Journal of Clinical Neuromuscular Disease最新文献

{"title":"Congenital Myasthenic Syndrome Caused by DOK7 Mutation in a Quinquagenarian Male with Calf Hypertrophy.","authors":"Saranya B Gomathy,&nbsp;Animesh Das,&nbsp;Ajay Garg,&nbsp;Achal Kumar Srivastava","doi":"10.1097/CND.0000000000000448","DOIUrl":"https://doi.org/10.1097/CND.0000000000000448","url":null,"abstract":"<p><strong>Abstract: </strong>Congenital myasthenic syndromes (CMS) are relatively rare neurologic syndromes of defective neuromuscular transmission that stem from mutations in various proteins at the myoneural junction. Classically, the patients present within the first 2 years of life; however, the disease can also have onset in the second or third decade of life. The disease characteristically involves the skeletal muscles and spares smooth and cardiac muscles. The patients present with weakness involving ocular, limb, axial, or bulbar muscles. The specific diagnosis in most cases is clinched by genetic testing. We report a 59-year-old man presenting with neuromuscular weakness for 3 years and calf hypertrophy. He had myopathic features on electrophysiologic studies with a decremental response on repetitive nerve stimulation. Genetic testing confirmed a diagnosis of DOK7 CMS. He was managed with salbutamol and showed significant improvement.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10122155","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}

{"title":"DMD Gene and Dystrophinopathy Phenotypes Associated With Mutations: A Systematic Review for Clinicians.","authors":"Jennifer G Andrews,&nbsp;Maureen Kelly Galindo,&nbsp;Shiny Thomas,&nbsp;Katherine D Mathews,&nbsp;Nedra Whitehead","doi":"10.1097/CND.0000000000000436","DOIUrl":"https://doi.org/10.1097/CND.0000000000000436","url":null,"abstract":"<p><strong>Abstract: </strong>The diagnosis of Duchenne and Becker muscular dystrophy (DBMD) is made by genetic testing in approximately 95% of cases. Although specific mutations can be associated with skeletal muscle phenotype, pulmonary and cardiac comorbidities (leading causes of death in Duchenne) have not been associated with Duchenne muscular dystrophy mutation type or location and vary within families. Therefore, identifying predictors for phenotype severity beyond frameshift prediction is important clinically. We performed a systematic review assessing research related to genotype-phenotype correlations in DBMD. While there are severity differences across the spectrum and within mild and severe forms of DBMD, few protective or exacerbating mutations within the dystrophin gene were reported. Except for intellectual disability, clinical test results reporting genotypic information are insufficient for clinical prediction of severity and comorbidities and the predictive validity is too low to be useful when advising families. Including expanded information coupled with proposed severity predictions in clinical genetic reports for DBMD is critical for improving anticipatory guidance.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135331","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}

{"title":"Greater Number of Plasma Exchanges Does Not Improve Outcome in Myasthenic Crisis.","authors":"Michael Hansen,&nbsp;Lee Neilson,&nbsp;Melanie Parikh,&nbsp;Bashar Katirji","doi":"10.1097/CND.0000000000000421","DOIUrl":"10.1097/CND.0000000000000421","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the relationship between the number of plasma exchanges and clinical outcome in patients experiencing myasthenic crisis.</p><p><strong>Methods: </strong>We retrospectively reviewed all episodes of myasthenia gravis exacerbation/crisis who received plasmapheresis in patients admitted to a single-center tertiary care referral center from July 2008 to July 2017. We performed statistical analyses to determine whether the increased number of plasma exchanges improves the primary outcome (hospital length of stay) and the secondary outcome (disposition to home, skilled nursing facility, long-term acute care hospital, or death).</p><p><strong>Results: </strong>There is neither clinically observable nor statistically significant improvement in length of stay or disposition on discharge in patients who received 6 or greater sessions of plasmapheresis.</p><p><strong>Conclusions: </strong>This study provides class IV evidence that extending the number of plasma exchanges beyond 5 does not correlate with decreased hospital length of stay or improved discharge disposition in patients experiencing myasthenic crisis.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517974","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}

{"title":"Attitudes and Beliefs Toward Thymectomy in the Myasthenia Gravis Patient Registry.","authors":"Ali G Hamedani, Tarrant O McPherson, Inmaculada Aban, Ikjae Lee, Mark J Kupersmith, Gil I Wolfe, Henry J Kaminski","doi":"10.1097/CND.0000000000000449","DOIUrl":"10.1097/CND.0000000000000449","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate patient attitudes and beliefs toward thymectomy for myasthenia gravis (MG).</p><p><strong>Methods: </strong>The Myasthenia Gravis Foundation of America administered a questionnaire to the MG Patient Registry, an ongoing longitudinal survey of adult MG patients. Questions assessed reasons for or against thymectomy and how hypothetical scenarios would have affected their decision.</p><p><strong>Results: </strong>Of 621 respondents, 190 (31%) reported a history of thymectomy. Of those who underwent thymectomy for nonthymomatous MG, 97 (51.6%) ranked symptom improvement as most important and 100 (53.2%) ranked reducing medication as least important. Among 431 nonthymectomy patients, the most frequent reason for not undergoing thymectomy was that their doctor did not discuss it (152 of 431 = 35.2%) and 235 (56.8%) said that they would have considered it more strongly if their doctor spent more time discussing it.</p><p><strong>Conclusions: </strong>Thymectomies are motivated more by symptoms than by medication, and a lack of neurologist discussion is the most common barrier to thymectomy.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521464","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}

