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Neuromuscular Ultrasound Training in Neuromuscular Fellowship Programs in Canada: Minding the Gap. 加拿大神经肌肉研究员计划中的神经肌肉超声培训:弥合差距。
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2025-01-15 DOI: 10.1002/mus.28352
Ankur Banerjee, Shahin Khayambashi, Gordon Jewett, Theodore Mobach, Cecile Phan, Vijay Daniels, Grayson Beecher
{"title":"Neuromuscular Ultrasound Training in Neuromuscular Fellowship Programs in Canada: Minding the Gap.","authors":"Ankur Banerjee, Shahin Khayambashi, Gordon Jewett, Theodore Mobach, Cecile Phan, Vijay Daniels, Grayson Beecher","doi":"10.1002/mus.28352","DOIUrl":"10.1002/mus.28352","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Neuromuscular ultrasound (NMUS) is gaining prominence as a valuable tool for diagnosing neuromuscular disorders at the point of care. Neuromuscular disorder diagnostic criteria guidelines have begun incorporating NMUS findings. As interest grows, fellowship programs must consider incorporating training into their curricula. This study evaluated the current state of NMUS training, potential barriers, and interest in training across Canadian neuromuscular fellowship programs.</p><p><strong>Methods: </strong>A 23-question online survey was developed and distributed via email to all 10 neuromuscular fellowship program directors across Canada.</p><p><strong>Results: </strong>Seven (70%) programs responded to the survey. There was general agreement among programs on the value of NMUS, however, only one (14.3%) program reported they would consider recent graduates to be competent in NMUS. Critical barriers to incorporation of NMUS training included lack of a formalized curriculum, faculty expertise and time, and equipment. Two (28.6%) programs reported that accessibility of equipment and one (14.3%) that faculty expertise was not a barrier to NMUS training. Two (28.6%) programs have local NMUS training options available to fellows (in only one program is NMUS training mandatory). All programs expressed interest in additional training opportunities, and three (43%) programs reported taking steps toward incorporating NMUS training into their curricula.</p><p><strong>Discussion: </strong>NMUS training is in its infancy in Canada, with several common barriers identified across programs. There is universal interest in further NMUS training opportunities for fellows, highlighting the importance of a common approach to addressing the educational gap to support development of formalized NMUS training mechanisms in Canada.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"457-462"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The JAK1/3 Inhibitor Tofacitinib Regulates Th Cell Profiles and Humoral Immune Responses in Myasthenia Gravis. JAK1/3抑制剂托法替尼调节重症肌无力患者的Th细胞谱和体液免疫反应。
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2025-01-17 DOI: 10.1002/mus.28348
Zhuajin Bi, Qing Zhang, Huajie Gao, Huizhen Ge, Jiayang Zhan, Mengge Yang, Bitao Bu
{"title":"The JAK1/3 Inhibitor Tofacitinib Regulates Th Cell Profiles and Humoral Immune Responses in Myasthenia Gravis.","authors":"Zhuajin Bi, Qing Zhang, Huajie Gao, Huizhen Ge, Jiayang Zhan, Mengge Yang, Bitao Bu","doi":"10.1002/mus.28348","DOIUrl":"10.1002/mus.28348","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Tofacitinib, a first-generation Janus kinase (JAK) 1/3 inhibitor, is commonly used for treating ulcerative colitis and rheumatoid arthritis. However, its role in myasthenia gravis (MG) remains unclear. This study aimed to evaluate the immunomodulatory effects of tofacitinib on experimental autoimmune myasthenia gravis (EAMG) and peripheral blood mononuclear cells (PBMCs) from patients with MG.</p><p><strong>Methods: </strong>Flow cytometry, enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot were used to evaluate the effects of tofacitinib on T helper (Th) cell profiles, humoral immune responses, and the JAK-signal transducer and activator of transcription (STAT) pathway proteins.</p><p><strong>Results: </strong>In vivo, tofacitinib significantly ameliorated EAMG severity in rats, reducing the proportions of Th1, Th17 and memory B cells, and anti-acetylcholine receptor (AChR) antibodies levels, while increasing the proportions of regulatory T (Treg) cells. In vitro, tofacitinib administration resulted in a significant decrease in the proportions of Th1 and IgG-secreting B cell, and a significant upregulation of Treg cells in mononuclear cells (MNCs) from EAMG rats, which was consistent with findings in PBMCs from MG patients. Further analysis revealed that tofacitinib inhibited CD4<sup>+</sup> T cell differentiation into Th1 by decreasing phosphorylated STAT1 levels, while promoting Treg differentiation via increased phosphorylated STAT5 levels in MNCs from EAMG rats.