JAMA neurologyPub Date : 2025-01-21DOI: 10.1001/jamaneurol.2024.4600
Felipe J S Jones,Christyn Edmundson,Jennifer Orthmann-Murphy
{"title":"A 61-Year-Old Man With Weakness and Gait Dysfunction.","authors":"Felipe J S Jones,Christyn Edmundson,Jennifer Orthmann-Murphy","doi":"10.1001/jamaneurol.2024.4600","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4600","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"37 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991687","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":"Novel Meningoencephalomyelitis Associated With Vimentin IgG Autoantibodies.","authors":"Dongshan Wan,Shufang Zhao,Chen Zhang,Fang Xu,Huizi Wang,Shaoxin Tao,Zhandong Qiu,Hao Jiang,Dawei Li,Fei Wang,Dong Li,Jiahao Chen,Yan Wang,Yao Yan,Yan Zhao,Xiaohan Gao,Bingxue Jin,Di Liu,Mengyao Zhang,Jingjing Feng,Shiyue Hou,Mingyang Wang,Teng Chen,Ming Lin,Jinming Han,Xinmei Wen,Wei Jiang,Liang Liu,Youming Long,Yinan Zhao,Jun-Ichi Kira,Zheng Liu,Guoliang Chai,Junwei Hao","doi":"10.1001/jamaneurol.2024.4763","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4763","url":null,"abstract":"ImportanceAutoantibodies targeting astrocytes, such as those against glial fibrillary acidic protein (GFAP) or aquaporin protein 4, are crucial diagnostic markers for autoimmune astrocytopathy among central nervous system (CNS) autoimmune disorders. However, diagnosis remains challenging for patients lacking specific autoantibodies.ObjectiveTo characterize a syndrome of unknown meningoencephalomyelitis associated with an astrocytic autoantibody.Design, Setting, and ParticipantsThis retrospective case series study included samples collected from April 2021 to May 2024 at a tertiary referral hospital among patients with uncharacterized CNS autoimmune disorders and similar clinical and radiological features. Single-cell RNA sequencing (scRNA-seq) was performed on cerebrospinal fluid (CSF) cells of 2 index patients to identify the putative target antigen of the clonally expanded B cells. A comprehensive screening for additional patients was conducted using blinded cell-based and tissue-based assay. Candidate patients were followed up for a median (range) duration of 23 (5-31) months.ExposuresscRNA-seq, autoantibody characterization, and testing.Main Outcomes and MeasuresDetection of the autoantibody and characterization of the associated autoimmune meningoencephalomyelitis.ResultsFourteen candidate patients (10 [71%] female; median [IQR] age, 33 [23-41] years) were identified. Initially, CSF from 2 female patients with unknown encephalomyelitis showed astrocytic reactivity on rat tissue but was negative for GFAP IgG. A total of 17 of 37 clonally expanded B cell clonotypes (46%) in their CSF expressed IgG autoantibodies targeting the astrocytic intermediate filament protein vimentin. Subsequent screening identified 12 additional patients. These 14 patients shared a unique clinical profile characterized by relapsing courses and symptoms prominently involving the cerebellum, brainstem, and corticospinal tract (CST). All patients also exhibited elevated CSF protein and cells, intrathecal immunoglobulin synthesis, and magnetic resonance imaging (MRI) showing bilateral lesions on CST. Notably, 8 of 12 patients (67%) who received first-line immunotherapy at their first episode responded well. At the last follow-up, 11 patients (79%) experienced significant disability (modified Rankin Scale ≥3).Conclusions and RelevanceIn this case series, autoantibodies targeting the astrocytic intermediate filament protein vimentin were identified in patients with previously undifferentiated meningoencephalomyelitis and common radiographic features.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"205 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991689","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}
JAMA neurologyPub Date : 2025-01-21DOI: 10.1001/jamaneurol.2024.4757
Suma Babu,Joshua M Sharfstein,Eva L Feldman
{"title":"Reimagining Care and Research for Amyotrophic Lateral Sclerosis.","authors":"Suma Babu,Joshua M Sharfstein,Eva L Feldman","doi":"10.1001/jamaneurol.2024.4757","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4757","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"81 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991690","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":"Prourokinase vs Standard Care for Patients With Mild Ischemic Stroke: The PUMICE Randomized Clinical Trial.","authors":"Yunyun Xiong,Xia Meng,Aoming Jin,Bruce C V Campbell,Anding Xu,Qiang Dong,Yun Xu,Yuesong Pan,Yong Jiang,Siying Niu,Zhiliang Li,Xianbo Zhuang,Na Guo,Zhimei Yuan,Zhenyu Kong,Lixia Zong,Chunmiao Duan,Zhixin Cao,Liyuan Wang,Manjun Hao,Shuangzhe Wu,Xueyan Feng,Hao Li,Na Wu,Zixiao Li,Xingquan Zhao,Yongjun Wang,","doi":"10.1001/jamaneurol.2024.4688","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4688","url":null,"abstract":"ImportanceTrials have not demonstrated