Epilepsia[JOURNAL]
Sun
200 papers
Responsible use of artificial intelligence in peer-reviewed publications in epilepsy.
Kerr WT, Pellinen J, Goldenholz DM
Epilepsia · 2026 Jul · PMID 42400454 · Publisher ↗
Abstract loading — click title to view on PubMed.
Altered autonomic balance drives the increase in cardiac output and arterial pressure during convulsive seizures in nonanesthetized sheep.
Pustovit RV, Lankadeva YR, Booth LC … +6 more , Hood SG, Soh MS, Berkovic SF, Lancefield TF, Reid CA, May CN
Epilepsia · 2026 Jul · PMID 42400445 · Publisher ↗
OBJECTIVE: Preclinical and human studies suggest that ictal and interictal modulation of the sympathetic and parasympathetic systems contributes to cardiovascular changes that may induce sudden unexpected death in epilep...
OBJECTIVE: Preclinical and human studies suggest that ictal and interictal modulation of the sympathetic and parasympathetic systems contributes to cardiovascular changes that may induce sudden unexpected death in epilepsy. We therefore investigated the effects of convulsive seizures on cardiovascular and autonomic function in nonanesthetized sheep. METHODS: Adult female sheep were instrumented to record arterial pressure, heart rate, electroencephalogram, electrocardiogram, and either cardiac output or cardiac and renal sympathetic nerve activity (SNA). Arterial blood samples were collected to assess blood biochemistry. Seizures were induced in nonanesthetized sheep by intravenous infusion of the proconvulsant pentylenetetrazol (PTZ; 5.0 mg/kg/min for 4 min). RESULTS: PTZ induced consistent generalized tonic-clonic seizures associated with abnormal activity on electroencephalogram. Convulsive seizures increased mean arterial pressure (79.1 ± 4.5 mmHg to 128.5 ± 5.6 mmHg, p < .0001) and cardiac output (4.1 ± .2 to 7.9 ± .5 L/min, p < .0001) at 10 min postseizure; these remained significantly above baseline for 60 min (both n = 12). Heart rate variability decreased (4826.1 ± 766.6 to 210.9 ± 97.7 ms, n = 6, p = .0155) at 10 min and corrected QT interval increased (399 ± 9.1 to 449.7 ± 11 ms, p = .003) at 30 min postictally. Seizures increased cardiac SNA (682 ± 86 to 7558 ± 3955 spikes/min, n = 4, p = .007), whereas renal SNA decreased (4296 ± 784 to 1139 ± 284 spikes/min (p = .047). Seizures decreased blood potassium (3.9 ± .1 to 3.4 ± .1 mmol·L, p = .0268) and increased lactate (.68 ± .05 to 12.2 ± 1.39 mmol·L; p < .0001). SIGNIFICANCE: Seizures induced by PTZ in nonanesthetized sheep caused autonomic and cardiovascular disturbances, including postictal tachycardia and arrhythmias, which may contribute to an increased risk of sudden unexpected death in epilepsy.
Diagnostic yield and copy number variants findings in 219 adult patients with developmental and epileptic encephalopathy.
Licchetta L, Bruschi G, Giangregorio T … +8 more , Stipa C, Mannini E, Minardi R, Mostacci B, Tontini V, Pippucci T, Bisulli F, Magini P
Epilepsia · 2026 Jul · PMID 42400436 · Publisher ↗
In a clinical setting, exome sequencing (ES) with copy number variant (CNV) analysis is currently the most effective approach for developmental and epileptic encephalopathies (DEE). However, trio-based ES is often not fe...
In a clinical setting, exome sequencing (ES) with copy number variant (CNV) analysis is currently the most effective approach for developmental and epileptic encephalopathies (DEE). However, trio-based ES is often not feasible in adults, its costs remain prohibitive in certain health care settings, and computational tools for CNV calling still lack sufficient accuracy. Chromosomal microarray (CMA) is indicated as a first-tier test for CNV detection in patients with DEE, dysmorphisms, and comorbidities. We investigate the role of CNVs in the etiology of DEE in an adult cohort, to define the most appropriate diagnostic approach in this population. A total of 219 patients (male/female: 104/115) with undiagnosed DEE underwent array-based comparative genomic hybridization/single nucleotide polymorphism arrays as adults. Causative CNVs were identified in 18 patients (8.2%); 14 were deletions (mean size ≈ 2.96 Mb), and four were duplications/triplications (mean size ≈ 3.63 Mb). Thirteen were responsible for known deletion/microduplication syndromes, and four were deletions involving haploinsufficient genes associated with epilepsy/neurodevelopmental disorders. For one deletion, population evidence, reports with overlapping deletions, and clinical databases support a likely pathogenic role. The mean age at CMA diagnosis was 32.4 ± 13 years. An additional 46 patients (21%) then received a molecular diagnosis through alternative approaches. Despite a diagnostic delay of 24.2 ± 14.5 years, CMA enabled a genetic diagnosis in 8.2% of our adult DEE patients, especially in those with dysmorphisms. The diagnostic yield rises to 10.4% when excluding patients diagnosed using other methods. A total of 66.7% of solved cases had direct implications from the diagnosis, supporting the clinical utility of CNV analysis inclusion in the diagnostic workflow for adult patients with DEE.
Prolonged fenfluramine use in open-label studies of Dravet or Lennox-Gastaut syndromes: Long-term safety, tolerability, patient global functioning, and considerations for interpreting effectiveness.
Gil-Nagel A, Knupp KG, Gunning B … +16 more , Battaglia DI, Thiele EA, Scheffer IE, Schoonjans AS, Nabbout R, Villeneuve N, Klotz KA, Specchio N, Sanchez-Carpintero R, Zolnowska M, Schulz AL, Perrin L, Dickson N, Langlois M, Lothe A, Sullivan J
Epilepsia · 2026 Jul · PMID 42400405 · Publisher ↗
OBJECTIVE: Long-term safety and global functioning are reported in patients with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) treated with fenfluramine in an open-label extension (OLE) study after participating...
