Seizure Onset Research Articles (Page 1)

DEPDC5 variants are the most common genetic cause of focal epilepsy, often linked to focal cortical dysplasia. Despite their clinical significance, up-to-date penetrance estimates and comprehensive genotype-phenotype correlations remain limited, particularly in diverse populations. This study synthesizes data from a large cohort, including reports from Asian populations, aiming to refine penetrance estimates and to identify genotype-phenotype correlations and outcomes to inform precision care in DEPDC5-related epilepsy in diverse patient populations. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews framework, we conducted a scoping review of PubMed for studies on "DEPDC5" published through August 2024. Studies in English, reporting genotype and phenotype information on families with DEPDC5 variants, were included; individual or sporadic cases, duplicates, and reports of recessive inheritance were excluded. Non-neurologic or nongenetic studies were excluded. Age-specific penetrance was calculated. Clinical characteristics were analyzed across individuals affected by DEPDC5-related epilepsy using the Fisher exact test and the Wilcoxon rank-sum test. Thirty-three publications comprising 170 families, 63.5% of which were of European ethnicity, and 586 variant carriers were included. By age 10, 76.1% of variant carriers developed epilepsy, with a cumulative penetrance of 64.9% (n = 380/586, 95% CI 60.8%-68.7%). Drug resistance occurred in 48.3% of cases, and cortical malformations were present in 28% of those with available MRI. Sudden unexpected death in epilepsy accounted for 16% (n = 4/25) of deaths among affected individuals. Early seizure onset strongly correlated with drug resistance (p = 2.4e-08, W = 2,220.5, median = 1.33 vs 7), intellectual disability (p = 2.1e-08, W = 1,525.5, median = 0.9 vs 7), and lesional MRI (p = 2.2e-08, W = 4,914.5, median = 0.5 vs 7). Among drug-resistant individuals undergoing surgery (34.7% [n = 35/101]), 88% achieved favorable outcomes (Engel I or II). By assembling the largest pooled cohort to date and including underrepresented populations, this study refines penetrance estimates and highlights the clinical severity linked to earlier seizure onset. The positive outcomes after epilepsy surgery observed in our review underscore the importance of early genetic testing and counseling, and tailored therapeutic approaches, including consideration of early surgical intervention, particularly for children with early-onset DEPDC5-related epilepsy. This retrospective review is limited to available genotype and phenotype information from families at the time of publication.

Despite strong evidence supporting timely surgical evaluation, many children with drug-resistant epilepsy undergo multiple antiseizure medication (ASM) trials before surgery. Because guidelines recommend evaluation after failure of 2 appropriate ASMs, evaluation after failure of >2 ASMs serves as a clinically relevant benchmark. The aim of this study was to identify factors associated with initiation of surgical evaluation after failure of >2 ASMs and evaluate its association with seizure freedom. We performed a retrospective analysis using the Pediatric Epilepsy Research Consortium Surgery Database, including 24 US pediatric epilepsy centers. Children aged 18 years and younger who initiated epilepsy surgery evaluation between January 2018 and February 2023 were included. Timing of evaluation was defined by the number of ASM failures before first phase I evaluation (≤2 vs >2). Unadjusted analyses and multivariable logistic regression were used to identify predictors of later evaluation and assess its association with seizure freedom, adjusting for etiology, seizure type, MRI findings, and surgical procedure. Among 1,767 patients, 802 (45.4%) initiated surgical evaluation after failing ≤2 ASMs and 965 (54.6%) after failing >2 ASMs, with a median age at seizure onset of 5.96 and 4.00 years, respectively. Factors independently associated with later initiation of surgical evaluation included genetic etiology (odds ratio [OR] 1.83, 95% CI 1.28-2.60), generalized seizures (OR 2.64, 95% CI 1.58-4.40), daily seizures (OR 1.69, 95% CI 1.33-2.14), multiple seizure types (OR 1.59, 95% CI 1.39-1.82), normal MRI (OR 1.82, 95% CI 1.52-2.18), and abnormal neurologic examination (OR 2.44, 95% CI 2.01-2.96). Surgical intervention rates were similar (∼50%) between groups. Patients who initiated surgical evaluation after failure of ≤2 ASMs had significantly higher seizure freedom rates (60.8% vs 39.3%, p < 0.001). On multivariable analysis, failure of >2 ASMs before surgical evaluation was independently associated with lower odds of seizure freedom (OR 0.66, 95% CI 0.45-0.96, p = 0.028). Initiation of surgical evaluation after failure of more than 2 ASMs is associated with more complex epilepsy phenotypes and lower rates of seizure freedom. However, 80% of these patients still experienced a >50% reduction in seizures, highlighting the therapeutic benefits of timely epilepsy surgery-even when seizure freedom is unlikely-regardless of epilepsy subtype.

