Journal of neuromuscular diseases最新文献

{"title":"A neuromuscular clinician's primer on machine learning.","authors":"Crystal Jing Jing Yeo, Savitha Ramasamy, F Joel Leong, Sonakshi Nag, Zachary Simmons","doi":"10.1177/22143602251329240","DOIUrl":"https://doi.org/10.1177/22143602251329240","url":null,"abstract":"<p><p>Artificial intelligence is the future of clinical practice and is increasingly utilized in medical management and clinical research. The release of ChatGPT3 in 2022 brought generative AI to the headlines and rekindled public interest in software agents that would complete repetitive tasks and save time. Artificial intelligence/machine learning underlies applications and devices which are assisting clinicians in the diagnosis, monitoring, formulation of prognosis, and treatment of patients with a spectrum of neuromuscular diseases. However, these applications have remained in the research sphere, and neurologists as a specialty are running the risk of falling behind other clinical specialties which are quicker to embrace these new technologies. While there are many comprehensive reviews on the use of artificial intelligence/machine learning in medicine, our aim is to provide a simple and practical primer to educate clinicians on the basics of machine learning. This will help clinicians specializing in neuromuscular and electrodiagnostic medicine to understand machine learning applications in nerve and muscle ultrasound, MRI imaging, electrical impendence myography, nerve conductions and electromyography and clinical cohort studies, and the limitations, pitfalls, regulatory and ethical concerns, and future directions. The question is not whether artificial intelligence/machine learning will change clinical practice, but when and how. How future neurologists will look back upon this period of transition will be determined not by how much changed or by how fast clinicians embraced this change but by how much patient outcomes were improved.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251329240"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753100","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":"Signs and symptoms of carriers of non-<i>DMD</i> X-linked neuromuscular diseases: A scoping review.","authors":"Job Simons, Amanda Dekker, Rosanne Govaarts, Anna Sarkozy, Christian Windpassinger, Saskia Houwen, Nicol Voermans","doi":"10.1177/22143602251330441","DOIUrl":"https://doi.org/10.1177/22143602251330441","url":null,"abstract":"<p><strong>Background: </strong>It has been known for long that females carrying pathogenic variants in the <i>DMD</i> gene often report symptoms and/or exhibit signs of the disease. However, a notable knowledge gap exists concerning the signs and symptoms of female carriers of other X-linked neuromuscular diseases (XLNMDs).</p><p><strong>Objective: </strong>This scoping review aims to provide a comprehensive outline of existing literature regarding the signs and symptoms of carriers of non-<i>DMD</i> XLNMDs to raise awareness among both researchers and clinicians.</p><p><strong>Methods: </strong>Three electronic databases were used for the literature search (PubMed, Embase, Web of Science). Studies on the signs and symptoms of carriers of non-<i>DMD</i> XLNMDs were included.</p><p><strong>Results: </strong>We included 44 articles for this review with a total of 354 carriers of non-<i>DMD</i> XLNMDs (mean age 43.9 years, std. deviation 17.4). Muscular signs and symptoms were reported for 125 carriers (X-linked myotubular myopathy (XLMTM): n = 96 (65%); Kennedy's disease (KD): n = 25 (32%); X-linked recessive Charcot-Marie-Tooth disease (CMTXR): n = 2 (15%); Uruguay faciocardiomusculoskeletal syndrome (FCMSU): n = 1 (33%); Barth syndrome (BS): n = 1 (100%)). In terms of ancillary investigations, abnormalities in histopathology and imaging were the most frequent with 44 carriers having abnormalities found by these testing (XLMTM: n = 36 (24%); Emery-Dreifuss muscular dystrophy 1 (EDMD1): n = 4 (5%); KD: n = 4 (5%) / XLMTM: n = 18 (12%); EDMD1: n = 1 (1%); KD: n = 5 (6%); X-linked myopathy with postural muscle atrophy (XMPMA): n = 19 (83%); BS: n = 1 (100%)). A difference between the number of EDMD1 carriers with cardiovascular signs and symptoms (n = 2 (1%)) and the number of carriers with abnormal electrocardiography tests (n = 20 (23%)) was also noted.</p><p><strong>Conclusion: </strong>Carriers of non-<i>DMD</i> XLNMDs exhibit a variety of signs and symptoms that could impact quality of life, making it vital for clinicians to be aware of these patients.