OBJECTIVE: Long-term safety and global functioning are reported in patients with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) treated with fenfluramine in an open-label extension (OLE) study after participating in a previous open-label feeder study. METHODS: Patients could enroll in this international, multicenter OLE (NCT03936777) after completing one of three fenfluramine open-label studies. The latest feeder study fenfluramine dose was continued, then flexibly titrated (maximum: .7 mg/kg/day [26 mg/day] without stiripentol or .4 mg/kg/day [17 mg/day] with stiripentol), with ≥1 concomitant antiseizure medication administered. Primary endpoint was fenfluramine long-term safety/tolerability. Global functioning using caregiver- and investigator-reported Clinical Global Impression of Improvement (CGI-I) ratings, globally and for subdomains (cognition, behavior, motor function), at last visit relative to study baseline was evaluated. Overall treatment exposure and age groups were analyzed post hoc. RESULTS: A total of 412 patients enrolled (DS: 265 [64.3%], LGS: 147 [35.7%]); 30.8% were ≥18 years old. Median fenfluramine treatment duration in this OLE was 729.5 days (range = 8-1544), and overall median fenfluramine exposure, including feeder studies, was 1464.5 days (range = 171-2800). In this OLE, ≥1 treatment-emergent adverse event (TEAE) was reported in 311 (75.5%) patients; fenfluramine-related (per investigator) serious TEAEs were reported in five (1.2%) patients. Three patients died in this OLE (deemed unrelated to fenfluramine by investigators). After starting this OLE already receiving fenfluramine, 373 of 401 (93.0%) and 376 of 401 (93.8%) patients were rated by caregiver and investigator, respectively, as "improved or no change" on CGI-I versus this study baseline; subdomain ratings of "improved or no change" were largely consistent with global assessment. SIGNIFICANCE: In our OLE study of patients with DS or LGS treated with fenfluramine (up to 4 years), no new or unexpected safety signals were observed; global functioning was improved or stable (vs. study baseline) in >90% of patients, supporting long-term fenfluramine use in pediatric and adult patients with DS or LGS.
Electrocardiography characteristics and long-term mortality in people with epilepsy from a resource-poor community.
Wang Y, Ge Y, Zhou X … +6 more , Yang B, Kwan P, Wang W, Sander JW, Wu X, Ding D
Epilepsia · 2026 Jul · PMID 42400380 · Publisher ↗
OBJECTIVE: Data on electrocardiography (ECG) characteristics and their associations with mortality in people with epilepsy from resource-poor communities remain limited. This study aimed to investigate these associations...
OBJECTIVE: Data on electrocardiography (ECG) characteristics and their associations with mortality in people with epilepsy from resource-poor communities remain limited. This study aimed to investigate these associations within a prospective cohort in rural China. METHODS: We conducted an exploratory analysis within a prospective epilepsy cohort in rural China. Baseline 12-lead ECG recordings were evaluated using the Minnesota Code and continuous interval measurements. Associations with long-term mortality, including sudden unexpected death in epilepsy (SUDEP), were assessed using Cox regression models. RESULTS: Among 442 participants included in the analysis, 30 deaths occurred during a mean follow-up of 5.9 years, including 12 SUDEP cases. Half of the participants exhibited at least one baseline ECG abnormality. The most prevalent morphological abnormalities were T-wave abnormalities (27.3%), arrhythmias (17.5%), and ST-segment depression (8.2%), with T-wave abnormalities showing a higher prevalence in older participants. Minnesota Code-defined ventricular conduction defects were associated with an increased risk of SUDEP (adjusted hazard ratio [HR] 6.53, 95% confidence interval [CI] 1.42-30.10). High-amplitude R waves were associated with non-epilepsy-related mortality (adjusted HR 15.68, 95% CI 3.37-72.92). SIGNIFICANCE: ECG abnormalities were common in people with epilepsy. Ventricular conduction defects or high-amplitude R waves were associated with SUDEP or non-epilepsy-related mortality. ECG could be helpful in recognizing people with epilepsy with high risk of premature death, particularly in resource-poor settings.
Factors associated with rapid pediatric acute seizure emergency treatment: Quality Improvement in Time to Treat Status Epilepticus baseline cohort.
Ostendorf AP, Brown-Mitchell G, Loddenkemper T … +14 more , Morgan LA, Appavu B, Farias-Moeller R, Harrar D, Press C, Mailo J, Abend NS, Gaillard WD, Bai S, Eisner M, Kroshus E, Vannatta K, Goodkin HP, QuITT‐SE Study Group
Epilepsia · 2026 Jul · PMID 42397688 · Publisher ↗
OBJECTIVE: Status epilepticus (SE) treatment is more effective when benzodiazepines (BZDs) are given soon after SE diagnosis. The Quality Improvement in Time to Treat Status Epilepticus (QuITT-SE) trial is a multicenter,...
OBJECTIVE: Status epilepticus (SE) treatment is more effective when benzodiazepines (BZDs) are given soon after SE diagnosis. The Quality Improvement in Time to Treat Status Epilepticus (QuITT-SE) trial is a multicenter, randomized, stepped-wedge effectiveness-implementation hybrid study aimed at improving time to SE treatment. We report the QuITT-SE baseline cohort and test the hypothesis that acute seizure emergency episodes treated promptly differ in clinical and demographic features from those with delayed treatment. METHODS: Data were summarized from 371 consecutive acute seizures episodes treated with a BZD in the inpatient, non-intensive care unit (ICU) setting from 207 individual patients across eight centers per the QuITT-SE protocol. To test our hypothesis, we utilized a multivariable negative binomial mixed effects model with random intercepts to estimate the incidence rate ratios for variables of interest for time to BZD treatment. RESULTS: The median age was 7 years (IQR = 3-12). Nonelective ICU transfers occurred with 26% of episodes, including 13% within 6 h of the episode. The median time from seizure onset to BZD treatment was 6 min (IQR = 4-10), with 74% of all episodes and 63% of SE treated within 10 min. BZD administration was faster when nurses made the treatment decision, when the intranasal (IN) route was used, when the patient received prior rescue medication within 24 h, or with certain elective admission types. Seizures were shorter when BZD administration was faster or when treatment was with IN midazolam versus intravenous lorazepam (median = 8 min [IQR = 6-15] vs. 10 min [IQR = 7-17], p = .04). Patients were less likely to be transferred to the ICU if they received IN midazolam (odds ratio = .3, p = .007). SIGNIFICANCE: Delayed BZD administration occurs in one third of SE treatment. Prolonged seizures and ICU transfers are associated with modifiable risk factors. Baseline drivers of delayed acute seizure treatment may be addressed using the QuITT-SE interventions, the study of which is currently ongoing.
