Neurology最新文献

{"title":"Two Meds Are Not Enough: The Need for Continued Prospective Antiseizure Medication Pregnancy Research.","authors":"Elizabeth E Gerard","doi":"10.1212/wnl.0000000000213959","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213959","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"1 1","pages":"e213959"},"PeriodicalIF":9.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645905","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: Crossed Vertical Gaze Paresis: A Sign of a Supranuclear Lesion.","authors":"Sofia Mônaco Gama,Pedro Fraiman,Gabriel Lopes da Silva,Flavio Moura Rezende Filho","doi":"10.1212/wnl.0000000000213870","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213870","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"10 1","pages":"e213870"},"PeriodicalIF":9.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639732","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":"It Is Time for Drug Repurposing in Parkinson Disease.","authors":"Carlo Colosimo,Luca Marsili","doi":"10.1212/wnl.0000000000213972","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213972","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"96 1","pages":"e213972"},"PeriodicalIF":9.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611482","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 Medication Use and 8-Year Mortality Risk in Patients With Parkinson Disease: Drug-Wide Trial Emulation.","authors":"Julia A Tuominen,Trond Riise,Julia Romanowska,Mario H Flores-Torres,Marianna Cortese,Clemens R Scherzer,Kjetil Bjornevik,Jannicke Igland","doi":"10.1212/wnl.0000000000213783","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213783","url":null,"abstract":"BACKGROUND AND OBJECTIVESThere are currently no treatments that can halt or slow the progression of Parkinson disease (PD). The aim of this study was to identify new drug repurposing candidates for PD among existing prescription drugs that could be used to modify the disease course.METHODSThis nationwide observational cohort study (2004-2020) used Norwegian health registries and was conducted as a high-throughput drug screen using an emulated target trial design. All individuals who met our prescription-based classification criteria for PD, were older than 25 years at the time of diagnosis, and were not prescribed the target drug in the past 2 years were included. We emulated a target trial for any drug filled by a minimum of 100 individuals at any pharmacy in Norway, which amounted to a total of 219 drugs. Mortality was used as an outcome to indicate disease progression. We estimated the effect of drug initiation, an observational analog of the intention-to-treat effect, on the 8-year risk of death, comparing initiators of the target drug with initiators of drugs within the same Anatomical Therapeutic Chemical classification system level 1 group. Inverse probability of treatment weighting was used to adjust for potential confounders.RESULTSThe study included 14,289 individuals with PD (mean age 72 at diagnosis, 59% male) and identified 23 drugs associated with reduced mortality risk at 8 years. These drugs included ranitidine (histamine-2 blocker); pantoprazole and esomeprazole (proton pump inhibitors); losartan (angiotensin receptor blocker); atorvastatin (for high cholesterol); tadalafil (for erectile dysfunction); levothyroxine sodium (thyroid hormone); phenoxymethylpenicillin, erythromycin, and azithromycin (antibiotics); 4 nonsteroidal anti-inflammatory drugs; combined codeine/paracetamol and tramadol (opioid analgesics); zopiclone and melatonin (sleep aids); mianserin (antidepressant); mometasone (nasal corticosteroid); 2 opium-derived cough medicines; and dexamethasone (ophthalmologic corticosteroid).DISCUSSIONOur study identified several drugs with potential disease-modifying properties that could be candidates for future clinical trials. It highlights the potential of repurposing existing medications to advance drug development. While these findings are exploratory and, therefore, insufficient to justify immediate clinical application, they warrant further investigation and potential inclusion in clinical trials.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"36 1","pages":"e213783"},"PeriodicalIF":9.