Annals of Neurology最新文献

{"title":"Elevated Risk of Cerebral Arteriovenous Malformation Rupture during Pregnancy and Puerperium.","authors":"Haibin Zhang, Heze Han, Yuqing Jiao, Yahui Zhao, Li Ma, Ruinan Li, Zhipeng Li, Anqi Li, Kexin Yuan, Qinghui Zhu, Chengzhuo Wang, Yukun Zhang, Junlin Lu, Debin Yan, Dezhi Gao, Geng Guo, Xun Ye, Youxiang Li, Shibin Sun, Hao Wang, Yuanli Zhao, Yu Chen, Rong Wang, Limin Feng, Xiaolin Chen","doi":"10.1002/ana.70014","DOIUrl":"https://doi.org/10.1002/ana.70014","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral arteriovenous malformations (AVM) pose a significant risk during pregnancy because of hormonal changes and increased hemodynamic stress. This study aims to assess the risk of AVM rupture during pregnancy and puerperium and to identify risk factors associated with rupture.</p><p><strong>Methods: </strong>This prospective cohort study included 588 women with AVMs and a history of pregnancy, enrolled from a nationwide registry in China between August 2011 and August 2021. A case-crossover design was used to compare rupture risk during pregnancy, puerperium, and non-pregnancy periods, adjusting for clinical and morphological factors. Multivariable logistic regression analysis identified independent risk factors.</p><p><strong>Results: </strong>The risk of AVM rupture was significantly higher during pregnancy compared to non-pregnancy periods (4.5% vs 1.6%; risk ratio [RR], 3.1; 95% confidence interval [CI], 2.3-4.2; p < 0.001). The risk was particularly elevated during the second and third trimesters. Key factors independently associated with increased rupture risk included adolescent or advanced-age pregnancy (adolescent ≤19 years or advanced ≥35 years, odds ratio [OR], 8.32; 95% CI, 2.09-28.12, p = 0.001), a history of AVM rupture before pregnancy (OR, 4.20; 95% CI, 1.37-11.40; p = 0.007), diffuse nidus (OR, 2.32; 95% CI, 1.07-5.12; p = 0.033), and multifetal pregnancy (OR 18.31; 95% CI, 1.14-293.27; p = 0.040).</p><p><strong>Interpretation: </strong>Pregnancy substantially increases the risk of AVM rupture, particularly during the second and third trimesters and compared to pre-first pregnancy periods. Risk factors such as adolescent or advanced-age pregnancy and multifetal pregnancy further increase the risk. These findings underscore the importance of tailored management during pregnancy for optimizing maternal and fetal outcomes. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793028","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":"Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.","authors":"Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff, Carol A Hitchon, Jan Hillert, Ingrid Kockum, Yi Lu, Fred D Lublin, Kyla McKay, Tomas Olsson, Scott Patten, Amit Patki, Hayley Riel, Klementy Shchetynsky, Pernilla Stridh, Hemant K Tiwari, Jerry S Wolinsky, Kaarina Kowalec","doi":"10.1002/ana.70020","DOIUrl":"https://doi.org/10.1002/ana.70020","url":null,"abstract":"<p><strong>Objective: </strong>A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.</p><p><strong>Methods: </strong>In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and tested its association with annualized relapse rate and worsening disability. In the US cohort, we additionally explored the time to relapse, number of enhancing lesions, and confirmed Expanded Disability Status Scale (EDSS) worsening during the study period.</p><p><strong>Results: </strong>We included 3,420 relapsing-onset PwMS of European genetic ancestry with a median follow-up of 3 to 5 years. Meta-analyses revealed for each 1-standard deviation increase in the depression PGS, the relapse rate increased (incidence rate ratio: 1.23, 95% confidence interval [CI] = 1.01-1.50). In the US cohort, higher depression PGS was associated with protocol-defined relapses (hazard ratio [HR] = 1.58, 95% CI = 1.03-2.43), and time to confirmed EDSS worsening (HR = 1.51, 95% CI = 1.03-2.22) with this effect largely direct.