Annals of Neurology最新文献

{"title":"About Primary Angiitis Central Nervous System: Time for a Shared Prospective Neurovascular Effort?","authors":"Marialuisa Zedde, Rosario Pascarella","doi":"10.1002/ana.78021","DOIUrl":"https://doi.org/10.1002/ana.78021","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937131","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 Letter to the Editor: \"About Primary Angiitis Central Nervous System: Time for a Shared Prospective Neurovascular Effort?\"","authors":"Carolin Beuker, Jens Minnerup","doi":"10.1002/ana.78022","DOIUrl":"https://doi.org/10.1002/ana.78022","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937161","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":"Polygenic Resistance to Blood Pressure Treatment and Stroke Risk: Insights from the All of Us Research Program.","authors":"Shufan Huo, Cyprien A Rivier, Santiago Clocchiatti-Tuozzo, Daniela Renedo, Nils Petersen, Adam de de Havenon, Daniella Meeker, Hongyu Zhao, Lucila Ohno-Machado, Kevin N Sheth, Guido J Falcone","doi":"10.1002/ana.78009","DOIUrl":"10.1002/ana.78009","url":null,"abstract":"<p><strong>Objective: </strong>Our goal was to investigate the impact of polygenic susceptibility to hypertension on systolic blood pressure (BP), uncontrolled hypertension, and stroke among hypertensive patients with BP treatment prescription.</p><p><strong>Methods: </strong>This genetic association study used data from the All of Us Research Program (2017-2023) and replicated findings using the United Kingdom Biobank (2006-2010). Participants prescribed BP medication ≥4 years, with diagnosed hypertension or ≥2 systolic BP measurements >130mmHg, and without a previous stroke were categorized as having low, intermediate, or high polygenic susceptibility to hypertension using percentiles (<20, 20-80, >80) of a polygenic risk score for systolic BP. Primary outcomes were systolic BP, and uncontrolled hypertension (systolic BP > 140mmHg). The secondary outcome was incident stroke during 4-years follow-up. Multivariable linear, logistic, and Cox proportional hazards regressions assessed the influence of polygenic susceptibility to hypertension on each outcome.</p><p><strong>Results: </strong>A total of 51,006 participants (mean age = 56, 55% female) were included. Intermediate and high genetic risk were associated with higher systolic BP (intermediate: beta = 2.55, standard error [SE] = 0.16, high: beta = 4.81, SE= 0.20, all p < 0.001), and with 36% (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.28-1.44) and 80% (OR = 1.80, 95% CI = 1.69-1.93) higher odds of uncontrolled hypertension, respectively. Furthermore, high genetic risk was associated with 23% (hazard ratio [HR] = 1.23, 95% CI = 1.03-1.46) increased stroke hazard. These results were replicated in 84,259 participants (mean age = 61, female sex = 46%).</p><p><strong>Interpretation: </strong>Among hypertensive adults who were prescribed BP medication, polygenic susceptibility to hypertension correlates with higher systolic BP and higher rates of uncontrolled hypertension and stroke. Our findings support further research on personalized interventions targeting high-risk individuals. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870538","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":"Behavior-iEEG-Spectral-Power-Correlation: Defining Neural Substrates of Naturalistic Behavior.","authors":"Brian Ervin, Clayton Frink, Jason Buroker, Paul S Horn, Anna W Byars, Craig Scholle, Hansel M Greiner, Francesco T Mangano, Katherine D Holland, Gregory Hickok, Nathan E Crone, Ravindra Arya","doi":"10.1002/ana.70002","DOIUrl":"https://doi.org/10.1002/ana.70002","url":null,"abstract":"<p><strong>Objective: </strong>Intracranial language localization with electrical stimulation mapping (ESM) and high-gamma modulation (HGM) mapping relies on artificial, repetitive tasks, requiring sustained cooperation from patients. Herein, we tested the validity of unstructured, interpersonal, naturalistic conversation for language localization, using a novel methodology: Behavior-iEEG-Spectral-Power correlation (BESPoC). We first validated BESPoC against ESM, HGM, and neuropsychological outcomes using well-established language tasks, then demonstrated the validity of naturalistic conversation.</p><p><strong>Methods: </strong>We included 134 patients (59 females), aged 2-29 years, undergoing standard-of-care stereo-electroencephalography monitoring who engaged in picture naming, auditory naming, story listening, and conversed with a family member. ESM and HGM analysis were performed using established methods. BESPoC methodology quantified correlation between stereo-electroencephalography spectral power from task recordings, obviating the need for any trial-based epochs, and behavioral markers. The large sample size allowed mixed-effects modeling to compare BESPoC with HGM and ESM.