JAMA neurology最新文献

{"title":"Verdiperstat in Amyotrophic Lateral Sclerosis: Results From the Randomized HEALEY ALS Platform Trial.","authors":"Jinsy Andrews, Sabrina Paganoni, Eric A Macklin, Lori B Chibnik, Melanie Quintana, Benjamin R Saville, Michelle A Detry, Matteo Vestrucci, Joseph Marion, Anna McGlothlin, Eufrosina Young, Marianne Chase, Lindsay Pothier, Brittney Harkey, Hong Yu, Alex Sherman, Jeremy Shefner, Meghan Hall, Gale Kittle, Mariah R Connolly, James D Berry, Derek D'Agostino, Eric Tustison, Elisa Giacomelli, Erica Scirocco, Gustavo Alameda, Eduardo Locatelli, Doreen Ho, Adam Quick, Daragh Heitzman, Senda Ajroud-Driss, Stanley H Appel, Sheetal Shroff, Jonathan Katz, Kevin Felice, Nicholas J Maragakis, Zachary Simmons, Stephen A Goutman, Nicholas Olney, Timothy Miller, Joseph Americo Fernandes, Hristelina Ilieva, Omar Jawdat, Michael D Weiss, Laura Foster, Tuan Vu, Shafeeq Ladha, Margaret Ayo Owegi, Daniel S Newman, Ximena Arcila-Londono, Carlayne E Jackson, Andrea Swenson, Terry Heiman-Patterson, James Caress, Dominic Fee, Amanda Peltier, Richard Lewis, Jeffrey Rosenfeld, David Walk, Kristin Johnson, Matthew Elliott, Edward J Kasarskis, Seward Rutkove, Courtney E McIlduff, Richard Bedlack, Lauren Elman, Namita A Goyal, Kourosh Rezania, Paul Twydell, Michael Benatar, Jonathan Glass, Jeffrey A Cohen, Vovanti Jones, Lindsay Zilliox, James P Wymer, Said R Beydoun, Jaimin Shah, Gary L Pattee, Jennifer Martinez-Thompson, Shakti Nayar, Volkan Granit, Mary Donohue, Katheryn Grossman, Daniel J Campbell, Irfan A Qureshi, Merit E Cudkowicz, Suma Babu","doi":"10.1001/jamaneurol.2024.5249","DOIUrl":"10.1001/jamaneurol.2024.5249","url":null,"abstract":"<p><strong>Importance: </strong>Myeloperoxidase is one of the most abundant peroxidase enzymes in activated myeloid cells. Myeloperoxidase inhibitors may have a clinical benefit in amyotrophic lateral sclerosis (ALS) by slowing neurodegeneration via reduced neuroinflammation and oxidative stress.</p><p><strong>Objective: </strong>To determine the safety, tolerability, and efficacy of verdiperstat, a selective myeloperoxidase inhibitor, in ALS.</p><p><strong>Design settings and participants: </strong>Verdiperstat was tested as a regimen of the HEALEY ALS Platform Trial, a multicenter, double-blind, perpetual platform design, randomized clinical trial, with sharing of trial infrastructure and placebo data across multiple regimens. The study was conducted at 54 ALS referral centers across the US from July 2020 to April 2022. Adult participants with a diagnosis of clinically possible, probable, laboratory-supported probable, or definite ALS defined by the revised El Escorial criteria were randomized to verdiperstat or regimen-specific placebo. An additional group of participants concurrently randomized to placebo from other regimens was included in the analyses.</p><p><strong>Interventions: </strong>Eligible participants were randomized in a 3:1 ratio to receive oral verdiperstat, 600 mg, twice daily or matching placebo for a planned placebo-controlled duration of 24 weeks.</p><p><strong>Main outcomes and measures: </strong>The primary efficacy outcome was change from baseline through week 24 in disease severity, as measured by a joint model of ALS Functional Rating Scale-Revised and survival, with the treatment effect quantified by the disease rate ratio (DRR), with DRR less than 1 indicating a slowing in disease progression of verdiperstat relative to placebo.</p><p><strong>Results: </strong>A total of 167 participants (mean [SD] age, 58.5 [11.4] years; 59 [35.3%] female; 108 [64.6%] male) were randomized to either verdiperstat (126 [75.4%]) or to placebo (41 [25.6%]). Among the participants randomized to the verdiperstat regimen, 130 (78%) completed the trial. The estimated DRR was 0.98 (95% credible interval, 0.77-1.24; posterior probability = 0.57 for slowing of disease progression [DRR <1]). Verdiperstat was estimated to slow progression by 2% vs placebo (95% credible interval, -23% to 24%; posterior probability 0.57). Verdiperstat was overall safe and well tolerated. Common adverse events in the verdiperstat group were nausea, insomnia, and elevated thyrotropin levels.</p><p><strong>Conclusions and relevance: </strong>Results demonstrate that treatment with verdiperstat was unlikely to alter disease progression in ALS.</p><p><strong>Trial registration: </strong>Clinical Trial Identifiers: NCT04297683 and NCT04436510.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":"333-343"},"PeriodicalIF":20.