Epilepsia Open最新文献

{"title":"Optimizing polytherapy management for Dravet syndrome in the United States: A National Expert Consensus","authors":"Elaine Wirrell, Joseph Sullivan","doi":"10.1002/epi4.70286","DOIUrl":"10.1002/epi4.70286","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Dravet syndrome (DS) is a severe, drug-resistant developmental and epileptic encephalopathy (DEE) that requires polytherapy for adequate seizure control. The need to combine multiple antiseizure medications (ASMs), together with variability in seizure types, safety considerations, and evolving patient needs, makes treatment optimization particularly complex for clinicians. As the United States (US) has one of the largest populations of DS patients and pediatric neurologists/epileptologists worldwide, this study aimed to develop US-focused consensus guidance to guide clinicians in managing treatment combinations in DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A modified Delphi consensus methodology was applied. 35 statements tailored to the US clinical context were developed, covering six key themes: general treatment principles; strategies to support and empower caregivers; stiripentol (STP) as an add-on to DS-specific and nonspecific ASMs; use of fenfluramine (FFA) in STP-containing regimens; use of cannabidiol (CBD) in STP-containing regimens; and patient follow-up during treatment initiation. Statements were submitted for online voting to 52 US clinicians with expertise in DS and experience with all approved DS-specific ASMs. Agreement was rated using a 9-point Likert scale, with predefined criteria used to determine strong, good, or absent consensus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>26 experts participated in the voting process. Of the 35 statements evaluated, 23 (66%) reached strong consensus, 6 (17%) reached good consensus, and 6 (17%) did not reach consensus. Strong agreement was observed for general principles of DS management, caregiver involvement, structured follow-up, and several practical aspects of initiating and managing STP- and FFA-containing regimens. Areas without consensus primarily concerned CBD efficacy expectations, dosing strategies, and pharmacokinetic interactions in complex polytherapy regimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This US-focused consensus provides structured guidance to support clinical decision-making in the management of polytherapy for DS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain language summary</h3>\u0000 \u0000 <p>Dravet syndrome is a rare and severe form of epilepsy that begins in early childhood and causes seizures that are difficult to control and often persist throughout life. Because most patients require treatment with multiple medication","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1450-1464"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging computational and clinical strategies for presurgical identification of epileptogenic networks","authors":"Tena Dubcek, Debora Ledergerber, Kristina Koenig, Adham Elshahabi, Rafael Polania, Lukas Imbach","doi":"10.1002/epi4.70311","DOIUrl":"10.1002/epi4.70311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>About one third of epilepsy patients are drug-resistant. Resective epilepsy surgery remains a key treatment option but depends critically on accurate identification of the seizure onset zone (SOZ), which is still guided mainly by subjective visual inspection of electrophysiological signals. Network-based metrics derived from intracranial EEG have recently shown promise for SOZ identification, but their evaluation and interpretation have remained disconnected from standard clinical procedures and reasoning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed stereotactic EEG (sEEG) recordings from 20 patients undergoing presurgical evaluation in the interictal state and during clinical mapping via electrical stimulation. We constructed patient-specific time-varying dynamic network models and addressed key questions for clinical translation: how sensitive network vulnerability estimates are to the choice among related published metrics, how they depend on the time of the day, and how the resulting conclusions relate to stimulation-evoked epileptiform discharges as a routine clinical reference for network vulnerability in 5 patients who underwent 50 Hz stimulation mapping. We then simulated virtual thermocoagulation in 6 patients who later underwent thermocoagulation by removing the clinically coagulated nodes and testing whether the resulting network changes went beyond pure network size reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The network metrics correlated with epileptiform discharges evoked by 50 