Neuromuscular Disorders最新文献_第6页

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 第288届ENMC国际研讨会。迈向更好地诊断、理解和治疗肌强直性营养不良的胃肠道症状：扩展的见解和实用的建议。2025年5月16日至18日，荷兰胡夫多普。

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 10.1016/j.nmd.2025.106250

Saskia Scholten , Janel A.M. Peterson , Lynn B. Orriëns , Luca Pastorelli , Giovanni Meola , Benedikt Schoser , Hilde M.H. Braakman

The 288^th 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.

第288届ENMC研讨会（2025年5月16日至18日）汇集了26名医疗保健专业人员、研究人员和患者代表，以促进对肌强直性营养不良（DM）患者胃肠道（GI）表现的理解和临床管理。胃肠道症状在糖尿病中很常见，但在临床护理中没有得到系统的解决，而且经常得不到治疗或治疗不当。本次研讨会强调了糖尿病胃肠道表现的广度和影响，讨论了口咽部、食道、肝脏、胆囊、胃、小肠和大肠以及盆底肌肉的症状。注意营养、认知和行为对这些症状的影响以及男女之间的差异。本文讨论了遗传和动物研究的进展，这些进展有助于提高对胃肠道病理生理学和潜在治疗方法的理解，并提出了使用这些研究的建议。在这些讨论的基础上，本报告通过纳入额外的文献和专家解释，扩展和充实了讲习班的内容。提供了实用的临床建议，以优化糖尿病患者胃肠道症状的护理和治疗，并与患者代表一起制定了一个包含10个问题的清单，可在咨询室中使用，以确定患者是否正在经历胃肠道症状。接下来的步骤包括开发针对胃肠道症状的dm特异性评估工具，并选择结果测量方法来监测随时间、治疗期间或临床试验中症状的变化。

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引用次数: 0

Neuropsychological and behavioral outcomes in childhood-onset myotonic dystrophy type 1 through lifespan: a scoping review 儿童期发病型1型强直性肌营养不良的神经心理和行为结局：一项范围综述。

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 10.1016/j.nmd.2025.106263

Isabelle Gaudet , Simon-Pierre Gagnon , Stéphanie Hamel , Noémie Gilbert , Filippia Doulou , Cynthia Gagnon , Nathalie Angeard

Unlike congenital and adult phenotypes, ChDM1 often involves minimal muscular symptoms with cognitive or behavioral difficulties being the most common early indicator of the disease. These difficulties, often exacerbated by fatigue and slowness, contribute to complex disability scenarios beginning as early as kindergarten but also persisting into early adulthood. This scoping review aims to explore the neuropsychological and behavioral profile associated with ChDM1 throughout the lifespan and seeks to understand how this profile evolves with age.

In total, 24 studies were included with 416 individuals identified as having ChDM1. Alongside visuospatial, attentional/executive and social difficulties, neuropsychiatric problems appeared also to be common in this population. Depressive and anxious symptoms were consistently reported in children and adolescents with ChDM1 but appear to be less frequent in adults.

The lack of standardized outcome measures for motor, cognitive and behavioral symptoms complicate efforts to determine the true prevalence and severity of impairments across studies. Identifying tools capable of capturing developmental trajectories over a sufficiently long period, from childhood to adulthood, remains a persistent challenge.

与先天性和成人表型不同，ChDM1通常涉及最小的肌肉症状，认知或行为困难是该疾病最常见的早期指标。这些困难往往因疲劳和行动迟缓而加剧，早在幼儿园就开始造成复杂的残疾情况，也会持续到成年早期。本综述旨在探讨ChDM1在整个生命周期中的神经心理和行为特征，并试图了解该特征如何随着年龄的增长而演变。总共有24项研究纳入了416名被确定患有ChDM1的个体。除了视觉空间、注意力/执行力和社交困难外，神经精神问题在这一人群中也很常见。抑郁和焦虑症状在患有ChDM1的儿童和青少年中一直有报道，但在成人中似乎不太常见。缺乏对运动、认知和行为症状的标准化结果测量使确定研究中损伤的真实患病率和严重程度的努力复杂化。寻找能够捕捉从童年到成年的足够长时期的发展轨迹的工具，仍然是一项持久的挑战。

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引用次数: 0

Novel missense variants associated with GNE myopathy 与GNE肌病相关的新型错义变异。

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 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.

