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.
CONTEXT:Reflex seizures (RS) are defined by their consistent provocation by specific stimuli, encompassing a broad range from elementary sensory inputs to complex cognitive tasks. While RS are often encountered in clinical practice, their surgical management remains sparsely reported and poorly systematized. METHODS:This Seminar reviews surgical cases of RS using a network-based analytical framework, with a focus on delineating the functional anatomy of (i) networks subserving the triggers (NsT), (ii) networks underlying seizure semiology (NuS), and (iii) seizure onset zones (SOZ), aiming to identify criteria predictive of surgical feasibility. RESULTS:Across the spectrum of reported RS-from those triggered by elementary somatosensory or auditory stimuli to more elaborate triggers such as eating, music, reading or praxis-we found that favorable surgical outcomes are more consistently associated with the localization of NuS than with NsT. In RS elicited by elementary stimuli, SOZ often lies adjacent to primary sensory or motor cortices. In contrast, RS provoked by complex or cognitive tasks tend to implicate associative cortical regions, and the latency to ictal onset reflects the degree of network involvement. Notably, specific semiologic patterns-particularly the presence or absence of an aura and the involvement of dorsal versus ventral processing streams-serve as clinical markers to infer SOZ location and its relationship to functional networks. IMPLICATIONS:We propose a tripartite framework for evaluating surgical candidacy in RS based on (1) clinical context (etiology, age), (2) stimulus characteristics (modality and latency), and (3) seizure semiology (ventral vs. dorsal stream involvement). This model enables clinicians to estimate the overlap between epileptogenic and physiological networks and guide the individualized surgical strategies, although advanced neurophysiological mapping remains essential. Despite limited data, our findings support the role of epilepsy surgery in selected RS cases and advocate for prospective studies leveraging multimodal network analyses to optimize patient selection and surgical outcomes.
We performed a systematic review of the literature regarding the localization value of déjà vu (DV), déjà vécu, dreamy state and reminiscence in focal epilepsy, with the aim to summarize the state-of-the-art anatomo-electroclinical correlations in the field and help guide interpretation of ictal semiology within the framework of pre-surgical evaluation of focal drug-resistant epilepsy (DRE). The review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Patient series were included if they provided sufficient anatomo-electroclinical correlation to allow determination of the epileptogenic zone (EZ) and assessment of the level of confidence in each report. We evaluated the risk of bias and the diagnostic accuracy quality of each publication using the Quality of Diagnostic Accuracy Studies (QUADAS-2) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools. For search terms déjà, dreamy state and reminiscence, we identified 22 eligible publications containing a total of 597 patients. The reports with the highest level of confidence suggest that ictal DV or dreamy state reflect an EZ located in both anterior and posterior mesial temporal structures; however, lateral temporal and insulo-opercular EZs have also been described. The anatomo-electroclinical correlation of ictal DV and related phenomena points most commonly to the mesial temporal structures; however, due to the heterogeneous quality of reports and the pooling and overlap of these related symptoms, our findings are regarded with moderate degree of reliability. Future reports should adopt a more refined classification and clinical description of these experiential memory-related ictal phenomena. The use of advanced imaging modalities and a broader implementation of stereoelectroencephalography should facilitate the accumulation of cases with higher level of evidence, which would result in a more robust anatomo-electroclinical correlations of these fascinating epileptic semiologies.
OBJECTIVE:Adrenocorticotropic hormone (ACTH) is an effective treatment for infantile epileptic spasms syndrome (IESS); however, its mechanism of action remains incompletely understood. This study aimed to evaluate ACTH treatment response at the level of protein-protein interactions (PPIs) in patients with confirmed and presumed monogenic developmental and epileptic encephalopathies (DEEs). METHODS:Medical records of patients with DEEs followed at our center between 2017 and 2025 were retrospectively reviewed. Patients receiving ACTH therapy who harbored pathogenic, likely pathogenic, or variants of uncertain significance (VUS) were included in the study, whereas those with chromosomal abnormalities and insufficient clinical or follow-up data were excluded. Clinical and electroencephalographic (EEG) responses to ACTH therapy were evaluated at the 2-week (day 14) and 3-month follow-up visits. Maintenance of a ≥50% reduction in seizure frequency at 3-month follow-up defined responders. Gene Ontology and PPI network analyses were performed to investigate relationships between genotype and treatment response. RESULTS:Among the 245 patients with DEEs, 69 had a confirmed genetic etiology, of whom 10 met the inclusion criteria. At 2-week follow-up, 5 of 10 patients (SCN2A, ELOVL4, CACNA1E, TRRAP) achieved seizure freedom, while 3 (PIGT, SCN1A, ZNF526) showed ≥50% reduction. At month 3, 66.6% (6/9) of patients were classified as responders. At 1 year, patients with SCN2A and PIGT variants showed sustained ≥50% seizure reduction, normalization of background EEG activity, and resolution of epileptiform discharges. PPI analysis revealed network interactions between CALM-SCN2A/CACNA1E and PRKAC-SCN1A, whereas the TRRAP-ATF2 interaction showed low confidence, and no reliable interaction was identified for PIGT. SIGNIFICANCE:These findings suggest that ACTH may be associated with sustained electroclinical improvement in selected genetically defined DEEs. The identified network-level interactions between ion channel-related genes and intracellular signaling pathways provide a potential molecular framework for understanding variability in treatment response.
