Clinical implications of galectin-3, N-cadherin, and E-cadherin as potential biomarkers in childhood epilepsy.

What is the psychological impact on parents of learning about SUDEP? A mixed methods systematic review.

School well-being in children with epilepsy and febrile seizures: A Danish nationwide cohort study.

Antiseizure medication discontinuation in pediatric epilepsy: Real-world insights.

Bridging genomics and digital health for paediatric epilepsy in Africa.

Quality of life in Epilepsy: a comparison between pediatric and adult onset.

To analyze the current state of primary pediatric epilepsy care, providing evidence for regional capacity-building strategies. The cross-sectional survey design was adopted to assess the epilepsy diagnostic and therapeutic capabilities of pediatric physicians from 37 medical institutions in the nine main urban districts and surrounding counties of Chongqing. Tertiary (56.8%, 21/37) and general hospitals (75.7%, 28/37) dominated healthcare, yet pediatric neurology lagged: only 48.7% (18/37) had dedicated teams. Key technologies like Video-EEG (43.2%) and genetic testing (54.1%) were underutilized; novel therapies (ketogenic diet 13.5%, neuromodulation 8.1%) were rarely applied. The median annual outpatient volume was 50 cases, and 33.3% of hospitals achieved >50% seizure freedom rate, yet 20.8% had >15% treatment inefficacy. Evident deficiencies of physician training: 52.4% (87/166) lacked systematic epilepsy training, and only 1.2% (2/166) had passed advanced EEG certification, resulting in only 19.3% (32/166) fully mastering epilepsy classification systems, while 31.9% demonstrated medication selection errors. Significant discrepancies in clinical decision-making: 18.7% (31/166) of physicians inappropriately selected carbamazepine for juvenile absence epilepsy, while 3.6% (6/166) adopted a high-risk immediate medication switching strategy. Fragmented patient management: 8.4% of physicians did not provide health education, and 59.0% (98/166) cited poor family adherence due to insufficient disease awareness. The regional referral rates varied widely (median: 17.5%, IQR: 35-5%). Tertiary hospitals undertake the main clinical burden but lack the construction of specialized infrastructure; lagging staff training leads to undermining the standardization of diagnosis and management; and the problem of the lack of systematic solutions in patient management persists. To enhance the overall service delivery, there are some proposed solutions including establishing hierarchical diagnosis and treatment networks, enhancing specialist training, and implementing regional quality control systems.

Psychometric properties of the Persian version of the childhood epilepsy questionnaire-16 (QOLCE-16) in a sample of parents of children with epilepsy.

Intracranial neuromodulation is an established therapy for drug-resistant epilepsy (DRE) in adults. Improving seizure outcomes and expanding its application to pediatric patients remain priorities. Off-label use of 2-lead and 4-lead devices targeting multiple network nodes, combined with varied stimulation parameters, has emerged in pursuit of better outcomes. Although early findings are promising, the safety of these approaches remains underexplored. This study evaluates adverse event (AE) rates associated with different intracranial neuromodulation devices from a single center. This retrospective study from the Mayo Clinic (Rochester, MN) included patients with DRE who underwent intracranial neuromodulation between August 2004 and December 2024. Demographic data, epilepsy characteristics, treatment indications, procedural details, and AEs were extracted from medical records. AEs are undesirable events associated with implantation and use of the device, regardless of causation. Serious AEs were life threatening or resulted in hospitalization, persistent or significant disability, or death. Patients were classified as children (<13 years), adolescents (13-18 years), or adults (≥19 years). A total of 217 patients (108 male patients, 109 female patients; 14 children, 43 adolescents, 160 adults) were analyzed. Devices included 2-lead deep brain stimulation (DBS) (111 patients), 4-lead DBS (51 patients), and responsive neurostimulation (55 patients). Device-related AEs included stimulation-related paresthesia (7.8%), infections (4.1%), asymptomatic intracranial hemorrhage (ICH) (3.7%), bowstring effect (extension wire tethering that limits neck mobility) (3.2%), operation-related focal weakness (2.3%), wound dehiscence (1.8%), device migration (1.8%), lead malposition (1.4%), lead fracture (1.4%), lead migration (0.5%), extensor wire fracture (0.5%), extrusion (0.5%), and symptomatic ICH (0.5%). While no significant difference in overall AE rates was found between sexes, device explantation was significantly higher in female patients than in male patients (11.9% [13/109] vs 1.9% [2/108], p = 0.006). Children and patients with 4-lead DBS had a higher risk of developing bowstringing compared with other age groups and device types. Intracranial neuromodulation demonstrated an acceptable safety profile across sexes and age groups. However, children and patients with 4-lead DBS systems were at increased risk of the bowstring effect. These findings highlight the need for tailored device design and surgical strategies to optimize safety, particularly in pediatric populations.

