The 288th ENMC workshop (16–18 May 2025) brought together a group of 26 healthcare professionals, researchers, and patient representatives to advance understanding and clinical management of gastrointestinal (GI) manifestations in individuals with myotonic dystrophy (DM). GI symptoms are common in DM but are not systematically addressed in clinical care and are frequently left untreated or treated incorrectly. This workshop highlighted the breadth and impact of GI manifestations in DM, addressing symptoms in the oropharynx, oesophagus, liver, gallbladder, stomach, small and large intestines, and pelvic floor muscles. Attention was given to nutritional, cognitive, and behavioural influences on these symptoms and differences across males and females. Developments in genetic and animal studies that contribute to an increased understanding of the pathophysiology and potential treatment of GI manifestations were discussed, and recommendations are provided for their use. Building on these discussions, this report extends and substantiates the workshop content by incorporating additional literature and expert interpretation. Practical clinical recommendations to optimise the care and treatment of GI symptoms in DM were provided and, together with patient representatives, a list of 10 questions has been developed that can be used in the consultation room to identify whether a patient is experiencing GI symptoms. Next steps include the development of a DM-specific assessment instrument for GI symptoms and the selection of outcome measures to monitor changes in symptoms over time, during treatment, or in clinical trials.
{"title":"288th ENMC International Workshop. Towards better diagnosing, understanding and treating gastrointestinal symptoms in myotonic dystrophy: extended insights and practical recommendations. 16-18 May 2025, Hoofddorp, the Netherlands","authors":"Saskia Scholten , Janel A.M. Peterson , Lynn B. Orriëns , Luca Pastorelli , Giovanni Meola , Benedikt Schoser , Hilde M.H. Braakman","doi":"10.1016/j.nmd.2025.106250","DOIUrl":"10.1016/j.nmd.2025.106250","url":null,"abstract":"<div><div>The 288<sup>th</sup> ENMC workshop (16<strong>–</strong>18 May 2025) brought together a group of 26 healthcare professionals, researchers, and patient representatives to advance understanding and clinical management of gastrointestinal (GI) manifestations in individuals with myotonic dystrophy (DM). GI symptoms are common in DM but are not systematically addressed in clinical care and are frequently left untreated or treated incorrectly. This workshop highlighted the breadth and impact of GI manifestations in DM, addressing symptoms in the oropharynx, oesophagus, liver, gallbladder, stomach, small and large intestines, and pelvic floor muscles. Attention was given to nutritional, cognitive, and behavioural influences on these symptoms and differences across males and females. Developments in genetic and animal studies that contribute to an increased understanding of the pathophysiology and potential treatment of GI manifestations were discussed, and recommendations are provided for their use. Building on these discussions, this report extends and substantiates the workshop content by incorporating additional literature and expert interpretation. Practical clinical recommendations to optimise the care and treatment of GI symptoms in DM were provided and, together with patient representatives, a list of 10 questions has been developed that can be used in the consultation room to identify whether a patient is experiencing GI symptoms. Next steps include the development of a DM-specific assessment instrument for GI symptoms and the selection of outcome measures to monitor changes in symptoms over time, during treatment, or in clinical trials.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106250"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355422","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}
Pub Date : 2025-11-01Epub Date: 2025-10-25DOI: 10.1016/j.nmd.2025.106258
Johanna Ranta-aho , Viviana Cetrangolo , Luca Bello , Giuliana Capece , Elena Pegoraro , Maria Francesca Di Feo , Violeta Mihaylova , Hans H. Jung , Fabien Hauw , Tanya Stojkovic , Anthony Behin , Norma Romero , Thierry Maisonobe , Matteo Lucchini , Miguel Oliveira Santos , Massimiliano Mirabella , Giorgio Tasca , Marco Savarese , Bjarne Udd , Mridul Johari
GNE myopathy is a rare autosomal recessive skeletal muscle disorder characterized by progressive distal muscle weakness, typically starting in the lower legs and gradually involving proximal muscle groups. It is an autosomal recessive disease, caused by biallelic variants in GNE. To date, over 350 causative GNE variants have been reported, however, establishing genotype-phenotype correlation remains difficult due to clinical heterogeneity and limited patient numbers. In this study, we describe 20 unrelated European families with a diagnosis of GNE myopathy and biallelic GNE variants identified in either homozygosity or compound heterozygosity. While the majority of variants observed in our cohort have been previously reported, we identified five novel missense variants: p.(G355R), p.(A679T), p.(I709T), p.(V727G), and p.(V744I). Using in silico prediction tools and ACMG/AMP criteria, we classified p.(G355R) and p.(V727G) as likely pathogenic. The clinical features of our cohort were consistent with the classical presentation of GNE myopathy. Our findings contribute new genotype data and support ongoing efforts to refine variant interpretation in GNE myopathy. This study expands the mutational spectrum of GNE and reinforces the phenotypic consistency across diverse populations.
