The Lancet Neurology最新文献

{"title":"Video games for people with neurological disorders","authors":"Francesco Brigo, Davide Mele, Luigi Lavorgna","doi":"10.1016/s1474-4422(25)00228-5","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00228-5","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645524","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 fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study","authors":"Amit Bar-Or, Michal Dufek, Hrvoje Budincevic, Jelena Drulovic, Mario Habek, Le H Hua, Martin S Weber, Piia Thomas, Julie Napieralski, Maresa Caunt Mitzner, John N Ratchford, David Clayton, Christopher T Harp, Denison Kuruvilla, Qi Qi, Ying-Fang Chen, Yan Xu, Alexandra Goodyear, Jiwon Oh, Kenneth Sharlin","doi":"10.1016/s1474-4422(25)00174-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00174-7","url":null,"abstract":"<h3>Background</h3>The prospect for Bruton's tyrosine kinase (BTK) inhibition to meaningfully affect relapsing multiple sclerosis has recently been questioned due to inconsistent findings in the magnitude and sustainability of the effect of BTK inhibitors on disease activity. We assessed the safety, efficacy, and CSF drug concentrations of fenebrutinib, a highly selective, noncovalent, reversible BTK inhibitor, in patients with relapsing multiple sclerosis.<h3>Methods</h3>This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial (FENopta) was conducted at 18 community centres and hospitals across six countries in Europe and North America. Patients with relapsing multiple sclerosis aged 18–55 years with an Expanded Disability Status Scale (EDSS) score of 0·0–5·5, and recent documented disease activity, were randomly assigned (2:1) to oral fenebrutinib (200 mg twice daily) or placebo for 12 weeks, using permuted blocks and stratified by the presence or absence of T1 gadolinium-enhancing (Gd+) lesions on the brain MRI at screening. The randomisation sequence was generated by an interactive voice or web response system and both patients and investigators were masked to treatment allocation. Participants could enter an optional open-label extension study to receive fenebrutinib for up to 192 weeks. The primary efficacy endpoint was the total number of new T1 Gd+ lesions on brain MRI at weeks 4, 8, and 12; with additional MRI assessments at 48-week intervals during the open-label extension. Efficacy analyses were done on randomised patients with evaluable post-baseline MRIs; safety analyses used the safety-evaluable population. This study is registered with <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>NCT05119569</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 EudraCT, 2021–003772–14; recruitment is closed and the trial is ongoing.<h3>Findings</h3>Between March 1, 2022 and March 29, 2023, 109 patients with relapsing multiple sclerosis were randomly assigned treatment: 73 received fenebrutinib and 36 received placebo. 106 patients had evaluable post-baseline brain MRI scans and were assessed for efficacy in the fenebrutinib group (n=70) and placebo group (n=36). The combined number of new T1 Gd+ lesions at weeks 4, 8, and 12 were 0·077 (95% CI 0·043–0·135) in the fenebrutinib group and 0·245 (0·144–0·418) in the placebo group (69% relative reduction [95% CI 34–85]; p=0·0022). During the open-label extension, through week 48, the unadjusted annualised relapse rate was 0·04 and 95 (96%) of 99 patients were relapse-free. During the double-blind treatment phase, th","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645585","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":"Rethinking neuromodulation in stroke: lessons from TRANSPORT2 – Authors' reply","authors":"Wuwei Feng, Christy Cassarly, George F Wittenberg, Gottfried Schlaug","doi":"10.1016/s1474-4422(25)00229-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00229-7","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645587","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":"Acute-onset axonal neuropathy following infection in children with biallelic RCC1 variants: a case series","authors":"J Robert Harkness, John H McDermott, Shea Marsden, Peter Jamieson, Kay A Metcalfe, Naz Khan, William L Macken, Robert D S Pitceathly, Christopher J Record, Reza Maroofian, Kleopas Kleopa, Kyproula Christodoulou, Ataf Sabir, Lily Islam, Saikat Santra, Enise Avci Durmusalioglu, Tahir Atik, Esra Isik, Ozgur Cogulu, Jill E Urquhart, William G Newman","doi":"10.1016/s1474-4422(25)00198-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00198-x","url":null,"abstract":"<h3>Background</h3>The reasons why some individuals have severe neuropathy following an infection are not known. Through the agnostic screening of children with acute axonal neuropathy after an infection, we identified several families with biallelic variants in <em>RCC1</em>. We aimed to describe the clinical phenotype of these patients, and the molecular and cellular pathology associated with the genetic variants identified in these families.