JAMA neurology最新文献

{"title":"Precision Antisense Oligonucleotide Therapy Amenability for Infantile Genetic Epilepsies.","authors":"Emma Sherrill, David Cheerie, Cara J Beck, Ella F Whittle, Yasin Shafi, Natalie J Chandler, John Christodoulou, Jerusalem Daniel, Jane Hassell, Maria Lachgar-Ruiz, Sarah Mulhern, Elizabeth Scotchman, Jashanpreet Sidhu, Celine Florentia Tedja, Lyn S Chitty, J Helen Cross, Ingrid E Scheffer, Haiyan Zhou, Timothy W Yu, Vann Chau, Sarah E M Stephenson, Annapurna Poduri, Katherine B Howell, Amy McTague, Gregory Costain, Alissa M D'Gama","doi":"10.1001/jamaneurol.2026.1021","DOIUrl":"10.1001/jamaneurol.2026.1021","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815400","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":"Cortical Temporal Stroke Presenting With Delayed Hemichorea-Dystonia.","authors":"Alice Calarco, Angelo Tiziano Cimmino, Marta Garbuglia","doi":"10.1001/jamaneurol.2026.0972","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0972","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815362","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":"Phenoconversion in Pure Autonomic Failure: A Systematic Review and Meta-Analysis.","authors":"Sasivimol Virameteekul, Ilenia Bonini, Nicole Campese, Philipp Mahlknecht, Manuela Tan, Werner Poewe, Alastair J Noyce, Alessandra Fanciulli, Eduardo de Pablo-Fernández","doi":"10.1001/jamaneurol.2026.0989","DOIUrl":"10.1001/jamaneurol.2026.0989","url":null,"abstract":"<p><strong>Importance: </strong>Pure autonomic failure (PAF) can be the prodromal presentation of Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), although phenoconversion rates and predictors have not been systematically reported.</p><p><strong>Objective: </strong>To estimate phenoconversion rates for MSA, PD, and DLB separately and grouped as central α-synucleinopathies and identify clinical predictors of phenoconversion in patients with PAF.</p><p><strong>Data sources: </strong>PubMed and Embase databases from inception to June 2025.</p><p><strong>Study selection: </strong>Longitudinal studies including patients with confirmed PAF reporting data on incidence and/or predictors of phenoconversion.</p><p><strong>Data extraction and synthesis: </strong>Studies were screened and data extracted by 2 independent investigators according to PRISMA guidelines. A meta-analysis was performed using generic inverse-variance random-effects models.</p><p><strong>Main outcomes and measures: </strong>PD, DLB, MSA, and central α-synucleinopathy phenoconversion incidence rates as per 100 person-years were the main outcomes. Incidence rates were log transformed and pooled using a random-effects meta-analysis. Clinical predictors of phenoconversion were reported as secondary outcomes. Prediction intervals and meta-regression explored study-level moderators.</p><p><strong>Results: </strong>A total of 9 studies comprising 900 individuals with PAF (mean [SD] age at onset, 63.1 [4.3] years; 63.8% male) were included. During the mean (SD) 6.4 (2.0) years of follow-up, 270 of 900 individuals with PAF (30%) experienced phenoconversion to a central α-synucleinopathy (12% to MSA, 11% to DLB, 7% to PD) with a pooled incidence rate of 5.09 per 100 person-years (95% CI, 3.79-6.85; approximately 5% per year). Phenoconversion rates for MSA (pooled incidence rate, 1.96; 95% CI, 1.29-2.99) were highest in the first years of follow-up, whereas Lewy body disorders showed more constant phenoconversion rates (DLB pooled incidence rate, 1.56; 95% CI, 0.94-2.61; PD pooled incidence rate, 1.35; 95% CI, 0.75-2.41). Hyposmia was the only predictor with diagnostic value to distinguish between those with phenoconversion to PD and DLB (hyposmia pooled risk ratio, 1.88; 95% CI, 1.26-2.97) and MSA, although rapid eye movement sleep behavior disorder (RBD) and subtle motor signs were consistent predictors of phenoconversion to any central α-synucleinopathy. Heterogeneity was partly explained by follow-up duration.