Epilepsia Open最新文献

{"title":"Electroclinical classification of idiopathic generalized epilepsy syndromes at initial evaluation: A prospective multicenter study.","authors":"Omar Nawfal, Heba Samara, Wassim Nasreddine, Fatima Jaafar, Mahasen Reda, Tarek Halabi, Ahmad Beydoun","doi":"10.1002/epi4.70349","DOIUrl":"https://doi.org/10.1002/epi4.70349","url":null,"abstract":"<p><strong>Objective: </strong>To determine the extent to which electroclinical information available at initial evaluation allows classification of idiopathic generalized epilepsy (IGE) syndromes, and to assess the contributions of seizure semiology and age at seizure onset to early syndromic diagnosis.</p><p><strong>Methods: </strong>We prospectively analyzed a cohort of patients with new-onset seizures who underwent a structured clinical evaluation, including detailed history-taking, 3-h video-EEG, and epilepsy-protocol MRI. Seizure semiology was assessed at three levels: index seizure, initial seizure type, and seizure types identified at initial evaluation. Syndromic classification followed International League Against Epilepsy criteria. Final electroclinical diagnosis, established after longitudinal follow-up, served as reference. Within patients ultimately diagnosed with one of the four IGE syndromes, baseline data were used to determine whether the final syndrome could be assigned at initial evaluation.</p><p><strong>Results: </strong>Of 2699 patients evaluated, 498 (18.4%) met criteria for genetic generalized epilepsy, of whom 401 (80.5%) were classified as having one of the IGE syndromes. Based on initial evaluation, the correct syndrome could be assigned in 366 patients (91.3%), whereas 7 (1.7%) would have been misclassified and 28 (7.0%) were not assignable. Non-assignability was confined to absence epilepsies, reflecting overlap between childhood (CAE) and juvenile absence epilepsy (JAE), whereas misclassification occurred only in juvenile myoclonic epilepsy (JME) presenting with isolated generalized tonic-clonic (GTC) seizures. Classification based on the index seizure alone showed limited accuracy (63.6%), whereas incorporation of seizure types identified through structured history improved classification to 95.0%. Myoclonic seizures were highly specific for JME, whereas absence and GTC seizures required integration with additional features. Age at seizure onset strongly differentiated CAE from JAE (AUC 0.935).</p><p><strong>Significance: </strong>Electroclinical classification of IGE syndromes is frequently achievable at initial evaluation when based on seizure semiology and age at onset. When classification is not possible, limitations follow predictable electroclinical patterns, supporting a structured, history-driven diagnostic approach.</p><p><strong>Plain language summary: </strong>This study examined how accurately doctors can identify specific types of generalized epilepsy when patients are first evaluated. Among 401 patients with generalized epilepsy, the correct epilepsy syndrome could be identified in more than 90% at the first visit. Looking beyond the first seizure and asking about all seizure types together with age at seizure onset greatly improved diagnosis. While some overlap exists between specific types (like childhood versus juvenile absence epilepsy), a thorough clinical evaluation from the start provides relia","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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, Elaine Kuan, Puneet Dheer, Viktor Vegh, David Reutens","doi":"10.1002/epi4.70315","DOIUrl":"https://doi.org/10.1002/epi4.70315","url":null,"abstract":"<p><strong>Objective: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Significance: </strong>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.</p><p><strong>Plain language summary: </strong>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 communication between the posterior vermis and lateral cerebellar regions. Alterations in other cerebellar connections with the thalamus and temporal lobe were related to temporal lobe epilepsy itself. These findings suggest that cerebellar networks may influence vulnerability to tonic-clonic seizure spread and may be relevant to future sudden unexpected death in epilepsy risk research.