Neurology最新文献

{"title":"Clinical Reasoning: A 72-Year-Old Man With Meningoencephalitis.","authors":"Daniel Francisco Isaza-Pierotti,Santiago Diaz Gonzalez,Jose Alfredo Sanchez","doi":"10.1212/wnl.0000000000213658","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213658","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"83 1","pages":"e213658"},"PeriodicalIF":9.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889267","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":"Impact of Brain Frailty on Clinical Presentation and Neurologic Recovery in Acute Ischemic Stroke Patients Undergoing Thrombectomy.","authors":"Joachim Fladt,Faysal Benali,Tanaporn Jaroenngarmsamer,Fouzi Bala,Nishita Singh,Raul G Nogueira,Ryan McTaggart,Andrew Demchuk,Alexandre Poppe,Brian H Buck,Michael Tymianski,Michael D Hill,Mayank Goyal,Aravind Ganesh,","doi":"10.1212/wnl.0000000000213619","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213619","url":null,"abstract":"BACKGROUND AND OBJECTIVESBrain frailty impairs the ability to compensate for brain dysfunction and is linked to worse outcomes after stroke. Stroke severity at presentation is a key determinant of outcomes in acute ischemic stroke. This study aimed to examine the impact of brain frailty on initial stroke severity and recovery in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT).METHODSWe conducted a post hoc analysis of the ESCAPE-NA1 randomized-controlled trial that investigated the efficacy and safety of the neuroprotectant nerinetide in patients with AIS who received EVT. Brain frailty markers (cortical atrophy, subcortical atrophy, white matter hyperintensities, chronic infarcts) were visually assessed from baseline noncontrast CT scans. We explored the association between these markers and admission stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) using multivariable quantile regression. We also assessed the NIHSS trajectory over 90 days using repeated-measures analysis. Models were adjusted for relevant covariates.RESULTSAmong 1,102 participants (mean age 69.5 years; 49.7% female), NIHSS scores at baseline were higher in patients with cortical atrophy and those with chronic infarcts compared with patients having no cortical atrophy or chronic infarcts after adjusting for confounders (adjusted difference for GCA1 vs GCA0 = 1.25 points [95% CI 0.18-2.31], p = 0.021; adjusted difference for presence of chronic infarcts = 1.27 points [95% CI 0.007-2.53, p = 0.049]). Subcortical atrophy, white matter hyperintensity burden, lacunes, and overall brain frailty were not associated with NIHSS scores at presentation. A repeated-measures analysis showed consistent higher NIHSS scores in individuals with brain frailty compared with those without, after the acute phase throughout the 90-day follow-up period (NIHSS score at 30 days, adjusted difference for total brain frailty score 1 vs 0 = 1.16 points [95% CI 0.35-1.96], p = 0.01; brain frailty score 2/3 vs 0 = 0.98 [95% CI 0.08-1.88], p = 0.03; NIHSS score at 90 days (adjusted difference for brain frailty score 1 vs 0 = 0.97 [95% CI 0.19-1.75], p = 0.01; brain frailty score 2/3 vs 0 = 0.85 [95% CI -0.01 to -1.71], p = 0.05).DISCUSSIONThis study highlights the association of brain frailty with the clinical presentation and recovery trajectory of patients with AIS undergoing EVT. Specifically, cortical atrophy was independently associated with baseline stroke severity, and the total burden of brain frailty was independently associated with NIHSS recovery trajectories. The results emphasize the importance of considering brain frailty in acute stroke management and prognostication.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"222 1","pages":"e213619"},"PeriodicalIF":9.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889263","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":"Survival Differences Between Individuals With Typical and Atypical Phenotypes of Alzheimer Disease.","authors":"Ilse Bader,Colin Groot,Wiesje M Van Der Flier,Yolande A L Pijnenburg,Rik Ossenkoppele","doi":"10.1212/wnl.0000000000213603","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213603","url":null,"abstract":"BACKGROUND AND OBJECTIVESSurvival estimates for individuals with Alzheimer disease (AD) are informative to understand the disease trajectory, but precise estimates for atypical AD variants are scarce. Atypical AD variants are characterized by nonamnestic phenotypes, an early onset, and lower prevalence of APOEε4 carriership, which affect the AD trajectory. We aimed to provide survival estimates for posterior cortical atrophy (PCA), logopenic variant