{"title":"Neonatal Fc Receptor Inhibitor Therapeutics in Neuromuscular Disease.","authors":"Mustafa Jaffry,&nbsp;Daniel L Menkes,&nbsp;Anam Shaikh,&nbsp;Kranthi Mandava,&nbsp;Om Kothari,&nbsp;Kazim Jaffry,&nbsp;Nizar Souayah","doi":"10.1097/CND.0000000000000451","DOIUrl":"https://doi.org/10.1097/CND.0000000000000451","url":null,"abstract":"<p><strong>Abstract: </strong>The Neonatal Fc Receptor (FcRn) is integral to a wide variety of processes including IgG recycling, serum albumin turnover, and bacterial opsonization. Thus, targeting FcRn will increase antibody degradation including pathogenic IgGs. FcRn inhibition provides a novel therapeutic mechanism by which autoantibody titers are reduced resulting in clinical improvement and disease abatement. The FcRn targeting mechanism is similar to that of intravenous immunoglobulin (IVIg) in which saturated FcRn facilitates accelerated pathogenic IgG degradation. Recently, the FcRn inhibitor efgartigimod was approved for the treatment of myasthenia gravis. Subsequently, clinical trials of this agent have been conducted for numerous inflammatory conditions involving pathogenic autoantibodies. These disorders include the Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and inflammatory myositis. Other disorders traditionally treated with IVIg may also benefit from FcRn inhibition in certain contexts. This manuscript discusses the mechanism of FcRn inhibition, preclinical data, and the results of clinical trials of this agent for a wide range of neuromuscular diseases.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923220","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}

{"title":"Clenbuterol Treatment Is Safe and Associated With Slowed Disease Progression in a Small Open-Label Trial in Patients With Amyotrophic Lateral Sclerosis.","authors":"Xiaoyan Li,&nbsp;Dwight D Koeberl,&nbsp;Michael W Lutz,&nbsp;Richard Bedlack","doi":"10.1097/CND.0000000000000438","DOIUrl":"https://doi.org/10.1097/CND.0000000000000438","url":null,"abstract":"<p><strong>Objective: </strong>Clenbuterol, a beta-agonist, has plausible mechanisms for treating amyotrophic lateral sclerosis (ALS). In this highly inclusive open-label trial (NCT04245709), we aimed to study the safety and efficacy of clenbuterol in patients with ALS.</p><p><strong>Methods: </strong>All participants received clenbuterol starting at 40 μg daily and increased to 80 μg twice daily. Outcomes included safety, tolerability, ALS Functional Rating Score (ALSFRS-R) progression, forced vital capacity (FVC) progression, and myometry. ALSFRS-R and FVC slopes measured during treatment were compared with slopes before treatment (calculated by assuming ALSFRS-R was 48 and FVC was 100% at ALS onset).</p><p><strong>Results: </strong>The 25 participants had a mean age of 59, mean disease duration of 43 months, ALSFRS-R score at enrollment 34, and FVC at enrollment 77%. Forty-eight percent were female, 68% were taking riluzole, and none were taking edaravone. Two participants experienced severe adverse events, neither related to the study. Twenty-four participants experienced adverse events, most commonly tremors/jitters, cramps/spasms, insomnia, and stiffness/spasticity. Fourteen participants withdrew early from the trial, 13 due to adverse events. Patients who withdrew early were significantly older and more likely to be male. Per-protocol and intention-to-treat analyses showed meaningfully slower ALSFRS-R and FVC progression during treatment. Hand grip dynamometry and myometry changes were highly variable between participants; most declined slowly, but some showed improvements.</p><p><strong>Conclusions: </strong>Clenbuterol was safe but less tolerable at the doses we selected compared with an earlier Italian case series. Consistent with that series, our study suggested benefits on ALS progression. However, the latter result should be interpreted with caution as our study is limited by small sample size, large drop out, lack of randomization, and blinding and placebo controls. A larger, more traditional trial now seems warranted.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135332","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}

