Epilepsia最新文献

{"title":"Epilepsia – April 2025 Announcements","authors":"","doi":"10.1111/epi.18379","DOIUrl":"https://doi.org/10.1111/epi.18379","url":null,"abstract":"<p>\u0000 \u0000 <b>7th ILAE School on EEG in the First Year of Life</b>\u0000 \u0000 </p><p>26–27 April 2025</p><p>Sanya City, Hainan, China</p><p>\u0000 \u0000 <b>ILAE School on Neuroimaging 2025</b>\u0000 \u0000 </p><p>15–17 May 2025</p><p>Potsdam, Germany</p><p>\u0000 \u0000 <b>5th African Epilepsy Congress</b>\u0000 \u0000 </p><p>16–18 May 2025</p><p>Lusaka, Zambia</p><p>\u0000 \u0000 <b>15th ILAE School for Neuropathology and Neuroimaging in Epilepsy</b>\u0000 \u0000 </p><p>31 July – 3 August 2025</p><p>Campinas, São Paulo, Brazil</p><p>\u0000 \u0000 <b>XVIII Workshop on Neurobiology of Epilepsy (WONOEP 2025)</b>\u0000 \u0000 </p><p>25–29 August 2025</p><p>Portugal</p><p>\u0000 \u0000 <b>36th International Epilepsy Congress</b>\u0000 \u0000 </p><p>30 August – 3 September 2025</p><p>Lisbon, Portugal</p><p>\u0000 <b>2026</b>\u0000 </p><p>\u0000 \u0000 <b>15th ILAE School on Pre-Surgical Evaluation for Epilepsy and Epilepsy Surgery</b>\u0000 \u0000 </p><p>19–23 January 2026</p><p>Brno, Czech Republic</p><p>\u0000 \u0000 <b>16th European Epilepsy Congress</b>\u0000 \u0000 </p><p>5–9 September 2026</p><p>Athens, Greece</p><p>\u0000 \u0000 <b>Focal Ictogenesis: When and why does interictal activity transition into ictal activity?</b>\u0000 \u0000 </p><p>10 April 2025</p><p>\u0000 \u0000 <b>ILAE e-Forum: Diagnosis and classification of Developmental and Epileptic Encephalopathies (DEE)</b>\u0000 \u0000 </p><p>22 April 2025</p><p>\u0000 \u0000 <b>Thalamo-cortical Network: How does coupling between focus and thalamus change before seizures?</b>\u0000 \u0000 </p><p>24 April 2025</p><p>\u0000 \u0000 <b>SUDEP: What are the mechanisms and risk factors?</b>\u0000 \u0000 </p><p>13 May 2025</p><p>\u0000 \u0000 <b>Neurodegeneration: When and how do neurodegenerative diseases lead to seizures?</b>\u0000 \u0000 </p><p>20 May 2025</p><p>\u0000 \u0000 <b>Seizures: Can they cause brain damage?</b>\u0000 \u0000 </p><p>22 May 2025</p><p>\u0000 \u0000 <b>Neuromodulation: How can we optimize DBS protocols?</b>\u0000 \u0000 </p><p>20 May 2025</p><p>\u0000 \u0000 <b>Understanding Functional Seizures in Children</b>\u0000 \u0000 </p><p>17 June 2025</p><p>\u0000 \u0000 <b>AD/PD™ 2025 International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders</b>\u0000 \u0000 </p><p>1–5 April 2025</p><p>Vienna, Austria & Online</p><p>\u0000 \u0000 <b>International Congress on Structural Epilepsy & Symptomatic Sei","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":"66 4","pages":"1347-1348"},"PeriodicalIF":6.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846065","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":"Embracing the future: Neonatal screening for epileptic syndromes.","authors":"Rima Nabbout, Mathieu Kuchenbuch","doi":"10.1111/epi.18285","DOIUrl":"https://doi.org/10.1111/epi.18285","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794764","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":"Circumstances surrounding sudden unexpected death in epilepsy in children: A national case series.","authors":"Robyn Whitney, Anne Keller, Shelly-Anne Li, Anita N Datta, Matthew MacDonald, Maryam Nabavi Nouri, Daniela Pohl, Erick Sell, Gabriel M Ronen, Mandeep Sidhu, Elisabeth Simard-Tremblay, Michael S Pollanen, Elizabeth J Donner","doi":"10.1111/epi.18339","DOIUrl":"https://doi.org/10.1111/epi.18339","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to understand the circumstances surrounding pediatric sudden unexpected death in epilepsy (SUDEP) and identify clinical factors that may be associated with SUDEP in childhood.</p><p><strong>Methods: </strong>A retrospective case series was conducted. Pediatric SUDEP cases were collected across Canada from the Ontario Forensic Pathology Service, Canadian Pediatric Surveillance Program, and Canadian Pediatric Epilepsy Network. Demographics, epilepsy history, comorbidities, and circumstances surrounding death were analyzed.