Epilepsia最新文献

{"title":"Folic acid supplementation and prevention of adverse offspring outcomes among women with epilepsy: An observational study.","authors":"Yutong Fu, Fanfan Shi, Leihao Sha, Ying Ma, Weihong Lin, Xiaoyi Li, Hua Yan, Pei Wang, Jiajia Fang, Qun Huang, Fang Chen, Yun Li, Qingxia Kong, Hua Huang, Xiangshu Hu, Changqing Liu, Jian Wang, Xiaohua Xiao, Qi Zhang, Rong Mei, Yanbing Han, Yuan Wu, Shixu He, Hua Zhang, Kuiyun Wang, Yanmei Zhu, Wanhui Lin, Zhanghui Peng, Xi Zhu, Xunyi Wu, Ming Yu, Mei Zou, Xin Zou, Ting Wu, Xuelian He, Haizhi Guo, Min Zhong, Qing Zhang, Yan Su, Yaqing Liu, Qin Feng, Houfen Wang, Wenwu Chen, Yanping Sun, Meizhen Sun, Jian Zhou, Hongjian Zhao, Chonglun Guo, Jing Gao, Yi Guo, Jiajun Huang, Hao Sun, Xiaojing Luo, Ruiqi Yang, Huan Qin, Torbjörn Tomson, Lei Chen","doi":"10.1002/epi.70264","DOIUrl":"https://doi.org/10.1002/epi.70264","url":null,"abstract":"<p><strong>Objective: </strong>Folic acid (FA) is essential for fetal development, while the benefits and optimal dose in pregnant women with epilepsy (PWWE) remain unclear. This study explores effects of FA supplementation, dose, and initiation time on offspring outcomes in PWWE.</p><p><strong>Methods: </strong>This multi-center cohort recruited PWWE from 58 hospitals in China. Anti-seizure medication (ASM) and FA exposures were categorized by first-trimester use. The primary outcome was a composite of preterm birth, low birth weight (LBW), major congenital anomalies (MCAs), fetal death, and neurodevelopmental delay. Logistic regression models assessed the associations between FA exposure, dose, initiation time, and adverse outcomes, adjusting for demographics and epilepsy characteristics, with stratification by maternal ASM use. Dose-response relationships were analyzed using restricted cubic splines.</p><p><strong>Results: </strong>Among 1013 women with 1209 pregnancies, 952 received FA. In ASM-exposed pregnancies, FA supplementation was associated with lower risks of composite adverse offspring outcomes (adjusted odds ratio [aOR] .59, 95% confidence interval [CI] .387-.911) and fetal death (aOR .127, 95% CI .054-.296), whereas no significant differences were observed between preconception and first-trimester initiation. Compared to no supplement, supplementation with .4 mg/day protected against fetal death (aOR .185, 95% CI .078-.428); doses exceeding .4 mg/day further reduced risk of composite adverse outcomes (aOR .343, 95% CI .162-.675), and doses above 1 mg additionally showed trends toward decreased preterm birth in ASM-exposed pregnancies (aOR .338, 95% CI .104-.943). Compared with .4 mg supplementation, doses above 1 mg/day were associated with a lower risk of LBW (aOR .208, 95% CI .05-.58).</p><p><strong>Significance: </strong>FA supplementation was associated with lower risks of composite adverse offspring outcomes in ASM-exposed pregnancies, specifically at doses exceeding .4 mg. No such associations were observed in pregnancies not exposed to ASMs. However, the optimal upper limit of high-dose FA supplementation requires further investigation.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835088","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":"Increased interval between seizure clusters across time in pediatric patients treated with the immediate-use seizure medication diazepam nasal spray.","authors":"James W Wheless, Eric Segal, Jurriaan M Peters, Steven M Wolf, Genei Bougher, Charles Davis, Leock Y Ngo, Enrique Carrazana, Adrian L Rabinowicz","doi":"10.1002/epi.70256","DOIUrl":"https://doi.org/10.1002/epi.70256","url":null,"abstract":"<p><strong>Objective: </strong>Seizure clusters, intermittent increases in seizure activity that differ from a patient's usual seizure pattern, may occur despite treatment with a daily anti-seizure medication. Benzodiazepine-containing immediate-use seizure medications (ISMs; also called rescue therapies) are the cornerstone of treatment for seizure clusters. Diazepam nasal spray is approved by the U.S. Food and Drug Administration to treat seizure clusters in patients with epilepsy ≥2 years of age. A prior long-term safety study of diazepam nasal spray showed an increased inter-seizure cluster interval (SEIzure interVAL [SEIVAL]) in days across a year in patients 6 to 65 years of age. The current analysis focused on changes in SEIVAL over time in a separate study in children with epilepsy 2 to 5 years of age.