Annals of Neurology最新文献

{"title":"2025 CNS Meeting Abstract","authors":"","doi":"10.1002/ana.78038","DOIUrl":"https://doi.org/10.1002/ana.78038","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 S35","pages":"S4-S170"},"PeriodicalIF":7.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243013","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":"Issue Information – TOC","authors":"","doi":"10.1002/ana.78051","DOIUrl":"https://doi.org/10.1002/ana.78051","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 S35","pages":"S1-S3"},"PeriodicalIF":7.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Annals of Neurology: Volume 98, Number S35, October 2025","authors":"","doi":"10.1002/ana.78052","DOIUrl":"https://doi.org/10.1002/ana.78052","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 S35","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clarifying the Moderating Role of Socioeconomic Status on Amyloid-Related Gray Matter Atrophy.","authors":"Yun-Xiang Zhou, Zheng-Yang Peng, Wen-Bo Wang","doi":"10.1002/ana.78059","DOIUrl":"https://doi.org/10.1002/ana.78059","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237611","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":"Reply to \"Clarifying the Moderating Role of Socioeconomic Status on Amyloid-Related Gray Matter Atrophy\".","authors":"Dario Bachmann, Valerie Treyer","doi":"10.1002/ana.78057","DOIUrl":"https://doi.org/10.1002/ana.78057","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237528","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":"Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early-Onset Parkinsonism.","authors":"Hormos Salimi Dafsari, Celine Deneubourg, Kritarth Singh, Reza Maroofian, Zita Suprenant, Ay Lin Kho, Neil J Ingham, Karen P Steel, Preethi Sheshadri, Franciska Baur, Lea Hentrich, Birgit Gerisch, Mina Zamani, Cesar Alves, Ata Siddiqui, Haidar S Dafsari, Mehri Salari, Anthony E Lang, Michael Harris, Alice Abdelaleem, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Gholamreza Shariati, Alireza Sedaghat, Jawaher Zeighami, Daniel Calame, Dana Marafi, Ruizhi Duan, Adrian Boehnke, Gary D Clark, Jill A Rosenfeld, Carrie A Mohila, Dora Steel, Saurabh Chopra, Suvasini Sharma, Nicolai Kohlschmidt, Steffi Patzer, Afshin Saffari, Darius Ebrahimi-Fakhari, Büşra Eser Çavdartepe, Irene J Chang, Erika Beckman, Renate Peters, Andrew Paul Fennell, Bernice Lo, Luisa Averdunk, Felix Distelmaier, Martina Baethmann, Frances Elmslie, Kairit Joost, Sheela Nampoothiri, Dhanya Yesodharan, Hanna Mandel, Amy Kimball, Antonie D Kline, Cyril Mignot, Boris Keren, Vincent Laugel, Katrin Õunap, Kalpana Devadathan, Frederique M C van Berkestijn, Arpana Silwal, Saskia Koene, Sumit Verma, Mohammed Yousuf Karim, Chahynez Boubidi, Majid Aziz, Gehad ElGhazali, Lauren Mattas, Mohammad Miryounesi, Farzad Hashemi-Gorji, Shahryar Alavi, Nayereh Nouri, Mehrdad Noruzinia, Saeideh Kavousi, Arveen Kamath, Sandeep Jayawant, Russell Saneto, Nourelhoda A Haridy, Pinar Ozkan Kart, Ali Cansu, Madeleine Joubert, Claire Beneteau, Kyra E Stuurman, Martina Wilke, Tahsin Stefan Barakat, Homa Tajsharghi, Annarita Scardamaglia, Sadeq Vallian, Semra Hız, Ali Shoeibi, Reza Boostani, Narges Hashemi, Meisam Babaei, Norah Saleh Alsaleh, Julie Porter, Tania Attié-Bitach, Pauline Marzin, Dorota Wicher, Jessica I Gold, Elisabeth Schuler, Amna Kashgari, Rakan F Alanazi, Wafaa Eyaid, Marc Engelen, Mirjam Langeveld, Burkhard Stüve, Yun Li, Gökhan Yigit, Bernd Wollnik, Mariana H G Monje, Dimitri Krainc, Niccolò E Mencacci, Somayeh Bakhtiari, Michael Kruer, Emanuela Argilli, Elliott Sherr, Yalda Jamshidi, Ehsan Ghayoor Karimiani, Yiu Wing Sunny Cheung, Ivan Karin, Giovanni Zifarelli, Peter Bauer, Wendy K Chung, James R Lupski, Manju A Kurian, Jörg Dötsch, Jürgen-Christoph von Kleist-Retzow, Thomas Klopstock, Matias Wagner, Calvin Yip, Andreas Roos, Rita Carsetti, Carlo Dionisi-Vici, Mathias Gautel, Michael R Duchen, Adam Antebi, Henry Houlden, Manolis Fanto, Heinz Jungbluth","doi":"10.1002/ana.78013","DOIUrl":"https://doi.org/10.1002/ana.78013","url":null,"abstract":"<p><strong>Objective: </strong>Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.