The Lancet Neurology最新文献

{"title":"Optimised medical therapy alone versus optimised medical therapy plus revascularisation for asymptomatic or low-to-intermediate risk symptomatic carotid stenosis (ECST-2): 2-year interim results of a multicentre randomised trial","authors":"Simone J A Donners, Twan J van Velzen, Suk Fun Cheng, John Gregson, Audinga-Dea Hazewinkel, Francesca B Pizzini, Bart J Emmer, Robert Simister, Toby Richards, Philippe A Lyrer, Marina Maurer, Gemma Smith, Gareth Tervit, Laurine van der Steen, Gwynedd E Pickett, Gordon Gubitz, Bob Roozenbeek, Maaike Scheele, John M Bamford, M Eline Kooi, Leo H Bonati","doi":"10.1016/s1474-4422(25)00107-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00107-3","url":null,"abstract":"<h3>Background</h3>Carotid revascularisation, comprising either carotid endarterectomy or stenting, is offered to patients with carotid stenosis to prevent stroke based on the results of randomised trials conducted more than 30 years ago. Since then, medical therapy for stroke prevention has improved. We aimed to assess whether patients with asymptomatic and symptomatic carotid stenosis with a low or intermediate predicted risk of stroke, who received optimised medical therapy (OMT), would benefit from additional revascularisation.<h3>Methods</h3>The Second European Carotid Surgery Trial (ECST-2) is a multicentre randomised trial with blinded outcome adjudication, which was conducted at 30 centres with stroke and carotid revascularisation expertise in Europe and Canada. Patients aged 18 years or older with asymptomatic or symptomatic carotid stenosis of 50% or greater, and a 5-year predicted risk of ipsilateral stroke of less than 20% (estimated using the Carotid Artery Risk [CAR] score), were recruited. Patients were randomly assigned to either OMT alone or OMT plus revascularisation (1:1) using a web-based system. The primary outcome for this 2-year, interim analysis was a hierarchical outcome composite of: (1) periprocedural death, fatal stroke, or fatal myocardial infarction; (2) non-fatal stroke; (3) non-fatal myocardial infarction; or (4) new silent cerebral infarction on imaging. Analysis was by intention-to-treat using the win ratio—ie, each patient in the OMT alone group was compared as a pair with each patient in the OMT plus revascularisation group, with a win declared for the patient with a better outcome within the pair (a tie was declared if neither patient in the pair had a better outcome). The win ratio was calculated as the number of wins in the OMT alone group divided by the number of wins in the OMT plus revascularisation group. This trial is registered with the ISRCTN Registry (ISRCTN97744893) and is ongoing.<h3>Findings</h3>Between March 1, 2012, and Oct 31, 2019, 429 patients were randomly assigned to OMT alone (n=215) or OMT plus revascularisation (n=214). One patient allocated to OMT alone withdrew consent within 48 h and was not considered further. The median age of patients was 72 years (IQR 65–78); 296 (69%) were male and 133 (31%) female. No benefit was recorded in favour of either treatment group with respect to the primary hierarchical outcome assessed 2 years after randomisation, with 5228 (11·4%) wins for the OMT alone group, 5173 (11·3%) wins for the OMT plus revascularisation group, and 35 395 (77·3%) ties between groups (win ratio 1·01 [95% CI 0·60–1·70]; p=0·97). For OMT alone versus OMT plus revascularisation, four versus three patients had periprocedural death, fatal stroke, or fatal myocardial infarction; 11 versus 16 had non-fatal stroke; seven versus five had non-fatal myocardial infarction; and 12 versus seven had new silent cerebral infarction on imaging. One periprocedural death occurred in the OMT plus","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841045","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":"Rehabilitation drives post-stroke motor recovery","authors":"Teresa J Kimberley, Ela B Plow","doi":"10.1016/s1474-4422(25)00100-0","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00100-0","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713231","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":"Safety and efficacy of transcranial direct current stimulation in addition to constraint-induced movement therapy for post-stroke motor recovery (TRANSPORT2): a phase 2, multicentre, randomised, sham-controlled triple-blind trial","authors":"Gottfried Schlaug, Christy Cassarly, Jody A Feld, Steve L Wolf, Veronica T Rowe, Stacy Fritz, Pratik Y Chhatbar, Anant Shinde, Zemin Su, Joseph P Broderick, Richard Zorowitz, Oluwole Awosika, Dylan Edwards, Chen Lin, Gerard E Franciso, George F Wittenberg, Svetlana Pundik, Christopher Gregory, Michael R Borich, Viswanathan Ramakrishnan, Wuwei Feng","doi":"10.1016/s1474-4422(25)00044-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00044-4","url":null,"abstract":"<h3>Background</h3>Motor impairments contribute substantially to long-term disability following stroke. Studies of transcranial direct current stimulation (tDCS), combined with various rehabilitation therapies, have shown promising results in reducing motor impairment. We aimed to evaluate the safety and efficacy of three doses of tDCS in combination with modified constraint-induced movement therapy (mCIMT) in people who have had their first ischaemic stroke in the preceding 1–6 months.