Journal of neuromuscular diseases最新文献

{"title":"Exon-skipping therapies for DMD in Kazakhstan: Progress and challenges.","authors":"Altynshash Jaxybayeva, Bakhytkul Myrzaliyeva, Marzhan Lepessova, Latina Tekebayeva, Dinmukhamed Ayaganov","doi":"10.1177/22143602261476365","DOIUrl":"10.1177/22143602261476365","url":null,"abstract":"<p><p>BackgroundDuchenne muscular dystrophy (DMD) progression has been evaluated in clinical trials; however, some ethnic populations-including Kazakhstan, a country with a genetically unique population-are still underrepresented. While the prevalence of DMD in Kazakhstan has yet to be reported, Kazakhstan is one of the only central Asian countries with access to exon-skipping therapies for DMD. Although these therapies have been provided through regional budget and public funds since 2021, due to high costs and inconsistent support, accessibility remains challenging.ObjectiveTo describe the disease progression of exon-skipping-treated patients with DMD in Kazakhstan and discuss treatment management challenges.MethodsData from exon-skipping-treated patients (January 2021-April 2025) were provided to an expert council for review every 6 months. Functional outcomes (Scott scale, Vignos scale, 6-minute walk test, and 4-stair climb) were extracted and analyzed.ResultsA total of 46 patients received eteplirsen (n = 24), golodirsen (n = 14), and casimersen (n = 8). Median ages at eteplirsen, golodirsen, and casimersen initiation were 9.1, 9.6, and 10.3 years, respectively. During the follow-up period, 10 of 46 patients discontinued their exon-skipping therapy, and one patient died (decompensated cardiomyopathy). Functional assessments showed that patients were generally stable or improved over time. Approximately one-third of patients experienced treatment interruptions or were anticipated to be unable to maintain their prescribed exon-skipping therapy due to inadequate funding.ConclusionsThese data reflect the challenges patients with DMD experience in Kazakhstan, and the need for improved funding to maximize the therapeutic potential of exon-skipping therapies.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261476365"},"PeriodicalIF":3.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delphi consensus on gene therapy of spinal muscular atrophy with onasemnogene abeparvovec in Germany, Austria and Switzerland - part II - expert based recommendations for surveillance and management of side-effects.","authors":"Andreas Ziegler, Claudia Weiß, Katharina Vill, Matthias Baumann, Günther Bernert, Astrid Blaschek, Astrid Eisenkölbl, Marina Flotats-Bastardas, Johannes Friese, Dorothea Holzwarth, Claudia Ganter, Klaus Goldhahn, Andreas Hahn, Maja von der Hagen, Hans Hartmann, Oswald Hasselmann, Veronka Horber, Ralf A Husain, Sabine Illsinger, David Jacquier, Jessika Johannsen, Cornelia Köhler, Heike Kölbel, Michael Kolodzig, Andrea Klein, Astrid Pechmann, Arpad von Moers, Wolfgang Müller-Felber, Christian Rauscher, Gudrun Schreiber, Oliver Schwartz, Joachim Sproß, Georg M Stettner, Corinna Stoltenburg, Eva Stumpe, Regina Trollmann, Gerd Wiegand, Ekkehard Wilichowski, Ulrike Schara, Janbernd Kirschner","doi":"10.1177/22143602261433270","DOIUrl":"10.1177/22143602261433270","url":null,"abstract":"<p><strong>Background: </strong>Systematic protocols for long-term surveillance of children with spinal muscular atrophy treated with onasemnogene abeparvovec are lacking. Together with best practice recommendations for safety monitoring and management, such recommendations should increase patient safety and confidence levels of healthcare providers.</p><p><strong>Objective: </strong>Based on systematic literature review and evidence grading from part 1, this initiative aims to develop a structured treatment plan applicable across all treatment centers in Germany, Austria and Switzerland. Additionally, it seeks to establish consensus recommendations for the clinical management of safety alerts.</p><p><strong>Methods: </strong>Part 2 describes the methodology used to formulate Delphi consensus statements, the development of a structured treatment plan for OA treatment, and the anonymous consensus voting process with standardized follow-up in case of disagreement.</p><p><strong>Results: </strong>A total of 12 consensus statements were developed, addressing diagnostic work-up, safety evaluation, and best practice management of common adverse drug reactions associated with OA gene therapy. All statements achieved >95% consensus in the anonymous Delphi voting. Additionally, two consensus recommendations for handling of positive newborn screening result achieved consensus of 97% and 87%, respectively. A structured treatment plan for gene therapy was consented with 100% agreement, as were standardized recommendations for laboratory testing and a consensus-based algorithm for management of liver transaminase elevations.