Lancet Neurology最新文献

{"title":"Optimising blood pressure control after stroke: established wisdom and new frontiers.","authors":"Sonali R Gnanenthiran, Lili Song, Anthony Rodgers, Craig S Anderson","doi":"10.1016/S1474-4422(26)00075-X","DOIUrl":"10.1016/S1474-4422(26)00075-X","url":null,"abstract":"<p><p>High blood pressure is the main modifiable risk factor for preventing cardiovascular events in people who have had a stroke or transient ischaemic attack; however, only approximately one in three people who have had a stroke have adequate blood pressure control, which highlights the need for a change to conventional models of care. New priorities include the broader adoption of combination antihypertensive therapy to maintain systolic blood pressure below 130 mm Hg, with an emphasis on simplified regimens and single pill combinations. Integrated multidisciplinary models of care, coupled with scalable community-based strategies, are essential to overcome therapeutic inertia and fragmentation. Digital health technologies, remote monitoring, potassium-enriched low-sodium salt substitutes, and novel pharmacological agents offer other opportunities to improve preventative care. Effective blood pressure control is a collective imperative to reduce the global burden of stroke and improve long-term outcomes in people with cerebrovascular disease.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 5","pages":"506-518"},"PeriodicalIF":45.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729252","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":"A step towards disease-modifying therapy for multiple system atrophy.","authors":"Maria Teresa Pellecchia","doi":"10.1016/S1474-4422(26)00165-1","DOIUrl":"https://doi.org/10.1016/S1474-4422(26)00165-1","url":null,"abstract":"","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":""},"PeriodicalIF":45.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775479","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 the anti-α-synuclein monoclonal antibody amlenetug for the treatment of patients with multiple system atrophy (AMULET): a phase 2, randomised, double-blind, multicentre trial.","authors":"Lotte Kjærsgaard, Jonas Wiedemann, Wolfgang Singer, Atsushi Takeda, Anna-Karin Berger, Mimi Folden Flensburg, Lene Hansen, Pekka Kallunki, Kristiina Kompus, Krishan Nighah, Simon Nitschky Schmidt, Mette Nørbæk Jørgensen, Bodil Svanholm Fogh, Stefano Zanigni, Johan Luthman","doi":"10.1016/S1474-4422(26)00100-6","DOIUrl":"https://doi.org/10.1016/S1474-4422(26)00100-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Pathological aggregation and propagation of α-synuclein species drive disease progression in multiple system atrophy (MSA). We assessed the efficacy and safety of amlenetug, a monoclonal antibody targeting aggregated α‑synuclein, versus placebo in slowing clinical disease progression in people with MSA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We did a randomised, controlled, parallel-group trial (AMULET) at 18 movement disorder and autonomic dysfunction specialist sites across the USA and Japan. Patients aged 40-75 years with MSA who had motor symptom onset in the past 5 years were randomly assigned (2:1) to intravenous amlenetug or placebo every 4 weeks for 48-72 weeks in a common close design. Randomisation was performed via an interactive response system, stratified by region and blood neurofilament light chain concentration, using a block size of three. The double-blind treatment period ended when the last randomised participant had concluded the week 48 visit. Participants, study partners, treating investigators, study site personnel, and the sponsor were masked to treatment allocation. The primary endpoint was disease progression, assessed using a Bayesian progression model of the longitudinal changes from baseline in the Unified Multiple System Atrophy Rating Scale (UMSARS) total (parts I and II) score up to week 72, in all participants who had a valid baseline assessment and at least one valid post-baseline assessment of UMSARS total score. Safety was assessed in all treated participants. This trial is registered at ClinicalTrials.gov (NCT05104476); the open-label phase of the trial is ongoing.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;Between Nov 16, 2021, and Oct 6, 2022, 91 unique participants were screened, of whom 64 were randomly assigned and 61 received treatment (amlenetug n=40; placebo n=21). Among treated participants, mean age was 60·8 years (SD 7·7); 32 (52%) were male and 29 (48%) female. 48 (79%) of 61 participants completed double-blind treatment (mean 56 weeks [SD 13] treatment). The Bayesian probability of 89·4% for a true slowing of clinical disease progression did not reach the predefined threshold of 97·5%, and accordingly, the primary endpoint was not met. The effect parameter of 0·81 (2·5th to 97·5th percentile 0·56 to 1·13) equates to a non-significant slowing of clinical progression by 19% (2·5th to 97·5th percentile -13 to 44) for amlenetug versus placebo. Amlenetug was generally well tolerated, with comparable rates of treatment‑emergent adverse events (n=40 [100%] with amlenetug vs n=20 [95%] with placebo) and serious treatment‑emergent adverse events (n=12 [30%] vs n=7 [33%]). The most common treatment-emergent adverse events were COVID‑19 infection (n=11 [28%] vs n=5 [24%]), back pain (n=6 [15%] vs n=2 [10%]), headache (n=5 [13%] vs n=1 [5%]), urinary tract infection (n=4 [10%] vs n=3 [14%]), peripheral oedema ([n=4] 10% vs n=1 [5%]), flushing (n=4 [10%] vs 0), and hypertension (n=4 [10%] vs 0).","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":" ","pages":""},"PeriodicalIF":45.