Neurology最新文献

{"title":"Deciphering the Natural History of SCN8A-Related Disorders.","authors":"Jan H Magielski,Stacey Cohen,Michael C Kaufman,Shridhar Parthasarathy,Julie Xian,Elise Brimble,Nasha Fitter,Francesca Furia,Elena Gardella,Rikke Steensbjerre Møller,Ingo Helbig,Jillian L McKee","doi":"10.1212/wnl.0000000000213533","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213533","url":null,"abstract":"BACKGROUND AND OBJECTIVESSCN8A-related disorders encompass a range of neurodevelopmental and epilepsy phenotypes. However, despite representing one of the most common epilepsy-associated channelopathies, its longitudinal phenotypes remain largely uncharacterized.METHODSIn this study, we harmonized electronic medical record data from 82 individuals with SCN8A-related disorders to reconstruct the natural history of the disorder in comparison with a cohort of 2,833 individuals with known or presumed genetic epilepsies.RESULTSCompared with the cohort of other known or presumed genetic epilepsies, those with SCN8A-related disorders (mean age = 8.3 years, 52% female) had >10-fold odds of bilateral tonic-clonic seizures as early as at 1 year (p = 1.70 × 10-14, OR 10.56, CI 5.85-18.90). Individuals carrying gain-of-function (GOF) SCN8A variants had particularly high seizure risk at 6 months (p = 0.007/pthreshold = 4.25 × 10-4, OR 4.71, CI 1.36-21.25) and an increased risk of global developmental delay as early as at 3 months (p = 0.002/pthreshold = 4.72 × 10-5, OR 5.67, CI 1.74-20.23) when compared with the broader SCN8A cohort. Individuals with loss-of-function variants were more likely to have atypical absence seizures, most prominently at 4.25 years (p = 0.013/pthreshold = 7.08 × 10-4, OR 32.71, CI 1.44-2,193.51). Compared with the broader SCN8A cohort, individuals with the recurrent p.Arg850Gln variant were more likely to have infantile spasms at 6 months and those with variants at the p.Arg1872Trp/Gln/Leu hotspot were more likely to have neonatal seizures. Individuals with the recurrent p.Gly1475Arg variant were more likely to have active epilepsy after 5 years of age. In later childhood, focal seizures were more prominent in individuals with the recurrent p.Arg1617Gln variant while generalized-onset seizures were more prominent with the p.Asn1877Ser variant. We also established the effectiveness of sodium channel blockers in managing SCN8A epilepsy in individuals carrying GOF variants and those whose variants have not been functionally characterized, suggesting that many unstudied SCN8A variants may have GOF mechanisms.DISCUSSIONSCN8A-related disorders distinguish themselves from other genetic epilepsies by the frequent bilateral tonic-clonic seizures in infancy, prominent early epileptic and developmental features in GOF variant carriers, and unique seizure phenotypes in those with recurrent variants. Our study provides a longitudinal perspective on SCN8A-related disorders, paving the way for future precision medicine approaches.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"22 1","pages":"e213533"},"PeriodicalIF":9.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836562","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":"Retirement of Guidelines: Assessment: Use of Epidural Steroid Injections to Treat Radicular Lumbosacral Pain: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.","authors":"","doi":"10.1212/wnl.0000000000213595","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213595","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"34 1","pages":"e213595"},"PeriodicalIF":9.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836501","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":"Rethinking the Significance of Hemorrhagic Transformation After Reperfusion Therapy for Acute Ischemic Stroke.","authors":"Craig S Anderson","doi":"10.1212/wnl.0000000000213647","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213647","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"108 1","pages":"e213647"},"PeriodicalIF":9.