</p><p><strong>Conclusions: </strong>Delphi-based expert recommendations, developed in co-creation with patient representatives, provide a framework to minimize complications associated with gene therapy and establish the basis for standardized post-marketing data collections. The methodology used in this Delphi-consensus-group can serve as a blueprint for future gene therapy approvals.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261433270"},"PeriodicalIF":3.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic <i>SIGMAR1</i> variants in early-onset distal hereditary motor neuropathy: A Japanese case series.","authors":"Kento Kodama, Masahiro Ando, Yujiro Higuchi, Jun-Hui Yuan, Akiko Yoshimura, Makoto Samukawa, Motomasa Suzuki, Shunsuke Ogaya, Yuka Kawata, Naoki Gamo, Shin Hisahara, Chikashi Yano, Risa Nagatomo, Takahiro Hobara, Fumikazu Kojima, Yu Hiramatsu, Satoshi Nozuma, Yusuke Sakiyama, Jun Mitsui, Shoji Tsuji, Hiroshi Takashima","doi":"10.1177/22143602261477464","DOIUrl":"10.1177/22143602261477464","url":null,"abstract":"<p><p>BackgroundDistal hereditary motor neuropathy (dHMN) is characterized by slowly progressive distal muscle weakness and amyotrophy, and it exhibits clinical overlap with Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis (ALS). Biallelic variants in <i>SIGMAR1</i>, encoding sigma nonopioid intracellular receptor 1, have been linked to autosomal recessive dHMN with pyramidal features. This study investigated the clinical and genetic features of patients with dHMN associated with <i>SIGMAR1</i> variants in Japan.MethodsWe conducted genetic screening of Japanese patients with clinically suspected inherited peripheral neuropathies using targeted gene panels and whole-exome sequencing. <i>SIGMAR1</i> variants were evaluated via segregation analysis using Sanger sequencing. Detailed clinical and electrophysiological data were systematically reviewed.ResultsBiallelic <i>SIGMAR1</i> variants, including three novel variants and one previously reported variant, were identified in six patients from five unrelated families. The genotypes comprised compound heterozygous variants in four patients and homozygous variants in two patients. All patients presented with early-onset distal muscle weakness and atrophy. Enhanced tendon reflexes and pyramidal tract signs were frequently observed, whereas bulbar or respiratory involvement was absent. Nerve conduction studies consistently revealed motor-predominant axonal neuropathy with minimal sensory involvement. Disease progression was slow, and all patients remained ambulatory for years to decades after onset.ConclusionOur findings expand the clinical and genetic spectrum of <i>SIGMAR1</i>-associated disease and support its classification as dHMN rather than ALS. <i>SIGMAR1</i> variants should be considered in the genetic evaluation of early-onset motor neuropathies, particularly in patients with dHMN accompanied by pyramidal features.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261477464"},"PeriodicalIF":3.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-SRP immune-mediated necrotizing myopathy from childhood to adulthood: A case series highlighting rituximab-responsive disease.","authors":"Seon-Jae Ahn, Jee Min Kim, Han Sang Lee, Seungbok Lee, Narae Kim, Soo Yeon Kim, Hye Jin Yoo, Eun Na Kim, Jae-Kyung Won, Jin Sook Lee, Jangsup Moon, Jong-Hee Chae","doi":"10.1177/22143602261478703","DOIUrl":"https://doi.org/10.1177/22143602261478703","url":null,"abstract":"<p><p>ObjectivesAnti-signal recognition particle (SRP) myositis is a rare subset of immune-mediated necrotizing myopathy (IMNM). It is characterized by proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor response to conventional therapies. Evidence for optimal management remains limited, particularly regarding the long-term outcomes of rituximab treatment.MethodWe retrospectively reviewed anti-SRP myositis patients who received rituximab at Seoul National University Hospital. Diagnosis was based on clinical features, elevated CK levels, and positivity for anti-SRP antibodies. Demographic, clinical, laboratory, radiological, histopathological, and treatment data were collected.ResultsFive patients, aged between 4 and 71 years, exhibited proximal muscle weakness, elevated CK levels, and variable disease severity. Rituximab induction followed by maintenance therapy led to a significant improvement in muscle strength and normalization of CK and aldolase levels. In patients with mild or subclinical phenotypes, aldolase elevations often preceded clinical relapses. Relapses during follow-up were managed with rituximab re-administration, which restored muscle strength and biochemical markers. MRI, EMG, and muscle biopsy findings were consistent with myopathic changes.ConclusionsThis case series highlights the heterogeneity in age, disease severity, and clinical course of anti-SRP myositis and the efficacy of rituximab in refractory and relapsing cases. Multimodal monitoring, including CK, aldolase, CD19+ B-cell counts, and clinical assessment, is essential for the early detection of relapses. Our findings support rituximab as a valuable component of individualized treatment strategies for anti-SRP myositis, though larger studies are warranted to establish standardized protocols and clarify long-term outcomes.