency (105 kHz) being the most reliable and accurate. EIM outcomes were affected by mouse strain and age, with D2-mdx mice showing considerably lower values consistent with typical muscle atrophy. Interestingly, histopathology evaluated at 8, 12, 28, or 52 weeks of age correlated well with EIM phase values in either strain, with the D2-mdx model showing far stronger correlations to features of disease severity. Globally, our findings highlight the applicability of EIM as a robust outcome measure for preclinical studies in DMD.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105542"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204500","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":"Cardiac MRI for early detection of subclinical cardiac dysfunction in dysferlinopathy","authors":"Aneesha Thomas ,&nbsp;Ashita Barthur ,&nbsp;Dipti Baskar ,&nbsp;Mariamma Philip ,&nbsp;Bhavana K Gutta ,&nbsp;Deepak Menon ,&nbsp;Saraswati Nashi ,&nbsp;Seena Vengalil ,&nbsp;Shriya Rajashekar ,&nbsp;Vijay Kumar Boddu ,&nbsp;MM Samim ,&nbsp;Atchayaram Nalini","doi":"10.1016/j.nmd.2025.106205","DOIUrl":"10.1016/j.nmd.2025.106205","url":null,"abstract":"<div><div>Dysferlinopathy [Limb Girdle Muscular Dystrophy (LGMD) R2] is due to deficient expression of the dysferlin protein in the sarcolemma. As dysferlin is expressed in skeletal and cardiac muscles, dysferlinopathy may affect the heart in addition to skeletal muscle. We aimed to detect cardiac abnormalities using Cardiac Magnetic Resonance (CMR) imaging and to investigate its association with clinical, biochemical, and genetic parameters in patients with genetically confirmed dysferlinopathy. Cardiac involvement was defined as abnormalities in ventricular volumes, systolic function or wall motion, myocardial oedema, late gadolinium enhancement, or valvular regurgitation on CMR. All 30 patients (43.3 % females) recruited were asymptomatic for cardiac involvement. The mean age of onset was 21.50 ± 6.29 years, and the mean duration of illness was 7.1 ± 3.89 years. 11 (36.7 %) had one or more cardiac abnormalities on CMR. 5 (16.7 %) had left ventricular systolic dysfunction, and 5 (16.7 %) had myocardial fibrosis. We found significant correlations between left ventricular end-diastolic volume (LVEDV) and indexed left ventricular end-systolic volume (LVESVi) with the Muscular Dystrophy Functional Rating Score (MDFRS); and between left ventricular ejection fraction (LVEF) and the Medical Research Council (MRC) sum score. To conclude, More than a third of dysferlinopathy patients had subclinical cardiac involvement.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"54 ","pages":"Article 106205"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045012","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":"02INVBeyond muscular dystrophies: roles of MD-related proteins in different organ systems","authors":"L. Winter","doi":"10.1016/j.nmd.2025.105456","DOIUrl":"10.1016/j.nmd.2025.105456","url":null,"abstract":"<div><div>Muscular dystrophies (MDs) are characterized by progressive muscle weakness and degeneration, caused by mutations in MD-related genes encoding proteins required for healthy muscle function. MD-related proteins are traditionally studied in the context of skeletal muscle, even though many are ubiquitously expressed, suggesting broader physiological roles. This presentation will first give an overview on the spectrum of additional organ involvements in MDs: while cardiac involvement is most frequently observed, MD-related proteins play crucial roles in various organ systems beyond muscle tissue, impacting nervous, ocular, vascular, respiratory, renal, hepatic, gastrointestinal, and metabolic functions, as well as various cellular processes. To address potential molecular mechanisms underlying the multi-organ manifestations of MDs, paradigmatic key proteins will be discussed in more detail. Exemplifying the clinical importance of exceeding skeletal muscle involvement, this presentation will then conclude on plectin, a multi-functional cytolinker and intermediate filament stabilizing protein essential for muscle fiber integrity and function. Mutations in the human plectin gene (PLEC) cause autosomal recessive epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), which is characterized by skin blistering and progressive weakness, but also multiple additional symptoms. As evaluating disease-mimicking cell and animal models is inevitable for the understanding of the pathomechanistic basis of MDs and the development of treatment strategies, central results from corresponding molecular analyses will be highlighted as well. In conclusion, gaining a multi-systemic pathophysiological and molecular insight into MDs is inevitable for a comprehensive understanding and the development of therapeutic perspectives.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"53 ","pages":"Article 105456"},"PeriodicalIF":2.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204179","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}