superiority of alteplase or tenecteplase vs standard care in patients with mild stroke and have raised safety concerns. Prourokinase is an alternative fibrinolytic that may have a favorable safety profile, and the benefit-risk profile of prourokinase in mild stroke is unknown.ObjectiveTo investigate the efficacy and safety of prourokinase in mild ischemic stroke within 4.5 hours of symptom onset.Design, Setting, and ParticipantsThis was a multicenter, prospective, open-label, blinded-end point randomized clinical trial conducted from November 2022 through December 2023 with 3 months of follow-up. The trial was conducted at 89 hospitals in China. Patients with a baseline National Institutes of Health Stroke Scale score of 5 or less (scores range from 0-42, with higher scores indicating more severe neurological deficit) within 4.5 hours from the time the patient was last known to be well. Patients with intention to proceed to endovascular treatment were excluded.InterventionsEligible patients were randomly assigned in a 1:1 ratio to receive prourokinase, 35 mg (15-mg bolus + 20-mg infusion over 30 minutes) or standard care, including antiplatelet or anticoagulant therapy, at the discretion of local investigators.Main Outcomes and MeasuresThe primary outcome was modified Rankin Scale score of 0 or 1 (range, 0-6, with higher scores indicating greater disability) at day 90. Safety outcomes were symptomatic intracranial hemorrhage and death.ResultsOf 3836 patients who underwent screening, 1446 (37.7%) were enrolled in the trial. Median (IQR) age was 65.9 (57.7-72.7) years, and 948 were male (65.5%). A total of 723 patients were assigned to prourokinase and 723 to standard care. The primary outcome occurred in 639 patients (88.5%) in the prourokinase group and 658 (91.0%) in the standard care group (relative risk, 0.97; 95% CI, 0.94-1.01; 2-sided P = .12). Symptomatic intracranial hemorrhage was 0.7% (5 of 723 patients) with prourokinase and 0% with standard care, and mortality at 90 days was 2.3% and 1.4%, respectively.Conclusions and RelevanceResults of this randomized clinical trial demonstrate that prourokinase was not superior to standard care to improve the functional outcomes for patients with mild ischemic stroke within 4.5 hours after symptom onset but had a similar safety profile.Trial RegistrationClinicalTrials.gov Identifier: NCT05507645.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"58 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991688","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}
JAMA neurologyPub Date : 2025-01-13DOI: 10.1001/jamaneurol.2024.4924
{"title":"Errors in the Title, Short Title, and Additional Contributions.","authors":"","doi":"10.1001/jamaneurol.2024.4924","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4924","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970873","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}
JAMA neurologyPub Date : 2025-01-13DOI: 10.1001/jamaneurol.2024.4631
David Adams, Jonas Wixner, Michael Polydefkis, John L Berk, Isabel M Conceição, Angela Dispenzieri, Amanda Peltier, Mitsuharu Ueda, Shaun Bender, Kelley Capocelli, Patrick Y Jay, Elena Yureneva, Laura Obici
{"title":"Five-Year Results With Patisiran for Hereditary Transthyretin Amyloidosis With Polyneuropathy: A Randomized Clinical Trial With Open-Label Extension.","authors":"David Adams, Jonas Wixner, Michael Polydefkis, John L Berk, Isabel M Conceição, Angela Dispenzieri, Amanda Peltier, Mitsuharu Ueda, Shaun Bender, Kelley Capocelli, Patrick Y Jay, Elena Yureneva, Laura Obici","doi":"10.1001/jamaneurol.2024.4631","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4631","url":null,"abstract":"<p><strong>Importance: </strong>There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN.</p><p><strong>Objective: </strong>To present the long-term efficacy and safety of patisiran in adults with hATTR-PN.</p><p><strong>Design, setting, and participants: </strong>This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE.</p><p><strong>Intervention: </strong>Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years.</p><p><strong>Main outcomes and measures: </strong>Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed.</p><p><strong>Results: </strong>At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and -3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival.</p><p><strong>Conclusions and relevance: </strong>In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02510261.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970875","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}
JAMA neurologyPub Date : 2025-01-13DOI: 10.1001/jamaneurol.2024.4604
Jinyi Zhu, Kun-Woo Rafael Kim, Hanxuan Yu, Ajay Gupta, Alvin I. Mushlin, Hooman Kamel, Ankur Pandya
