Neuromuscular Disorders最新文献

{"title":"Safety and efficacy of tamoxifen in patients with duchenne muscular dystrophy: open label extension of TAMDMD trial","authors":"Gaëtan Zwingli ,&nbsp;Niveditha Putananickal ,&nbsp;Simone Schmidt ,&nbsp;Sara Nagy ,&nbsp;Daniela Rubino–Nacht ,&nbsp;Sabine Schaedelin ,&nbsp;Helge Amthor ,&nbsp;Anne–Marie Childs ,&nbsp;Nicolas Deconinck ,&nbsp;Iain Horrocks ,&nbsp;Saskia Houwen–van Opstal ,&nbsp;Vincent Laugel ,&nbsp;Mercedes Lopez Lobato ,&nbsp;Andrés Nascimento Osorio ,&nbsp;Ulrike Schara–Schmidt ,&nbsp;Stefan Spinty ,&nbsp;Arpad von Moers ,&nbsp;Fiona Lawrence ,&nbsp;Patricia Hafner ,&nbsp;Olivier M. Dorchies ,&nbsp;Bettina C. Henzi","doi":"10.1016/j.nmd.2026.106366","DOIUrl":"10.1016/j.nmd.2026.106366","url":null,"abstract":"<div><div>Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy was assessed in the double-blind, randomised, placebo-controlled, multicenter phase 3 trial (TAMDMD), which was followed by an 48 weeks open label extension study. The aim of the open label extension study was to investigate if earlier initiation of tamoxifen could reduce the progression of the disease compared to delayed initiation of tamoxifen. Of the initial TAMDMD trial participants, 66 patients were enrolled in the open label extension (OLE). The objective was to investigate the efficacy of prolonged treatment with tamoxifen 20 mg daily, adjunct to corticosteroids, in individuals with DMD over 48 weeks. We aimed to analyse the sustained effect and the timing effect of tamoxifen in patients with DMD on the basis of a set of motor function tests. The sustained effect corresponds to the treatment effect seen in the tamoxifen treatment arm of the RCT phase of the trial being sustained after all patients got the treatment in the OLE phase. The timing effect addresses if patients with earlier tamoxifen initiation show more favourable disease trajectory than patients with delayed tamoxifen initiation. This study was registered with ClinicalTrials.gov (NCT03354039). Between May 28th 2019 and July 28th 2021, 66 patients in 10 study centres in seven European countries could be enrolled into the OLE phase. Of those, 32 had previously been treated with tamoxifen and 34 had been assigned to placebo. The efficacy outcome defined as the change in the motor function did not differ significantly between the early tamoxifen treatment group and the delayed tamoxifen treatment group. There was neither a sustained nor a timing effect of tamoxifen. Overall tamoxifen was well tolerated. No deaths or life-threatening serious adverse events occurred. The OLE phase of the TAMDMD trial showed that treatment with tamoxifen continued to be well tolerated overall; however, there was neither a sustained nor a timing effect of tamoxifen treatment in patients with DMD. We cannot provide statistical nor clinical evidence that prolonged treatment with tamoxifen is effective in delaying disease progression in DMD when used as an adjunct to corticosteroids.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"61 ","pages":"Article 106366"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172993","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":"Correspondence on ‘Cardiac MRI for early detection of subclinical cardiac dysfunction in dysferlinopathy’ by Thomas et al.","authors":"Holly Borland,&nbsp;John Bourke,&nbsp;Volker Straub","doi":"10.1016/j.nmd.2026.106357","DOIUrl":"10.1016/j.nmd.2026.106357","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"61 ","pages":"Article 106357"},"PeriodicalIF":2.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166086","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":"Urinary glucose tetrasaccharide tracks disease activity in late-onset Pompe disease","authors":"Cristina Domínguez-González ,&nbsp;Domenico Iannucci ,&nbsp;James Clark ,&nbsp;Paloma Martín-Jiménez ,&nbsp;Stephan Hold ,&nbsp;Petra Oliva ,&nbsp;Anita Bischinger ,&nbsp;Eduard Gallardo ,&nbsp;Jordi Díaz-Manera","doi":"10.1016/j.nmd.2026.106359","DOIUrl":"10.1016/j.nmd.2026.106359","url":null,"abstract":"<div><div>Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy caused by acid α-glucosidase deficiency, leading to glycogen accumulation in skeletal muscle. Reliable biomarkers for monitoring disease progression and treatment response are lacking. Urinary glucose tetrasaccharide (Glc4), a marker of glycogen turnover, is well established in infantile-onset Pompe disease, but its prognostic value in LOPD under longitudinal real-world conditions