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836500","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":"Updated Multiple Sclerosis Incidence in France, 2011-2021.","authors":"Octave Guinebretiere,Chloe Pierret,Quentin Calonge,Edouard Januel,Celine Louapre,Thomas Nedelec","doi":"10.1212/wnl.0000000000213586","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213586","url":null,"abstract":"BACKGROUND AND OBJECTIVESMultiple sclerosis (MS) is a chronic neurologic disorder with significant implications for public health as being the first cause of nontraumatic neurologic disability in young adults. Although the global prevalence of MS has been increasing, recent temporal trends in incidence remain unclear. We aimed to evaluate current MS incidence trends in France over 11 years using the Système National des Données de Santé, a nationwide administrative database covering 99% of the French population.METHODSWe used a published algorithm that incorporates multiple data sources, including benefits from long-term diseases, specific disease-modifying treatment prescriptions, and hospital discharge, to identify incident MS cases from January 1, 2011, to December 31, 2021. Sex-standardized and age-standardized incidence and prevalence were estimated using a \"specific\" and a \"sensitive\" definition providing bounds on the evolution of recent incidence. We used multivariable Poisson regression models to estimate temporal trends in incidence rates, calculating incidence rate ratios (IRRs) along with corresponding 95% CIs. In a sensitivity analysis, the time lag between past visits to neurologists and the database recording of MS was analyzed to ensure that the diagnosis extraction date was reliable.RESULTSA total of 67,311 individuals with suspected MS were identified between 2011 and 2021, with 50,320 individuals classified as incident MS using the specific definition. The sensitive definition identified 56,918 individuals with incident cases. The median age at diagnosis was 40.6 years for the specific definition and 41.5 years for the sensitive definition. The study found stable incidence of MS over the 11-year period (adjusted IRR: 0.998 [95% CI 0.996-1.001] for the specific cohort). The female-to-male ratio of incident MS cases remained stable while sex-standardized and age-standardized prevalence of MS continued to rise. The median time lag between probable diagnosis and database recording was estimated to be less than 18 months, with variations depending on age and method of patient identification.DISCUSSIONThis study provides a comprehensive analysis of MS epidemiology in France, demonstrating stable incidence and sex ratio. The increase in prevalence suggests improved management and survival and highlights the ongoing need for health care systems to support the growing population of individuals with MS.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"1 1","pages":"e213586"},"PeriodicalIF":9.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836566","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 of Body Mass Index in Late Life, and Change from Midlife to Late Life, With Incident Dementia in the ARIC Study Participants.","authors":"Ethan J Cannon,B Gwen Windham,Michael Griswold,Priya Palta,David S Knopman,Sanaz Sedaghat,Pamela L Lutsey","doi":"10.1212/wnl.0000000000213534","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213534","url":null,"abstract":"BACKGROUND AND OBJECTIVESMidlife obesity is a risk factor of dementia, but late-life obesity has been associated with lower dementia risk. We investigated this paradox by exploring the relationship between late-life body mass index (BMI) category and dementia, with and without considering midlife to late-life BMI change.METHODSThis observational cohort study included participants of the community-based Atherosclerosis Risk in Communities (ARIC) study who were dementia-free at visit 5 (2011-2013). Dementia was ascertained by expert-adjudicated, algorithmic classification from an in-person neuropsychological battery, as well as telephone interviews and International Classification of Diseases codes from medical records. We first assessed the association of incident dementia with visit 5 BMI categories (normal weight, overweight, obese). Next, we used a cross-classification of visit 5 BMI categories with visit 4-visit 5 BMI change (decrease [loss of ≥2 kg/m2], increase [gain of ≥2 kg/m2], or stable [loss or gain of <2 kg/m2]) occurring during the 15 years before baseline. Cox regression was used.RESULTSA total of 5,129 participants were included in the study (59% female; 22% identified as Black; mean (standard deviation) age at visit 5 of 75 (5) years). Over 8 years of follow-up, 20% of the sample developed dementia (n = 1,026). After covariate adjustment, participants with