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying extra-lesional interhemispheric cortical asymmetry in focal cortical dysplasia type II.","authors":"Faezeh Heidari, Mastaneh Torkamani-Azar, Jussi Tohka, Reetta Kälviäinen","doi":"10.1002/epi4.70336","DOIUrl":"https://doi.org/10.1002/epi4.70336","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Focal cortical dysplasia type II (FCDII) is a cortical malformation representing a common cause of surgically treatable drug-resistant epilepsy. We studied whether FCDII disrupts normal structural interhemispheric asymmetry beyond the lesion location and quantified these asymmetries derived from structural magnetic resonance imaging (MRI) between individuals with FCDII and healthy controls (HC) as well as within FCDII subtypes using surface-based morphometry (SBM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Using an open MRI dataset from University Hospital Bonn, we processed T1-weighted images from HC and individuals with FCDII aged over 15 years at the time of scan. We designed a three-stage workflow consisting of SBM using FreeSurfer, visual inspection of atlas-based cortical parcellations, and lesion projection. We extracted five cortical measures of intensity, thickness, volume, curvature, and surface area from 34 regions of interest (ROIs) and computed unsigned interhemispheric asymmetry indices beyond the lesion location.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The majority of FCDII lesions annotated in the original dataset were located in the frontal lobe (64.0%). Compared to the HC, individuals with MRI-diagnosed FCDII showed significantly reduced unsigned interhemispheric intensity asymmetry across parietal, temporal, and occipital cortices (q &lt; 0.001). We observed an increase in the unsigned interhemispheric volume asymmetry in the lateral orbitofrontal cortex and in the unsigned interhemispheric surface-area asymmetry in the inferior temporal cortex for FCDII compared to HC (q &lt; 0.001). Subtype analyses revealed greater unsigned interhemispheric intensity asymmetry in caudal anterior cingulate and superior temporal cortices in FCDIIb compared with FCDIIa (q &lt; 0.001). Conversely, precentral unsigned surface-area and volume asymmetries were smaller in FCDIIb relative to FCDIIa (q &lt; 0.001). We observed no significant differences for unsigned interhemispheric cortical thickness and curvature asymmetries after multiple-comparison corrections.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&gt;SBM-derived interhemispheric asymmetry captures cortical alterations in FCDII beyond the focal lesions. Observed differences in group-level unsigned interhemispheric intensity, volume, and surface-area asymmetry indicated cortical alterations that are consistent with distributed cortical involvement between FCDIIa and FCDIIb. These findings may enhance presurgical evaluation by highlighting cortical areas outside the primary lesion that could contribute to seizure generation and achieving seizure-freedom after the operation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;Focal cortical dysplasia type II (FCDII) is a malformation of cortical development associated with drug-resistant epilepsies. FCDII may disrupt normal cortical interhemispheric asymmetries which are understudied in focal, extratemporal epilepsies. We discovered that individuals with FCD","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilateral detection, prediction, and lateralization of seizures using white matter.","authors":"Nrupen Pakalapati, Chia-Chu Chiang, Siddharth Lokam, Dominique M Durand","doi":"10.1002/epi4.70348","DOIUrl":"10.1002/epi4.70348","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To determine how the corpus callosum handles interhemispheric seizure propagation and to assess its potential as a strategic recording locus for state-dependent biomarkers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Epileptiform activity was induced in vitro and in vivo using 4-aminopyridine. Propagation dynamics were examined using cross-correlation analysis. Signal features were quantified using root mean square amplitudes, Shannon entropy, and spectral coherence. A previously unreported callosal evoked response, the corpus callosum evoked echo, was characterized pharmacologically (hypocalcemia, hypoxia) and anatomically (callosal disconnection) to determine synaptic dependence and cortical origin. The echo amplitude was evaluated as a predictive biomarker using logistic regression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Epileptiform discharges propagated through the corpus callosum with delays consistent with polysynaptic cellular transmission (24.81 ± 4.09 ms in vitro), and directionality was resolved in vivo. Although the propagation attenuated the seizure signal power, the spectral content of seizures was largely preserved within the corpus callosum. Following epileptogenic induction (pre-seizure), the corpus callosum signal's root mean square increased significantly, supporting its value as a physiological marker of propagated seizure activity. The corpus callosum-evoked echoes were temporally distinct from compound action potentials, were eliminated by synaptic blockade and callosal disconnection, and were selectively vulnerable to metabolic compromise, supporting their dependence on a cortico-callosal feedback loop. The echo amplitude increased during the pre-ictal period, achieving an area under the curve of 0.77 for seizure prediction in vitro.