Outcome trajectories after pediatric epilepsy surgery vary by biopsychosocial phenotypes.
Widjaja E, Puka K, Smith ML
Epilepsia · 2026 Jul · PMID 42397687 · Publisher ↗
OBJECTIVE: The aims of this study were to examine whether there are distinct biopsychosocial phenotypes among children with drug-resistant epilepsy (DRE) and to determine whether these phenotypes are related to the longi...
OBJECTIVE: The aims of this study were to examine whether there are distinct biopsychosocial phenotypes among children with drug-resistant epilepsy (DRE) and to determine whether these phenotypes are related to the longitudinal trajectories of child, parent, and family outcomes after epilepsy surgery compared to medical treatment. METHODS: This prospective cohort study recruited children with DRE aged 4-18 years who were evaluated for epilepsy surgery and their parents. Baseline clinical variables, child characteristics, parent depressive and anxiety symptoms, and family factors (household income, family demands, family resources, and satisfaction with family relationships) were used to identify distinct phenotypes using hierarchical k-means clustering. The trajectories of child health-related quality of life (HRQOL), parent depressive and anxiety symptoms, family resources, and satisfaction with family relationships over 2 years in the surgical and medical treatment groups were compared across the phenotypes using linear mixed models. RESULTS: There were 105 surgical and 197 medical patients. Three distinct biopsychosocial phenotypes were identified among children with DRE: the psychosocial vulnerability phenotype had the poorest psychological and social (family) functioning, the well functioning phenotype had substantially better clinical and psychosocial functioning, and the neurological burden phenotype demonstrated the highest seizure burden and intermediate psychosocial functioning. The most pronounced improvements in child HRQOL, parent emotional functioning, and family functioning over time were observed among those with psychosocial vulnerability, especially after epilepsy surgery. The well functioning and neurological burden phenotypes showed more limited change across most outcomes in both treatment groups. SIGNIFICANCE: Identifying biopsychosocial phenotypes may enhance prediction of child, parent, and family outcomes and identify children and families who could benefit from targeted interventions. Despite experiencing more psychosocial disadvantages, the psychosocial vulnerability phenotype demonstrated the largest improvement in outcomes following surgery, suggesting that surgical treatment has the potential to promote more equitable psychosocial outcomes, alongside clinical and HRQOL outcomes.
Comparative risk of epilepsy with SGLT2 inhibitors versus incretin-based therapies in type 2 diabetes.
Yen FS, Yen YH, Hung YM … +6 more , Wei JC, Sung CY, Huang YH, Tsai FJ, Hwu CM, Hsu CC
Epilepsia · 2026 Jul · PMID 42397685 · Publisher ↗
OBJECTIVE: This study was undertaken to compare the risk of seizures and epilepsy among patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagonlike peptide-1 receptor...
OBJECTIVE: This study was undertaken to compare the risk of seizures and epilepsy among patients with type 2 diabetes (T2D) initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagonlike peptide-1 receptor agonists (GLP-1 RAs), or dipeptidyl peptidase-4 (DPP-4) inhibitors using nationwide real-world data. METHODS: Using propensity score matching, we identified 20 096 matched pairs of SGLT2i and DPP-4 inhibitor users, 8671 matched pairs of SGLT2i and GLP-1 RA users, and 1611 matched pairs of GLP-1 RA and DPP-4 inhibitor users from the Taiwanese National Health Insurance Research Database, spanning January 1, 2000 to December 31, 2021. Cox proportional hazards model was used to compare outcome risks between the respective treatment groups. RESULTS: SGLT2i users had significantly lower cumulative incidences of seizure, epilepsy, and the composite outcome compared to DPP-4 inhibitor users (log-rank p < .001). Adjusted hazard ratios (aHRs) were .49 for seizure, .38 for epilepsy, and .46 for the composite outcome. Compared to GLP-1 RA users, SGLT2i users had a lower risk of the composite outcome (aHR = .66, p = .016), but not individual seizure or epilepsy outcomes. No significant differences were found between GLP-1 RAs and DPP-4 inhibitors. SIGNIFICANCE: In this population-based study, SGLT2i use among patients with T2D was associated with lower risks of seizure and epilepsy compared to DPP-4 inhibitors, and lower composite seizure/epilepsy risk compared to GLP-1 RAs. These findings suggest a potential association between SGLT2i use and a lower risk of seizure- and epilepsy-related outcomes.
Long-term mortality after status epilepticus: A 5-year analysis study.
Alanís-Bernal M, Campos-Fernández D, Abraira L … +8 more , Gómez-Dabó L, Rodrigo-Gisbert M, Quintana M, Lallana S, Fonseca E, López-Maza S, Toledo M, Santamarina E
Epilepsia · 2026 Jul · PMID 42396999 · Publisher ↗
OBJECTIVE: To describe 5-year mortality after status epilepticus (SE) and identify factors associated with long-term survival. We also validated the prognostic performance of the Age, Consciousness, Duration (ACD) score...