</p><p><strong>Methods: </strong>We investigated clinical, radiological, and molecular features from the largest cohort of EPG5-related patients identified to date, complemented by experimental investigation of cellular and animal models of EPG5 defects.</p><p><strong>Results: </strong>Through worldwide collaboration, we identified 211 patients, 97 of them previously unpublished, with recessive EPG5 variants. The phenotypic spectrum ranged from antenatally lethal presentations to milder isolated neurodevelopmental disorders. A novel Epg5 knock-in mouse model of a recurrent EPG5 missense variant featured motor impairments and defective autophagy in brain areas particularly relevant for the neurological disorders in milder presentations. Novel age-dependent neurodegenerative manifestations in our cohort included adolescent-onset parkinsonism and dystonia with cognitive decline, and myoclonus. Radiological features suggested an emerging continuum with brain iron accumulation disorders. Patient fibroblasts showed defects in PINK1-Parkin-dependent mitophagic clearance and α-synuclein overexpression, indicating a cellular basis for the observed neurodegenerative phenotypes. In Caenorhabditis elegans, EPG5 knockdown caused motor impairments, defective mitophagic clearance, and changes in mitochondrial respiration comparable to observations in C. elegans knockdown of parkinsonism-related genes.</p><p><strong>Interpretation: </strong>Our findings illustrate a lifetime neurological disease continuum associated with pathogenic EPG5 variants, linking neurodevelopmental and neurodegenerative disorders through the common denominator of defective autophagy. ANN NEUROL 2025 ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237608","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":"Reply to \"Methodological Considerations in the Nationwide Cohort Study of Cerebral Amyloid Angiopathy\".","authors":"Samuel S Bruce, Hooman Kamel, Santosh B Murthy","doi":"10.1002/ana.78019","DOIUrl":"https://doi.org/10.1002/ana.78019","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211112","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":"From Diagnosis to Disease Staging: Multisite Validation of Cerebrospinal Fluid Molecular Tests in Multiple Sclerosis.","authors":"Laura Ghezzi, Peter Kosa, Mark Greenwood, Enrique Alvarez, C L Freedman, Anne H Cross, Francesca Pace, Mark S Freedman, Joanna Kocot, Laura Piccio, Bibiana Bielekova","doi":"10.1002/ana.78047","DOIUrl":"https://doi.org/10.1002/ana.78047","url":null,"abstract":"<p><strong>Objective: </strong>The growing demand for personalized treatment in multiple sclerosis (MS) highlights the need for more precise biomarkers that can outperform magnetic resonance imaging and clinical assessment in patient stratification. Advances in multiplex proteomic technologies suggest that cerebrospinal fluid (CSF) analysis at MS onset may not only improve diagnostic accuracy, but also offer prognostic and staging information, as well as insight into molecular therapeutic targets.</p><p><strong>Methods: </strong>This multicenter study retrospectively analyzed cryopreserved CSF samples from 160 individuals undergoing diagnostic evaluation for possible neuroimmunological disorder, and among these, followed a cohort of 96 people with confirmed MS for at least 3 years. The goal was to externally validate previously published CSF-based diagnostic and prognostic classifiers.