</p><p><strong>Discussion: </strong>Tofacitinib modulates Th cell profiles and humoral immune responses by targeting the JAK-STAT pathway, suggesting its potential as a therapeutic candidate for MG. Further clinical studies are warranted to evaluate the efficacy and safety of tofacitinib in MG patients.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"474-486"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-Term Outcomes From a Randomized Controlled Trial of Acceptance and Commitment Therapy (ACT) Compared to Standard Medical Care for Improving Quality of Life in Muscle Disorders. 接受和承诺治疗(ACT)与标准医疗护理相比改善肌肉疾病患者生活质量的长期结果随机对照试验
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2024-12-29 DOI: 10.1002/mus.28322
Christopher D Graham, Michael Rose, Victoria Edwards, Chiara Vari, Nicola O'Connell, Emma Taylor, Lance M McCracken, Aleksander Radunovic, Wojtek Rakowicz, Sam Norton, Trudie Chalder
{"title":"Long-Term Outcomes From a Randomized Controlled Trial of Acceptance and Commitment Therapy (ACT) Compared to Standard Medical Care for Improving Quality of Life in Muscle Disorders.","authors":"Christopher D Graham, Michael Rose, Victoria Edwards, Chiara Vari, Nicola O'Connell, Emma Taylor, Lance M McCracken, Aleksander Radunovic, Wojtek Rakowicz, Sam Norton, Trudie Chalder","doi":"10.1002/mus.28322","DOIUrl":"10.1002/mus.28322","url":null,"abstract":"<p><strong>Introduction/aims: </strong>A previous randomized controlled trial showed that guided self-help acceptance and commitment therapy plus standard medical care (ACT+SMC) was superior to standard medical care alone (SMC) for improving quality of life (QoL) and mood at 9-weeks post randomization in a sample of people with muscle disorders (MD). This follow-up study evaluated whether these effects were maintained in the longer term alongside individual patterns of response.</p><p><strong>Methods: </strong>The original study was a two-arm parallel group randomized controlled trial, which compared ACT+SMC to SMC. The primary outcome of QoL was assessed with the Individualized Neuromuscular Quality of Life Questionnaire. We recruited people with different MDs from UK National Health Service clinics and patient registries. In this follow-up study, we re-administered all outcome measures to participants at 6 months post randomization.</p><p><strong>Results: </strong>Questionnaires were completed by 109 participants (70.3% of the original sample). At six months, the adjusted group difference in QoL continued to favor ACT+SMC, which was significant with moderate effect size. Improvements in secondary outcomes of mood and aspects of psychological flexibility also favored ACT+SMC. Reliable improvement was evident in 33.9% of the ACT+SMC group and 5.7% of the SMC group. Reliable deterioration was uncommon following ACT+SMC (1.8% of participants.) DISCUSSION: The beneficial impacts of guided self-help ACT for QoL and mood were maintained in the longer-term. A third of participants showed response to this brief intervention, and negative individual outcomes were very rare. As is common in psychological interventions, there was a considerable group of non-responders.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"398-405"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pitfalls of the E-Ref Procedure: Tie Values and the Proportion of the Abnormal Data. E-Ref程序的缺陷:Tie值和异常数据的比例。
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2025-01-06 DOI: 10.1002/mus.28338
Keisuke Tachiyama, Takamichi Kanbayashi, Akiko Kawabata, Satoshi Hoshino, Yosuke Miyaji, Shunsuke Kobayashi, Hirofumi Maruyama, Masahiro Sonoo