primary progressive aphasia (lvPPA), and behavioral AD (bvAD) and to evaluate the effect of these atypical AD diagnoses beyond known mortality determinants.METHODSFrom the Amsterdam Dementia Cohort, we retrospectively selected patients with biomarker-confirmed sporadic AD presenting at the memory clinic in the mild cognitive impairment or dementia stage. Patients were classified into atypical AD phenotypes (PCA, lvPPA, bvAD; multidisciplinary consensus and retrospective case finding) and a typical AD reference group (excluding unclassifiable atypical presentations or unconfirmed future AD dementia). Survival estimates from the first visit to death/censoring (Central Public Administration) were determined (Kaplan-Meier analysis) and compared (log-rank tests) across diagnostic groups. To assess associations of atypical AD with mortality, Cox proportional hazard models were constructed including age, sex, education, MMSE score, and APOEε4 carriership (model 1), followed by adding the atypical AD group (model 2) or atypical AD variants (model 3). A likelihood ratio test was performed to compare the fit of model 1 and model 2.RESULTSA total of 2,081 patients (aged 65 ± 8 years, 52% female) were classified as typical AD (n = 1,801) or atypical AD (n = 280; PCA [n = 112], lvPPA [n = 86], and bvAD [n = 82]). The estimated median survival time for atypical AD of 6.3 years (95% CI [5.8-6.9]) was shorter than for typical AD (7.2 [7.0-7.5], p = 0.02). Median survival durations across the atypical AD variants were consistently, albeit nonsignificantly, shorter (PCA: 6.3 [5.5-7.3], p = 0.055; lvPPA: 6.6 [5.7-7.7], p = 0.110; bvAD: 6.3 [5.0-9.1], p = 0.121, 48% deceased). Including atypical AD improved the model fit (model 2; χ2 = 8.88, p = 0.003) and was associated with 31% increased mortality risk compared with typical AD (hazard ratio [HR] = 1.31 [1.10-1.56], p = 0.002). In model 3, contributions of the variants were as follows: HRPCA = 1.35 (1.05-1.73), p = 0.019; HRlvPPA = 1.27 (0.94-1.69), p = 0.114; HRbvAD = 1.31 (0.94-1.83), p = 0.105.DISCUSSIONSurvival in atypical AD (PCA, lvPPA, bvAD) was shorter compared with typical AD. These atypical variants are associated with increased mortality beyond age, sex, education, APOEε4 carriership, and disease severity. Future studies are required to address generalizability of these findings and to identify factors that explain the observed survival differences.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"46 1","pages":"e213603"},"PeriodicalIF":9.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889266","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":"Reader Response: Quantitative Characterization of Rhythmic and Periodic EEG Patterns in Patients in a Coma After Cardiac Arrest and Association With Outcome.","authors":"Calixto Machado","doi":"10.1212/wnl.0000000000209978","DOIUrl":"https://doi.org/10.1212/wnl.0000000000209978","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"10 1","pages":"e209978"},"PeriodicalIF":9.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876410","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":"Author Response: Quantitative Characterization of Rhythmic and Periodic EEG Patterns in Patients in a Coma After Cardiac Arrest and Association With Outcome.","authors":"Michel J A M Van Putten,Jeannette Hofmeijer","doi":"10.1212/wnl.0000000000210036","DOIUrl":"https://doi.org/10.1212/wnl.0000000000210036","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"1 1","pages":"e210036"},"PeriodicalIF":9.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876404","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":"Investigating Plasma Metabolomics and Gut Microbiota Changes Associated With Parkinson Disease: A Focus on Caffeine Metabolism.","authors":"Chieh-Chang Chen,Jian-Ying Chiu,Ai Huey Tan,Tzi Shin Toh,Shen-Yang Lim,Eng King Tan,Sven Pettersson,Cheng-Chih Hsu,Jyh-Ming Liou,Ming-Shiang Wu,Chia-Lang Hsu,Chin-Hsien Lin","doi":"10.1212/wnl.0000000000213592","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213592","url":null,"abstract":"BACKGROUND AND OBJECTIVESCoffee intake is linked to a reduced risk of Parkinson disease (PD), but whether this effect is mediated by gut microbiota and metabolomic changes remains unclear. This study examines PD-associated metabolomic shifts, caffeine metabolism, and their connection to gut microbiome alterations in a multicenter study.METHODSWe conducted an untargeted serum metabolomic assay using liquid chromatography with high-resolution mass spectrometry on an exploratory cohort recruited from National Taiwan University Hospital (NTUH). A