Hz intracranial stimulation in four of five stimulated patients, supporting a link between model-based network fragility and interictal epileptiform discharges evoked in clinical stimulation mapping. Using virtual thermocoagulation, we quantified the expected network-level change under model node removal, capturing both local and global effects depending on individual network architecture. Across patients, more fragile network metrics pointed toward clinically defined SOZ contacts and yielded stable conclusions across time, conditions, and perturbation properties, supporting their reliability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Together, these findings provide a clinically interpretable calibration of published network vulnerability metrics against routine clinical references, using interictal sEEG data only.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Some peopl","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1525-1540"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive Hippocampal Volume Reduction Beyond Normal Aging in Temporal Lobe Epilepsy: A Longitudinal MRI Study.","authors":"Daichi Sone, Yoko Shigemoto, Risa Kagaya, Yukio Kimura, Hiroshi Matsuda, Noriko Sato","doi":"10.1002/epi4.70373","DOIUrl":"10.1002/epi4.70373","url":null,"abstract":"<p><p>Recent neuroimaging studies have suggested that epilepsy may show progressive brain structural changes over time. However, longitudinal hippocampal volume changes in temporal lobe epilepsy (TLE) have not been adequately compared with those observed in normal aging. In this study, we enrolled 46 patients with unilateral TLE and 25 healthy controls with longitudinal structural MRI scans using the same scanner. Hippocampal volumes were quantified using the Hipposeg software, and the annual percentage volume reduction relative to baseline (%Reduction/year) was calculated for each hippocampus. Compared to healthy hippocampi (median -0.37% per year, IQR = 3.97), both ipsilateral (median -1.04% per year, IQR = 3.65) and contralateral (median -1.08% per year, IQR = 3.17) hippocampi in TLE showed significantly greater volume reduction over time (both p < 0.05). Furthermore, annual ipsilateral hippocampal volume reduction was significantly correlated with disease duration (Spearman's rs = 0.366, FDR-corrected p = 0.036), suggesting that hippocampal atrophy progresses more rapidly during the early stage after epilepsy onset. These findings indicate that hippocampal volume loss in TLE exceeds that expected from normal aging and provide further evidence supporting progressive structural alterations during the course of the disease. PLAIN LANGUAGE SUMMARY: Temporal lobe epilepsy may cause progressive changes in the brain beyond those expected from normal aging. Using repeated MRI scans, we found that the hippocampus showed greater volume loss over time in people with temporal lobe epilepsy than in healthy individuals. This volume loss occurred bilaterally and appeared to be greater during the earlier stages of the disease. These results provide further evidence supporting progressive structural brain changes in TLE and contribute to a better understanding of disease progression and abnormal brain aging in epilepsy.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten-year cognitive outcomes following epilepsy surgery: Temporal lobectomy versus selective amygdalohippocampectomy","authors":"Tehran Aliyeva,&nbsp;Fadime Çadırcı Tungaç,&nbsp;Beyza Tagraf,&nbsp;Çigdem Ozkara,&nbsp;Mustafa Uzan,&nbsp;Lutfu Hanoglu","doi":"10.1002/epi4.70295","DOIUrl":"10.1002/epi4.70295","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to assess long-term memory outcomes in patients with temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH), compared to nonoperated TLE over a 10-year follow-up period.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 48 participants were studied: 10 ATL, 26 SAH, and 12 patients with nonoperated mesial temporal lobe epilepsy (MTLE). Verbal memory was assessed using the Sözel Bellek Süreçleri Testi (SBST—a test of verbal memory processes), and nonverbal memory was evaluated with the Wechsler memory scale—visual reproduction (WMS) (Turkish adaptation). Given the small and unbalanced groups, linear mixed-effects models (LMMs) were used as the primary inferential analyses to test group × time interactions. Statistically reliable individual changes were identified using the reliable change index (RCI). Neuropsychological outcomes were analyzed longitudinally over a 10-year follow-up period.