{"title":"Novel missense variants associated with GNE myopathy","authors":"Johanna Ranta-aho , Viviana Cetrangolo , Luca Bello , Giuliana Capece , Elena Pegoraro , Maria Francesca Di Feo , Violeta Mihaylova , Hans H. Jung , Fabien Hauw , Tanya Stojkovic , Anthony Behin , Norma Romero , Thierry Maisonobe , Matteo Lucchini , Miguel Oliveira Santos , Massimiliano Mirabella , Giorgio Tasca , Marco Savarese , Bjarne Udd , Mridul Johari","doi":"10.1016/j.nmd.2025.106258","DOIUrl":"10.1016/j.nmd.2025.106258","url":null,"abstract":"<div><div>GNE myopathy is a rare autosomal recessive skeletal muscle disorder characterized by progressive distal muscle weakness, typically starting in the lower legs and gradually involving proximal muscle groups. It is an autosomal recessive disease, caused by biallelic variants in <em>GNE</em>. To date, over 350 causative <em>GNE</em> variants have been reported, however, establishing genotype-phenotype correlation remains difficult due to clinical heterogeneity and limited patient numbers. In this study, we describe 20 unrelated European families with a diagnosis of GNE myopathy and biallelic <em>GNE</em> variants identified in either homozygosity or compound heterozygosity. While the majority of variants observed in our cohort have been previously reported, we identified five novel missense variants: p.(G355R), p.(A679T), p.(I709T), p.(V727G), and p.(V744I). Using <em>in silico</em> prediction tools and ACMG/AMP criteria, we classified p.(G355R) and p.(V727G) as likely pathogenic. The clinical features of our cohort were consistent with the classical presentation of GNE myopathy. Our findings contribute new genotype data and support ongoing efforts to refine variant interpretation in GNE myopathy. This study expands the mutational spectrum of <em>GNE</em> and reinforces the phenotypic consistency across diverse populations.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106258"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513536","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}
Pub Date : 2025-11-01Epub Date: 2025-11-05DOI: 10.1016/j.nmd.2025.106264
Barry J. Byrne , Jeff Castelli , Vipul Jain , Sheela Sitaraman Das , Jennifer Zhang
Pompe disease is a rare disorder characterized by progressive loss of muscle and respiratory function. Data are limited in non-ambulatory patients or those switching from high-dose, high-frequency (HDHF; 40 mg/kg every week) alglucosidase alfa (alg) to cipaglucosidase alfa plus miglustat (cipa+mig). We analyzed outcomes in two non-ambulatory patients in study ATB200–02 who received alg for >13 years (including >2 years’ HDHF) before switching to cipa+mig (20 mg/kg + 260 mg every 2 weeks). In both, upper limb quantitative muscle test scores markedly increased over 54 months. Subject and Physician Global Impression of Change scores were improved or unchanged at 6 months and maintained throughout. Fatigue severity improved versus baseline after 12 months. Rotterdam Handicap Scale scores fluctuated over time. Biomarker levels (urine hexose tetrasaccharide and serum creatine kinase) improved versus baseline at all visits. The two patients experienced 11 non-serious adverse events (no infusion-associated reactions). Data provide information for clinicians considering a transition from HDHF alg to cipa+mig.