OBJECTIVE:This study aims to investigate the expression pattern of long noncoding RNA SNHG16 in pediatric temporal lobe epilepsy (TLE), its clinical diagnostic value, and its molecular mechanisms in epilepsy-related neuronal damage. METHODS:This study included 78 newly diagnosed pediatric TLE patients and 75 healthy control children. SNHG16 expression was detected via RT-qPCR, and its diagnostic efficacy was evaluated using ROC curves. In vitro, a TLE model was established in human hippocampal neuronal cells treated with magnesium-free medium. Cell viability, apoptosis, inflammatory factor levels (IL-6, IL-1β, TNF-α), and oxidative stress markers (SOD, GSH, MDA) were assessed using MTT assay, flow cytometry, ELISA, and biochemical kits, respectively. The targeting relationship between SNHG16 and miR-485-5p was validated through dual-luciferase reporter assays and RIP experiments. RESULTS:Serum SNHG16 expression was significantly upregulated in TLE pediatric patients, with an area under the curve (AUC) of 0.895. In cell models, silencing SNHG16 significantly alleviated magnesium-deprivation-induced decreases in cell viability, increased apoptosis, oxidative stress, and inflammatory responses. Mechanistically, SNHG16 directly binds and negatively regulates miR-485-5p expression in the cytoplasm. Inhibiting miR-485-5p reversed the neuroprotective effects induced by SNHG16 knockdown. CONCLUSION:SNHG16 is highly expressed in pediatric TLE and has certain diagnostic potential. It exacerbates epilepsy-related neuronal damage by binding to and suppressing miR-485-5p function. This study provides novel insights into understanding the disease mechanism.
OBJECTIVE:Nonspecific occipital irregular delta activity (OID) is a common finding in focal epilepsy (FE). However, the significance of OID and its relationship to the underlying etiology of FE remain largely unstudied. This study aimed to investigate the relationship between OID and the etiology of FE, as well as the relationship between OID and the clinical characteristics of patients with FE. PATIENTS AND METHODS:We retrospectively reviewed the clinical data and electroencephalography (EEG) reports of 963 patients with FE (full study sample) and 116 healthy controls to assess the prevalence of OID in both groups. Statistical associations were computed between OID and the following clinical variables: age at onset of the illness, sex, and family history of seizures. After excluding patients with no definite etiological diagnosis, the remaining patients comprised the reduced study sample (n = 772). In this reduced sample, we analyzed the relationship between OID and etiology (symptomatic vs. idiopathic). Statistical analysis was performed using multiple chi-square tests with False Discovery Rate correction. RESULTS:The prevalence of OID was significantly higher in the full study sample (7.8%) than in the controls (.9%; p = .0059). OID showed a positive statistical association with idiopathic etiology and a negative association with symptomatic etiology (p = .0001). OID was positively associated with younger age at onset (1-25 years) and a positive family history of seizures, and negatively associated with adult age (26-78 years; p = .0004) and a negative family history of seizures (p = .0205). DISCUSSION:The relationship between OID and idiopathic FE was statistically significant. Several lines of evidence suggest a neurobiological relationship between the presence of OID, age-dependent epilepsies, and delayed brain maturation, particularly in younger individuals. CONCLUSION:From the practical perspective, OID could serve as a potential age-dependent EEG marker of idiopathic FE. In most cases, the presence of OID contradicts a symptomatic etiology.
BACKGROUND AND OBJECTIVES:KBG syndrome is a rare autosomal developmental disorder caused by pathogenic variants of the ANKRD11 gene. This scoping review aimed to explore all current literature data regarding clinical and electroencephalographic features of patients with KBG syndrome and epilepsy. MATERIALS AND METHODS:We conducted a literature review of previously published cases of patients with KBG syndrome and epilepsy in PubMed, Scopus, and Web of Science databases in English, focusing on seizure semiology and electroencephalographic features. RESULTS:Fifty-four studies were included in the review, including 233 patients with KBG syndrome and epilepsy. Most children with KBG syndrome and epilepsy (89.7%) had developmental delay and intellectual disability. The most common neurological symptoms were hypotonia (30.7%), sleep disturbances (20%), ataxia (18.7%), migraine (8.3%), and stereotypies (6.7%) (N = 75, available data on neurological symptoms). The median age of developing seizures was 4 years (range 1 month-51 years). Patients with KBG syndrome had most commonly generalized seizures (73.9%), although focal seizures occurred in 37.9% of cases (N = 140, available data on seizure type). Generalized tonic-clonic seizures were the most common seizure type (38.2%), followed by absences (26.6%), and focal seizures with or without preserved consciousness (21.9% and 19.1%, respectively). Interictal EEG showed focal and, less frequently, generalized discharges (24.6% vs. 15%) in the 118 patients with available EEG data. Almost 70% of patients were seizure-free after a mean follow-up of 9.9 years, while drug-resistant epilepsy was reported in 22.6% of cases. Patients with focal impaired consciousness seizures had significantly lower odds of achieving seizure freedom. CONCLUSION:Epileptic seizures in patients with KBG syndrome are usually generalized and have an onset between infancy and mid-teens. Common epileptological features in KBG syndrome comprise the good response to antiseizure medication and, in most cases, the remitting nature of epilepsy. Drug-resistant epilepsy can be observed in up to one-third of cases.
