The Lancet Neurology最新文献

{"title":"Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy","authors":"Rubika Balendra, Jemeen Sreedharan, Martina Hallegger, Raphaëlle Luisier, Hilal A Lashuel, Jenna M Gregory, Rickie Patani","doi":"10.1016/s1474-4422(25)00109-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00109-7","url":null,"abstract":"Mutations in the <em>TARDBP</em> gene, which encodes the TDP-43 protein, account for only 3–5% of familial cases of amyotrophic lateral sclerosis and less than 1% of cases that are apparently idiopathic. However, the discovery of neuronal inclusions of TDP-43 as the neuropathological hallmark in the majority of cases of amyotrophic lateral sclerosis has transformed our understanding of the pathomechanisms underlying neurodegeneration. An individual <em>TARDBP</em> mutation can cause phenotypic heterogeneity. Most mutations lie within the C-terminus of the TDP-43 protein. In pathological conditions, TDP-43 is mislocalised from the nucleus to the cytoplasm, where it can be phosphorylated, cleaved, and form insoluble aggregates. This mislocalisation leads to dysfunction of downstream pathways of RNA metabolism, proteostasis, mitochondrial function, oxidative stress, axonal transport, and local translation. Biomarkers for TDP-43 dysfunction and targeted therapies are being developed, justifying cautious optimism for personalised medicine approaches that could rescue the downstream effects of TDP-43 pathology.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841354","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":"Margaret Pericak-Vance: a force of nature in human genetics","authors":"Jules Morgan","doi":"10.1016/s1474-4422(25)00119-x","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00119-x","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841010","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":"Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis","authors":"Nadia Soliman, Xavier Moisset, Michael C Ferraro, Daniel Ciampi de Andrade, Ralf Baron, Joletta Belton, David L H Bennett, Margarita Calvo, Patrick Dougherty, Ian Gilron, Aki J Hietaharju, Koichi Hosomi, Peter R Kamerman, Harriet Kemp, Elena K Enax-Krumova, Ewan McNicol, Theodore J Price, Srinivasa N Raja, Andrew S C Rice, Blair H Smith, Mohammad D Zunaid","doi":"10.1016/s1474-4422(25)00068-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00068-7","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;There remains a substantial unmet need for effective and safe treatments for neuropathic pain. The Neuropathic Pain Special Interest Group aimed to update treatment recommendations, published in 2015, on the basis of new evidence from randomised controlled trials, emerging neuromodulation techniques, and advances in evidence synthesis.&lt;h3&gt;Methods&lt;/h3&gt;For this systematic review and meta-analysis, we searched Embase, PubMed, the International Clinical Trials Registry, and &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt; from data inception for neuromodulation trials and from Jan 1, 2013, for pharmacological interventions until Feb 12, 2024. We included double-blind, randomised, placebo-controlled trials that evaluated pharmacological and neuromodulation treatments administered for at least 3 weeks, or if there was at least 3 weeks of follow-up, and which included at least ten participants per group. Trials included participants of any age with neuropathic pain, defined by the International Association for the Study of Pain. We excluded trials with enriched enrolment randomised withdrawal designs and those with participants with mixed aetiologies (ie, neuropathic and non-neuropathic pain) and conditions such as complex regional pain syndrome, low back pain without radicular pain, fibromyalgia, and idiopathic orofacial pain. We extracted summary data in duplicate from published reports, with discrepancies reconciled by a third independent reviewer on the platform Covidence. The primary efficacy outcome was the proportion of responders (50% or 30% reduction in baseline pain intensity or moderate pain relief). The primary safety outcome was the number of participants who withdrew from the treatment owing to adverse events. We calculated a risk difference for each comparison and did a random-effects meta-analysis. Risk differences were used to calculate the number needed to treat (NNT) and the number needed to harm (NNH) for each treatment. Risk of bias was assessed by use of the Cochrane risk of bias tool 2 and certainty of evidence assessed by use of GRADE. Recommendations were based on evidence of efficacy, adverse events, accessibility, and cost, and feedback from engaged lived experience partners. This study is registered on PROSPERO, CRD42023389375.&lt;h3&gt;Findings&lt;/h3&gt;We identified 313 trials (284 pharmacological and 29 neuromodulation studies) for inclusion in the meta-analysis. Across all studies, 48 789 adult participants were randomly assigned to trial groups (20 611 female and 25 078 male participants, where sex was reported). Estimates for the primary efficacy and safety outcomes were tricyclic antidepressants (TCAs) NNT=4·6 (95% CI 3·2–7·7), NNH=17·1 (11·4–33·6; moderate certainty of evidence), α2δ-ligands NNT=8·9 (7·4–11·10), NNH=26·","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841047","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":"Biological effects of pathologies in Lewy body diseases: why timing matters","authors":"Elie Matar, Glenda M Halliday","doi":"10.1016/s1474-4422(25)00085-7","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00085-7","url":null,"abstract":"The emergence of promising biomarkers of α-synuclein Lewy pathology has led to new biological definitions and staging systems for Parkinson's disease and dementia with Lewy bodies. These research frameworks aim to enhance patient selection for studies of biomarkers and disease-modifying therapies. Building on approaches developed for Alzheimer's disease, these new frameworks focus on hallmark neuropathological findings in Lewy body diseases, including abnormal α-synuclein aggregates and neurodegeneration, particularly nigrostriatal dopaminergic loss. Understanding the temporal inter-relationships between Lewy pathology, Alzheimer's disease, and other co-pathologies and symptom manifestation is central to any biological staging system. Neuropathological and in vivo evidence demonstrates substantial temporal and biological heterogeneity in the progression of clinical and pathological events across Lewy body disorders, highlighting knowledge gaps. Staging systems must incorporate this evidence into a nuanced conceptual framework of biological progression. Such revision will be crucial for the appropriate selection of participants and correct timing of targeted interventions in clinical research.","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841353","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":"CGRP blockade and cluster headache: another step forward","authors":"Elizabeth Leroux","doi":"10.1016/s1474-4422(25)00103-6","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00103-6","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841000","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":"Carotid revascularisation for carotid stenosis","authors":"Jan K Ho, Graeme J Hankey","doi":"10.1016/s1474-4422(25)00106-1","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00106-1","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841107","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":"Neuropathic pain: which treatment for which patient?","authors":"Claudia Sommer","doi":"10.1016/s1474-4422(25)00101-2","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00101-2","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840999","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":"Prioritising faster, individualised rescue treatment in status epilepticus","authors":"Nathalia Penagos Vargas, Oscar Mauricio Espitia Segura","doi":"10.1016/s1474-4422(25)00104-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00104-8","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"218 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841002","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":"AI and neurology: an ethical path to innovation","authors":"","doi":"10.1016/s1474-4422(25)00118-8","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00118-8","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841106","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":"Neurology cannot be embedded in non-communicable disease agendas","authors":"Matilde Leonardi, Elena Moro, Paul Boon, Kailash P Bhatia, Claudio Bassetti, Alberto Raggi","doi":"10.1016/s1474-4422(25)00102-4","DOIUrl":"https://doi.org/10.1016/s1474-4422(25)00102-4","url":null,"abstract":"No Abstract","PeriodicalId":22676,"journal":{"name":"The Lancet Neurology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841004","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}