</p><p><strong>Results: </strong>BESPoC showed high specificity (0.79-0.83) and sensitivity (0.64-0.86) for localizing HGM language sites across the tasks. BESPoC also compared well with HGM across all language tasks for localizing ESM speech/language sites. With conventional tasks, BESPoC was superior to HGM for modeling neuropsychological deficits seen, despite preserving ESM speech/language sites. Naturalistic conversation compared well with standard tasks for localization of HGM and ESM language sites, and determined neuropsychological outcomes better than conventional tasks.</p><p><strong>Interpretation: </strong>Using BESPoC methodology naturalistic conversation is shown to produce valid cortical language maps of both expressive and receptive language, and determine neuropsychological outcomes after epilepsy surgery. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858666","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":"Biallelic Variants in the DARS2 Gene as a Novel Cause of Axonal Charcot-Marie-Tooth Disease.","authors":"Berta Estévez-Arias, Siiri Sarv, Nathalie Bonello-Palot, Laura Carrera-García, Carlos Ortez, Jesica Expósito-Escudero, Delia Yubero, Jordi Muchart, Emilien Delmont, Eve Õiglane-Shlik, Teele Meren, Sanna Puusepp, Ülle Murumets, Gajja S Salomons, Bjarne Udd, Liis Väli, Lara Cantarero, Carsten G Bönnemann, Andrés Nascimento, Santiago Ramón-Maiques, Katrin Õunap, Janet Hoenicka, Daniel Natera-de Benito, Francesc Palau","doi":"10.1002/ana.78005","DOIUrl":"https://doi.org/10.1002/ana.78005","url":null,"abstract":"<p><strong>Objective: </strong>Charcot-Marie-Tooth (CMT) disease is a heterogeneous group of genetic neuropathies, with >90 genes identified. Several aminoacyl-tRNA synthetases have been linked to CMT. DARS2, encoding the mitochondrial aspartyl-tRNA synthetase, has been typically associated with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. This study aimed to investigate the association between biallelic DARS2 variants and axonal CMT.</p><p><strong>Methods: </strong>We investigated 5 individuals from 3 unrelated families with axonal CMT and biallelic DARS2 variants. Functional studies in fibroblasts assessed their effects on DARS2 expression, localization, and mitochondrial function. Enzymatic activity was evaluated in HEK293 cells.</p><p><strong>Results: </strong>The 5 individuals, including 4 adults, presented with childhood-onset progressive axonal CMT. None had leukoencephalopathy, but one showed central nervous system involvement, with intellectual disability and epilepsy. Genetic analysis identified compound heterozygous DARS2 variants: family A, p.Ser238Phe and p.Arg336Cys; family B, p.Ser238Phe and p.Ile25Thrfs*38; family C, c.492+2T>C and p.Pro503Leu. Functional studies revealed reduced DARS2 protein levels, mitochondrial network abnormalities, and impaired mitochondrial function. p.Ser238Phe behaves as a hypomorphic allele, whereas p.Pro503Leu reduced DARS2 enzymatic activity by 75%.</p><p><strong>Interpretation: </strong>Our findings expand the DARS2-related disease spectrum, establishing a novel association with axonal CMT. Hypomorphic variants, such as p.Ser238Phe, when paired with more deleterious variants, result in isolated axonal CMT, whereas more severe combinations-although not as deleterious as those seen in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation-result in axonal CMT with central nervous system involvement, albeit without leukoencephalopathy. These observations raise the possibility that DARS2-associated diseases form a continuum rather than representing strictly distinct central or peripheral nervous system disorders. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854099","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":"Reassessing the Impact of Endovascular Thrombectomy on Cerebral Edema and Functional Outcomes.","authors":"Brijesh Sathian, Hanadi Al Hamad","doi":"10.1002/ana.78007","DOIUrl":"https://doi.org/10.1002/ana.78007","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833591","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 \"Reassessing the Impact of Endovascular Thrombectomy on Cerebral Edema and Functional Outcomes\".","authors":"Ximing Nie, Liping Liu","doi":"10.1002/ana.78008","DOIUrl":"https://doi.org/10.1002/ana.78008","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833596","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":"Adjunctive Thrombolytics After Successful Endovascular Reperfusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Mohamed F Doheim, Mahmoud H Mohammaden, Ammar Jumah, Qingwu Yang, Wenjie Zi, Yangmei Chen, Yamei Tang, Yajie Liu, Xiaochuan Huo, Liping Liu, Bernard Yan, Zhongrong Miao, Wei Hu, Chunrong Tao, Xinfeng Liu, Liqun Jiao, Xuesong Bai, Wenhuo Chen, Diogo C Haussen, Thanh Nguyen, Raul G Nogueira","doi":"10.1002/ana.70021","DOIUrl":"https://doi.org/10.1002/ana.70021","url":null,"abstract":"<p><strong>Objective: </strong>The efficacy and safety of intra-arterial thrombolysis (IAT) as an adjunct to endovascular thrombectomy (EVT) in large vessel occlusion strokes (LVOS) remain uncertain, with recent randomized controlled trials (RCTs) yielding conflicting results. This meta-analysis aimed to assess the impact of IAT following successful EVT in patients with LVOS.