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&gt;These findings identify the corpus callosum as a physiologically active component of epileptic networks rather than a passive transmission pathway. By revealing a previously unrecognized cortico-callosal response and demonstrating its predictive potential, this work supports a network-level framework for epilepsy in which white matter structures contribute directly to seizure generation and may provide targets for physiological monitoring and intervention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;White matter tracts, such as the corpus callosum, have long been dismissed as passive \"wires\" that merely route seizure activity. This study challenges that paradigm by demonstrating that white matter signals reflect complex epileptic network behavior. By tapping directly into the corpus callosum, we achieved bilateral epilepsy monitoring and a new approach to pinpointing seizure origins within the brain. Furthermore, we uncovered a novel network response called the corpus callosum evoked echo (ccEE), which shows promise as a biomarker for seizure onset. These findings establish white matter as a critical therapeutic target for early seizure foreca","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879456","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":"Auditory gamma-band synchronization and attentional performance in juvenile myoclonic epilepsy.","authors":"Ryo Mitoma, Shunsuke Tamura, Yoji Hirano, Takako Mitsudo, Yubin Sung, Takahiko Mukaino, Takahiro Yamaguchi, Kou Matsumoto, Toshiaki Onitsuka, Shogo Hirano, Tomohiro Nakao, Noriko Isobe, Hiroshi Shigeto","doi":"10.1002/epi4.70330","DOIUrl":"10.1002/epi4.70330","url":null,"abstract":"<p><strong>Objective: </strong>Cognitive difficulties in juvenile myoclonic epilepsy (JME) are part of the clinical phenotype alongside epileptic seizures; however, the underlying neurophysiological mechanisms remain unclear. Auditory steady-state responses (ASSRs) to repetitive 40- and 80-Hz stimuli are widely used measures of gamma-band oscillations (GBOs) relevant to cognition, but have not yet been investigated in JME. To address this gap, we examined 40- and 80-Hz ASSRs using magnetoencephalography and their relationship with cognitive function in JME.</p><p><strong>Methods: </strong>In this cross-sectional case-control study, we recorded ASSRs in 16 patients with JME and 16 age- and sex-matched healthy controls (HC). Evoked power and phase-locking factor (PLF) were quantified from magnetic resonance imaging-based source estimates in the bilateral primary auditory cortices and compared between groups using linear mixed-effects models (LMMs). Cognitive function was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Within the JME group, associations between RBANS indices and ASSR measures were examined using age- and sex-adjusted linear regression. Where applicable, p values were adjusted using the Benjamini-Hochberg false discovery rate (FDR) procedure.</p><p><strong>Results: </strong>LMMs showed lower evoked power and PLF in JME than in HC (both group effects p < 0.001). Among the five RBANS indices, only the Attention Index was lower in JME (FDR-adjusted p = 0.02). Within the JME group, the Attention Index was positively associated with both measures (evoked power: B = 16.65, 95% confidence interval [CI], 5.81 to 27.49; PLF: B = 38.82, 95% CI, 13.82 to 63.83; both FDR-adjusted p = 0.03), whereas other indices showed no significant associations.</p><p><strong>Significance: </strong>Gamma-band ASSRs were reduced in JME and were consistently associated with attentional performance across evoked power and PLF. These exploratory findings suggest that gamma-band ASSRs may help investigate network-level mechanisms, potentially involving thalamocortical dysfunction that link gamma synchronization to attentional performance in JME.</p><p><strong>Plain language summary: </strong>Juvenile myoclonic epilepsy (JME) is associated with cognitive difficulties beyond seizures, but the underlying brain physiology is not fully understood. Using magnetoencephalography, we found that patients with JME showed weaker gamma-band auditory steady-state responses (ASSRs) than healthy participants. Within the JME group, stronger and more synchronized responses were associated with better attention scores, suggesting that gamma-band brain activity may be linked to attentional performance in JME. Together, these findings indicate that ASSRs may provide a useful window into brain mechanisms related to cognitive difficulties, particularly those involving attention, in JME.