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261478703"},"PeriodicalIF":3.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathological and serological spectrum of idiopathic inflammatory myopathies: Experience from a neuromuscular referral center in Cyprus.","authors":"Tasos Tsokkos, Eleni Zamba-Papanicolaou, Revekka Papacharalambous, Christodoulos Taliadoros, Kleopas A Kleopa","doi":"10.1177/22143602261476765","DOIUrl":"https://doi.org/10.1177/22143602261476765","url":null,"abstract":"<p><p>BackgroundThe classification of idiopathic inflammatory myopathies (IIMs) has evolved substantially with the identification of myositis-specific autoantibodies (MSAs). However, how contemporary classification frameworks are applied in routine clinical practice remains variable. This study provides a clinicopathological and serological characterization of IIMs from a national neuromuscular referral center in Cyprus.MethodsWe conducted a retrospective, single-center cohort study of adult patients diagnosed with IIM between 2007 and 2025. Patients were classified using a clinicopathological and serological approach into dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), antisynthetase syndrome (ASyS), overlap myositis (OM), inclusion body myositis (IBM), and polymyositis (PM), with the 2017 EULAR/ACR criteria used as a reference framework and historical diagnoses re-evaluated.Results36 patients were included. Final subtype distribution: IMNM in 14 patients (39%), DM in 7 (19%), IBM in 4 (11%), OM in 5 (14%), ASyS in 3 (8%), PM in 2 (6%). Only one patient remained non-classifiable. Autoantibody testing was performed in 26/36 patients; MSAs were detected in 19/26 tested (73%; 53% of the total cohort), most commonly anti-HMGCR, while anti-NT5C1A antibodies were detected in three additional patients. Muscle biopsy was performed in the majority of patients, reflecting historical diagnostic practices.ConclusionThis study demonstrates real-world application of contemporary IIM classification, enabling accurate disease subtyping with direct implications for malignancy surveillance and interstitial lung disease monitoring, as well as reclassification of cases, most notably those previously labelled as PM. The findings further underscore the role of muscle biopsy, particularly when serology is negative, discordant, or unavailable.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261476765"},"PeriodicalIF":3.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal overview of symptomatic and immunosuppressive drugs in LEMS.","authors":"Wisse R Bakker, Linda Remijn-Nelissen, Teun van Gelder, Romina Shahini, Jan J G M Verschuuren, Martijn R Tannemaat","doi":"10.1177/22143602261477475","DOIUrl":"10.1177/22143602261477475","url":null,"abstract":"<p><p>Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular junction disorder characterized by muscle weakness and autonomic dysfunction. While amifampridine is the established first-line symptomatic treatment, longitudinal data regarding the evolution of therapeutic regimens over time and the use of immunosuppressive therapies remain limited. This retrospective study analyzed 70 LEMS patients treated at the Leiden University Medical Center (LUMC) between 1992 and 2023. Treatment was evaluated and a four-point \"leg score\" was developed and used to retrospectively quantify functional impairment and response to amifampridine. Sixty-six percent of the cohort was female, the median age of diagnosis was 54 years and non-tumor LEMS was more prevalent (77%). All patients used amifampridine at some point, and 91% initiated it within six months of diagnosis. Amifampridine improved leg scores in 57% of patients. Although 58% of patients reported side effects (mostly paresthesia), discontinuation was rare (7%). Pyridostigmine was used in 81% of patients. Immunosuppressive drug use-predominantly prednisolone and azathioprine -increased over time, reaching 44% after five years. Conversely, azathioprine, prednisolone and pyridostigmine were discontinued by 50%, 38% and 32% of patients, respectively, often due to adverse effects. In conclusion, amifampridine provides significant clinical benefits and remains the cornerstone of LEMS therapy. Immunomodulatory therapies were introduced gradually and their use increased over time. Compared with autoimmune myasthenia gravis, immunomodulatory therapy was used less frequently during the early disease course of LEMS.