{"title":"Pitfalls of the E-Ref Procedure: Tie Values and the Proportion of the Abnormal Data.","authors":"Keisuke Tachiyama, Takamichi Kanbayashi, Akiko Kawabata, Satoshi Hoshino, Yosuke Miyaji, Shunsuke Kobayashi, Hirofumi Maruyama, Masahiro Sonoo","doi":"10.1002/mus.28338","DOIUrl":"10.1002/mus.28338","url":null,"abstract":"<p><strong>Introduction: </strong>Extrapolated reference values (E-Ref) procedure is a new method for determining the cutoff value without collecting the control data. We tried to apply this method to determine the cutoff value for the distal motor latency of the median nerve (median DML). During this process, we found two pitfalls of the E-Ref method. First, the E-Ref procedure did not correctly work when the DML values measured with 0.1 ms accuracy frequently took on tie values. Second, the result was influenced by the proportion of abnormal values. This study investigated these issues.</p><p><strong>Methods: </strong>Data of the median DML were extracted from our laboratory database. To solve the problem of tie values, we tried a wider post-smoothing window in the original E-Ref method. We also devised a modified method conducting pre-smoothing. To see the effect of the proportion of abnormal data, we simulated many datasets having different proportion of abnormal data.</p><p><strong>Results: </strong>In total, 1016 DML values were identified. False deflections due to tie values were often identified as the E-Ref point using the original methods even using a wider window, resulting in unrealistically low values. Modified method was free from this drawback. For all methods, the E-Ref value increased as the proportion of abnormal values increased.</p><p><strong>Discussion: </strong>The problem of tie values, a pitfall of the E-Ref method, might be solved by pre-smoothing the data. The E-Ref value is influenced by the proportion of the normal data, and datasets containing less than 20% abnormal data may achieve appropriate results.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"435-441"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
International Consensus Guidance for the Management of Glucocorticoid Related Complications in Neuromuscular Disease. 神经肌肉疾病中糖皮质激素相关并发症管理的国际共识指南
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2025-01-03 DOI: 10.1002/mus.28328
Corey Bacher, Pushpa Narayanswami, Mark Bromberg, Frank Buttgereit, Dubravka Dodig, Eoin P Flanagan, Chloe Gottlieb, John K Marshall, Rozalina G McCoy, Sara Mitchell, Pritish K Tosh, Partha S Sinha, Ruple S Laughlin, Charles D Kassardjian
{"title":"International Consensus Guidance for the Management of Glucocorticoid Related Complications in Neuromuscular Disease.","authors":"Corey Bacher, Pushpa Narayanswami, Mark Bromberg, Frank Buttgereit, Dubravka Dodig, Eoin P Flanagan, Chloe Gottlieb, John K Marshall, Rozalina G McCoy, Sara Mitchell, Pritish K Tosh, Partha S Sinha, Ruple S Laughlin, Charles D Kassardjian","doi":"10.1002/mus.28328","DOIUrl":"10.1002/mus.28328","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Glucocorticoid (GC)-related adverse reactions and risks are commonly seen during the treatment of immune-mediated and inflammatory neuromuscular disorders. There is wide variation in the management of associated complications. The aim of this study is to develop international consensus guidance on the management of GC-related complications in neuromuscular disorders.</p><p><strong>Methods: </strong>Through the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM), an international task force of 15 experts was convened to develop clinical guidance for the management of GC-related complications in neuromuscular patients. The RAND/UCLA appropriateness method (RAM) was used to develop consensus guidance statements. Initial guidance statements were crafted after a thorough literature review and were modified after anonymous panel input, with up to three rounds of voting via email to achieve consensus.</p><p><strong>Results: </strong>Statements were developed and achieved consensus for general care, monitoring of patients while on GC, osteoporosis prevention, vaccinations, infection screening, and Pneumocystis jiroveci pneumonia prophylaxis. A multidisciplinary approach to the management of GC-related complications was emphasized.</p><p><strong>Discussion: </strong>These formal consensus statements provide guidance to clinicians who use GC in the treatment of neuromuscular diseases regarding prevention and management of the more common associated adverse events and risks that arise with long and short-term GC use and serve as a springboard for investigation and updates.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"309-316"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High-Speed Video Blink Analysis Improves Detection of Facial Palsy in Early Guillain-Barré Syndrome. 高速视频眨眼分析提高早期格林-巴罗综合征面瘫的检测。
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2025-01-03 DOI: 10.1002/mus.28332