<h3>Methods</h3>For this case series, we identified children affected by a severe, acute-onset axonal neuropathy following infection through an international research consortium of paediatric neurologists and clinical geneticists from nine countries (Canada, Cyprus, Czechia, Germany, Iran, Saudi Arabia, Slovakia, Türkiye, and the UK). Clinical assessments included nerve conduction studies and neuroimaging. We did exome or genome sequencing in DNA samples from all patients. We characterised the proteins encoded by the genetic variants by use of thermal stability and enzymatic assays, using recombinantly expressed proteins. We assessed cellular protein transport under heat or oxidative stress by use of immunofluorescence in primary fibroblasts, obtained from patients. We generated a humanised <em>Drosophila</em> knock-in model to assess the effects of stress on the in vivo function of RCC1.<h3>Findings</h3>Between Nov 2, 2011, and July 10, 2024, we identified 24 individuals from 12 families who had severe, acute-onset axonal neuropathy following infection (13 female and 11 male patients, with a mean age at diagnosis of 1 year 10 months [SD 2·27]). Eight biallelic missense variants in <em>RCC1</em> were identified in affected individuals with autosomal recessive inheritance. Patients had variable phenotypes, ranging from rapidly progressive fatal axonal neuropathy to mild motor neuropathy with impaired walking. Neurological presentation was often secondary to an infection, resulting in initial misdiagnoses of Guillain-Barré syndrome in several patients. 15 children had disease recurrence. The disease was fatal in 15 patients. The <em>RCC1</em> variants in these patients code for proteins that alter GDP-to-GTP exchange activity and have reduced thermal stability in vitro. In primary fibroblasts, heat shock or oxidative stress revealed defects in Ran nuclear localisation and impaired nucleocytoplasmic transport. A <em>Drosophila</em> model of the disease revealed a fatal intolerance to oxidative stress.<h3>Interpretation</h3>We describe an autosomal recessive, acute-onset paediatric axonal neuropathy, seemingly triggered by infection, that affects individuals with biallelic <em>RCC1</em> variants. In these children, the disease can mimic Guillain-Barré syndrome. The pathological mechanisms underlying this novel axonal neuropathy might overlap with those of amyotrophic lateral sclerosis. Cellular studies indicate that <em>RCC1</em> variants affect nucleocytoplasmic transport, which is crucial for healthy axonal f","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645269","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":"Bruton's tyrosine kinase inhibitors for multiple sclerosis","authors":"Laura Airas","doi":"10.1016/s1474-4422(25)00238-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00238-8","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645380","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":"Fiona Baumer","authors":"","doi":"10.1016/s1474-4422(25)00246-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00246-7","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645453","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":"Focused ultrasound therapy for movement disorders","authors":"Raúl Martínez-Fernández, Steffen Paschen, Marta del Álamo, Rafael Rodríguez-Rojas, Jose A Pineda-Pardo, Javier Blesa, Michael G Kaplitt, Günther Deuschl, José A Obeso","doi":"10.1016/s1474-4422(25)00210-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00210-8","url":null,"abstract":"Functional neurosurgery, such as deep brain stimulation, is an established therapeutic option for many patients with movement disorders. MR-guided focused ultrasound has emerged as an incisionless and minimally invasive neurofunctional treatment. This new approach is based on the delivery of high-intensity ultrasound energy to produce therapeutic thermoablation. Several randomised controlled trials have shown safety and symptomatic efficacy of focused ultrasound ablation, particularly to treat patients with essential tremor or Parkinson's disease. The use of focused ultrasound therapy is expanding to many centres worldwide, and its application for other indications—such as tremor of other origin and dystonia—has also been preliminarily investigated. MR-guided focused ultrasound has been explored in the modality of low-intensity ultrasound, which allows mechanical effects on brain tissue, primarily transient blood–brain barrier opening and neuromodulation, both of which could offer a wide array of experimental and clinical possibilities. Therefore, MR-guided focused ultrasound might have an important role in the future treatment of patients with movement disorders and neurodegenerative diseases.