</p><p><strong>Results: </strong>Upon unblinding, the CSF-based molecular diagnostic test distinguished 96 people with confirmed MS from 30 individuals with other inflammatory neurological diseases, and 34 individuals with non-inflammatory neurological diseases, achieving an area under the receiver operating characteristic curve of 0.94 (p = 4.7 × 10^-21). The test also differentiated 65 individuals with relapsing-remitting MS from 31 individuals with progressive MS, with an area under the receiver operating characteristic curve of 0.76 (p = 1.4 × 10^-5). The prognostic classifier predicted prospectively measured Expanded Disability Status Scale scores at follow up (rho = 0.43, p = 2.54 × 10^-5).</p><p><strong>Interpretation: </strong>This multicenter external validation study demonstrates that CSF-based molecular tests can robustly distinguish MS from other neurological conditions, stratify MS subtypes, and predict future disability progression in real-world settings. These results lay the groundwork for development of next-generation molecular tools to personalize care in MS. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211162","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":"Neurosyphilis with Abnormal in the Bilateral Pons and Multifocal Cranial Nerve Enhancement.","authors":"Yu Zhang, Peng Chao, Ling Liu","doi":"10.1002/ana.78055","DOIUrl":"https://doi.org/10.1002/ana.78055","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197576","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":"Skeletal Muscle Biomarkers of Amyotrophic Lateral Sclerosis: A Large-Scale, Multi-Cohort Proteomic Study.","authors":"Oleksandr Dergai, Joanne Wuu, Magdalena Koziczak-Holbro, Andrea Malaspina, Volkan Granit, Jessica P Hernandez, Anne Cooley, Ruchika Sachdev, Lili Yu, Michael Bidinosti, Ludivine Flotte, Mark Nash, Lori L Jennings, James D Berry, Lucie I Bruijn, Sophie Brachat, Michael Benatar","doi":"10.1002/ana.78046","DOIUrl":"10.1002/ana.78046","url":null,"abstract":"<p><strong>Objective: </strong>Biomarkers with clear contexts of use are important tools for amyotrophic lateral sclerosis (ALS) therapy development. Understanding their longitudinal trajectory in the untreated state is key to their use as potential markers of pharmacodynamic response. To this end, we undertook a large-scale proteomic study in well-phenotyped cohorts to identify biomarker candidates of ALS disease state and disease progression.</p><p><strong>Methods: </strong>Clinical phenotypic data and biofluid samples, collected from patients with ALS and healthy controls through multiple longitudinal natural history studies, were used to identify biomarker candidates. Slow off-rate modified aptamer (SOMAmer)-based relatively quantitative measurement of ~7,000 proteins was performed in plasma and cerebrospinal fluid (CSF), with immunoassay validation of candidates of interest.</p><p><strong>Results: </strong>We identified 329 plasma proteins significantly differentially regulated between ALS and controls (adjusted p-value <0.05), with 25 showing >40% relative abundance. PDLIM3, TNNT2, and MYL11 had the greatest log-fold elevation, whereas ANTXR2 and ART3 had the greatest log-fold reduction. A similar set of plasma proteins was found to increase (eg, PDLIM3, TNNT2, and MYL11) or decrease (eg, ANTXR2, ART3, and MSTN) with disease progression. CSF proteins with the greatest log-fold elevation included NEFL, NEFH, CHIT1, CA3, MYL11, and GPNMB. These results were confirmed in an independent replication cohort. Moreover, tissue-specific signature enrichment suggests a significant contribution of muscle as a source of these biomarkers. Plasma KCNIP3 was elevated by ~60% in those on riluzole. Immunoassays provided orthogonal validation of plasma TNNT2 and CSF GPNMB.</p><p><strong>Interpretation: </strong>We identified an array of novel biomarkers with the potential to serve as response biomarkers to aid therapy development, as well as to shed light on the underlying biology of disease. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184303","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}