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886623","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, Johanna Van Hulle, Eva Brilstra, Andreas Brunklaus, Gaetano Cantalupo, Martin Geroldinger, Amy McTague, Reetta Kälviäinen, Eulalia Turón-Viñas, Alexis Arzimanoglou, Rikke S Møller, Rima Nabbout","doi":"10.1002/epi4.70304","DOIUrl":"10.1002/epi4.70304","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&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;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&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;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&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;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&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;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;Genetic testing is increasingly integrated in the diagnostic pathway for rare and complex epilepsies and treatment decisions. An ERN EpiCARE survey assessed how genetic testing is implemented across specialist epilepsy centers in Europe and identified persistent organizational, financial, and clinical barriers. Although most centers had access to advanced genomic testing, important differences were identified in access, reimbursement, turnaround times, and multidisciplinary expertise. European collaboration and harmonized practices are needed to support equitable access to high-quality genetic care for peo","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-02","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":"Evaluation of current practices and communication surrounding sudden unexpected death in epilepsy (SUDEP): A survey analysis of healthcare practitioners.","authors":"Katherine C Nickels, Carly Katterman, Kelly Gwin, Carla Schad","doi":"10.1002/epi4.70318","DOIUrl":"10.1002/epi4.70318","url":null,"abstract":"<p><strong>Objective: </strong>To characterize healthcare providers' awareness and education regarding SUDEP and their approaches to SUDEP counseling.</p><p><strong>Methods: </strong>A voluntary, observational 14-question survey was administered at the 2024 American Epilepsy Society Annual Meeting to healthcare providers who treat patients with epilepsy. The survey was designed to assess SUDEP awareness, clinical training, counseling patterns, and application of SUDEP guidelines.</p><p><strong>Results: </strong>A total of 114 responses were analyzed. Most respondents were epileptologists or neurologists and completed residency or fellowship between 2010 and 2024. A substantial portion of respondents (41%) reported that SUDEP training was not provided during their residency or fellowship. Nearly all respondents were aware of SUDEP risk in epilepsy patients, and 61% reported losing a patient to SUDEP. Despite endorsement by two professional medical associations, 26% of respondents were unaware of the 2017 AAN/AES SUDEP Practice Guidelines. Although almost all respondents reported counseling patients and families about SUDEP risk, only 52% counseled all patients in accordance with the 2017 guidelines, typically at or after the second visit, if at all. Respondents most frequently selected uncontrolled seizures as the top risk factor for SUDEP, followed by >3 generalized tonic-clonic seizures (GTCS), reflecting a discrepancy with guideline recommendations identifying GTCS as the primary risk factor. However, respondents prioritized 'targeting GTCS' similarly to 'seizure freedom' as a mitigation strategy. Most respondents rated SUDEP counseling practices negatively (needs improvement or unsatisfactory), were divided on preferred education/training delivery, and reported not using available counseling resources (PAME, EF, CURE, etc.).</p><p><strong>Significance: </strong>The survey responses demonstrate modifiable gaps between SUDEP counseling recommendations and clinical practice. Improving residency/fellowship training, awareness of the 2017 AAN/AES SUDEP Practice Guidelines, and use of available counseling resources may help align care with established recommendations.</p><p><strong>Plain language summary: </strong>SUDEP, or sudden unexpected death in epilepsy, is when a person with epilepsy dies suddenly and without another clear cause. This survey of epilepsy care providers asked about SUDEP awareness and how providers discuss SUDEP risk with patients and caregivers. Formal SUDEP education is inconsistent during training, and 26% were unaware of guidelines that help providers discuss SUDEP risk. Counseling is recommended for all patients and caregivers, but just over half of providers do so. Many also did not realize that generalized tonic-clonic seizures are the main risk factor. Increased SUDEP education and improved guideline awareness may improve SUDEP counseling.