</p><p><strong>Results: </strong>Forty-nine children with pediatric SUDEP were analyzed; 25 (51%) were females, and the median age at death was 8 years. Six children (12%) were <2 years of age at the time of death. Information on seizure types 6 months before death was known in 35 children. Twenty-two had tonic-clonic seizures within the last 6 months prior to death (63%). Seven children (18%) had no tonic-clonic seizures in their lifetime. Two thirds of children were treated with ≥2 antiseizure medications. Genetic etiologies were most common (55%). Data on global developmental delay (GDD) was known in 46 children; 12 children (26%) had no impairment, and 34 were globally delayed (74%). Children with GDD had earlier age at seizure onset (p < .001); however, epilepsy duration was similar to those without GDD (p = .170). Similar to adult cohorts, death was often unwitnessed (n = 41/46, 89%). Information on recent infection before death was known in 37 children. Seventeen children (46%) had a recent infection.</p><p><strong>Significance: </strong>Our study represents the largest pediatric SUDEP case series to date. SUDEP occurred in children of all ages, including infants, with a spectrum of epilepsies with and without neurodevelopmental impairment. The circumstances around death (i.e., timing of death, witnessed/unwitnessed) were similar to previous SUDEP cohorts. A recent infection was often observed, which could decrease seizure threshold and trigger a terminal seizure and may suggest that times of increased seizure risk could warrant heightened surveillance for SUDEP. However, further research is needed to determine the significance of this finding.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788089","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 whole genome sequencing in pediatric epilepsy: Genetic and phenotypic spectrum of 733 individuals.","authors":"Olivia J Henry, Sofia Ygberg, Michela Barbaro, Nicole Lesko, Leif Karlsson, Lucía Peña-Pérez, Ann Båvner, Virpi Töhönen, Anna Lindstrand, Tommy Stödberg, Anna Wedell","doi":"10.1111/epi.18403","DOIUrl":"https://doi.org/10.1111/epi.18403","url":null,"abstract":"<p><strong>Objective: </strong>A large proportion of pediatric epilepsies have an underlying genetic etiology. Limited studies have explored the efficacy of whole genome sequencing (WGS) in a clinical setting. Our academic-clinical center implemented clinical whole exome sequencing (WES) in 2014, then transitioned to WGS from 2015. We report the diagnostic yield, genetic and phenotypic findings, and prognostic factors following WGS/WES in pediatric epilepsy.</p><p><strong>Methods: </strong>The cohort included 733 families with pediatric epilepsy who received clinical WGS/WES between 2014 and 2022. WGS/WES was performed at the Genomic Medicine Center Karolinska for Rare Diseases and analyzed at the Center for Inherited Metabolic Diseases at Karolinska University Hospital. Phenotypic information was extracted from referrals and medical records. Genetic and phenotypic data were analyzed using descriptive statistics, and univariable and multivariable analyses.</p><p><strong>Results: </strong>The median age at seizure onset was 9 months. Developmental delay and/or intellectual disability (DD/ID) was observed in 61.3% of the cohort; 38.1% of individuals received an International League Against Epilepsy epilepsy syndrome diagnosis. WGS/WES was performed in 640 (87.3%) and 143 (19.5%) families, respectively, totaling 2029 individuals. A molecular diagnosis was identified in 278 of 733 individuals (37.9%), including 51 of 211 individuals analyzed more than once (24.2% of reanalyzed cases). Independent predictors for receiving a genetic diagnosis included female sex (adjusted odds ratio [aOR] = 1.8, 95% confidence interval [CI] = 1.3-2.4, p < .001), neonatal seizure onset (aOR = 2.5, 95% CI = 1.6-4, p < .001), mortality (aOR = 2.2, 95% CI = 1.3-4.0, p = .0048), and an ID/DD/developmental and epileptic encephalopathy (DEE) diagnosis (aOR = 1.8, 95% CI = 1.2-2.5, p = .0019). The strongest independent predictor of ID/DD/DEE was microcephaly (aOR = 7.8, 95% CI = 2-53, p = .0099). In the solved cohort, gene group did not predict cognitive outcome.