Antony Winkel, Lauren Sanders, Mark Cook, Leslie Roberts
{"title":"High-Speed Video Blink Analysis Improves Detection of Facial Palsy in Early Guillain-Barré Syndrome.","authors":"Antony Winkel, Lauren Sanders, Mark Cook, Leslie Roberts","doi":"10.1002/mus.28332","DOIUrl":"10.1002/mus.28332","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Electrophysiological investigations in early Guillain-Barré Syndrome (GBS) can be nondiagnostic. Improved testing for facial weakness in the early phase of GBS may improve diagnostic processes, as such weakness is found in approximately 50% of patients with GBS. This work pilots the utility of high-speed video analysis to complement blink reflex testing in early GBS.</p><p><strong>Methods: </strong>This work prospectively evaluated consecutive patients admitted to a metropolitan teaching hospital in Melbourne, Australia, with suspected acute GBS within the first 14 days of neurological symptoms and compared them to a cohort of healthy controls. Blink reflex testing, mechanically-activated masseter reflexes, and analysis of high-speed video recordings of the evoked blinks were performed at admission (day 0), day 7, and day 21 (±2 days).</p><p><strong>Results: </strong>19 suspected GBS patients (12 GBS and 7 mimics) were compared to 22 healthy controls. At the first test, 83% of GBS patients and 29% of mimics demonstrated blink reflex abnormalities. 50% of GBS manifested video abnormalities (14% mimics), but abnormalities preceded electrophysiological changes in two GBS patients. The calculated reference values for peak lid velocity and lid excursion by video analysis were ~160 mm/s and 7-8 mm, respectively, with slightly different values for ipsilateral versus contralateral responses.</p><p><strong>Discussion: </strong>Combining high-speed video analysis and blink reflex testing improves the detection of facial involvement in early GBS and helps discriminate from mimic disorders. Further work in a larger cohort is required to validate the sensitivity and specificity of this technique.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"429-434"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transitioning From Nusinersen to Risdiplam for Spinal Muscular Atrophy in Clinical Practice: A Single-Center Experience. 临床实践中从Nusinersen到Risdiplam治疗脊髓性肌萎缩症的过渡:单中心经验。
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2025-01-02 DOI: 10.1002/mus.28329
Can Ebru Bekircan-Kurt, Sharmada Subramanian, Shannon Chagat, Samuel J Mackenzie, Megan Iammarino, Natalie Reash, Carson Richardson, Chang-Yong Tsao, Garey Noritz, Courtney Gushue, Kavitha Kotha, Grace Paul, Richard Shell, Lindsay N Alfano, Linda P Lowes, Anne M Connolly, Megan A Waldrop
{"title":"Transitioning From Nusinersen to Risdiplam for Spinal Muscular Atrophy in Clinical Practice: A Single-Center Experience.","authors":"Can Ebru Bekircan-Kurt, Sharmada Subramanian, Shannon Chagat, Samuel J Mackenzie, Megan Iammarino, Natalie Reash, Carson Richardson, Chang-Yong Tsao, Garey Noritz, Courtney Gushue, Kavitha Kotha, Grace Paul, Richard Shell, Lindsay N Alfano, Linda P Lowes, Anne M Connolly, Megan A Waldrop","doi":"10.1002/mus.28329","DOIUrl":"10.1002/mus.28329","url":null,"abstract":"<p><strong>Background: </strong>Nusinersen and risdiplam are U.S. Food and Drug Administration (FDA)-approved treatments for spinal muscular atrophy (SMA). No head-to-head clinical trials to assess efficacy exist. Observational studies are needed to determine if transitioning to risdiplam is safe and efficacious.</p><p><strong>Methods: </strong>This retrospective study at Nationwide Children's Hospital included individuals with SMA treated with nusinersen who switched to risdiplam. Motor, pulmonary and bulbar function were assessed before and 2 years after nusinersen and risdiplam initiation.</p><p><strong>Results: </strong>Forty-four individuals were included: 11 with SMA type 1, 25 with SMA type 2 and 8 with SMA type 3. Motor function improved after initiation of nusinersen treatment with the most significant improvements seen in the first year. After transition to risdiplam, motor function remained largely stable. Need for noninvasive ventilation (NIV) overnight occurred in both groups. Cough peak flow significantly improved in the risdiplam group. Hospitalizations were the same in both groups. One individual in the nusinersen group gained the ability to take some food by mouth; two individuals in the risdiplam group achieved some oral feeding and two became exclusively orally fed.