</p><p><strong>Interpretation: </strong>Meta-analyses showed a higher depression genetic burden was associated with increased MS disease activity. In the US clinical trial cohort only, we found a significant association between higher depression PGS and time to relapse and confirmed EDSS worsening. These findings may provide insights into MS disease activity and disability worsening. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793027","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":"Venous Hypertension in the Medulla Due to a DAVF.","authors":"Long Yan, Ning Ma","doi":"10.1002/ana.70001x","DOIUrl":"https://doi.org/10.1002/ana.70001x","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936785","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":"Recurrent Ischemic Strokes Due to Os Odontoideum.","authors":"Jian Wang, Li He, Shihong Zhang, Fayun Hu","doi":"10.1002/ana.70024","DOIUrl":"https://doi.org/10.1002/ana.70024","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937087","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":"Proteomics and the Risk of Incident Embolic and Thrombotic Stroke.","authors":"Michelle C Johansen, Jinyu Chen, Keenan A Walker, Ziqiao Wang, Wendy Wang, Lin Yee Chen, Rizwan Kalani, James Floyd, Myriam Fornage, James Russell Pike, Rebecca F Gottesman, Josef Coresh","doi":"10.1002/ana.70011","DOIUrl":"10.1002/ana.70011","url":null,"abstract":"<p><strong>Objective: </strong>Personalized approaches to ischemic stroke diagnosis are needed. We determine differences in proteomic signatures of incident embolic (EIS) and thrombotic stroke (TIS) by age and resultant pathways using large-scale proteomics.</p><p><strong>Methods: </strong>Participants in the Atherosclerosis Risk in Communities Study (ARIC) from visit 2 (V2, 1990-1992) until 2020 without prevalent stroke with available SomaScan data (4,955 protein targets) at V2 (mid-life, n = 10,929), and then again at visit 5 (V5, 2011-2013, n = 4,463) were included. Covariate adjusted Cox hazard models determined the association between proteins, and adjudicated incident EIS or TIS from V2 to V5 and from V5 to 2020.</p><p><strong>Results: </strong>Among 10,929 participants (56% female, 23% Black, follow-up ~20 years), 20 proteins measured in mid-life were associated with either EIS (n = 168) or TIS (n = 459) in mid-life, and 4 measured in late-life were associated with late-life stroke (73 EIS and 124 TIS events) at the Bonferroni threshold p < 1E-5. In mid-life, N-terminal pro-B-type natriuretic peptide (NPPB) was significantly associated with EIS, but not TIS (p-difference = 9.14E-7). Nineteen mid-life proteins were strongly associated with TIS; 7 strongly associated with TIS and only nominally (p < 0.05) with EIS and the remaining 12 with TIS only. In late-life, NPPB, serine protease inhibitor Kazal-type 4, oligodendrocyte-myelin-glycoprotein, and neurocan-core protein were significantly associated with EIS, but not TIS. Ingenuity Pathway Analysis tools implicated cancer for EIS-associated proteins, whereas TIS pathways reflected cell-structure and atherogenesis.</p><p><strong>Interpretation: </strong>We identified plasma proteins associated with risk of EIS versus TIS reflecting distinct stroke mechanisms: cardiac dysfunction protein in EIS (eg, NPPB) and inflammation dysregulation in TIS (eg, interleukins). ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774369","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":"Heart Rate Profiles During Exercise and Incident Parkinson's Disease.","authors":"Stefan van Duijvenboden, Julia Ramírez, Job Scheurink, Sirwan K L Darweesh, Michele Orini, Andrew Tinker, Patricia B Munroe, Jos Thannhauser, Luc Evers, Joanna IntHout, Pier D Lambiase, Bastiaan R Bloem, Aiden Doherty, Marc A Brouwer","doi":"10.1002/ana.70010","DOIUrl":"https://doi.org/10.1002/ana.70010","url":null,"abstract":"<p><strong>Objective: </strong>To determine whether established heart rate parameters of exercise, related to cardiac autonomic function, are associated with incident Parkinson's disease, independent of both clinical and autonomic prodromal features.