{"title":"Cipaglucosidase alfa plus miglustat in Pompe disease: two non-ambulatory patients switching from high‑dose, high-frequency alglucosidase alfa","authors":"Barry J. Byrne , Jeff Castelli , Vipul Jain , Sheela Sitaraman Das , Jennifer Zhang","doi":"10.1016/j.nmd.2025.106264","DOIUrl":"10.1016/j.nmd.2025.106264","url":null,"abstract":"<div><div>Pompe disease is a rare disorder characterized by progressive loss of muscle and respiratory function. Data are limited in non-ambulatory patients or those switching from high-dose, high-frequency (HDHF; 40 mg/kg every week) alglucosidase alfa (alg) to cipaglucosidase alfa plus miglustat (cipa+mig). We analyzed outcomes in two non-ambulatory patients in study ATB200–02 who received alg for >13 years (including >2 years’ HDHF) before switching to cipa+mig (20 mg/kg + 260 mg every 2 weeks). In both, upper limb quantitative muscle test scores markedly increased over 54 months. Subject and Physician Global Impression of Change scores were improved or unchanged at 6 months and maintained throughout. Fatigue severity improved versus baseline after 12 months. Rotterdam Handicap Scale scores fluctuated over time. Biomarker levels (urine hexose tetrasaccharide and serum creatine kinase) improved versus baseline at all visits. The two patients experienced 11 non-serious adverse events (no infusion-associated reactions). Data provide information for clinicians considering a transition from HDHF alg to cipa+mig.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106264"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573943","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}
Pub Date : 2025-11-01Epub Date: 2025-10-22DOI: 10.1016/j.nmd.2025.106253
L. Edel , M. Civitello , F. Muntoni , R. Finkel , E. Mercuri , G. Baranello , O. Mayer
Spinal muscular atrophy is a multisystem neuromuscular condition which crosses a spectrum of paediatric care. With disease modifying therapies demonstrating a range of clinical responses, effectively monitoring change is vital. The need for a respiratory longitudinal outcome measure is important due to the large impact on patient quality of life and cost to healthcare. The International Spinal Muscular Atrophy Consortium is developing a global scale for assessing the overall status of patients with SMA. We report the process of creating and piloting the pulmonary module. 10 respiratory specialists, with experience managing patients with SMA, developed a single module to be used across the developmental spectrum. Modules included Clinical History, Physical Exam, and Pulmonary Function Testing. The module was piloted at three institutions, demonstrating the module was easy to use and produced data in 51 subjects representing SMA types 1, 2 and 3. The data demonstrated differences between the three types: patients with SMA1 had the lowest score, and increasing scores for patients with SMA2 and SMA3, respectively. Designing the module to assess the respiratory status in SMA is both feasible and allows for discrimination between SMA subtypes. While results are encouraging, more data is needed to validate the module and determine its precision.
{"title":"Respiratory management in spinal muscular atrophy: development of a global outcome measure","authors":"L. Edel , M. Civitello , F. Muntoni , R. Finkel , E. Mercuri , G. Baranello , O. Mayer","doi":"10.1016/j.nmd.2025.106253","DOIUrl":"10.1016/j.nmd.2025.106253","url":null,"abstract":"<div><div>Spinal muscular atrophy is a multisystem neuromuscular condition which crosses a spectrum of paediatric care. With disease modifying therapies demonstrating a range of clinical responses, effectively monitoring change is vital. The need for a respiratory longitudinal outcome measure is important due to the large impact on patient quality of life and cost to healthcare. The International Spinal Muscular Atrophy Consortium is developing a global scale for assessing the overall status of patients with SMA. We report the process of creating and piloting the pulmonary module. 10 respiratory specialists, with experience managing patients with SMA, developed a single module to be used across the developmental spectrum. Modules included Clinical History, Physical Exam, and Pulmonary Function Testing. The module was piloted at three institutions, demonstrating the module was easy to use and produced data in 51 subjects representing SMA types 1, 2 and 3. The data demonstrated differences between the three types: patients with SMA1 had the lowest score, and increasing scores for patients with SMA2 and SMA3, respectively. Designing the module to assess the respiratory status in SMA is both feasible and allows for discrimination between SMA subtypes. While results are encouraging, more data is needed to validate the module and determine its precision.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106253"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145496284","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}
Pub Date : 2025-11-01Epub Date: 2025-10-21DOI: 10.1016/j.nmd.2025.106252
Susanna Pozzi , Dirk J.J. Sweere , Federica Trucco , Nicholas E. Johnson , Valeria A. Sansone , Workshop Study Group
In anticipation to clinical trials in pediatric DM1, the 284th ENMC workshop aimed to establish diagnostic and management protocols for CNS involvement based on international expert-consensus by 1) reviewing existing translational research findings on CNS involvement in pediatric DM1, 2) sharing current clinical and diagnostic approaches to CNS involvement in the international pediatric DM1 population and 3) discuss protentional CNS biomarkers relevant to future clinical and research applications in pediatric DM1. Patient and family perspectives on the impact on quality of life were considered. The workshop highlighted the complexity of the spectrum of CNS involvement from a research and clinical care perspective and confirmed the need for international harmonization of clinical assessment of cognitive-behavioral abnormalities. Consensus was reached on 1) disease classification based on age of symptom-onset and 2) a core neuropsychological assessment protocol to be used in clinical practice. Implications for trial design and further research are discussed.