Rasmussen's encephalitis (RE) affects the structure and function of one cerebral hemisphere, typically during childhood. Hemispherotomy is a surgical treatment that functionally disconnects the affected hemisphere. The cognitive consequences of surgery and the potential for postoperative recovery remain poorly understood, however, due to their complex and multifactorial nature. This study aimed to examine the long-term cognitive outcomes of patients with RE following hemispherotomy and identify the clinical factors influencing recovery. Forty-four patients who underwent childhood hemispherotomy for RE (28 girls, 23 with left RE) were included in this retrospective study. Neuropsychological assessments were conducted during postoperative follow-up, and verbal (VIQ) and nonverbal (performance IQ [PIQ]) IQ scores from the most recent evaluation were analyzed. The impact of age at seizure onset (ASO), age at hemispherotomy, preoperative epilepsy duration, side of hemispherotomy, age at neuropsychological evaluation, and postoperative follow-up duration on intellectual efficiency scores was assessed using partial least squares analysis. The mean ASO was 5.9 years, the mean age at hemispherotomy was 9.6 years, the mean epilepsy duration was 3.7 years, and the mean postoperative follow-up duration was 9.5 years. After hemispherotomy, 91% of patients were seizure free (Engel class I), and 86% were no longer receiving antiepileptic medication. Patients who underwent hemispherotomy of the language-dominant hemisphere (Hdom) had lower VIQ scores but higher PIQ scores compared to those with hemispherotomy of the nondominant hemisphere (Hnondom). Results showed that higher VIQ was significantly associated with several clinical factors, including a shorter epilepsy duration before surgery, a younger age at surgery, and hemispherotomy of the nondominant hemisphere for language. In contrast, no clear link was found between clinical variables and PIQ. In RE, early hemispherotomy performed soon after disease onset appears to be associated with better long-term intellectual outcomes. Verbal functions can be recovered following hemispherotomy of the dominant hemisphere, highlighting the preferential reorganization of language in postoperative cognitive recovery. These findings underscore the critical importance of early surgical decision-making in optimizing patient care and maximizing postoperative recovery.

Blind source separation (BSS), decomposing signals into mixed sources, remains underexplored in ictal source imaging. We evaluated its ability to extract ictal components localizing the seizure onset zone (SOZ) using routine low-density scalp EEG across multiple settings. We analyzed 20 seizures from ten patients with stereo-EEG-defined SOZs, all seizure-free after surgery or RF-thermocoagulation. BSS was computed over 10-, 30-, and 300-s periods preceding clinically and EEG-defined seizure onsets, using FastICA, InfoMax, and SOBI algorithms. Components were visually categorized as ictal or non-ictal. For each computation, the clearest ictal component was labeled best-of-BSS; one per seizure was further labeled unique when enhancing the ictal discharge. We estimated distances between components' localization and the SOZ and assessed sublobar concordance. Across 360 BSS computations (8164 components), sublobar SOZ localization occurred in 38.5% of ictal components (mean distance: 44.4mm), 48.2% of best-of-BSS (36.8mm), 56.7% of unique (28.9mm), versus 17.9% of non-ictal components (62.9mm). InfoMax computed on 300-s periods preceding clinical onset achieved the highest F-scores. Under these settings, best-of-BSS components localized the SOZ in 13/20 seizures (8/10 patients), with a median distance of 29.9mm. InfoMax algorithm incorporating longer time windows improves SOZ localization from routine scalp-EEG.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT-DBS) has demonstrated potential in reducing seizure frequency (SF) in patients with drug-resistant epilepsy (DRE). This multicenter retrospective study aimed to comprehensively evaluate the long-term effects of ANT-DBS on seizure reduction and neuropsychological outcomes, as well as to identify prognostic factors associated with postoperative efficacy. We retrospectively analyzed data from DRE patients who underwent ANT-DBS across three epilepsy centers between July 2019 and December 2022. SF, responder rate, neuropsychological outcomes, and quality of life (QoL) were assessed using seizure diaries and standardized rating scales at baseline and annual follow-up. Univariate and multivariate regression analyses were performed to identify predictors of postoperative SF reduction. A total of 40 patients were included, with a mean age at surgery of 28.6 ± 11.1years. The average monthly SF decreased from 15 at baseline to 6.5 at the 5-year follow-up (a 56.7% reduction, p < 0.001), with a responder rate of 62.5%. Therapeutic effect was most pronounced within the first 24months after implantation. The Liverpool Seizure Severity Scale (LSSS) scores improved from 26.7 ± 5.2 to 17.9 ± 8.6 (p < 0.001). Mood conditions (measured by the Hamilton Depression and Anxiety Rating Scales) improved from baseline to the final follow-up, while cognitive status remained stable. QoL also improved significantly, particularly in Overall QoL, Emotional Well-being, Energy/Fatigue and Social Functioning. Multivariate logistic regression identified temporal lobe seizures (OR 8.3, p = 0.022) and stimulation amplitude (OR 4.2, p = 0.034) as independent predictors of responder status following DBS implantation. Multivariate linear regression identified baseline LSSS scores (standardized β: 3.5, p = 0.016) and temporal lobe seizures (standardized β 35.4, p = 0.024) as independent predictors of SF reduction. ANT-DBS significantly reduces SF in patients with DRE and shows stable long-term efficacy. The seizure onset zone, preoperative seizure severity and stimulation amplitude are critical predictors of postoperative outcomes, providing valuable information for optimal patient selection for this intervention.