</p><p><strong>Methods: </strong>A study of UK Biobank participants who performed a standardized bicycle exercise test (2009-2013), followed until November 2022, and analyzed in January 2024, was carried out. Heart rate increase from rest to exercise, and heart rate decrease from peak exercise to recovery were associated with incident Parkinson's disease. Multivariable adjustment was performed both for clinical characteristics and for prodromal non-cardiac autonomic features.</p><p><strong>Results: </strong>A total of 69,288 eligible participants (men 48%, mean age 56.8 years [SD 8.2 years]) were followed for 12.5 years: among the 319 (0.5%) who developed Parkinson's disease, recognized prodromal markers (constipation, bladder dysfunction) were more common at baseline. The median lag time to diagnosis was 9.3 years (interquartile range 4.4). Both heart rate increase (37.5 [SD 11.5] vs 40.8 [SD 12.4] b.p.m., p < 0.001) and recovery (23.4 [SD 8.8] vs. 27.8 [SD 10.3] b.p.m., p < 0.001) were significantly lower in incident cases compared with controls. Heart rate recovery was independently associated with incident Parkinson's disease, whereas heart rate increase was not. Specifically, a blunted heart rate lowering during recovery was associated with a 30% higher risk of incident Parkinson's disease (HR 1.3; 95% CI 1.1-1.4; p < 0.001 per 10 beats less recovery).</p><p><strong>Interpretation: </strong>Collectively, this suggests that cardiac autonomic involvement precedes clinically manifest Parkinson's disease, and that heart rate recovery might serve as a quantitative prodromal marker. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768152","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":"Use of FDG-PET in Balamuthia mandrillaris Amebic Encephalitis.","authors":"Kristoffer E Leon, Andreas M Rauschecker, Felicia C Chow","doi":"10.1002/ana.70012","DOIUrl":"https://doi.org/10.1002/ana.70012","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936797","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":"Ruptured Intracranial Aneurysm Re-Ruptured During Real-Time Rotational Angiography.","authors":"Xiheng Chen, Siming Gui, Ming Lv","doi":"10.1002/ana.70005","DOIUrl":"https://doi.org/10.1002/ana.70005","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937115","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":"Frequency of Microvascular Pathology and Hippocampal Atrophy on Magnetic Resonance Imaging in a Community Study of Alzheimer's Disease with Blood-Based Biomarkers.","authors":"Tamil Iniyan Gunasekaran, Danurys Sanchez, Dolly Reyes-Dumeyer, Rabel Ventura, Clarissa Morales, Mohamad Alshikho, Annie J Lee, Rafael A Lantigua, Yian Gu, Lawrence S Honig, Badri N Vardarajan, Adam M Brickman, Richard Mayeux","doi":"10.1002/ana.70006","DOIUrl":"https://doi.org/10.1002/ana.70006","url":null,"abstract":"<p><strong>Objective: </strong>Blood-based biomarkers for Alzheimer's disease (AD), representing antemortem indicators of AD pathophysiology, have greatly improved the accuracy of diagnosis. However, these biomarkers may not capture a frequent coincident pathology, such as cerebrovascular disease.</p><p><strong>Methods: </strong>We measured plasma amyloid-β40, amyloid-β42, total tau, tau phosphorylated at threonine 181, tau phosphorylated at threonine 217, glial fibrillary acidic protein, and neurofilament light chain in 685 multiancestral individuals who had clinical assessments and brain magnetic resonance imaging. The cohort was represented by individuals of European, African American, and Caribbean Hispanic ancestry. Participants were then classified as biomarker-positive or -negative for AD based on previously established cutoffs: 2.65 pg/mL for, tau phosphorylated at threonine 181 and 0.39 pg/mL for tau phosphorylated at threonine 217. We used magnetic resonance images to compare white matter hyperintensity volume (WMH), silent brain infarcts, microhemorrhages, and hippocampus volume across groups by their clinical diagnosis and biomarker status.