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A significant group × time interaction was observed for verbal total learning (&lt;i&gt;p&lt;/i&gt; = 0.001). The nonoperated TLE group showed a significant decline over time, whereas both surgical groups differed significantly from it. The ATL group demonstrated significant improvement. For delayed verbal recall, a significant main effect of group was observed; however, the group × time interaction was not statistically significant. Visual immediate recall showed a significant group × time interaction (&lt;i&gt;p&lt;/i&gt; = 0.004), with a significant interaction effect in the ATL group. Visual delayed recall demonstrated a significant group × time interaction (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), with significant interaction effects in both surgical groups. Seizure freedom was achieved in 90% of ATL and 80% of SAH cases; however, seizure outcome was not significantly associated with memory outcomes. Reliable change index analyses indicated lateralization-dependent patterns of change.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;ATL, particularly left-sided ATL, was associated with statistically significant long-term improvements in verbal memory and significant longitudinal changes in visual memory. SAH demonstrated significant longitudinal effects in selected memory domains. In contrast, nonoperated TLE patients showed significant cognitive decline over time. These findings highlight differential long-term cognitive trajectories across treatment approaches and the role of lateralization in memory outcomes following epilepsy","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1502-1512"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic testing practices across European epilepsy centers: An ERN EpiCARE survey","authors":"Sébile Tchaicha,&nbsp;Johanna Van Hulle,&nbsp;Eva Brilstra,&nbsp;Andreas Brunklaus,&nbsp;Gaetano Cantalupo,&nbsp;Martin Geroldinger,&nbsp;Amy McTague,&nbsp;Reetta Kälviäinen,&nbsp;Eulalia Turón-Viñas,&nbsp;Alexis Arzimanoglou,&nbsp;Rikke S. Møller,&nbsp;Rima Nabbout","doi":"10.1002/epi4.70304","DOIUrl":"10.1002/epi4.70304","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Genetic testing plays an increasing role in the diagnostic pathway for rare and complex epilepsies. However, significant heterogeneity persists in access, implementation, and interpretation across Europe. This study aimed to assess genetic testing practices, accessibility, and challenges across expert epilepsy centers within the European Reference Network for Rare and Complex Epilepsies (ERN EpiCARE) and to identify key challenges and areas for harmonization.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A cross-sectional survey was developed by the ERN EpiCARE Clinical Genetics Working Group and distributed to 50 EpiCARE member centers across 27 European countries. The questionnaire collected quantitative and qualitative information on available genetic testing modalities, turnaround times, use of rapid testing, multidisciplinary team (MDT) organization, genetic counseling practices, and perceived challenges. Survey findings were complemented by a structured discussion held during the ERN EpiCARE General Assembly.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Responses were received from 46 centers (51 responses). Most centers reported access to genetic testing, predominantly through in-house facilities. Whole-exome sequencing was available in 85% of centers, and gene panels were available in 78%. Whole-genome sequencing was available in 59% of centers, frequently restricted to research or performed externally. Turnaround times for standard genetic testing were most commonly between 1 and 6 months. Genetic testing strategies varied by epilepsy subtype, with gene panels most frequently used as first-tier testing, and exome sequencing preferentially applied in developmental and epileptic encephalopathies. Considerable heterogeneity was observed in MDT organization, access to genetic counseling, reimbursement, data-sharing and registry infrastructures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Although genetic testing is widely available across ERN EpiCARE centers, substantial disparities persist in its organization, accessibility, and implementation. Addressing these gaps through strengthened multidisciplinary collaboration, harmonized diagnostic strategies, and enhanced European-level coordination will be essential to ensure equitable access to high-quality genetic care for individuals with epilepsy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Genetic testing is increasingly integrate","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1556-1569"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genetic architecture of epilepsy across molecular mechanisms and clinical heterogeneity","authors":"Mohammad Reza Seyedtaghia,&nbsp;Jina Babanzadeh,&nbsp;Marcello