Annals of Neurology最新文献

{"title":"Annals of Neurology: Volume 100, Number S37, October 2026","authors":"","doi":"10.1002/ana.78396","DOIUrl":"https://doi.org/10.1002/ana.78396","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 S37","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177149","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":"Cerebral No-Reflow after Thrombectomy: International Delphi Consensus on Definition and Imaging Assessment.","authors":"Adnan Mujanovic, Samantha Rivet, Adrien Ter Schiphorst, Jean-Claude Baron, Johannes Kaesmacher, Felix Ng","doi":"10.1002/ana.78387","DOIUrl":"https://doi.org/10.1002/ana.78387","url":null,"abstract":"<p><strong>Background: </strong>The operational definition and imaging assessment of the no-reflow phenomenon, a potential contributor to poor clinical outcome despite successful thrombectomy, remains debated. We aimed to develop expert-based international consensus on the definition, assessment, and reporting standard of cerebral no-reflow post-thrombectomy.</p><p><strong>Methods: </strong>Three-rounds of a modified Delphi web-based survey was conducted among corresponding authors of peer-reviewed clinical studies on cerebral no-reflow between 2020 and 2025. Responses at each round were used to develop structured questionnaires for subsequent rounds. Consensus was predefined as ≥65% agreement.</p><p><strong>Results: </strong>Among 27 panelists, the response rate was 70%, 74%, and 74% over all rounds. There was broad agreement to conceptualize no-reflow as macrovascular recanalization with impaired microvascular reperfusion. Consensus was reached that macrovascular recanalization is ideally assessed as (1) digital subtraction angiography with expanded thrombolysis in cerebral infarction (eTICI) grades 2c without clear distal vessel occlusions and/or eTICI 3 only, and (2) absence of a wedge-shaped time-to-maximum (Tmax) or time-to-peak (TTP) delay on post-recanalization perfusion computed tomography (CT) or magnetic resonance imaging (MRI). Regarding impaired microvascular reperfusion assessment, cerebral blood flow, and/or volume were preferred over time-based perfusion parameters (Tmax/TTP). The panel expressed a preference that no-reflow should ideally be assessed ≤6 hours post-recanalization. Pending formal validation, histopathological-radiological correlation in animal models would sufficiently validate the use of imaging-based definitions in humans.</p><p><strong>Interpretation: </strong>Based on currently available literature and expert opinions, this Delphi study provides a framework for systematically reporting cerebral no-reflow after endovascular treatment (EVT). The variability in opinions regarding quantitative thresholds highlights priorities for future methodological standardization and validation studies. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163526","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":"151st Annual Meeting of the American Neurological Association","authors":"","doi":"10.1002/ana.78378","DOIUrl":"10.1002/ana.78378","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 S37","pages":"S4-S375"},"PeriodicalIF":7.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78378","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163552","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":"Issue Information – TOC","authors":"","doi":"10.1002/ana.78397","DOIUrl":"https://doi.org/10.1002/ana.78397","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"100 S37","pages":"S1-S3"},"PeriodicalIF":7.5,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.78397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177191","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":"Centrum Semiovale Perivascular Spaces Predict First Hemorrhagic Lesion in Asymptomatic Amyloid-Positive Individuals.","authors":"Baris Alten, Elif Gokcal, Reisa A Sperling, Zahra Shirzadi, Jasmeer P Chhatwal, M Edip Gurol, Scott E Kasner, Steven M Greenberg, Brett L Cucchiara","doi":"10.1002/ana.78388","DOIUrl":"https://doi.org/10.1002/ana.78388","url":null,"abstract":"<p><strong>Objective: </strong>Identification of cerebral amyloid angiopathy (CAA) before its hemorrhagic manifestations remains limited. We aimed to determine whether severe enlarged perivascular spaces in the centrum semiovale (EPVS-CSO) identify a prehemorrhagic stage of sporadic CAA by predicting the first appearance of CAA-related hemorrhagic lesions or incident cognitive decline in amyloid-positive, cognitively unimpaired, hemorrhage-free older adults.</p><p><strong>Methods: </strong>We performed a secondary analysis of the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial, a phase 3 randomized study in cognitively unimpaired, amyloid-positive older adults. Participants with baseline hemorrhagic lesions were excluded. Baseline EPVS-CSO severity was dichotomized as severe versus nonsevere. Severe basal ganglia EPVS, more closely associated with hypertensive small vessel disease, was evaluated as a topographical negative-control exposure. The primary outcome was incident strictly lobar cerebral microbleeds or cortical superficial siderosis. The secondary outcome was longitudinal cognitive trajectories measured by the Preclinical Alzheimer Cognitive Composite.