Developmental and epileptic encephalopathy 9 (DEE9) is an X-linked genetic disorder characterized by the onset of seizures during infancy. Mutations in protocadherin 19 (PCDH19) are the main cause of DEE9. Our study aims to demonstrate the diagnostic process and long-term follow-up of a female pediatric case presenting with recurrent seizures. In the present study, a female child presented with recurrent epileptic seizures and findings of abnormal synchronous discharges on electroencephalograms. Whole exome sequencing (WES) was performed on the proband and her parents to identify potential genetic variants. A heterozygous variant (NM_001105243: c.695A>G) in PCDH19 was identified and validated using Sanger sequencing. Based on clinical features and genetic analyses, the patient was diagnosed with PCDH19-female limited epilepsy. Furthermore, a 4-year follow-up was conducted to assess the impact of the pathogenic variant on phenotype and treatment outcomes. The patient exhibited normal intelligence, which differed with the clinical features reported in other studies involving the same variant. WES confirmed the diagnosis of DEE9, and subsequent follow-up highlighted the effectiveness of the treatment. Therefore, genetic testing can improve the diagnosis of DEE9, particularly in cases with atypical symptoms, and provide valuable insights for genetic counseling and clinical treatment strategies.

Abstract Magnetic Resonance Imaging (MRI) is a well-established technique for the evaluation of pediatric epilepsy. This retrospective study includes 57 cases of children with epilepsy (33 boys and 24 girls), with an age range from 1 month to 14 years, who underwent brain MRI evaluation. The aim of this study was to identify predictive factors for pathological MRI. Through our series, we identified three predictive factors for pathological MRI findings: early onset of epileptic seizures, developmental delay, and, finally, an abnormal neurological examination.

BackgroundAltered excitation/inhibition (E/I) balance is a key mechanism in epilepsy, but its dynamic changes before seizure onset remain unclear. The interictal suppression hypothesis suggests that inhibitory input isolates epileptic regions, yet little is known about E/I dynamics in the pre-ictal phase.MethodsWe analyzed high-density EEG recordings from patients with drug-resistant focal epilepsy, each with at least one recorded seizure. Cortical activity was reconstructed using source modeling, and time-resolved changes in the aperiodic exponent—a non-invasive marker of E/I balance—were computed. Directed functional connectivity was assessed via spectral Granger causality. These metrics were correlated with cortical thickness and neurotransmitter receptor density maps.ResultsThe aperiodic exponent increased progressively in the minutes preceding seizures, reflecting a global shift toward cortical inhibition, with no significant differences between epileptic and non-epileptic regions. Delta and theta power also increased preictally. Epileptic regions showed significantly more outward than inward connectivity, and more outward connectivity than non-epileptic areas. In non-epileptic regions, higher inhibition was associated with greater outward connectivity. Cortical thickness positively correlated with inhibition only in non-epileptic areas. Lower muscarinic receptor density was associated with stronger inhibitory shifts.ConclusionsSeizure onset is preceded by a widespread shift toward inhibition, possibly representing a compensatory mechanism that fails as ictal thresholds are crossed. This shift is linked to altered connectivity and disrupted structure–function coupling in epileptic regions. The dynamic aperiodic exponent emerges as a promising biomarker for seizure prediction and a potential target for neuromodulation strategies.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-025-04447-7.