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611523","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":"Anatomic Staging of H3 G34-Mutant Diffuse Hemispheric Glioma.","authors":"Kevin Akeret,Luis Padevit,Guido Reifenberger,Andreas von Deimling,Michael Weller,Emilie Le Rhun, ","doi":"10.1212/wnl.0000000000213861","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213861","url":null,"abstract":"OBJECTIVESH3 G34-mutant diffuse hemispheric gliomas are rare, aggressive primary brain tumors predominantly affecting young patients. We investigated the prognostic value of anatomic staging (AS)-a system previously validated in adult-type diffuse gliomas-in this molecularly distinct tumor type.METHODSPatients from an international cohort with H3 G34-mutant gliomas underwent AS based on pretreatment imaging, performed independently by 2 raters blinded to clinical outcomes. Inter-rater reliability was evaluated using Cohen kappa. Kaplan-Meier curves and Cox proportional hazards models-unadjusted and adjusted for sex, extent of resection, and O6-methylguanine DNA-methyltransferase (MGMT) status-were used to analyze overall survival across stages.RESULTSThirty-seven patients were included (median age 22 years; 54% female). Inter-rater reliability was high (weighted κ = 0.93, 95% CI 0.85-1.0). Median overall survival was 36 months for stage 1 (95% CI 16-67 months), 25 months for stage 2 (95% CI 8-41), and 9 months for stage 3 (95% CI 3-26). After adjustment for sex, extent of resection, and MGMT status, survival differences persisted (hazard ratio [HR]Stage 2 adjusted 2.25, 95% CI 0.67-7.5, p = 0.19; HRStage 3 adjusted 4.37, 95% CI 1.39-13.7, p = 0.01).DISCUSSIONAS is reproducible and prognostically relevant for H3 G34-mutant gliomas, providing insights into tumor spread. It may inform treatment decisions, but larger studies are needed to confirm its clinical utility.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"59 1","pages":"e213861"},"PeriodicalIF":9.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603680","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":"Lifetime Risk of First Symptomatic ICH or Seizure in Familial Cerebral Cavernous Malformations: A Multicenter Patient Data Analysis.","authors":"Philipp Dammann,Alejandro N Santos,Laven Mavarani,Stéphanie Guey,Hugues Chabriat,Dominique Herve,Jacob Croft,Mellisa Renteria,David Jang,Jun Zhang,Da Li,Zhen Wu,Jian-Cong Weng,Antonio Petracca,Carmela Fusco,Leonardo D'Agruma,Marco Castori,Matthias Rath,Robin A Pilz,Ute Felbor,Gary K Steinberg,Jeanne Gu,David Bervini,Johannes Goldberg,Andreas Raabe,Andrés Cervio,Facundo Villamil,Julieta Rosales,Laurèl Rauschenbach,Christoph Riess,Marvin Darkwah Oppong,Hannah Karadachi,Yahya Ahmadipour,Karsten H Wrede,Ramazan Jabbarli,Cornelius Deuschl,Yan Li,Guilherme Santos Piedade,Martin Köhrmann,Benedikt Frank,Thomas Wälchli,Börge Schmidt,Manou Overstijns,Jürgen Beck,Christian Fung,Rustam Al-Shahi Salman,Kelly D Flemming,Giuseppe Lanzino,Atif Zafar,Shantel Weinsheimer,Jeffrey Nelson,Joseph M Zabramski,Amy Akers,Leslie Morrison,Charles E McCulloch,Helen Kim,Ulrich Sure, ","doi":"10.1212/wnl.0000000000213798","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213798","url":null,"abstract":"BACKGROUND AND OBJECTIVESFamilial cavernous malformations (FCMs) are vascular lesions that pose a lifelong risk of symptomatic hemorrhage (SH) and seizures, yet their natural history remains unclear. This study aims to determine the cumulative lifetime risk of a first SH and/or seizure and assess whether genetic variations influence these risks.METHODSThis international, multicenter retrospective cohort study included data from 16 tertiary referral centers and 1 patient advocacy group. Eligible patients had confirmed or suspected FCM, available magnetic resonance imaging (MRI) data, documented baseline clinical features, and longitudinal follow-up (FU). Functional outcomes were assessed using the modified Rankin Scale (mRS) at last FU. Direct adjusted survival curves and mixed-effects Cox regression analyses were performed to estimate cumulative lifetime risk. The association between genetic variations and SH/seizure rates was evaluated, and