{"title":"Rapid Conversion to a Completely Virtual Multidisciplinary ALS Clinic in Response to the COVID-19 Pandemic: Implications for Future Care Delivery.","authors":"James Grogan,&nbsp;Susan Walsh,&nbsp;Anne Haulman,&nbsp;Habib Yazgi,&nbsp;Andrew Geronimo,&nbsp;Mansoureh Mamarabadi,&nbsp;Zachary Simmons","doi":"10.1097/CND.0000000000000430","DOIUrl":"https://doi.org/10.1097/CND.0000000000000430","url":null,"abstract":"<p><strong>Objectives: </strong>The goals of this study were to assess the feasibility of maintaining multidisciplinary remote care, patient preferences, and outcomes of this transition because of COVID-19.</p><p><strong>Methods: </strong>From March 18, 2020 to June 3, 2020, 127 patients with amyotrophic lateral sclerosis (ALS) who were scheduled to be seen in our ALS clinic were contacted and scheduled according their preference for a telemedicine visit, telephone visit, or postponement until the next available in-person visit. Age, time from disease onset, ALS Functional Rating Scale-Revised, patient choices, and outcomes were recorded.</p><p><strong>Results: </strong>Patient visit preferences were 69% telemedicine, 21% telephone, and 10% postpone for a later in-clinic visit. Patients with higher ALS Functional Rating Scale-Revised were more likely to choose the next in-person opening (P = 0.04). Age and time from disease onset were not related to visit type preference. There were 118 virtual encounters, of which 91 (77%) began as telemedicine and 27 (23%) as telephone visits. Most telemedicine visits were conducted successfully, but 10 were converted to a telephone visit. The clinic maintained 88.6% of patient volume compared with the prior year, during which most visits were in-person.</p><p><strong>Conclusions: </strong>Telemedicine care using synchronous videoconferencing is preferable and feasible for most patients on short notice, with telephone as back-up. Clinic volumes can be maintained. These findings support the conversion of a multidisciplinary ALS clinic to 1 with exclusively virtual visits when future events again disrupt in-person care.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517972","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}

{"title":"Head and Neck Squamous Cell Carcinoma Presenting With Leptomeningeal Carcinomatosis and Myeloradiculopathy via Perineural Growth.","authors":"Carmela V San Luis,&nbsp;Sarah Breaux,&nbsp;Houman Sotoudeh,&nbsp;Kenneth Fallon,&nbsp;Kenkichi Nozaki","doi":"10.1097/CND.0000000000000425","DOIUrl":"https://doi.org/10.1097/CND.0000000000000425","url":null,"abstract":"","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341387","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}

{"title":"What Is in the Myopathy Literature?","authors":"David Lacomis","doi":"10.1097/CND.0000000000000440","DOIUrl":"https://doi.org/10.1097/CND.0000000000000440","url":null,"abstract":"<p><strong>Abstract: </strong>This update begins with the results of a positive trial of intravenous immunoglobulin in dermatomyositis and a study of molecular and morphologic patterns in inclusion body myositis that may explain treatment refractoriness. Single center reports of muscular sarcoidosis and immune-mediated necrotizing myopathy follow. There is also a report of caveolae-associated protein 4 antibodies as a potential biomarker and cause of immune rippling muscle disease. The remainder covers updates on muscular dystrophies as well as congenital and inherited metabolic myopathies with an emphasis on genetic testing. Rare dystrophies, including one involving ANXA11 mutations and a series on oculopharyngodistal myopathy, are discussed.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10136923","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}

{"title":"Landscape of Guillain-Barré Syndrome Interventional Clinical Trials.","authors":"Mustafa Saleh,&nbsp;Mona Boukhdoud,&nbsp;Hayam Boukhdoud,&nbsp;Mohammad Al Zein,&nbsp;Pascale Salameh","doi":"10.1097/CND.0000000000000441","DOIUrl":"https://doi.org/10.1097/CND.0000000000000441","url":null,"abstract":"<p><strong>Introduction: </strong>Guillain-Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy that remains a debilitating disease despite medical treatment. Numerous challenges still exist, including the development of disease-modifying therapies that can improve prognosis, particularly in patients with poor prognostic outcomes. In this study, we explored clinical trials related to GBS, analyzed the trial characteristics, suggested some ideas for improvement, and discussed recent advances.</p><p><strong>Methods: </strong>On December 30, 2021, the authors searched ClinicalTrials.gov for all interventional and therapeutic clinical trials related to GBS, without any restrictions on the date or location. Trial characteristics including trial duration, location, phase, sample size, and publications were retrieved and analyzed.</p><p><strong>Results: </strong>Twenty-one trials fulfilled the selection criteria. Clinical trials were conducted in 11 different countries, most of them occurring in Asia. On average, the trial duration across the phases was around 2 years. About two-thirds of trials were completed, and 39% of trials were in the early phases (1 and 2). Only 24% of all trials and 60% of completed trials have publications in this study.</p><p><strong>Conclusions: </strong>The study revealed a low number of trials, lack of geographic diversity, scanty enrollment of patients, and paucity of clinical trial duration and publications regarding GBS clinical trials. Optimization of GBS trials is fundamental to achieving effective therapies for this disease.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764046","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}