</p><p><strong>Conclusions and relevance: </strong>Findings of this systematic review and meta-analysis suggest that PAF may be a prodromal presentation of PD, DLB, or MSA with phenoconversion incidence rates similar to those of RBD. A combination of clinical (RBD, subtle motor signs, hyposmia) and in-development biomarkers may help refine the phenoconversion trajectories of people with PAF providing an invaluable opportunity for early diagnosi","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815322","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":"Pure Autonomic Failure and Central Synucleinopathy Risk.","authors":"Paul Beach, Roy Freeman","doi":"10.1001/jamaneurol.2026.0986","DOIUrl":"10.1001/jamaneurol.2026.0986","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147814340","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":"Temporal Patterns in Stroke Recurrence at Younger Ages: A Systematic Review and Meta-Analysis.","authors":"Ahmad Nehme,Linxin Li","doi":"10.1001/jamaneurol.2026.0873","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0873","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"150 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751385","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":"Efficacy and Safety of Vemircopan in Generalized Myasthenia Gravis: A Randomized Clinical Trial.","authors":"Francesco Saccà,Gino Gialdini,James F Howard,Tuan H Vu,Andreas Meisel,Stojan Peric,Jan D Lünemann,Manlio Sgarzi,Aziz Shaibani,Vera Bril,Jiann-Horng Yeh,Virginia Reyes-Garrido,Serena Liao,Camille Metais,Ralf J P van der Valk, ","doi":"10.1001/jamaneurol.2026.0902","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0902","url":null,"abstract":"ImportanceInhibition of terminal complement component 5 has proven effective in acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG) but requires intravenous or daily subcutaneous administration and is associated with an increased meningococcal infection risk. Targeting the complement alternative pathway (AP) may offer similar benefits while sparing the classical and lectin pathways, preserving some immune responses against infection.ObjectiveTo evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of vemircopan, an oral, selective factor D inhibitor that blocks AP-mediated complement activation and amplification, in adults with AChR-Ab+ gMG.Design, Setting, and ParticipantsThis double-blind, parallel-group, placebo-controlled phase 2 randomized clinical trial was conducted between April 14, 2022, and April 3, 2024, at 60 sites across 8 countries. Adults with AChR-Ab+ gMG, Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 5 or greater, and Myasthenia Gravis Foundation of America classes II through IV classification were eligible for inclusion. Data were unblinded in June 2024; final analysis was completed October 2024.InterventionRandomization 2:1:2 to twice-daily oral vemircopan, 180 mg or 120 mg, or placebo.Main Outcomes and MeasuresThe primary end point was the proportion of participants achieving a 2-point or greater reduction in MG-ADL total score from baseline for 4 consecutive weeks, without rescue therapy, during the 8-week, double-blind primary evaluation period. Secondary end points were change from baseline to week 8 in MG-ADL total score, Quantitative Myasthenia Gravis total score, and Neurological Disorders Fatigue questionnaire score.ResultsOf 99 individuals screened, 70 met eligibility criteria, and 29 were excluded. Of 70 participants randomized (vemircopan, 180 mg: n = 28; vemircopan, 120 mg: n = 14; placebo: n = 28), 38 participants (54%) were female; mean (SD) age at diagnosis was 45.4 (18.5) years. The proportion of participants achieving the primary end point did not differ significantly between placebo (18 of 28 [64%]; 90% CI, 47%-79%) and either vemircopan group (180 mg: 16 of 28 [57%]; 90% CI, 40%-73%; 120 mg: 8 of 14 [57%]; 90% CI, 33%-79%). No significant differences were observed for the secondary end points. No cases of meningococcal infection were reported; 1 participant died due to hepatic failure and 1 discontinued study treatment due to herpes simplex meningitis.Conclusions and RelevanceIn this double-blind, parallel-group, placebo-controlled phase 2 randomized clinical trial, vemircopan did not meet the prespecified threshold for efficacy, and consequently, the study was terminated.Trial RegistrationClinicalTrials.gov Identifier: NCT05218096.