Focal cortical dysplasia (FCD) is a common cause of focal, pediatric, drug-resistant epilepsy. For FCDs in the frontal lobe, resection may be hampered by both difficult access and proximal eloquent cortex. Stereo-EEG (sEEG) can help define the boundaries of the suspected seizure onset zone (SOZ); however, subsequent epilepsy resections often rely on lateral approaches, requiring electrode removal before resection. Nevertheless, for some lesions, especially those in the frontopolar region, skull base approaches provide an in-line, minimally invasive trajectory that allows electrodes to remain in situ during resection as both anatomical landmarks and a source of intraoperative, continuous electrocorticography (ECoG). A 17-year-old, otherwise healthy male presented with 2 years of epilepsy secondary to a left frontopolar FCD. Left frontal and temporal sEEG confirmed a lesion-confined SOZ. The patient underwent a left supraorbital keyhole craniotomy via eyebrow incision for resection of the identified epileptogenic focus. All sEEG electrodes remained implanted during resection, serving as anatomical and electrophysiological surgical adjuncts. The authors present a case of frontopolar FCD-associated epilepsy resected using a supraorbital craniotomy via eyebrow approach. We highlight the utility of leveraging previously placed sEEG electrodes for intraoperative ECoG, resulting in gross-total resection and seizure freedom a year postoperatively. https://thejns.org/doi/10.3171/CASE25428.

Neuroimaging evidence of structural and network disruptions in adolescents with conversion disorder with seizures.

Childhood-onset epilepsy: Longitudinal seizure outcomes in a large single-center cohort.

Pre-treatment seizures and cognition at the time of focal epilepsy diagnosis.

Discriminating clinical profiles in epilepsy, in functional/dissociative seizures (FDS) and co-occurrence.

Evidence of language network reorganization and compromised cognitive functioning in pediatric patients with focal refractory epilepsy.

Functional connectivity linking the hippocampus, retrosplenial, and orbitofrontal cortex correlates with increased seizure severity in temporal lobe epilepsy.

Clinical and radiological evaluation of children with hemimegalencephaly and epilepsy: A single-center study.

Assessing the utility of SISCOM and PISCOM in mapping the epileptogenic zone for epilepsy surgery: A comparative outcome-based study.

Up to 30% of people with epilepsy are refractory to current antiseizure medications (ASMs). JNJ-40411813 is a positive allosteric modulator of metabotropic glutamate 2 receptor, a presynaptic glutamate release inhibitor, and was hypothesized to reduce glutamate-mediated neuronal toxicity through inhibition of excessive glutamate release during seizures. This 12-week, double-blinded, placebo-controlled phase 2a study, which employed a rational polypharmacy approach using a novel time-to-event endpoint for epilepsy clinical trials, evaluated JNJ-40411813 (Cohort 1: 50/100 mg; Cohort 2: 100/200 mg) as adjunctive treatment for focal seizures in participants aged 18-64 years receiving levetiracetam or brivaracetam and ≤3 other ASMs. Participants were stratified as induced or noninduced based on treatment or no treatment with a cytochrome P450 3A4 enzyme-inducing ASM. The primary endpoint was time-to-baseline monthly seizure count. Cohorts 1 and 2 randomized 60 and 50 patients, respectively. No significant clinical benefits were observed in the median time (95% confidence interval [CI]) to reach the baseline monthly seizure count in Cohort 1 (JNJ-40411813: 34 days [27-48], placebo 32 days [28-37], hazard ratio [HR] = .75 [.41-1.38], p = .36) or Cohort 2 (JNJ-40411813: 38 days [28-48], placebo: 29 days [22-69], HR = .83 [.40-1.75], p = .63). Similarly, no clinical benefits of JNJ-40411813 were observed for any of the secondary endpoints. JNJ-40411813 displayed an acceptable safety profile; treatment-emergent adverse events were mild to moderate in severity and not treatment limiting. JNJ-40411813 adjunctive to levetiracetam or brivaracetam showed no significant clinical benefit over placebo in reducing time-to-baseline monthly seizure count or improvement in other key measures in patients with focal onset seizures. The time-to-event study design was successful at reducing participant exposure to ineffective treatment. Despite an acceptable safety profile, the overall efficacy and benefit-risk assessment of JNJ-40411813 does not support its use for patients with focal seizures.