mixed-effects logistic regression assessed the effect of SH/seizures on mRS outcomes.RESULTSA total of 1,592 patients with FCM were included, with a mean age of 37.6 years (SD 17.1) and 55.7% female. The median FU was 42 years (IQR: 27-55), totaling 64,146 person-years. Of these, 869 (54.6%) had confirmed FCM, 775 (48.7%) experienced at least 1 hemorrhage, and 447 (28.1%) had at least 1 seizure. Genetic testing was performed in 47.7%, identifying CCM1 (31.0%), CCM2 (4.8%), and CCM3 (1.9%) variations. The lifetime risk of a first SH was ∼80%, with an event rate that remained constant beyond age 20. The lifetime risk of a first seizure was ∼45%. Patients with CCM3 variations exhibited a more aggressive hemorrhagic course than those with CCM1 (hazard ratio 1.799, 95% CI 1.008-3.208). SH and seizures were independently associated with worse mRS outcomes at last FU.DISCUSSIONThe event rate of SH and seizures remained stable over time, leading to high cumulative lifetime risks. Patients with CCM3 variations exhibited a more aggressive disease course. Limitations include the non-population-based design, selection bias from tertiary centers, retrospective data collection, and variability in data extraction across centers. However, this study represents the largest international FCM cohort to date, improving the precision of risk estimates and providing valuable insights into disease progression.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"14 1","pages":"e213798"},"PeriodicalIF":9.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603794","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":"Clinical Reasoning: A 27-Year-Old Man With Progressive Bilateral Vision Loss Resistant to Steroid Therapy.","authors":"Wenli Zhang,Junfeng Huo,Weian Chen,Yue Zhang,Jiajia Zheng,Tingfang Zhang,Donglei Song,Dongyang Heng,Yuan Tian","doi":"10.1212/wnl.0000000000213897","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213897","url":null,"abstract":"This case involves a 27-year-old man who presented with progressive bilateral visual impairment that initially improved with steroid therapy but subsequently worsened. The clinical problem centers on diagnosing optic nerve damage with meningeal involvement unresponsive to standard interventions. The patient's vision loss began insidiously in the right eye and later affected the left, with fundoscopy showing bilateral optic nerve atrophy. Although steroids provided temporary relief, the condition deteriorated, necessitating further investigation. MRI revealed dural thickening and enhancement near the optic canals, suggesting an infiltrative or compressive process. The diagnostic approach required considering inflammatory, compressive, and infiltrative etiologies, with a biopsy ultimately proving critical when initial treatments failed. This case underscores the importance of a stepwise diagnostic strategy and highlights the need to consider rare conditions in atypical presentations, guiding readers through the differential diagnosis.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"693 1","pages":"e213897"},"PeriodicalIF":9.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603787","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":"What Physiological Features May Contribute to Purkinje Cell Vulnerability in Cerebellar Ataxias?","authors":"Eduardo Benarroch","doi":"10.1212/wnl.0000000000213961","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213961","url":null,"abstract":"","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"4 1","pages":"e213961"},"PeriodicalIF":9.9,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603786","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":"Geographic Disparities in Stroke Clinical Trials Across the United States: A Decade of Data (2010-2020).","authors":"Chaitali Dagli,Evan Liu,Adrian Matias Bacong,Yihan Zhong,Mudasir Andrabi,Chen Lin","doi":"10.1212/wnl.0000000000213829","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213829","url":null,"abstract":"BACKGROUND AND OBJECTIVESGeographic disparities in stroke clinical trials may limit access to innovative treatments in high-burden regions. This study examines the distribution of completed stroke trials (2010-2020) relative