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"48 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751386","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":"Risk of Cancer in Patients With First-Time Seizure.","authors":"Andreas Lund Pedersen,Dóra Körmendiné Farkas,Cecilia Hvitfeldt Fuglsang,Victor W Henderson,Sofie Kejlberg Al-Mashhadi,Holly Elser,Henrik Toft Sørensen","doi":"10.1001/jamaneurol.2026.0894","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0894","url":null,"abstract":"ImportanceSeizures are a known complication of cancer, but whether they may be the first sign of undiagnosed neurological and nonneurological cancer remains unclear.ObjectiveTo examine neurological and nonneurological cancer risk in patients with first-time seizures vs the general population.Design, Setting, and ParticipantsThis population-based cohort study was conducted using nationwide Danish medical registries from January 1996 through December 2022. Follow-up extended until cancer diagnosis (excluding nonmelanoma skin cancer), emigration, death, or December 31, 2022. Analyses were performed from January 2025 through December 2025. All persons aged 18 years or older with a first-time hospital diagnosis of seizure and no preceding cancer were included.ExposureFirst-time seizure diagnosis.Main Outcomes and MeasuresThe primary outcomes were absolute risks (ARs) of cancer and standardized incidence ratios (SIRs) relative to the general Danish population with 95% confidence intervals, which were computed for all cancers, neurological and nonneurological cancers, and site-specific cancer within 1 year, from 1 to less than 5 years, and from 5 to 20 years after the first seizure.ResultsAmong 49 894 adults with first-time seizure (median [IQR] age at seizure diagnosis, 51.5 [35.6-67.8] years; 20 648 [41.4%] women), a total of 1172 neurological and 850 nonneurological cancers were observed within the first year of follow-up; 87 neurological and 1226 nonneurological cancers were observed during the period from 1 to less than 5 years; and 112 neurological and 2120 nonneurological cancers were observed during the period from 5 to 20 years. In these time periods, the ARs for any cancer were 4.1%, 3.5%, and 13.4%, with SIRs of 5.30 (95% CI, 5.07-5.54), 1.18 (95% CI, 1.12-1.25), and 1.34 (95% CI, 1.28-1.40). ARs for neurological cancers were 2.4%, 0.2%, and 0.7%, with SIRs of 76.1 (95% CI, 71.8-80.6), 1.85 (95% CI, 1.48-2.28), and 1.46 (95% CI, 1.20-1.75). ARs for nonneurological cancers were 1.7%, 3.3%, and 12.8%, with SIRs of 2.32 (95% CI, 2.17-2.48), 1.15 (95% CI, 1.09-1.22), and 1.33 (95% CI, 1.28-1.39).Conclusions and RelevancePer the results of this cohort study, first-time seizures were associated with clearly elevated short-term relative risk of cancer and slightly elevated long-term risk, indicating they may be an early clinical sign of both neurological and nonneurological occult cancers. These findings highlight the importance of considering broader diagnostic assessments after first-time seizures in select patients.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"20 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751391","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":"Acute Brain Injury in New-Onset Refractory Status Epilepticus and Etiology-Defined Status Epilepticus.","authors":"Stefano Meletti,Aurelie Hanin,Giada Giovannini,Roberta Bedin,Margherita Burani,Lisa Taruffi,Niccolò Orlandi,Teresa Urbano,Fabio D'Achille,Mara Malerba,Maysaa M Basha,Krista Eschbach,Brandon Foreman,Raquel Farias-Moeller,Nicolas Gaspard,Elisabeth E Gerard,Teneille Gofton,Margaret T Gopaul,Hiba A Haider,Stephen T Hantus,Susan Herman,Peter Kang,Gregory S Day,Padmaja Kandula,Claude Steriade,Aaron F Struck,Olga Taraschenko,Mark Wainwright,Ji Yeoun Yoo,Daniel J Zhou,Simona Lattanzi,Vincent Navarro,Lawrence J Hirsch","doi":"10.1001/jamaneurol.2026.0865","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0865","url":null,"abstract":"ImportanceSeizure-induced brain injury is central to the treatment urgency of new-onset refractory status epilepticus (NORSE). Identifying biomarkers that reflect ongoing neuronal damage could inform therapeutic timing and improve outcomes.ObjectiveTo quantify acute brain injury in patients with cryptogenic NORSE (cNORSE), etiology-defined status epilepticus (eSE), and chronic epilepsy.Design, Setting, and ParticipantsThis was an international cross-sectional study conducted between 2013 and 2025. Patients were enrolled at 36 hospitals in the US, 2 in Canada, and 1 in Italy, France, and Belgium. Patients with cNORSE and eSE for which biological samples were obtained during ongoing seizure activity were enrolled in the study. Comparison groups without status epilepticus comprised individuals with chronic epilepsy and healthy participants. None were excluded.ExposuresNeurofilament light chain (NfL) and S100-beta (S100B) protein concentrations in serum and cerebrospinal fluid (CSF).Main Outcomes and MeasuresDegree of neuronal and glial damage, indexed by NfL and S100B levels, and their association with short-term functional outcomes.ResultsA total of 78 