BackgroundEpilepsy, a prevalent neurological disorder in children, is characterized by recurrent unprovoked seizures and developmental challenges. Although pediatric epilepsy is well-studied globally, research in Palestine is limited, which affects targeted healthcare interventions. Furthermore, socioeconomic barriers and limited resources make it difficult to manage epilepsy locally. This study addresses the clinical, diagnostic, and therapeutic aspects of pediatric epilepsy in Palestine to inform evidence-based healthcare planning and improve outcomes for affected children.MethodsA retrospective cross-sectional study was conducted between December 2023 and October 2024, analyzing medical records of 411 pediatric epilepsy patients (aged 2 months to 18 years) diagnosed between 2019 and 2024 at two major pediatric neurology clinics in the West Bank. The data on demographics, seizure types, diagnostic tools, etiology, comorbidities, and treatment approaches were collected retrospectively. The statistical analysis was conducted using IBM SPSS version 24, which employed both descriptive and analytical statistics to identify associations.ResultsOf the 411 patients, 67.2% were male, and 38.3% were school-age children at the time of seizure onset. Focal seizures were the most common type (62.8%). Among epilepsy syndromes, self-limited epilepsy with centrotemporal spikes (SeLECTs) was the most frequently identified (10.9%). The etiology was unknown in 53.8% of cases; genetic and structural causes were identified in 7.3% and 13.6%, respectively. Monotherapy was used in 62% of patients, including 71.6% of those without comorbidities. A statistically significant association was found between the number of antiseizure medications (ASMs) and the presence of comorbidities (p = 0.001), with patients without comorbidities more likely to receive monotherapy. Significant correlations were also identified between seizure type and age of onset (p = 0.000), etiology (p = 0.001), and type of comorbidities (excluding mood disorders). Drug-resistant epilepsy affected 3.4% of patients and was significantly associated with younger age at seizure onset (p = 0.042), cognitive and developmental comorbidities (p < 0.05), and genetic etiology (p = 0.02). Only 1% of patients received surgical intervention, and none were treated with ketogenic diets.ConclusionThis study focused on the clinical characteristics of pediatric epilepsy and highlighted the challenges associated with the availability of treatment modalities, advanced diagnostic tools such as genetic testing, and the limited use of dietary and surgical interventions in Palestine.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12883-025-04447-3.

The transition from interictal discharges to ictal high-frequency activity (HFA) remains poorly understood. We investigated whether spike-associated high-frequency oscillations (Sp-HFOs) during interictal and preictal periods contribute to the emergence of ictal HFA. We retrospectively analyzed the interictal to ictal transition in seizures from six patients with drug-resistant focal epilepsy who underwent stereo-electroencephalography (EEG) and subsequent surgical resection. Various interictal periods preceding seizure onset were selected for comparison. Time-frequency analysis (TFA) was used to characterize Sp-HFOs and ictal HFA. Frequency overlap was measured using the Ideal Fusion (I-Fusion) metric, a novel metric inspired by the F-measure that integrates frequency range overlap and band matching. I-Fusion values range from 0 (no overlap) to 1 (perfect match). Linear regression analyzed changes in I-Fusion values over time, with R2 indicating the strength of the correlation. Visual analysis of the time series revealed a preictal phase in all patients, during which brief HFA gradually emerged within spikes (Sp-HFOs), ultimately transitioning into sustained ictal HFA at the same frequency. TFA demonstrated increasing frequency similarity with time between Sp-HFOs and ictal HFA. I-Fusion values and R2 coefficients rose consistently, indicating a progressive convergence in frequency content. Notably, Sp-HFOs and ictal HFA shared narrow-band frequency features within the same electrode contacts, especially in the epileptogenic zone (EZ). Our findings support a dynamic, frequency-specific evolution from interictal Sp-HFOs to ictal HFA, suggesting that seizure onset is preceded by a gradual preparatory phase rather than an abrupt transformation. The progressive nature and spectral continuity of Sp-HFOs may reflect increasing neuronal synchrony, providing potential early biomarkers for seizure prediction and improved localization of the EZ.