</p><p><strong>Methods: </strong>Patients with epilepsy 2 to 5 years of age were enrolled in an open-label, Phase 1/2a trial of diazepam nasal spray that included a single-dose pharmacokinetics period, 180-day safety period, and optional extension period. Doses of 5, 10, or 15 mg were administered based on weight (0.5 mg/kg). A post hoc analysis evaluated SEIVAL for consecutive 90-day periods overall and in a consistent cohort of patients with persistent use and SEIVALs in each period.</p><p><strong>Results: </strong>Among enrolled patients (n = 36), 22 (61.1%) had ≥1 SEIVAL, with a total of 315 SEIVALs recorded. Mean SEIVAL (±SD) doubled from 25.2 (±21.3) days in Period 1 (n = 20) to 51.9 (±72.4) days in Period 3 (n = 8). In the consistent cohort (n = 7), mean SEIVAL increased from 22.1 (±12.7) days in Period 1 to 27.7 (±25.4) days in Period 3.</p><p><strong>Significance: </strong>These results corroborate those of the earlier post hoc analysis of data from patients 6 to 65 years of age who received diazepam nasal spray for seizure clusters. These findings suggest a beneficial long-term treatment effect of diazepam nasal spray beyond acute use as an ISM.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835147","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 International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) Portal: An open source resource for neuropsychological research in epilepsy.","authors":"Robyn M Busch, Tobias Brünger, Kayela Arrotta, Lisa Ferguson, Julie K Janecek, Sara J Swanson, Anny Reyes, Brook Hurd, Mark St John, Carrie R McDonald, Bruce P Hermann, Dennis Lal","doi":"10.1002/epi.70263","DOIUrl":"https://doi.org/10.1002/epi.70263","url":null,"abstract":"<p><strong>Objective: </strong>The International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) is a consensus-based, empirically-driven approach to standardize cognitive phenotyping in epilepsy research that has quickly garnered interest within the epilepsy community. However, manually generating IC-CoDE phenotypes in group data is laborious and time-consuming, particularly in datasets containing heterogenous cognitive measures or batteries, limiting the widespread adoption of IC-CoDE phenotypes to further multicenter epilepsy research.</p><p><strong>Methods: </strong>To remove this barrier, we developed the IC-CoDE Portal (https://ic-code-portal.ccf.org/), an interactive and user-friendly, web-based platform to support the scientific community in performing IC-CoDE individual level classification through web interface or bulk classification through uploading of data files. The Portal also allows the user to generate and visualize cohort summary statistics of cognitive phenotypes in their dataset, with the option of filtering the data interactively by specified demographic or clinical variables of interest. We further made the resulting IC-CoDE phenotypes downloadable as a spreadsheet to foster offline analysis of cognitive data by members of the epilepsy research community.</p><p><strong>Significance: </strong>Ascertainment of cognitive profiles is key to understanding the natural heterogeneity in the clinical presentation of the epilepsies and their comorbidities. The IC-CoDE taxonomy can be applied to any comprehensive neuropsychological battery, regardless of the specific test measures and normative data used or the language and culture in which the assessment took place, making it an ideal tool to accelerate international multi-center studies on cognition in epilepsy. We hope that by eliminating some of the barriers associated with cognitive phenotyping, the IC-CoDE Portal will springboard large-scale collaborative efforts to further our understanding of the neuropsychology of the epilepsies.