JAMA neurologyPub Date : 2025-10-20DOI: 10.1001/jamaneurol.2025.3916
Theresa A Zesiewicz,Peter A LeWitt,Elan D Louis
{"title":"Neuromodulation and Tremor Suppression in the Periphery.","authors":"Theresa A Zesiewicz,Peter A LeWitt,Elan D Louis","doi":"10.1001/jamaneurol.2025.3916","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.3916","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"72 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319183","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}
JAMA neurologyPub Date : 2025-10-20DOI: 10.1001/jamaneurol.2025.3919
Lukas A Grajauskas
{"title":"The Cost of Armor.","authors":"Lukas A Grajauskas","doi":"10.1001/jamaneurol.2025.3919","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.3919","url":null,"abstract":"","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":" ","pages":""},"PeriodicalIF":21.3,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329182","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":"Seizure Frequency Trends Over Time in Treatment-Resistant Focal Epilepsy.","authors":"Ojas Potnis,Gabriel Biondo,Rachel Sukonik,Caitlin Grzeskowiak,Gary Cutter,Hamada Altalib,Ruben Kuzniecky,Daniel Lowenstein,Jacqueline French, ","doi":"10.1001/jamaneurol.2025.4085","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.4085","url":null,"abstract":"ImportanceOpen-label trials of antiseizure medications (ASMs) and devices suggest seizure reduction in focal treatment-resistant epilepsy (FTRE) may demonstrate treatment-related disease-modifying effects. Understanding FTRE trends can provide insight into treatment responses.ObjectiveTo determine whether seizure frequency in FTRE improves over time.Design, Setting, and ParticipantsThe Human Epilepsy Project 2 was a prospective, observational, multicenter study of patients with FTRE from May 2018 to September 2021 who were followed up for 18 to 36 months at 10 US-based comprehensive epilepsy centers. Analysis was performed from 2021 to 2024. Study data included seizure frequency, medication use, device use, surgeries tracked using daily electronic diaries, monthly check-ins, medical record review, and case report forms. Eligibility criteria included focal epilepsy diagnosis, age between 16 and 65 years, and failure of 4 or more ASMs (≥2 due to seizure control failure). Participants were recruited as a volunteer sample.ExposuresParticipants were treated with multiple interventions at their physicians' discretion.Main Outcomes and MeasuresThe primary outcome was seizure frequency trends, evaluated by quantifying seizure freedom rates and frequency reductions. Medication and device treatment responses were assessed by tracking ASM and device changes.ResultsOf 196 approached participants, 146 met eligibility criteria and were included in the study. Mean (SD) participant age was 40 (12) years, and epilepsy was diagnosed at a mean (SD) age of 19.8 (13.6) years. The cohort had 84 (57.5%) female participants. A total of 35 participants had implantable devices; 1 had epilepsy surgery during the study. Of 146 participants, 128 provided sufficient seizure data for analysis, and 2 were excluded as outliers. Seizure frequency was reduced in 86 participants (68.3%) during the second half of study participation compared to the first half. In the overall cohort, mean modeled monthly seizure frequency percentage reduction was 68.73% (95% CI, 52.92%-84.54%). From 0 to 12 months (cohort 1), mean modeled percentage reduction was 67.76% (95% CI, 19.42%-116.09%); for 12 to 24 months (cohort 2), 36.00% (95% CI, 9.27%-53.46%); and for longer than 24 months (cohort 3), 66.03% (95% CI, 48.25%-83.80%) (all P < .001). An ASM was added in 69 participants (54.7%), of whom 46 (66.7%) experienced seizure frequency reduction, including seizure freedom. Seizure trajectories in participants with devices did not significantly differ from those without devices.Conclusions and RelevanceFindings from the HEP2 study imply that FTRE improves over time, ASM additions had low probability of achieving seizure freedom but contributed to seizure reduction, and device-treated participants exhibited similar seizure trajectories to those without devices. Whether improvements reflected the natural history of FTRE or active management remains unclear, but our findings suggest cautious interpretat","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"99 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319185","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}
JAMA neurologyPub Date : 2025-10-20DOI: 10.1001/jamaneurol.2025.3905
William G Ondo,Wen Lv,Xiaodong Zhu,Yongsheng Hu,Stuart H Isaacson,Yuan Yuan,Alberto J Espay,David Kreitzman,Sheng-Han Kuo,Salima Brillman,Holly A Shill,Kelly E Lyons,Zhi Yang,Qi Zhao,Zhen Zhang,Rajesh Pahwa