{"title":"284th ENMC International Workshop: Cognitive and behavioral abnormalities in pediatric DM1; what should we measure in preparation for clinical trials? Hoofddorp, The Netherlands, January 24-26 2025","authors":"Susanna Pozzi , Dirk J.J. Sweere , Federica Trucco , Nicholas E. Johnson , Valeria A. Sansone , Workshop Study Group","doi":"10.1016/j.nmd.2025.106252","DOIUrl":"10.1016/j.nmd.2025.106252","url":null,"abstract":"<div><div>In anticipation to clinical trials in pediatric DM1, the 284th ENMC workshop aimed to establish diagnostic and management protocols for CNS involvement based on international expert-consensus by 1) reviewing existing translational research findings on CNS involvement in pediatric DM1, 2) sharing current clinical and diagnostic approaches to CNS involvement in the international pediatric DM1 population and 3) discuss protentional CNS biomarkers relevant to future clinical and research applications in pediatric DM1. Patient and family perspectives on the impact on quality of life were considered. The workshop highlighted the complexity of the spectrum of CNS involvement from a research and clinical care perspective and confirmed the need for international harmonization of clinical assessment of cognitive-behavioral abnormalities. Consensus was reached on 1) disease classification based on age of symptom-onset and 2) a core neuropsychological assessment protocol to be used in clinical practice. Implications for trial design and further research are discussed.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106252"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145419919","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}
Pub Date : 2025-11-01Epub Date: 2025-11-12DOI: 10.1016/j.nmd.2025.106280
Jonathan Morena , James Hiana , Ryan Naum , Vern Juel
A 50-year-old man with hypothyroidism was referred for refractory myasthenia gravis (MG). He developed progressive, painless right-sided shoulder and leg weakness, dysphagia, and fatigable diplopia. Acetylcholine receptor (AChR) antibodies were positive. Immunosuppressive therapies provided only transient improvement in oculo-bulbar symptoms, while hemiparesis progressed. Examination showed fatigable ptosis with curtain sign, vertical gaze limitation, and diplopia localizing to left lateral rectus weakness. Upper motor neuron signs included brisk masseteric reflex, right spastic hemiparesis, and hyperreflexia. EMG demonstrated chronic reinnervation in right cervical and lumbosacral regions. MRI revealed T2 hyperintensity in the left upper cervical cord and adjacent medulla without enhancement. A diagnosis of AChR+ MG and Mills’ syndrome was made. While MG has previously been reported to coexist with ALS, this is the first known case associated with Mills’ syndrome. This highlights the importance of recognizing overlapping autoimmune and neurodegenerative disorders and the need for further research into shared mechanisms.
{"title":"Mills' syndrome and myasthenia gravis: a case report","authors":"Jonathan Morena , James Hiana , Ryan Naum , Vern Juel","doi":"10.1016/j.nmd.2025.106280","DOIUrl":"10.1016/j.nmd.2025.106280","url":null,"abstract":"<div><div>A 50-year-old man with hypothyroidism was referred for refractory myasthenia gravis (MG). He developed progressive, painless right-sided shoulder and leg weakness, dysphagia, and fatigable diplopia. Acetylcholine receptor (AChR) antibodies were positive. Immunosuppressive therapies provided only transient improvement in oculo-bulbar symptoms, while hemiparesis progressed. Examination showed fatigable ptosis with curtain sign, vertical gaze limitation, and diplopia localizing to left lateral rectus weakness. Upper motor neuron signs included brisk masseteric reflex, right spastic hemiparesis, and hyperreflexia. EMG demonstrated chronic reinnervation in right cervical and lumbosacral regions. MRI revealed T2 hyperintensity in the left upper cervical cord and adjacent medulla without enhancement. A diagnosis of AChR+ MG and Mills’ syndrome was made. While MG has previously been reported to coexist with ALS, this is the first known case associated with Mills’ syndrome. This highlights the importance of recognizing overlapping autoimmune and neurodegenerative disorders and the need for further research into shared mechanisms.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106280"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605065","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}
Pub Date : 2025-11-01Epub Date: 2025-09-24DOI: 10.1016/j.nmd.2025.106222
Murva Asad , Iwona Skorupinska , Natalie James , Dipa Jayaseelan , Michael G Hanna , Vinojini Vivekanandam
The non-dystrophic myotonias are rare genetic conditions characterised by delayed muscle relaxation, muscle stiffness, pain and fatigue. This study examines the experience of the UK National Referral Centre in using lamotrigine to treat non-dystrophic myotonias. A prospective cohort of 37 patients with genetically confirmed non-dystrophic myotonias (23 with CLCN1 variants and 14 with SCN4A variants) who were prescribed lamotrigine as part of routine clinical care were followed for a mean of 26 months. Treatment efficacy was assessed using the Myotonia Behaviour Score. 26 participants were included in the efficacy analysis where lamotrigine was found to reduce the mean Myotonia Behaviour Score from 3.3 to 1.8 (p < .001, Cohen’s d = 1.2), demonstrating significant symptom improvement. Side effects, mainly rash and headache, led to discontinuation in nine out of 37 patients, but no severe adverse events occurred. In most cases, lamotrigine was chosen due to prior side effects with mexiletine or cardiac contraindications to mexiletine and proved to be an effective alternative. This study provides real-world evidence supporting the long-term use of lamotrigine and the integration of lamotrigine into personalised treatment strategies for non-dystrophic myotonias.