OBJECTIVE: To describe 5-year mortality after status epilepticus (SE) and identify factors associated with long-term survival. We also validated the prognostic performance of the Age, Consciousness, Duration (ACD) score and evaluated long-term survival across etiological categories defined by the Lattanzi classification of acute symptomatic SE. METHODS: Retrospective cohort analysis of a prospectively maintained database of consecutive patients ≥16 years of age with confirmed SE admitted to a tertiary epilepsy center (2011-2022). We excluded unclear diagnoses, hypoxic-anoxic etiologies, and incomplete follow-up. We recorded clinical variables and prognostic scores modified Status Epilepticus Severity Score (mSTESS), Epidemiology-based Mortality Status Epilepticus (EMSE), and Age, Consciousness, Duration (ACD). Mortality was assessed at discharge and annually up to 5 years. RESULTS: We included 786 patients (mean age 63.4 years, 43.5% female). Five-year mortality was 50.3%, with 44.0% of deaths occurring within the first 2 years. Neurological causes accounted for 60.8% of deaths, and direct seizure-related causes represented 74.6% of neurological deaths. Independent predictors of higher long-term mortality were older age, higher premorbid mRS, absence of prior seizure history, comorbidity burden, systemic complications, and impaired consciousness during SE; convulsive and focal motor SE were associated with lower mortality risk. mSTESS and EMSE were associated with long-term mortality. In patients with less damaging etiologies, ACD predicted 5-year mortality (hazard ratio [HR] 1.163, 95% confidence interval [CI] 1.063-1.273; area under the curve [AUC] 0.717); ACD ≥10 corresponded to >50% 2-year mortality. Five-year mortality was 61.3% (acute-primary Central Nervous System (CNS) and 58.3% (acute-secondary CNS). SIGNIFICANCE: SE carries substantial long-term mortality, particularly within the first 2 years. Neurological and seizure-related causes were the most frequent. The Lattanzi classification and the ACD score retained long-term prognostic value.
The Epilepsy-Cog study: Methods to establish a harmonized study of late onset epilepsy in a metacohort of six population-based cohorts in the United States.
Choi H, Gutierrez J, Wang T … +33 more , Liu M, Leu CS, Misiewicz S, Han J, Bello N, Biggs ML, Briceño EM, Brickman AM, Burke JF, Chen L, Colantonio LD, Diaz Andino SP, Elkind MSV, Fitzpatrick AL, Corona CG, Gottesman RF, Gross AL, Huang L, Johnson EL, Johnson WC, Levine DA, Longstreth WT, Maia SP, Mayeux RP, Petersen BC, Obalana O, Reyes-Dumeyer D, Rundek T, Sanchez D, Shea SJ, Strobino K, Zhu CW, Thacker EL
Epilepsia · 2026 Jul · PMID 42390300 · Publisher ↗
OBJECTIVE: With the expected demographic shift toward those ≥65 years of age in the United States, late onset epilepsy (LOE) poses a significant public health issue, yet it has been historically understudied. We are unde...
OBJECTIVE: With the expected demographic shift toward those ≥65 years of age in the United States, late onset epilepsy (LOE) poses a significant public health issue, yet it has been historically understudied. We are undertaking an effort in the Epilepsy-Cog study to pool individual participant data from six United States-based prospective cohort studies. In this paper, we outline the process for ascertaining epilepsy, harmonizing, and pooling individual participant data across the six cohorts. METHODS: The Epilepsy-Cog study includes individual participant data from six United States-based longitudinal cohort studies: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Multi-Ethnic Study of Atherosclerosis, Northern Manhattan Study (NOMAS), Reasons for Geographic and Racial Differences in Stroke, and Washington Heights/Inwood Columbia Aging Project. In all cohorts except NOMAS, prevalent and incident epilepsy were ascertained using Medicare claims-based algorithms. In NOMAS, epilepsy cases were identified through cohort-based reporting and medical record review. To perform cross-cohort harmonization of variables, we used the lowest common denominator approach, assigning response categories or value levels in common across all cohorts. RESULTS: From a total of 68 544 participants across six cohorts, 43 753 participants met eligibility criteria for Epilepsy-Cog. Among them, we identified 551 (1.3%) participants with prevalent epilepsy and 1500 (3.4%) participants with incident epilepsy. We have harmonized demographic characteristics, health behaviors, vascular risk factors (VRFs), one genetic variable, medication use, subjective health status measures, incident events, and cause-of-death variables. SIGNIFICANCE: The Epilepsy-Cog pooled cohort of 43 753 participants with and without epilepsy, combined with harmonized demographic, VRF, and event data, offers a unique resource to yield new insights into LOE.
Systematic review and meta-analysis of lifestyle modification interventions and their impact on seizure reduction and quality of life.
Spurgeon E, Ivanuik A, Sodani S … +7 more , Butler E, Martinez D, Schleicher M, Sylvester S, Saper R, Najm I, Lal D
Epilepsia · 2026 Jul · PMID 42390279 · Publisher ↗
OBJECTIVE: This study was undertaken to provide an overview of the research landscape and evaluate the impact of lifestyle modifications on seizure reduction and quality of life in people with epilepsy receiving standard...
OBJECTIVE: This study was undertaken to provide an overview of the research landscape and evaluate the impact of lifestyle modifications on seizure reduction and quality of life in people with epilepsy receiving standard medical treatment. METHODS: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic review of major databases (Medline, Embase, American Psychological Association PsycInfo, Cochrane Library, and Web of Science) through November 2025. After screening 5151 articles, 118 studies met inclusion criteria: prospective trials reporting seizure frequency in adults or mixed populations with epilepsy. Four epilepsy-trained reviewers independently assessed studies. A random-effects meta-analysis was performed on studies reporting ≥50% seizure reduction or data allowing its calculation. Short-term response was defined as the earliest postintervention time point, and long-term response as the final reported time point. RESULTS: The 118 studies covered diet (n = 33), supplements (n = 20), biofeedback (n = 14), psychosocial/behavioral therapy (n = 13), yoga/meditation/mindfulness (n = 8), music therapy (n = 7), and others. Fifty-two (44%) included control groups, whereas 91 (77%) reported statistical analysis of seizure frequency. Among those, 68% showed significant seizure reduction. Quality of life was assessed in 31 studies, 68% reporting improvement. Seventy-one studies (60%) were included in the meta-analysis. Overall, the ≥50% seizure reduction response rate was 44% for short-term outcomes (95% confidence interval [CI] = 38%-50%) and 50% for long-term outcomes (95% CI = 44%-56%). Dietary interventions had the largest evidence base (n = 33), with short- and long-term response rates of 40% and 51%, respectively. Meditation/yoga/mindfulness had the highest response rate (62% short term, 79% long term), whereas exercise and supplements had the lowest (30%-35%). SIGNIFICANCE: Lifestyle modifications may offer beneficial, adjunctive effects on seizure control. However, the current evidence is limited by variability in study design and quality. Larger, well-designed trials with standardized outcomes are needed to clarify how these interventions can complement epilepsy treatment. This systematic review and meta-analysis serves as a foundation for future research to better define the role of lifestyle interventions in epilepsy care.