GNE肌病是一种罕见的常染色体隐性骨骼肌疾病，其特征是进行性远端肌肉无力，通常从下肢开始，逐渐累及近端肌肉群。它是一种常染色体隐性遗传病，由双等位基因变异引起。迄今为止，已经报道了350多种GNE致病变异，然而，由于临床异质性和患者数量有限，建立基因型-表型相关性仍然很困难。在这项研究中，我们描述了20个无血缘关系的欧洲家庭，他们被诊断为GNE肌病，并在纯合性或复合杂合性中发现了双等位基因的GNE变异。虽然在我们的队列中观察到的大多数变异之前已经报道过，但我们发现了五个新的错义变异：p.(G355R), p.(A679T), p.(I709T), p.（V727G）和p.（V744I）。使用计算机预测工具和ACMG/AMP标准，我们将p.（G355R）和p.（V727G）分类为可能致病的。我们队列的临床特征与GNE肌病的经典表现一致。我们的发现提供了新的基因型数据，并支持正在进行的改进GNE肌病变异解释的努力。本研究扩大了GNE的突变谱，并加强了不同人群的表型一致性。

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引用次数: 0

Respiratory management in spinal muscular atrophy: development of a global outcome measure 脊髓性肌萎缩的呼吸管理：全球结果测量的发展。

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 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.

脊髓性肌萎缩症是一种多系统神经肌肉疾病，它跨越了儿科护理的频谱。随着疾病修饰疗法显示出一系列临床反应，有效监测变化至关重要。由于对患者生活质量和医疗保健成本有很大影响，因此对呼吸纵向结果测量的需求很重要。国际脊髓性肌萎缩症联盟正在开发一个评估SMA患者总体状况的全球量表。我们报告了创建和驾驶肺模块的过程。10位具有管理SMA患者经验的呼吸系统专家开发了一个单一模块，用于整个发育范围。模块包括临床病史、体格检查和肺功能测试。该模块在三家机构进行了试点，证明该模块易于使用，并在代表SMA类型1、2和3的51名受试者中产生了数据。数据显示了三种类型之间的差异：SMA1患者得分最低，SMA2和SMA3患者得分分别升高。设计评估SMA呼吸状态的模块既可行，又允许对SMA亚型进行区分。虽然结果令人鼓舞，但需要更多的数据来验证该模块并确定其精度。

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引用次数: 0

Cipaglucosidase alfa plus miglustat in Pompe disease: two non-ambulatory patients switching from high‑dose, high-frequency alglucosidase alfa Pompe病的西葡糖苷酶加米卢司他：两名非门诊患者从高剂量、高频α葡糖苷酶切换

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 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.

庞贝病是一种罕见的疾病，其特征是肌肉和呼吸功能的进行性丧失。非门诊患者或从高剂量、高频（HDHF；每周40 mg/kg） alfa （alg）切换到cipa+ miglustat （cipa+mig）的患者的数据有限。我们分析了ATB200-02研究中两名非门诊患者的结局，他们在转换为cipa+mig （20 mg/kg + 260 mg/ 2周）之前接受了>3年的alg（包括>2年的HDHF）。在54个月内，两者的上肢定量肌肉测试得分均显著提高。受试者和医生整体印象评分在6个月时得到改善或保持不变，并一直保持。12个月后，疲劳程度较基线有所改善。鹿特丹障碍量表得分随时间而波动。生物标志物水平（尿己糖四糖和血清肌酸激酶）与基线相比均有所改善。2例患者均发生11例非严重不良事件（无输液相关反应）。数据为临床医生考虑从HDHF过渡到cipa+mig提供了信息。

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引用次数: 0

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 第284届ENMC国际研讨会：儿童DM1的认知和行为异常；在准备临床试验时我们应该衡量什么？荷兰Hoofddorp， 2025年1月24日至26日

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 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.

针对儿童DM1的临床试验，第284届ENMC研讨会旨在根据国际专家共识，通过1)回顾现有的儿童DM1中中枢神经系统参与的转化研究成果，建立中枢神经系统参与的诊断和管理方案；2)分享目前国际儿童DM1人群中CNS参与的临床和诊断方法；3)讨论与未来儿童DM1临床和研究应用相关的保护性CNS生物标志物。考虑了患者和家属对生活质量影响的看法。研讨会从研究和临床护理的角度强调了中枢神经系统参与范围的复杂性，并确认了对认知行为异常的临床评估进行国际协调的必要性。在以下方面达成了共识：1)基于症状出现年龄的疾病分类；2)在临床实践中使用的核心神经心理学评估方案。讨论了试验设计和进一步研究的意义。

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引用次数: 0

ENMC Themed Workshops ENMC主题工作坊

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 10.1016/S0960-8966(25)01013-2

引用次数: 0

Mills' syndrome and myasthenia gravis: a case report 米尔斯综合征合并重症肌无力1例。

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 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.