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13537074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879442","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":"Structural morphometry distinguishes vagus nerve stimulation outcomes in individuals with epilepsy.","authors":"Harry J Clifford, Sonja Fenske, Yujiang Wang, Tiago da Silva Costa, Rhys H Thomas, Sabahat Iqbal, Cameron A Elliott, Davide Giampiccolo, John S Duncan, Peter N Taylor","doi":"10.1002/epi4.70339","DOIUrl":"10.1002/epi4.70339","url":null,"abstract":"<p><strong>Objective: </strong>Vagus nerve stimulation (VNS) is a commonly used treatment for drug-resistant epilepsy. However, response to VNS is variable, while understanding of this response variability is limited. The vagus afferent network (VagAN), the neural circuits thought to be involved in response to vagal afferents, has been implicated in response prediction in modalities such as diffusion-weighted imaging, functional imaging, and neurophysiology. Structural abnormality in the VagAN from T1w MRI has not yet been studied.</p><p><strong>Methods: </strong>We assessed if VagAN abnormalities, derived from pre-implantation T1w MRI, were associated with VNS response in 92 individuals with epilepsy two years post-implantation (42 responders, 50 non-responders). We used the first principal component (PC1) from a robust principal component analysis for a variety of region sets trained using 100 healthy controls. We investigated two primary hypotheses. (i) If VagAN regions' PC1 differentiates response groups, (ii) if other region sets did not differentiate response groups.</p><p><strong>Results: </strong>Non-responders had significantly higher VagAN PC1 abnormality scores than both responders ( <math><mrow><mi>r</mi> <mo>=</mo> <mn>0.30</mn></mrow> </math> , <math><mrow><mi>p</mi> <mo>=</mo> <mn>0.008</mn></mrow> </math> ) and controls ( <math><mrow><mi>r</mi> <mo>=</mo> <mn>0.37</mn></mrow> </math> , <math><mrow><mi>p</mi> <mo><</mo> <mn>0.005</mn></mrow> </math> ). By contrast, non-VagAN PC1 showed no discriminatory value ( <math><mrow><mi>r</mi> <mo>=</mo> <mo>-</mo> <mn>0.03</mn></mrow> </math> , <math><mrow><mi>p</mi> <mo>></mo> <mn>0.05</mn></mrow> </math> ). VagAN outperformed all other region sets.</p><p><strong>Significance: </strong>Structural abnormality of VagAN was associated with non-response to VNS. This suggests that volume abnormalities in key VNS regions correlate negatively with reduction of seizures. Abnormalities in other regions, such as the non-VagAN region set, were not associated with VNS response. This metric, when combined with other modalities, may be a useful measure to improve the selection of individuals with drug-resistant epilepsy for VNS therapy.</p><p><strong>Plain language summary: </strong>Vagus nerve stimulation (VNS) is a common treatment for drug-resistant epilepsy; however, it is not always effective. We tested whether volumes of brain regions related to VNS efficacy and found that abnormality within a set of regions known to be affected by VNS related to non-response. No other set of regions showed this effect implying that this set of regions is uniquely placed to determine if someone may respond to VNS. This work supports the idea that VNS efficacy is limited by an individual's brain abnormality and should be considered in further studies.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864104","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":"Rare genetic variation in adults with surgically treated temporal lobe epilepsy: An exome sequencing study.","authors":"Antonia P Pirker, Margot Ernst, Matias Wagner, Silvia B Bonelli, Karin Trimmel, Judith Jud, Elisabeth Graf, Christian Dorfer, Karl Rössler, Susanne Aull-Watschinger, Ekaterina Pataraia, Fritz Zimprich, Martin Krenn","doi":"10.1002/epi4.70350","DOIUrl":"10.1002/epi4.70350","url":null,"abstract":"<p><strong>Objective: </strong>To determine the frequency of monogenic variants and pathogenic copy number variants (CNVs) in adults with surgically treated temporal lobe epilepsy (TLE).</p><p><strong>Methods: </strong>We performed exome sequencing (ES), including CNV analysis, in 45 adults with TLE who had previously undergone epilepsy surgery. A diagnostic exome-wide analysis was conducted to identify (likely) pathogenic variants related to epilepsy. In an exploratory approach, we screened a curated list of 45 common epilepsy genes for rare deleterious variants based on AlphaMissense and REVEL in silico predictions.</p><p><strong>Results: </strong>No highly penetrant monogenic variants were identified in this cohort. Pathogenic CNVs were detected in two individuals, corresponding to 4.4% of the cohort: a 16p13.11 deletion in a surgery responder and a 22q11.2 duplication in a surgery nonresponder. Both CNVs are characterized by reduced penetrance and broad phenotypic variability. Moreover, we identified two predicted deleterious missense variants in the epilepsy-associated genes KCNT1 and SLC2A1, both of which were detected in surgery nonresponders. In silico analyses, including structural evidence, suggested a potential impact on protein function; however, their clinical significance remains uncertain.