Vagus nerve stimulation for patients with tuberous sclerosis complex-related drug-resistant epilepsy: A prospective cohort study.
Liu T, Wei Z, Zhou J … +14 more , Zhao R, Kuang S, Xu J, Yan Z, Cao D, Chen B, Peng J, Lin J, Meng Y, Peng Y, Wang L, Wang X, Zhai F, Liang S
Epilepsia · 2026 Jul · PMID 42390215 · Publisher ↗
OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with a high prevalence of drug-resistant epilepsy (DRE), significantly affecting patients' quality of life. For patients with TSC lacking loca...
OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic multisystem disorder with a high prevalence of drug-resistant epilepsy (DRE), significantly affecting patients' quality of life. For patients with TSC lacking localizing epileptogenic tuber, resective surgery is often not feasible. Vagus nerve stimulation (VNS) has been proposed as an alternative surgical therapy, although robust evidence in TSC-related DRE remains limited. METHODS: A prospective cohort study was conducted between December 2019 and July 2024 across multiple epilepsy centers in China. Seventy patients with TSC-related DRE were enrolled, all lacking resectable epileptogenic tubers on multidisciplinary evaluation and ineligible for resective surgery. Participants were divided into VNS (n = 20) and medication-only (n = 50) groups based on actual treatment, and followed for up to 3 years. Seizure outcomes, anti-seizure medication use, IQ, and quality of life were evaluated longitudinally. RESULTS: The VNS group demonstrated significantly higher response rates at 1-, 2-, and 3-year follow-ups (65%-75%) compared to the medical treatment group (31%-36%). Median and average seizure frequency reductions were also greater in the VNS group. VNS was associated with significantly higher treatment response than medication, with the relative risk (RR) of response being 1.81 (95% confidence interval [CI]: 1.22-2.67), 2.21 (95% CI: 1.42-3.44), and 2.42 (95% CI: 1.49-3.93) at 1-, 2-, and 3-year follow-ups (p < 0.01). Seizure recurrence was significantly lower in the VNS group (p < 0.01). Moreover, VNS treatment led to significant reductions in anti-seizure medication (ASM) use and improvement in intelligence quotient and quality of life at the 2-year follow-up. Treatment modality was the only independent predictor of clinical response. VNS was well tolerated, with only mild surgical complications and no permanent adverse events reported. SIGNIFICANCE: VNS significantly improves seizure control, cognitive outcomes, and quality of life, with a favorable safety profile. These findings support VNS as an effective and safe alternative for this specific TSC population. Future randomized controlled trials are warranted to further validate these results.
Semiology of functional/dissociative seizures in idiopathic generalized epilepsy: An inpatient video-electroencephalographic study.
Peña-Ceballos J, Radhakrishna K, Choekyi T … +11 more , O'Keeffe C, Ali M, O'Donnell A, Munteanu T, Moloney PB, El Naggar H, Mullins G, Widdess-Walsh P, Kilbride RD, Delanty N, McNicholas N
Epilepsia · 2026 Jun · PMID 42377999 · Publisher ↗
OBJECTIVE: This study was undertaken to estimate the prevalence and characterize the semiology of co-occurring functional/dissociative seizures (FDSs) and identify clinical features potentially associated with the develo...
OBJECTIVE: This study was undertaken to estimate the prevalence and characterize the semiology of co-occurring functional/dissociative seizures (FDSs) and identify clinical features potentially associated with the development of video-electroencephalography (video-EEG)-diagnosed FDSs in patients with idiopathic generalized epilepsy (IGE). METHODS: In this retrospective single-center inpatient video-EEG study, we characterized clinical features of FDSs recorded in patients with IGE aged ≥16 years admitted into our epilepsy monitoring unit between January 2008 and December 2024. We compared clinical characteristics of IGE patients with FDSs to an IGE cohort without FDSs. FDSs were classified as akinetic nonmotor, subjective nonmotor, motor, or mixed FDSs. RESULTS: Among 123 patients with IGE, 29 (23.5%) had co-occurring documented FDSs recorded on video-EEG. Twenty-eight (96.5%) were females. Median age at admission was 25 years (interquartile range [IQR] = 14). The median length of admission was 5 days (IQR = 3). Twenty-eight patients (96.5%) had generalized interictal discharges, emerging on the first day of admission in 24 of 28 (85.7%). Epileptic seizures were also captured in 13 patients (44.8%). Twenty-four patients (82.7%) had multiple FDSs episodes, whereas 19 (65.5%) presented with a single FDSs subtype. Subjective FDSs was the most common subtype (17/29, 58.6%), followed by pure motor (6/29, 20.7%), mixed motor-akinetic (6/29, 20.7%), pure akinetic (5/29, 17.2%), mixed akinetic-subjective (4/29, 13.8%), and mixed motor-subjective (1/29, 3.4%). Among the clinical variables analyzed, female sex was associated with co-occurring FDSs, although this association did not remain significant after Bonferroni correction. SIGNIFICANCE: Approximately one quarter of patients with IGE who underwent video-EEG had co-occurring FDSs. Almost half had epileptic seizures during the same admission. Video-EEG referral should be considered in patients with suspected drug-resistant IGE with active seizures or if there is a clinical suspicion of FDSs.
