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PubMed2024

Bidirectional association between abnormal cardiac conditions and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies have consistently indicated a significant correlation between abnormal cardiac conditions and epilepsy. However, the association and direction of this relationship remain a subject of debate. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to investigate the association between abnormal cardiac conditions and epilepsy. METHODS: Instrumental variables, represented by single nucleotide polymorphisms (SNPs) associated with epilepsy and various abnormal cardiac conditions, were derived from large-scale genome-wide association studies databases, including FinnGen and UK Biobank. Bidirectional MR analysis was conducted to estimate the association between epilepsy and abnormal cardiac conditions. Sensitivity analyses were performed using MR-Egger, weighted median, Inverse Variance Weighted, and MR pleiotropy residual sum and outlier methods. RESULTS: The forward MR analysis suggested a potential positive effect of atrial fibrillation and flutter (AF) and valvular heart diseases (VHD) on the risk of epilepsy. Conversely, the reverse MR analysis indicated that epilepsy might increase the susceptibility to AF, VHD, and heart failure. CONCLUSION: The findings support a bidirectional relationship between AF, VHD, and epilepsy, indicating that AF and VHD can elevate the risk of developing epilepsy, while epilepsy, in turn, can also increase the risk of developing AF and VHD. Furthermore, the study suggest that epilepsy may contribute to the development of heart failure. These results underscore the importance of screening for cardiac abnormalities in patients with epilepsy and vice versa, to better understand their clinical significance and potential as modifiable risk factors.

Humans↗

PubMed2024

Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study.

BACKGROUND: Neuroinflammation plays an important pathophysiological role in epilepsy; however, the precise connection between immune cells and epilepsy remains unclear. This study used Mendelian randomization (MR) to analyze the causal relationship between 731 immune cell traits and epilepsy. METHODS: Based on data from a genome-wide association study (GWAS), a bidirectional two-sample MR analysis was conducted to investigate the potential influence of immune cell phenotypes on epilepsy. Five MR methods were used to analyze the results, with the inverse variance weighted (IVW) method as the primary method, and the results were corrected using the false discovery rate (FDR) method. Sensitivity analyses were performed to test for heterogeneity and horizontal pleiotropy. RESULTS: After correction for FDR, four immune traits remained significantly associated with epilepsy risk: CD25 expression on memory (OR = 1.04, 95 % CI = 1.02 ∼ 1.06,P = 2.55 × 10-4), IgD+CD38dim (OR = 1.05, 95 % CI = 1.02 ∼ 1.08, P = 4.73 × 10-4), CD24+CD27+ (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 4.82 × 10-4), and IgD-CD38dim (OR = 1.04, 95 % CI = 1.02 ∼ 1.06, P = 1.04 × 10-3) B cells. The risk of generalized epilepsy was significantly associated with two immune cell traits, whereas that of focal epilepsy was significantly associated with seven immune cell traits. Furthermore, immune cell phenotypes are not affected by genetically predicted epilepsy. CONCLUSION: This MR study affirms the causal connection between circulating immune cells and epilepsy, offering guidance for further understanding of the immune mechanisms that underlie epilepsy and the discovery of novel targets for therapy.

Humans↗

PubMed2024

Dissecting the association between blood pressure traits, hypertension, antihypertensive medications and epilepsy: A Mendelian randomization study.