</p><p><strong>Methods: </strong>A comprehensive search was conducted across PubMed, ClinicalTrials.gov, the Cochrane Library databases, and the International Stroke Conference 2025 abstracts to identify RCTs evaluating IAT following successful EVT from January 2015 to February 2025. The primary outcome was the odds of achieving an excellent functional outcome (defined as a modified Rankin Scale [mRS] = 0-1 at 90 days). Secondary outcomes included 90-day functional independence (mRS = 0-2). Safety measures included symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. The protocol was registered in PROSPERO (CRD420250651602).</p><p><strong>Results: </strong>The primary pooled analysis of 6 RCTs (N = 1,974) showed that IAT significantly increased the likelihood of achieving excellent functional outcome at 90 days (mRS = 0-1: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.21-1.80, p < 0.001), with a notable effect in anterior circulation (OR = 1.48, 95% CI = 1.18-1.87, p < 0.001) but not in posterior circulation LVOS (OR = 1.51, 95% CI = 0.83-2.74, p = 0.18). Among thrombolytic drugs, alteplase was most strongly associated with favorable outcomes (mRS = 0-1: OR = 1.94, 95% CI = 1.31-2.87, p < 0.001), followed by tenecteplase (OR = 1.43, 95% CI = 1.08-1.89, p = 0.01). No significant safety concerns were observed, as there was no increase in the odds of sICH (OR = 1.15, 95% CI = 0.75-1.75, p = 0.51) or 90-day mortality (OR = 1.00, 95% CI = 0.79-1.26, p = 0.99). Sensitivity analyses for all outcomes yielded consistent results.</p><p><strong>Interpretation: </strong>IAT following successful EVT significantly enhances the likelihood of achieving an excellent functional outcome, particularly in anterior circulation strokes. Although the benefit in posterior circulation strokes remains uncertain, the lack of significant differences in sICH risk and mortality across thrombolytic drugs and stroke locations support the safety of IAT. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833588","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":"Anterior Versus Posterior Insular Epilepsy: Correlations with Semiology Based on Stereoelectroencephalography.","authors":"Jason Chisholm, Balu Krishnan, Jean Khoury, Andreas Alexopoulos, William Bingaman, Demitre Serletis, Imad Najm, Juan C Bulacio","doi":"10.1002/ana.70015","DOIUrl":"https://doi.org/10.1002/ana.70015","url":null,"abstract":"<p><strong>Objective: </strong>To characterize insular seizure semiology and correlate with stereoelectroencephalography (SEEG) seizure onset in a well-defined cohort, in particular examining differences between anterior and posterior insular seizures.</p><p><strong>Methods: </strong>We documented all semiological signs and the timing of emergence for 45 patients with SEEG-confirmed insular epilepsy, along with the precise location of the seizure onset zone (SOZ) within the insula. Semiological signs and other non-invasive data were compared between those with anterior and posterior insula SOZ, with more detailed insular subregion description when appropriate. Co-occurrence patterns of insular semiological signs were also investigated.</p><p><strong>Results: </strong>A total of 87% reported auras and the corresponding insular SOZ demonstrated an anterior-to-posterior gradient by aura type. The absence of aura was significantly associated with an anterior insula SOZ (p = 0.01). Late grunting/moaning (p = 0.07), symmetric mouth elementary motor (p = 0.1), blinking (p = 0.05), and chewing/repetitive swallowing (p = 0.09) also suggested an anterior insula SOZ. Unilateral non-painful somatosensory aura (p = 0.07) and early arm/hand elementary motor (p = 0.1) suggested a posterior insular SOZ.</p><p><strong>Interpretation: </strong>We report the characteristics and semiological features in a large cohort of primary insular epilepsy patients. The type of aura is crucial for identifying the SOZ and the timing of semiological emergence contributes to the anatomo-electro-clinical localization of an insular SOZ. These findings can enhance identification of insular epilepsy, making targeted curative treatment feasible. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833589","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":"Molecular and Genetic Mechanisms in Autism Spectrum Disorder.","authors":"April Pruitt, Abha R Gupta, Ellen J Hoffman","doi":"10.1002/ana.70013","DOIUrl":"https://doi.org/10.1002/ana.70013","url":null,"abstract":"<p><p>Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by deficits in social communication and interaction and the presence of repetitive and restricted behaviors. ASDs are clinically and genetically heterogeneous with hundreds of genes identified through large-scale whole exome and genome sequencing studies contributing to risk. Recent studies are beginning to illuminate shared mechanisms across ASD-associated genes at the molecular, cellular, circuit, and behavioral levels, identifying neurogenesis and excitatory-inhibitory neuron development as points of biological convergence. These functional analyses of ASD genes provide substantial promise for gaining a deeper understanding of ASD pathophysiology and elucidating novel therapeutic targets. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833590","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}