Perineuronal net abnormalities in epileptic human tissue.
De Santis D, Cagnoli C, Biancheri D … +8 more , Pastori C, Medici V, Calatozzolo C, Poloni TE, Tassi L, de Curtis M, Garbelli R, Rossini L
Epilepsia · 2026 Jun · PMID 42377317 · Publisher ↗
OBJECTIVE: The extracellular matrix (ECM) performs several functions during development and in mature nervous tissue plasticity; ECM concentrates in lattice-like envelopes called perineuronal nets (PNNs), which surround...
OBJECTIVE: The extracellular matrix (ECM) performs several functions during development and in mature nervous tissue plasticity; ECM concentrates in lattice-like envelopes called perineuronal nets (PNNs), which surround the cell bodies and proximal dendrites, mainly of parvalbumin (PV) γ-aminobutyric acidergic interneurons. PNNs are proposed to serve synaptic plasticity regulation, synapse stabilization, and neuron protection, by forming a physical barrier from potentially damaging neurochemical stimuli. We analyzed aggrecan expression, a major component of adult PNNs, in human specimens obtained from epilepsy surgery. METHODS: Postsurgical tissues were obtained from 20 patients with drug-resistant epilepsy: six cases with no histological alterations (cryptogenic epilepsy) and 14 patients showing type IIa and IIb focal cortical dysplasia (FCDII). For comparison, cortices from three autoptic controls with short postmortem delay were analyzed. Immunohistochemistry, confocal microscopy, and RNAscope technique were applied. RESULTS: Control autoptic cases showed high aggrecan expression in the cortex, with a clear decreasing expression gradient from occipital to frontal and temporal areas. This expression gradient was lost in cryptogenic cases, which showed severe aggrecan loss, with residual immunoreactive arrangements mainly around PV interneurons. In FCDII, altered immunolabeling was evident in the core of the dysplastic lesion, and PNNs were identified around both PV interneurons and dysmorphic neurons (DNs) presenting abnormal vGLUT1 and vGAT perisomatic basket formations. Diffuse weak staining of the white matter without PNNs was also found in FCDII. As for cryptogenic cases, FCDII perilesional cortex showed a marked aggrecan staining loss. RNAscope findings confirmed that aggrecans are produced by FCDII pathological neurons, such as DNs. SIGNIFICANCE: These data support the notion that etiology-specific PNN remodeling is part of the epileptogenic process. FCDII tissues show altered PNN expression in DNs suggestive of a pathogenic role within the FCD lesion, and the disappearance of histochemical PNN labeling in cryptogenic and FCDII perilesional area suggests a possible role mediated by seizure activity.
Cortical stimulation reveals effective disconnection of the epileptogenic network at seizure onset.
Davis P, B Tomlinson S, Armstrong C … +7 more , Conrad EC, Ojemann WKS, Peters J, Litt B, Gilman C, Kennedy BC, Marsh ED
Epilepsia · 2026 Jun · PMID 42377316 · Publisher ↗
OBJECTIVE: Seizure onset, the transition from interictal to ictal network states, remains poorly understood despite decades of research. To date, most analyses of seizure onset rely on descriptors of passively recorded n...
OBJECTIVE: Seizure onset, the transition from interictal to ictal network states, remains poorly understood despite decades of research. To date, most analyses of seizure onset rely on descriptors of passively recorded network variables such as spectral features or functional connectivity. However, direct causal analysis of brain network dynamics across the ictal transition have yet to be systematically studied. We therefore sought to characterize the ictal transition using active network probing via corticocortical evoked potentials (CCEPs) generated by direct cortical stimulation. METHODS: We analyzed a unique dataset of pediatric and adult epilepsy patients in whom electroclinical seizures were triggered by low-frequency (<2 Hz) direct cortical stimulation. CCEP amplitudes were quantified preceding, during, and following seizure onset, comparing responses within versus outside the spontaneous seizure onset zone (SOZ) across anatomic locations and seizure onset patterns. RESULTS: Seizure onset was characterized by a rapid, dramatic reduction of CCEP amplitudes within the SOZ. CCEPs were relatively preserved at sites outside the SOZ, indicating preferential loss of incoming, rather than outgoing, responses to the SOZ, a phenomenon we term "effective disconnection." This effect was independent of SOZ anatomic location but was preferentially associated with a low-voltage fast activity seizure onset pattern on exploratory analysis. In a subset of patients, CCEPs returned during seizure evolution after the fast activity phase, at times with reversal of response polarity. SIGNIFICANCE: These findings provide a novel characterization of the ictal transition based on the sensitivity of the seizure-generating network to external perturbation and provide a framework for causal network interrogation during seizure onset and early evolution. The described pattern of effective disconnection indicates preferential loss of incoming connectivity to the SOZ at seizure onset. We propose an integrative, hypothesis-generating model linking local inhibitory dynamics and network connectivity at seizure onset and demonstrate the utility of peri-ictal cortical stimulation as a tool for interrogating epilepsy networks.
Anterior cingulate cortex neuron subtypes differentially regulate seizures.
Yan Z, Tang T, Wang K … +10 more , Fu B, Li Z, Liu M, Huang H, Yang Y, Zheng Q, Zheng Y, Shan Y, Luo Y, Zhao G
Epilepsia · 2026 Jun · PMID 42377056 · Publisher ↗
OBJECTIVE: This study aimed to investigate the regulatory roles of distinct neuronal subtypes within the anterior cingulate cortex (ACC) in acute seizures and to identify cell type-specific mechanisms underlying seizure...
