Journal of Clinical Neuromuscular Disease最新文献

{"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":"24 4","pages":"188-198"},"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":"24 4","pages":"214-221"},"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":"24 4","pages":"207-213"},"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":"24 3","pages":"164-165"},"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":"24 3","pages":"130-139"},"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":"24 3","pages":"119-129"},"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}

{"title":"Camptocormia as an Unusual Presenting Symptom of Myotonic Dystrophy Type 2: An Overlooked Cause of Axial Myopathy.","authors":"Efthalia Angelopoulou,&nbsp;Georgia Karadima,&nbsp;Efstratios-Stylianos Pyrgelis,&nbsp;Thomas Zambelis,&nbsp;Vasiliki Zouvelou","doi":"10.1097/CND.0000000000000417","DOIUrl":"https://doi.org/10.1097/CND.0000000000000417","url":null,"abstract":"","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":"24 3","pages":"165-166"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341385","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":"Characteristics of Peripheral Neuropathy in Patients With Livedoid Vasculopathy.","authors":"Harish Eswaran,&nbsp;Rebecca Traub,&nbsp;Paul Googe,&nbsp;Stephan Moll","doi":"10.1097/CND.0000000000000435","DOIUrl":"https://doi.org/10.1097/CND.0000000000000435","url":null,"abstract":"<p><strong>Abstract: </strong>Livedoid vasculopathy (LV) is an ulcerative disorder of the lower extremities characterized by dermal vessel thrombosis with unclear cause. Recent reports of LV-associated upper extremity peripheral neuropathy and epineurial thrombosis suggest a systemic etiology for the condition. We sought to outline the characteristics of peripheral neuropathy in patients with LV. Cases of LV with concurrent peripheral neuropathy and reviewable electrodiagnostic testing reports were identified by electronic medical record database query and examined in detail. Of 53 patients with LV, 33 (62%) had peripheral neuropathy, 11 had reviewable electrodiagnostic reports, and 6 had no clear alternative explanation for neuropathy. Distal symmetric polyneuropathy was the most commonly observed pattern of neuropathy (n = 3) followed by mononeuropathy multiplex (n = 2). Most patients experienced symptoms in both upper and lower extremities (n = 4). Peripheral neuropathy is common in patients with LV. Whether this association is reflective of a systemic, prothrombotic etiology remains to be determined.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":"24 3","pages":"157-161"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314363","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":"Guillain-Barre Syndrome After the Third BNT162b2 Dose in an Adolescent Without Side Effects After the First and Second Jab.","authors":"Josef Finsterer","doi":"10.1097/CND.0000000000000434","DOIUrl":"https://doi.org/10.1097/CND.0000000000000434","url":null,"abstract":"","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":"24 3","pages":"162-163"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341388","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":"Neuropathy, Ataxia, and Retinitis Pigmentosa Syndrome.","authors":"Josef Finsterer","doi":"10.1097/CND.0000000000000422","DOIUrl":"https://doi.org/10.1097/CND.0000000000000422","url":null,"abstract":"<p><strong>Objectives: </strong>To provide an overview about the phenotype, genotype, treatment, and outcome of neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome.</p><p><strong>Methods: </strong>Systematic review by application of appropriate search terms.</p><p><strong>Results: </strong>NARP syndrome is a syndromic mitochondrial disorder due to pathogenic variants in MT-ATP6. The canonical phenotypic features of NARP syndrome include proximal muscle weakness, axonal neuropathy, cerebellar ataxia, and retinitis pigmentosa. Noncanonical phenotypic features in NARP include epilepsy, cerebral or cerebellar atrophy, optic atrophy, cognitive impairment, dementia, sleep apnea syndrome, hearing impairment, renal insufficiency, and diabetes. So far, 10 pathogenic variants in MT-ATP6 have been associated with NARP, NARP-like syndrome, or NARP/maternally inherited Leigh overlap syndrome. Most pathogenic MT-ATP6 variants are missense, but a few truncating pathogenic variants have been reported. The most common variant responsible for NARP is the transversion m.8993T>G. Only symptomatic treatment for NARP syndrome is available. In most of the cases, patients die prematurely. Patients with late-onset NARP survive longer.</p><p><strong>Conclusions: </strong>NARP is a rare, syndromic, monogenic mitochondrial disorder due to pathogenic variants in MT-ATP6. The nervous system and the eyes are most commonly affected. Although only symptomatic treatment is available, the outcome is usually fair.</p>","PeriodicalId":39645,"journal":{"name":"Journal of Clinical Neuromuscular Disease","volume":"24 3","pages":"140-146"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10131957","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}