patients with cNORSE (mean [95% CI] age, 37 [30-41] years; 44 female [56%]) and 2 independent cohorts of 211 patients (mean [95% CI] age, 69 [66-71] years; 128 female [61%]) and 73 patients (mean [95% CI] age, 56 [45-65] years; 39 male [53%]) with eSE were included. NfL concentrations were markedly elevated in cNORSE-approximately 10-fold higher in CSF and 4-fold higher in serum-compared with the eSE cohorts (CSF: median [IQR], 6408 [1503-22 963] pg/mL compared with 694 [219-2389] pg/mL; serum: median [IQR], 231 [99-855] pg/mL compared with 55 [20-135] pg/mL; P <.001). Serum NfL levels were nearly 20-fold higher in cNORSE than in the cohort with epilepsy and in healthy controls (median [IQR], 11 [7-19 ] and 7 [5-14 ] pg/mL, respectively). Serum and CSF NfL levels were strongly correlated (Spearman ρ = 0.75; P < .001) and rose sharply between week 1 (median [IQR], 101 [51-137] pg/mL), week 2 (median [IQR], 197 [117-324] pg/mL), and week 3 (median [IQR], 598 [163-1000] pg/mL) after onset (P < .001). In contrast, S100B concentrations did not differ between groups and showed no consistent temporal pattern. NfL discriminated cNORSE from eSE (area under the receiver operating characteristic curve [AUROC], 0.79; 95% CI, 0.68-0.90) and from cohorts without status epilepticus (AUROC, 0.99; 95% CI, 0.78-1.00). Higher serum NfL was independently associated with poor functional outcome at discharge (Glasgow Outcome Scale extended score, 1-4; odds ratio, 1.01; 95% CI, 1.00-1.03; P = .03).Conclusions and RelevanceResults of this cross-sectional study suggest that acute neuroaxonal injury, as reflected by elevated NfL levels, was substantially greater in cNORSE than in the cohorts with eSE and in controls without status epilepticus. The rapid early rise in NfL highlights a narrow therapeutic window, emphasizing the","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"26 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751384","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":"Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for AIS in the Posterior Circulation: The IAT-TOP Randomized Clinical Trial.","authors":"Wenhuo Chen,Bin Yang,Xuesong Bai,Tingyu Yi,Haibo Wang,Changming Wen,Yifeng Liu,Lin Ma,Shaoguang Wu,Sheng Liu,Liyong Zhang,Ya Peng,Yanxin Zhao,Cunfeng Song,Xueli Cai,Guang Zhang,Wei Zheng,Tao Cheng,Liping Wei,Lihua Xu,Wenhua Liu,Hongxing Han,Hua Cao,Wansheng Chang,Pu Fang,Chenghua Xu,Dongsheng Ju,Yongchang Liu,Jin Zhang,Jinglun Li,En Wang,Guilian Zhang,Jia Yu,Guoyong Zeng,Fei Chen,Xin Li,Yufu Dai,Xiaofan Guo,Yangfeng Wu,Thanh N Nguyen,Urs Fischer,Adnan I Qureshi,Raul G Nogueira,Xunming Ji,Liqun Jiao, ","doi":"10.1001/jamaneurol.2026.1074","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.1074","url":null,"abstract":"ImportanceThe impact of adjunctive intra-arterial alteplase after successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the posterior circulation requires further investigation.ObjectiveTo assess the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.Design, Setting, and ParticipantsThis was a multicenter, prospective, randomized, open-label, blinded-end point (PROBE design) clinical trial. The study was conducted between September 5, 2023, and November 29, 2024, with the 3-month follow-up completed on February 18, 2025. The trial was conducted in 37 comprehensive stroke centers in China. Patients in China with acute basilar artery occlusion presenting within 24 hours of the time last known well were randomly assigned to the treatment group or control group. Eligible participants were adults who achieved successful recanalization after EVT.InterventionsEligible patients were randomly assigned to the intra-arterial alteplase group (0.225 mg/kg, maximum dose limit 22.5 mg infused at a concentration of 1.0 mg/mL within 15 minutes distal to the origin of posterior inferior cerebellar artery) or control group (no intra-arterial thrombolysis).Main Outcomes and MeasuresThe primary efficacy outcome was the proportion of patients achieving functional independence (modified Rankin Scale score of 0-2) at 90 days. The primary safety outcomes were mortality at 90 days and incidence of symptomatic intracranial hemorrhage within 48 hours.ResultsA total of 247 patients were enrolled, and 1 patient was excluded from the full analysis set due to basilar artery reocclusion before intra-arterial alteplase. The remaining 246 patients (median [IQR] age, 65.0 [56.0-72.0] years; 176 male [71.5%]) were included in this analysis, 124 (50.4%) in the