Neurology最新文献

{"title":"α-Synuclein Seed Amplification Assay Amplification Parameters and the Risk of Progression in Prodromal Parkinson Disease.","authors":"David G Coughlin, Ben Shifflett, Carly M Farris, Yihua Ma, Douglas Galasko, Steven D Edland, Brit Mollenhauer, Michael C Brumm, Kathleen L Poston, Kenneth Marek, Andrew D Siderowf, Claudio Soto, Luis Concha-Marambio","doi":"10.1212/WNL.0000000000210279","DOIUrl":"10.1212/WNL.0000000000210279","url":null,"abstract":"<p><strong>Objectives: </strong>Tools are needed to evaluate the risk of developing Parkinson disease (PD) in at-risk populations. In this study, we examine differences in alpha-synuclein seed amplification assay (αSyn-SAA) qualitative results and amplification parameters between nonmanifesting carriers (NMCs) of PD-related pathogenic variants, prodromal PD, and PD and the risk of developing a synucleinopathy in participants with prodromal PD.</p><p><strong>Methods: </strong>Cross-sectional and longitudinal CSF αSyn-SAA results from participants in the Parkinson's Progression Markers Initiative were analyzed. αSyn-SAA positivity and amplification parameters (maximum fluorescence [Fmax], time-to-threshold [TTT], time-to-50% Fmax [T50], and area under the curve [AUC]) were compared between NMCs, participants with prodromal PD, and participants with PD, and their relationship with the likelihood of phenoconversion in participants with prodromal PD was investigated.</p><p><strong>Results: </strong>Samples from 1,027 participants were analyzed (159 healthy controls [HCs], 247 NMCs, 96 participants with prodromal PD, and 525 participants with PD). TTT and T50 were faster, and AUC was higher in αSyn-SAA+ participants with prodromal PD and PD than αSyn-SAA+ NMCs and HC participants (Kruskal-Wallis χ² = 4.15-13.96, <i>p</i> < 0.0002-0.04). Participants with prodromal PD with positive αSyn-SAA tests and faster TTT had higher rates of phenoconversion (log-rank <i>p</i> = 0.001 and log-rank test-for-trend <i>p</i> < 0.0001). There were no changes in 48 participants with prodromal PD with longitudinal assays.</p><p><strong>Discussion: </strong>αSyn-SAA positivity and faster seed amplification are associated with a greater risk of developing PD in at-risk individuals and may aid in predicting phenoconversion.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e210279"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365367","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":"Right Brain: Of Puddles and Pinnacles: A Letter to My Fearless Little Girl.","authors":"Erin D'Agostino, Christopher LaRocca","doi":"10.1212/WNL.0000000000213411","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213411","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213411"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071053","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":"Next-Day Serum Glial Fibrillary Acidic Protein Levels to Aid Diagnosis of Sport-Related Concussion.","authors":"William T O'Brien, James W Hickey, Steven Mutimer, Lauren J Evans, Blake D Colman, Becca Xie, Lauren P Giesler, Brendan P Major, Biswadev Mitra, Gershon Spitz, Terence J O'Brien, Sandy R Shultz, Stuart J McDonald","doi":"10.1212/WNL.0000000000210308","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210308","url":null,"abstract":"<p><strong>Background and objectives: </strong>Previous studies on sport-related concussion (SRC) may have measured brain injury blood-based biomarker, glial fibrillary acidic protein (GFAP), either before or after its peak, potentially underestimating the diagnostic value. The primary aim of this study was to evaluate the diagnostic performance of serum GFAP at 24 hours post-SRC. Secondary objectives included assessing whether the timing of sample collection relative to an Australian football match (with or without SRC) affected GFAP levels, evaluating if combining GFAP with symptoms improved discrimination of SRC compared with symptoms alone, and determining the diagnostic utility of serum neurofilament light (NfL) levels at 24 hours post-SRC.</p><p><strong>Methods: </strong>In a prospective cohort study, adult male and female Australian football players of the Victorian Amateur Football Association (Melbourne, Australia) with and without SRC had blood sampled around 24 hours postinjury/postmatch. GFAP and NfL levels were quantified using Simoa assays, and area under the curve (AUC) values were calculated for time bins of 16-24 hours, 24-32 hours, and 36-52 hours. Symptom severity at blood collection was assessed using the Sport Concussion Assessment Tool 5 (SCAT).</p><p><strong>Results: </strong>A total of 151 athletes with SRC (median age 22.5 years; 85% male) and 97 controls (median age 24.3 years; 86% male) were sampled at a median of 24.5 hours (interquartile range [IQR] 21.7-28.0; min-max 16-51.5). Time to sample postmatch did not affect GFAP levels in controls; however, higher GFAP levels correlated with shorter time post-SRC (Spearman <i>r</i> = -0.25, 95% CI -0.40 to -0.09). Median GFAP concentrations were 65.9 pg/mL (IQR 49.1-81.3) in controls, and for SRC, 124.6 pg/mL (IQR 86.7-190.7) at 16-24 hours, 94.5 pg/mL (IQR 61.6-163.9) at 24-32 hours, and 59.9 pg/mL (IQR 49.1-94.7) at 36-52 hours. AUC values at 16-24 and 24-32 hours were 0.83 (95% CI 0.76-0.90) and 0.72 (95% CI 0.64-0.80), respectively. Furthermore, combining GFAP with SCAT symptoms at 16-24 hours enhanced discriminatory capability compared with SCAT symptoms alone (AUC increased from 0.91 to 0.97; <i>z</i> = 2.48, <i>p</i> = 0.01). Serum NfL had a limited diagnostic value (AUC ≤0.60).</p><p><strong>Discussion: </strong>Serum GFAP measured at 16-24 hours following potential or suspected SRC may be a useful objective aid to SRC diagnosis.