Lancet Neurology最新文献

{"title":"Advancing migraine prevention with comparative evidence.","authors":"Cristina Tassorelli","doi":"10.1016/S1474-4422(26)00279-6","DOIUrl":"10.1016/S1474-4422(26)00279-6","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"790-791"},"PeriodicalIF":54.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579250","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":"Epstein-Barr virus and multiple sclerosis: from associations to mechanisms to potential therapies.","authors":"Jan D Lünemann, Christian Münz","doi":"10.1016/S1474-4422(26)00177-8","DOIUrl":"10.1016/S1474-4422(26)00177-8","url":null,"abstract":"<p><strong>Background: </strong>Epstein-Barr virus, a widespread herpesvirus that establishes lifelong latency after primary infection, has emerged in serological and epidemiological studies as a strong and consistent risk factor for multiple sclerosis.</p><p><strong>Recent developments: </strong>Emerging evidence indicates that Epstein-Barr virus can interact with several multiple sclerosis susceptibility loci to modify the transcriptional programmes and differentiation trajectories of B cells. Specifically, Epstein-Barr virus infection has been associated with the expansion of neuroinvasive, atypical B cells, which are enriched in inflamed CNS compartments in people with multiple sclerosis and exhibit a strong capacity to stimulate autoreactive T cells. Dysregulation of Epstein-Barr virus latency by B cells, together with subtle deficiencies in T-cell-mediated control of Epstein-Barr virus, might further amplify the effect of these B cell-T cell interactions and predispose individuals to multiple sclerosis. WHERE NEXT?: These insights support the development of hypothesis-driven therapeutic strategies aimed at attenuating hyperactive autoimmune responses induced by Epstein-Barr virus and the autoimmune responses' access to the CNS. Strategies under investigation include prophylactic and therapeutic vaccines; allogeneic cytotoxic T lymphocytes specific for Epstein-Barr virus and designed to eliminate virus-infected cells; antibody-based and chimeric antigen receptor T-cell-based therapies targeting B-cell subsets induced by Epstein-Barr virus and migrate into the CNS; and conventional antiviral treatments. Together, these approaches might open new perspectives for both prevention and treatment of multiple sclerosis. Furthermore, they might help to clarify whether Epstein-Barr virus infection influences not only susceptibility to multiple sclerosis, but also disease activity and disability accrual after disease onset.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"755-763"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283967","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":"UCL Queen Square Institute of Neurology: 75 years of innovation.","authors":"Dimitri M Kullmann, Martina F Callaghan, Olga Ciccarelli, Nicholas Fox, Gabriele Lignani, Mary M Reilly, Robert D S Pitceathly, Anthony H V Schapira, David J Werring, Simon Shorvon, Michael G Hanna","doi":"10.1016/S1474-4422(26)00245-0","DOIUrl":"10.1016/S1474-4422(26)00245-0","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"716-717"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368856","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":"Parkinson's disease genetics across diverse ancestries: an observational genetic study of causal and risk variants with translational implications.","authors":"Lara M Lange, Zih-Hua Fang, Mary B Makarious, Nicole Kuznetsov, Kajsa Atterling Brolin, Shannon Ballard, Soraya Bardien, Maria Leila Doquenia, Peter Heutink, Henry Houlden, Hirotaka Iwaki, Simona Jasaityte, Lietsel Jones, Johanna Junker, Rauan Kaiyrzhanov, Mathew J Koretsky, Kishore R Kumar, Hampton L Leonard, Kristin S Levine, Shen-Yang Lim, Niccoló E Mencacci, Wael M Y Mohamed, Mike A Nalls, Alastair J Noyce, Rajeev Ojha, Njideka U Okubadejo, Shoaib Ur Rehman, Laurel Screven, Chingiz Shashkin, Sophia Sopromadze, Eleanor J Stafford, Ai Huey Tan, Manuela Tan, Zaruhi Tavadyan, Joanne Trinh, Bayasgalan Tserensodnom, Enza Maria Valente, Dan Vitale, Nazira Zharkinbekova, Katja Lohmann, Sara Bandres-Ciga, Cornelis Blauwendraat, Andrew B Singleton, Huw R Morris, Christine Klein","doi":"10.1016/S1474-4422(26)00198-5","DOIUrl":"10.1016/S1474-4422(26)00198-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The