Annals of Neurology最新文献

{"title":"Alzheimer's Co-Pathology Burden on Basal Forebrain Atrophy and Cognitive Impairment in Dementia with Lewy Bodies: A Cross-Sectional Pilot Study.","authors":"Daniele Urso, Thomas Giannelli, Benedetta Tafuri, Stefano Giannoni-Luza, Valentina Gnoni, Alessia Giugno, Davide Vilella, Chiara Zecca, Roberto De Blasi, Salvatore Nigro, Dag Aarsland, Giancarlo Logroscino","doi":"10.1002/ana.78357","DOIUrl":"https://doi.org/10.1002/ana.78357","url":null,"abstract":"<p><strong>Objective: </strong>Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease (AD), with significant pathological overlap between the two conditions. However, the impact of Alzheimer's co-pathology on basal forebrain (BF) atrophy and its relationship with neurodegeneration and cognitive decline in patients with DLB remains underexplored.</p><p><strong>Methods: </strong>Forty patients with DLB and 14 healthy controls (HCs) were included from the Centre for Neurodegenerative Diseases, University of Bari. Participants underwent neuropsychological evaluations, 3T magnetic resonance imaging (MRI) scans, and Alzheimer's biomarkers assessment. Patients with DLB were grouped by AD co-pathology using in vivo biomarkers. BF and hippocampal volumes and mean cortical thickness values were analyzed using analysis of covariance (ANCOVA), adjusted for age, sex, and total intracranial volume. Mediation analyses were conducted to examine the indirect effects of Alzheimer's pathology and BF atrophy on neurodegeneration (hippocampal volume and cortical thickness) and cognitive function (Mini-Mental State Examination [MMSE]).</p><p><strong>Results: </strong>Patients with DLB exhibited significant BF atrophy compared with HCs (p < 0.001). AD co-pathology was associated with greater BF atrophy (p = 0.046) and reduced mean cortical thickness (p = 0.025). Significant correlations were found between BF volume and the pTAU₁₈₁/Aβ_1-42 ratio (p = 0.009) and between BF volume and MMSE scores (p = 0.016). Mediation analysis revealed that BF atrophy mediated the relationship between the pTau/Aβ42 ratio and neurodegeneration, and that the BF has a direct association with cognitive impairment.</p><p><strong>Interpretation: </strong>AD co-pathology in DLB exacerbates BF atrophy, correlating with cognitive decline. These results emphasize the need to consider AD co-pathology in evaluating neurodegeneration in DLB, suggesting future studies should explore targeted interventions to address this pathological overlap. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975127","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":"Mechanical Thrombectomy for Medium Vessel Occlusions.","authors":"Ifrah Zawar, Omar Al-Janabi, Jennifer Hurley, Mayank Goyal","doi":"10.1002/ana.78365","DOIUrl":"https://doi.org/10.1002/ana.78365","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975076","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":"ALS Research and Healey ALS MyMatch.","authors":"Ryan Jacobson, Suma Babu, Jennifer Hurley, Ifrah Zawar","doi":"10.1002/ana.78364","DOIUrl":"https://doi.org/10.1002/ana.78364","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965824","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":"Neutrophil Extracellular Traps Block Fibrinolysis in Ischemic Stroke.","authors":"Mialitiana Solo Nomenjanahary, Jean-Philippe Desilles, Fatima Zemali, Astride Perrot, Lucas Di Meglio, Sara Zalghout, Jéromine Fasille, Jérémy Neel, Stéphane Loyau, Julien Labreuche, Marie-Charlotte Bourrienne, Dorothée Faille, François Delvoye, Véronique Ollivier, Sébastien Dupont, Jasmina Rogozarski, Nahida Brikci-Nigassa, Robert L Medcalf, Nadine Ajzenberg, Mikael Mazighi, Benoît Ho-Tin-Noé","doi":"10.1002/ana.78346","DOIUrl":"https://doi.org/10.1002/ana.78346","url":null,"abstract":"<p><strong>Objectives: </strong>Intravenous thrombolysis (IVT) failure in acute ischemic stroke (AIS) is frequent, but its causes remain elusive. We investigated whether biologically relevant intrathrombus concentrations of tissue plasminogen activator (tPA) were achieved in failed IVT and whether neutrophil extracellular traps (NETs) contributed to this therapeutic failure.</p><p><strong>Methods: </strong>In this monocenter cohort study, 205 thrombi from AIS patients were analyzed. A total of 83 of these thrombi were compared for tPA content and 53 for their susceptibility to ex vivo thrombolysis according to IVT status. An additional subset of 69 AIS thrombi was used to decipher if and how NETs interfere with intrathrombus fibrinolysis.</p><p><strong>Results: </strong>Thrombi from IVT patients contained twice as much tPA than those from no-IVT patients (p < 0.0001). Plasminogen and tPA in AIS thrombi were associated with fibrin, leukocytes, and NETs. Although ex vivo addition of plasminogen did not cause lysis of either no-IVT or IVT thrombi, combining plasminogen with deoxyribonuclease 1 (DNase 1) helped translate the increased tPA content of IVT thrombi into increased thrombolysis. We further show that DNase 1 enables tPA- and plasmin-mediated thrombolysis by eliminating fibrinolysis inhibitors from AIS thrombi.