The Lancet Neurology最新文献

{"title":"Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer's disease: an open-label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU trial","authors":"Randall J Bateman, Yan Li, Eric M McDade, Jorge J Llibre-Guerra, David B Clifford, Alireza Atri, Susan L Mills, Anna M Santacruz, Guoqiao Wang, Charlene Supnet, Tammie L S Benzinger, Brian A Gordon, Laura Ibanez, Gregory Klein, Monika Baudler, Rachelle S Doody, Paul Delmar, Geoffrey A Kerchner, Tobias Bittner, Jakub Wojtowicz, Peter R Schofield","doi":"10.1016/s1474-4422(25)00024-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00024-9","url":null,"abstract":"<h3>Background</h3>Amyloid plaque removal by monoclonal antibody therapies slows clinical progression in symptomatic Alzheimer's disease; however, the potential for delaying the onset of clinical symptoms in asymptomatic people is unknown. The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) is an ongoing platform trial assessing the safety and efficacy of multiple investigational products in participants with dominantly inherited Alzheimer's disease (DIAD). Based on findings of amyloid removal and downstream biological effects from the gantenerumab group of the platform trial, we continued a 3-year open-label extension (OLE) study to assess the safety and efficacy of long-term treatment with high doses of gantenerumab.<h3>Methods</h3>The randomised, placebo-controlled, double-blind, phase 2/3 multi-arm trial (DIAN-TU-001) assessed solanezumab or gantenerumab versus placebo in participants who were between 15 years before and 10 years after their estimated years to symptom onset and who had a Clinical Dementia Rating (CDR) global score of 0 (cognitively normal) to 1 (mild dementia). This study was followed by an OLE study of gantenerumab treatment, conducted at 18 study sites in Australia, Canada, France, Ireland, Puerto Rico, Spain, the UK, and the USA. For inclusion in the OLE, participants at risk for DIAD had participated in the double-blind period of DIAN-TU-001 and were required to know their mutation status. We investigated increasing doses of subcutaneous gantenerumab up to 1500 mg every 2 weeks. Due to the lack of a regulatory path for gantenerumab, the study was stopped early after a prespecified interim analysis (when most participants had completed 2 years of treatment) of the clinical measure CDR-Sum of Boxes (CDR-SB). The primary outcome for the final analysis was the amyloid plaque measure <sup>11</sup>C-Pittsburgh compound-B positron emission tomography (PiB-PET) standardised uptake value ratio (SUVR [PiB-PET SUVR]) at 3 years, assessed in the modified intention-to-treat group (mITT; defined as participants who received any gantenerumab treatment post-OLE baseline, had at least one PiB-PET SUVR assessment before gantenerumab treatment, and a post-baseline assessment). All participants who received at least one dose of study drug in the OLE were included in the safety analysis. DIAN-TU-001 (NCT01760005) and the OLE (NCT06424236) are registered with ClinicalTrials.gov.<h3>Findings</h3>Of 74 participants who were recruited into the OLE study between June 3, 2020, and April 22, 2021, 73 were enrolled and received gantenerumab treatment. 47 (64%) stopped dosing due to early termination of the study by the sponsor, and 13 (18%) prematurely discontinued the study for other reasons; 13 people completed 3 years of treatment. The mITT group for the primary analysis comprised 55 participants. At the interim analysis, the hazard ratio for clinical decline of CDR-SB in asymptomatic mutation carriers was 0·79 (n=53 [95% CI 0·47 to 1","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple sclerosis and COVID-19: interactions and unresolved issues","authors":"Ana Zabalza, Alan Thompson, Dalia L Rotstein, Amit Bar-Or, Xavier Montalban","doi":"10.1016/s1474-4422(25)00006-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00006-7","url":null,"abstract":"Serious symptomatic SARS-CoV-2 infection and COVID-19 complications are particular concerns for people with multiple sclerosis, especially those receiving immunosuppressants or immunomodulators. Studies have aimed to identify individuals with multiple sclerosis who are at high risk for SARS-CoV-2 infection, to analyse the interplay between SARS-CoV-2 and multiple sclerosis and to evaluate immunological responses to SARS-CoV-2 infection and vaccines. The emergence of evolving dominant SARS-CoV-2 variants, a range of available vaccines, and novel therapeutic approaches requires that clinical neurologists be regularly updated with the latest information. Unresolved issues include optimisation of vaccination strategies to enhance vaccine efficacy and the management of patients who do not show seroconversion post vaccination. Tailored vaccination has the potential to improve patient care, and future studies should focus on evaluating novel therapies and preventive measures while constantly updating our knowledge of potential SARS-CoV-2 variants, in preparation for future outbreaks or pandemics.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombolysis before endovascular treatment of tandem lesions","authors":"Bertrand Lapergue, Benjamin Gory","doi":"10.1016/s1474-4422(25)00084-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00084-5","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid immunotherapy to prevent Alzheimer's disease: the wrong drug at the right time?","authors":"Jonathan M Schott","doi":"10.1016/s1474-4422(25)00066-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00066-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raising awareness of degenerative cervical myelopathy","authors":"Jay John Wardropper, Andreas K Demetriades, David B Anderson","doi":"10.1016/s1474-4422(25)00074-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00074-2","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological therapy for cerebral cavernous malformations","authors":"Rustam Al-Shahi Salman, Michael