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251330441"},"PeriodicalIF":3.2,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742602","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":"Painful muscle stiffness with markedly elevated serum creatine kinase (CK) levels after twenty weeks of gestation in four patients with myotonic dystrophy type 1 (DM1) and a patient with paramyotonia congenita (PMC).","authors":"Masanobu Kinoshita, Masaomi Yamamoto, Ryuichi Machida, Masahiro Misawa, Shinichiro Yabe, Norihito Yoshida, Akihiko Kikuchi, Hikoaki Fukaura, Kenichi Kaida, Kinji Ohno","doi":"10.1177/22143602251329168","DOIUrl":"https://doi.org/10.1177/22143602251329168","url":null,"abstract":"<p><p>Four patients with myotonic dystrophy type 1 (DM1) and a patient with paramyotonia congenita (PMC) developed devastating painful muscle stiffness with markedly elevated serum creatine kinase (CK) levels after 20 weeks of gestation. Immediately after delivery, painful muscle stiffness completely disappeared and the CK levels returned to the baseline. In a patient with DM1, muscle biopsy at delivery and skeletal muscle MRI in six days after delivery showed inflammatory changes, which disappeared in MRI on postpartum day 41. Pregnancy-associated aggravation of myotonia has been reported in myotonic disorders, but painful muscle stiffness has been scarcely reported. Inactivation of muscle Cl channel by progesterone that is prominently increased in the middle phase of gestation is likely to be the underlying mechanism of the pregnancy-associated painful muscle stiffness in myotonic disorders.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251329168"},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730376","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":"Epidemiology of spinal muscular atrophy in Aotearoa-New Zealand.","authors":"Richard H Roxburgh, Alana Cavadino, Miriam Rodrigues, Sharron Meadows, Juliette Meyer, Gina O'Grady","doi":"10.1177/22143602251319165","DOIUrl":"https://doi.org/10.1177/22143602251319165","url":null,"abstract":"<p><strong>Background: </strong>The advent of three effective disease modifying therapies for SMA has highlighted the need to understand the epidemiology of spinal muscular atrophy (SMA) and its disability impact.</p><p><strong>Objective: </strong>We aimed to establish the nationwide incidence and prevalence of SMA in Aotearoa-New Zealand, and to estimate the patients' disability and the impact of this on health resource utilisation.</p><p><strong>Methods: </strong>We used multiple sources to identify patients with SMA and verified the diagnosis, disabilities and resources utilisation by review of the individual patient notes and genetic results. The four year incidence period was from 1st July 2015 to 30th June 2019. Prevalence date was 1st March 2019. Of note, this time period pre-dated access to disease modifying therapy in New Zealand. Census data for 2018 was used for denominators. Descriptive statistics and capture-recapture were used to analyse the data. For context, we reviewed international SMA epidemiology.</p><p><strong>Results: </strong>The incidence per 100,000 live births was 8.0 (95% confidence interval (CI): 4.8-12.5). The standardised prevalence rate of SMA on 1st March 2019 was 1.78 per 100,000 (95% CI: 1.24, 2.33). Prevalence was significantly lower amongst Māori at 0.34 (95% CI: 0.08, 1.13; p = 0.006). Substantial decline from best motor milestone performance was seen; seven patients with SMA1 died without access to disease modifying therapy. 74% of the total cohort used wheelchairs. 23% required respiratory support. 62% had scoliosis, of whom 61% had had surgery. Surviving SMA1 patients had very high health service utilisation.</p><p><strong>Conclusions: </strong>Incidence and prevalence figures match closely with international studies. This is the first record of low SMA rates in Māori. While the largest burden of disease falls on patients with SMA1 and 2 there is still substantial use of health resources among SMA3 and SMA4 patients.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251319165"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730437","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":"Antisense RNA therapies for muscular dystrophies.","authors":"Virginia Arechavala-Gomeza, Andrea López-Martínez, Annemieke Aartsma-Rus","doi":"10.1177/22143602251324858","DOIUrl":"https://doi.org/10.1177/22143602251324858","url":null,"abstract":"<p><p>Inherited muscular dystrophies are a heterogeneous group of diseases, caused by different types of genetic mutations. RNA therapies, and particularly antisense oligonucleotides, offer a palette of therapeutic strategies to either reduce the production of harmful proteins or to restore or increase protein expression. Consequently, they offer therapeutic promise for multiple forms of muscular dystrophies. This review outlines the different RNA therapy types considered for the treatment of Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy and myotonic dystrophy, emphasizing the strategies used to deliver these therapies to skeletal muscle with a focus on approaches that have reached the clinical trial stage.