Annals of Neurology最新文献

{"title":"Hippocampal Seizure-Related Burden is Associated with Accelerated Long-Term Forgetting in Focal Epilepsy.","authors":"Ionuț-Flavius Bratu, Isabelle Lambert, Olivier Felician, Samuel Medina Villalon, Agnès Trébuchon, Fabrice Bartolomei","doi":"10.1002/ana.78354","DOIUrl":"https://doi.org/10.1002/ana.78354","url":null,"abstract":"<p><strong>Objective: </strong>Memory impairment is a frequent comorbidity of focal epilepsy, incompletely explained by seizure frequency or structural pathology. Ictal and postictal hippocampal dysfunction disrupt memory processes, but their cumulative impact remains poorly quantified. This study introduces cumulative hippocampal seizure-related burden metrics and examines their association with long-term memory consolidation.</p><p><strong>Methods: </strong>A total of 20 consecutive patients undergoing stereo-electroencephalography in Marseille (2016-2018) were prospectively included. Continuous stereo-electroencephalogram recordings between 2 memory assessments (30 minutes and 1 week postencoding) were analyzed. Hippocampal ictal involvement and durations were assessed using epileptogenicity markers and visual stereo-electroencephalogram analysis. The postictal period was quantified using permutation entropy. Cumulative hippocampal seizure-related burden metrics (ictal, postictal, and combined) were computed across hippocampus-involving ictal events. Verbal and visual memory were assessed using standardized recall and recognition tasks. One-week performance was defined as the percentage score obtained at the 1-week assessment, whereas retention was defined as 1-week performance expressed as a percentage of 30-min performance. Associations were examined using univariate and multivariate analyses.</p><p><strong>Results: </strong>Higher dominant-hemisphere hippocampal burden was associated with poorer 1-week verbal memory (performance and retention), independently of most covariates. Higher cumulative hippocampal seizure-related burden was associated with lower total recall performance (free + cued) and total recall retention (β = -25.04 and -23.88; R² = 0.57 and 0.53; p < 0.05), and accounted for the greatest variance in both outcomes (adjusted R² = 0.59 and 0.53; β = -25.45 and -24.27; p < 0.01), particularly when adjusting for epilepsy duration. No robust associations were observed between nondominant-hemisphere hippocampal seizure-related burden metrics and visual memory. Effects predominantly involved recall.</p><p><strong>Interpretation: </strong>Cumulative ictal-postictal hippocampal dysfunction is a major predictor of impaired long-term verbal memory consolidation in focal epilepsy. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885773","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":"T Cell-Mediated Targeting of Interneurons in Mice Shapes Hippocampal Remodeling and Epilepsy.","authors":"Daniel S Galvis-Montes, Lukas Henning, Karen M J van Loo, Rainer Surges, Susanne Schoch, Albert J Becker, Julika Pitsch","doi":"10.1002/ana.78349","DOIUrl":"https://doi.org/10.1002/ana.78349","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune encephalitis (AE) is associated with autoantibodies targeting distinct neuronal populations. In AE, antibodies against glutamate decarboxylase 65 (GAD65), expressed in GABAergic interneurons, are frequently detected. In GAD65-AE, hippocampal biopsies often show infiltrates of CD8⁺ cytotoxic T cells (CTLs), suggesting a prominent T cell-associated pathology. This has led to the hypothesis that CTLs contribute to neuronal injury in GABAergic circuits. We investigated whether selective CTL-mediated dysfunction of hippocampal interneurons may contribute to temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS).</p><p><strong>Methods: </strong>We developed a mouse model based on virus-mediated expression of ovalbumin (OVA) selectively in CA1 hippocampal interneurons into transgenic mice harboring OVA-specific CD8⁺ T cells. This approach enables interneuron-specific immune targeting within the hippocampus.</p><p><strong>Results: </strong>Interneuron-specific OVA expression in hippocampal CA1 resulted in rapid CD8⁺ T cell infiltration and targeting of inhibitory neuronal populations, accompanied by acute symptomatic seizures beginning 4 to 6 days after transduction. This acute inflammation-associated phase was followed by a chronic phase characterized by persistent spontaneous recurrent seizures (SRS), HS, sustained microglial activation, and astrogliosis. In the chronic stage, reduced Reelin expression coincided with interneuron vulnerability, granule cell dispersion (GCD), and mossy fiber reorganization. Proliferation analyses suggest that GCD results from displacement of pre-existing granule cells rather than aberrant neurogenesis, and is associated with gliosis and reduced Reelin expression.</p><p><strong>Interpretation: </strong>These findings demonstrate that selective CTL-mediated targeting of hippocampal CA1 interneurons induces seizures and hippocampal remodeling. This model shapes current concepts of epileptogenesis by showing that cell type-specific autoimmune mechanisms recapitulate key features of TLE, including GCD. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872536","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":"Aspergillus Ventriculitis.","authors":"Yu-Wei Hsu, Hao-Hsiang Hsu, Pang-Shuo Perng","doi":"10.1002/ana.78360","DOIUrl":"https://doi.org/10.1002/ana.78360","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872443","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":"Clinical Value of Aneurysm Wall Enhancement in Unruptured Intracranial Aneurysm.","authors":"Zhancheng Li, Pinchao Yang, Qizhi Zhao, Wei Peng","doi":"10.1002/ana.78271","DOIUrl":"10.1002/ana.78271","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"672"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350005","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":"Cofilin 1 Is an Extracellular Vesicle-Associated Plasma Biomarker of Parkinson's Disease in Humans.","authors":"Deepthy Chandran, Unnati Agrawal, Deepa Damayanthi, Divya T Nair, Geetha Mandagini, Sruthi S Nair, Deepti Narasimhaiah, Francis Boniface Fernandez, Poonam Thakur, Cibin T Raghavan, Syam Krishnan, Srinivas Gopala, Madhusoodanan Urulangodi","doi":"10.1002/ana.78348","DOIUrl":"https://doi.org/10.1002/ana.78348","url":null,"abstract":"<p><strong>Objective: </strong>Parkinson's disease (PD) lacks reliable, minimally invasive biomarkers for diagnosis. This study aimed to identify and validate PD-specific plasma extracellular vesicle (EV)-associated proteins.</p><p><strong>Methods: </strong>Plasma EVs were isolated by ultracentrifugation and characterized. Proteomic profiling of total plasma EVs from PD patients and healthy controls was performed, and a candidate protein identified after analysis was validated by enzyme-linked immunosorbent assay. Diagnostic accuracy was evaluated using receiver operating characteristic and precision-recall curve analysis. Disease specificity was examined in progressive supranuclear palsy and amyotrophic lateral sclerosis. Histochemical and immunofluorescence analyses were conducted in human and mouse PD brain tissue.</p><p><strong>Results: </strong>Proteomic analysis identified distinct PD-specific EV proteins, including cofilin 1 (CFL1), which was significantly enriched in EVs isolated from PD. EV-CFL1 levels were significantly elevated in PD compared with healthy controls (p < 0.0001). Receiver operating characteristic analysis showed strong diagnostic performance for EV-CFL1 (area under the curve 0.87). Also, EV CFL1 levels could distinguish PD from progressive supranuclear palsy patients (area under the curve 0.914). CFL1 was enriched in L1 cell adhesion molecule-positive EVs, indicating a possible neuronal origin. CFL1 was detected in both human and mouse PD brain sections. Importantly, EV-CFL1 levels were independent of age, disease stage, and motor severity.</p><p><strong>Interpretation: </strong>EV-associated CFL1 represents a PD-specific, blood-based marker with strong diagnostic accuracy and can distinguish PD from atypical parkinsonism. The presence of CFL1 was confirmed in human and mouse PD brain tissue, and its accumulation in PD brain suggests a possible role in disease pathogenesis. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862674","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 \"Clinical Value of Aneurysm Wall Enhancement in Unruptured Intracranial Aneurysm\".","authors":"Laura T van der Kamp, Maarten J Kamphuis, Olivier Naggara, Thomas Le Tat, Gabriel J E Rinkel, Gérard A P de Kort, Ruben P A van Eijk, Jeroen Hendrikse, Irene C van der Schaaf, Mervyn D I Vergouwen","doi":"10.1002/ana.78270","DOIUrl":"10.1002/ana.78270","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":"673"},"PeriodicalIF":7.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358567","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":"Effects of an Inpatient Program on Medication Errors in Hospitalized People with Parkinson's Disease.","authors":"Camila C Piccinin, Jeryl Ritzi T Yu, Victoria Stepanyants, Olivia Hogue, Claire Sonneborn, Anne Brooks, Patricia Clark, Shannon Shaffer, Laurie Moser, Tatiana Lopez-Gonzalez, Brent S Sokola, Kim Lewin, Roman Popov, Scott A Sperling, Hubert H Fernandez, Benjamin L Walter","doi":"10.1002/ana.78345","DOIUrl":"https://doi.org/10.1002/ana.78345","url":null,"abstract":"<p><strong>Objective: </strong>Hospitalized people with Parkinson's disease (PwP) face increased risks of medication errors and discharge to non-home settings, both of which are associated with adverse outcomes. This study assessed differences in medication error rates and discharge outcomes before and after implementation of a dedicated inpatient program for hospitalized PwP.</p><p><strong>Methods: </strong>During 2023, a Parkinson's disease (PD) inpatient program was implemented and refined combining: (1) an electronic health record (EHR) census for identification of hospitalized PwP; (2) inpatient monitoring and alignment of inpatient and outpatient regimens by movement-disorders-trained advanced practitioners; (3) customized EHR alerts and levodopa orders; (4) pharmacist support, and (5) staff education. Medication error rates and clinical outcomes were compared between January and June 2024 (post-implementation phase) and a pre-implementation retrospective cohort from 2018.