</p><p><strong>Results: </strong>In the P-tau181 group (n = 685), 70 individuals (10.2%) had dementia or amnestic mild cognitive impairment. A total of 40 (57%) were biomarker-positive for AD, and 30 were classified as other dementia. Among 615 without dementia, 265 (40.3%) were preclinical AD, and 348 (50.8%) were biomarker-negative controls. In the tau phosphorylated at threonine 217 group (n = 535), 54 (10.1%) had dementia or amnestic mild cognitive impairment, including 33 biomarker-positive for AD and 21 with other dementia, whereas 183 (38.0%) were preclinical AD and 298 (61.9%) were biomarker-negative controls. Across both classifications, biomarker-positive for AD and other dementia individuals showed greater WMH volumes, more infarcts, and smaller hippocampus. However, P-tau217 positivity was more sensitive to WMH volume differences, whereas tau phosphorylated at threonine 181 better captured hippocampal atrophy and silent brain infarcts. Interestingly, ethnic differences may also influence detection of changes in WMH volumes, hippocampal volume, and infarcts in relation to specific biomarkers.</p><p><strong>Interpretation: </strong>The results indicate that cerebrovascular disease is consistently involved in dementia either directly or as a coincident pathology in AD. These results underscore the need to incorporate both blood-based biomarkers and structural imaging in the evaluation of patients with dementia. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740730","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":"Exenatide Once Weekly in the Treatment of Patients with Multiple System Atrophy.","authors":"Nirosen Vijiaratnam, Christine Girges, Martin Wiegand, Claudia Ismail, Alexandra Lameirinhas, Alison Yarnall, Cameron Kirk, Silvia Del-Din, Lynn Rochester, Christopher Kobylecki, Gareth Ambler, Simon Skene, Henry Houlden, Viorica Chelban, Amanda Heslegrave, Wendy Phillips, Alan Whone, Niall Quinn, Christian Lambert, Charlotte Dore, Huw R Morris, Mathew H Horrocks, Ji Eun Lee, Judi O'Shaughnessy, Yazhou Li, Nigel H Greig, Sonia Gandhi, Vincenzo Libri, Dilan Athauda, Tom Foltynie","doi":"10.1002/ana.70004","DOIUrl":"https://doi.org/10.1002/ana.70004","url":null,"abstract":"<p><strong>Objective: </strong>Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has neuroprotective effects in preclinical models of multiple system atrophy (MSA). We investigated these effects in a proof-of-concept clinical trial.</p><p><strong>Methods: </strong>In this single-center, randomized, open label trial, participants with MSA were randomly assigned (1:1) to receive subcutaneous injections of exenatide 2 mg weekly for 48 weeks, or as controls, followed by a 48-week washout period. The primary outcome was the Unified Multiple System Atrophy Rating Scale (UMSARS) parts I + II combined score at 48 weeks. Objective secondary outcome measures included the numbers of participants losing ambulation; scoring ≥ 3 on UMSARS part I items for falls, speech, swallowing, as well as timed walking and measures of quality of life and cognition.</p><p><strong>Results: </strong>Between September 23, 2020, and May 6, 2022, 50 participants were recruited (25 in each group). At 48 weeks, UMSARS parts I + II scores had worsened by 6.1 points (95% confidence interval [CI] = 3.0 to 9.3, SD = 6.9) in the exenatide group and by 13 3 points (95% CI = 9.2 to 17.3, SD = 9.4) in the control group, an adjusted mean difference of -7.4 points (-11.3 to -3.6, p = 0.0003). There were no statistically significant differences at either 48 or 96 weeks in the secondary outcome measures. Biomarker analysis of neurofilament light chain and cerebral spinal fluid (CSF) alpha-synuclein oligomer load, sensor-derived gait measures, and imaging findings were also similar between groups.</p><p><strong>Interpretation: </strong>Exenatide was associated with positive effects on participant-reported symptoms and clinician-rated MSA severity. In contrast, none of the objective comparisons differed according to randomization. Given the open label trial design, the discrepancy between the primary outcome and the objective measures may be explicable as placebo effects/observer bias. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726178","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}