treatment group and 122 (49.6%) in the control group. Among the patients recruited and followed up, functional independence at 90 days was achieved in 52 (41.9%) in the intra-arterial alteplase group and 57 (46.7%) in the control group (adjusted risk ratio, 0.93; 95% CI, 0.73-1.18; P = .55). Mortality at 90 days (29.6% vs 27.0%, respectively; adjusted hazard ratio, 1.07; 95% CI, 0.71-1.61; P = .75) and incidence of symptomatic intracranial hemorrhage (2.4% vs 2.5%, respectively; unadjusted risk ratio, 0.98; 95% CI, 0.20-4.74; P = .97) were similar across groups.Conclusions and RelevanceResults of this randomized clinical trial reveal that in patients with posterior circulation stroke due to acute basilar artery occlusion, intra-arterial alteplase after successful endovascular recanalization appeared to be safe but was not associated with improvement of functional outcomes at 90 days.Trial RegistrationClinicalTrials.gov Identifier: NCT05897554.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"428 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735547","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":"Hypertension With High-Risk Features in Cryptogenic Stroke","authors":"Mohamed Ridha, Raed Hailat, Robert Stanton, Alexander E. Merkler, Mitchell S. V. Elkind, W. T. Longstreth, David L. Tirschwell, Richard A. Kronmal, Yousef Hannawi, Hooman Kamel, James Burke, Daniel Woo","doi":"10.1001/jamaneurol.2026.0855","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.0855","url":null,"abstract":"Importance Multiple trials have found no difference in secondary stroke prevention between anticoagulation and antiplatelet therapy after cryptogenic stroke. Due to limitations of current stroke mechanism classification, one possible explanation is the failure to exclude patients with hypertension-related cerebrovascular disease. Objective To determine whether hypertension with high-risk features is associated with treatment effect modification of anticoagulation vs antiplatelet therapy. Design, Setting, and Participants This exploratory analysis of the Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy (ARCADIA) randomized clinical trial was conducted between April and August 2025. The original trial was conducted from February 2018 to February 2023 at 185 sites in North America. From 1015 randomized patients with a recent cryptogenic stroke and atrial cardiopathy, 945 with available hypertension data were included in this analysis after exclusions for missing blood pressure and echocardiography data. Interventions Apixaban, 5 mg or 2.5 mg, twice daily vs aspirin, 81 mg, once daily. Main Outcomes and Measures The primary outcome was recurrent ischemic stroke or systemic embolism. Hypertension with high-risk features was defined as systolic blood pressure ≥160 mm Hg at enrollment, left ventricular hypertrophy on echocardiography, or both. Cox proportional hazards models evaluated treatment interaction with hypertension with high-risk features and estimated hazard ratios within hypertension with high-risk features subgroups. Results Among 945 patients (mean [SD] age, 68.0 [10.8] years; 513 [54.3%] female), 351 (37.1%) met criteria for hypertension with high-risk features. Over a median (IQR) follow-up of 1.6 (0.7-3.0) years within the analytic cohort, 67 patients experienced a recurrent ischemic stroke or systemic embolism. A significant interaction between hypertension with high-risk features and antithrombotic treatment was observed. In 594 patients without hypertension with high-risk features, apixaban was associated with lower risk compared to aspirin (hazard ratio [HR], 0.43; 95% CI, 0.22-0.85; annualized rate difference: −3.4%), whereas no significant association was observed in patients with hypertension with high-risk features (HR, 1.68; 95% CI, 0.78-3.62; annualized rate difference: 2.4%). Conclusions and Relevance The findings in this study indicate that hypertension with high-risk features may be associated with modifications in the effect of antithrombotic treatment in patients with cryptogenic stroke. An unappreciated inclusion of strokes due to hypertensive arteriopathy may account for the lack of benefit with anticoagulation in prior trials of embolic stroke of undetermined source. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT03192215\">NCT03192215</jats:ext-link>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"22 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719987","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}