Scala,&nbsp;Lorenzo Perilli,&nbsp;Pasquale Striano","doi":"10.1002/epi4.70310","DOIUrl":"10.1002/epi4.70310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Epilepsy comprises a highly heterogeneous group of neurological disorders unified by a persistent predisposition to recurrent seizures, yet driven by remarkably diverse genetic, molecular, and network-level mechanisms. Advances in genomic technologies have revealed that epilepsy arises from a multilayered genetic architecture encompassing rare high-penetrance monogenic variants, common polygenic risk factors, brain-restricted somatic mosaicism, and extensive gene–environment interactions. These genetic substrates converge on core biological pathways regulating neuronal excitability, synaptic transmission, metabolic homeostasis, neuroinflammation, and circuit development. In this review, we synthesize contemporary insights into the genetic and molecular pathophysiology of seizures and epilepsy, with emphasis on mechanisms that destabilize excitation–inhibition balance, promote epileptogenesis, and drive pharmacoresistance. We highlight how ion channel dysfunction, synaptic vesicle cycling defects, mTOR pathway hyperactivation, glial and metabolic failure, and inflammatory cascades interact to lower seizure threshold and remodel neural networks. Beyond classical monogenic and polygenic models, we discuss the emerging role of somatic mutations, polygenic modifiers of rare variants, and dynamic brain-state–dependent seizure susceptibility. We further integrate genetic mechanisms with clinical heterogeneity, including age of onset, seizure type, penetrance, pleiotropy, and treatment response, and review translational implications for precision medicine, pharmacogenomics, and emerging molecular therapies such as antisense oligonucleotides, gene regulation strategies, and cell-based interventions. Understanding the genetic architecture of epilepsy is increasingly informing diagnostic pathways, prognostic stratification, and the development of precision-based therapeutic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Epilepsy genetics extends beyond single-gene disorders and involves multiple interacting layers of genomic variation. In this review, we integrate evidence across rare variants, polygenic risk, somatic mosaicism, and genetic modifiers to provide a broader framework for understanding seizure susceptibility and clinical diversity. By highlighting convergent biological pathways and their effects on neuronal networks, this work supports more refined approaches to epilepsy classification and future precision medicine strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1395-1412"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted cerebellar networks in uncontrolled focal to bilateral tonic–clonic seizures","authors":"John Phamnguyen,&nbsp;Elaine Kuan,&nbsp;Puneet Dheer,&nbsp;Viktor Vegh,&nbsp;David Reutens","doi":"10.1002/epi4.70315","DOIUrl":"10.1002/epi4.70315","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Focal to bilateral tonic–clonic seizures (FBTC) are associated with significant morbidity and an elevated risk of sudden unexpected death in epilepsy (SUDEP). The cerebellum has been implicated in modulating the frequency and severity of tonic–clonic seizures. The present study aimed to identify alterations in cerebellar functional connectivity (FC) associated with susceptibility to FBTC in individuals diagnosed with temporal lobe epilepsy (TLE).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This prospective study involved the recruitment of 30 patients with unilateral TLE, who were classified into two groups: active FBTC (≥1 FBTC in the past year) and inactive FBTC (ongoing focal seizures but no FBTC within the past year, and in some cases no lifetime history), each consisting of 15 patients. Additionally, 20 demographically matched control subjects were included. Resting-state functional MRI (rs-fMRI) and high-resolution T1-weighted imaging were utilised. FC analysis was performed using the CONN toolbox, with a focus on cerebellar and subcortical regions. Group comparisons were executed using Kruskal–Wallis tests, followed by post hoc pairwise analyses.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The findings indicated that FC between the posterior vermis and lateral cerebellar lobules (Crus I/II) bilaterally were significantly lower in the active FBTC group compared to healthy controls. In comparison to the inactive group, the active FBTC group exhibited significantly lower FC with the contralateral Crus I and Crus II. In comparison to controls, the TLE groups exhibited lower FC between the posterior vermis and the mediodorsal and pulvinar thalamic nuclei as well as between the flocculonodular lobe and mesial temporal structures (hippocampus, parahippocampus, and amygdala).