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645552","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":"Rethinking neuromodulation in stroke: lessons from TRANSPORT2","authors":"Fernando Zanela da Silva Arêas, Guilherme Peixoto Tinoco Arêas","doi":"10.1016/s1474-4422(25)00230-3","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00230-3","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645522","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 effectiveness of the Walk ‘n Watch structured, progressive exercise protocol delivered by physical therapists for inpatient stroke rehabilitation in Canada: a phase 3, multisite, pragmatic, stepped-wedge, cluster-randomised controlled trial","authors":"Sue Peters, Stanley H Hung, Mark T Bayley, Krista L Best, Louise A Connell, Sarah J Donkers, Sean P Dukelow, Victor E Ezeugwu, Marie-Hélène Milot, Brodie M Sakakibara, Lisa Sheehy, Hubert Wong, Yuwei Yang, Jennifer Yao, Janice J Eng","doi":"10.1016/s1474-4422(25)00201-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00201-7","url":null,"abstract":"<h3>Background</h3>Although clinical guidelines support high repetitions of walking after stroke, practice is slow to change. We undertook an implementation trial to enable entire stroke units to use the Walk ‘n Watch structured, progressive exercise protocol. Our objective was to evaluate the effectiveness of the Walk ‘n Watch implementation package on patient outcomes after 4 weeks in an inpatient stroke rehabilitation setting.<h3>Methods</h3>This pragmatic phase 3, stepped-wedge, cluster-randomised controlled trial took place in 12 sites (inpatient stroke rehabilitation units) across seven Canadian provinces. Each site was randomly allocated (1:1:1:1) to one of four transition sequences with three sites in each sequence. Sites changed practice from usual care to Walk ‘n Watch at different times according to their allocation. All front-line physical therapists were trained to deliver the Walk ‘n Watch protocol. Walk ‘n Watch required completion of a minimum of 30 min of walking-related activities per session, which progressively increased in intensity based on heart rate and step count monitors. Progressions were prescribed on the basis of a screening 6-minute walk test (6MWT) done by the front-line physical therapist as part of the protocol. The primary endpoint was walking endurance (6MWT) at 4 weeks after randomisation. Masked assessors completed evaluations at baseline and 4 weeks later. The primary analysis used a linear mixed-effects model adjusted for unit size, stratum, calendar time, age, sex, and baseline 6MWT. This trial is registered with <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>NCT04238260</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 is complete.<h3>Findings</h3>Between June 4, 2021, and March 1, 2024, we enrolled 12 sites with 314 participants, of whom eight were deemed ineligible after enrolment and 306 were included in the primary analysis (162 in the usual care group, 144 in the Walk ‘n Watch group). Participants had a mean age of 68 years (SD 13), a mean time since stroke of 29 days (17), and a baseline 6MWT of 152 m (106). 188 (61%) were male and 118 (39%) were female. The mean 6MWT in the usual care group was 137·1 m (100·9) at baseline and 223·6 m (130·4) after 4 weeks. The mean 6MWT in the Walk ‘n Watch group was 163·6 m (112·7) at baseline and 297·2 m (133·2) after 4 weeks. The 6MWT improvement was 43·6 m (95% CI 12·7–76·1) greater in the Walk ‘n Watch group than in the usual care group. No serious adverse events occurred during a Walk ‘n Watch session. Nine serious adverse events were reported and required admission to acute care (four were ","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645521","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":"Interpreting the evidence on gantenerumab for dominantly inherited Alzheimer's disease – Authors' reply","authors":"Yan Li, Jorge J Llibre-Guerra, Charlene Supnet, Alireza Atri, Eric M McDade, David B Clifford, Randall J Bateman","doi":"10.1016/s1474-4422(25)00239-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00239-x","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645449","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}