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251324858"},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730432","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":"Sarcoglycanopathies: From clinical diagnosis to new promising therapies.","authors":"Holly Borland, Jordi Diaz-Manera","doi":"10.1177/22143602251324855","DOIUrl":"https://doi.org/10.1177/22143602251324855","url":null,"abstract":"<p><p>The sarcoglycanopathies are a severe form of limb girdle muscular dystrophy caused by mutations in the sarcoglycan genes SGCA, SGCB, SGCG, and SGCD, leading to reduced or absent expression of the alpha-, beta-, gamma-, and delta-sarcoglycan proteins respectively. Most patients develop a severe disease starting in the first decade of life that progresses quickly and eventually leads to a loss of ambulation before the age of 20. However, there is a marked heterogeneity in the prognosis, and several patients develop a milder phenotype. The factors correlating with disease progression are not completely known, but recent data suggest that remaining protein expression can be a key factor. The diagnosis is confirmed by genetic studies, which are sometimes not confirmative in the case of identifying variants of unknown significance or just one variant. New tools to understand the potential pathogenesis of missense variants have been developed; these are helping in the diagnosis of these diseases. Additionally, recent data on muscle MRI have revealed a characteristic pattern of involvement that can also support the diagnosis of the disease. In recent years, data coming from international collaborative studies have allowed an understanding of disease progression; however, this is only through retrospective data. There are no prospective studies collecting longitudinal data on skeletal and respiratory muscle function or cardiac structure and function progression over time which is hampering the development of new drugs in the field. Clinical trials with gene therapy are underway or are being designed in some of the subtypes of sarcoglycanopathies to advance therapeutic management.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251324855"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700577","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":"Automated analysis of quantitative muscle MRI and its reliability in patients with Duchenne muscular dystrophy.","authors":"Sara Nagy, Olga Kubassova, Patricia Hafner, Sabine Schädelin, Simone Schmidt, Michael Sinnreich, Jonas Schröder, Oliver Bieri, Mikael Boesen, Dirk Fischer","doi":"10.1177/22143602251319184","DOIUrl":"https://doi.org/10.1177/22143602251319184","url":null,"abstract":"<p><strong>Background: </strong>Quantitative muscle MRI is one of the most promising biomarkers to detect subclinical disease progression in patients with neuromuscular disorders, including Duchenne muscular dystrophy (DMD). However, its clinical application has been limited partly due to the time-intensive process of manual segmentation.</p><p><strong>Objective: </strong>We present a simple and fast automated approach to obtain quantitative measurement of thigh muscle fat fraction and investigate its reliability in patients with DMD.</p><p><strong>Methods: </strong>Clinical and radiological baseline and 6-month follow-up data of 41 ambulant patients with DMD were analysed retrospectively. Axial 2-point Dixon MR images of all thigh muscles were used to quantify mean fat fraction, while clinical outcomes were measured by the Motor Function Measure (MFM) and its D1 domain. Data obtained by automated segmentation were compared to manual segmentation and correlated with clinical outcomes. Results were also used to compare the statistical power when using automated or manual segmentation.</p><p><strong>Results: </strong>A mean increase of 3.55% in thigh muscle fat fraction at 6-month follow-up could be detected by both methods without any significant difference between them (p=0.437). The automated muscle segmentation method demonstrated a strong correlation with manually segmented data (Pearson's ρ = 0.97). Additionally, there was no statistically significant difference between the automated and manual segmentation methods in their association with clinical progression, as measured by the total MFM score and its D1 domain (p = 0.235 and p = 0.425, respectively).</p><p><strong>Conclusions: </strong>The presented automated segmentation technique is a fast and reliable tool for assessing disease progression, particularly in the early stages of DMD. It is one of the few studies validated using manual segmentation, and with further refinement, it has the potential to become a good surrogate marker for disease progression in various neuromuscular disorders.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251319184"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700566","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":"Patient-reported assessment of bulbar function in spinal muscular atrophy (SMA): Validation of a self-report scale.","authors":"Maureen A Lefton-Greif, Lisa Belter, Jill Jarecki, Mary Schroth, Yong Zeng, Thomas O Crawford, Cyd Eaton","doi":"10.1177/22143602251325741","DOIUrl":"https://doi.org/10.1177/22143602251325741","url":null,"abstract":"<p><p><b>Background:</b> Bulbar dysfunction is a well-recognized burden experienced by individuals with spinal muscular atrophy (SMA). Metrics that capture the impact of these problems are lacking. <b>Objectives:</b> To develop and validate an SMA-Bulbar Scale that captures and quantifies patient-reported experiences with bulbar dysfunction. <b>Methods:</b> Cure