Epilepsia Open最新文献

{"title":"Neurometabolite abnormalities and associations with epilepsy duration and cognition in patients with idiopathic generalized epilepsies.","authors":"Yun Lien, Christina Bankston, Ayushe A Sharma, Brandon S Mitchell, Rodolphe Nenert, Anna Moyana, Jennifer Pilkington, Roy C Martin, Charity J Morgan, Lawrence Ver Hoef, Jerzy P Szaflarski, Jane B Allendorfer","doi":"10.1002/epi4.70366","DOIUrl":"10.1002/epi4.70366","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated whether idiopathic generalized epilepsies (IGEs) are associated with neuroinflammation by measuring neurometabolite levels and brain temperature using whole-brain magnetic resonance spectroscopy imaging (MRSI). We compared patients with IGEs to healthy controls (HCs), and in IGEs examined relationships with seizure control, MRSI markers, epilepsy duration, and cognitive performance.</p><p><strong>Methods: </strong>Seventeen patients with IGEs and 15 HCs underwent 3T-MRI scans. IGEs were also administered the Montreal Cognitive Assessment (MoCA) and Flanker test. Whole-brain <sup>1</sup>H-MRSI provided metabolite and water maps. Levels for myo-inositol (MI; glial marker), glutamate-glutamine complex (Glx), and N-acetylaspartate (NAA) were normalized to creatine (Cr) levels. Brain temperature was obtained by frequency difference between water and Cr. IGEs were stratified into seizure-free (IGE-) and treatment-resistant (IGE+) groups. Group analyses were performed using permutation-based threshold-free cluster enhancement (TFCE) within bilateral regions of interest: anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), hippocampus, parietal cortex, and thalami.</p><p><strong>Results: </strong>Compared with HCs, IGEs showed higher MI/Cr in the parietal cortex, PCC, and thalamus; higher hippocampus Glx/Cr; and lower parietal cortex NAA/Cr. Brain temperature did not differ between groups. IGE- exhibited higher hippocampal NAA/Cr and better MoCA scores than IGE+. Longer epilepsy duration was associated with lower NAA/Cr in the ACC and PCC, and parietal cortex, as well as lower Glx/Cr in the ACC, PCC, parietal cortex, and hippocampus. Lower NAA/Cr in the ACC, PCC, hippocampus, and thalamus, together with higher thalamus MI/Cr, was associated with lower MoCA scores in IGEs. Lower NAA/Cr in the ACC, thalamus, and hippocampus was associated with poorer Flanker performance in IGEs.</p><p><strong>Significance: </strong>We provide novel evidence of neurometabolic abnormalities in IGEs. The associations between metabolite levels and clinical and cognitive variables suggest potential biomarkers for disease progression and treatment response. Furthermore, these results highlight the roles of abnormal glial activation, neuronal loss, and hyperexcitability in IGE pathophysiology.</p><p><strong>Plain language summary: </strong>We compared patients with idiopathic generalized epilepsies (IGEs) to healthy controls (HCs) to investigate brain chemistry and temperature differences and their relationships to seizure control, epilepsy duration, and cognitive performance. We found group differences in brain N-acetylaspartate (NAA; neuronal marker), myo-inositol (MI; glial cell marker), and glutamate/glutamine (Glx; excitatory neurotransmission) levels, but not in brain temperature. Longer epilepsy duration was associated with brain chemistry levels. In IGEs, lower NAA levels and higher MI levels were associ","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135588","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":"Sudden unexpected death in epilepsy: An Italian expert consensus statement on risk, mechanisms, prevention, and therapeutic strategies.","authors":"Vincenzo Belcastro, Fedele Dono, Giovanni Falcicchio, Lorenzo Gigli, Angela La Neve, Sara Matricardi, Barbara Mostacci, Angelo Pascarella, Leandro Pecchia, Emilio Russo, Pasquale Striano","doi":"10.1002/epi4.70358","DOIUrl":"10.1002/epi4.70358","url":null,"abstract":"<p><strong>Objective: </strong>Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature mortality in people with epilepsy, particularly in those with tonic-clonic seizures (TCSs), developmental and epileptic encephalopathies (DEEs), and drug-resistant epilepsy. Although awareness of SUDEP has increased, major uncertainties remain regarding individualized risk stratification, mechanistic interpretation, and implementation of preventive strategies in routine care. This Italian expert consensus statement was developed to formalize a shared multidisciplinary position on SUDEP risk profiles, pathophysiological mechanisms, and preventive and therapeutic strategies.</p><p><strong>Methods: </strong>The consensus was supported by a focused narrative appraisal of current evidence, rather than a systematic review, and developed through a structured multidisciplinary process based on a nominal group technique. The panel comprised 11 Italian experts: nine epileptologists from the Italian League Against Epilepsy (LICE) and its SUDEP Working Group, one cardiologist with expertise in epilepsy-related cardiac complications and SUDEP, and one biomedical engineer with expertise in seizure-detection devices and wearable technologies. Statements were generated across three macro-areas, discussed in working groups and plenary sessions, prioritized through an initial in-person vote, refined after discussion, and submitted to a second online round. Consensus was predefined as at least 75% agreement on a 5-point Likert scale.