OBJECTIVE: This study aimed to investigate the regulatory roles of distinct neuronal subtypes within the anterior cingulate cortex (ACC) in acute seizures and to identify cell type-specific mechanisms underlying seizure modulation in this region. METHODS: Acute seizure models were established in mice via pentylenetetrazol injection. In vivo fiber photometry and miniscope calcium imaging were employed to monitor neuronal calcium activity, and multichannel electroencephalography was used to record brain electrical signals simultaneously. Subsequently, bidirectional chemogenetic and optogenetic manipulations were performed on calcium/calmodulin-dependent protein kinase II (CaMKII) excitatory neurons and vesicular γ-aminobutyric acid (GABA) transporter (vGAT)-expressing GABAergic interneurons, as well as parvalbumin (PV) and somatostatin (SST) interneuron subpopulations. RESULTS: Calcium recordings demonstrated that both excitatory and inhibitory neurons in the ACC exhibited significant, temporally coordinated hyperactivity during acute seizures. Inhibition of CaMKII neurons significantly reduced seizure severity, whereas their activation induced spontaneous seizurelike activity. Enhancing GABAergic interneuron activity significantly decreased seizure frequency and severity. Notably, inhibition of GABAergic interneurons resulted in markedly more severe seizures. Further examination of interneuron subtypes revealed functional heterogeneity; activation of SST interneurons effectively suppressed seizures, whereas PV activation did not produce significant antiseizure effects. Critically, inhibition of either PV or SST interneurons triggered spontaneous seizurelike activity, indicating that both subtypes are necessary for maintaining network stability. SIGNIFICANCE: This study elucidates the differential roles of ACC neuronal populations in acute seizure dynamics. Activating GABAergic interneurons or inhibiting CaMKII-positive neurons effectively suppresses seizure activity. Among interneuron subtypes, SST activation reduces seizures, whereas PV activation does not. However, inhibiting either subtype triggers spontaneous epileptiform activity, indicating both are indispensable and play complementary roles in maintaining network homeostasis. These findings reveal the microcircuit mechanisms by which the ACC modulates acute seizures, highlighting that cortical stability relies on both the classical excitation-inhibition balance and the cooperative interplay of multiple interneuron subtypes.
Ultrafast oscillations in the human brain and their functional significance.
Brázdil M, Trávníček V, Curot J … +11 more , Pail M, Służewska-Niedźwiedź M, Roman R, Plešinger F, Barbeau E, Kucewicz M, Klimeš P, Cimbálník J, Jurák P, Stacey WC, Worrell GA
Epilepsia · 2026 Jun · PMID 42363785 · Publisher ↗
OBJECTIVE: The upper frequency limit of human brain activity remains unknown. Using ultrahigh sampling rate (≥20 kHz) intracranial microelectroencephalography, this study aimed to systematically explore and quantitativel...
OBJECTIVE: The upper frequency limit of human brain activity remains unknown. Using ultrahigh sampling rate (≥20 kHz) intracranial microelectroencephalography, this study aimed to systematically explore and quantitatively characterize brain field oscillations beyond the established high-frequency oscillation range (>2 kHz), and to determine their relationship to epileptogenic tissue. METHODS: We analyzed intracranial electroencephalographic recordings from 15 patients with drug-resistant epilepsy, comprising 466 microcontacts and 434 macrocontacts implanted in mesiotemporal structures across four international epilepsy centers. A custom spectrogram-based detector optimized for ultrahigh frequencies was developed to identify ultrafast oscillations (UFOs; >2 kHz). UFO rates were assessed in epileptic (successfully resected) and nonepileptic hippocampi and compared with established electrophysiological biomarkers, including interictal epileptiform discharges, ripples, and fast ripples. Statistical comparisons were performed using mixed-effects models to account for intersubject and interelectrode variability. RESULTS: We identified a previously undescribed class of short-duration oscillatory events spanning 2-8 kHz. UFOs occurred at significantly higher rates in epileptic compared with nonepileptic mesiotemporal regions, with the strongest differentiation observed in the 2-3-kHz band. Two distinct UFO phenotypes were consistently observed: (1) spindlelike, narrow-band oscillations and (2) sharp-onset, rapidly decaying bursts. Both forms were prevalent within epileptic hippocampi but were exceedingly rare in nonepileptic structures. UFOs exhibited pronounced temporal intermittency and spatial focality and frequently arose independently of ripples, fast ripples, and very high-frequency oscillations, indicating that they represent a distinct electrophysiological phenomenon. Macrocontacts detected UFOs only exceptionally, highlighting the necessity of microelectrode recordings to capture activity in this ultrahigh-frequency regime. SIGNIFICANCE: These findings substantially extend the known frequency range of human brain field activity and identify ultrafast oscillations as a novel biomarker of neuronal hyperexcitability. UFOs likely reflect pathological microcircuit dynamics inaccessible to conventional clinical recordings and provide new insights into the organization and pathophysiology of epileptogenic networks.
Magnetoencephalographic source imaging improves localization of the epileptogenic zone in multimodal imaging evaluation.
Bouet R, Hermier M, Ostrowsky-Coste K … +8 more , Daligault S, Bouvard S, Catenoix H, Montavont A, Boulogne S, Mauguière F, Rheims S, Jung J
Epilepsia · 2026 Jun · PMID 42360308 · Publisher ↗
OBJECTIVE: To assess the added diagnostic value of magnetoencephalographic source imaging (MSI) beyond conventional magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) in locali...