</p><p><strong>Results: </strong>Among 932 participants (mean age 71.7 ± 4.8 years; 61.3% female), 101 (10.8%) had severe EPVS-CSO at baseline. Over a median follow up of 5.1 years (IQR 3.3-5.5 years), 33.7% of those with severe EPVS-CSO developed incident CAA-related hemorrhagic lesions compared with 13.6% of those with nonsevere EPVS-CSO (adjusted HR 2.85, 95% CI 1.91-4.25; p < 0.0001). Severe basal ganglia EPVS was not associated with incident hemorrhagic lesions (adjusted HR 0.87, 95% CI 0.35-2.18; p = 0.77). Severe EPVS-CSO was not associated with early cognitive differences, and participants who developed incident hemorrhagic lesions showed more pronounced cognitive decline.</p><p><strong>Interpretation: </strong>These findings identify severe EPVS-CSO as a strong predictor of first appearance of CAA-related hemorrhagic lesions in amyloid-positive individuals, supporting integration of amyloid biomarkers into magnetic resonance imaging-based Boston criteria. Identifying markers of the transition of CAA from a nonhemorrhagic to a hemorrhagic stage provides a potential foundation for approaching primary prevention of CAA-related hemorrhage. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147155","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":"Serum Chitotriosidase Links to Activated Glia at Chronic Active Lesion Rims in Multiple Sclerosis Brain.","authors":"Venla Ahola, Maija Saraste, Edoardo Pedrini, Joel Tuomaala, Luzia Buchholz, Markus Matilainen, Johanna Lindenberg, Eeva-Christine Brockmann, Maria Sofia Martire, Sofia Sandgren, David Leppert, Jens Kuhle, Tanja Kuhlmann, Martina Absinta, Laura Airas","doi":"10.1002/ana.78386","DOIUrl":"https://doi.org/10.1002/ana.78386","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to explore the association between 18 kDa translocator protein (TSPO)-positron emission tomography (PET)-measurable glial activation and serum chitotriosidase (CHIT1) in people with multiple sclerosis (pwMS), and its expression in postmortem MS brain tissue.</p><p><strong>Methods: </strong>In this cross-sectional study, 89 pwMS (19 progressive MS [PMS] and 70 relapsing-remitting MS [RRMS]) and 16 age- and sex-matched healthy controls underwent [¹¹C]PK11195 TSPO-PET. Serum CHIT1 concentration was measured using enzyme-linked immunosorbent assay (ELISA). T1-weighted hypointense lesions were phenotyped as rim-active, overall-active, or inactive based on [¹¹C]PK11195-binding in lesion centers and edges. Spearman correlation was used to analyze associations between CHIT1 and study variables. Postmortem CHIT1 and TSPO expressions were assessed immunohistochemically and by re-analyzing spatial transcriptomics as well as single-nucleus and pseudobulk RNA-sequencing datasets.</p><p><strong>Results: </strong>CHIT1 correlated positively with the number (ρ = 0.33, 95% confidence interval [CI] = 0.01-0.58, p = 0.038), volume (ρ = 0.39, 95% CI = 0.08-0.63, p = 0.013), and percentage (ρ = 0.31, 95% CI = 0.003-0.57, p = 0.046) of rim-active lesions and with TSPO-binding in the T1-weighted perilesional area (ρ = 0.36, 95% CI = 0.05-0.61, p = 0.020) in the exploratory CHIT1-high cohort divided based on median CHIT1 concentration in pwMS (22.1 ng/ml). CHIT1 correlated with GFAP (ρ = 0.23, 95% CI = 0.003-0.44, p = 0.042) and neurofilament light chain (NfL; ρ = 0.26, 95% CI = 0.03-0.46, p = 0.022) in the pwMS cohort. Spatial transcriptomics demonstrated significantly higher CHIT1 expression in active lesions and at the edge of chronic active lesions than in white matter (ANOVA p < 0.0001; post hoc multiple comparison analysis p < 0.0001).</p><p><strong>Interpretation: </strong>High serum CHIT1 correlated with the presence of TSPO-PET-identified chronic active lesions. The potential utility of serum CHIT1 as a biomarker for concomitant detrimental glial activation at the edge of chronic active lesions in MS brain warrants further validation. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101482","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":"Selective Limbic and Striatal Atrophy Corresponds to Regional Gene Expression in Leucine-Rich Glioma-Inactivated-1 Immunoglobulin G Autoimmune Encephalitis.","authors":"Albert Aboseif, Laura Cacciaguerra, Andreu Vilaseca, Sravya Kondrakunta, Naveen K Paramasivan, Andrea Stabile, Anuja Patil, Xiaoyang Li, Pallab Sarker, Luke R Christenson, Benjamin Brinkmann, Christopher G Schwarz, Kejal Kantarci, Andrew McKeon, Anastasia Zekeridou, Michael R Basso, Dean M Wingerchuk, Sarosh R Irani, Sean J Pittock, Burcu Zeydan, Divyanshu Dubey","doi":"10.1002/ana.78389","DOIUrl":"https://doi.org/10.1002/ana.78389","url":null,"abstract":"<p><strong>Objective: </strong>To characterize regional brain atrophy patterns, evaluate their association with regional leucine-rich glioma-inactivated-1 (LGI1) gene expression, and identify clinical predictors of hippocampal atrophy in LGI1 autoimmune encephalitis (AE).</p><p><strong>Methods: </strong>This study compared regional brain volumes in LGI1-AE patients versus age- and sex-matched healthy controls (HC) and Alzheimer's disease (AD) patients. LGI1 gene expression was derived from the Allen Human Brain Atlas. Multivariable linear regression and generalized linear models were utilized.