high late-life BMI had a lower risk of dementia; the hazard ratio (95% CI) was 0.86 (0.73-1.00) for overweight and 0.81 (0.68-0.96) for obesity. In stratified models, elevated dementia risk was observed only for participants of each late-life BMI category whose BMI had decreased from midlife to late life. Compared with normal-weight individuals who had maintained BMI from midlife to late life, the hazard ratio (95% CI) for those with BMI loss was 2.08 (1.62-2.67) for normal-weight individuals, 1.62 (1.25-2.10) for those with overweight, and 1.36 (1.00-1.85) for those with obesity.DISCUSSIONOur results provide insight into the dementia obesity paradox at older ages, tempering a causal interpretation of high late-life BMI as protective against dementia. Instead, they highlight the importance of considering weight loss from midlife to late life in conjunction with late-life BMI in dementia risk stratification.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"110 1","pages":"e213534"},"PeriodicalIF":9.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824752","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 of Early- to Midlife Weight Trajectories With Mid- to Late-Life Cognitive Decline in the ELSA-Brasil Study.","authors":"Paulo Henrique Lazzaris Coelho,Natalia Gomes Goncalves,Itamar Souza Santos,Alessandra C Goulart,Sandhi Maria Barreto,Luana Giatti,Paulo Caramelli,Paulo A Lotufo,Isabela Bensenor,Claudia Kimie Suemoto","doi":"10.1212/wnl.0000000000213581","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213581","url":null,"abstract":"BACKGROUND AND OBJECTIVESWhile midlife obesity is consistently associated with cognitive decline in later life, there is limited understanding of how weight variations from early life to midlife affect cognitive decline. We investigated the association between early- to midlife weight trajectories and mid- to late-life cognitive decline.METHODSThis is a longitudinal cohort study that used data from 3 waves (2008-2019) of the Brazilian Longitudinal Study of Adult Health, a multicenter cohort study that enrolled active and retired public servants aged 35+ years from public universities in Brazil. Participants with a history of stroke, missing cognitive data at baseline, and with incomplete body shape data were excluded from the analyses. Self-reported body shapes from ages 5 to 40 using the Stunkard Figure Rating Scale were categorized as underweight, normal, overweight, and obese. Sequence analysis and hierarchical clustering identified weight trajectories. Global cognition Z-scores were derived from memory (immediate recall, delayed recall, and recognition of a word list), phonemic and semantic verbal fluency, and Trail Making Test part B (TMT-B). Linear mixed models adjusted for sociodemographic, clinical, and lifestyle covariates investigated associations between clusters of weight trajectories and global cognition Z-scores. Inverse probability of attrition weighting was used to account for attrition bias.RESULTSAmong 11,361 participants (mean age: 51.5 ± 8.6, 55% women, 42.4% Black/mixed race), \"normal to overweight,\" \"underweight to normal,\" and \"stable overweight\" trajectories exhibited faster global cognitive decline than \"stable normal\" trajectory (β = -0.024; 95% CI -0.043 to -0.005; p = 0.015; β = -0.026; 95% CI -0.040 to -0.012; p < 0.001; β = -0.034; 95% CI -0.066 to -0.001; p = 0.043, respectively), representing 4.6-6.5 excess years of cognitive aging over a median follow-up of 8 years. Cognitive decline associated with weight trajectories was driven mainly by declines in memory and TMT-B performance. Associations were observed only in Black/mixed races and women when stratified.DISCUSSIONWeight gain and stable overweight trajectories from early life to midlife were associated with faster cognitive decline than stable normal weight trajectories. Weight management during early life may mitigate cognitive decline. Study limitations include reliance on self-reported body shape data, potential recall bias, and residual confounding from unmeasured early-life factors.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"70 1","pages":"e213581"},"PeriodicalIF":9.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824773","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":"Teaching NeuroImage: Gordon Holmes Syndrome Due to PNPLA6 Gene Variation.","authors":"Eti Muharremi,Altin Kuqo,Jera Kruja","doi":"10.1212/wnl.0000000000213628","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213628","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"16 1","pages":"e213628"},"PeriodicalIF":9.