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e210308"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370807","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":"Editors' Note: Association of Cardiovascular Health With Brain Age Estimated Using Machine Learning Methods in Middle-Aged and Older Adults.","authors":"James E Siegler, Steven L Galetta","doi":"10.1212/WNL.0000000000213451","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213451","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 5","pages":"e213451"},"PeriodicalIF":7.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414753","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":"Teaching Video NeuroImage: Synkinetic Wrist Extension: A Simple Clinical Test to Help Localize Wrist Drop.","authors":"Roald Alexander Lambrechts","doi":"10.1212/WNL.0000000000213344","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213344","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 4","pages":"e213344"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008829","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":"Prevalence of Pathogenic Variants and Eligibility Criteria for Genetic Testing in Patients Who Visit a Memory Clinic.","authors":"Sven J Van Der Lee, Marc Hulsman, Rosalina Van Spaendonk, Jetske Van Der Schaar, Janna Dijkstra, Niccoló Tesi, Fred van Ruissen, Mariet Elting, Marcel Reinders, Itziar De Rojas, Corien C Verschuuren-Bemelmans, Wiesje M Van Der Flier, Mieke M van Haelst, Christa de Geus, Yolande Pijnenburg, Henne Holstege","doi":"10.1212/WNL.0000000000210273","DOIUrl":"10.1212/WNL.0000000000210273","url":null,"abstract":"<p><strong>Background and objectives: </strong>Identifying genetic causes of dementia in patients visiting memory clinics is important for patient care and family planning. Traditional clinical selection criteria for genetic testing may miss carriers of pathogenic variants in dementia-related genes. This study aimed identify how many carriers we are missing and to optimize criteria for selecting patients for genetic counseling in memory clinics.</p><p><strong>Methods: </strong>In this clinical cohort study, we retrospectively genetically tested patients during 2.5 years (2010-2012) visiting the Alzheimer Center Amsterdam, a specialized memory clinic. Genetic tests consisted of a 54-gene dementia panel, focusing on Class IV/V variants per American College of Medical Genetics and Genomics guidelines, including <i>APP</i> duplications and the <i>C9ORF72</i> repeat expansion. We determined the prevalence of pathogenic variants and propose new eligibility criteria for genetic testing in memory clinics. The eligibility criteria were prospectively applied for 1 year (2021-2022), and results were compared with the retrospective cohort.</p><p><strong>Results: </strong>Genetic tests were retrospectively performed in in 1,022 of 1,138 patients (90%) who consecutively visited the memory clinic. Among these, 1,022 patients analyzed (mean age 62.1 ± 8.9 years; 40.4% were female), 34 pathogenic variant carriers were identified (3.3%), with 24 being symptomatic. Previous clinical criteria would have identified only 15 carriers (44% of all carriers, 65% of symptomatic carriers). The proposed criteria increased identification to 22 carriers (62.5% of all carriers, 91% of symptomatic carriers). In the prospective cohort, 148 (28.7%) of 515 patients were eligible for testing under the new criteria. Of the 90 eligible patients who consented to testing, 13 pathogenic carriers were identified, representing a 73% increase compared with the previous criteria.</p><p><strong>Discussion: </strong>We found that patients who visit a memory clinic and carry a pathogenic genetic variant are often not eligible for genetic testing. The proposed new criteria improve the identification of patients with a genetic cause for their cognitive complaints. In systems without practical or financial barriers to genetic testing, the new criteria can enhance personalized care. In other countries where the health care systems differs and in other genetic ancestry groups, the performance of the criteria may be different.</p>","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 4","pages":"e210273"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053147","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":"A Charcot-Marie-Tooth Disease Type 1J Case With Diffuse Thickening of Peripheral Nerves.","authors":"Xiaowei Zhu, Feixia Zhan, Xiya Shen, Weiqing Jiang, Li Cao, Xinghua Luan","doi":"10.1212/WNL.0000000000213359","DOIUrl":"10.1212/WNL.0000000000213359","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 4","pages":"e213359"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008801","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":"Editor's Note: Thrombectomy vs Medical Management for Posterior Cerebral Artery Stroke: Systematic Review, Meta-Analysis, and Real-World Data.","authors":"Ariane Lewis, Steven L Galetta","doi":"10.1212/WNL.0000000000213383","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213383","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 4","pages":"e213383"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024129","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":"Peripartum Mental Illness in Mothers With Multiple Sclerosis Merits Neurologists' Attention.","authors":"Lindsay A Ross","doi":"10.1212/WNL.0000000000213366","DOIUrl":"https://doi.org/10.1212/WNL.0000000000213366","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 4","pages":"e213366"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024134","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":"Interpreting the Results of 9-Year Open-Label Extension of Ocrelizumab in Treatment-Naïve Patients With Relapsing MS.","authors":"Olga Ciccarelli, Alan J Thompson","doi":"10.1212/WNL.0000000000210307","DOIUrl":"https://doi.org/10.1212/WNL.0000000000210307","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"104 4","pages":"e210307"},"PeriodicalIF":7.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066966","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}