</p><p><strong>Results: </strong>A total of 55 LGI1-AE patients were included. Median age was 68 years (IQR 62.5-74.2 years) at volumetric analysis, after 19 months (IQR 11-45 months) from symptom onset. Compared with HC (n = 55) and AD patients (n = 55), LGI1-AE patients had greater regional atrophy of the hippocampus, insula, caudate, and putamen (p < 0.002). Longitudinal analyses demonstrated hippocampal and pallidal atrophy after covariate adjustment. Among those who did not fulfill limbic encephalitis criteria and/or had non-lesional magnetic resonance imaging, limbic and striatal atrophy were identified compared with HC (p < 0.01). Regions with the greatest differential atrophy corresponded to higher LGI1 gene expression (Spearman ρ = 0.7, p = 0.005). Severe cognitive deficits at diagnosis (β = -0.56; p = 0.002) and longer disease duration (β = -0.01; p = 0.001) independently predicted total hippocampal volume (R² = 0.31).</p><p><strong>Interpretation: </strong>LGI1-AE demonstrates a distinct pattern of limbic and striatal atrophy that differs from AD and aligns with regional LGI1 expression, supporting a model of selective network vulnerability. Greater baseline cognitive impairment and longer disease duration independently associated with hippocampal atrophy, underscoring the potential importance of early diagnosis and treatment to limit structural brain injury. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101444","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":"Associations Between Prediagnosis Plasma Neurofilament Light Polypeptide and Amyotrophic Lateral Sclerosis Risk in the Danish EPIC Cohort.","authors":"Aline Davias, Johnni Hansen, Cezmi A Akdis, Marc G Weisskopf","doi":"10.1002/ana.78382","DOIUrl":"https://doi.org/10.1002/ana.78382","url":null,"abstract":"<p><strong>Objective: </strong>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a rapid time from symptoms onset to diagnosis. Elevated neurofilament light polypeptide (NfL) is well-established in symptomatic ALS and up to 5 years prediagnosis, but earlier timeframes remain understudied. We aimed to assess plasma NfL levels up to 23 years before ALS diagnosis and the relation to ALS risk.</p><p><strong>Methods: </strong>We conducted a nested matched case-control study within the Danish EPIC cohort (baseline 1993-1997) including 166 ALS cases (diagnosed 1997-2017) and 332 controls matched on birth year and sex. Plasma samples collected 0.4 to 23.2 years (median 14.1 years) prediagnosis were analyzed for NfL using Olink Target 96. Odds ratios were estimated using conditional logistic regression. Discriminatory performance was evaluated using receiver operating characteristic curves.</p><p><strong>Results: </strong>NfL levels were elevated in ALS cases relative to controls up to 14.6 years before diagnosis. Among those with blood samples collected <5, 5 to 14.6, and >14.6 years before diagnosis, the odds ratios (95% CI) for ALS per standard deviation increase in the normalized protein expression value of NfL were 3.8 (1.4-10.3), 1.7 (1.2-2.3), and 1.3 (0.9-1.7), respectively. The areas under the curve for ALS discrimination by NfL among those with blood collected <5 and 5-14.6 years before diagnosis were 0.78 and 0.63, respectively.</p><p><strong>Interpretation: </strong>Plasma NfL elevation may occur significantly earlier than previously reported, indicating a much longer ALS prodrome. Assuming other biomarker changes may also occur earlier, this raises the possibility of identifying at-risk individuals early that could benefit epidemiologic analyses, clinical trials, and prevention efforts. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101160","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":"Memory and Plasma pTau217 Refine Prognosis in Down Syndrome.","authors":"Casey R Vanderlip, Sigan L Hartley, Sharon Krinsky-McHale, Christy Hom, Adam M Brickman, Melissa E Petersen, Elizabeth Head, Craig E L Stark","doi":"10.1002/ana.78366","DOIUrl":"https://doi.org/10.1002/ana.78366","url":null,"abstract":"<p><p>Individuals with Down syndrome (DS) are at high risk for Alzheimer's disease (AD), yet accessible tools for routine clinical screening of AD in individuals with DS remain limited. Using data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS), we show that integrating plasma pTau217 with performance on the modified cued recall task identifies a subgroup of cognitively stable individuals at markedly elevated risk of developing clinical impairment in the next 7 years. This low-burden, multimodal framework improves prognosis, supports more informed clinical management and efficient trial enrichment in Down syndrome. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101468","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 and Sampling Considerations in the Evaluation of Intravascular Inflammation during Ischemic Stroke\".","authors":"Justine Münsterberg, Mathias Gelderblom","doi":"10.1002/ana.78335","DOIUrl":"10.1002/ana.78335","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"903-904"},"PeriodicalIF":7.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786228","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}