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604844","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":"Correction to Table 2 Heading and Figure 2 Text.","authors":"","doi":"10.1001/jamaneurol.2025.0916","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0916","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"82 4","pages":"423"},"PeriodicalIF":20.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015794","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":"Errors in Abstract, Methods, Results, Figure 2, and Conflicts of Interest.","authors":"","doi":"10.1001/jamaneurol.2025.0947","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0947","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"82 4","pages":"423"},"PeriodicalIF":20.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11997720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002741","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":"N-Acetylcysteine for Hereditary Cystatin C Amyloid Angiopathy","authors":"Asbjorg Osk Snorradottir, Alvaro Gutierrez-Uzquiza, Paloma Bragado, Michael E. March, Charlly Kao, Enrico Bernardo Arkink, Solveig Jonsdottir, Arna Sigurdardottir, Helgi J. Isaksson, Hekla Liv Mariasdóttir, Olga Yr Bjorgvinsdottir, Natalia M. Kowal, Hugrun L. Heimisdottir, Astros Sverrisdottir, Astridur Palsdottir, Hans Tomas Bjornsson, Hakon Hakonarson","doi":"10.1001/jamaneurol.2025.0326","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0326","url":null,"abstract":"ImportanceHereditary cystatin C amyloid angiopathy (HCCAA) is a lethal, dominantly inherited disease primarily affecting Icelandic young adults that leads to severe cerebral amyloid angiopathy, with no effective therapy.ObjectiveTo investigate safety, tolerance, and therapeutic potential of <jats:italic>N</jats:italic>-acetylcysteine (NAC) in lowering disease-associated biomarkers in sequence variation carriers.Design, Setting, and ParticipantsThis phase 2a open-label clinical trial was conducted from March 2019 to December 2021 at a single study center at Landspitali University Hospital in Reykjavik, Iceland, and included 17 confirmed carriers of the L68Q-<jats:italic>CST3 </jats:italic>sequence variation.InterventionHigh-dose NAC treatment was administered at 2400 mg daily for 9 months. Participants underwent regular monitoring for hemorrhages and disease progression, including blood and skin biopsy samples obtained every 3 months for biomarker testing.Main Outcomes and MeasuresThe primary outcomes were drug tolerability and safety, cognitive status, and reduction in disease-associated biomarkers in skin biopsies. Secondary outcomes included changes in blood and plasma biomarker levels.ResultsOf 17 carriers treated, 6 were male and 11 were female, and mean (SD) participant age was 40.0 (4.2) years. Analysis of the primary outcomes showed that NAC was safe and well tolerated. Five cerebral bleeds occurred during the treatment period without permanent neurological sequela; no death occurred. There was significant reduction in median (IQR) disease-specific biomarker levels in skin after treatment, including collagen IV (baseline: 3.69% [2.48%-5.16%]; after treatment: 2.60% [1.99%-2.97%]; <jats:italic>P</jats:italic> &amp;amp;lt; .001), fibronectin (baseline: 3.17% [2.09%-5.05%]; after treatment: 2.37% [1.87%-3.42%]; <jats:italic>P</jats:italic> = .01), vimentin (baseline: 1.60% [1.24%-2.37%]; after treatment: 1.31% [0.97%-1.68%]; <jats:italic>P</jats:italic> &amp;amp;lt; .001), and SMAD (baseline: 2.25% [0.55%-4.36%]; after treatment: 1.56% [0.20%-2.54%]; <jats:italic>P</jats:italic> &amp;amp;lt; .001) via Wilcoxon matched-pairs signed rank test. Secondary outcomes included a significant increase in reduced glutathione levels and decreased high-molecular-weight cystatin C aggregate levels in plasma after NAC treatment.Conclusions and RelevanceIn this single-center nonrandomized clinical trial, NAC was safe and well tolerated and decreased disease-associated biomarker and amyloid deposition, suggesting NAC may offer a preventive strategy against HCCAA.Trial RegistrationClinicalTrialsRegister.eu Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004776-56/results\">2017-004776-56</jats:ext-link>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"61 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737091","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":"Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation","authors":"Steven J. Warach, Lisa A. Davis, Patrick Lawrence, Byron Gajewski, Jo Wick, Fred Shi, Ty