</p><p><strong>Results: </strong>A final set of 33 statements was generated, of which 26 reached consensus; two of these (serotonergic modulation as a preventive strategy and fenfluramine's mechanisms beyond seizure control) reached the threshold only narrowly and are discussed as hypothesis-generating rather than as established clinical guidance. The resulting framework supports an extension of seizure-centered prevention toward an integrated, individualized, and mechanism-informed approach, in which reduction of convulsive seizure burden remains central while post-ictal respiratory, autonomic, cardiac, arousal, genetic, and treatment-related vulnerabilities are considered in selected high-risk patients.</p><p><strong>Significance: </strong>This consensus provides the first formalized Italian multidisciplinary position on SUDEP, offering an evidence-informed and mechanism-aware framework intended to support more consistent risk communication, individualized risk stratification, and preventive care in clinical practice.</p><p><strong>Plain language summary: </strong>Sudden unexpected death in epilepsy (SUDEP) is uncommon but is more likely in people with frequent tonic-clonic seizures and some severe epilepsy syndromes. An Italian multidisciplinary expert panel developed consensus statements on SUDEP risk, possible mechanisms, monitoring, and prevention. Reducing convulsive seizures and supporting treatment adherence remain the mai","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105835","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":"Transcutaneous auricular vagus nerve stimulation in drug-resistant epilepsy: A randomized, sham-controlled crossover trial with exploratory EEG and MRI response phenotyping.","authors":"Sung Jun Hong, Seok-Yeol Yang, Eun Kyung Bok, Jung Chul Lee, Yeonggin Kim, Kyousik Min, Young-Min Shon","doi":"10.1002/epi4.70354","DOIUrl":"10.1002/epi4.70354","url":null,"abstract":"<p><strong>Objective: </strong>Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation strategy for drug-resistant epilepsy, but clinical response is heterogeneous. We examined whether electroencephalographic (EEG) and structural magnetic resonance imaging (MRI) phenotypes were associated with active-specific clinical benefit from taVNS.</p><p><strong>Methods: </strong>In this single-center, randomized, double-blind, sham-controlled crossover exploratory pilot trial, 14 patients with drug-resistant focal epilepsy received 8 weeks of active taVNS and 8 weeks of sham stimulation, separated by a 4-week washout, in randomized sequence. The primary clinical outcome was seizure reduction ratio (SRR) during active versus sham stimulation. Active-specific clinical benefit was defined as ΔSRR = SRR_active - SRR_sham. Resting-state EEG was obtained at baseline and at the end of the protocol. Changes in regional relative band power were correlated with ΔSRR, with a focus on the β band based on prior evidence of vagal stimulation-related desynchronization. Baseline structural MRI findings were explored by active-phase responder status.</p><p><strong>Results: </strong>Active taVNS did not significantly outperform sham stimulation. Mean SRR was 46.26 ± 40.96% during active stimulation and 48.62 ± 37.27% during sham stimulation, with a mean within-subject difference of -2.37 ± 16.64% (p = 0.604). Greater β-band attenuation was associated with larger active-specific clinical benefit in the occipital (ρ = -0.723, p = 0.003, q = 0.017) and frontal regions (ρ = -0.657, p = 0.011, q = 0.027). Parietal β-band attenuation showed a nominal association (ρ = -0.552, p = 0.041, q = 0.068). Bilateral structural abnormalities and limbic involvement were more frequent among nonresponders (both p = 0.021, uncorrected).</p><p><strong>Significance: </strong>Although primary clinical efficacy was not demonstrated, EEG β-band modulation and limbic structural network burden may help explain interindividual variability in taVNS benefit. The substantial sham response underscores the need for rigorous sham-controlled taVNS trials.</p><p><strong>Plain language summary: </strong>About one-third of people with epilepsy keep having seizures despite medication. taVNS is a noninvasive treatment that stimulates a nerve at the outer ear. In this small, carefully blinded trial, active taVNS did not reduce seizures more than an inactive (sham) treatment, and the sham response was large. However, people whose EEG β brain waves decreased during the study tended to benefit more, and those with more widespread limbic or structural brain changes tended to benefit less. If confirmed in larger studies, these EEG and MRI markers might help identify who is most likely to respond to taVNS.