<h3>Methods</h3>We conducted a phase 2, multicentre, randomised, triple-blind, sham-controlled study with a blinded centrally scored primary outcome. The trial was conducted at 15 medical centres in the USA. Eligible participants were enrolled between 1 month and 6 months after their first ischaemic stroke. Inclusion criteria required participants to have a persistent motor deficit, defined as a Fugl–Meyer Upper-Extremity (FM-UE) score of 54 or lower (out of 66), and two consecutive baseline visits (separated by 7–14 days) with an absolute difference of 2 or fewer points on the FM-UE scale. Participants were randomly assigned to treatment groups by an adaptive randomisation algorithm hosted on the TRANSPORT2 WebDCU study website. Participants received either sham, 2 mA, or 4 mA of bi-hemispheric tDCS for the first 30 min and mCIMT with 120 min of active therapy time per session, administered over ten sessions during a 2-week period. The primary endpoint was the change in FM-UE score from baseline to day 15, which was analysed in all participants who have data both at baseline and post-baseline (modified intention-to-treat group). Safety outcomes were analysed in all participants. TRANSPORT2 is registered at <span><span>clinicaltrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT03826030</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and its status is completed.<h3>Findings</h3>129 participants were recruited between Sept 9, 2019, and June 14, 2024, and 43 participants were randomly assigned to each group. 54 (42%) of 129 participants were female, and 69 (53%) were White. Two participants in the sham plus mCIMT group withdrew consent before the day 15 assessment and were excluded from the primary analysis. The median baseline FM-UE score was 39·0 (IQR 30·0–46·0) in the sham plus mCIMT group, 39·0 (27·0–48·0) in the 2 mA plus mCIMT group, and 40·0 (27·0–48·0) in the 4 mA plus mCIMT group. For the primary outcome, the adjusted mean change from baseline to day 15 in FM-UE was 4·91 (3·00–6·82) for sham plus mCIMT, 3·87 (2·00–5·74) for 2 mA plus mCIMT, and 5·53 (3·64–7·42) for 4 mA plus mCIMT (p=0·39). No clinically importan","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713236","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":"Fraud, arrogance, and tragedy: the case of Doctored | Charles Piller, Doctored: fraud, arrogance and tragedy in the quest to cure Alzheimer's disease, Icon Books (2025), p. 352, £20·00, ISBN: 978-1-837-73259-3","authors":"John Hardy","doi":"10.1016/s1474-4422(25)00112-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00112-7","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713232","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":"Correction to Lancet Neurol 2024; 23: 1013–24","authors":"","doi":"10.1016/s1474-4422(25)00108-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00108-5","url":null,"abstract":"<em>Allen JA, Lin J, Basta I, et al. Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial.</em> Lancet Neurol <em>2024;</em> 23: <em>1013–24</em>—In this Article, corrections have been made to definitions of safety populations in tables 1 and 3, the first footnote of table 1, and the indentation of “Atypical CIDP” row of table 1, and the appendix has also been corrected. These corrections have been made to the online version as of March 25, 2025.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703042","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":"Consciousness contextualised | Francisco Aboitiz, A History of Bodies, Brains and Minds: The Evolution of Life and Consciousness, The MIT Press (2024), p. 360, $65.00, ISBN: 978-0-262-04902-3","authors":"Robert Stirrups","doi":"10.1016/s1474-4422(25)00082-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00082-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660925","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":"Augusta Dejerine-Klumpke, a neurologist ahead of her time","authors":"Emmanuel Drouin, Laurent Tatu, Patrick Hautecour","doi":"10.1016/s1474-4422(25)00081-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00081-x","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"183 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660505","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":"Gianfranco De Stefano","authors":"","doi":"10.1016/s1474-4422(25)00080-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00080-8","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660558","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":"SARS-CoV-2 infection in people with multiple sclerosis","authors":"Kathryn C Fitzgerald","doi":"10.1016/s1474-4422(25)00069-9","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00069-9","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660569","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":"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":"&lt;h3&gt;Background&lt;/h3&gt;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.&lt;h3&gt;Methods&lt;/h3&gt;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 &lt;sup&gt;11&lt;/sup&gt;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.&lt;h3&gt;Findings&lt;/h3&gt;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}