</p><p><strong>Significance: </strong>Clinical WGS is an effective diagnostic tool in pediatric epilepsy. We identified female sex as a novel prognostic factor for receiving a genetic diagnosis and highlight the value of reanalyzing previously unsolved cases to improve diagnostic yield.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779564","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":"Neurobehavioral therapy in functional seizures: Investigation of mechanism of action with resting-state functional magnetic resonance imaging.","authors":"Jerzy P Szaflarski, W Curt LaFrance, Rodolphe Nenert, Jane B Allendorfer, Stephen Correia, Tyler E Gaston, Adam M Goodman, Leslie E Grayson, Noah Philip","doi":"10.1111/epi.18401","DOIUrl":"https://doi.org/10.1111/epi.18401","url":null,"abstract":"<p><strong>Objective: </strong>Functional seizures (FS) often disrupt the key regions integral to cognitive processing and emotional regulation (anterior insula, anterior cingulate, and temporoparietal junction). We investigated the potential neurophysiologic mechanism of action (MOA) of neurobehavioral therapy (NBT) using resting-state functional MRI seed-based whole-brain functional connectivity within these regions in adults with FS. We hypothesized that NBT would induce changes in functional connectivity in parallel with improving seizure frequency and behavioral outcomes.</p><p><strong>Methods: </strong>Forty patients with traumatic brain injury and FS (TBI+FS) underwent 12 weekly sessions of NBT and provided pre-/post-intervention resting-state functional magnetic resonance imaging (MRI), seizure logs, and behavioral assessments. Fifty-five individuals with TBI without FS (TBI-only) completed the same measures, received standard medical care but not NBT, and functional MRI ~12 weeks apart. For each key region, two-sample t-tests assessed direct group comparison. Repeated measures analysis of covariance assessed how group differences evolved over time and how these changes were modulated by the changes in seizure frequency, diagnosis duration, or behavioral scores (false discovery rate corrected at p < .05).</p><p><strong>Results: </strong>With NBT, seed-based whole-brain functional connectivity was significantly higher between right anterior insula and left supplementary motor area in TBI+FS compared to TBI-only, and between left anterior insula and left postcentral gyrus in seizure-free TBI+FS compared to those who were not seizure-free. Percentage decrease in seizure frequency with NBT was associated with lower functional connectivity between bilateral insula and left superior medial frontal gyrus in patients with FS. Improvements in behavioral measures did not correspond to changes in functional connectivity.</p><p><strong>Significance: </strong>The study underscores the relationship between the changes in resting-state functional connectivity of the anterior insula in FS and treatment response to NBT and illustrates the potential neurophysiologic MOA of NBT for the treatment of FS; it suggests an independence of this MOA from the potential effects of NBT on behavioral measures.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779569","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":"Neuropsychological outcomes of hippocampus-sparing anterior temporal lobectomy versus stereotactic laser amygdalohippocampectomy in language-dominant temporal lobe epilepsy.","authors":"Zeegan George, Keaton Piper, Elliot G Neal, Adam Alayli, Samantha Schimmel, Molly Monsour, Long Di, Ushtar Amin, Joseph J Boscarino, Michael R Schoenberg, Fernando L Vale, Yarema B Bezchlibnyk","doi":"10.1111/epi.18388","DOIUrl":"https://doi.org/10.1111/epi.18388","url":null,"abstract":"<p><strong>Objective: </strong>Postoperative neuropsychological deficits pose a significant challenge for temporal lobe epilepsy (TLE) surgery, particularly in the language-dominant hemisphere. Two surgical approaches have been suggested to mitigate such adverse outcomes: stereotactic laser amygdalohippocampectomy (SLAH) and hippocampus-sparing anterior temporal lobectomy (HSATL). This retrospective cohort study compares the seizure control and neuropsychological outcomes of HSATL and SLAH in language-dominant TLE.