BACKGROUND: Observational studies suggest that hypertension and epilepsy have a high co-occurrence, and antihypertensive medications may have impacts on the prevention and treatment of epilepsy. However, the directionality of causation between them is elusive. METHOD: By leveraging genome-wide association studies (GWAS) summary data of each trait, we firstly performed bidirectional univariate Mendelian randomization (UVMR) to assess the strength and direction of the associations between pairs of traits, then multivariate MR (MVMR) was conducted to adjust for potential confounders in causalities. Cochran's Q statistics, leave-one-out analysis, MR-Egger regression and MR-Pleiotropy Residual Sum and Outlier methods (MR-PRESSO) were employed to evaluate the robustness of the results. Drug target MR was proceeded to assess the association between five classes of first-line antihypertensive medications and epilepsy. Specifically, single nucleotide polymorphisms (SNPs) extracted from GWAS data on systolic blood pressure (SBP)/diastolic blood pressure (DBP), along with expression quantitative trait loci (eQTL) were utilized as proxies for antihypertensive medications, respectively. RESULTS: Forward UVMR results provided evidence that genetically predicted blood pressure traits and hypertension have causal effects on epilepsy, while reverse UVMR indicated no causal impacts of epilepsy on blood pressure traits or hypertension. The sensitivity analysis results were robust. The causalities between DBP, hypertension and epilepsy remained remarkable after adjustment by MVMR. Inverse-variance-weighted MR (IVW-MR) yielded evidence of positive association only between Beta-Blockers target genes based on DBP GWAS screening and epilepsy. Summary-data-based MR (SMR) identified a positive correlation between Beta-Blockers target gene ADRA1D and epilepsy risk. CONCLUSIONS: Hypertension has a causal effect on epilepsy and managing DBP in patients with hypertension through Beta-Blockers may help prevent epilepsy.

Humans↗

PubMed2026

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41 ± 0.24 vs. 2.35 ± 0.06, P < 0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans↗

PubMed2024

Relationship between inflammation/immunity and epilepsy: A multi-omics mendelian randomization study integrating GWAS, eQTL, and mQTL data.

OBJECTIVES: Increasing evidence suggests that activated innate/adaptive immunity induces an inflammatory response, thereby participating in epileptogenesis. However, the biological explanation of inflammation/immunity as a potential cause for epilepsy remains largely unknown. This research aimed to determine the causal effects of inflammation/immune-related genes in epilepsy based on multi-omics mendelian randomization (MR). METHODS: We employed summary-data-based MR (SMR) approach to combine GWAS for epilepsy (12,891 cases and 312,803 control) with gene expression quantitative trait loci (cis-eQTL, 31,684 participants) and DNA methylation QTL (cis-mQTL, 1,980 participants) data. Five additional MR methods were then used for sensitivity analyses to confirm the reliability of causal associations. In addition, enrichment analysis of key genes was conducted to provide insight into the biological functions of epilepsy risk variants. RESULTS: A total of 386 inflammation/immune-related genes were selected for further analyses. Primary SMR analysis indicated that 37 DNA methylation sites and six genes regulated by them had potential causal relationship with epilepsy. MR analysis further refined the results, identifying three genes that had a causal effect on epilepsy. Notably, VEGFA (OR: 0.925; 95 % CI: 0.862-0.994) expression was negatively correlated with epilepsy risk, whereas IL16 (OR: 1.076; 95 % CI: 1.028-1.126) and HLA-DPA1 (OR: 1.041; 95 % CI: 1.009-1.074) expressions were positively associated with epilepsy risk. Functional enrichment analysis revealed that the identified genes were involved in GO-BP terms related to VEGF activation signaling and chemotaxis regulation. CONCLUSION: This analysis confirms the causal role of inflammation/immunity in epilepsy, and the identified candidate genes provide clues for drug development in clinical practice.

Humans↗

PubMed2026

Genetic testing practices across European epilepsy centers: An ERN EpiCARE survey.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. SIGNIFICANCE: 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. PLAIN LANGUAGE SUMMARY: 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 people living with epilepsy.

European reference networks↗

PubMed2024

Association between Branched-Chain amino acids and Epilepsy: A Mendelian randomized study.