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824775","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":"Acute Symptomatic Seizures During CAR T-Cell Therapy for Hematologic Malignancies: Tri-Site Mayo Clinic Experience.","authors":"Brin E Freund,Anteneh M Feyissa,Oluwatoni E Betiku,Andy Shar,Cornelia Drees,Wendy Sherman,Hong Qin,Jeffrey W Britton,Maria Silvana Barrios,Alfredo Quinones-Hinojosa,William O Tatum","doi":"10.1212/wnl.0000000000213535","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213535","url":null,"abstract":"BACKGROUND AND OBJECTIVESChimeric antigen receptor T-cell (CAR T-cell) therapy is associated with neurotoxicity, which may include acute symptomatic seizures (ASySs). Specific risk factors and short-term and long-term outcomes of ASyS associated with CAR T-cell therapy have not been well investigated.METHODSThis retrospective cohort study evaluated incidence and risk factors for ASyS during CAR T-cell therapy. We included patients treated at Mayo Clinic in Minnesota, Florida, and Arizona who underwent CAR T-cell therapy for hematologic malignancies from October 2019 to November 2023. Pretreatment demographics, clinical information, type of CAR T-cell therapy, neuroimaging, laboratories during treatment, and clinical features during admission were analyzed. Data on treatment and prevalence of seizures, EEG, and survival at the last follow-up were assessed. T-tests and nonparametric testing were performed on categorical and continuous data, respectively. Multivariable analysis was also performed.RESULTSWe included 180 patients (mean age 62.3 years, 57.2% women) with 8 (4.4%) developing ASyS at a mean of 8.0 ± 5.3 days after therapy. Earlier onset of cytotoxic release syndrome (odds ratio [OR] 1.81, 95% CI 0.62-2.99, p = 0.007), higher grade immune effector cell-associated neurotoxicity syndrome (ICANS) (OR -1.43, 95% CI -1.86 to -1.00, p < 0.001), focal neurologic deficits (OR 7.15, 95% CI 1.60-32.14, p = 0.007), and cefepime (OR 0.58, 95% CI 0.51-0.65, p = 0.022) exposure were significantly associated with a higher risk of ASyS. A multivariable model accounting for age and sex fit best using the lowest minimum immune effector cell encephalopathy score and highest ICANS grade (R2 = 0.555, χ2 = 28.507, p < 0.001). ASyS was associated with death at the last follow-up (OR 0.48, 95% CI 0.41-0.56, p = 0.007), although short-term outcomes were not affected by ASyS. Nonprotocolized antiseizure medication (ASM) prophylaxis did not affect ASyS incidence.DISCUSSIONThis study suggests a low risk of ASyS because of CAR T-cell therapy, with certain risk factors that may be predictive of ASyS and lack of a definitive and direct association of ASyS with outcomes. The current approach to ASM prophylaxis should be reconsidered when ICANS is encountered. This study is limited by its retrospective nature and the use of ASM prophylaxis in all patients with ICANS, which requires further study to assess its necessity.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"1 1","pages":"e213535"},"PeriodicalIF":9.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824772","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":"Teaching Video NeuroImage: Touch-Screen Automatisms With Stereotyped Postictal Texting Behavior.","authors":"Luca Micci,Teena Micci,Ammar Kheder,Spencer Nam,Angelica Lee","doi":"10.1212/wnl.0000000000213588","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213588","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"5 1","pages":"e213588"},"PeriodicalIF":9.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822674","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":"Acute Hemorrhagic Leucoencephalitis: A Rare CNS Complication of Abrus precatorius Poisoning.","authors":"Ramanathan Venkateswaran,Govindan Dinakar,Haris Abin,Vellathussery Chakkalakkoombil Sunitha,Pari Thenmozhi Hariswar,Abdoul Hamide","doi":"10.1212/wnl.0000000000213600","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213600","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"25 1","pages":"e213600"},"PeriodicalIF":9.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822679","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}