</p><p><strong>Methods: </strong>A retrospective cohort study compared 27 patients (nine male, mean age = 35.8 years) with drug-resistant TLE and normal imaging localized to the language-dominant left temporal lobe, undergoing either HSATL (n = 22) or SLAH (n = 5) between 2014 and 2021. Comprehensive pre- and ≥1-year postoperative neuropsychological testing and imaging were performed, with seizure outcomes tracked for at least 1 year postoperatively. However, to assess the impact of mesial temporal sclerosis (MTS) on SLAH outcomes, we included seven additional patients with MTS who underwent SLAH in a secondary analysis.</p><p><strong>Results: </strong>HSATL led to significant declines in logical memory (p = .04) despite sparing the hippocampus, which were not seen following SLAH in patients regardless of MTS status. SLAH trended toward improved semantic fluency, immediate verbal memory, and executive function despite hippocampal ablation. Including both MTS(+) and MTS(-) patients, there was a significant decline in letter fluency following SLAH (.04), with subgroup analyses demonstrating significantly greater declines in MTS(+) patients undergoing SLAH (.02). Additionally, 100% of patients undergoing SLAH achieved seizure freedom versus 72.7% following HSATL (p = .046, including MTS[+] patients) at last follow-up.</p><p><strong>Significance: </strong>In language-dominant TLE, SLAH demonstrated comparable seizure outcomes and superior verbal memory retention compared to HSATL, albeit with greater letter fluency impairment. Preliminary findings challenge prioritizing hippocampal preservation for verbal memory function, suggesting potential cognitive advantages with SLAH specifically targeting mesial structures while maximally preserving cortical structures and white matter tracts critical for language networks. However, this intervention may negatively impact letter fluency, suggesting careful preoperative screening and discussion.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779571","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":"Differences in patterns of outpatient epilepsy-specific medication initiation after acute ischemic stroke in the Medicare population.","authors":"Maria A Donahue, Julianne D Brooks, John Hsu, Mary Price, Deborah Blacker, Lee H Schwamm, Joseph P Newhouse, M Brandon Westover, Sebastien Haneuse, Lidia M V R Moura","doi":"10.1111/epi.18396","DOIUrl":"https://doi.org/10.1111/epi.18396","url":null,"abstract":"<p><strong>Objective: </strong>Acute ischemic stroke (AIS) is a leading hospitalization cause and significantly contributes to seizures among older adults. We examined outpatient epilepsy-specific medication (ESM) initiation patterns after AIS discharge in adults 65 years and older, trends over time (by stratifying the analysis from 2013 to 2021), and racial/ethnic differences.</p><p><strong>Methods: </strong>We analyzed nationwide administrative claims data for a 20% sample of US Medicare beneficiaries (enrolled in Traditional Medicare Parts A, B, and D for at least 12 months before admission) aged ≥65 years and hospitalized for AIS between 2013 and 2021. We estimated the cumulative incidence of ESM initiation within 90 days after AIS discharge, with mortality as a competing risk and censoring person time if individuals experienced an inpatient readmission. We described drug type and stratified our analysis by race, ethnicity, US geographic region, hospital region, and year of discharge.