{"title":"Acute Ischemic Stroke Care Quality Improvement","authors":"Jinyi Zhu, Kun-Woo Rafael Kim, Hanxuan Yu, Ajay Gupta, Alvin I. Mushlin, Hooman Kamel, Ankur Pandya","doi":"10.1001/jamaneurol.2024.4604","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4604","url":null,"abstract":"This economic evaluation analyzes retrospective and prospective data in 9 quality measures to determine their value in improving care for patients who have had a stroke.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"89 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967897","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}
JAMA neurologyPub Date : 2025-01-13DOI: 10.1001/jamaneurol.2024.4671
Joshua L Bonkowsky, Deepa S Rajan, Florian Eichler
{"title":"An Imperative for Public Sharing of Adverse Events of Gene Therapy Trials.","authors":"Joshua L Bonkowsky, Deepa S Rajan, Florian Eichler","doi":"10.1001/jamaneurol.2024.4671","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4671","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":20.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970872","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}
JAMA neurologyPub Date : 2025-01-13DOI: 10.1001/jamaneurol.2024.4643
Daniel Ferreira, Scott A. Przybelski, Timothy G. Lesnick, Patricia Diaz-Galvan, Christopher G. Schwarz, Melissa M. Murray, Dennis W. Dickson, Aivi Nguyen, Ross R. Reichard, Matthew L. Senjem, Jeffrey L. Gunter, Clifford R. Jack, Paul H. Min, Manoj K. Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, Vijay K. Ramanan, David T. Jones, Hugo Botha, Erik K. St. Louis, David S. Knopman, Neill R. Graff-Radford, Gregory S. Day, Tanis J. Ferman, Walter K. Kremers, Ronald C. Petersen, Bradley F. Boeve, Val J. Lowe, Kejal Kantarci
{"title":"Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum","authors":"Daniel Ferreira, Scott A. Przybelski, Timothy G. Lesnick, Patricia Diaz-Galvan, Christopher G. Schwarz, Melissa M. Murray, Dennis W. Dickson, Aivi Nguyen, Ross R. Reichard, Matthew L. Senjem, Jeffrey L. Gunter, Clifford R. Jack, Paul H. Min, Manoj K. Jain, Toji Miyagawa, Leah K. Forsberg, Julie A. Fields, Rodolfo Savica, Jonathan Graff-Radford, Vijay K. Ramanan, David T. Jones, Hugo Botha, Erik K. St. Louis, David S. Knopman, Neill R. Graff-Radford, Gregory S. Day, Tanis J. Ferman, Walter K. Kremers, Ronald C. Petersen, Bradley F. Boeve, Val J. Lowe, Kejal Kantarci","doi":"10.1001/jamaneurol.2024.4643","DOIUrl":"https://doi.org/10.1001/jamaneurol.2024.4643","url":null,"abstract":"ImportanceAlthough <jats:sup>18</jats:sup>F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized.ObjectiveTo investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB.Design, Setting, and ParticipantsLongitudinal case-control study with mean (SD) follow-up of 3.8 (2.3) years. Cases were recruited consecutively between 2007 and 2022 at a referral center and among the population. Patients with probable DLB or mild cognitive impairment with Lewy bodies (MCI-LB) were included. Individuals without cognitive impairment were included from a population-based cohort balanced on age and sex for comparison. All participants completed at least 1 follow-up assessment by design.ExposurePatients with MCI-LB and DLB.Main Outcomes and MeasuresRate of change in FDG-PET was assessed as standardized uptake value ratios (SUVr). Clinical progression was assessed with the Clinical Dementia Rating Sum of Boxes (CDR-SB) score.ResultsThirty-five patients with probable DLB, 37 patients with MCI-LB, and 100 individuals without cognitive impairment were included. The mean (SD) age of the DLB and MCI-LB groups combined (n = 72) was 69.6 (8.2) years; 66 patients (92%) were men and 6 (8%) were women. At follow-up, 18 participants (49%) with MCI-LB had progressed to probable DLB. Patients with MCI-LB had a faster decline in FDG-SUVr, compared with that of participants without cognitive impairment, in the posterior cingulate, occipital, parietal, temporal, and lateral frontal cortices. The same regions showed greater metabolic decline in patients with DLB than in participants without cognitive impairment, with the addition of anterior-middle cingulate, insula, and medial frontal orbital cortices. Rates of change in FDG-PET in these brain regions were combined into a region of interest (ROI) labeled longitudinal FDG-PET LB meta-ROI. The rate of change in FDG-SUVr in the meta-ROI correlated with the rate of change in CDR-SB, and sample size estimates were reported for potential clinical trials in DLB. Findings were confirmed in the subsample with neuropathologic confirmation (n = 20).Conclusions and RelevanceThis study found that brain hypometabolism begins to evolve during the prodromal stages of DLB with changes paralleling symptomatic progression. These data may inform clinical practice and trials planning to use FDG-PET for biologic staging, monitoring disease progression, and potentially assessing treatment response.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"356 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967895","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}