to stroke mortality and hospitalization rates.METHODSData on completed trials were obtained from ClinicalTrials.gov and stroke burden metrics from the Control and Prevention. We calculated relative study frequency (RSF) by dividing the number of stroke deaths, age-adjusted stroke death rates, and stroke hospitalizations per 100,000 Medicare beneficiaries by the number of available trials. RSF values were stratified by quartiles.RESULTSA total of 649 stroke-related clinical trials were completed across 40 states, with 10 states having no registered trials. RSF varied widely, with the lowest quartile, including Mississippi (RSF = 14.40) and Louisiana (RSF = 13.90), having high stroke hospitalizations with minimal research activity, while California (RSF = 0.09) and New York (RSF = 0.19) had greater clinical trial availability to address stroke burden.DISCUSSIONStroke trial availability is disproportionately low in high-burden regions, particularly in the Southeast and Midwest. States with high stroke mortality and hospitalization rates but low clinical trial availability may face barriers to trial access, potentially exacerbating disparities in stroke care.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"12 1","pages":"e213829"},"PeriodicalIF":9.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594102","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":"Ambient Outdoor Air Pollution and Risk of Tumors of the Central Nervous System.","authors":"Ulla A Hvidtfeldt,Mette Sørensen,Aslak H Poulsen,Matthias Ketzel,Jørgen Brandt,Lau C Thygesen,Jan Wohlfahrt,Ole Raaschou-Nielsen","doi":"10.1212/wnl.0000000000213920","DOIUrl":"https://doi.org/10.1212/wnl.0000000000213920","url":null,"abstract":"BACKGROUND AND OBJECTIVESThe incidence of CNS tumors has increased over the recent decades, and few risk factors are identified. Ultrafine particles (UFPs) can cross the blood-brain barrier and thereby cause direct intracranial exposure. The aim of this cohort study was to study the possible relationship between air pollution exposure including UFPs and tumors of the CNS.METHODSThe study base included all Danish adults (aged 20 years and older) identified from nationwide registries since 1991. We defined the end point as the first, primary CNS tumor identified in the Danish Cancer Registry. We applied Danish national registers for address histories and covariates and a state-of-the-art, validated model for assessment of residential air pollution. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs for tumors of the cranial nerves, meningioma, and glioma associated with air pollution exposure. We conducted analyses based on a national emission inventory to allocate air pollution concentrations to contributions from local traffic and other sources. Covariates included socioeconomic and demographic factors at both individual and area levels.RESULTSThe study included 3,959,619 adults (mean age 35 years, 49.6% female) and 16,596 cases of CNS tumors. Ten-year mean exposure to UFPs, fine particulate matter (PM2.5), nitrogen dioxide (NO2), and elemental carbon (EC) was associated with the risk of developing meningioma with confounder-adjusted HRs (95% CI) of 1.10 (1.05-1.16) per interquartile range (IQR) for UFPs; 1.21 (1.10, 1.34) per IQR for PM2.5; 1.12 (1.07, 1.18) per IQR for NO2; and 1.03 (1.00, 1.05) per IQR for EC. Source-specific analyses indicated that air pollution from both local traffic and other sources could be influential. Corresponding HRs observed for the other CNS groups were as follows: tumors of the cranial nerves (n = 2,342): 0.94 (0.86-1.02), 0.89 (0.76-1.03), 0.90 (0.83-0.97), and 0.92 (0.87-0.98); glioma (n = 6,197): 1.01 (0.96-1.06), 0.95 (0.87-1.04), 1.02 (0.97-1.06), and 1.01 (0.99-1.04); and other CNS tumors (n = 3,412): 0.96 (0.90-1.02), 0.89 (0.80-1.00), 0.99 (0.94-1.05), and 1.01 (0.98, 1.05).DISCUSSIONThe findings of this nationwide register-based cohort study indicated that air pollution might contribute to the development of meningioma.","PeriodicalId":19256,"journal":{"name":"Neurology","volume":"11 1","pages":"e213920"},"PeriodicalIF":9.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594107","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}