非营养不良性肌强直是一种罕见的遗传性疾病，其特征是肌肉松弛延迟、肌肉僵硬、疼痛和疲劳。本研究考察了英国国家转诊中心使用拉莫三嗪治疗非营养不良性肌强直的经验。37例经基因证实的非营养不良性肌强直患者（23例CLCN1变异体，14例SCN4A变异体）接受拉莫三新作为常规临床护理的一部分，平均随访26个月。使用肌强直行为评分评估治疗效果。26名参与者被纳入疗效分析，发现拉莫三嗪将平均肌强直行为评分从3.3降至1.8 (p < .001, Cohen’s d = 1.2)，显示出显著的症状改善。副作用，主要是皮疹和头痛，导致37例患者中有9例停药，但没有发生严重的不良事件。在大多数情况下，选择拉莫三嗪是由于先前与美西汀的副作用或美西汀的心脏禁忌症，并被证明是一种有效的替代品。这项研究提供了真实的证据，支持长期使用拉莫三嗪，并将拉莫三嗪整合到非营养不良性肌强直的个性化治疗策略中。
{"title":"Long term safety and efficacy of lamotrigine in patients with non-dystrophic myotonia, a single-centre prospective study","authors":"Murva Asad , Iwona Skorupinska , Natalie James , Dipa Jayaseelan , Michael G Hanna , Vinojini Vivekanandam","doi":"10.1016/j.nmd.2025.106222","DOIUrl":"10.1016/j.nmd.2025.106222","url":null,"abstract":"<div><div>The non-dystrophic myotonias are rare genetic conditions characterised by delayed muscle relaxation, muscle stiffness, pain and fatigue. This study examines the experience of the UK National Referral Centre in using lamotrigine to treat non-dystrophic myotonias. A prospective cohort of 37 patients with genetically confirmed non-dystrophic myotonias (23 with <em>CLCN1</em> variants and 14 with <em>SCN4A</em> variants) who were prescribed lamotrigine as part of routine clinical care were followed for a mean of 26 months. Treatment efficacy was assessed using the Myotonia Behaviour Score. 26 participants were included in the efficacy analysis where lamotrigine was found to reduce the mean Myotonia Behaviour Score from 3.3 to 1.8 (<em>p</em> < .001, Cohen’s <em>d</em> = 1.2), demonstrating significant symptom improvement. Side effects, mainly rash and headache, led to discontinuation in nine out of 37 patients, but no severe adverse events occurred. In most cases, lamotrigine was chosen due to prior side effects with mexiletine or cardiac contraindications to mexiletine and proved to be an effective alternative. This study provides real-world evidence supporting the long-term use of lamotrigine and the integration of lamotrigine into personalised treatment strategies for non-dystrophic myotonias.</div></div>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":"56 ","pages":"Article 106222"},"PeriodicalIF":2.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467719","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}
Pub Date : 2025-10-24DOI: 10.1016/j.nmd.2025.106256
Craig M Zaidman, Crystal Proud, Bing M Liao, Nassim Rad, Doreen Ho, Mary-Lynn Chu, Shafeeq Ladha, Thomas O Crawford, Shakti Nayar, Angela Genge, Margaret Frey, Chad Heatwole, Daphne Lew
Nusinersen, an antisense oligonucleotide, modulates pre-mRNA splicing to produce full length survival motor neuron protein in spinal muscular atrophy (SMA). It was approved in the US for SMA in all ages based on evidence in children. In adults, studies of nusinersen rely on real-world observational data and show stability or small improvements over time. We performed a prospective, 30 month longitudinal, observational multi-center study of adults initiating nusinersen with SMA types II/III to examine its safety, tolerability, and effectiveness. 43 participants (20 female; 14 ambulatory; 3, 17, and 23 with 2, 3, and ≥4 SMN2 copies, respectively), mean (SD) age 37.1 (11.9) years) enrolled and completed baseline assessments. Serial assessments over 30 months showed small but not significant improvements in the six minute walk test (16.1 m), Revised Upper Limb Module (0.7), Revised Hammersmith Scale (0.8), maximal inspiratory (-2.6 cm H20) and expiratory pressure (12.3 cm H20). Muscle strength and forced vital capacity did not change. The patient reported outcome Total SMA-HI improved (-11 (95% CI: -17,-5); p < 0.001)). No new safety effects were identified. This study of nusinersen in adults with SMA demonstrates stability over time in contrast to the expected decline in untreated patients, with a favorable safety profile.