targeted metabolomic assay focusing on caffeine and its 12 downstream metabolites was conducted and validated in an independent cohort from University Malaya Medical Centre (UMMC). In the exploratory cohort, the association of each caffeine metabolite with gut microbiota changes was investigated by metagenomic shotgun sequencing. A clustering-based approach was used to correlate microbiome changes with plasma caffeine metabolite level and clinical severity. Body mass index, antiparkinsonism medication use, and dietary habits (including coffee and tea intake) were recorded.RESULTSSixty-three patients with PD and 54 controls from NTUH formed the exploratory cohort while 36 patients with PD and 20 controls from UMMC served as an validation cohort to replicate the plasma caffeine findings. A total of 5,158 metabolites were detected from untargeted metabolomic analysis, with 3,131 having high confidence for analysis. Compared with controls, the abundance of 56 metabolites was significantly higher and that of 7 metabolites was significantly lower (adjusted p < 0.05 and log2 fold change >1) in patients with PD. Caffeine metabolism was significantly lower in patients with PD (p = 0.0013), and serum levels of caffeine and its metabolites negatively correlated with motor severity (p < 0.01). Targeted metabolomic analysis confirmed reduced levels of caffeine and its metabolites, including theophylline, paraxanthine, 1,7-dimethyluric acid, and 5-acetylamino-6-amino-3-methyluracil, in patients with PD; these findings were replicated in the validation cohort (p < 0.05). A clustering approach found that 56 microbiome species enriched in patients with PD negatively correlated with caffeine and its metabolites paraxanthine and theophylline (both p < 0.05), notably Clostridium sp000435655, Acetatifactor sp900066565, Oliverpabstia intestinalis, and Ruminiclostridium siraeum.DISCUSSIONThis study identifies PD-related changes in microbial-caffeine metabolism compared with controls. Our findings offer insights for future functional research on caffeine-microbiome interactions in PD.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"7 1","pages":"e213592"},"PeriodicalIF":9.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876409","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: Reflex Epilepsy-Seizures Triggered by a Geometric Pattern.","authors":"Jennifer Meylor,Shannon Pollock,Katie Ricciardi,Avantika Singh","doi":"10.1212/wnl.0000000000213664","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213664","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"37 1","pages":"e213664"},"PeriodicalIF":9.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876432","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 Newly Validated Gold Standard for Measuring Multiple Sclerosis Disability Worsening.","authors":"Robert J Fox,Richard A Rudick","doi":"10.1212/wnl.0000000000213672","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213672","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"53 1","pages":"e213672"},"PeriodicalIF":9.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872029","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":"Multiple Sclerosis-Specific Reference Curves for Brain Volumes to Explain Disease Severity.","authors":"David Rudolf van Nederpelt,Lonneke Bos,Rozemarijn M Mattiesing,Eva M M Strijbis,Bastiaan Moraal,Joost Kuijer,Jeroen Hoogland,Henk J M M Mutsaerts,Bernard Uitdehaag,Joep Killestein,Lizette Heine,Bas Jasperse,Frederik Barkhof,Menno M Schoonheim,Hugo Vrenken","doi":"10.1212/wnl.0000000000213618","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213618","url":null,"abstract":"BACKGROUND AND OBJECTIVESBrain atrophy is relevant for understanding disease progression and treatment response in people with multiple sclerosis (pwMS). Automatic brain volume-reporting tools often rely on healthy control (HC) reference curves to interpret brain volumes, whereas brain volume loss is different in pwMS. This observational study aimed to develop an MS-specific reference model for brain volumes and evaluate its performance compared with HC-based curves, as a proof-of-concept.METHODSParticipants, pwMS and HCs, from the Amsterdam MS cohort were included based on the availability of T1-weighted MR scans. Normalized brain volumes (NBVs) were obtained using commercially available software. The software program also provides NBV percentiles, based on age-specific and sex-specific HC curves, grouped into NBV quartiles, describing deviation from expected NBVs. Disease severity was determined with the MS severity score (MSSS), Symbol Digit