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The results demonstrate impaired intracerebellar FC, particularly between the posterior vermis and lateral cerebellar lobules, in individuals with active FBTC, thereby supporting the hypothesis that the cerebellum has a regulatory role in modulating susceptibility to tonic–clonic seizures.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Focal to bilateral tonic–clonic seizures are severe seizures that start in one brain region and spread to both sides of the brain. In this study, people with temporal lobe epilepsy who had recent tonic–clonic seizures showed reduced communi","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1624-1634"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Infantile Epileptic Spasms Syndrome: A survey of US pediatric hospitals","authors":"Akshat Katyayan,&nbsp;Christina Briscoe,&nbsp;Sonam Bhalla,&nbsp;Sonal Bhatia,&nbsp;Gozde Erdemir,&nbsp;Chellamani Harini,&nbsp;Senyene E. Hunter,&nbsp;John R. Mytinger,&nbsp;Duyu Nie,&nbsp;Archana Pasupuleti,&nbsp;Shital H. Patel,&nbsp;Debopam Samanta,&nbsp;Amanda Sandoval Karamian,&nbsp;Avantika Singh,&nbsp;Deepa Sirsi,&nbsp;Danielle S. Takacs,&nbsp;Shaun A. Hussain","doi":"10.1002/epi4.70309","DOIUrl":"10.1002/epi4.70309","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the management practices of Infantile Epileptic Spasms Syndrome (IESS) across tertiary pediatric hospitals in the United States using a survey-based approach.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A 21-question survey focused on management setting, work-up, follow-up and treatment was created and sent to 45 member institutions of the Pediatric Epilepsy Research Consortium (PERC). Results were analyzed by a working group of PERC focused on IESS.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Thirty-three institutions completed the survey. Most institutions (91%) managed new-onset IESS in-patient, with 76% using overnight video EEG (vEEG) monitoring for diagnosis. Nearly all (&gt; 90%) obtained an MRI brain and genetic testing at initial diagnosis. The most common modalities of genetic evaluation were an epilepsy panel (47%) and trio whole exome sequencing (44%). For assessment of response at the first follow-up, 45% used extended vEEG (1–6 h), with 36% continuing to obtain overnight vEEG. The 2021 BASED score (Burden of Amplitude and Epileptiform Discharges) was the preferred method of assessing response (58%) compared to resolution of hypsarrhythmia (39%). High-dose prednisolone was the first treatment for most institutions, irrespective of the etiology (apart from Tuberous Sclerosis Complex). Combined treatment (hormonal + vigabatrin) was less commonly used as first treatment (9%–12%, depending on etiology). Most institutions (63%) looked for failure of both hormonal therapy and vigabatrin (sequential or combined) before pursuing surgical treatment in patients with identifiable brain MRI lesions, but would also consider surgical treatment in patients with remission of electro-clinical epileptic spasms but continued epileptiform EEGs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;There are areas of consensus and variability in management of IESS in US institutions. Updated consensus guidelines addressing the comprehensive management of IESS are needed to help standardize and optimize care in these patients.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Infantile Epileptic Spasms Syndrome requires prompt diagnosis and initiation of appropriate treatment to improve developmental outcomes. In this survey of tertiary pediatric centers in the United States, we found areas of consensus (use of overnight video EEG at initial diagnosis, use of high-dose prednisolone as initial tr","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1478-1489"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13452135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging of the ictal–interictal continuum: Where do we stand? A systematic review and meta-analysis of current evidence","authors":"Panagiota-Eleni Tsalouchidou,&nbsp;Kateriine Orav,&nbsp;Tiago Lerda-Casaccia,&nbsp;Leona Möller,&nbsp;Georgios Tsivgoulis,&nbsp;Anastasios Bonakis,&nbsp;Lukas Machegger,&nbsp;Giorgi Kuchukhidze,&nbsp;Susanne Knake,&nbsp;Eugen Trinka,&nbsp;Pilar Bosque-Varela","doi":"10.1002/epi4.70335","DOIUrl":"10.1002/epi4.70335","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Patterns within the ictal–interictal continuum (IIC) are frequently encountered in critically ill patients undergoing continuous electroencephalographic studies and may reflect ongoing ictal activity or secondary brain injury. Peri-ictal neuroimaging abnormalities (PNA) have been described in association with status epilepticus (SE), but their occurrence in patients with IIC across different neuroimaging modalities remains incompletely characterized. We aimed to assess the occurrence of PNA in adults with IIC across structural and functional neuroimaging techniques.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a systematic review and meta-analysis following PRISMA 2020 guidelines. PubMed, Embase, and Scopus were searched up to January 2026 for studies reporting PNA in adults with IIC. Eligible modalities included magnetic resonance imaging (MRI), CT perfusion (CTP), and positron emission tomography (PET). Pooled detection rates were estimated using random-effects generalized linear mixed models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 8400 records identified, seven studies met the inclusion criteria. Of these, four contributed MRI data (98 patients), two—CTP data (38 patients), and two—PET data (30 patients); no SPECT study was identified. One study contributed data to two modalities. Pooled proportion of PNA was 0.41 (95% CI: 0.30–0.52; <i>I</i>² = 30.4%) for MRI, 0.34 (95% CI: 0.21–0.50; <i>I</i>² = 0%) for CTP, and 0.90 (95% CI: 0.73–0.97; <i>I</i>² = 0%) for PET.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>There are currently a limited number of studies evaluating PNA in IIC. PET showed the highest pooled proportion of PNA, although these findings should be interpreted cautiously. Further studies are required to better define the neuroimaging spectrum within the IIC and to clarify its clinical and diagnostic implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1426-1436"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational protein stability analysis of SCN1A missense variants reveals domain-dependent stability patterns","authors":"Youngkyu Shim,&nbsp;Eungu Kang,&nbsp;Naeun Kwak,&nbsp;Suhyun Kim","doi":"10.1002/epi4.70312","DOIUrl":"10.1002/epi4.70312","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To determine whether computational protein-stability predictions discriminate pathogenic from benign SCN1A missense variants, and to characterize the structural distribution of predicted destabilization among pathogenic variants.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;On an AlphaFold3-predicted Nav1.1 structure, FoldX, and Rosetta Cartesian ΔΔG were computed for a single ClinVar snapshot of pathogenic/likely-pathogenic (P/LP) and benign/likely-benign (B/LB) missense variants and its extension to ClinVar variants of uncertain significance (VUS) and gnomAD v4.1 variants; membrane-aware RosettaMP was applied to the patch-clamp subgroup. Pathogenic variants were stratified by functional domain.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pathogenic variants were more destabilizing than benign (FoldX 2.61 vs. 0.31 kcal/mol, &lt;i&gt;p&lt;/i&gt; = 1.27 × 10&lt;sup&gt;−11&lt;/sup&gt;; ROC-AUC = 0.760), concordant with Rosetta (ROC-AUC = 0.697; &lt;i&gt;ρ&lt;/i&gt; = 0.660). Destabilization was domain-dependent: pore (P-loop/selectivity-filter) pathogenic variants were depleted of stability-neutral variants (0.40-fold; Bonferroni-adjusted &lt;i&gt;p&lt;/i&gt; = 4.3 × 10&lt;sup&gt;−7&lt;/sup&gt;), whereas S4 voltage-sensor variants were enriched for them (2.32-fold; &lt;i&gt;p&lt;/i&gt; = 0.013). Across ~3300 non-redundant variants, gnomAD-common variants resembled benign controls and VUS were intermediate (mean ΔΔG 0.98 kcal/mol; 18.5% strongly destabilizing), with the domain pattern preserved. Among 64 patch-clamp variants, stability did not separate gain- from loss-of-function, though gain-of-function variants clustered in voltage-sensing domains and were absent from the pore.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Computational stability analysis thus adds a mechanistic layer complementary to the conventional gating-dysfunction view, distinguishing a destabilized pore-region subset—for which proteostasis impairment is a candidate, though unproven, mechanism—from a structurally tolerated S4 subset whose pathogenicity is stability-independent. As a hypothesis-generating rather than mechanism-defining approach, this stratification prioritizes candidate variants—including the 18.5% of VUS that are strongly destabilizing—for direct functional and surface-expression validation in SCN1A-related epilepsies. &lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We used computational modeling to predict how thousands of SCN1A genetic variants influence the stability ","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"11 5","pages":"1590-1602"},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}