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775453","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":"Advances in migraine prevention.","authors":"Daniele Martinelli, Roberto De Icco, Haidar M Al-Khazali, Sait Ashina, Hans-Christoph Diener, Freda Dodd-Glover, Maria Teresa Goicochea, Bronwyn Jenkins, Antoinette MaassenVanDenBrink, Mi Ji Lee, Aynur Özge, Mario Fernando Prieto Peres, Patricia Pozo-Rosich, Francesca Puledda, Simona Sacco, Todd Schwedt, Gisela M Terwindt, Cristina Tassorelli","doi":"10.1016/S1474-4422(25)00477-6","DOIUrl":"10.1016/S1474-4422(25)00477-6","url":null,"abstract":"<p><p>Migraine imposes a heavy burden on patients and societies. Preventive treatments aimed at reducing the occurrence of migraine attacks and their intensity have been largely underused, leaving a multitude of people with migraine to rely exclusively on acute treatments, which, when used in excess, might even worsen the clinical situation. Large, randomised trials have established the tolerability and efficacy of calcitonin gene-related peptide (CGRP)-targeting drugs, a new class of migraine-specific treatment. The increased adherence to longer treatment cycles with migraine-specific preventive drugs, such as CGRP-targeting therapies, compared with non-migraine specific treatments has the potential to improve control of the disease. These migraine-specific drugs also provide benefits to individuals with migraine who previously did not benefit from non-specific migraine preventive medications. Increased reliance on preventive treatment with migraine-specific options is progressively optimising the management of migraine for mounting numbers of patients disabled by the disease, thereby improving disease control and their quality of life.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 3","pages":"279-293"},"PeriodicalIF":45.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776732","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":"Current evidence and knowledge gaps in family planning and pregnancy in myasthenia gravis, NMOSD, and MOGAD.","authors":"Dalia L Rotstein, Raed Alroughani, Georgina Arrambide, Edgar Carnero Contentti, Mashina Chomba, Kazuo Fujihara, Nils E Gilhus, Riadh Gouider, Jeannine M Heckmann, Ho Jin Kim, Hai-Feng Li, Maria Isabel Leite, Mastura Monif, Sasitorn Siritho, Sandra Thiel, Anastasia Vishnevetsky, Shanthi Viswanathan, Sandra Vukusic, Bassem Yamout, Tania Kümpfel, Kerstin Hellwig","doi":"10.1016/S1474-4422(25)00479-X","DOIUrl":"10.1016/S1474-4422(25)00479-X","url":null,"abstract":"<p><p>Myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated neuroimmune disorders that frequently affect women in their reproductive years and require careful treatment planning around pregnancy. Disease exacerbations (for myasthenia gravis) and attacks (for NMOSD and MOGAD) can occur during pregnancy, are common postpartum, and can cause preventable, long-term maternal disability. Many drug labels are conservative or recommend unnecessary prolonged washouts or avoidance of breastfeeding, creating uncertainty for physicians and patients. This Personal View integrates available evidence on conventional immunosuppressants and biological therapies, including complement inhibition, B-cell depletion, and neonatal Fc receptor blockade. Although data on pregnancy safety for newer treatments are few, preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding. We offer expert recommendations for therapy choice, infant vaccinations, and fetal and infant monitoring in myasthenia gravis, NMOSD, and MOGAD.</p>","PeriodicalId":17989,"journal":{"name":"Lancet Neurology","volume":"25 3","pages":"308-324"},"PeriodicalIF":45.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776740","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":" ","pages":"1085"},"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":"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":" ","pages":"1072-1073"},"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":"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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 &gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;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":" ","pages":"1097-1107"},"PeriodicalIF":45.5,"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":" ","pages":"1068-1070"},"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Findings: &lt;/strong&gt;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":" ","pages":"1119-1132"},"PeriodicalIF":45.5,"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}