J Thrippleton","doi":"10.1016/s1474-4422(25)00075-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00075-4","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous thrombolysis before endovascular treatment versus endovascular treatment alone for patients with large vessel occlusion and carotid tandem lesions: individual participant data meta-analysis of six randomised trials","authors":"Fabiano Cavalcante, Kilian Treurniet, Johannes Kaesmacher, Manon Kappelhof, Roman Rohner, Pengfei Yang, Jianmin Liu, Kentaro Suzuki, Bernard Yan, Theodora van Elk, Lei Zhang, Maarten Uyttenboogaart, Wenjie Zi, Derraz Imad, Yongwei Zhang, Papagiannaki Chrysanthi, Hal Rice, Pengfei Xing, Kazumi Kimura, Peter Mitchel, Zifu Li","doi":"10.1016/s1474-4422(25)00045-6","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00045-6","url":null,"abstract":"<h3>Background</h3>For patients with large vessel occlusion and carotid tandem lesions, the best treatment approach is not clear. Intravenous thrombolysis in addition to endovascular treatment might increase the risk of intracranial haemorrhage and decrease effectiveness in this cohort, particularly for patients receiving acute carotid stenting. In an individual participant data meta-analysis of six randomised controlled trials (RCTs), no clear benefit was seen of intravenous thrombolysis in patients with large-vessel occlusion stroke who were eligible for direct endovascular treatment. We aimed to assess whether the presence of carotid tandem lesions would modify the safety and efficacy of intravenous thrombolysis in patients who could directly undergo endovascular treatment, in a prespecified secondary subgroup analysis of this individual participant data meta-analysis.<h3>Methods</h3>We previously did a systematic review and individual participant data meta-analysis of six RCTs comparing intravenous thrombolysis plus endovascular treatment with endovascular treatment alone in patients with anterior circulation stroke presenting directly at centres capable of endovascular treatment. The principal investigators of the six identified trials provided individual participant data for 2313 patients, which we pooled. The primary outcome was functional outcome, as measured by 90-day modified Rankin Scale score. Heterogeneity of treatment effect was assessed in the intention-to-treat population using ordinal regression models, with interaction terms for treatment and carotid tandem lesions, followed by a mixed-effects meta-analysis. A sensitivity analysis included only patients who received acute carotid stenting. The study is registered with PROSPERO, CRD42023411986.<h3>Findings</h3>Of the 2313 patients who were included in the individual patient data meta-analysis, 2267 (98%) had data for carotid tandem lesions, of whom 1136 were assigned intravenous thrombolysis plus endovascular treatment and 1131 were assigned endovascular treatment alone. 340 patients had carotid tandem lesions (161 intravenous thrombolysis plus endovascular treatment, 179 endovascular treatment alone) and 1927 did not have tandem lesions (975 intravenous thrombolysis plus endovascular treatment, 952 endovascular treatment alone). The median age of patients was 71 years (IQR 62–78); 1003 (44·2%) patients were female and 1264 (55·8%) were male. Compared with endovascular treatment alone, the addition of intravenous thrombolysis did not improve functional outcome in patients with tandem lesions (adjusted common odds ratio [acOR] 1·00, 95% CI 0·62–1·62) or in those without tandem lesions (1·17, 0·99–1·37). No significant heterogeneity of treatment effect was observed between patients with tandem lesions and those without (ratio of odds ratios 0·81, 95% CI 0·48–1·37; p<sub><em>interaction</em></sub>=0·44). Intracranial haemorrhage rates in patients with tandem lesions were similar for","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing policies for rare diseases in Europe","authors":"","doi":"10.1016/s1474-4422(25)00079-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00079-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy with myoclonic-atonic seizures: an update on genetic causes, nosological limits, and treatment strategies","authors":"Renzo Guerrini, Ingrid Scheffer, Simona Balestrini","doi":"10.1016/s1474-4422(25)00032-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00032-8","url":null,"abstract":"Epilepsy with myoclonic-atonic seizures is a childhood-onset epilepsy syndrome characterised by a range of seizure types, including myoclonic-atonic, atonic, myoclonic, absence, and generalised tonic-clonic seizures. The causes and outcomes of this syndrome are highly variable, with many uncertainties surrounding its classification and prognosis. Traditional antiseizure medications and the ketogenic diet remain the main treatment options. Although two-thirds of children attain remission from seizures without cognitive or behavioural sequelae, some continue to have drug-resistant seizures, intellectual disability, and behavioural problems. The identification of single-gene causes in a substantial subset of patients highlights the importance of genetic testing for development of personalised treatment strategies. However, diagnostic complexities have hindered the development of trials for new therapies. Better recognition of the distinct features of epilepsy with myoclonic-atonic seizures, combined with advances in molecular genetic testing, will pave the way for more focused clinical research and drug development. Future studies should aim to identify genetic causes and tailor treatment options, offering hope for improved long-term outcomes.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paediatric neurology in Ukraine: a call for help","authors":"Alla Nechai, Oxana Nazar, Kevin Rostasy, Sameer M Zuberi, Dana Craiu, Anna Jansen, Coriene E Catsman-Berrevoets","doi":"10.1016/s1474-4422(25)00083-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00083-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}