genetic architecture of Parkinson's disease varies considerably across ancestries, yet most previous genetic studies have focused on individuals of European ancestry. We aimed to characterise the distribution of established Parkinson's disease causal variants, as well as risk-associated variants with clinical implications (ie, variants in genes involved in pathways targeted by ongoing clinical trials), across ancestrally diverse populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a multi-ancestry, observational, cross-sectional genetic study using retrospective data from the Global Parkinson's Genetics Program (GP2) release 11 (released in December, 2025). The study investigated causal and risk variants, including copy number variants, in established Parkinson's disease and parkinsonism-associated genes, following the recommendations of the Movement Disorder Society (MDS) Task Force on the Nomenclature of Genetic Movement Disorders, including GBA1, LRRK2, SNCA, VPS35, RAB32, PINK1, PRKN, PARK7, ATP13A2, DCTN1, DNAJC6, FBXO7, JAM2, RAB39B, SLC20A2, SYNJ1, VPS13C, and WDR45. Individuals with Parkinson's disease were diagnosed based on established clinical criteria, including the Parkinson's UK Brain Bank or MDS diagnostic criteria (or both), and healthy control participants were defined as individuals without evidence of neurodegenerative disease and unrelated to participants with Parkinson's disease. We analysed genome and exome sequencing and array genotyping data of 99 783 individuals, including 58 559 individuals with Parkinson's disease and 41 224 controls, from 11 genetically inferred ancestries (African, African admixed, Ashkenazi Jewish, Latino and Indigenous people of the Americas, central Asian, complex admixture, east Asian, European, Finnish, Middle Eastern, and south Asian), defined using reference population-based ancestry inference methods. We calculated allele frequencies for all investigated variants in individuals with Parkinson's disease and controls, both overall and stratified by ancestry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Approximately 29% of individuals (29 001 of 99 783; 15 443 [26·4%] of 58 559 individuals with Parkinson's disease and 13 558 [32·9%] of 41 224 controls) were from under-represented populations (ie, non-European and non-Ashkenazi Jewish). Our findings indicated both shared genetic contributors across ancestries as well as ancestry-specific differences in variant frequencies and the spectrum of variants within Parkinson's disease-associated genes. Overall, 1217 (2·1%) of 58 559 individuals with Parkinson's disease carried a causal variant, with substantial variations across ancestries ranging from ten (0·4%) of 2844 African individuals to 251 (10·7%) of 2343 individuals of Ashkenazi Jewish ancestry. Risk variants in GBA1 and LRRK2 were identified in 6893 (11·8%) of 58 559 individuals with Parkinson's disease and 3578 (8·7%) of 41 224 controls. GBA1 risk variants were mos","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 8","pages":"741-754"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456160","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 Lancet Neurol 2026; 25: 631.","authors":"","doi":"10.1016/S1474-4422(26)00236-X","DOIUrl":"10.1016/S1474-4422(26)00236-X","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":"e13"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302383","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":"Survival estimates and their predictors in genetic frontotemporal dementia: an international, retrospective, cohort study.","authors":"Arabella Bouzigues, Mario Grassi, Valentina Cantoni, Enrico Premi, Sonia Bellini, Giuliano Binetti, Giancarlo Logroscino, Lucy L Russell, Eve Ferry-Bolder, Phoebe H Foster, John C van Swieten, Lize C Jiskoot, Harro Seelaar, Raquel Sanchez-Valle, Robert Laforce, Caroline Graff, Daniela Galimberti, Rik Vandenberghe, Alexandre de Mendonça, Giuseppe Di Fede, Isabel Santana, Alexander Gerhard, Tobias Langheinrich, Johannes Levin, Benedetta Nacmias, Markus Otto, Maxime Bertoux, Thibaud Lebouvier, Simon Ducharme, Christopher Butler, Isabelle le Ber, Rose Bruffaerts, Eino Solje, Mika Kinnunen, Johanna Krüger, Elizabeth Finger, Maria Carmela Tartaglia, Mario Masellis, James B Rowe, Matthis Synofzik, Fermin Moreno, Roberta Ghidoni, Raffaella Migliaccio, Jonathan D Rohrer, Barbara