</p><p><strong>Significance: </strong>Monogenic causes are exceedingly rare in adults with surgically treated TLE, whereas CNVs may contribute to disease susceptibility in a small subset of patients. Our findings are consistent with previous reports indicating a low diagnostic yield of presurgical genetic testing and further support a predominantly polygenic architecture of TLE.</p><p><strong>Plain language summary: </strong>Temporal lobe epilepsy (TLE) is a common type of epilepsy in adults, and some patients undergo surgery when medications fail. It is unclear whether genetic testing can help predict surgical success. In this study, we used comprehensive genetic testing in 45 adult TLE patients who had undergone epilepsy surgery. We did not find single-gene causes of epilepsy. Two patients had structural genetic changes, which increase epilepsy risk but show variable effects. We also identified a few rare variants in epilepsy-related genes, but their clinical relevance remains uncertain. Overall, our results suggest that single-gene causes are rare in adults with TLE. Genetic testing may therefore have a low diagnostic rate in this population.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13523678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839114","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":"Efficacy and safety of fenfluramine in Dravet syndrome: The impact of patient clinical characteristics.","authors":"Rima Nabbout, Joseph Sullivan, Stéphane Auvin, J Helen Cross, Orrin Devinsky, Antonio Gil-Nagel, Renzo Guerrini, Kelly G Knupp, M Scott Perry, Rocío Sánchez-Carpintero, An-Sofie Schoonjans, Ingrid E Scheffer, Nicola Specchio, Adam Strzelczyk, James Wheless, Elaine C Wirrell, Diego Morita, Patrick Healy, Mélanie Langlois, Amélie Lothe, Lieven Lagae","doi":"10.1002/epi4.70340","DOIUrl":"10.1002/epi4.70340","url":null,"abstract":"<p><strong>Objective: </strong>To assess the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) stratified by age, number of previously attempted antiseizure medications (ASMs), and SCN1A pathogenic variant status.</p><p><strong>Methods: </strong>In this post hoc analysis, data from three randomized controlled trials (RCTs) in patients with DS (2-18 years) were pooled and stratified by age (<4; ≥4 years), number of previous ASMs (1-3; 4-6; ≥7), and SCN1A pathogenic variant status (SCN1A+; SCN1A-). Stratified groups were assessed and compared with the pooled placebo group (change in monthly convulsive seizure frequency [MCSF], longest convulsive seizure-free interval, and Clinical Global Impression-Improvement [CGI-I] scale scores rated by parents/caregivers and investigators), and safety (treatment-emergent adverse events [TEAEs]: frequency, days to onset, and proportion resolved).</p><p><strong>Results: </strong>Among 348 patients included in the RCTs, 216 were randomized to fenfluramine (0.7 mg/kg/day, n = 88; 0.4 mg/kg/day [with stiripentol], n = 43; 0.2 mg/kg/day, n = 85) and 132 to placebo. Compared with placebo, fenfluramine treatment (all doses combined) resulted in greater MCSF reductions, greater increases in longest convulsive seizure-free intervals, and a higher proportion of parents/caregivers and investigators reporting clinically meaningful improvement (\"Much Improved\", \"Very Much Improved\") on CGI-I scores across all stratified groups. CGI-I scores were consistent across fenfluramine doses in most stratified groups, but patients with the fewest number of previous ASMs had the greatest frequency of clinically meaningful improvement on investigator-rated CGI-I scores. Safety outcomes were similar across all strata. Most TEAEs resolved by end-of-study.</p><p><strong>Significance: </strong>Fenfluramine treatment was associated with improved seizure outcomes and global functioning compared with placebo regardless of age, number of previous ASMs, and SCN1A status in patients with DS. Fenfluramine was well-tolerated; no new safety signals were identified. Further studies with larger sample sizes (including adults) and a priori inferential analyses of stratified groups are warranted.</p><p><strong>Plain language summary: </strong>Patients with Dravet syndrome struggle with seizures and everyday life. In three studies, patients aged 2-18 years received fenfluramine or placebo (sugar pill). Fenfluramine lowered seizures without many side effects. Researchers combined results from these studies to see how fenfluramine worked in different patient groups based on age, number of previous medications, and a gene called SCN1A. They looked at seizure reduction and whether doctors felt patients had improved. In all groups, fenfluramine worked better than placebo, with similar side effects. Researchers believe fenfluramine helped these patients, but some groups were small, so these results need to be confirmed.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789983","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}