Annals of Neurology最新文献

{"title":"Reply to “Revolutionizing Neuroprognostication: The Enduring Value of Pupillary Reflexes Enhanced by Quantitative Pupillometry”","authors":"Yili Du MS, Charlene J. Ong MD, MPHS","doi":"10.1002/ana.27257","DOIUrl":"10.1002/ana.27257","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956486","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":"Revolutionizing Neuroprognostication: The Enduring Value of Pupillary Reflexes Enhanced by Quantitative Pupillometry","authors":"Calixto Machado MD, PhD, FAAN, Jose Jesus Sanchez MD","doi":"10.1002/ana.27255","DOIUrl":"10.1002/ana.27255","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953413","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":"Prevalence of Cerebral Amyloid Angiopathy and Associated Risk of Subsequent Ischemic and Hemorrhagic Stroke and Mortality in a Nationwide Cohort.","authors":"Samuel S Bruce, Cenai Zhang, Ava L Liberman, Alexander E Merkler, Babak B Navi, Gloria C Chiang, Costantino Iadecola, Hooman Kamel, Santosh B Murthy","doi":"10.1002/ana.27253","DOIUrl":"https://doi.org/10.1002/ana.27253","url":null,"abstract":"<p><strong>Objective: </strong>There are limited population-based data regarding the prevalence of cerebral amyloid angiopathy (CAA) and associated risks of mortality and incident cerebrovascular events.</p><p><strong>Methods: </strong>We performed a retrospective cohort study using inpatient and outpatient claims from 2008 to 2022 from a 5% national sample of Medicare beneficiaries. CAA and ischemic and hemorrhagic stroke were identified using validated International Classification of Diseases 10th Revision (ICD-10) codes. We ascertained CAA from October 1, 2015 through 2022, and used data from 2008 through September 30, 2015 to ascertain comorbidities including prevalent stroke. We used Cox regression to examine the association of CAA with subsequent death and incident stroke subtypes after adjustment for demographics, vascular risk factors, and Charlson comorbidities.</p><p><strong>Results: </strong>Among 1,920,312 Medicare beneficiaries in our sample, 2,161 (11.3 per 10,000) had a diagnosis of CAA. In adjusted Cox regression analysis, there was an association between CAA and subsequent mortality (HR 4.9; 95% CI 4.6-5.2). Among 1,872,474 patients without prevalent stroke, including 900 of the CAA patients, there was a significant association between CAA and an increased risk of any stroke (HR 8.0; 95% CI 6.7-9.6), ischemic stroke (HR 4.6; 95% CI 3.6-6.0), intracerebral hemorrhage (HR 26.9; 95% CI 20.3-35.6), and subarachnoid hemorrhage (HR 21.6; 95% CI 12.2-38.1). After a diagnosis of CAA, absolute risks of ischemic stroke and intracerebral hemorrhage were broadly similar.</p><p><strong>Interpretation: </strong>In a large, nationwide cohort of Medicare beneficiaries, the prevalence of clinically diagnosed CAA was approximately 11 per 10,000. CAA was associated with an increased risk of mortality and incident stroke, both hemorrhagic and ischemic. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952244","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":"Elevated α-Synuclein Aggregate Levels in the Urine of Patients with Isolated REM Sleep Behavior Disorder and Parkinson's Disease","authors":"Laura Müller MS,&nbsp;Pelin Özdüzenciler MS,&nbsp;Charlotte Schedlich-Teufer MD,&nbsp;Aline Seger MD,&nbsp;Hannah Jergas MD,&nbsp;Gereon R. Fink MD,&nbsp;Dieter Willbold PhD,&nbsp;Michael Sommerauer MD,&nbsp;Michael T. Barbe MD,&nbsp;Gültekin Tamgüney PhD","doi":"10.1002/ana.27250","DOIUrl":"10.1002/ana.27250","url":null,"abstract":"<p>Parkinson's disease (PD) is a neurodegenerative disorder characterized by α-synuclein aggregation in neurons. Recent advances suggest α-synuclein aggregates could serve as a biomarker for PD and related synucleinopathies. This study used surface-based fluorescence intensity distribution analysis (sFIDA) to measure α-synuclein aggregates in urine. Patients with PD and isolated rapid eye movement sleep behavior disorder, a precursor to PD, had elevated concentrations compared with healthy controls. Sensitivity and specificity were 83% and 65% for PD versus controls and 89% and 62% for isolated rapid eye movement sleep behavior disorder versus controls. The findings highlight sFIDA's potential for diagnosing synucleinopathies. ANN NEUROL 2025;98:147–151</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"147-151"},"PeriodicalIF":8.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.27250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956431","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":"Phosphatemia is an Independent Prognostic Factor in Amyotrophic Lateral Sclerosis.","authors":"Rosario Vasta, Emanuele Koumantakis, Antonio Canosa, Umberto Manera, Maurizio Grassano, Francesca Palumbo, Sara Cabras, Enrico Matteoni, Francesca Di Pede, Filippo De Mattei, Filippo Vergnano, Jessica Mandrioli, Cecilia Simonini, Ilaria Martinelli, Fabiola De Marchi, Letizia Mazzini, Cristina Moglia, Andrea Calvo, Adriano Chiò","doi":"10.1002/ana.27252","DOIUrl":"https://doi.org/10.1002/ana.27252","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to evaluate the prognostic value of several muscle damage biomarkers.