Borroni","doi":"10.1016/S1474-4422(26)00197-3","DOIUrl":"10.1016/S1474-4422(26)00197-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;What drives the heterogeneity of survival estimates in genetic frontotemporal dementia is unknown. We sought to understand the natural history and predictors of disease trajectory, which are crucial not only for effective care but also for the design of therapeutic clinical trials and efficacy evaluation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this international, cohort study, we used the Kaplan-Meier method to retrospectively assess survival estimates in patients enrolled in the GENFI cohort, which included 32 research sites located in Belgium, Canada, Finland, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and the UK, and comprised participants carrying a causal C9orf72 expansion or a causal mutation in GRN or MAPT genes. Survival was calculated as the time from symptom onset to time of death or censoring date; median survival estimate for all patients was the primary endpoint. Cox proportional hazards models were used to identify predictors of survival, which were subsequently externally validated in an independent cohort. We further designed a structural equation model to assess the relationships between predictors, applying a least absolute shrinkage and selection operator method.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Of 278 participants of the GENFI cohort included in this study, 160 (58%) were men and 118 (42%) were women. 162 died during follow-up (58%) and 116 were still alive (42%) on June 1, 2024, the chosen censoring date. 138 participants carried a C9orf72 expansion, 94 carried a GRN mutation, and 46 a MAPT mutation. 179 participants were diagnosed with behavioural variant frontotemporal dementia, 46 with primary progressive aphasia, and 31 with frontotemporal dementia-amyotrophic lateral sclerosis. 22 participants had other diagnoses. The median survival estimate for all patients with genetic frontotemporal dementia was 6·94 years (95% CI 6·59-7·80) from symptom onset. The median survival estimate for patients with GRN mutations was 6·63 years (6·08-7·98), for patients with a C9orf72 expansion was 7·04 years (6·45-8·77), and for patients with MAPT mutations was 8·56 years (7·06-13·50). Older age at onset, shorter disease duration from onset to enrolment in the GENFI study, clinical presentation (ie, frontotemporal dementia-amyotrophic lateral sclerosis), domain of first symptom (ie, motor or language onset), and geographical area of residency (ie, central and southern Europe) were associated with poorer prognosis. Genetic group did not directly affect survival estimates; rather its effect was mediated by age at onset and clinical phenotype. We computed a genetic frontotemporal dementia survival risk index, which can be used at an individual patient level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;Our results highlight that motor impairment in addition to cognitive and behavioural symptoms should be considered when estimating prognosis in genetic frontotemporal dementia. Individual risk scores m","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 8","pages":"731-740"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456186","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":"Safety, tolerability, and efficacy of flexible-dose tavapadon for Parkinson's disease (TEMPO-2): a phase 3, randomised, placebo-controlled, double-blind trial.","authors":"Hubert H Fernandez, Perminder Bhatia, Leslie Cloud, Urban M Fietzek, Michele Matarazzo, Eric Molho, Elizabeth Peckham, Arjun Tarakad, Cari Combs, Matthew Leoni, Ih Chang, Stacey Tringali, Joey Boiser, Raymond Sanchez, Cindy Zadikoff","doi":"10.1016/S1474-4422(26)00215-2","DOIUrl":"10.1016/S1474-4422(26)00215-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Current dopaminergic therapies for Parkinson's disease carry significant limitations: levodopa can cause long-term motor complications, while D2/D3 receptor-targeting dopamine agonists can produce non-motor adverse effects. Tavapadon is an oral, once-daily, selective D1/D5 agonist that might improve Parkinson's disease motor symptoms. We aimed to evaluate the safety, tolerability and efficacy of flexible-dose tavapadon in people with early-stage Parkinson's disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;TEMPO-2 