T. Shang, DaiWai M. Olson, Sidarrth Prasad, Lee Birnbaum, Jody M. Richardson, Sean I. Savitz, Mark P. Goldberg, Salvador Cruz-Flores, Israel Alba, Jane Anderson, Barbara Kimmel, Chethan P. Venkatasubba Rao, Ben King, Adrienne N. Dula, Truman J. Milling","doi":"10.1001/jamaneurol.2025.0285","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0285","url":null,"abstract":"ImportanceClinical practice guidelines recommend initiation of anticoagulation within 2 weeks after stroke with atrial fibrillation. It is unknown whether there is an optimal starting day within the 14-day period that balances the risks of recurrent embolic events against serious hemorrhagic events.ObjectiveTo determine if there is an optimal delay time to initiate treatment with a direct oral anticoagulant after atrial fibrillation–related stroke that minimizes the risk of a composite outcome of ischemic or hemorrhagic events.Design, Setting, and ParticipantsThis phase 2, pragmatic, response-adaptive randomized clinical trial was conducted between June 2017 and June 2023 at acute care hospitals in Texas and included patients who had a mild to moderate ischemic stroke (minimum lesion diameter of 1.5 cm) with atrial fibrillation and were prescribed a direct oral anticoagulant within 2 weeks from stroke onset.InterventionWithin 3 to 4 days after atrial fibrillation–associated ischemic stroke, patients were randomized to a group for treatment start date (group 1 was day 3 or 4 after stoke onset; group 2 was day 6; group 3 was day 10; and group 4 was day 14) with a direct oral anticoagulant for secondary stroke prevention.Main Outcomes and MeasuresThe composite primary outcome was an ischemic (stroke or systemic embolism) or hemorrhagic (symptomatic intracranial hemorrhage or major systemic hemorrhage) event observed within 30 days from the index stroke time of onset. Posterior probabilities were used to estimate which timing groups were optimal for treatment initiation and were recalculated at predefined intervals. The randomization allocations were adjusted to favor the groups with higher probabilities.ResultsThe trial enrolled and randomized 200 patients (50% were female; the median age was 75 years [IQR, 65-81 years]; 17.5% were Asian, Black, or &amp;amp;gt;1 race; 16.5% were Hispanic; the median National Institutes of Health Stroke Scale score was 6.5 [IQR, 4-14]; and the median lesion diameter was 3.1 cm [IQR, 2.0-4.4 cm]). No ischemic events were observed for group 1, 3 events were observed for group 2, 2 events were observed for group 3, and 2 events were observed for group 4. One hemorrhagic event was observed for group 1, 1 event was observed for group 2, 1 event was observed for group 3, and 0 events were observed for group 4. Group 1 had a posterior probability of 0.41 for being the optimal day for treatment initiation and it was 0.26 for group 2, 0.17 for group 3, and 0.15 for group 4. The use of response-adaptive randomization was feasible and favored groups with earlier initiation times for use of a direct oral anticoagulant.Conclusions and RelevanceA clearly superior day to initiate use of a direct oral anticoagulant for secondary stroke prevention in patients with atrial fibrillation was not identified, but the evidence suggests that initiating use of a direct oral anticoagulant earlier is better than at later times within the first ","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"53 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737092","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":"Accuracy of New John Cunningham Virus Antibody Assay in Natalizumab-Treated Patients With Multiple Sclerosis","authors":"Liza M. Y. Gelissen, Martijn T. Wijburg, Eva M. M. Strijbis, Bob W. van Oosten, Brigit A. de Jong, Bernard M. J. Uitdehaag, Theo Rispens, Mariet C. W. Feltkamp, Zoé L. E. van Kempen, Joep Killestein","doi":"10.1001/jamaneurol.2025.0337","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.0337","url":null,"abstract":"This cross-sectional study examines the increase in positive results for John Cunningham virus antibodies and higher risk for progressive multifocal leukoencephalopathy among patients with multiple sclerosis receiving natalizumab.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"72 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737090","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":"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":"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":"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}