</p><p><strong>Methods: </strong>Data from Piemonte and Valle d'Aosta Amyotrophic Lateral Sclerosis (PARALS) were considered for this study. Survival was defined as the time from diagnosis to death, tracheostomy, or the censoring date. Blood levels of potassium, creatinine, creatine kinase, phosphorus, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) diagnosis were evaluated as potential prognostic biomarkers. A Cox model was developed for each biomarker and adjusted for sex, onset age, onset site, and diagnostic delay. Significant findings from PARALS were evaluated in the Pooled Resource Open-Access Amyotrophic Lateral Sclerosis Clinical Trials (PRO-ACT) database. Additionally, a joint model was constructed to evaluate the prognostic role of phosphatemia slope over time using longitudinal data from PRO-ACT.</p><p><strong>Results: </strong>A total of 1,444 and 1,023 patients were included in the PARALS and PRO-ACT cohorts, respectively. Only creatinine (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.50-0.85) and phosphorus (HR = 1.14, 95% CI = 1.04-1.24) showed a significant association with survival in the PARALS cohort. These findings were further validated in the PRO-ACT cohort (creatinine HR = 0.21, 95% CI = 0.13-0.35, p < 0.0001; phosphorus HR = 2.35, 95% CI = 1.13-4.88, p = 0.02). Longitudinal data from the PRO-ACT database showed that an increase of 0.1 mmol/l per month in phosphate levels was also associated with a HR of 8.26 (95% CI = 1.07-96.6, p = 0.044).</p><p><strong>Interpretation: </strong>Creatininemia was confirmed as a prognostic marker in amyotrophic lateral sclerosis (ALS). Additionally, both phosphatemia levels at diagnosis and its rate of change over time were identified as a potential prognostic marker for ALS. As with other blood biomarkers, phosphate levels are cost-effective and minimally invasive to measure, supporting their potential use in clinical trials. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953759","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":"Detecting New Lesions Using a Large Language Model: Applications in Real-World Multiple Sclerosis Datasets.","authors":"Shane Poole, Nikki Sisodia, Kanishka Koshal, Kyra Henderson, Jaeleene Wijangco, Danelvis Paredes, Chelsea Chen, William Rowles, Amit Akula, Jens Wuerfel, Vishakha Sharma, Andreas M Rauschecker, Roland G Henry, Riley Bove","doi":"10.1002/ana.27251","DOIUrl":"https://doi.org/10.1002/ana.27251","url":null,"abstract":"<p><strong>Objective: </strong>Neuroimaging is routinely utilized to identify new inflammatory activity in multiple sclerosis (MS). A large language model to classify narrative magnetic resonance imaging reports in the electronic health record (EHR) as discrete data could provide significant benefits for MS research. The objectives of the current study were to develop such a prompt and to illustrate its research applications through a common clinical scenario: monitoring response to B-cell depleting therapy (BCDT).</p><p><strong>Methods: </strong>An institutional ecosystem that securely connects healthcare data with ChatGPT4 was applied to clinical MS magnetic resonance imaging reports in a single institutional EHR (2000-2022). A prompt (msLesionprompt) was developed and iteratively refined to classify the presence or absence of new T2-weighted lesions (newT2w) and contrast-enhancing lesions (CEL). The multistep validation included evaluating efficiency (time and cost), comparison with manually annotated reports using standard confusion matrix, and application to identifying predictors of newT2w/CEL after BCDT start.</p><p><strong>Results: </strong>Accuracy of msLesionprompt was high for detection of newT2w (97%) and CEL (96.8%). All 14,888 available reports were categorized in 4.13 hours ($28); 79% showed no newT2w or CEL. Data extracted showed expected suppression of new activity by BCDT (>97% monitoring magnetic resonance images after an initial \"rebaseline\" scan). Neighborhood poverty (Area Deprivation Index) was identified as a predictor of inflammatory activity (newT2w: OR 1.69, 95% CI 1.10-2.59, p = 0.017; CEL: OR 1.54, 95% CI 1.01-2.34, p = 0.046).</p><p><strong>Interpretation: </strong>Extracting discrete information from narrative imaging reports using an large language model is feasible and efficient. This approach could augment many real-world analyses of MS disease evolution and treatment response. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955956","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":"Nitrilase 1 Associated Cerebrovascular Small Vessel Disease","authors":"Seby John MD,&nbsp;Praveen Kesav DM,&nbsp;Syed Irteza Hussain MD","doi":"10.1002/ana.27249","DOIUrl":"10.1002/ana.27249","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"98 1","pages":"197-198"},"PeriodicalIF":8.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954190","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":"Association Between Vascular NOTCH3 Aggregation and Disease Severity in a CADASIL Cohort - Implications for NOTCH3 Variant-Specific Disease Prediction.","authors":"Minne N Cerfontaine, Gido Gravesteijn, Remco J Hack, Kyra L Dijkstra, Mar Rodríguez-Girondo, Benno Gesierich, Marie-Noëlle W Witjes-Ané, Remco van Doorn, Marco Duering, Julie W Rutten, Saskia A J Lesnik Oberstein","doi":"10.1002/ana.27240","DOIUrl":"https://doi.org/10.1002/ana.27240","url":null,"abstract":"<p><strong>Objective: </strong>Vascular NOTCH3 protein ectodomain aggregation is a pathological hallmark of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a monogenic small vessel disease typically caused by cysteine-altering variants in NOTCH3. Given their high population frequency, these NOTCH3 variants are an important genetic contributor to stroke and vascular dementia worldwide. Disease severity in CADASIL is highly variable and is mainly determined by the position of the pathogenic NOTCH3 variant in the NOTCH3 ectodomain. Here, we aimed to investigate the association between NOTCH3 aggregation load in skin vessels, cysteine-altering NOTCH3 variants, and disease severity in a prospective cohort study of 212 patients with CADASIL with 39 distinct cysteine-altering NOTCH3 variants.</p><p><strong>Methods: </strong>NOTCH3 aggregation load in skin vessels was determined by calculating the NOTCH3 score; the fraction of skin vessel wall area positive for NOTCH3 staining. Variant-specific NOTCH3 scores were calculated for variants present in 10 or more participants, by averaging the NOTCH3 scores of individuals with that distinct variant. The associations between the NOTCH3 score, NOTCH3 variants, and neuroimaging and clinical outcomes were investigated using multivariable linear mixed models, Cox regression, and mediation analyses.</p><p><strong>Results: </strong>The NOTCH3 score was significantly associated with lifetime stroke probability and small vessel disease neuroimaging outcomes, but not with age. Variant-specific NOTCH3 scores reflected differences in disease severity associated with distinct NOTCH3 variants.</p><p><strong>Interpretation: </strong>These findings suggest that differences in NOTCH3 aggregation propensity underlie the differences in disease severity associated with NOTCH3 cysteine-altering variants, and show that NOTCH3-variant specific NOTCH3 scores can contribute to improved individualized disease prediction in CADASIL. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951543","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":"Pragmatic Clinical Trials in Neurology","authors":"Adnan I. Qureshi MD,&nbsp;Gillian Bartlett-Esquilant PhD,&nbsp;Alexandra Brown PhD,&nbsp;James McClay MD, MS,&nbsp;Mamatha Pasnoor MD,&nbsp;Richard J. Barohn MD","doi":"10.1002/ana.27244","DOIUrl":"10.1002/ana.27244","url":null,"abstract":"<p>The need for pragmatic clinical trials evaluating therapeutic interventions in patients with neurological disease is continually increasing due to availability of multiple therapeutic interventions (comparative effectiveness), multifaceted approaches (multiple concurrent synergistic therapeutic interventions), and gaps in trial-specific and real-world population outcomes. Several designs for pragmatic trials are available, including individual randomized trials with pragmatic characteristics, cluster-randomized and non-randomized trials, and observational prospective cohort studies. Cluster trials may have parallel cluster and crossover (unidirectional, bidirectional, and alternating crossover) designs. There are unique aspects of consenting and data collection leveraging existing registries, electronic health records (EHRs), and claims data that make pragmatic trials most suited to study the effectiveness of therapeutic interventions in patients with neurological diseases in real-world settings. ANN NEUROL 2025;97:1022–1037</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 6","pages":"1022-1037"},"PeriodicalIF":8.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955751","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":"Annals of Neurology: Volume 97, Number 5, May 2025","authors":"","doi":"10.1002/ana.26981","DOIUrl":"https://doi.org/10.1002/ana.26981","url":null,"abstract":"","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":"97 5","pages":"C1"},"PeriodicalIF":8.1,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ana.26981","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852857","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}