JAMA neurology最新文献

{"title":"Reldesemtiv in Amyotrophic Lateral Sclerosis: Results From the COURAGE-ALS Randomized Clinical Trial.","authors":"Jeremy M Shefner, Merit E Cudkowicz, Angela Genge, Orla Hardiman, Ammar Al-Chalabi, Jinsy A Andrews, Adriano Chio, Philippe Corcia, Philippe Couratier, Mamede de Carvalho, Terry Heiman-Patterson, Robert D Henderson, Caroline Ingre, Wendy Johnston, Albert Ludolph, Nicholas J Maragakis, Timothy M Miller, Jesus S Mora, Susanne Petri, Zachary Simmons, Leonard H van den Berg, Lorne Zinman, Stuart Kupfer, Fady I Malik, Lisa Meng, Tyrell J Simkins, Jenny Wei, Andrew A Wolff, Stacy A Rudnicki","doi":"10.1001/jamaneurol.2025.0241","DOIUrl":"10.1001/jamaneurol.2025.0241","url":null,"abstract":"<p><strong>Importance: </strong>Treatment options for amyotrophic lateral sclerosis (ALS) remain suboptimal. Results from a phase 2 study of reldesemtiv in ALS suggested that it may slow disease progression.</p><p><strong>Objective: </strong>To assess the effect of reldesemtiv vs placebo on functional outcomes in ALS.</p><p><strong>Design, setting, and participants: </strong>A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (COURAGE-ALS) was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted at 83 ALS centers in 16 countries from August 2021 to July 2023. The first 24-week period was placebo controlled vs reldesemtiv. All participants received reldesemtiv during the second 24-week period with a 4-week follow-up. Two interim analyses were planned, the first for futility and the second for futility and possible resizing. This was a hybrid decentralized trial with approximately half the trial visits performed remotely and the remaining visits in the clinic. Eligible participants met criteria for definite, probable, or possible ALS with lower motor neuron signs by modified El Escorial Criteria, ALS symptoms for 24 months or less, ALS Functional Rating Scale-Revised (ALSFRS-R) total score of 44 or less, and forced vital capacity of greater than or equal to 65% of predicted.</p><p><strong>Interventions: </strong>Oral reldesemtiv, 300 mg, or placebo twice daily.</p><p><strong>Main outcomes and measures: </strong>The primary end point was change in ALSFRS-R total score from baseline to week 24.</p><p><strong>Results: </strong>Of the 696 participants screened, 207 were screen failures. A total of 486 participants (mean [SD] age, 59.4 [10.9] years; 309 male [63.6%]) were randomized to reldesemtiv (n = 325) or placebo (n = 161); 3 randomized patients were not dosed. The second interim analysis at 24 weeks after randomization included 256 participants. The data monitoring committee recommended that the trial should end due to futility, and the sponsor agreed. The mean (SE) group difference in the ALSFRS-R score from baseline to week 24 was -1.1 (0.53; 95% CI, -2.17 to -0.08; P = .04, favoring placebo). Given excess missing data from early termination, the combined assessment assumed greater importance; it, too, failed to show a benefit from treatment with reldesemtiv (win probability was 0.44 for reldesemtiv and 0.49 for placebo, with a win ratio of 0.91; 95% CI of win ratio, 0.77-1.10; P = .11).</p><p><strong>Conclusions and relevance: </strong>This randomized clinical trial failed to demonstrate efficacy for reldesemtiv in slowing functional decline in ALS.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT04944784.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sonographic Demonstration of Myopathy in Mycosis Fungoides.","authors":"David Kravitz, Erel Joffe, Alon Abraham","doi":"10.1001/jamaneurol.2025.0254","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0254","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neurologist's Imperative in Brain Death.","authors":"David M Greer, Ariane Lewis, Matthew P Kirschen","doi":"10.1001/jamaneurol.2025.0191","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0191","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated Imaging Differentiation for Parkinsonism.","authors":"David E Vaillancourt, Angelos Barmpoutis, Samuel S Wu, Jesse C DeSimone, Marissa Schauder, Robin Chen, Todd B Parrish, Wei-En Wang, Eric Molho, John C Morgan, David K Simon, Burton L Scott, Liana S Rosenthal, Stephen N Gomperts, Rizwan S Akhtar, David Grimes, Sol De Jesus, Natividad Stover, Ece Bayram, Adolfo Ramirez-Zamora, Stefan Prokop, Ruogu Fang, John T Slevin, Prabesh Kanel, Nicolaas I Bohnen, Paul Tuite, Stephen Aradi, Antonio P Strafella, Mustafa S Siddiqui, Albert A Davis, Xuemei Huang, Jill L Ostrem, Hubert Fernandez, Irene Litvan, Robert A Hauser, Alexander Pantelyat, Nikolaus R McFarland, Tao Xie, Michael S Okun, Alicia Leader, Áine Russell, Hannah Babcock, Karen White-Tong, Jun Hua, Anna E Goodheart, Erin Colleen Peterec, Cynthia Poon, Max B Galarce, Tanya Thompson, Autumn M Collier, Candace Cromer, Natt Putra, Reilly Costello, Eda Yilmaz, Crystal Mercado, Tomas Mercado, Amanda