remains uncertain. Urinary Glc4 was evaluated in 35 genetically confirmed LOPD patients followed for four years with annual functional assessments, spirometry, and quantitative muscle MRI. Glc4 was measured by liquid chromatography–tandem mass spectrometry and normalized to creatinine. Associations with changes in six-minute walk test (6MWT), forced vital capacity (FVC), and thigh fat fraction (FF) were analyzed. Receiver operating characteristic (ROC) analysis assessed the ability of baseline Glc4 to predict clinically meaningful motor decline (&gt;30 m reduction in 6MWT). Multivariate linear regression evaluated whether baseline Glc4 independently predicted 6MWT decline. Glc4 levels were elevated in all patients and showed considerable intra-individual variability. Higher baseline Glc4 was associated with greater functional decline and increased muscle fat replacement. ROC analysis showed good predictive performance (AUC 0.78), with an optimal threshold of approximately 13 mmol/mol creatinine. Baseline Glc4 remained an independent predictor of 6MWT decline in multivariate analysis (<em>p</em> = 0.042). Baseline urinary Glc4 provides relevant prognostic information in LOPD and may serve as a complementary biomarker for routine disease monitoring.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106359"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118857","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":"Meeting report: Expanding access to advanced cardiac therapies, including ventricular assist devices (VADs) and heart transplantation in muscular dystrophy","authors":"Seth A. Hollander,&nbsp;David Rosenthal","doi":"10.1016/j.nmd.2026.106338","DOIUrl":"10.1016/j.nmd.2026.106338","url":null,"abstract":"<div><div>Cardiomyopathy remains a leading cause of mortality in Duchenne muscular dystrophy (DMD), yet advanced therapies such as ventricular assist devices (VAD) and heart transplantation are rarely considered. In September 2024, a multidisciplinary group of neuromuscular specialists, cardiologists, intensivists, anesthesiologists, surgeons, respiratory therapists, rehabilitation specialists, and patient advocates convened to challenge the clinical challenges and institutional barriers that have historically excluded individuals with DMD from these life-prolonging interventions. The charge of the meeting was to develop a practical roadmap to guide the timely referral, evaluation, and management of DMD patients with advanced heart failure. Presentations focused on the evolving treatment landscape and reviewed limitations of standard heart failure assessments—including ejection fraction and symptomatology—while exploring alternative evaluation tools such as cardiac MRI, biomarkers, adapted exercise testing, and patient-reported outcomes. Discussions addressed candidacy, surgical considerations, respiratory and nutritional optimization, and psychosocial supports. Participants determined that VAD and transplant should be offered to appropriate candidates and began collaborative development of clinical protocols, which were then completed and published online approximately one year after the meeting concluded.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106338"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024597","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":"277th ENMC international workshop: Congenital myopathies: revising and revisiting nomenclature and diagnostic guidelines, 21–23 June 2024, Hoofddorp, The Netherlands","authors":"RN Villar-Quiles ,&nbsp;LH Hayes ,&nbsp;S Raga ,&nbsp;C Bönnemann ,&nbsp;E Oates ,&nbsp;J Dowling ,&nbsp;A Ferreiro ,&nbsp;277th ENMC workshop participants","doi":"10.1016/j.nmd.2025.106328","DOIUrl":"10.1016/j.nmd.2025.106328","url":null,"abstract":"<div><div>The 277th ENMC workshop on Congenital Myopathies was held in Amsterdam, The Netherlands, on 21–23 June, with 26 clinical, research, and curation experts and patient representatives from five continents. The workshop aimed to 1) establish an updated nomenclature and 2) update recommendations for their diagnostic evaluation. It was agreed that the preferred acronym for congenital myopathies is CMYO. Consensus defined CMYOs as a heterogeneous group of genetic muscle disorders typically presenting perinatally or in infancy with hypotonia and muscle weakness, usually non- or slowly progressive, with distinctive structural, non-dystrophic histopathological features. A nomenclature framework integrating gene, mode of inheritance, and histopathology was proposed, exemplified by “autosomal recessive RYR1-congenital myopathy with cores.” Diagnostic consensus emphasized a genetics-first approach, using targeted massively parallel sequencing panels, exome, or genome sequencing, complemented by electromyography, muscle imaging, and biopsy when indicated and available. The workshop highlighted the need for harmonized classification across databases, patient engagement, and global representation to support precise diagnosis, genotype–phenotype correlation, and equitable access to care and research.