</p><p><strong>Interpretation: </strong>These results indicate that intrathrombus tPA concentrations reached in failed IVT bear a therapeutic potential that is impaired by NETs, which favor intrathrombus retention of fibrinolysis inhibitors and may limit the availability of tPA and plasminogen for fibrinolysis. Our results stress the interest of DNase 1 to enhance the efficacy of current IVT tPA regimens. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148965819","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":"Circulating Exosomes Drive Persistent Neuronal Dysfunction in Post-Herpetic Neuralgia Patients.","authors":"Christy S Niemeyer, Seth Frietze, Serena W R Lewis, Emily C Artman, Christina Coughlan, Safa I Vaseemuddin, Arianna Gentile Polese, Maria A Nagel, Stephen K Tyring, Fyona Okundia, Anthony J Saviola, Gary C Curhan, Sharon G Curhan, Diego Restrepo, Andrew N Bubak","doi":"10.1002/ana.78352","DOIUrl":"https://doi.org/10.1002/ana.78352","url":null,"abstract":"<p><strong>Objective: </strong>Post-herpetic neuralgia (PHN) is a debilitating chronic pain condition persisting beyond 3 months after herpes zoster (HZ), yet the mechanisms driving the transition from acute viral injury to chronic neuropathic pain remain poorly characterized. We tested whether circulating exosomes are sufficient to drive sensory neuron dysfunction independent of direct varicella zoster virus infection.</p><p><strong>Methods: </strong>Human nociceptive neurons were either directly infected with varicella zoster virus or exposed to exosomes isolated from sera of control individuals, patients with acute HZ, or patients with post-herpetic neuralgia. Neuronal responses were assessed by bulk RNA sequencing (RNA-seq), gene set enrichment analysis, multiplex cytokine and matrix metalloproteinase-9 immunoassays, lactate dehydrogenase cytotoxicity assays, live-cell imaging of neurite dynamics, and mass spectrometry-based proteomic profiling of exosome cargo.</p><p><strong>Results: </strong>Direct viral infection induced a pro-inflammatory, metabolically active neuronal state with increased interleukin-8 and interleukin-13 secretion and elevated extracellular matrix remodeling pathways. PHN exosomes recapitulated and amplified this phenotype in uninfected neurons, suppressing neurite extension gene networks through predicted inhibition of the RNA-binding protein ELAVL4, functionally impairing neurite outgrowth, and inducing matrix metalloproteinase-9 secretion without cytotoxicity. Proteomic profiling identified complement C3b and HSPA5 enriched on PHN exosomes. Canonical nociceptive ion channels were downregulated whereas substance P was upregulated, indicating a shift toward neuropeptide-mediated signaling.</p><p><strong>Interpretation: </strong>These findings establish a failure-to-resolve model in which persistent exosome-mediated signaling sustains maladaptive neuronal remodeling after viral clearance, identifying circulating exosome cargo as previously unreported mechanistic contributors to PHN pathogenesis and potential therapeutic targets. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962734","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":"Atherosclerotic Cardiovascular Diseases Increase ALS Risk by 82% While Optimal Cardiovascular Health Halves It: A 0.5-Million Prospective Cohort Study.","authors":"Jiali Xie, Haobo Xie, Yaojia Li, Wenhua Jiang, Xinglin Wang, Qingjian Xie, Xueqin Song, Dongsheng Fan, Hong-Fu Li, Binbin Deng","doi":"10.1002/ana.78321","DOIUrl":"https://doi.org/10.1002/ana.78321","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to determine whether prevalent atherosclerotic cardiovascular diseases (ASCVDs) increase the risk of amyotrophic lateral sclerosis (ALS) and whether high cardiovascular health (CVH) can offset this risk.</p><p><strong>Methods: </strong>We prospectively analyzed 502,279 UK Biobank participants (37-73 years) with linked electronic health records. Prevalent ASCVD (coronary artery disease [CAD], ischemic stroke [IS], and peripheral artery disease [PAD]) was ascertained at baseline. CVH was quantified using Life's Essential 8 and categorized as low, moderate, or high. Cox models, joint analyses, and Mendelian randomization were applied.</p><p><strong>Results: </strong>Over a median follow-up of 13.74 years, 675 incident ALS cases were documented. A history of ASCVD was associated with a 43% higher risk of ALS (hazard ratio [HR] = 1.43, 95% confidence interval [CI] = 1.16-1.78, p = 0.001), primarily driven by CAD and IS. Conversely, high CVH was associated with a lower risk of ALS compared with low CVH (HR = 0.52, 95% CI = 0.33-0.81, p = 0.004). Joint analysis revealed that individuals with low CVH and pre-existing ASCVD exhibited the highest ALS risk. Mendelian randomization analyses provided supportive evidence consistent with the observational associations among CAD, IS, and ALS. The inverse association between CVH and ALS risk was most pronounced among participants aged ≤65 years.</p><p><strong>Interpretation: </strong>Prevalent ASCVD was associated with a higher risk of ALS, whereas high CVH was associated with a lower risk of ALS. These findings support a potential link between CVH and ALS susceptibility, particularly among individuals aged ≤65 years. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954590","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":"Gyriform Susceptibility Rim in Early Progressive Multifocal Leukoencephalopathy.","authors":"Thor Linnet, Karan Dixit, Shailee Shah","doi":"10.1002/ana.78368","DOIUrl":"https://doi.org/10.1002/ana.78368","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954515","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":"Non-contrast CT Markers of Hematoma Expansion and Andexanet Response in Factor Xa Inhibitor-Associated Intracerebral Hemorrhage: An Analysis from ANNEXa-I Trial.","authors":"Koji Tanaka, Umberto Pensato, Mohamed Alshamrani, Aristeidis H Katsanos, Pargol Balali, Sucharita Ray, Scott E Kasner, Jan Beyer-Westendorf, Danilo Toni, David J Seiffge, Carlos Molina, David Tanne, Anna Członkowska, Arne G Lindgren, Daniel Bereczki, Else C Sandset, Georgios Tsivgoulis, Hanne Christensen, Jonathan M Coutinho, Peter Verhamme, Pierre Amarenco, Robin Lemmens, Roland Veltkamp, Saskia Middeldorp, Thompson Robinson, Truman J Milling, Wilfried Lang, Vitor Tedium-Cruz, Mark Crowther, Lizhen Xu, Mikael Knutsson, Per Ladenvall, John W Eikelboom, Mukul Sharma, Ashkan Shoamanesh, Andrew M Demchuk","doi":"10.1002/ana.78347","DOIUrl":"https://doi.org/10.1002/ana.78347","url":null,"abstract":"<p><p>In this post hoc analysis of the ANNEXa-I trial (n = 434), we evaluated non-contrast computed tomography (NCCT) markers of hematoma expansion (HE) in factor Xa inhibitor (FXai) -associated intracerebral hemorrhage (ICH). At least one NCCT marker was present in 72.1%, and HE (≥12.5 mL or ≥ 35% increase in hematoma volume) occurred in 31.8%. Heterogeneous density, hypodensity, and the black hole sign were independently associated with HE. The effect of andexanet on HE was generally consistent across NCCT marker subgroups. These findings support the utility of NCCT markers for identifying patients at high risk of HE in FXai-associated ICH. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904705","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":"Tracking Socio-emotional Brain Changes in Premanifest C9orf72 Repeat Expansion Carriers: A Structural and Functional 2-Year Longitudinal Magnetic Resonance Imaging Study.","authors":"Jiaze Sun, Joke De Vocht, Maarten Laroy, Daphne Stam, Chih-Hao Lien, Nikita Lamaire, Ann D'Hondt, Ronald Peeters, Stefan Sunaert, Philip Van Damme, Mathieu Vandenbulcke, Jan Van den Stock","doi":"10.1002/ana.78355","DOIUrl":"https://doi.org/10.1002/ana.78355","url":null,"abstract":"<p><strong>Objectives: </strong>The C9orf72 hexanucleotide repeat expansion (C9RE) is the most frequent genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. Although structural alterations have been reported decades before symptom onset, the longitudinal evolution of socioemotional network dysfunction in premanifest C9RE carriers remains poorly understood.</p><p><strong>Methods: </strong>In this multimodal 2-year longitudinal study, we examined 21 premanifest C9RE carriers and 24 controls using structural magnetic resonance imaging (MRI), resting-state, and task-based functional MRI (fMRI), and multivariate pattern analysis. Participants completed facial emotion processing tasks during fMRI scanning, alongside behavioral assessments. We assessed regional activation, network connectivity, and voxel-wise structural integrity at baseline and follow up.</p><p><strong>Results: </strong>At baseline, premanifest C9RE carriers showed reduced emotion recognition efficiency, accompanied by bilateral thalamic atrophy, decreased activation in the anterior and posterior cingulate cortex, and increased activation in the posterior cerebellum, along with altered multivoxel activity patterns in the anterior cingulate and posterior cerebellum. Resting-state fMRI revealed decreased functional connectivity involving the thalamus, anterior, and posterior cingulate cortex. Longitudinal analyses indicated declining emotion-evoked responses in the posterior cingulate cortex and cerebellum, alongside further thalamic volume loss, whereas functional connectivity showed no significant change over time. Despite these progressive neural alterations, behavioral performance remained stable.</p><p><strong>Interpretation: </strong>Socioemotional circuit dysfunction emerges early in C9RE carriers and progresses over time, preceding overt clinical symptoms. Functional imaging, especially task-based fMRI combined with multivariate pattern analysis, captures early circuit-level alterations that may serve as sensitive biomarkers for premanifest neurodegeneration. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899741","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":"Coiled and Intertwined Middle Cerebral Artery.","authors":"Mingyao Li, Zhen Liu, Yongnan Hao, Shuhu Zhou","doi":"10.1002/ana.78359","DOIUrl":"https://doi.org/10.1002/ana.78359","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899750","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}