</p><p><strong>Conclusions: </strong>As expected, motor function was most improved in treatment naïve individuals in the first year after nusinersen initiation. Over half of our study population had posterior spinal fusion surgery (57%) which significantly impacted motor and respiratory outcomes, though slightly less so in the risdiplam group. Overall, our data demonstrates that transitioning from nusinersen to risdiplam is associated with a favorable safety profile and stable motor outcomes.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"414-421"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physical Activity Correlates With Skeletal Muscle MRI Findings in Individuals With Duchenne Muscular Dystrophy. 体育活动与杜氏肌营养不良患者骨骼肌MRI表现相关
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-03-01 Epub Date: 2024-12-24 DOI: 10.1002/mus.28323
Jaclyn Tamaroff, Nicholas Joy, Bruce Damon, Larry W Markham, Thomas Donnelly, Karry Su, Maciej S Buchowski, Kimberly Crum, James C Slaughter, Meng Xu, W Bryan Burnette, Jonathan Soslow
{"title":"Physical Activity Correlates With Skeletal Muscle MRI Findings in Individuals With Duchenne Muscular Dystrophy.","authors":"Jaclyn Tamaroff, Nicholas Joy, Bruce Damon, Larry W Markham, Thomas Donnelly, Karry Su, Maciej S Buchowski, Kimberly Crum, James C Slaughter, Meng Xu, W Bryan Burnette, Jonathan Soslow","doi":"10.1002/mus.28323","DOIUrl":"10.1002/mus.28323","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Skeletal muscle magnetic resonance imaging (MRI) is a validated noninvasive tool to assess Duchenne muscular dystrophy (DMD) progression. There is interest in finding DMD biomarkers that decrease the burden of clinical trial participation, such as wearable devices. Our aim was to evaluate the relationship between activity, via accelerometry, and skeletal muscle MRI, particularly T<sub>2</sub> mapping.</p><p><strong>Methods: </strong>DMD children and young adults completed skeletal muscle MRI and were asked to wear an accelerometer on the dominant wrist for 7 days. MRI data included fat-suppressed transverse relaxation time (T<sub>2</sub>) mapping of the calves and longitudinal relaxation time (T<sub>1</sub>) mapping. Activity was assessed as vector magnitudes (VMs) and fraction of time (FOT) in activity groups (sedentary 1 or 2, low 1 or 2, moderate-to-vigorous physical activity (MVPA)).</p><p><strong>Results: </strong>Participants (n = 22; median age 11.4 years, 41% ambulatory) wore the accelerometer for a median of 7 days. Longer T<sub>2</sub> in multiple lower extremity muscles was negatively correlated with VMs per minute (tibialis posterior Spearman's rho = -0.68, p < 0.001), even when accounting for age, ambulatory status, or glucocorticoid use. Longer T<sub>2</sub> of the tibialis posterior was positively correlated with FOT in sedentary 1 (rho = 0.49, p = 0.02) and negatively correlated with FOT in higher activity levels (low 1 (rho = -0.58, p = 0.004), low 2 (rho = -0.67, p = 0.002), MVPA (rho = -0.7, p < 0.001)).</p><p><strong>Discussion: </strong>In individuals with DMD, longer T<sub>2</sub> on skeletal muscle MRI of the calves moderately correlated with lower activity levels indicating the potential use of home accelerometry as a future clinical trial biomarker of skeletal muscle health and progression in DMD.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":"353-359"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis.
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-02-27 DOI: 10.1002/mus.28372
Alexandra Lovett, Sowmya Chary, Suma Babu, Gaëlle Bruneteau, Jonathan D Glass, Merete Karlsborg, Shafeeq Ladha, Keith Mayl, Christopher McDermott, Robert C Bucelli, Adriano Chiò, Toby A Ferguson, Thos Cochrane, Stephanie Fradette, Karen Smirnakis, Jennifer Inra, Sohail Malek, Laura Fanning