</p><p><strong>Results: </strong>From January to June 2024, 366 post-implementation admissions were monitored. Among those receiving contraindicated medications, the median number of doses decreased from 2 (interquartile range [IQR] = 1-6) during pre-implementation to 1 (IQR: 1-2) post-implementation (p = 0.015). Days with a levodopa dose deviation decreased from 43.1% to 38.3%, p < 0.0001, improper levodopa formulation substitutions from 18.6% to 5%, p < 0.0001, timing deviations from 72.2% to 51.8%, p < 0.00001, missed doses from 21.5% to 16.8%, p = 0.013, and discharged to non-home settings from 44.8% to 38.3%, p = 0.038.</p><p><strong>Interpretation: </strong>Following implementation of a multidisciplinary and proactive inpatient program, reductions in medication errors and improved discharge outcomes were observed among PwP. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862738","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":"Multimodal Characterization of Glymphatic-Related Magnetic Resonance Imaging Markers in Huntington's Disease: A Multi-Cohort Retrospective Study.","authors":"Alexia Solomon, Zexi Wang, Francesco Sanvito, Zheng Zhou, Adys Mendizabal, Jingwen Yao","doi":"10.1002/ana.78344","DOIUrl":"https://doi.org/10.1002/ana.78344","url":null,"abstract":"<p><strong>Objective: </strong>To characterize magnetic resonance imaging (MRI)-based glymphatic surrogates in Huntington's disease (HD) using MRI measures of perivascular diffusivity and structural perivascular alterations across multiple large cohorts.</p><p><strong>Methods: </strong>We analyzed 2,731 MRI sessions from 880 participants across 3 large retrospective HD cohorts. HD gene carriers were grouped by the HD Integrated Staging System into stage 0 to 3. We assessed the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and MRI-visible enlarged perivascular spaces (EPVS). Linear mixed-effects models examined group differences and associations with motor, cognitive, and functional measures. Likelihood ratio tests evaluated their added explanatory value beyond established imaging, genetic, and demographic variables.</p><p><strong>Results: </strong>Left ALPS indices were lower at more advanced disease stages (stage 1: -3.71%, Cohen's d: -0.25; stage 2: -4.33%, Cohen's d: -0.31; Stage 3: -6.43%, Cohen's d: -0.46; all p < 0.05) compared with controls, independent of demographic and clinical variables. EPVS burden showed region-specific patterns, with subcortical EPVS volume fraction increased in HD (stage 1-3: +49.9% to +63.7%, Cohen's d: 0.47 to 0.55, p < 0.0001), whereas white matter EPVS volume fraction decreased at Stage 3 (-13.8%, Cohen's d: -0.21, p < 0.05). Lower ALPS indices correlated with higher motor impairment (p < 0.0001) and reduced functional capacity (p < 0.01). Both ALPS and EPVS improved prediction of composite HD progression beyond CAG-Age Product Score and striatal volume.</p><p><strong>Interpretation: </strong>Multimodal MRI revealed stage-dependent alterations in MRI-based glymphatic surrogates with low to moderate effect sizes. These findings suggest that DTI-ALPS and EPVS metrics offer complementary, noninvasive indicators of HD pathology derivable from routine imaging protocols. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862726","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":"Therapeutic Prospects of Ketamine for Cataplexy in Narcolepsy Type 1: Evidence from a Human Case and a Murine Model.","authors":"Francois Ricordeau, Sebastien Arthaud, Leila Langbour, Silvia Melzi, Aurelie Richard-Mornas, Hannah Doudoux, Benjamin Rolland, Laure Peter-Derex, Christelle Peyron","doi":"10.1002/ana.78343","DOIUrl":"https://doi.org/10.1002/ana.78343","url":null,"abstract":"<p><p>Narcolepsy type 1 is characterized by cataplexy, for which current treatments targeting monoaminergic, histaminergic, and GABAergic pathways may be ineffective or poorly tolerated. We report the case of a 34-year-old man with narcolepsy type 1, intolerant to standard therapies, who experienced marked and sustained cataplexy reduction with morning intranasal ketamine, with symptom recurrence upon discontinuation. To confirm this observation, ketamine was compared with vehicle in a crossover study in orexin knockout mice implanted for polysomnography. Ketamine dramatically reduced time spent in cataplexy (-76%, p = 0.008) without affecting sleep architecture. These translational findings suggest ketamine as a potential anticataplectic agent, warranting further clinical investigation. ANN NEUROL 2026.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838685","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":"Degos Disease Presenting as a Hemorrhagic Brain Mass.","authors":"Junjiang Wu, Fan Lin","doi":"10.1002/ana.78338","DOIUrl":"https://doi.org/10.1002/ana.78338","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838586","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}