Lancet Neurology最新文献

{"title":"Looking beyond the neurological diagnosis: considering frailty.","authors":"A Jon Stoessl","doi":"10.1016/S1474-4422(24)00355-7","DOIUrl":"10.1016/S1474-4422(24)00355-7","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290342","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":"On how a brain beholds beauty.","authors":"Rui Araújo","doi":"10.1016/S1474-4422(24)00285-0","DOIUrl":"10.1016/S1474-4422(24)00285-0","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759585","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 memantine and trazodone versus placebo for motor neuron disease (MND SMART): stage two interim analysis from the first cycle of a phase 3, multiarm, multistage, randomised, adaptive platform trial.","authors":"Suvankar Pal, Jeremy Chataway, Robert Swingler, Malcolm R Macleod, Neil O Carragher, Giles Hardingham, Bhuvaneish Thangaraj Selvaraj, Colin Smith, Charis Wong, Judith Newton, Dawn Lyle, Amy Stenson, Rachel S Dakin, Amarachi Ihenacho, Shuna Colville, Arpan R Mehta, Nigel Stallard, James R Carpenter, Richard A Parker, Catriona Keerie, Christopher J Weir, Bruce Virgo, Stevie Morris, Nicola Waters, Beverley Gray, Donald MacDonald, Euan MacDonald, Mahesh K B Parmar, Siddharthan Chandran","doi":"10.1016/S1474-4422(24)00326-0","DOIUrl":"10.1016/S1474-4422(24)00326-0","url":null,"abstract":"<p><strong>Background: </strong>Motor neuron disease represents a group of progressive and incurable diseases that are characterised by selective loss of motor neurons, resulting in an urgent need for rapid identification of effective disease-modifying therapies. The MND SMART trial aims to test the safety and efficacy of promising interventions efficiently and definitively against a single contemporaneous placebo control group. We now report results of the stage two interim analysis for memantine and trazodone.</p><p><strong>Methods: </strong>MND SMART is an investigator-led, phase 3, double-blind, placebo-controlled, multiarm, multistage, randomised, adaptive platform trial recruiting at 20 hospital centres in the UK. Individuals older than 18 years with a confirmed diagnosis of either amyotrophic lateral sclerosis classified by the revised El Escorial criteria, primary lateral sclerosis, progressive muscular atrophy, or progressive bulbar palsy, regardless of disease duration, were eligible for screening. Participants were randomised (1:1:1) to receive oral trazodone 200 mg once a day, oral memantine 20 mg once a day, or matched placebo using a computer-generated minimisation algorithm delivered via a secure web-based system. Co-primary outcome measures were clinical functioning, measured by rate of change in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R), and survival. Comparisons were conducted in four stages, with predefined criteria for stopping at the end of stages one and two. We report interim analysis from the stage two results, which was done when 100 participants per group (excluding long survivors, defined as >8 years since diagnosis at baseline) completed a minimum of 12 months of follow-up for the candidate investigational medicinal products. The trial is registered on the European Clinical Trials Registry, 2019-000099-41, and ClinicalTrials.gov, NCT04302870, and is ongoing.</p><p><strong>Findings: </strong>Between Feb 27, 2020, and July 24, 2023 (database lock for interim analysis two), 554 people with a motor neuron disease were randomly allocated to memantine (183 [33%]), trazodone (185 [33%]), or placebo (186 [34%]). The primary interim analysis population comprised 530 participants, of whom 175 (33%) had been allocated memantine, 175 (33%) had been allocated trazodone, and 180 (34%) had been allocated placebo. Over 12 months of follow-up, the mean rate of change per month in ALSFRS-R was -0·650 for memantine, -0·625 for trazodone, and -0·655 for placebo (memantine versus placebo estimated mean difference 0·033, one-sided 90% CI lower level -0·085; one-sided p=0·36; trazodone vs placebo: 0·065, -0·051; one-sided p=0·24). The one-sided p values were both above the significance threshold of 10%, indicating that neither memantine nor trazodone groups met the criteria for continuation. There were 483 participants with at least one adverse event (145 [77%] on placebo, 170 [91%] on memantine, and 168 [9","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290344","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":"Evobrutinib in multiple sclerosis: challenges and unmet goals.","authors":"Anneke van der Walt","doi":"10.1016/S1474-4422(24)00391-0","DOIUrl":"10.1016/S1474-4422(24)00391-0","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290339","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 evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials.","authors":"Xavier Montalban, Patrick Vermersch, Douglas L Arnold, Amit Bar-Or, Bruce A C Cree, Anne H Cross, Eva Kubala Havrdova, Ludwig Kappos, Olaf Stuve, Heinz Wiendl, Jerry S Wolinsky, Frank Dahlke, Claire Le Bolay, Li Shen Loo, Sathej Gopalakrishnan, Yann Hyvert, Andrija Javor, Hans Guehring, Nadia Tenenbaum, Davorka Tomic","doi":"10.1016/S1474-4422(24)00328-4","DOIUrl":"10.1016/S1474-4422(24)00328-4","url":null,"abstract":"<p><strong>Background: </strong>Evobrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown preliminary efficacy in people with relapsing multiple sclerosis in a phase 2 trial. Here, we aimed to compare the safety and efficacy of evobrutinib with the active comparator teriflunomide in people with relapsing multiple sclerosis.