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835150","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":"Stereo-electroencephalography-guided cross-electrode radiofrequency thermocoagulation in focal epilepsy: A review of current methodologies and outcomes.","authors":"Bethany Campbell, Andrew Neal, Emily Cockle, Genevieve Rayner, Rubina Alpitsis, Eliza Blomfield, Terence J O'Brien, Matthew Gutman, Joshua Laing, Martin Hunn, Alissandra McIlroy","doi":"10.1002/epi.70261","DOIUrl":"https://doi.org/10.1002/epi.70261","url":null,"abstract":"<p><p>Advances in stereo-electroencephalography-guided radiofrequency thermocoagulation (SEEG-guided RFTC) have led to the development of cross-electrode RFTC, which has been shown to result in significantly larger lesions and higher seizure-freedom rates compared to standard RFTC methods. Given the novelty of cross-electrode RFTC, herein we review the reported surgical techniques and treatment-related outcomes to date to identify current research gaps and future directions. Ten articles were identified for review including 187 participants who underwent cross-electrode RFTC. Hypothalamic hamartoma (HH) and hippocampal sclerosis (HS) accounted for 52% and 26% of all cases, respectively. The proportion of cases with seizure freedom at last follow-up was 71%, including 84% of the HH cases, 54% of all temporal lobe cases, and 56% of the HS cases. Long-term efficacy in one HS study dropped from 72% at 12 months to 43% at 5 years post-treatment. Most (94%) reported complications resolved. One study reported favorable neuropsychological outcomes in HS cross-electrode RFTC compared to standard resective epilepsy surgery; however, it did not use memory tasks known to be reliable proximal markers of mesial temporal dysfunction/disease. In conclusion, extending RFTC boundaries through cross-electrode methods may improve RFTC efficacy and produce seizure-freedom rates comparable to established epilepsy surgical interventions in the treatment of HH and HS at 12 months, with a low risk of postoperative complications. There is limited research exploring efficacy in non-lesional epilepsy despite these cases often undergoing SEEG for diagnostic purposes and being well placed for cross-electrode RFTC. In addition, there is a lack of research exploring the neurocognitive and psychiatric risks of cross-electrode RFTC.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835245","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":"Quantitative electroencephalographic measures during postmalarial epileptogenesis.","authors":"Rasesh B Joshi, Suzanna Mwanza, Hitten P Zaveri, Joseph Kasolo, Angela Masempela, Thelma Musakanya, Tina Mwale, Violet Nambeye, Rosemary Nyriongo, Ruth A Tembo, Christopher Cortina, Bo Zhang, Gretchen L Birbeck, Alexander Rotenberg, Archana A Patel","doi":"10.1002/epi.70257","DOIUrl":"https://doi.org/10.1002/epi.70257","url":null,"abstract":"<p><strong>Objective: </strong>Severe malaria with neurologic involvement contributes significantly to the global burden of acquired pediatric epilepsy. We studied quantitative electroencephalographic (EEG) measures in postmalarial epileptogenesis.</p><p><strong>Methods: </strong>A total of 186 patients, aged 6 months to 11 years, with confirmed central nervous system malaria were enrolled in a prospective observational study conducted in Chipata, Zambia. EEG data were collected during acute illness for 179 patients. Patients were followed for 12 months postdischarge with EEG and clinical reviews to assess postmalarial epilepsy (PME) outcomes. A total of 155 patients were seen for 1-month, 144 for 6-month, and 142 for 12-month follow-up. Twenty-six patients were diagnosed with PME. We examined EEG measures (relative power, magnitude-squared coherence [MSC], and approximate entropy [ApEn]) to identify differences between patients who developed PME and those who did not.</p><p><strong>Results: </strong>Relative gamma power at admission was significantly greater in the PME group, whereas at 1-month and 6-month follow-up it was greater in the nonepilepsy group. Alpha and beta power increased in both groups over time, suggesting a prolonged process of neurologic recovery, with greater power in both bands observed in the nonepilepsy group at 12-month follow-up. ApEn was greater in the nonepilepsy group at admission and 1-month and 6-month follow-up. At admission and 1-month follow-up, we observed a significant decrease in beta and gamma MSC in the epilepsy group as compared to the nonepilepsy group. These differences were absent at 6-month follow-up but became more prominent again at 12-month follow-up.</p><p><strong>Significance: </strong>These and related EEG measures may provide value for risk stratification of patients with severe malaria.