Fessenden, Renee Wagner, C Chauncey Spears, Jacqueline L Caswell, Marina Bryants, Kristyn Kuzianik, Youshra Ahmed, Nathaniel Bendahan, Joy O Njoku, Amy Stiebel, Hengameh Zahed, Sarah S Wang, Phuong T Hoang, Joseph Seemiller, Guangwei Du","doi":"10.1001/jamaneurol.2025.0112","DOIUrl":"10.1001/jamaneurol.2025.0112","url":null,"abstract":"<p><strong>Importance: </strong>Magnetic resonance imaging (MRI) paired with appropriate disease-specific machine learning holds promise for the clinical differentiation of Parkinson disease (PD), multiple system atrophy (MSA) parkinsonian variant, and progressive supranuclear palsy (PSP). A prospective study is needed to test whether the approach meets primary end points to be considered in a diagnostic workup.</p><p><strong>Objective: </strong>To assess the discriminative performance of Automated Imaging Differentiation for Parkinsonism (AIDP) using 3-T diffusion MRI and support vector machine (SVM) learning.</p><p><strong>Design, setting, and participants: </strong>This was a prospective, multicenter cohort study conducted from July 2021 to January 2024 across 21 Parkinson Study Group sites (US/Canada). Included were patients with PD, MSA, and PSP with established criteria and unanimous agreement in the clinical diagnosis among 3 independent, blinded neurologists who specialize in movement disorders. Patients were assigned to a training set or an independent testing set.</p><p><strong>Exposure: </strong>MRI.</p><p><strong>Main outcomes and measures: </strong>Area under the receiver operating characteristic curve (AUROC) in the testing set for primary model end points of PD vs atypical parkinsonism, MSA vs PSP, PD vs MSA, and PD vs PSP. AIDP was also paired with antemortem MRI to test against postmortem neuropathology in a subset of autopsy cases.</p><p><strong>Results: </strong>A total of 316 patients were screened and 249 patients (mean [SD] age, 67.8 [7.7] years; 155 male [62.2%]) met inclusion criteria. Of these patients, 99 had PD, 53 had MSA, and 97 had PSP. A retrospective cohort of 396 patients (mean [SD] age, 65.8 [8.9] years; 234 male [59.1%]) was also included. Of these patients, 211 had PD, 98 had MSA, and 87 had PSP. Patients were assigned to the training set (78%; 104 prospective, 396 retrospective) or independent testing set, which included 145 (22%; 60 PD, 27 MSA, 58 PSP) prospective patients (mean age, 67.4 [SD 7.7] years; 95 male [65.5%]). The model was robust in differentiating PD vs atypical parkinsonism (AUROC, 0.96; 95% CI, 0.93-0.99; positive predictive value [PPV], 0.91; negative predictive value [NPV], 0.83), MSA vs PSP (AUROC, 0.98; 95% CI, 0.96-1.00; PPV, 0.98; NPV, 0.81), PD vs MSA (AUROC, 0.98; 95% CI, 0.96-1.00; PPV, 0.97; NPV, 0.97), and PD vs PSP (AUROC, 0.98; 95% CI, 0.96-1.00; PPV, 0.92; NPV, 0.98). AIDP predictions were confirmed neuropathologically in 46 of 49 brains (93.9%).</p><p><strong>Conclusions and relevance: </strong>This prospective multicenter cohort study of AIDP met its primary end points. Results suggest using AIDP in the diagnostic workup for common parkinsonian syndromes.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Error in Author Name.","authors":"","doi":"10.1001/jamaneurol.2025.0539","DOIUrl":"10.1001/jamaneurol.2025.0539","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAMA Neurology Peer Reviewers in 2024.","authors":"","doi":"10.1001/jamaneurol.2025.0293","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0293","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"e250293"},"PeriodicalIF":20.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAMA Neurology-The Year in Review 2024.","authors":"S Andrew Josephson","doi":"10.1001/jamaneurol.2025.0177","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0177","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belly Dancer’s Dyskinesia Following Acute Corpus Callosum Infarction","authors":"Juntao Yin, Yuqing Wei, Lixin Guo","doi":"10.1001/jamaneurol.2025.0086","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0086","url":null,"abstract":"This case report describes a patient with spontaneous, arrhythmic, spasmodic contractions of the abdominal muscles whose imaging confirmed involvement of the genu, body, and splenium of the corpus callosum.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"16 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venture Capital Investment in Neurology Companies.","authors":"Ravi Dhawan, Alex B Boyle, Hithardhi Duggireddy, Margherita Rampichini, Denys Shay","doi":"10.1001/jamaneurol.2025.0137","DOIUrl":"10.1001/jamaneurol.2025.0137","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health Information Seeking-CTE Perception and Suicide-Reply.","authors":"Rachel Grashow, Douglas P Terry, Aaron L Baggish","doi":"10.1001/jamaneurol.2025.0051","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0051","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}