BACKGROUND: Branched-chain amino acids (BCAAs) have been affected epilepsy, yet conclusions remain inconclusive, lacking causal evidence regarding whether BCAAs affect epilepsy. Systematic exploration of the causal relationship between BCAAs and epilepsy could hand out new ideas for the treatment of epilepsy. METHODS: Utilizing bidirectional Mendelian randomization (MR) study, we investigated the causal relationship between BCAA levels and epilepsy. BCAA levels from genome-wide association studies (GWAS), including total BCAAs, leucine levels, isoleucine levels, and valine levels, were employed. Causal relationships were explored applying the method of inverse variance-weighted (IVW) and MR-Egger, followed by sensitivity analyses of the results to evaluate heterogeneity and pleiotropy. RESULTS: Through strict genetic variant selection, we find some related SNPs, total BCAA levels (9), leucine levels (11), isoleucine levels (7), and valine levels (6) as instrumental variables for our MR analysis. Following IVW and sensitivity analysis, total BCAAs levels (OR = 1.14, 95 % CI = 1.019 ∼ 1.285, P = 0.022) and leucine levels (OR = 1.15, 95 % CI = 1.018 ∼ 1.304, P = 0.025) had significant correlation with epilepsy. CONCLUSIONS: There exists a causal relationship between the levels of total BCAAs and leucine with epilepsy, offering the new ideas into epilepsy potential mechanisms, holding significant implications for its prevention and treatment.

Humans↗

PubMed2025

Causal relationship between white matter structural connectivity and epilepsy.

White matter structural connectivity has recently been linked to epilepsy pathogenesis, yet its causal role remains unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between white matter structural connectivity and epilepsy. GWAS summary statistics for white matter structural connectivity were sourced from the UK Biobank, while epilepsy data were obtained from FinnGen R10 and the International League Against Epilepsy (ILAE). Our MR analysis revealed significant causal links between white matter structural connectivity and epilepsy risk. Increased connectivity between the right hemisphere visual and salience/ventral attention networks (RH Vis to RH Sal/VentAttn WMSC) was associated with higher epilepsy risk in FinnGen_R10_FE_STRICT (OR = 2.25, 95 % CI = 1.43-3.56, p < 0.01, FDR P = 0.019). Conversely, increased connectivity between left and right hemisphere salience/ventral attention networks (LH Sal/VentAttn to RH Sal/VentAttn WMSC) was linked to reduced epilepsy risk in FinnGen_R10_GE_STRICT (OR = 0.17, 95 % CI = 0.07-0.46, p < 0.01, FDR P = 0.033). A total of 15 nominally significant associations were identified across datasets. These findings suggest a causal relationship between white matter structural connectivity and epilepsy, offering insights into disease mechanisms and potential therapeutic targets.

Humans↗

PubMed2024

Genetic association between epilepsy and gliomas: Insights from Mendelian randomization and single-cell transcriptomic analyses.

BACKGROUND: Seizures are prevalent in glioma patients, especially in those with low-grade gliomas. The interaction between gliomas and epilepsy involves complex biological mechanisms that are not fully understood. METHODS: We collected Genome-Wide Association Study data for epilepsy and gliomas, performed differential expression analysis, and conducted Gene Ontology (GO) enrichment analysis on the identified genes. Single-cell RNA sequencing data (scRNA-seq) from GSE221534 dataset in Gene Expression Omnibus (GEO) were used to analyze cell-cell interactions within glioma samples from patients with and without epilepsy. RESULTS: Mendelian Randomization (MR) analysis revealed significant associations between genetic variants related to epilepsy and glioma risk, suggesting a potential causal relationship, especially in astrocytomas. Differential expression analysis identified epilepsy-related genes that were significantly upregulated in astrocytoma tissues compared to normal brain tissues. GO enrichment analysis indicated that these genes are involved in critical biological processes such as neurogenesis and cellular signaling. The scRNA-seq analysis showed, compared to non-epileptic samples, glioma stem cells, microglia, and NK cells are increased in the core regions of astrocytomas in epileptic patients. Additionally, intercellular communication between tumor cells and other non-tumor cells is markedly enhanced in astrocytoma samples from epileptic patients. CONCLUSION: This study provides evidence of a genetic association between epilepsy and gliomas and elucidates the biological mechanisms through which epilepsy may influence glioma progression.

Humans↗

PubMed2026

Epilepsy: Bridging Epidemiological Landscapes, Molecular Mechanisms, and Emerging Precision Therapeutics.

