CONTINUUM Lifelong Learning in Neurology最新文献_第2页

Facioscapulohumeral Muscular Dystrophy. 面肩肱肌营养不良症。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001614

Renatta N Knox

{"title":"Facioscapulohumeral Muscular Dystrophy.","authors":"Renatta N Knox","doi":"10.1212/cont.0000000000001614","DOIUrl":"https://doi.org/10.1212/cont.0000000000001614","url":null,"abstract":"Objective: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy, affecting individuals across the lifespan with variable severity. This article provides an overview of the distinctive genetic mechanisms underlying FSHD, its clinical manifestations, including pediatric-specific features, treatment, and the evolving landscape of clinical trials targeting disease-modifying therapies.Latest developments: FSHD arises from derepression of the transcription factor DUX4, which is toxic to skeletal muscle. This misexpression leads to a characteristic and progressive pattern of muscle weakness involving the facial, shoulder girdle, upper extremity, trunk, and leg muscles. Extramuscular manifestations, such as pain and fatigue, are frequently reported. Children with a severe, early-onset phenotype experience higher rates of extramuscular features, including hearing loss, cognitive impairment, and spinal deformities. Advances in the understanding of DUX4 as the causative gene, combined with innovations in gene therapy, gene editing, small-molecule development, and drug delivery, have catalyzed the initiation of several clinical trials focusing on disease-targeted treatments in the near future.Essential points: FSHD is caused by toxic expression of DUX4 and presents with progressive, often asymmetric muscle weakness and extramuscular manifestations in a subset of patients. Advances in genetic understanding and therapeutic development have led to clinical trials targeting DUX4. Although care remains supportive, the field is entering an era of promising disease-modifying strategies.","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"31 5","pages":"1329-1343"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Botulism, Lambert-Eaton Myasthenic Syndrome, and Congenital Myasthenic Syndromes. 肉毒杆菌中毒，兰伯特-伊顿肌无力综合征和先天性肌无力综合征。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001613

Sithara Ramdas

{"title":"Botulism, Lambert-Eaton Myasthenic Syndrome, and Congenital Myasthenic Syndromes.","authors":"Sithara Ramdas","doi":"10.1212/cont.0000000000001613","DOIUrl":"https://doi.org/10.1212/cont.0000000000001613","url":null,"abstract":"Objective: This article covers the clinical presentations, investigations, differential diagnosis, and principles of management of botulism, Lambert-Eaton myasthenic syndrome (LEMS), and congenital myasthenic syndromes.Latest developments: Well-recognized guidelines exist for the management of botulism and LEMS, but resource limitations may affect implementation globally. Several genes recently reported to cause congenital myasthenic syndromes are involved in ubiquitously expressed proteins and present with a complex non-neuromuscular junction phenotype, wherein abnormal neuromuscular junction transmission is only one component of the gene defect. There have been a few promising preclinical studies on novel treatments in congenital myasthenic syndromes, including gene replacement therapy, raising the prospect of clinical trials in the near future.Essential points: Early recognition, diagnosis, and initiation of treatment are crucial in managing all three disorders to reduce morbidity and mortality. Congenital myasthenic syndromes should be considered in patients with seronegative myasthenia gravis. Tumor screening is essential in patients with LEMS. Botulism can mimic other cranial neuropathies.","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"31 5","pages":"1303-1328"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety, Costs, and Ethical Issues in Drug Development and Gene Therapy for Rare Diseases. 罕见病药物开发和基因治疗的安全性、成本和伦理问题。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001619

Nicholas Johnson, A Gordon Smith

引用次数: 0

Dystrophinopathies. Dystrophinopathies。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001618