</p><p><strong>Results: </strong>Of 128 174 community-dwelling beneficiaries after AIS discharge, 2435 (1.9%, 95% confidence interval [CI] = 1.8%-2.0%) initiated ESM within the 90-day follow-up period and levetiracetam was the most common medication across all years (81%). Mean age was 79 years (range = 65-110), 56% were female, 81% were non-Hispanic White, 10% were Black/African American, 5% were Hispanic, and 3% were Asian. The cumulative incidence of ESM initiation at 90 days in the overall sample was 1.4% (95% CI = 1.3%-1.4%); it was 1.8% (95% CI = 1.6%-2.1%) for Black/African American, 1.9% (95% CI = 1.6%-2.3%) for Hispanic, and 1.2% (95% CI = 1.2%-1.3%) for non-Hispanic White beneficiaries. The 90-day cumulative incidence also varied by US Census division, from 1.0% (95% CI = .8-1.3; West North Central) to 1.5% (95% CI = 1.3%-1.8%; East South Central). We observed an increase in ESM 90-day initiation over time, from 1.2% (95% CI = 1.0%-1.5%) in 2013 to 1.7% (95% CI = 1.5%-1.9%) in 2021. ESM initiation was 1.6% (95% CI = 1.4%-1.8%) in the 65-70-year age group and decreased in older age groups.</p><p><strong>Significance: </strong>Black/African American and Hispanic beneficiaries had a higher 90-day incidence of post-AIS ESM initiation than non-Hispanic Whites. ESM initiation decreased in older age groups.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779567","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 trials of prevention of acquired epilepsy: New proof-of-concept approach to restart trials.","authors":"Pavel Klein, Matthias Koepp, Alexander Rotenberg, Mustafa Hameed, Wolfgang Löscher","doi":"10.1111/epi.18394","DOIUrl":"https://doi.org/10.1111/epi.18394","url":null,"abstract":"<p><p>Approximately 20% of epilepsy is caused by acute central nervous system insults such as traumatic brain injury (TBI), stroke, and infection. There is a latent period of weeks to years between the insult and epilepsy onset, which offers an opportunity to prevent epilepsy. No preventive treatments exist. Their development is a major unmet need in neurology. For logistical reasons, epilepsy acquired after TBI, posttraumatic epilepsy (PTE), is most suitable for epilepsy prevention studies. In the past 20 years, preclinical PTE research has flourished, offering potential treatments to prevent PTE, but clinical development has been dormant. The major barrier in the development of PTE preventive treatment is the lack of a viable proof of concept (POC) trial design. PTE trials use the first late unprovoked posttraumatic seizure as an outcome measure, which necessitates a long (~2-year) follow-up and makes POC studies nonfeasible. A reliable biomarker of early PTE detection would allow shorter follow-up duration and facilitate POC studies, but such a biomarker is not yet available. Biomarker, POC, and randomized clinical trial studies have virtually identical designs in terms of patient inclusion and follow-up. Done sequentially, the studies would take a generation to complete. We propose a novel trial design for studies of PTE prevention that combines discovery of biomarker(s) of early PTE detection with POC study and uses an adaptive study POC-phase 3 continuation design approach to incorporate POC study into phase 3 study following an interim futility analysis after 6 months of treatment of the first 25% of the cohort, the POC population. This approach would establish a POC model for treatment of PTE prevention, shorten development of PTE prevention treatment, and reopen the door to clinical trials to prevent epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784358","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":"Protective effect of CACNA1A deficiency in oligogenic refractory epilepsy with CACNA1A-CELSR2 digenic mutations.","authors":"Chu-Qiao Liu, Mei-Zhen Sun, Yong-Miao Lin, Xi-Xing Zhang, Rui-Na Huang, Ming-Feng He, Sheng Luo, Si-Yuan Luo, Tao Huang, Nan Jiang, Jie Luo, Jia-Xin Zhang, Pei-Run Chen, Xi Dai, Tian-Ai Han, Wei-Ping Liao, Rong-Chao Peng, Jing-Da Qiao","doi":"10.1111/epi.18390","DOIUrl":"https://doi.org/10.1111/epi.18390","url":null,"abstract":"<p><strong>Objective: </strong>The vast majority of refractory epilepsy cases have a complex oligogenic/polygenic origin, which presents a challenge to precision medicine in individual patients. Nonetheless, the high workload and lack of effective guidelines have limited the number of in-depth animal studies.