Epilepsy ranks among the most prevalent neurological disorders worldwide, and recent years have witnessed significant advancements in understanding its epidemiological features, pathophysiological mechanisms, diagnostic methodologies, and therapeutic approaches. This review systematically examines the epidemiology of epilepsy, highlighting pronounced regional and population-based disparities, particularly the substantial treatment gap observed in low-income countries. Regarding pathogenesis, epilepsy development involves aberrant ion channel function, neuroinflammatory processes, dysregulation of the mTOR signaling pathway, and genetic predispositions. Diagnostic innovations, including ultra-high field magnetic resonance imaging, artificial intelligence-enhanced electroencephalogram analysis, and liquid biopsy techniques, have markedly enhanced the precision of epileptogenic focus localization and etiological identification. Genetic investigations have uncovered numerous epilepsy-associated genes, thereby underpinning the advancement of targeted therapies. Therapeutically, novel antiepileptic drugs, neuromodulation modalities such as vagus nerve stimulation and deep brain stimulation, alongside gene therapy, have expanded treatment options for refractory epilepsy. Nonetheless, global epilepsy management continues to confront challenges including limited drug accessibility, social stigma, and pharmacoresistance. The future trajectory emphasizes individualized and precision medicine approaches, integrating genomics, biomarker discovery, and intelligent monitoring technologies to foster comprehensive improvements in epilepsy diagnosis and treatment.

epidemiology↗

PubMed2026

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid α-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient ≤66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score ≥7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article↗

PubMed2026

A next-generation sequencing-based pharmacogenetic study of ABCB1, ABCC1, and ABCC2 variants associated with antiseizure medication response in Turkish epilepsy patients.

OBJECTIVES: Epilepsy is a chronic neurological disorder characterized by a tendency to have recurrent seizures due to abnormal and excessive neuronal activity in the brain. Genetic variants in adenosine triphosphate (ATP)-binding cassette (ABC) transporter genes, including ABCB1, ABCC1, and ABCC2, may contribute to pharmacoresistance in epilepsy by altering the transport of anti-seizure medications (ASMs) across the blood-brain barrier (BBB). This study aims to explore genetic polymorphisms in the ABCB1, ABCC1, and ABCC2 genes in Turkish epilepsy patients and to assess their impact on responsiveness to ASMs. METHODS: Targeted next-generation sequencing was used for molecular genotyping of the ABCB1, ABCC1, and ABCC2 genes in genomic DNA from 35 patients. RESULTS: A total of nine common variants were analyzed in ABCB1 (rs2032582, rs1045642, rs1128503), ABCC1 (rs35626, rs212087, rs246221), and ABCC2 (rs717620, rs22773697, rs3740066). A statistically significant association was found between ABCB1 rs2032582:T>G and ASMs response in the recessive model (TT + TG vs. GG, p = 0.018, OR = 13.13; 95% CI: 1.69-160.1; Benjamini-Hochberg (BH) FDR-adjusted q = 0.09), with the TT + TG genotypes being more frequent among drug-responsive patients. Haplotype analysis showed that only the ABCB1 rs2032582 G allele was significantly more frequent in drug-persistent patients compared with drug-responsive patients (χ2 = 3.916, p = 0.047). However, none of these associations remained statistically significant after false discovery rate (FDR) correction, and all findings should therefore be interpreted as exploratory. SIGNIFICANCE: The findings suggest that the ABCB1 rs2032582:T>G polymorphism may be associated with variability in treatment response among Turkish epilepsy patients. These results emphasize the potential involvement of ABC transporter-mediated drug efflux mechanisms in impacting the effectiveness of ASMs.

ABCB1↗

PubMed2026

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE↗

PubMed2026

Integrating rare and common variation in epilepsy genetics: from genetic architecture to penetrance and clinical expressivity.