</p><p><strong>Methods: </strong>EvolutionRMS1 and evolutionRMS2 were two multicentre, randomised, double-blind, double-dummy, active-controlled, phase 3 trials conducted at 701 multiple sclerosis centres and neurology clinics in 52 countries. Adults aged 18-55 years with relapsing multiple sclerosis (Expanded Disability Status Scale [EDSS] score of 0·0-5·5) were included. Participants were randomly assigned (1:1) using a central interactive web response system to receive either evobrutinib (45 mg twice per day with placebo once per day) or teriflunomide (14 mg once per day with placebo twice per day), all taken orally and in an unfasted state, with randomisation stratified by geographical region and baseline EDSS. All study staff and participants were masked to the study interventions. The primary endpoint for each study was annualised relapse rate based on adjudicated qualified relapses up to 156 weeks, assessed in the full analysis set (defined as all randomly assigned participants) with a negative binomial model. These studies are registered with ClinicalTrials.gov (NCT04338022 for evolutionRMS1 and NCT04338061 for evolutionRMS2, both are terminated).</p><p><strong>Findings: </strong>The primary analysis was done using data for 2290 randomly assigned participants collected from June 12, 2020, to Oct 2, 2023. 1124 participants were included in the full analysis set in evolutionRMS1 (560 in the evobrutinib group and 564 in the teriflunomide group) and 1166 in evolutionRMS2 (583 in each group). 751 (66·8%) participants were female and 373 (33·1%) were male in evolutionRMS1, whereas 783 (67·2%) were female and 383 (32·8%) were male in evolutionRMS2. Annualised relapse rate was 0·15 (95% CI 0·12-0·18 with evobrutinib vs 0·14 [0·11-0·18] with teriflunomide (adjusted RR 1·02 [0·75-1·39]; p=0·55) in evolutionRMS1 and 0·11 (0·09-0·13 vs 0·11 [0·09-0·13]; adjusted RR 1·00 [0·74-1·35]; p=0·51) in evolutionRMS2. The pooled proportion of participants with any treatment-emergent adverse event (TEAE) was similar between treatment groups (976 [85·6%] of 1140 with evobrutinib vs 999 [87·2%] of 1146 with teriflunomide). The most frequently reported TEAEs were COVID-19 (223 [19·6%] with evobrutinib vs 223 [19·5%] with teriflunomide), alanine aminotransferase increased (173 [15·2%] vs 204 [17·8%]), aspartate aminotransferase increased (110 [9·6%] vs 131 [11·4%]), and headache (175 [15·4%] vs 176 [15·4%]). Serious TEAE incidence rates were higher with evobrutinib than teriflunomide (86 [7·5%] vs 64 [5·6%]). Liver enzyme elevations at least 5 × upper limit of normal were more common with evobrutinib than with teriflunomide, particularly","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290343","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":"Learning to be an adult with a disability.","authors":"Jules Morgan","doi":"10.1016/S1474-4422(24)00314-4","DOIUrl":"10.1016/S1474-4422(24)00314-4","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290341","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":"Trial designs for motor neuron disease in the 21st century.","authors":"Steve Vucic","doi":"10.1016/S1474-4422(24)00353-3","DOIUrl":"10.1016/S1474-4422(24)00353-3","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290345","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":"Equitable access to levetiracetam for people with epilepsy.","authors":"Arjune Sen, Neerja Chowdhary, Asma Hallab, Michele Romoli, J Helen Cross, Bernadette Cappello","doi":"10.1016/S1474-4422(24)00376-4","DOIUrl":"10.1016/S1474-4422(24)00376-4","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290338","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":"Frailty for neurologists: perspectives on how frailty influences care planning.","authors":"Marco Canevelli, Caitlin Jackson-Tarlton, Kenneth Rockwood","doi":"10.1016/S1474-4422(24)00291-6","DOIUrl":"10.1016/S1474-4422(24)00291-6","url":null,"abstract":"<p><p>The concept of frailty, now being adopted in most medical disciplines, is attracting growing interest in neurology. Every day, most neurologists care for patients with varying degrees of frailty, from very mild to very severe. Frailty exacerbates patients' health needs, complicates clinical decision making, and negatively affects their health outcomes. Increasing evidence suggests that frailty affects the risk, clinical presentation, and course of common age-related neurological disorders, including dementia, Parkinson's disease, stroke, and multiple sclerosis. Most neurologists should become familiar with assessing and measuring frailty. Doing so can provide information that is crucial for diagnosis, prognostication, and care planning. Consideration of frailty can help to elucidate the pathophysiological underpinnings of age-related neurological disorders, clarify the clinical validity and utility of candidate biomarkers, and identify novel therapeutic targets. Randomised controlled trials investigating late-life neurological diseases that address frailty have the potential to provide insight into these complex disorders.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290340","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":"RAB32 mutation in Parkinson's disease.","authors":"Pilar Gómez-Garre, Miguel Martín-Bórnez, Pablo Mir","doi":"10.1016/S1474-4422(24)00325-9","DOIUrl":"10.1016/S1474-4422(24)00325-9","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":null,"pages":null},"PeriodicalIF":46.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290367","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}