{"title":"Serious Neurologic Adverse Events in Tofersen Clinical Trials for Amyotrophic Lateral Sclerosis.","authors":"Alexandra Lovett, Sowmya Chary, Suma Babu, Gaëlle Bruneteau, Jonathan D Glass, Merete Karlsborg, Shafeeq Ladha, Keith Mayl, Christopher McDermott, Robert C Bucelli, Adriano Chiò, Toby A Ferguson, Thos Cochrane, Stephanie Fradette, Karen Smirnakis, Jennifer Inra, Sohail Malek, Laura Fanning","doi":"10.1002/mus.28372","DOIUrl":"https://doi.org/10.1002/mus.28372","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations (SOD1-ALS). Here we report serious neurologic adverse events (AEs) that occurred in the tofersen clinical trials in people with SOD1-ALS.</p><p><strong>Methods: </strong>Serious neurologic AEs of myelitis, radiculitis, aseptic meningitis, and papilledema reported in the tofersen clinical trials are described. Serious AEs were defined according to International Conference for Harmonization guidelines, and neurologic AEs in clinical trials were diagnosed by investigators based on symptoms, clinical examination findings, and diagnostic workup.</p><p><strong>Results: </strong>Ten participants (approximately 7% of tofersen 100-mg-treated trial participants) experienced a total of 12 serious neurologic AEs-4 of myelitis, 2 of radiculitis, 2 of aseptic meningitis, and 4 of intracranial hypertension (ICH) and/or papilledema. All events but one resolved either spontaneously, with dosing interruption/modification, or with concomitant therapies. One event was ongoing but improved as of December 2022. While 3 events led to tofersen treatment discontinuation, all other participants were able to remain on treatment. No event was life-threatening or fatal.</p><p><strong>Discussion: </strong>Some antisense oligonucleotides (ASOs) have been described as having pro-inflammatory properties. Aseptic meningitis has been reported with nusinersen; however, myelitis, radiculitis, increased intracranial pressure, and papilledema have not been reported with ASO treatment. These neurologic AEs should be considered when assessing the overall benefit/risk of tofersen treatment for SOD1-ALS. Safety data from the open-label extension and expanded access program will continue to characterize these events and further inform the safety profile of tofersen in SOD1-ALS.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Frequent Tetanic Exercise Through Electrical Muscle Stimulation May Reduce Immobilization-Induced Muscle Fibrosis by Suppressing Myonuclear Apoptosis.
IF 2.8 3区 医学
Muscle & Nerve Pub Date : 2025-02-27 DOI: 10.1002/mus.28381
Yuichiro Honda, Moeka Yoshimura, Ayumi Takahashi, Seima Okita, Jumpei Miyake, Yudai Ishiki, Chiaki Seguchi, Junya Sakamoto, Minoru Okita
{"title":"Frequent Tetanic Exercise Through Electrical Muscle Stimulation May Reduce Immobilization-Induced Muscle Fibrosis by Suppressing Myonuclear Apoptosis.","authors":"Yuichiro Honda, Moeka Yoshimura, Ayumi Takahashi, Seima Okita, Jumpei Miyake, Yudai Ishiki, Chiaki Seguchi, Junya Sakamoto, Minoru Okita","doi":"10.1002/mus.28381","DOIUrl":"https://doi.org/10.1002/mus.28381","url":null,"abstract":"<p><strong>Introduction/aims: </strong>Immobilization-induced fibrosis is the primary pathogenesis of muscle contracture, and its trigger is myonuclear apoptosis. Tetanic exercise through electrical muscle stimulation may be able to mitigate myonuclear apoptosis; this could be an intervention strategy for Immobilization-induced fibrosis. In the present study, this was tested using rat skeletal muscles.</p><p><strong>Methods: </strong>Rats were divided into the control, immobilization, low-contraction frequency (LCF), and high-contraction frequency (HCF) groups. The soleus muscles were used as specimens.</p><p><strong>Results: </strong>The number of TUNEL-positive myonuclei was 0.36 ± 0.11, 4.66 ± 0.90, 4.25 ± 0.99, and 1.90 ± 0.46 in the control, immobilization, LCF, and HCF groups, respectively. The HCF group was lower than the immobilization and LCF groups (all p < 0.001). The number of myonuclei and cross-sectional area (CSA) in the HCF group was higher than in the immobilization and LCF groups (all p < 0.001). The number of macrophages, mRNA expression of IL-1β, TGF-β1, and α-SMA, and hydroxyproline contents in the HCF group was lower than in the immobilization and LCF groups (all p < 0.001). There were moderate to strong negative correlations between the number of TUNEL-positive myonuclei and the number of myonuclei and between the CSA and the number of macrophages. Moderate to strong positive correlations were found between the number of myonuclei and the CSA, the number of macrophages and IL-1β, IL-1β and TGF-β1, TGF-β1 and α-SMA, and α-SMA and hydroxyproline contents.</p><p><strong>Discussion: </strong>Frequent tetanic exercise might mitigate macrophage accumulation caused by myonuclear apoptosis and suppress immobilization-induced muscle fibrosis due to fibrosis-associated molecule overexpression.</p>","PeriodicalId":18968,"journal":{"name":"Muscle & Nerve","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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