Epilepsy genetics has often been interpreted through a useful but simplified dichotomous framework in which severe epilepsies, particularly developmental and epileptic encephalopathies, are attributed mainly to rare, high-effect variants, whereas more common epilepsies are viewed as arising largely from the cumulative effects of common, small-effect variation. Although this framework has been instrumental for gene discovery, molecular diagnosis, and mechanism-based treatment, it does not fully explain incomplete penetrance, intrafamilial phenotypic heterogeneity, or marked differences in severity among individuals sharing the same molecular diagnosis. Evidence from exome sequencing, copy number variant (CNV) studies, and genome-wide association studies increasingly suggests that rare SNVs/indels, CNVs, and common variant should not be interpreted as entirely independent risk sources, but may partially converge on shared genes, pathways, cell types, and neurobiological processes relevant to neuronal excitability, network stability, and seizure susceptibility. Here, we review evidence across epilepsy subtypes, focusing on convergence and divergence across the allelic spectrum, and discuss how polygenic background and other modifiers may influence penetrance and clinical expressivity among carriers of rare pathogenic variants and CNVs. We also consider implications for variant interpretation, genetic counseling, risk stratification, and precision medicine, while emphasizing that most rare-common integrated models remain insufficiently validated for routine clinical decision-making.

common variants↗

PubMed2026

Altered EEG microstate dynamics reflect depressive symptoms in temporal lobe epilepsy.

BACKGROUND: Depressive symptoms are a common and disabling comorbidity in temporal lobe epilepsy (TLE), yet the neural mechanisms linking seizure networks to affective symptoms remain unclear. Although limbic network dysfunction has been implicated in both epilepsy and depressive disorders, it is unknown whether the time-varying dynamics of large-scale electrophysiological brain states reflect depressive symptom severity in TLE. In this study, we examined whether EEG microstate dynamics capture network alterations associated with depressive symptoms in individuals with unilateral TLE. METHODS: We analyzed resting-state, visually normal scalp EEG from 26 individuals with unilateral TLE. EEG microstates were identified by clustering global field power peaks into four canonical classes, with electrode positions mirrored to align the ictal hemisphere across subjects. Microstate dwell time, fractional occupancy, global transition entropy, and Markov transition probabilities were quantified and related to Beck Depression Inventory-II (BDI) scores. RESULTS: Individuals with high depressive symptoms (BDI ≥ 13; N = 12) exhibited longer mean dwell time in the ictal hemisphere-aligned microstate compared with individuals with low depressive symptom burden (BDI < 13; N = 14). Across subjects, dwell time in this microstate correlated with depressive symptom severity (r = 0.57, p = 0.002). TLE individuals with higher depressive symptoms exhibited reduced global transition entropy (p = 0.02), which also correlated with depressive symptom severity (r = -0.54, p = 0.004), indicating decreased flexibility of microstate transitions. Despite similar fractional occupancy of this state between groups, individuals with higher depressive symptoms were less likely to transition into the ictal hemisphere-aligned microstate from non-ictal or posterior configurations. Once engaged, however, the ictal-aligned microstate showed increased persistence, indicating prolonged stabilization of this network configuration. CONCLUSION: Higher depressive symptom burden in unilateral TLE is associated with increased temporal rigidity of the ictal hemisphere-aligned brain microstate, reflecting impaired disengagement of epileptogenic network configurations. These findings suggest that depressive symptoms in TLE may be associated with epilepsy-related disruptions in large-scale neural dynamics.

Humans↗

PubMed2026

Infertility treatment in women with epilepsy: A systematic review.