was a phase 3, randomised, double-blind, placebo-controlled trial conducted at 75 clinical sites (both hospital or academic and community settings) across 13 countries. Adults aged 40-80 years with early-stage Parkinson's disease (&lt;3 years' disease duration) who were treatment-naive or had less than 3 months of previous dopaminergic treatment were eligible. Participants were randomly assigned 1:1 to flexible-dose tavapadon (5-15 mg) or placebo orally once daily for 27 weeks. The primary endpoint was change from baseline to week 26 in the combined score of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III (reflecting activities of daily living and motor performance). Safety endpoints included adverse events, clinical laboratory values, vital signs, and electrocardiograms. The primary endpoint was assessed in the modified intent-to-treat population (participants who received one dose or more of study drug and had both a baseline and one or more post-baseline MDS-UPDRS assessments) and safety was assessed in the safety analysis set (all participants who received one dose or more of tavapadon or placebo). This study is registered with ClinicalTrials.gov (NCT04223193) and is now complete.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Jan 6, 2020, and Feb 22, 2024, 473 individuals were screened and 304 were randomly assigned to receive tavapadon 5-15 mg (n=151) or placebo (n=153). The majority of participants were male (169 [56%] of 304 male; 135 [44%] of 304 female), the mean age was 62·9 (SD 9·2) years, and the mean disease duration was 0·86 (0·79) years. 80 (26%) of 304 participants discontinued from the trial (57 [38%] of 151 on tavapadon and 23 [15%] of 153 on placebo), most commonly due to adverse events (42 [14%] of 304; 36 [24%] of 151 on tavapadon and six [4%] of 153 on placebo). The primary endpoint of change from baseline to week 26 in the MDS-UPDRS Parts II and III combined score was significantly improved with tavapadon versus placebo (least squares mean [LSM] decrease of 10·3 [95% CI -12·2 to -8·3] points vs 1·2 [-2·9 to 0·6] points; LSM treatment difference -9·1 [95% CI -11·7 to -6·5]; p&lt;0·0001). Most adverse events were non-serious and mild to moderate in severity. More adverse events were observed with tavapadon than with placebo (115 [76%] of 151 participants vs 84 [55%] of 153 participants). The incidence of adverse events in the tavapadon group was higher ","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 8","pages":"721-730"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456139","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":"Deep brain stimulation for the treatment of patients with dystonia: advances towards network-based personalised care.","authors":"Anna Latorre, Kathryn J Peall, Andreas Horn, Antonio Pisani, Emmanuel Roze, Marie Vidailhet","doi":"10.1016/S1474-4422(26)00192-4","DOIUrl":"10.1016/S1474-4422(26)00192-4","url":null,"abstract":"<p><p>Dystonia is a complex movement disorder that can cause functional disability and reduce quality of life. Deep brain stimulation (DBS) provides meaningful benefits in patients with medically refractory dystonia, but clinical outcomes can vary substantially. This variability likely reflects the heterogeneity in clinical presentations, genetic background, and brain networks involved in motor control. Dystonia is a network disorder involving abnormal interactions across cortico-basal ganglia-cerebellar circuits. Therapeutic effects of DBS therefore arise from modulation of distributed motor circuits rather than a single anatomical target. Advances in non-invasive neurophysiological techniques, intraoperative recordings, and connectome-based neuroimaging have provided new insights into how DBS modulates these pathological networks. Individual response to DBS and long-term outcomes are shaped by the interaction between clinical and genetic factors, neurophysiological abnormalities, and distributed network connectivity. Combining these variables can help refine patient selection for clinical studies and support individualised neuromodulation strategies.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 8","pages":"781-788"},"PeriodicalIF":54.