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835164","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":"Management of ring chromosome 20 syndrome: Narrative review and consensus recommendations.","authors":"Asma Khamis, Emilia Ricci, Maria Paola Canevini, Lieven Lagae, Kentaro Tokumoto, Yushi Inoue, Tim Buckinx, Allison Watson, Kenneth A Myers","doi":"10.1002/epi.70266","DOIUrl":"https://doi.org/10.1002/epi.70266","url":null,"abstract":"<p><p>Ring chromosome 20 (ring 20) is a rare genetic condition usually presenting as developmental and epileptic encephalopathy. The disease is caused by fusion of the long and short arms of chromosome 20. Patients are symptomatic even if there is no loss of genetic material. Epilepsy in ring 20 is usually drug-resistant, with seizures often significantly debilitating and severely impacting quality of life. We assembled a taskforce of clinician-scientists with expertise in ring 20, as well as caregivers of individuals with ring 20. We then reviewed published literature on ring 20 with a focus on management with the aim of developing recommendations for the treatment of this disorder. Our review found that there are very few high-quality data available to guide treatment in ring 20. The majority of publications are individual case reports or small case series. Based on these limited data, as well as personal experience, we recommend the following. (1) The care team should be multidisciplinary and include at least an epileptologist and allied health specialists (e.g., speech therapist, occupational therapist, physiotherapist, psychologist); (2) patients and families should be referred for genetic counseling; (3) if patients are diagnosed with epilepsy, they and their families should be counseled that seizures are likely to be drug-resistant and life-long; (4) as there is a high incidence of non-convulsive status epilepticus (NCSE), there should be a low threshold for video-EEG monitoring if patients have a change in behavior or level of consciousness; (5) initial epilepsy treatment should be with an oral anti-seizure medication; (6) home rescue medication should be considered given the risk for prolonged seizures and NCSE; (7) for patients with drug-resistant epilepsy, ketogenic diet, vagus nerve stimulation, or deep brain stimulation could all be considered; and (8) caregiver burnout and stress should be screened for and supports provided.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835236","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":"WONOEP XVII appraisal: The role of the extracellular matrix in epilepsy.","authors":"Eleonora Lugara, Erwin A van Vliet, Alessia Romagnolo, Kevin Staley, Kyle P Lillis, Chris Dulla, David C Henshall, Katja Kobow","doi":"10.1002/epi.70278","DOIUrl":"https://doi.org/10.1002/epi.70278","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is composed of proteoglycans and glycoproteins that regulate the external environment surrounding neurons, glia, and the vascular system. The ECM is vital for maintaining the structure and function of the brain and also acts as a reservoir for various signaling molecules and neurotransmitters, modulating synaptic transmission and plasticity. Recent research highlights the important role of ECM proteins in both brain development and various neurological diseases, including epilepsy. Alterations in ECM composition and subsequent remodeling may disrupt physiological network excitability and synaptic connectivity, triggering neuroinflammation with active participation from glial cells, including astrocytes and microglia, and blood-brain barrier function. This influences neuronal function and contributes to the formation of epileptic foci and the development of drug-resistant epilepsy. Understanding the intricate interplay between the ECM and epilepsy may enable the identification of novel biomarkers and development of therapeutic strategies targeting this dynamic microenvironment. In this review, we provide a summary of the discussions held at the XVII Workshop on Neurobiology of Epilepsy (WONOEP), organized in 2023 by the International League Against Epilepsy, on the role of the extracellular space in epilepsy. Specifically, we summarize recent advances in understanding the ECM, its alterations in epilepsy, advanced imaging and omics tools for ECM analysis, and the implications for the development of ECM-based therapeutics and biomarkers for acquired and genetic forms of epilepsy. To complement the material presented at WONOEP, we performed targeted, nonsystematic literature searches in PubMed using topic-specific terms (e.g., \"perineuronal nets\", \"extracellular matrix\", \"traumatic brain injury\", \"post-traumatic epilepsy\", \"chloride\") and citation tracking to ensure that key experimental and translational studies relevant to these themes were included.