</p><p><strong>Methods: </strong>Whole-exon sequencing identified a case with refractory epilepsy caused by a combination of two rare and de novo heterozygous variants in CACNA1A and CELSR2, respectively. Polygenic mutation flies were established and logistic regression were applied to study the gene-gene interaction and quantify the seizure-risk weight of epilepsy-associated genes in a polygenic background. In addition, calcium imaging, pharmacology, and transgenic rescue experiments were used to explore the mechanism and the precision medicine strategy for this model.</p><p><strong>Results: </strong>Seizure-like activity was mitigated in the Cacna1a-Celsr2 digenic knockdown flies, whereas it was aggravated in the Cacna1a knockin-Celsr2 knockdown flies, and all relevant monogenic mutation flies showed seizures. Logistic regression suggested that the Cacna1a deficiency provided a protective effect against seizures in Celsr2 knockdown flies. The severe seizures from Cacna1a knockin-Celsr2 knockdown, the genotype mimicking that of the patient, can be completely rescued by inhibiting the calcium channel via genetic (Cacna1a knockdown) or pharmacologic (pregabalin) treatment during a limited period of development. Calcium imaging results suggested a synaptic cleft balance mechanism for the protective effect of CACNA1A deficiency in the polygenic background.</p><p><strong>Significance: </strong>CACNA1A presented multiple effects on epileptogenesis in diverse genetic backgrounds and provided an effective preclinical approach to clarify the net impact of polygenic variants for designing a precisive medicine strategy against refractory epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784365","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":"Achieving epilepsy care for all: Ecosystem-based transformation.","authors":"Susanna Gallani, Bernice Martin Lee, Lidia M V R Moura","doi":"10.1111/epi.18400","DOIUrl":"https://doi.org/10.1111/epi.18400","url":null,"abstract":"<p><p>Epilepsy exemplifies many of the systemic challenges of modern health care-fragmented care delivery, inequitable access, financial strain, and so on. The current \"system of systems\" (SoS) structure of U.S. health care fosters siloed operations among its member systems (e.g., insurers, health care institutions, providers, researchers, pharmaceutical companies, and technology vendors), failing to address interconnected issues like care continuity, clinician burnout, and appropriate resource allocation. This article proposes embracing a health care ecosystem approach as a solution, emphasizing interdependence, collaboration, and equity. Section 1 examines the shortcomings of the current care model, with a focus on its financial challenges and the systemic inefficiencies it perpetuates. Section 2 explains the concept of a health care ecosystem and its potential to drive equity through organic coordination and collective accountability. It highlights the role of key member systems-patients, advocacy groups, professional organizations, health care providers, payers, purchasers, policymakers, researchers, and industry leaders-in achieving equity in brain health care. Finally, Section 3 presents a roadmap for transitioning from SoS to ecosystem, outlining multiple actionable strategies, such as enhancing advocacy and data sharing by professional organizations, adopting integrated and multidisciplinary care models by health care providers, and prioritizing affordability and collaboration by industry leaders. Policymakers and federal research organizations can support the transition by incentivizing collaboration, expanding funding for health services research, and supporting data-driven decision-making. Advocacy groups can amplify collective voices and help prioritize improvement opportunities. Using epilepsy care as an example condition, this article argues that coordinated, multi-sector, and multi-level efforts can successfully and efficiently address systemic challenges, improve outcomes, and reduce inequities. It offers a replicable framework for achieving sustainable, scalable, and equitable care for chronic neurological conditions.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779513","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}