SMA database members were invited to complete online surveys and a 31-item Bulbar Scale developed by the authors with reference to both bulbar dysfunction in the literature and consultations with SMA-dedicated health care providers, pharmaceutical companies, and persons affected by SMA. <b>Results:</b> 166 adults with SMA reported a range of bulbar dysfunctions. The most common problems, occurring more than 80% of the time, were prolonged meal times, difficulty with mouth opening, and swallowing pills. In addition, 10% of the respondents reported a worsening feeding function over the course of their lives. Across the diverse array of bulbar functions, exploratory and confirmatory factor analyses of responses identified three coherent dimensions of bulbar dysfunction: Swallowing; Mealtimes and Communication; and Breath Sounds, Speech, Voice, and Secretion Management. Higher scores of overall bulbar dysfunction, (p < .001) and each factor (p < .001), were reported by respondents with any degree of feeding restrictions. Sex, age, or use of SMA disease-modifying treatment did not correlate with bulbar scores. <b>Conclusions:</b> This patient-reported scale of bulbar function in adults with a wide range of SMA severity captures and quantifies the variable manifestations of experienced bulbar impairment. With preliminary evidence of validity, the scale supports efforts to standardize accurate identification of bulbar dysfunction, incorporate the perspectives of people with SMA on key areas of their daily functioning, provide metrics essential for meaningful endpoints in clinical trials, inform practice guidelines, and promote advancement of the regulatory science needed for the evaluation and development of therapeutic interventions. Identification of three coherent dimensions of bulbar dysfunction may improve further investigations.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251325741"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670220","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":"Preclinical development of genome editing to treat Duchenne muscular dystrophy by exon skipping.","authors":"Made Harumi Padmaswari, Shilpi Agrawal, Christopher E Nelson","doi":"10.1177/22143602251326993","DOIUrl":"https://doi.org/10.1177/22143602251326993","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is caused by loss-of-function mutations to the gene encoding dystrophin. Restoring the reading frame of dystrophin by removing internal out-of-frame exons may address symptoms of DMD. Therefore, the principle of exon skipping has been at the center stage in drug development for Duchenne muscular dystrophy (DMD) over the past two decades. Antisense oligonucleotides (AONs) have proven effective in modulating splicing sites for exon skipping, resulting in the FDA approval of several drugs using this technique in recent years. However, due to the temporary nature of AON, researchers are actively exploring genome editing as a potential long-term, single-administration treatment. The advancements in genome-editing technology over the last decade have boosted this transition. While no clinical trials for exon skipping in DMD via genome editing have been conducted as of this writing, preclinical studies show encouraging results. This review describes the preclinical landscape of genome editing for exon skipping in DMD treatment. Along with highlighting the adaptability of genome editing in exon skipping, this review also describes delivery challenges and outlines future research directions that could set a new stage for enhanced therapeutic development in DMD.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602251326993"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657505","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":"Visualizing ambulatory performance by age and rates of decline among patients with Duchenne muscular dystrophy.","authors":"Anna G Mayhew, James Signorovitch, Michaela Johnson, Molly Frean, Susan J Ward, Nate Posner, Valeria Merla, Matthias Mahn, Georgia Stimpson, Michela Guglieri, Volker Straub, Robert Muni-Lofra, Adnan Manzur, Giovanni Baranello, Francesco Muntoni","doi":"10.1177/22143602241313116","DOIUrl":"https://doi.org/10.1177/22143602241313116","url":null,"abstract":"<p><p>In Duchenne muscular dystrophy (DMD), age at symptom onset and rate of decline thereafter vary considerably. This study contrasted disease progression over time using the North Star Ambulatory Assessment (NSAA) in an overall sample of patients with DMD (mean age 7.1 years; baseline total NSAA score 22.2) with that of a centrally representative subgroup (mean age 6.9 years; NSAA score 24.0) defined according to median age at loss of ambulation. The average disease trajectory in the overall sample understated the more rapid rates of decline experienced by patients in the centrally representative subgroup.</p>","PeriodicalId":16536,"journal":{"name":"Journal of neuromuscular diseases","volume":" ","pages":"22143602241313116"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648228","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}