Modalities Test (SDMT), and 9-Hole Peg Test (9HPT). An MS-specific model was developed by regressing NBVs against age, sex, disease duration, and MS phenotype. The resulting MS model was also used to classify pwMS into quartiles describing deviation from expected NBV, given the modeled patient characteristics, with leave-one-out predictions. Quartile classification from HC-based and MS-based reference curves was compared with MSSS using analysis of variance (ANOVA).RESULTSRegressions for NBVs from 713 pwMS and 259 HCs (mean age: 49.1 ± 9.7 and 48.3 ± 10.1, %female: 70.4% and 67.2%, respectively) were significant for age, sex, disease duration, and phenotype, which were included in the MS-specific model. MS-specific model quartile designations significantly improved associations with MSSS values (p = 2.2*10-9, η2 = 0.06) compared with HC-based quartiles. MSSS values worsened with lower NBV quartiles in the MS-specific model (difference between quartiles 1-4 = -0.84, p = 6.1*10-3, 95% CI [-1.5 to -0.18])), which was not observed for HC-based quartiles (p = 0.98). Quartile group differences were observed for 9HPT (MS: p = 3.5*10-3, η2 = 0.02, HC: p = 6.6*10-3, η2 = 0.02) and SDMT (MS: p = 3.1*10-4, η2 = 0.05, HC: p = 5.4*10-4, η2 = 0.04) values, but MS-specific quartiles again improved quartile associations (p = 0.036, η2 = 0.01 and p = 0.02, η2 = 0.01, respectively).DISCUSSIONNBV values derived from an MS-specific reference model offer improved relevance for assessing disease severity compared with curves derived from age-specific and sex-specific HC reference models. Improving the model toward application in individual people could enhance clinical implementation.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"6 1","pages":"e213618"},"PeriodicalIF":9.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872027","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":"Association Between Metabolic Syndrome and Young-Onset Dementia: A Nationwide Population-Based Study.","authors":"Jeong-Yoon Lee,Kyungdo Han,Jonguk Kim,Jae-Sung Lim,Dae Young Cheon,Minwoo Lee","doi":"10.1212/wnl.0000000000213599","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213599","url":null,"abstract":"BACKGROUND AND OBJECTIVESYoung-onset dementia (YOD) poses substantial societal and health care burdens. Although metabolic syndrome (MetS) is recognized as a contributor to late-onset dementia, its effect on YOD remains unclear. This study aimed to determine whether MetS and its individual components increase the risk of YOD, including all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD).METHODSWe conducted a nationwide population-based cohort study using data from the Korean National Insurance Service. Individuals aged 40-60 who underwent national health check-ups in 2009 were included and followed until December 31, 2020, or age 65, whichever came first. MetS was defined according to established guidelines, incorporating measurements of waist circumference, blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Covariates included age, sex, income level, smoking status, alcohol consumption, and comorbidities such as hypertension, diabetes, dyslipidemia, and depression. The primary outcome was incident all-cause YOD, defined as a dementia diagnosis before age 65; secondary outcomes included young-onset AD and VaD. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs.RESULTSA total of 1,979,509 participants (mean age, 49.0 years; 51.3% men; 50.7% with MetS) were included. Over an average follow-up of 7.75 years, 8,921 individuals (0.45%) developed YOD. MetS was associated with a 24% higher risk of all-cause YOD (adjusted HR 1.24, 95% CI 1.19-1.30), a 12.4% increased risk of AD (HR 1.12, 95% CI 1.03-1.22), and a 20.9% increased risk of VaD (HR 1.21, 95% CI 1.08-1.35). Significant interactions were noted with younger age (40-49 vs 50-59), female sex, drinking status, obesity, and depression.DISCUSSIONIn this large Korean cohort, MetS and its individual components were significantly associated with an increased risk of YOD. These findings suggest that interventions targeting MetS may help mitigate YOD risk. However, the observational design precludes definitive causal inferences, and reliance on claims data could introduce misclassification bias. Future research using longitudinal designs and comprehensive data collection is needed to validate and expand on these associations.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"7 1","pages":"e213599"},"PeriodicalIF":9.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872028","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}