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106328"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100546","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":"Beyond motor function: cognitive and language impairments in spinal muscular atrophy children treated with modern therapies","authors":"Mathilde Guibert ,&nbsp;Marie Canton ,&nbsp;Delphine Saunier ,&nbsp;Sandra Gharbi ,&nbsp;Melodie Campiglia ,&nbsp;Hélène Vincent ,&nbsp;Mathieu Kuchenbuch ,&nbsp;Cyril Schweitzer ,&nbsp;Clémentine Lambert","doi":"10.1016/j.nmd.2026.106340","DOIUrl":"10.1016/j.nmd.2026.106340","url":null,"abstract":"<div><div>Recent disease-modifying treatments have markedly improved the motor prognosis of spinal muscular atrophy, yet the neurocognitive and language outcomes of treated children remain insufficiently characterized. This monocentric observational study included sixteen children with genetically confirmed Spinal muscular atrophy types I–III (10 males; age 2.6–15.4 years; 5 with type I, 5 type II, and 6 type III) treated with at least one disease-modifying therapy and followed at our center. Participants underwent standardized assessments of intellectual abilities, executive functions, social cognition, memory, and language, complemented by parent questionnaires. Data were analyzed descriptively given the small and heterogeneous sample. Intellectual functioning was preserved (mean IQ = 102 ± 4), with no cases of intellectual disability, although 15% showed executive dysfunctions (e.g., inhibition, cognitive flexibility) not perceived by parents. Oral language disorders were found in 73% of individuals, affecting phonology, lexicon, and morphosyntax, and were more frequent in children with more severe motor phenotypes and fewer SMN2 copies. Written language disorders were identified in 29% of individuals, even without major motor impairment. Routine neuropsychological and speech-language assessments should be integrated into multidisciplinary care to enable earlier detection, targeted interventions, and improved long-term outcomes.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106340"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079818","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":"Refining functional phenotypes in an international cohort of untreated paediatric type 2 and 3 SMA patients using the Revised Hammersmith Scale","authors":"E Milev ,&nbsp;G Stimpson ,&nbsp;D Ramsey ,&nbsp;A Mayhew ,&nbsp;M Scoto ,&nbsp;G Baranello ,&nbsp;R Muni Lofra ,&nbsp;E O’Reilly ,&nbsp;Wolfe Amy ,&nbsp;M Main ,&nbsp;ES Mazzone ,&nbsp;J Montes ,&nbsp;AM Glanzman ,&nbsp;A Pasternak ,&nbsp;T Duong ,&nbsp;M Civitello ,&nbsp;G Coratti ,&nbsp;C Marini-Bettolo ,&nbsp;J Day ,&nbsp;BT Darras ,&nbsp;F Muntoni","doi":"10.1016/j.nmd.2026.106336","DOIUrl":"10.1016/j.nmd.2026.106336","url":null,"abstract":"<div><div>Spinal muscular atrophy types 2 and 3 encompass a wide spectrum of motor abilities ranging from non-sitting to sitting and walking. This study refines a functional group termed high functioning sitter-standers, positioned between traditional categories, and examined in relation to both the Revised Hammersmith Scale and a World Health Organization motor milestone-based framework. Among 178 participants completing 618 assessments, 109 were classified as type 2, 59 as type 3a, and 10 as type 3b, with ages ranging from 1 to 17.5 years. Twenty-seven non-sitters completed 54 assessments, 110 sitters completed 347, and 50 walkers completed 169, while the high functioning sitter-standers accounted for 48 assessments of 21 individuals. This newly defined group scored significantly lower than walkers and higher than both sitters and non-sitters, highlighting a distinct and measurable functional profile. Although no significant differences in age distribution were observed between the high functioning sitter-standers and walkers or non-sitters, sitters were notably younger. This intermediate phenotype captures patients with partial standing and assisted walking abilities, often overlooked in previous analyses. Recognition of this group is important for understanding emerging functional trajectories in treated spinal muscular atrophy and for informing future outcome measures and quality of life assessments.