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13640803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105856","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":"Outcomes of patients with post-stroke epilepsy: A scoping review on quality of life, readmissions, costs, seizure recurrence, and medication adherence.","authors":"Nega Dagnew Baye, Emma Foster, Muideen T Olaiya, Nigel C Jones, Monique F Kilkenny, Lachlan L Dalli","doi":"10.1002/epi4.70362","DOIUrl":"10.1002/epi4.70362","url":null,"abstract":"<p><strong>Objective: </strong>Post-stroke epilepsy (PSE) affects ≈10% of patients with stroke and is associated with adverse health and economic outcomes. We aimed to review published literature on health and economic outcomes for patients with PSE, with a specific focus on quality of life, hospital readmissions, healthcare costs, seizure recurrence, and medication adherence.</p><p><strong>Methods: </strong>A protocol was developed and registered in the Open Science Framework (OSF). Ovid Medline, Embase, Scopus, and Web of Science databases were searched from database inception until January 5, 2026. One human reviewer and an AI-assisted reviewer independently screened the titles and abstracts for eligibility (92.9% agreement), with disagreements resolved by a second human reviewer. Full-text review was undertaken independently by two human reviewers. Data were extracted from each study and entered into a standardized proforma and qualitatively synthesized.</p><p><strong>Results: </strong>Of the 3557 studies screened, 103 passed to full-text review and 61 were included. The majority of studies were from the United States (n = 11) followed by China (n = 9). The follow-up duration ranged from time at hospital discharge to 16 years post-discharge. Outcomes reported included: quality of life (n = 14), hospital readmission (n = 8), healthcare costs (n = 2), seizure recurrence (n = 38), and medication adherence (n = 6). PSE was associated with reduced quality of life and greater healthcare costs compared to stroke survivors without epilepsy. Seizure recurrence was more likely in younger adults. No clear sex differences were noted for any outcomes. Compared to enzyme-inducing antiseizure medications, non-enzyme inducing medications were associated with fewer recurrent seizures and readmissions and less medication discontinuation.</p><p><strong>Significance: </strong>PSE was associated with poorer quality of life compared to stroke survivors who did not develop epilepsy. Additional studies are needed to definitively establish the association between PSE and other outcomes. Understanding the burden of PSE, including long-term outcomes, is critical to guide future research, incentivize earlier diagnosis, and optimize treatment.</p><p><strong>Plain language summary: </strong>This review comprehensively examined the current evidence on health and economic outcomes for patients with PSE, covering important outcomes such as quality of life, hospital readmission, healthcare costs, seizure recurrence, and medication adherence. Across studies, those with PSE had a reduced quality of life than stroke survivors without epilepsy. The use of newer antiseizure medications was linked with fewer recurrent seizures, readmissions, and medication discontinuations compared to older antiseizure medications. The findings of this study can help guide further research and practice improvement to reduce the immense health and economic burden of PSE.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105556","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":"Shared molecular pathways in pediatric genetic epilepsies: Insights from a single-center cohort of 80 patients.","authors":"Laura Hecher, Mathias Woidy, Franziska Plein, Tatjana Bierhals, Leonie von Elsner, Theresia Herget, Maja Hempel, Fanny Kortüm, Lev Grinstein, Julia V Cramer, Jessika Johannsen, Jonas Denecke","doi":"10.1002/epi4.70357","DOIUrl":"https://doi.org/10.1002/epi4.70357","url":null,"abstract":"<p><strong>Objective: </strong>Genetic epilepsies in childhood are highly heterogeneous, and approaches to identify shared biological mechanisms across distinct genetic etiologies remain limited. We aimed to investigate whether genes associated with pediatric genetic epilepsies in our heterogeneous cohort converge on common functional pathways.</p><p><strong>Methods: </strong>We conducted a single-center retrospective study involving 80 children who met the International League Against Epilepsy (ILAE) criteria for epilepsy with a confirmed monogenetic etiology, with or without other neurological conditions. These children were part of a cohort of pediatric patients with a broad spectrum of neurological disorders that had been genetically diagnosed using trio-based whole-exome sequencing. Clinical data were systematically collected. Gene Ontology (GO)-based enrichment analysis was performed to explore functional convergence.</p><p><strong>Results: </strong>The cohort comprised 80 patients (39% female, 61% male) with a median age at seizure onset of seven months and included 66 distinct disease-causing genes and four pathogenic copy number variants. Despite marked genetic heterogeneity, enrichment analyses revealed convergence in functional pathways related to synaptic signaling, membrane channels and transport processes, and neurodevelopmental and neuronal plasticity pathways. Age-stratified analyses suggested variation in the relative contribution of these pathways across developmental stages, while no significant differences were observed with respect to neurodevelopmental delay or neuroimaging abnormalities.</p><p><strong>Significance: </strong>These findings demonstrate shared molecular pathways across clinically and genetically diverse pediatric neurological conditions associated with epilepsies and support a pathway-oriented perspective that may complement gene-based classification and inform future therapeutic strategies.</p><p><strong>Plain language summary: </strong>Childhood epilepsies caused by genetic changes can arise from many different genes, making them difficult to understand and classify. In this study, we analyzed 80 children with genetically confirmed epilepsy and found that, despite different genetic causes, many of the affected genes are involved in similar biological processes, particularly those related to brain signaling and development. These findings suggest that different genetic epilepsies may share common underlying mechanisms. A better understanding of these shared pathways may help improve how epilepsy is classified and treated in the future.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105786","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":"From first seizure to specific antiseizure medication in Dravet syndrome: Quantifying delays in the DS'coverED study.","authors":"Loucas Christodoulou, Maria Ballarà Petitbò, Sergio Aguilera Albesa, Simona Borroni, Perrine Hugon, Ratna Kumar, Tullio Messana, Pierre Meyer, Frédéric Villéga, Kerstin A Klotz","doi":"10.1002/epi4.70328","DOIUrl":"10.1002/epi4.70328","url":null,"abstract":"<p><strong>Objective: </strong>Dravet syndrome (DS) is a rare early-onset developmental and epileptic encephalopathy with persistent delays between seizure onset and diagnosis. The DS'coverED study aimed to characterize current diagnostic timelines by examining each step and its duration, identifying residual barriers, and actionable solutions to optimize the diagnostic process within real-world clinical pathways.</p><p><strong>Methods: </strong>A steering committee-eight pediatric neurologists and one representative from the DS European Federation-developed a survey addressed to European pediatric neurologists experienced in DS management. Responders reported information on their medical practice and data on patients' diagnostic pathways from seizure onset to initiation of DS-specific antiseizure medications (ASMs).</p><p><strong>Results: </strong>Fifty-three physicians participated in the study. Analysis of 45 patient diagnostic pathways revealed marked heterogeneity in the DS diagnostic pathway. The median age at formal diagnosis was 15 months, with a median interval of 11 months between seizure onset and diagnosis. While half of the patients received a diagnosis within 1 year of seizure onset, 25% were diagnosed after 23 months of age. Diagnostic delays were primarily associated with late referral to expert centers and prolonged access or turnaround times for genetic testing. Although 45% of responders requested genetic testing promptly after initial consultation, more than half waited for confirmatory results before formally communicating the diagnosis. Initiation of DS-specific ASMs was inconsistent-occurring a median of 3 months after diagnosis but exceeding 9 months in 27% of cases-likely influenced by clinician caution, drug availability, and parental concerns regarding the treatment regimen.</p><p><strong>Significance: </strong>DS'coverED seeks to fill a critical knowledge gap in the DS diagnostic pathway. The study provides healthcare professionals with benchmarks for refining their diagnostic practices and guiding clinical improvements-ongoing clinician education, better healthcare system coordination, and active caregiver engagement.</p><p><strong>Plain language summary: </strong>The diagnosis of Dravet syndrome, a rare and severe form of childhood epilepsy, is still often delayed after the first seizure. The DS'coverED European survey explored each step of the diagnostic journey and identified residual barriers and opportunities to optimize the time to diagnosis and access to Dravet syndrome-specific antiseizure medications. It provides physicians with actionable solutions that can help improve the diagnostic process of the condition.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1729-1741"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758895","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 spatial learning task of Lhermitte and Signoret: Marker of bilateral hippocampal dysfunction in temporal lobe epilepsy.","authors":"Andy Sitoh, David Weintrob, Jacqueline F I Anderson, Marie F O'Shea, Graeme D Jackson, Piero Perucca, Chris Tailby","doi":"10.1002/epi4.70332","DOIUrl":"10.1002/epi4.70332","url":null,"abstract":"<p><strong>Objective: </strong>Bilateral hippocampal compromise in temporal lobe epilepsy (TLE) substantially increases the risk of significant adverse memory outcomes following unilateral anterior temporal lobectomy and may contraindicate surgery. The Spatial Learning Task (SLT) of Lhermitte and Signoret (1972) is a simple object-location arbitrary associative learning task proposed as a marker of bitemporal dysfunction. Here, we test whether the SLT might serve as a useful marker in TLE by examining, in individuals with TLE and hippocampal sclerosis (HS), whether performance on the SLT depends on the laterality of the HS (left, right, bilateral). We hypothesize that performance will be worst in the setting of bilateral HS.</p><p><strong>Methods: </strong>Retrospective analysis of 63 surgically naïve TLE-HS patients (16 bilateral HS, 28 left HS, 19 right HS) who underwent neuropsychological evaluation at a tertiary epilepsy center.</p><p><strong>Results: </strong>Bilateral HS cases showed significantly poorer SLT learning and learning efficiency compared to right HS cases (p ≤ .005, BF₁₀ ≥ 25). Left HS cases performed comparably to bilateral HS cases on early trials but typically achieved ceiling performance with repetition, reflecting inefficiency rather than capacity loss. An SLT learning score <13 yielded high specificity (96% [95% CI: 0.85-0.99]) but modest sensitivity (44% [95% CI 0.20-0.70]) for identifying bilateral HS cases.</p><p><strong>Significance: </strong>In the setting of TLE-HS, poor performance on the SLT increases the probability of bilateral hippocampal pathology, supporting its utility as a rule-in indicator. Although intact scores do not reliably exclude bilateral pathology, a low score on this task should prompt further investigations as to possible bitemporal compromise, and suggest risk of adverse memory outcomes following surgery. Prospective, post-operative studies will be required to quantify this risk.</p><p><strong>Plain language statement: </strong>The results of the study show that the ability to learn arbitrary object-location pairings is compromised in the setting of temporal lobe epilepsy with bilateral hippocampal sclerosis (HS). In contrast, patients with unilateral HS generally retained sufficient capacity to learn the task, though those with left HS were slower to acquire the pairings across repeated trials. A low score on this task was a strong indicator of bilateral hippocampal pathology, whereas an intact score did not reliably exclude it. Our results suggest that performance on this simple learning task provides a useful marker of bilateral hippocampal compromise in epilepsy and may be particularly valuable in patients for whom standard memory tests are less suitable. We provide a cutoff score to facilitate clinical interpretation.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1773-1785"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711409","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":"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":"1825-1840"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","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":"Phenotype-guided etiologic workup in a prospective cohort of 144 adults with developmental and epileptic encephalopathy.","authors":"Giuseppe d'Orsi, Umberto Costantino, Maria Teresa Di Claudio, Carmela Pia Ferro, Pietro Palumbo, Mario Benvenuto, Massimiliano Copetti, Leonardo D'Agruma, Massimo Carella, Marco Castori, Orazio Palumbo","doi":"10.1002/epi4.70316","DOIUrl":"10.1002/epi4.70316","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Adults with developmental and epileptic encephalopathies (DEEs) often enter adult neurology care without etiologic clarification because of incomplete transition from pediatric services, outdated investigations, and attenuation of childhood electro-clinical features over time. We aimed to assess the clinical utility and diagnostic yield of a structured, phenotype-guided etiologic workup in adults meeting study criteria for DEE and to explore associations between electro-clinical phenotype and etiologic category.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We prospectively enrolled consecutive adults (≥18 years) with drug-resistant epilepsy and neurodevelopmental impairment temporally related to epileptic activity, consistent with the ILAE operational definition of DEE, referred to a tertiary epilepsy center between May 2022 and December 2025. Patients underwent a 4-phase reassessment pathway including critical review of prior documentation, detailed clinical and semiologic phenotyping, prolonged video-EEG monitoring, phenotype-guided genetic testing (targeted resequencing, chromosomal microarray), high-resolution neuroimaging, and multidisciplinary case review to support etiologic clarification and treatment planning.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 144 patients (mean age 28.4 years; 57.6% male), a confirmed etiology was identified in 91 (63.2%). Genetic causes predominated (65 patients, 45.1%), including monogenic (53, 36.8%) and chromosomal (12, 8.3%) disorders, primarily resolved via targeted resequencing gene panels and via chromosomal microarray analysis respectively, while structural-metabolic etiologies accounted for 26 cases (18.1%). Lennox-Gastaut syndrome was significantly associated with structural-metabolic and chromosomal etiologies (69.2% and 58.3% vs. 9.4% in monogenic; p &lt; 0.0001), whereas, excluding patients with a broader Lennox-Gastaut syndrome phenotype, absence seizures occurred exclusively in monogenic cases (p = 0.024). Etiologic clarification changed clinical management in 27.1% of the cohort, including antiseizure medication optimization/precision therapies (25%) and pre-surgical referral (2.1%).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&gt;In adults with suspected DEE, the practical value of this approach lies not only in diagnostic yield, but in showing that structured adult reassessment remains clinically worthwhile. Electro-clinical phenotype can help prioritize etiologic testing, and etiologic clarification can support more informed treatment planning and counseling even long after transition from pediatric care.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;Adults with developmental and epileptic encephalopathy (DEE) often reach adult epilepsy services without a clear diagnosis. In this study, we used a structured approach combining clinical review, video-EEG, MRI, genetic testing, and multidisciplinary discussion in 144 adults with suspected DEE. We identified a confirmed cause in 63.2% of patien","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1635-1650"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148653188","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":"Salience network hub dysfunction is associated with cognitive impairment in self-limited epilepsy with centrotemporal spikes: An OPM-MEG study.","authors":"Chen Yang, Guangsheng Wu, Nan An, Tiejia Jiang, Yilong Wang, Wenbin Zhao, Wangyang Cao, Xiaofang Wang, Haiteng Jiang, Zhefeng Yuan","doi":"10.1002/epi4.70326","DOIUrl":"10.1002/epi4.70326","url":null,"abstract":"<p><strong>Objective: </strong>Self-limited epilepsy with centrotemporal spikes (SeLECTS), although characterized by well-controlled seizures, is frequently associated with persistent cognitive deficits in affected children. This study aimed to investigate whether hub dysfunction of the salience network (SN) is associated with cognitive impairment in SeLECTS, using optically pumped magnetometer- magnetoencephalography (OPM-MEG) within the framework of the triple network model (TNM), which encompasses the salience, default mode, and central executive networks (CENs).</p><p><strong>Methods: </strong>This cross-sectional case-control study enrolled 30 children with SeLECTS and 15 matched healthy controls (HC). Data acquisition comprised resting-state OPM-MEG, structural MRI, and the Das-Naglieri Cognitive Assessment System (CAS). Within the framework of the TNM, graph theory was employed to analyze hub function in the SN across multiple frequency bands.</p><p><strong>Results: </strong>The SeLECTS group exhibited widespread reductions in functional connectivity across the theta, alpha, and beta bands, with the beta band demonstrating the most pronounced decrease. Graph-theoretical analysis revealed that betweenness centrality of the SN was significantly lower in the SeLECTS group and was independently associated with cognitive scores (B = 248.98, 95% CI 57.95-440.02; β = 0.28, p < 0.05). Exploratory mediation analysis suggested that beta-band SN hub function was statistically consistent with an indirect pathway linking disease status and cognitive performance.</p><p><strong>Significance: </strong>This OPM-MEG study suggests that beta-band hub dysfunction of the SN is associated with cognitive impairment in children with SeLECTS. These findings provide hypothesis-generating evidence that altered SN hub topology may contribute to cognitive vulnerability in SeLECTS and may serve as a potential MEG-based biomarker of cognitive risk.</p><p><strong>Plain language summary: </strong>Children with a common childhood epilepsy called self-limited epilepsy with centrotemporal spikes may have learning and attention difficulties even when seizures are well controlled. We used a child-friendly magnetic brain-recording method to study how key brain networks communicate at rest. These children showed weaker network communication, especially in the beta frequency band, and a less central role of the salience network was linked to poorer cognitive performance. These findings may help identify children at greater risk of cognitive difficulties.</p>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":" ","pages":"1706-1717"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13468730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721718","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}