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835228","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":"Integrating multivariate resting-state fMRI features to localize epileptic networks in common childhood epilepsy.","authors":"Qirui Zhang, Zixuan Zhang, Yvzhuo Li, Yan He, Fang Yang, Jacqueline Kim, Joseph I Tracy, Guangming Lu, Zhiqiang Zhang","doi":"10.1002/epi.70243","DOIUrl":"https://doi.org/10.1002/epi.70243","url":null,"abstract":"<p><strong>Objective: </strong>Accurate localization of epileptic activity remains challenging when interictal discharges are absent or sparse. Although resting-state functional MRI (rs-fMRI) is noninvasive, individual rs-fMRI metrics provide inconsistent and incomplete localization. We aimed to determine whether multivariate integration of rs-fMRI features could robustly identify syndrome-specific epileptic activity in childhood epilepsy.</p><p><strong>Methods: </strong>Using simultaneous EEG-fMRI, we studied children with self-limited epilepsy with centrotemporal spikes (SeLECTS, n = 60) and childhood absence epilepsy (CAE, n = 30) alongside typically developing controls (n = 108). Forty-two rs-fMRI metrics spanning amplitude, connectivity, temporal dynamics, and directional measures were computed for each session. Individual abnormality maps were also generated relative to controls. Partial least squares (PLS) regression was then applied to identify a latent component (PLS1) that maximally covaried with syndrome-specific epileptic activation patterns derived from EEG-fMRI. Spatial correspondence, localization accuracy, non-discharge session sensitivity, and classification performance were evaluated.</p><p><strong>Results: </strong>PLS1 showed strong spatial correspondence with EEG-fMRI-defined epileptic activation patterns in both SeLECTS (rolandic cortex) and CAE (thalamocortical network) (both spin-test r = .68, p < .001). PLS1 showed superior localization performance compared with most single-metric rs-fMRI measures and reached EEG-fMRI-level localization accuracy. Notably, PLS1 detected graded, syndrome-specific abnormalities during non-discharge sessions and distinguished discharge, no-discharge, and control states, an effect that has not been observed with individual rs-fMRI metrics. In classification analyses, PLS1 differentiated CAE from SeLECTS with high accuracy (AUC = .79), performing comparably to the EEG-fMRI-based classification.</p><p><strong>Significance: </strong>Multivariate integration of rs-fMRI features using a template-guided PLS framework enables sensitive and syndrome-specific detection of epileptic activity, even in the absence of overt discharges. This approach provides a clinically translatable strategy for noninvasive epilepsy network mapping.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835153","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":"Can we predict surgical outcomes: A systematic review and critical appraisal of clinical prediction models in epilepsy surgery.","authors":"Alyssa A Federico, Mandavi Kashyap, Chantelle Q Y Lin, Karl M Klein, Olayinka I Arimoro, Samuel Wiebe","doi":"10.1002/epi.70274","DOIUrl":"https://doi.org/10.1002/epi.70274","url":null,"abstract":"<p><strong>Objective: </strong>Prediction models are increasingly being sought in epilepsy surgery to predict postoperative outcomes and support clinical decision-making. Studies summarizing the evidence in this area can provide insight into the type of surgical prediction models, their methodology, and their performance and inform areas for future research. Our aim was to address these knowledge gaps through a comprehensive systematic review of prediction models in epilepsy surgery.