{"title":"Transcutaneous Peripheral Nerve Stimulation for Essential Tremor: A Randomized Clinical Trial.","authors":"William G Ondo,Wen Lv,Xiaodong Zhu,Yongsheng Hu,Stuart H Isaacson,Yuan Yuan,Alberto J Espay,David Kreitzman,Sheng-Han Kuo,Salima Brillman,Holly A Shill,Kelly E Lyons,Zhi Yang,Qi Zhao,Zhen Zhang,Rajesh Pahwa","doi":"10.1001/jamaneurol.2025.3905","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.3905","url":null,"abstract":"ImportanceEssential tremor (ET) is the most common form of arm tremor. Transcutaneous peripheral nerve stimulation (TPNS) can modulate the central tremor-generating network.ObjectiveTo investigate whether an artificial intelligence (AI)-driven TPNS device is superior to a sham device in reducing ET.Design, Setting, and ParticipantsA randomized clinical trial was conducted from February 7 through August 9, 2024, in 12 outpatient neurology clinics in the United States and China. Participants were adults with upper-extremity tremor and a clinical diagnosis of ET, a tremor severity score of 2 or higher on 1 of the Essential Tremor Rating Assessment Scale (TETRAS) performance subscale tasks, a total performance subscale score of at least 7, and familiarity with operating a smartphone and connecting to Wi-Fi at home. They were randomized 2:1 to receive active TPNS or sham stimulation, stratified by use of ET medications and tremor severity. After the devices were fitted, the participants were instructed to use them during waking hours for 90 days.InterventionA wearable neuromodulation device that stimulates the radial, median, and ulnar nerves and uses AI to continuously adjust stimulation settings in real time.Main Outcome and MeasuresThe primary outcome was change in daily activities as measured by the modified Activities of Daily Living (mADL) subscale of TETRAS at 90 days in the intention-to-treat population.ResultsOf 133 screened, 125 were randomized to receive TPNS (n = 83) or sham (n = 42) treatment. The mean (SD) age was 64.9 (13.1) years, 62 (49.6%) were female and 63 (50.4%) male, and the mean (SD) tremor duration was 11.4 (13.1) years. At 90 days, the mADL score was reduced by 6.9 points (95% CI, 5.4-8.4) in the TPNS group vs 2.7 points (95% CI, 1.3-4.0) in the sham group (P < .001). Skin irritation, the most common device-related adverse event, occurred in 28 of 83 participants (33.7%) in the TPNS group and 2 of 42 (4.8%) in the sham group. Nausea, arthralgia, worsening of existing arthritis in the thumb, muscular weakness, and involuntary muscle contractions each occurred in 1 participant, all in the TPNS group.Conclusions and RelevanceThe TPNS device improved activities related to upper limb tremor at 90 days and could be an effective noninvasive ET treatment.Trial RegistrationClinicalTrials.gov Identifier: NCT06235190.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"51 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319184","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}
JAMA neurologyPub Date : 2025-10-13DOI: 10.1001/jamaneurol.2025.3869
Ming Lu,Min Jung Kim,Emily C Collins,Sergey Shcherbinin,Amy K Ellinwood,Yuma Yokoi,Dawn A Brooks,Oskar Hansson,David S Knopman,John R Sims,Mark A Mintun
{"title":"Posttreatment Amyloid Levels and Clinical Outcomes Following Donanemab for Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ 2 Randomized Clinical Trial.","authors":"Ming Lu,Min Jung Kim,Emily C Collins,Sergey Shcherbinin,Amy K Ellinwood,Yuma Yokoi,Dawn A Brooks,Oskar Hansson,David S Knopman,John R Sims,Mark A Mintun","doi":"10.1001/jamaneurol.2025.3869","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.3869","url":null,"abstract":"ImportanceAccumulation of amyloid plaque drives pathogenesis of Alzheimer disease (AD). Reduction of amyloid via amyloid-targeting therapies may result in clinical benefit.ObjectiveTo assess the correlation of posttreatment amyloid levels with clinical outcomes and biomarkers in AD.Design, Setting, and ParticipantsThis was a post hoc exploratory analysis from the randomized, placebo-controlled phase 3 trial, TRAILBLAZER-ALZ 2, conducted June 2020 through April 2023 at 277 medical research centers/hospitals in 8 countries. A total of 8240 participants aged 60 to 85 years with early symptomatic AD with amyloid and tau pathology based on positron emission tomography (PET) imaging were assessed for eligibility. Of these, 6504 participants were excluded predominantly due to inadequate amyloid or tau pathology. The current analysis included 1582 participants (766 in the donanemab group and 816 in the placebo group) with baseline and at least 1 posttreatment assessment. Data analysis took place from July 2024 to March 2025.InterventionsParticipants were randomized 1:1 to receive donanemab (700 mg for the first 3 doses and 1400 mg thereafter) or placebo intravenously every 4 weeks for up to 72 weeks, with outcomes assessed through 76 weeks.Main Outcomes and MeasuresParticipants were categorized into 1 of 10 groups (deciles) based on their lowest amyloid value observed posttreatment. Clinical progression was assessed via changes in integrated Alzheimer's Disease Rating Scale (iADRS) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. Plasma