Nusinersen是一种反义寡核苷酸，在脊髓性肌萎缩症（SMA）中调节mrna前剪接产生全长存活运动神经元蛋白。基于儿童的证据，它在美国被批准用于所有年龄段的SMA。在成人中，对nusinersen的研究依赖于真实世界的观察数据，并随着时间的推移显示出稳定性或小幅改善。我们对患有II/III型SMA的成人进行了一项为期30个月的前瞻性、纵向、多中心观察研究，以检验其安全性、耐受性和有效性。43名参与者（20名女性；14名流动患者；3名、17名和23名分别携带2、3和≥4个SMN2拷贝），平均（SD）年龄为37.1（11.9）岁)入组并完成基线评估。超过30个月的系列评估显示，6分钟步行测试（16.1 m）、修订上肢模块（0.7）、修订Hammersmith量表（0.8）、最大吸气压（-2.6 cm H20）和呼气压（12.3 cm H20）有微小但不显著的改善。肌肉力量和肺活量没有变化。患者报告的结果总SMA-HI改善(-11 (95% CI: -17,-5)；P < 0.001))。没有发现新的安全效应。这项研究表明，与未经治疗的患者的预期下降相比，nusinersen在成人SMA患者中的稳定性随着时间的推移而下降，具有良好的安全性。
{"title":"A prospective, multi-center, observational study of the safety, tolerability and effectiveness of Nusinersen in adult patients with spinal muscular atrophy.","authors":"Craig M Zaidman, Crystal Proud, Bing M Liao, Nassim Rad, Doreen Ho, Mary-Lynn Chu, Shafeeq Ladha, Thomas O Crawford, Shakti Nayar, Angela Genge, Margaret Frey, Chad Heatwole, Daphne Lew","doi":"10.1016/j.nmd.2025.106256","DOIUrl":"https://doi.org/10.1016/j.nmd.2025.106256","url":null,"abstract":"<p><p>Nusinersen, an antisense oligonucleotide, modulates pre-mRNA splicing to produce full length survival motor neuron protein in spinal muscular atrophy (SMA). It was approved in the US for SMA in all ages based on evidence in children. In adults, studies of nusinersen rely on real-world observational data and show stability or small improvements over time. We performed a prospective, 30 month longitudinal, observational multi-center study of adults initiating nusinersen with SMA types II/III to examine its safety, tolerability, and effectiveness. 43 participants (20 female; 14 ambulatory; 3, 17, and 23 with 2, 3, and ≥4 SMN2 copies, respectively), mean (SD) age 37.1 (11.9) years) enrolled and completed baseline assessments. Serial assessments over 30 months showed small but not significant improvements in the six minute walk test (16.1 m), Revised Upper Limb Module (0.7), Revised Hammersmith Scale (0.8), maximal inspiratory (-2.6 cm H20) and expiratory pressure (12.3 cm H20). Muscle strength and forced vital capacity did not change. The patient reported outcome Total SMA-HI improved (-11 (95% CI: -17,-5); p < 0.001)). No new safety effects were identified. This study of nusinersen in adults with SMA demonstrates stability over time in contrast to the expected decline in untreated patients, with a favorable safety profile.</p>","PeriodicalId":19135,"journal":{"name":"Neuromuscular Disorders","volume":" ","pages":"106256"},"PeriodicalIF":2.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434391","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}
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