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456191","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":"Balancing awareness and empathy in Tourette's syndrome.","authors":"Robert Stirrups","doi":"10.1016/S1474-4422(26)00211-5","DOIUrl":"10.1016/S1474-4422(26)00211-5","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 7","pages":"632"},"PeriodicalIF":54.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272041","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":"Safety and efficacy of decompressive craniectomy versus standard craniotomy for large acute epidural haematoma with tentorial herniation in China (PREDICT-AEDH): a nationwide, multicentre, open-label, parallel-group, randomised controlled trial.","authors":"Junfeng Feng, Chun Yang, Li Xie, Dan Jin, Qiuhua Jiang, Yuhai Wang, Chunlong Zhong, Xianjian Huang, Qinghua Wang, Jie Mao, Yu Song, Yijun Bao, Jianrong Huang, Liansheng Long, Dong Luo, Yun Zhen, Li Zhang, Qiang Yun, Richu Liang, Jun Jia, Wanli Zhao, Xuezheng Fan, Jinxian Pan, Li Bie, Jinlong Liu, Yongming Zhang, Huachao Hao, Weitai Tang, Jingli Zhang, Zhiwei Wang, Wenhua Fang, Likun Yang, Zhenghui He, Min Liu, Jiyao Jiang","doi":"10.1016/S1474-4422(26)00143-2","DOIUrl":"10.1016/S1474-4422(26)00143-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Decompressive craniectomy has been widely evaluated across heterogeneous types of brain injury but its effect in patients with large acute epidural haematoma complicated by tentorial herniation remains unclear. We aimed to assess whether decompressive craniectomy improves functional and safety outcomes compared with standard craniotomy in this patient group.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The Prospective Randomised Evaluation of Decompressive Ipsilateral Craniectomy for Traumatic Acute Epidural Haematoma (PREDICT-AEDH) trial was a nationwide, multicentre, open-label, parallel-group, randomised controlled trial conducted at 28 hospitals in China. Adults aged 18-65 years with clinical signs of transtentorial herniation, CT-confirmed large acute epidural haematoma, and obliterated ambient cistern within 12 h of injury were randomly assigned (1:1) to primary decompressive craniectomy or standard craniotomy with bone-flap replacement, using a secure, central, web-based randomisation system with block sizes of four. Although masking of patients and surgeons was not feasible, all assessments and analyses were done by masked investigators. The primary outcome was functional status at 6 months in all randomised patients according to intention to treat (ITT), assessed using the Glasgow Outcome Scale-Extended (GOSE) and analysed with a proportional-odds model. No imputation for missing outcome data was done since no participants were lost to follow-up. Safety outcomes were assessed in the ITT population. The trial is registered with ClinicalTrials.gov (NCT04261673) and is complete.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Sept 7, 2020, and March 14, 2025, 142 patients were screened for eligibility, of whom 120 patients (15 [12%] females and 105 [88%] males) were randomly assigned to decompressive craniectomy (n=58) or standard craniotomy (n=62). One patient assigned to the decompressive craniectomy group received craniotomy and ten patients assigned to craniotomy received decompressive craniectomy. At 6 months, a favourable functional outcome (GOSE ≥5) occurred in 46 (79%) of 58 patients assigned to decompressive craniectomy and 52 (84%) of 62 patients assigned to standard craniotomy. Ordinal analysis of GOSE failed to show a significant difference between groups (common OR 0·79 [0·41-1·58]; p=0·51). Rates were similar between the decompressive craniectomy and standard craniotomy groups for 30-day mortality (five [9%] of 58 patients vs three [5%] of 62 patients) and postoperative cerebral infarction (11 [19%] vs 11 [18%]). Delayed intracranial haemorrhage occurred more frequently after decompressive craniectomy (21 [36%] of 58 patients) than after standard craniotomy (eight [13%] of 62 patients; OR 3·79, 95% CI 1·43-11·00; p=0·0049).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interpretation: &lt;/strong&gt;In patients with large acute epidural haematoma and tentorial herniation, decompressive craniectomy did not improve 6-month functional outcomes compared wi","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 7","pages":"645-653"},"PeriodicalIF":54.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272145","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}