一个50岁的男性甲状腺功能减退症是难治性重症肌无力（MG）。他出现进行性、无痛性右肩和腿部无力、吞咽困难和疲劳性复视。乙酰胆碱受体（AChR）抗体阳性。免疫抑制治疗仅提供短暂改善眼球症状，而偏瘫进展。检查显示疲劳性上睑下垂伴帘征，垂直凝视受限，复视定位于左外侧直肌无力。上运动神经元征象包括咬肌反射活跃、右侧痉挛性偏瘫和反射亢进。肌电图显示右侧颈、腰骶区有慢性神经再支配。MRI显示左上颈髓及邻近髓质T2高信号，无强化。诊断为AChR+ MG及Mills综合征。虽然MG先前有报道与ALS共存，但这是已知的第一例与米尔斯综合征相关的病例。这突出了认识自身免疫和神经退行性疾病重叠的重要性，以及进一步研究共同机制的必要性。

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引用次数: 0

Long term safety and efficacy of lamotrigine in patients with non-dystrophic myotonia, a single-centre prospective study 拉莫三嗪在非营养不良性肌强直患者中的长期安全性和有效性，一项单中心前瞻性研究

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-11-01 DOI: 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。

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引用次数: 0

287th ENMC international workshop: Harmonization and federated analysis of myotonic dystrophy registries to model heterogeneous disease trajectories. Hoofddorp, the Netherlands, 28–30 March 2025 第287届ENMC国际研讨会：协调和联合分析肌强直性营养不良登记模型异质疾病轨迹。霍夫多普，荷兰，2025年3月28日至30日

IF 2.8 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders

Pub Date : 2025-10-24 DOI: 10.1016/j.nmd.2025.106257

Leandre A. la Fontaine , Daniël van As , Guillaume Bassez , Nicholas E. Johnson , Catharina G. Faber , Peter A.C.’t Hoen , 287th ENMC workshop participants

The 287th ENMC International Workshop convened experts from ten countries to address the harmonization and federated analysis of Myotonic Dystrophy Type 1 (DM1) registries. With over 10,500 patients enrolled globally, registries remain fragmented, limiting their utility in modeling disease trajectories and supporting clinical trials. As new therapies enter advanced clinical testing, registries must evolve - not only to enable trial readiness but also to support downstream functions like pharmacovigilance. The workshop focused on four objectives: re-defining a core dataset, enabling FAIRification of registries, establishing federated analysis infrastructure, and developing longitudinal modeling strategies. Key outcomes included a revised core set of clinical and patient reported outcome measures that is feasible to collect in a routine care setting, strategies for FAIR data integration, and governance models for federated analysis. Pragmatic and interpretable statistical approaches such as latent variable modeling and unsupervised clustering were discussed, with key prediction targets identified across motor, cardiac, and pulmonary domains. The workshop emphasized the need for sustainable funding, patient-centered design, and international collaboration.

第287届ENMC国际研讨会召集了来自10个国家的专家，讨论了1型肌强直性营养不良（DM1）登记的统一和联合分析。全球有超过10,500名患者注册，但注册仍然分散，限制了它们在建模疾病轨迹和支持临床试验方面的效用。随着新疗法进入高级临床试验阶段，注册必须不断发展——不仅要为试验做好准备，还要支持药物警戒等下游功能。研讨会主要关注四个目标：重新定义核心数据集、启用注册中心的标准化、建立联邦分析基础设施以及开发纵向建模策略。关键结果包括修订后的临床和患者报告的核心结果测量，这些测量在常规护理环境中是可行的，FAIR数据整合的策略，以及联邦分析的治理模型。讨论了实用和可解释的统计方法，如潜在变量建模和无监督聚类，并确定了跨运动，心脏和肺域的关键预测目标。研讨会强调了可持续资金、以患者为中心的设计和国际合作的必要性。

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引用次数: 0