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261477475"},"PeriodicalIF":3.5,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical, histopathological, and biomarker characterization of XLMTM and ADCNM: Operational lessons, screening and baseline data of the Unite-CNM study.","authors":"Olga Prikhodko, Tatyana A Vetter, Sophie Colombo, Chris Freitag, Dominique Nijkamp, Louise Eyler, Leen Thielemans, Jonathan Baets, Mads Stemmerik, John Vissing, Ros Quinlivan, Michela Guglieri, Federica Montagnese, Benedikt Schoser, Frederik Braun, Ulrike Schara, Kris E Leeuwenberg, Nens van Alfen, Michael W Lawlor, Belinda S Cowling, Nicol C Voermans","doi":"10.1177/22143602261471202","DOIUrl":"https://doi.org/10.1177/22143602261471202","url":null,"abstract":"<p><p>BackgroundX-linked myotubular myopathy (XLMTM) and autosomal dominant centronuclear myopathy (ADCNM) are rare neuromuscular disorders characterized by severe weakness and respiratory impairment and have recently been the focus of therapeutic development. Robust baseline data are essential to understand disease trajectories and enable trial readiness. We present baseline clinical, functional, and biomarker findings from the terminated Unite-CNM trial (NCT04033159), a basket study of the antisense oligonucleotide DYN101, designed to modulate <i>DNM2</i> expression in adolescents and adults with XLMTM or ADCNM.MethodsScreening and baseline evaluations included medical history, patient-reported outcomes, quantitative muscle strength and motor function, respiratory testing, muscle ultrasound and histology, and biomarker analyses (DNM2 protein, creatinine, creatine kinase, cystatin C, myostatin, and microRNAs) in plasma and muscle.ResultsTwenty-six patients were screened (15 <i>DNM2</i>, 11 <i>MTM1</i>); 14 entered the study. Patient-reported measures highlighted swallowing challenges and variable personal goals. Baseline respiratory impairment was variable in <i>DNM2</i> and female <i>MTM1</i> patients but consistently reduced in males with <i>MTM1</i> (FVC% and FEV1% stable over follow-up to 78 weeks). MFM32 scores were similar across genotypes and sexes, while Myogrip strength was reduced versus age norms yet stable longitudinally. Muscle pathology was comparable across groups. Biomarker analyses showed altered DNM2 protein, reduced myostatin, and specific abnormalities in creatinine, creatine kinase, cystatin C, and microRNAs.ConclusionThis dataset provides valuable phenotypic, functional, and biomarker characterization of adult XLMTM and ADCNM, emphasizes the importance of baseline data for ultrarare disease trials, and highlights the need for protocol flexibility in response to safety signals and disruptions (e.g. COVID-19).</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261471202"},"PeriodicalIF":3.5,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Total energy expenditure assessed by doubly labeled water in patients with myotonic dystrophy type 1: Associations with body composition and functional status.","authors":"George Umemoto, Yoichi Hatamoto, Hajime Arahata, Shinsuke Fujioka, Yukiya Tanoue, Yosuke Yamada, Rie Tomiga-Takae, Yasuki Higaki","doi":"10.1177/22143602261477473","DOIUrl":"10.1177/22143602261477473","url":null,"abstract":"<p><p>Background & AimsMyotonic dystrophy type 1 (DM1) is frequently associated with metabolic abnormalities and altered body composition, yet energy metabolism under free-living conditions remains incompletely characterized. This study aimed to characterize total energy expenditure (TEE) using the doubly labeled water (DLW) method and to examine its associations with body composition and functional status. Estimated energy balance was also explored as a secondary variable.MethodsTwelve patients with genetically confirmed DM1 were included. TEE was assessed using the DLW method. Body composition was evaluated using multifrequency bioelectrical impedance analysis. Energy intake was estimated from dietary records, and energy balance was calculated as energy intake minus TEE. Associations were examined using correlation analyses.ResultsThe mean TEE was 990 ± 169 kcal/day. TEE showed moderate positive associations with skeletal muscle mass and fat-free mass, and functional status was moderately associated with body weight-adjusted TEE. The mean energy intake was 1,355 ± 229 kcal/day, resulting in a positive energy balance of 366 ± 282 kcal/day; however, energy balance was not associated with body fat percentage or fat mass.ConclusionsDLW-measured free-living TEE was markedly low in DM1 patients with severe mobility limitation and reduced lean body mass despite largely normal BMI values. Estimated energy balance was not associated with adiposity. These findings suggest that functional severity and body composition should be considered when interpreting energy expenditure in DM1.