Divya Jayaraman, Partha S Ghosh

{"title":"Dystrophinopathies.","authors":"Divya Jayaraman, Partha S Ghosh","doi":"10.1212/cont.0000000000001618","DOIUrl":"https://doi.org/10.1212/cont.0000000000001618","url":null,"abstract":"Objective: This article provides an overview of the dystrophinopathies, which are primary muscle disorders inherited in an X-linked recessive fashion due to pathogenic variants in DMD on chromosome Xp21 encoding the protein dystrophin. These include Duchenne and Becker muscular dystrophies, as well as an intermediate phenotype, dilated cardiomyopathy, and manifesting female carriers. Clinical examples illustrate the workup and management of patients with suspected dystrophinopathy.Latest developments: Historically, the management of the dystrophinopathies was largely supportive, with corticosteroids as the only pharmacologic option to delay loss of ambulation and respiratory and cardiac complications. Newer formulations of corticosteroids aim to improve their side effect profile while preserving efficacy. The US Food and Drug Administration (FDA) recently approved treatments directed at the underlying genetic defect in Duchenne muscular dystrophy, including exon-skipping and microdystrophin-based gene therapies and a new class of histone deacetylase inhibitors. The impact of these newer therapies on the natural history of the disease is unknown. Two patient deaths in the spring of 2025 were deemed related to delandistrogene moxeparvovec use in nonambulatory patients, and dosing in these patients has been paused.Essential points: Dystrophinopathies may present with motor delay, progressive proximal and axial weakness, calf hypertrophy, and elevated creatine kinase greater than 1000 U/L. Elevated transaminases in the setting of elevated creatine kinase with normal γ-glutamyl transferase and speech delay or autism in boys are less common initial presentations. Genetic testing is typically the next step in diagnosis and, depending on the nature of the variation and predicted severity of the phenotype, can guide the choice of treatment.","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"31 5","pages":"1462-1485"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Idiopathic Inflammatory Myopathies. 特发性炎性肌病。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001617

Mohammad Kian Salajegheh, Anthony A Amato

{"title":"Idiopathic Inflammatory Myopathies.","authors":"Mohammad Kian Salajegheh, Anthony A Amato","doi":"10.1212/cont.0000000000001617","DOIUrl":"https://doi.org/10.1212/cont.0000000000001617","url":null,"abstract":"Objective: This article describes the various idiopathic inflammatory myopathies, including their clinical presentation, pathogenesis, diagnosis, and treatments. While many disorders fall under this umbrella, this article focuses on dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy, polymyositis, and overlap syndrome.Latest developments: The diagnosis of inflammatory myopathy has traditionally relied heavily on muscle biopsy, which continues to be an essential diagnostic tool. However, the identification of myositis-specific antibodies has allowed for the deferment of biopsy in some cases, while also providing guidance on severity, prognosis, risk for underlying cancer, other organ involvement, and therapy. The treatment of inflammatory myopathy hinges on the use of evolving immunotherapies.Essential points: Given that highly effective treatments exist for inflammatory myopathy, neurologists must use all available diagnostic tools to quickly identify inflammatory myopathy and initiate appropriate therapy. While the primary goal is to treat muscle weakness, it is important to consider other organs that may be affected by these conditions, including the lungs, heart, joints, and skin, and to exclude underlying malignancy or infection when appropriate.","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"31 5","pages":"1385-1408"},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Key Points for Issue. 问题的关键点。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/01.cont.0001168344.21565.c4

引用次数: 0

List of Abbreviations. 缩略语列表。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/01.cont.0001168680.87781.e6

引用次数: 0

SELF-ASSESSMENT AND CME. 自我评估和继续教育。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001624

引用次数: 0

Postreading Self-Assessment and CME Test-Preferred Responses. 阅读后自我评估和CME测试偏好反应。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-10-01 Epub Date: 2025-10-02 DOI: 10.1212/cont.0000000000001629

Douglas J Gelb, Nuri Jacoby

引用次数: 0

Paroxysmal Movement Disorders. 阵发性运动障碍。

CONTINUUM Lifelong Learning in Neurology Pub Date : 2025-08-01 DOI: 10.1212/cont.0000000000001596

Abhimanyu Mahajan

{"title":"Paroxysmal Movement Disorders.","authors":"Abhimanyu Mahajan","doi":"10.1212/cont.0000000000001596","DOIUrl":"10.1212/cont.0000000000001596","url":null,"abstract":"Objective: This article summarizes the current understanding of paroxysmal movement disorders, including clinical features, pathophysiology, assessment, genetics, and treatment. It additionally discusses the intriguing overlap of these disorders with epilepsy.Latest developments: There is an expansion of the traditional genotype-phenotype correlation among paroxysmal movement disorders. A single genotype may present with many clinical presentations, and different genetic variations may present with a similar phenotype. In addition to recognizing the clinical presentation through careful history and examination, the approach to patients with paroxysmal movement disorders increasingly includes genetic testing for treatment and prognostication.Essential points: The spectrum of paroxysmal movement disorders continues to expand. Prompt and accurate recognition of the presenting syndrome can lead to effective treatment and symptomatic relief. It is imperative to recognize secondary causes of paroxysmal movement disorders. A greater understanding of shared molecular mechanisms and genetics may help to better tailor therapeutic strategies in the future.","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"31 4","pages":"1152-1181"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0