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106336"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118525","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":"WMS Congress 2026 Hiroshima","authors":"","doi":"10.1016/S0960-8966(26)00040-4","DOIUrl":"10.1016/S0960-8966(26)00040-4","url":null,"abstract":"","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106372"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147384765","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":"285th ENMC international workshop: SMN-associated neurodevelopmental disorder: type 1 spinal muscular atrophy and the brain, 31st January - 2nd February 2025, Hoofddorp, The Netherlands","authors":"David Gómez-Andrés ,&nbsp;Michelle A Farrar ,&nbsp;Mireia Alvarez-Molinero ,&nbsp;Rocío Garcia-Uzquiano ,&nbsp;Chiara Brusa ,&nbsp;Giovanni Baranello ,&nbsp;Susana Quijano-Roy ,&nbsp;285th ENMC Workshop participants","doi":"10.1016/j.nmd.2025.106331","DOIUrl":"10.1016/j.nmd.2025.106331","url":null,"abstract":"<div><div>Recent advances in spinal muscular atrophy (SMA) early diagnosis and treatment have significantly improved survival and motor outcomes, particularly for those with severe phenotypes. However, clinicians have observed unexpected cognitive, social, communication, and behavioural differences in a proportion of children. The 285th ENMC workshop convened 28 experts from 13 countries to address these neurodevelopmental concerns. Key outcomes included confirming the presence of challenges in neurodevelopment in a substantial proportion of treated SMA type 1 children, identifying higher-risk subgroups, and emphasizing the need for early identification, timely referrals, and family support. Participants agreed on a core screening strategy and highlighted the importance of international collaboration to develop specific diagnostic and intervention guidelines. Future steps involve launching an online survey to assess the prevalence of neurodevelopmental disorders and study their characteristics and trajectories, developing care guidelines, and promoting research working groups to further understand brain development in SMA and improve patient care.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106331"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024494","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":"Preemptive immunotherapy for fetal acetylcholine receptor antibody disorder (FARAD): from recurrent pregnancy losses to a healthy infant - a case report","authors":"Stefan Verlohren ,&nbsp;Christof Dame ,&nbsp;Beate Mayer ,&nbsp;Iris Dressler-Steinbach ,&nbsp;Claus-Eric Ott ,&nbsp;Inga Koneczny ,&nbsp;Marlene Wolfsgruber ,&nbsp;Sarah Hoffmann ,&nbsp;Andreas Meisel","doi":"10.1016/j.nmd.2026.106354","DOIUrl":"10.1016/j.nmd.2026.106354","url":null,"abstract":"<div><div>Maternal antibodies against the fetal acetylcholine receptor (fAChR) can cause fetal acetylcholine receptor antibody-related disorders (FARAD), a rare but important cause of arthrogryposis multiplex congenita (AMC) and Fetal Akinesia Deformation Sequence (FADS), with recurrence rates up to 100%. Unlike genetic causes, FARAD may respond to maternal immunotherapy, yet standardized treatment protocols are lacking. We report four pregnancies in an asymptomatic mother with confirmed fAChR antibodies. After three fetal losses due to FARAD and two unsuccessful treatment attempts initiated only after sonographic abnormalities, a healthy infant was delivered in the fourth pregnancy following a pre-planned preemptive approach. Treatment, initiated at week 10 of gestation, consisted of plasmapheresis (PLEX) and subsequent weekly high-dose intravenous immunoglobulin (IVIg). Fetal serum after birth confirmed fAChR antibodies on cell-based assays (live and fixed). This case series underscores the importance of recognizing fAChR antibodies as differential diagnosis of AMC in asymptomatic mothers and of early, consistent antibody-reducing therapy to prevent FARAD-related pregnancy losses.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"60 ","pages":"Article 106354"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132521","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}