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261477473"},"PeriodicalIF":3.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective study of efgartigimod in severe myasthenia gravis exacerbations requiring ventilatory or enteral support.","authors":"Shahar Shelly, Ayal Rosenberg, Mohamad Zoabi, Saliba Makhoul, Roni Ramon-Gonen, Gil I Wolfe","doi":"10.1177/22143602261450402","DOIUrl":"10.1177/22143602261450402","url":null,"abstract":"<p><p>Background and objectivesTo evaluate the safety and clinical efficacy of efgartigimod in adults with severe generalized myasthenia gravis (MG) exacerbations requiring ventilatory or enteral support.MethodsProspective, single-arm, open-label study conducted between November 2024 and April 2025. Sixteen consecutive adults with AChR- or MuSK-antibody-positive generalized MG requiring invasive or non-invasive ventilatory support or enteral feeding were enrolled; all met 2016 MG Guidelines criteria for impending myasthenic crisis. MGFA classification included Class IIIb (n=14), IIIa (n=1), and IVb (n=1). The primary endpoint was clinically meaningful improvement (CMI) in MG Activities of Daily Living (MG-ADL), defined as ≥2-point reduction from baseline at weeks 4 and 8.ResultsAll 16 participants (mean age 58.5±17.4 years; 8 women) completed eight weeks of follow-up. At week 8, 12 patients (75%; 95% CI 47-91%) achieved the primary endpoint. Median MG-ADL decreased from 11 (IQR 9-13) to 7 (IQR 6-9) (median change -5 points; p=0.003). Median QMG decreased from 21 (IQR 19-23) to 13 (IQR 11-16) (median change -7.5 points; p<0.001), with 56% meeting QMG-CMI by week 1. Among 12 participants receiving corticosteroids (mean starting dose 21.2 mg/day), 50% reduced or discontinued by week 8. No treatment-related serious adverse events occurred.DiscussionEfgartigimod produced rapid, clinically meaningful improvement in severe MG exacerbations without safety concerns. FcRn blockade may represent a practical alternative to plasma exchange or IVIG in acute care settings. Findings are limited by the absence of a control arm, which precludes definitive attribution of clinical improvement to efgartigimod alone.Clinical trials registrationNCT06688253.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261450402"},"PeriodicalIF":3.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and functional outcome measures in LAMA2-related muscular dystrophy and SELENON-related myopathy; a 1.5-year natural history study.","authors":"Elisabeth C M de Laat, Jan T Groothuis, Karlijn Bouman, Saskia L S Houwen-van Opstal, Corrie E Erasmus, Nicol C Voermans","doi":"10.1177/22143602261465467","DOIUrl":"10.1177/22143602261465467","url":null,"abstract":"<p><p>BackgroundLAMA2-related muscular dystrophy (LAMA2-MD) and SELENON-related myopathy (SELENON-RM) are rare congenital muscle diseases characterized by slowly progressive proximal muscle weakness, spinal rigidity and respiratory insufficiency. The LAST STRONG study is a natural history study to identify suitable outcome measures and reach trial readiness for LAMA2-MD and SELENON-RM.MethodsPatients had four visits over 1.5-years. Assessments included neurological examination, hand-held dynamometry (HHD), functional assessments (Motor Function Measurements(MFM)-20/32, graded and timed function tests), accelerometry, and questionnaires on quality of life, activities and participation, pain, and fatigue.ResultsA total of 27 LAMA2-MD (21 years, range 3-50; 9 males) and 11 SELENON-RM (20 years, range 3-42; 8 males) patients were included. In LAMA2-MD, mean HHD scores for neck extensors, biceps brachii, quadriceps, foot plantar flexors and handgrip strength increased (all p < 0.02). In SELENON-RM, biceps brachii and foot plantar flexors increased (p < 0.01). In LAMA2-MD, functional assessments did not change significantly. In SELENON-RM, MFM-20/32 total score and domain 1 decreased (p < 0.05), 6-Minute Walk Test (6MWT) decreased (p < 0.01) and 10-Meter Walk Test (10MWT) increased (p < 0.01). Accelerometry showed a significant change in moderate activity in LAMA2-MD (p <0.01), no changes were observed in SELENON-RM.DiscussionOver 1.5 years, LAMA2-MD remained mostly stable, while SELENON-RM showed minimal functional decline on select outcome measures. Both cohorts showed HHD increases, likely reflecting age-related development. Most measures did not capture disease progression, however MFM-20/32, 6MWT and 10MWT showed small significant changes in SELENON-RM, suggesting potential trial endpoints.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602261465467"},"PeriodicalIF":3.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13438859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}