BACKGROUND: The impact of assisted reproductive technologies (ART) on seizure control in women with epilepsy remains incompletely understood. METHODS: A systematic review was conducted according to PRISMA guidelines. EMBASE, MEDLINE, CINAHL, Scopus, and the Cochrane Library were searched from inception to March 2025. Eligible studies included observational studies and case-based reports involving women undergoing infertility treatment. RESULTS: A total of 1216 publications were identified, of which four studies met the inclusion criteria, including case reports, a case series, and a cohort study. These studies included 16 women aged 25-46 years undergoing infertility treatment, all but one of whom had epilepsy. Interventions involved in vitro fertilization (IVF), ovulation induction, and hormonal therapies. Patients were treated with a range of antiseizure medications (ASMs), including carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, valproate, and zonisamide, either as monotherapy or in combination. Seizure frequency was generally stable, with most patients maintaining baseline seizure control. Seizure exacerbations were uncommon and primarily associated with hormonal therapy and reduced ASM levels, particularly reduced lamotrigine levels. Reported events included breakthrough seizures in the setting of decreased lamotrigine concentrations, seizure clusters associated with follitropin beta, and a new-onset seizure following dehydroepiandrosterone exposure. Across studies, multiple ART attempts resulted in live births with different ASM regimens, as well as in patients not receiving ASMs. CONCLUSION: Available evidence suggests that ART is feasible in women with epilepsy, with most patients maintaining stable seizure control. Hormonal therapy may affect ASM pharmacokinetics and seizure threshold, thereby warranting close monitoring. Larger prospective studies are needed to better define ASM-specific effects and optimize care.

Humans↗

PubMed2025

TMS-EEG in postictal psychosis of epilepsy.

BACKGROUND: Postictal psychosis (PIP) is a poorly understood complication affecting 2 % of individuals with epilepsy. Genomic and neuroimaging studies suggest parallels with schizophrenia. OBJECTIVES: To determine whether Transcranial Magnetic Stimulation coupled with Electroencephalography (TMS-EEG), can reveal schizophrenia-like changes in PIP, especially in Natural Frequency (NF), gamma band Event-Related Spectral Perturbation (ERSP), the N100 peak, and global mean field power (GMFP). METHODS: We applied TMS-EEG targeting the non-dominant hemisphere premotor area in people with focal epilepsy (PWE) with a history of PIP (n = 7) and PWE without any history of psychosis (n = 14). Two-tailed t-tests were applied to TMS-EEG metrics previously studied in schizophrenia to look for differences between the groups, with subgroup analyses excluding participants using benzodiazepines. RESULTS: Demographic and clinical characteristics were similar across the two groups. No significant differences were seen in NF (p = 0.98). We observed a delayed N100 peak latency in the PIP group when excluding those with regular benzodiazepine use (p = 0.05) and increased global mean field power during the 400-600 ms phase of the TEP (p = 0.02). Mean ERSP within the gamma band was lower in the PIP group, though this did not reach statistical significance (p = 0.08). CONCLUSION: This is the first study to apply TMS-EEG in individuals with PIP, demonstrating feasibility and providing methodological insights for future studies. Preliminary findings, including increased GMFP and delayed N100 latency in PIP, suggest possible disruptions in cortical excitability similar to schizophrenia, warranting further investigation.

Humans↗

PubMed2026

A human-specific non-coding RNA for EFHC1, an epilepsy-associated gene, regulates neural stem cell proliferation for cortical development.

Epilepsy is a prevalent brain disorder in humans but rarely occurs naturally in other species, highlighting the potential for human-specific mechanisms in its pathogenesis, and thus, current animal models fail to recapitulate human symptoms. Comparing RNA sequencing (RNA-seq) datasets from human and mouse neural stem cells (NSCs), we identified EFHC1, a juvenile myoclonic epilepsy gene, as exhibiting a human-biased expression. EFHC1 knockdown reduced human NSC proliferation, while its overexpression in mouse embryonic brains increased cortical NSC number. Mechanistically, EFHC1 prevented endoplasmic reticulum stress, thereby reducing inflammatory activation of p38 MAPK and promoting continuous proliferation of human NSCs. We also identified pancEFHC1, a bidirectional promoter-associated non-coding RNA (pancRNA), located at the human EFHC1 promoter. Knockdown of pancEFHC1 in human NSCs increased DNA methylation to reduce EFHC1 expression, with the resulting phenotype rescued by EFHC1 overexpression. We propose that the evolutionary acquisition of pancEFHC1 has introduced a complex regulatory mechanism for EFHC1 expression that allows distinguishing it in humans.

Humans↗