OBJECTIVE: To assess the added diagnostic value of magnetoencephalographic source imaging (MSI) beyond conventional magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET) in localizing the epileptogenic zone, with stereo-electroencephalography (SEEG) and surgical resection serving as reference standards. METHODS: Among 101 patients prospectively enrolled with drug-resistant focal epilepsy in the EPIMAGE study to assess the diagnostic yield of non-invasive multimodal imaging (MSI, MRI, FDG-PET), those undergoing SEEG and/or surgery were analyzed to compare imaging with SEEG seizure-onset zone (SOZ) or resection zone. We employed binomial generalized linear mixed models (GLMMs) to evaluate the detection accuracy of MRI, PET, and MSI, individually and in combination, for identifying the SEEG-defined SOZ and resection zones. We further assessed the spatial concordance between imaging abnormalities and these reference standards. RESULTS: Using SEEG as reference, MSI identified additional SOZ regions beyond MRI in 55.6% of patients, beyond PET in 29.6%, and beyond combined MRI + PET in 33.3%. When the resection zone served as reference, MSI added new localizing value beyond MRI in 55.6% of patients, beyond PET in 29.6%, and beyond MRI + PET in 33.3%. GLMM analysis revealed that bimodal combinations improved detection rates (MRI + PET: 73.7%; MRI + MSI: 81.3%; PET+MSI: 79.8%). The trimodal combination (MRI + PET+MSI) achieved the highest detection probability at 85.3%, significantly higher than MRI, PET, or MSI alone (p = .003, p = .008, and p = .008, respectively). MSI significantly enhanced SOZ detection when added to either MRI (p = .01) or PET (p = .05). SIGNIFICANCE: MSI adds significant localizing value to the presurgical workup of focal epilepsy by expanding the detection of the epileptogenic network beyond the limits of structural MRI and metabolic PET. The primary clinical benefit of MSI lies in its ability to identify additional seizure-onset regions in complex cases, without increasing false-positive localizations. These findings demonstrate that a multimodal approach incorporating MSI optimizes surgical planning by increasing the probability of capturing the full extent of the epileptogenic zone.
Intermittent fasting with medium-chain triglycerides in drug-resistant epilepsy: A pilot crossover trial.
Hahn W, Falk E, Balzter A … +9 more , Foer T, Maierhofer S, Jaumann S, Strehlau S, Möller L, Tsalouchidou PE, Menzler K, Timmermann L, Knake S
Epilepsia · 2026 Jun · PMID 42360174 · Publisher ↗
OBJECTIVE: Ketogenic dietary therapies can reduce seizure frequency in drug-resistant epilepsy, but adherence to the classical ketogenic diet is often poor. Intermittent fasting supplemented with medium-chain triglycerid...
OBJECTIVE: Ketogenic dietary therapies can reduce seizure frequency in drug-resistant epilepsy, but adherence to the classical ketogenic diet is often poor. Intermittent fasting supplemented with medium-chain triglycerides (MCTs) may offer a more feasible and less restrictive alternative. We assessed whether 16:8 intermittent fasting with exogenous MCT supplementation improves seizure outcomes in adults with drug-resistant epilepsy. METHODS: This prospective, single-center, two-period crossover pilot trial included adults (≥18 years) with drug-resistant epilepsy and at least three seizures per month during the initial 4-week baseline period. Participants completed two, 12-week intervention periods-(1) 16:8 intermittent fasting plus MCT supplementation (IF-MCT) and (2) 16:8 intermittent fasting alone (IF)-separated by a 4-week washout period. Participants were allocated 1:1 to the initial sequence using deterministic alternating allocation. The primary endpoint was seizure frequency during IF-MCT compared with IF and standard therapy during the baseline period. The trial was registered with ClinicalTrials.gov (NCT06013761). RESULTS: Of 36 enrolled participants, 22 completed both intervention periods with evaluable seizure diary data and were included in per-protocol analyses. During IF-MCT, two participants (9%) achieved sustained seizure freedom. In post hoc analyses, the proportion of participants achieving earlier ≥50% seizure reduction was numerically higher during IF-MCT than during IF (Breslow: p = .233), although not statistically significant. Concentrations of ketone bodies and octanoic and decanoic acids increased during IF-MCT, without an apparent correlation with seizure reduction. SIGNIFICANCE: In this exploratory crossover pilot trial, intermittent fasting combined with MCT supplementation was associated with a numerical, although not statistically significant, reduction in seizure frequency compared with intermittent fasting alone in adults with drug-resistant epilepsy. Although the study was not powered to detect definitive differences, the observed trend suggests a potential signal of efficacy. As one of the first studies to evaluate this combined dietary approach using a crossover design, the results support further investigation in larger, adequately powered multicenter efficacy trials.
Exploring the relationship between everyday functioning and cognitive performance in individuals with late onset unexplained epilepsy.
Abi Chakra N, Hankerson A, Marshall GA … +1 more , Sarkis RA
Epilepsia · 2026 Jun · PMID 42360158 · Publisher ↗
OBJECTIVE: Late onset unexplained epilepsy (LOUE) is linked to cognitive and functional decline, yet determinants of functional impairment are not well defined. We evaluated the Functional Activities Questionnaire (FAQ)...
OBJECTIVE: Late onset unexplained epilepsy (LOUE) is linked to cognitive and functional decline, yet determinants of functional impairment are not well defined. We evaluated the Functional Activities Questionnaire (FAQ) in LOUE and examined its association with cognitive and epilepsy-related factors. METHODS: This cross-sectional study included adults with unexplained seizure onset after age 55 years, nonlesional magnetic resonance imaging, seizure onset within 5 years, and stable antiseizure medication (ASM) use. Study partners completed the FAQ; scores ≥ 6 indicated functional impairment. A delayed verbal recall composite was calculated and standardized using Harvard Aging Brain Study norms. Firth penalized logistic regression identified predictors of functional impairment. RESULTS: Among 82 participants, 12.2% were functionally impaired. Demographic characteristics were similar between groups. Impaired participants showed significantly worse cognitive performance, greater ASM use, higher rates of drug-resistant epilepsy, longer epilepsy duration, and more frequent focal impaired consciousness and generalized tonic-clonic seizures, with memory-related tasks most affected. A higher ASM number (odds ratio [OR] = 2.74, 95% confidence interval [CI] = 1.31-6.74) and a lower delayed verbal recall z-score (OR = .37, 95% CI = .14-.69) were associated with increased odds of functional impairment. SIGNIFICANCE: Functional impairment in LOUE is associated with poorer cognition and greater ASM burden. The FAQ may serve as a practical screening tool to assess functional impairment. Our study emphasizes the importance of minimizing medication burden in this population.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe