JAMA neurology最新文献

{"title":"Risk of Inflammatory Bowel Disease After Anti-CD20 Treatment in Multiple Sclerosis","authors":"Sandra Kallin, Anders Svenningsson, Ola Olén, Charlotte Hedin, Jan Lycke, Peter Alping","doi":"10.1001/jamaneurol.2026.3439","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3439","url":null,"abstract":"Importance Anti-CD20 biologics are widely used as disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), but recent reports have raised concerns about an increased risk of inflammatory bowel disease (IBD) during treatment. This study aimed to assess treatment-associated IBD risk in individuals with RRMS. Objective To compare the risk of new-onset IBD across different therapies for RRMS and relative to the general population. Design, Setting, and Participants This was a population-based cohort study conducted in Sweden. Through the Swedish MS register, initiations of rituximab, natalizumab, dimethyl fumarate, and fingolimod were identified between January 1, 2011, and December 31, 2023, in individuals with RRMS aged 18 to 55 years with at least 10 years of lookback time (5 years for dispensed drugs) and no evidence of previous IBD. These initiations were matched with general population comparator episodes selected from the Swedish population. Exposures Rituximab, comparator DMTs (natalizumab, dimethyl fumarate, fingolimod), or general population comparator. Main Outcomes and Measures New-onset IBD, defined as 2 or more records on separate dates with the <jats:italic toggle=\"yes\">International Statistical Classification of Diseases and Related Health Problems</jats:italic> , <jats:italic toggle=\"yes\">Tenth Revision</jats:italic> , codes K50 (Crohn disease), K51 (ulcerative colitis), and/or K52.3 (indeterminate colitis). Results Among the 13 748 therapy episodes (6481 rituximab, 2976 natalizumab, 2767 dimethyl fumarate, 1524 fingolimod) in 9251 individuals (range in mean ages of the exposure groups, 35-38 years) and 61 065 matched general population episodes, 164 IBD events occurred during follow-up (40 with rituximab, 4 with comparator DMTs, and 120 in the general population). The crude incidence rate of IBD was 110 (95% CI, 76-147) per 100 000 person-years for rituximab, 13 (95% CI, 3-30) for the comparator DMTs, and 41 (95% CI, 34-48) for the general population. After adjustment for demographics and MS characteristics, the hazard ratio for the comparator DMTs vs rituximab was 0.10 (95% CI, 0.04-0.22). In the rituximab group, 62% of IBD events were classified as Crohn disease compared with 29% in the general population. The number needed to harm for rituximab vs the comparator DMTs was 131 (95% CI, 93-228) at 5 years, after full adjustment. Conclusions and Relevance Results of this cohort study show that rituximab was associated with an increased risk of IBD compared with other modern MS therapies, after adjustment for differences in characteristics at therapy start. Clinicians and individuals with MS should consider IBD risk in treatment decisions and remain vigilant for gastrointestinal symptoms during anti-CD20 therapy.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"9 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229901","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":"Vascular Risk Factors and Late-Onset Epilepsy","authors":"Hyunmi Choi, Jose Gutierrez, Tian Wang, Minghua Liu, Cheng-Shiun Leu, Sylwia Misiewicz, Jiying Han, Natalie A. Bello, Mary L. Biggs, Emily M. Briceño, Adam M. Brickman, James F. Burke, Ligong Chen, Lisandro D. Colantonio, Stefany P. Diaz Andino, Mitchell S. V. Elkind, Annette L. Fitzpatrick, Christopher Gonzalez Corona, Rebecca F. Gottesman, Alden L. Gross, Lei Huang, Emily L. Johnson, W. Craig Johnson, Deborah A. Levine, W. T. Longstreth, Sofia Pelagalli Maia, Richard P. Mayeux, Brian C. Petersen, Oluwadamilola Obalana, Dolly Reyes-Dumeyer, Tatjana Rundek, Danurys Sanchez, Steven J. Shea, Kevin Strobino, Sarah E. Tom, Carolyn W. Zhu, Evan L. Thacker","doi":"10.1001/jamaneurol.2026.3708","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3708","url":null,"abstract":"Importance Late-onset epilepsy (LOE; onset at age ≥65 years) is increasingly recognized in older adults and may be associated with vascular risk. Objective To identify vascular risk factors (VRFs) associated with incident LOE in older adults. Design, Setting, and Participants This study is an individual participant data meta-analysis of 6 US population-based prospective cohort studies (the Epilepsy-Cog Study). In 5 cohorts linked to Medicare for epilepsy case ascertainment, follow-up for LOE began when a participant had accrued 2 years of continuous fee-for-service enrollment and was 65 years of age or older and extended to the end of continuous enrollment. Claims linkage covered 1991-2018 in the Atherosclerosis Risk in Communities Study (ARIC), 1992-2019 in the Cardiovascular Health Study (CHS), 2000-2019 in the Multi-Ethnic Study of Atherosclerosis (MESA), 2000-2020 in the Reasons for Geographic and Racial Differences in Stroke Study (REGARDS), and 1999-2019 in the Washington Heights/Inwood Columbia Aging Project (WHICAP). In the Northern Manhattan Study (NOMAS), which was not Medicare linked and used cohort-based epilepsy case ascertainment, follow-up for LOE began at cohort entry in 1993-2008 and extended to 2024. Data analysis was completed in January 2026. Exposures Sociodemographic characteristics and VRFs assessed by self-report, examinations, laboratory measures, and medication use. Main Outcome and Measures The primary outcome was incident LOE. Associations between risk factors and incident LOE were evaluated using multivariable Cox proportional hazards models to estimate hazard ratios. Results From 43 753 participants in Epilepsy-Cog, 551 participants with prevalent epilepsy and 945 with no follow-up after Epilepsy-Cog baseline were excluded. Among 42 257 participants (mean [SD] age, 71.4 [6.9] years; 23 383 [56.0%] female) followed up for a mean (SD) of 9.3 (6.2) years, 1500 participants (3.5%) developed LOE (3.8 per 1000 person-years). In fully adjusted models, LOE risk was higher with current smoking (HR = 1.39; 95% CI, 1.18-1.64), hypertension (HR = 1.17; 95% CI, 1.04-1.31), diabetes (HR = 1.42; 95% CI, 1.25-1.62), chronic kidney disease (HR = 1.29; 95% CI, 1.13-1.48), history of stroke (HR = 1.99; 95% CI, 1.63-2.43), and apolipoprotein E ε4 allele (1 ε4 allele: HR = 1.22; 95% CI, 1.07-1.39; 2 ε4 alleles: HR = 1.84; 95% CI, 1.36-2.50). Associations of VRFs with LOE were similar across age, sex, and race and ethnicity subgroups. Conclusions and Relevance In this pooled analysis of 6 US cohorts, multiple VRFs and a history of stroke were associated with incident LOE. These findings suggest that LOE may reflect the underlying burden of brain vascular disease.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"73 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218460","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":"The Patient I Could Not Save","authors":"Merry Huang","doi":"10.1001/jamaneurol.2026.3759","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3759","url":null,"abstract":"This essay describes the author’s experience with severe postpartum anxiety and depression, suicidal ideation, and her time on an inpatient psychiatry unit.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218459","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":"Plasma Phosphorylated Tau 217 Percentage by Race and Ethnicity in Preclinical Alzheimer Disease","authors":"Doris P. Molina-Henry, Andy Liu, Oliver Langford, Rema Raman, Dina Dass, Emily Clark, Gregory S. Day, Hamid R. Okhravi, Pallavi Joshi, Paulette Cazares, Raymond Scott Turner, Joel B. Braunstein, Philip Verghese, Venky Venkatesh, Tim West, Shobha Dhadda, Michael Irizarry, Keith Johnson, Robert A. Rissman, Joshua D. Grill, Paul Aisen, Reisa A. Sperling","doi":"10.1001/jamaneurol.2026.3598","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3598","url":null,"abstract":"Importance In trials targeting preclinical Alzheimer disease (AD), defined as amyloid pathology without cognitive symptoms, racial and ethnic differences in plasma phosphorylated tau 217 percentage (%p-tau217) may influence screening eligibility. Objective To characterize racial and ethnic differences in %p-tau217 and determine whether associations between %p-tau217, cognition, and amyloid positron emission tomography (PET) differ across groups. Design, Setting, and Participants This was a cross-sectional analysis of AHEAD 3-45 screening participants conducted from July 2020 to October 2024 at 106 sites across 4 world regions. Adults aged 55 to 80 years with %p-tau217 measured before medical and cognitive exclusions (N = 15 612) were included. Exposures Self-reported race (Asian, Black, and White) and ethnicity (Hispanic and non-Hispanic) and apolipoprotein E ε4 ( &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4) carrier status. Main Outcomes and Measures %p-tau217 levels and associations of %p-tau217 with Preclinical Alzheimer Cognitive Composite 5 (PACC5) score and amyloid PET were evaluated across racial and ethnic groups using multivariable linear regression. Results Among 15 612 participants, the mean (SD) age was 68.4 (6.2) years; 9941 (63.7%) were female and 5755 (36.9%) were &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 carriers. %p-tau217 levels were lower among Asian, Black, and Hispanic participants than among White and non-Hispanic participants. &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 status was associated with higher %p-tau217 across all groups. The association between &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 status and %p-tau217 differed by race ( &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 × race: &lt;jats:italic toggle=\"yes\"&gt;F&lt;/jats:italic&gt; &lt;jats:sub&gt;2,14 973&lt;/jats:sub&gt; = 10.06; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; &amp;amp;lt; .001) and ethnicity ( &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 × ethnicity: β, 0.042; 95% CI, 0.017 to 0.067; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = .005) (Asian: β, 0.05; 95% CI, 0.02 to 0.08; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = .01; Black: β, 0.05; 95% CI, 0.03 to 0.08; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = .002; Hispanic: β, 0.04; 95% CI, 0.02 to 0.07; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = .005). The %p-tau217–PACC5 association showed no pairwise differences across racial groups but differed by ethnicity (β, −0.53; 95% CI, −0.85 to −0.21; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = .008) and &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 × ethnicity (β, 0.78; 95% CI, 0.26 to 1.30; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; = .02). The %p-tau217–PET association showed no significant pairwise differences across racial groups but differed by ethnicity (β, −6.30; 95% CI, −9.10 to −3.51; &lt;jats:italic toggle=\"yes\"&gt;P&lt;/jats:italic&gt; &amp;amp;lt; .001) and &lt;jats:italic toggle=\"yes\"&gt;APOE&lt;/jats:italic&gt; ε4 × ethnicity (β, 7.12; 95% CI, 2.52 to 11.73; &lt;jats:italic ","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"185 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151785","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":"Global Incidence of All-Cause Dementia: A Meta-Analysis.","authors":"Ashleigh S Vella, Rachel Visontay, Darren M Lipnicki, Emma Nichols, Jaimie D Steinmetz, Theo Vos, Anh Thy H Nguyen, Juan J Llibre-Rodriguez, Jorge Llibre-Guerra, Richard B Lipton, Mindy J Katz, Nikolaos Scarmeas, Maëlenn Guerchet, Pierre-Marie Preux, Karen Ritchie, Maria Skaalum Petersen, Ingmar Skoog, Elena Rolandi, Annalisa Davin, Michele Rossi, Ki Woong Kim, Ji Won Han, Dae Jong Oh, Steffi G Riedel-Heller, Susanne Röhr, Alexander Pabst, Ding Ding, Qianhua Zhao, Xiaowen Zhou, Kaarin J Anstey, Moyra E Mortby, Nicolas Cherbuin, Antonio Lobo, Shifu Xiao, Hugh C Hendrie, Sujuan Gao, Sebastian Köhler, Pascual Sánchez-Juan, Teodoro Del Ser, Meritxell Valentí-Soler, Marcia Scazufca, Allison E Aiello, Jacqueline Dominguez, Roger Ho, John D Crawford, Henry Brodaty, Louise Mewton, Perminder S Sachdev","doi":"10.1001/jamaneurol.2026.3540","DOIUrl":"10.1001/jamaneurol.2026.3540","url":null,"abstract":"<p><strong>Importance: </strong>Global dementia incidence estimates are limited by underrepresentation of low- and middle-income countries and heterogeneous analytic methods. Due to these limitations, true understanding of the global dementia landscape remains incomplete.</p><p><strong>Objective: </strong>To identify dementia incidence rates by age and sex in various regions worldwide (high-income countries and low- and middle-income countries) where data on clinically based dementia diagnoses were available.</p><p><strong>Data sources: </strong>Retrospective community-based cohorts from the Cohort Studies of Memory in an International Consortium (COSMIC); baseline recruitment commenced between January 1990 and December 2011 and follow-up data were collected through the end of 2021. Data were analyzed from June 2024 to June 2025.</p><p><strong>Study selection: </strong>Eligible studies included longitudinal COSMIC cohort studies with a clinically based diagnosis of dementia. Individual participant-level data from 22 population-based longitudinal cohorts (N = 38 418) spanning 18 countries or territories across 6 continents were included.</p><p><strong>Data extraction and synthesis: </strong>Data extraction and assessment of study quality and validity were conducted according to Meta-Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. Individual participant-level data were meta-analyzed in a 2-step process using random intercepts for country and study at the global and regional levels and by country income level.</p><p><strong>Main outcomes and measures: </strong>For each study with a clinically based diagnosis, incidence rates for all-cause dementia were calculated and a 2-step meta-analysis was conducted. Using a person-years at risk framework with inverse-probability censoring weights and Poisson models, age- and sex-specific incidence were estimated and then standardized to the 2023 global age-sex population structure.</p><p><strong>Results: </strong>Across 287 632 person-years at risk, 3001 participants developed dementia. Age- and sex-standardized incidence was 9.7 (95% CI, 7.89-11.97) per 1000 person-years at risk. Age-standardized incidence was higher in women than men (10.6; 95% CI, 8.61-13.11 vs 8.6; 95% CI, 6.94-10.72). Standardized incidence was higher in low- and middle-income countries (13.6; 95% CI, 9.67-19.24) than in high-income countries (8.3; 95% CI, 6.57-10.54). Applying age- and sex-specific rates to the projected 2050 population yielded a projected 24.7 million new cases, assuming constant incidence over time.</p><p><strong>Conclusions and relevance: </strong>The harmonized estimates presented in this study provide a comparable benchmark for global dementia incidence and inform planning for prevention, diagnosis, and memory-care services, particularly in underrepresented low- and middle-income country settings.</p>","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":23.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167564","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":"Optic Embolism in a 30-Year-Old Woman.","authors":"Arturo Sánchez Gómez, José Manuel Flores Barragán","doi":"10.1001/jamaneurol.2026.3562","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3562","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":23.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166715","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":"Early Pregnancy Use of Anti-CGRP Monoclonal Antibodies and Propranolol and Spontaneous Abortion Risk","authors":"Leah K. Flatman, Lisiane F. Leal, Elizabeth Leroux, Richard B. Lipton, Anick Bérard","doi":"10.1001/jamaneurol.2026.3573","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3573","url":null,"abstract":"Importance Migraine affects individuals of reproductive age, but treatment options during pregnancy are limited due to safety concerns. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are effective for migraine prevention; however, CGRP is important in placental development. Objective To determine whether early pregnancy exposure to anti-CGRP mAbs or propranolol is associated with spontaneous abortion compared with no exposure. Design, Setting, and Participants This retrospective cohort study used data from the AM-PREGNANT cohort, derived from the Merative MarketScan Commercial Database, from 2018 to 2021. Participants were followed up through 20 weeks’ gestation or until spontaneous abortion or censoring. Among 7 991 200 pregnancies identified in the AM-PREGNANT cohort, 7119 individuals contributing 7579 singleton pregnancies met the predefined eligibility criteria, including age 15 to 45 years, continuous insurance enrollment, last menstrual period (LMP) on or after November 1, 2018, pregnancy end or 20-week censoring by December 31, 2021, and pregestational migraine, defined as a migraine diagnosis or triptan or ergot prescription within 6 months before LMP. Data were analyzed in early 2026. Exposures Anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) or propranolol, defined as 1 or more filled prescription or injection procedure claim during follow-up and modeled as time-varying. Main Outcome and Measures Spontaneous abortion occurring at 20 weeks’ or less gestation. Multivariable Cox proportional hazards models adjusted for comorbidities and concomitant medications estimated the risk of spontaneous abortion. Results Among 7579 pregnancies in 7119 individuals (mean [SD] age, 31.6 [5.5] years), 1862 spontaneous abortions occurred. There were 100 spontaneous abortions (28.6%) during anti-CGRP mAb-exposed person-time, compared with 37 events among propranolol-exposed person-time without anti-CGRP mAbs (12.8%). Compared with unexposed individuals, anti-CGRP mAbs exposure was associated with an increased risk of spontaneous abortion (adjusted hazard ratio [aHR], 1.42; 95% CI, 1.12-1.80), which remained similar in bias-adjusted analyses (HR, 1.33; 95% simulation interval [SI], 1.23-1.45). Propranolol exposure was not associated with increased risk (aHR, 1.02; 95% CI, 0.71-1.47; bias-adjusted HR, 1.00; 95% SI, 0.96-1.03). Conclusion and Relevance In this study, early pregnancy exposure to anti-CGRP mAb was associated with a higher risk of spontaneous abortion, while no association was observed with propranolol. These findings support further evaluation of anti-CGRP mAb safety and emphasize counseling for individuals of childbearing potential.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"19 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151786","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":"Whole Genomes, Clearer Diagnoses—Precision Care for Children With Neurologic Disease","authors":"Terrie E. Inder","doi":"10.1001/jamaneurol.2026.3008","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3008","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088999","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":"Rapid Whole-Genome Sequencing in Pediatric Neurology Inpatients","authors":"Man Amanat,Asma Ali,Queenie Tan,Paul E. Youssef,Laura Rust,Nicole Boczek,Natasha Strande,Sarah Barnett,Lisa A. Schimmenti,Keith Coffman,Elaine Wirrell,Radhika Dhamija","doi":"10.1001/jamaneurol.2026.3410","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3410","url":null,"abstract":"Importance Rapid whole-genome sequencing (WGS) has advanced inpatient genetic diagnosis, although most evidence comes from neonatal and pediatric intensive care unit (ICU) populations. Its utility for pediatric neurology inpatients across broader acute settings remains insufficiently established. Objective To assess the diagnostic yield, clinical impact, and factors associated with phenotype-concordant rapid WGS diagnoses. Design, Setting, and Participants This was a retrospective cohort study conducted from June 1, 2022, through January 17, 2026, at a tertiary medical center. Pediatric inpatients in the neonatal ICU, pediatric ICU, or general floor with an unexplained neurologic presentation were included. Those with established nongenetic etiology were excluded from analyses. Exposures Trio (77.8%), duo (9.1%), or singleton (13.1%) rapid WGS. Main Outcomes and Measures The primary outcome was the initial phenotype-concordant diagnostic yield at the point of care. Secondary outcomes were reanalysis yield (new diagnoses from reinterpreting nondiagnostic cases prompted by a new unexplained phenotype or family request), cumulative yield, and management change. Associations were assessed by logistic regression (odds ratios [ORs] and 95% CIs). Results Among 175 children (median [IQR] age, 4 months [1 day-4 years]; 93 male [53.1%]) who met inclusion criteria (82 neonates, 93 nonneonates), initial rapid WGS established a phenotype-concordant diagnosis in 79 (45.1%), higher in nonneonates (49 of 93 [52.7%]) than neonates (30 of 82 [36.6%]). Preliminary results returned at mean (SD) 4.0 (1.6) days and final reports at 10.4 (4.5) days. Positive nonconcordant findings occurred in 33 children (18.9%). Reanalysis of 14 nondiagnostic cases yielded 3 additional diagnoses, for a cumulative yield of 82 of 175 children (46.9%). Most diagnoses were monogenic (63 [76.8%]). Management changed in 54 of 82 phenotype-concordant cases (65.9%; 53 at the point of care, 1 after reanalysis) and 8 of 33 (24.2%) positive nonconcordant cases. Family history was most strongly associated with diagnosis (adjusted OR [aOR], 6.46; 95% CI, 3.23-12.93; P  &amp;amp;lt; .001), followed by multisystem involvement (aOR, 2.85; 95% CI, 1.24-6.54; P  = .01) and congenital anomaly or dysmorphism (aOR, 2.47; 95% CI, 1.07-5.68; P  = .03). Hypotonia was most strongly associated in neonates (OR, 20.63; 95% CI, 5.46-77.87; P  &amp;amp;lt; .001); ICU admission (OR, 10.25; 95% CI, 2.79-37.67; P  &amp;amp;lt; .001) predominated in nonneonates. Conclusions and Relevance Results of this cohort study suggest that rapid WGS diagnosed nearly half of pediatric neurology inpatients and changed management in two-thirds of diagnosed cases, supporting its potential use as early diagnostic testing. Associated features may guide patient selection, and reanalysis extends yield longitudinally.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"36 1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092436","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":"Ten Years of Ocrelizumab in Relapsing Multiple Sclerosis","authors":"Stephen L. Hauser,Amit Bar-Or,Gavin Giovannoni,Xavier Montalban,Christine Lebrun-Frenay,Lilyana Amezcua,Luisa M. Villar,Douglas L. Arnold,Martin S. Weber,Massimo Filippi,Noemi Pasquarelli,Cathy Chognot,Qing Wang,Hans-Martin Schneble,Licinio Craveiro,Ludwig Kappos","doi":"10.1001/jamaneurol.2026.3507","DOIUrl":"https://doi.org/10.1001/jamaneurol.2026.3507","url":null,"abstract":"Importance Preventing irreversible disability accumulation is a primary treatment goal in multiple sclerosis (MS). Objective To assess 10-year safety and efficacy of ocrelizumab (OCR) in patients with relapsing MS (RMS). Design, Setting, and Participants In 2 phase 3 multicenter randomized clinical trials (OPERA I and II), patients were randomized to OCR or interferon beta-1a (IFN) throughout a 2-year double-blind period (DBP) and entered an open-label extension (OLE) to receive OCR for up to an additional 8 years. Study periods were August 2011 to December 2022, with clinical cutoff on July 15, 2023. Data analyses were run between March 2023 and May 2026. Patients with RMS, aged 18 to 55 years, with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5, and at least 1 relapse within the year before screening were eligible for inclusion. Interventions OCR (600 mg every 24 weeks) or IFN (44 µg 3 times weekly) in the DBP, then OCR during the OLE. Main Outcomes and Measures Outcomes included time to onset of 48-week confirmed disability progression (CDP) or progression independent of relapse activity (PIRA); time to reach EDSS score of 4.0 and 6.0; relapse rates; and incidence of adverse events (AEs) and serious AEs. Results A total of 1656 patients were randomized, and 1651 patients received either OCR (n = 825) or IFN (n = 826). A total of 1325 patients (80.0%) entered the OLE, of whom 853 (64.4%) completed the studies. A total of 1093 of 1656 patients (66.0%) were female; mean (SD) baseline age was 37.1 (9.2) years vs 37.2 (9.2) years in the OCR vs IFN arms, respectively. Over 10 years, continuous OCR (OCR-OCR) significantly reduced the hazard of 48-week CDP by 24% compared with delayed initiation (IFN-OCR; hazard ratio, 0.76; 95% CI, 0.61-0.95; P  = .02), with 680 patients (82.2%) receiving OCR-OCR remaining free of 48-week CDP and 712 (86.1%) free of PIRA. OCR-OCR treatment reduced the hazard of progressing to key disability milestones, including EDSS of 4.0 (34%; hazard ratio, 0.66; 95% CI, 0.43-1.03; P  = .06) and 6.0 (43%; hazard ratio, 0.57; 95% CI, 0.40-0.82; P  = .002), with 502 (93.3%) and 774 (94.2%) retaining scores less than 4.0 and 6.0, respectively. In patients receiving OCR-OCR, relapse rates decreased from 0.139 at year 1 to 0.016 at year 10. Rates of AEs and SAEs, including serious infections, did not increase over the 8-year OLE. Conclusions and Relevance In the OPERA I and II randomized clinical trials, continuous OCR treatment over 10 years provided greater benefit in preserving function than a 2-year delay in initiating OCR, reinforcing the importance of early high-efficacy treatment. Trial Registrations ClinicalTrials.gov Identifiers: NCT01247324 and NCT01412333","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088997","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}