biomarkers measured included phosphorylated tau 217 (p-tau217), p-tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). Correlations between the median amyloid level in each decile were assessed with 76-week least-squares mean changes in each outcome and biomarker.ResultsAnalyses included 1582 participants, including 766 treated with donanemab and 816 with placebo. The mean (SD) age was 72.9 (6.2) years, and 900 participants (56.9%) were female. Participants who received donanemab had lower posttreatment amyloid values than those in the placebo group. Across the trial population, lower posttreatment amyloid levels were correlated with slower clinical progression as measured by iADRS score (R2, 0.73 [95% CI, 0.37-0.97]) and CDR-SB score (R2, 0.87 [95% CI, 0.70-0.97]) and with decreases in p-tau217 (R2, 0.86 [95% CI, 0.73-0.97]), p-tau181 (R2, 0.88 [95% CI, 0.77-0.97]), and GFAP (R2, 0.87 [95% CI, 0.76-0.97]). There was no correlation between posttreatment amyloid value and NfL (R2, 0.03 [95% CI, 0.00-0.54]).Conclusions and RelevanceThe findings in this secondary analysis of a randomized clinical trial demonstrating a correlation between posttreatment amyloid plaque level and clinical benefit support amyloid plaque removal as the mechanism of action for donanemab treatment and the level of amyloid plaque as a potential surrogate biomarker in amyloid-targeting therapies.Trial Registra","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"4 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277161","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}
JAMA neurologyPub Date : 2025-10-13DOI: 10.1001/jamaneurol.2025.3775
Peng Roc Chen,Carlos A Artime,Sunil A Sheth,Claudia Pedroza,Santiago Ortega-Gutierrez,Stacey Wolfe,Clark Sitton,Peter Kan,Omar Tanweer,Alex Chebl,Clemens M Schirmer,Jay T Morrow,Yazan J Alderazi,Bradley Bohnstedt,Kadir Erkmen,Edgar A Samaniego,Elena Garrido,Sean I Savitz,Allison Engstrom,Eddie Aguilar,Tien Nguyen,Andrew D Barreto,
{"title":"Sedation vs General Anesthesia for Endovascular Therapy in Acute Ischemic Stroke: The SEGA Randomized Clinical Trial.","authors":"Peng Roc Chen,Carlos A Artime,Sunil A Sheth,Claudia Pedroza,Santiago Ortega-Gutierrez,Stacey Wolfe,Clark Sitton,Peter Kan,Omar Tanweer,Alex Chebl,Clemens M Schirmer,Jay T Morrow,Yazan J Alderazi,Bradley Bohnstedt,Kadir Erkmen,Edgar A Samaniego,Elena Garrido,Sean I Savitz,Allison Engstrom,Eddie Aguilar,Tien Nguyen,Andrew D Barreto, ","doi":"10.1001/jamaneurol.2025.3775","DOIUrl":"https://doi.org/10.1001/jamaneurol.2025.3775","url":null,"abstract":"ImportanceThe optimal anesthetic strategy for patients undergoing endovascular therapy (EVT) for acute ischemic stroke (AIS) from large vessel occlusion (LVO) remains unclear.ObjectiveTo determine if general anesthesia (GA) or moderate sedation for patients who undergo EVT for AIS with LVO is associated with a different functional outcome in 90 days.Design, Setting, and ParticipantsThis was a multicenter randomized clinical trial conducted from July 2018 to August 2023 of patients with AIS who were receiving EVT due to LVO. Patients were recruited from 10 comprehensive stroke centers in the US. Adult patients with occlusion of the carotid artery and the proximal middle and anterior cerebral artery who underwent EVT were eligible for enrollment.InterventionsPatients were randomized to receive either moderate sedation or GA in 1:1 ratio.Main Outcomes and MeasuresThe primary outcome was the ordinal modified Rankin Scale (mRS) score at 90 days.ResultsA total of 1931 patients were screened for eligibility, and 1671 were excluded due to failure meeting the inclusion criteria. Among 260 individuals with a mean (SD) age of 66.8 (13.3) years included in this intention-to-treat study, 133 were male (52%), and 130 (50%) were randomized to GA and sedation each. At 90 days, a shift in the distribution of ordinal mRS was found favoring GA (odds ratio [OR], 1.22; 95% credible interval [CrI], 0.79-1.87) with an 81% posterior probability of GA superiority. The probability that GA was superior to sedation was 89% (relative risk [RR], 1.2; 95% CrI, 0.9-1.66) and 69% (RR, 1.01; 95% CrI, 0.96-1.08) for 90-day mRS 0 to 2 and successful reperfusion, respectively. Other secondary outcomes were similar. Symptomatic intracerebral hemorrhage was 0.8% (1 of 125 patients) in GA vs 2.4% (3 of 125 patients) in sedation with a posterior probability of GA was superior to sedation of 72% (RR, 0.71; 95% CrI, 0.23-2.16).Conclusions and RelevanceThis randomized clinical trial found that patients with LVO AIS who were treated with EVT using GA had improved rates of 90-day outcomes and higher rates of successful reperfusion compared with those treated using moderate sedation.Trial RegistrationClinicalTrials.gov Identifier: NCT03263117.","PeriodicalId":14677,"journal":{"name":"JAMA neurology","volume":"39 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277196","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}