</p><p><strong>Methods: </strong>A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using four databases. Papers were included if they were primary research studies, human-based, studied adult or pediatric populations, studied people with epilepsy undergoing surgical management, and developed or validated a multivariable tool to predict epilepsy surgery outcomes. Data extraction was reviewed in triplicate, and the quality of evidence in each paper was assessed using the Prediction Model Risk of Bias Assessment Tool.</p><p><strong>Results: </strong>The literature search yielded a total of 11 614 papers, with 42 papers and 113 prediction models included in the final analysis. The median area under the curve and accuracy for all models were .75 (interquartile range = .68-.83) and .76 (interquartile range = .69-.83), respectively. Overall, 54.0% of models underwent internal validation, and 20.4% underwent external validation. Models of cognitive-language outcomes seemed to perform better than those for other outcomes. Overall risk of bias was high in 81% of models, with weakest performance in outcomes and analyses, but trended toward improvement over time. Concerns for applicability were low in 89% of the models.</p><p><strong>Significance: </strong>Prediction models in epilepsy surgery are rapidly proliferating, but most lack external validation, and many still exhibit a high risk of bias. Therefore, caution is needed when interpreting and applying these predictive tools. Evidence of improvement in methodological quality holds promise for enhancing patient care, if coupled with improved model performance.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834892","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":"Disrupted inhibitory interneuron development in SCN1A Dravet syndrome revealed by patient-derived subpallial organoids.","authors":"Cristiana Mattei, Miaomiao Mao, Sean Byars, Erlina Mohamed Syazwan, Megan Oliva, Timothy J Karle, Kay Richards, Ingrid E Scheffer, Steven Petrou, Snezana Maljevic","doi":"10.1002/epi.70267","DOIUrl":"https://doi.org/10.1002/epi.70267","url":null,"abstract":"<p><strong>Objective: </strong>Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by loss-of-function variants in SCN1A, with seizures typically emerging during the first year of life. Although DS pathophysiology has largely been attributed to inhibitory network dysfunction underlying seizures, early developmental alterations in inhibitory interneurons remain poorly understood.</p><p><strong>Methods: </strong>We generated inhibitory interneuron-enriched subpallial organoids from patient-derived induced pluripotent stem cells carrying an SCN1A loss-of-function variant and the corresponding isogenic control. Using complementary molecular and functional approaches, including quantitative polymerase chain reaction, bulk RNA sequencing, whole-cell patch-clamp electrophysiology, and two-photon calcium imaging, we investigated early inhibitory interneuron development and functional maturation in a human cellular context.</p><p><strong>Results: </strong>Transcriptomic profiling revealed early dysregulation of ventral forebrain interneuron developmental programs, including altered expression of medial ganglionic eminence-associated transcriptional regulators, preceding inhibitory network dysfunction. Patient-derived organoids exhibited marked reductions in intrinsic neuronal excitability and synaptic activity. Acute application of fenfluramine, a clinically approved antiseizure medication for DS, partially restored neuronal activity, demonstrating the translational relevance of this model.</p><p><strong>Significance: </strong>These findings demonstrate that SCN1A loss of function disrupts early inhibitory interneuron development and functional maturation, defining a developmental vulnerability that likely precedes the emergence of epilepsy in DS. This work establishes patient-derived inhibitory organoids as a human-relevant platform for dissecting disease mechanisms and evaluating therapeutic responses in SCN1A-related epileptic encephalopathies.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":" ","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835049","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}