This study developed and validated a clinical scoring tool for predicting epilepsy development in pediatric patients with first-onset afebrile seizures using easily accessible clinical and laboratory parameters. We conducted a retrospective, multicenter study involving pediatric patients aged 1 month to 18 years who presented to the EDs of 3 university hospitals in Korea with first-onset afebrile seizures between March 2018 and March 2021. Stepwise multivariable logistic regression analysis was performed to identify predictors of epilepsy. A point-based risk score was derived from the regression coefficients, and the performance of the prediction model was evaluated using a receiver operating characteristic (ROC) curve. In total, 328 children were included, of whom 132 (40.2%) developed epilepsy. Five variables remained significant in the final multivariable model: age group at onset, 2 or more seizures within 24 hours, lactate >2.27mg/dL, total calcium <9.25mg/dL, and abnormal brain imaging findings. The area under the ROC curve (AUROC) was 0.813 [95% confidence interval (CI): 0.763-0.859], and the mean AUROC from 5-fold cross-validation was 0.810 (95% CI: 0.760-0.857). This clinical scoring tool may help stratify epilepsy risk in children with first-onset afebrile seizures in the ED. If prospectively validated, it could help identify high-risk patients early for appropriate referral and follow-up without requiring specialized equipment such as electroencephalography, thereby supporting clinical decision-making.

Interictal epileptiform discharges (IEDs) are pathological hypersynchronous bursts of electrical brain activity that occur between seizures in patients with epilepsy. IEDs are caused by transient brain states that are difficult to predict, making them a challenging neurophysiological and technological case for brain-state-dependent stimulation. Administering stimulation at IED onset may provide insight into the epileptic network and optimize neurostimulation therapies. Here, we assessed the feasibility of IED-triggered transcranial magnetic stimulation (TMS) in two children with self-limited epilepsy with centrotemporal spikes (SeLECTS), a common pediatric epilepsy in which IEDs emerge from the motor cortex. A convolutional neural network (CNN) was trained on the participants' pre-recorded electroencephalography (EEG) data with IEDs annotated by an epileptologist. The CNN was integrated into an EEG-processing pipeline that classified EEG segments as "IED" or "non-IED" in real time. With this pipeline, TMS pulses were administered during IED or non-IED periods in an interleaved, randomized design. We stimulated both the motor cortex generating the IEDs and the contralateral motor cortex and tested the impact of IEDs on TMS-evoked potentials (TEPs). Our study demonstrated that TMS can be timed to IEDs and that there is a site-specific increase in TEP amplitude when stimulating during IEDs. Out of the TMS pulses aimed at an IED, 39% and 19% were successfully delivered during an IED for the two participants, respectively. For future research, we propose ways to address the methodological challenges of IED-timed TMS, enabling brain-state-dependent TMS for epilepsy research and treatment.

Drug-resistant epilepsy (DRE) is increasingly linked to neuroinflammatory mechanisms driven by gut dysbiosis. These mechanisms compromise blood-brain barrier integrity, enhance seizure susceptibility, and modulate immune pathways. These insights underscore the therapeutic potential of microbiota-targeted interventions in epilepsy. The study aimed at assessing the effectiveness of probiotics as an adjunctive therapy to enhance drug sensitivity and clinical outcomes in children with DRE. This randomized, double-blind, placebo-controlled trial enrolled 60 pediatric patients with DRE who were assigned to either the control group (n = 30), which received a standard antiepileptic regimen (valproic acid, oxcarbazepine, and levetiracetam at the maximum tolerated doses) plus a daily placebo capsule, or the probiotic group (n = 30), which received the same antiepileptic regimen plus a daily probiotic (Lactobacillus acidophilus) supplement. The study duration was 6 months. Assessments of clinical and biochemical outcomes were conducted at baseline and 6 months after intervention. Primary end points included seizure frequency and change in quality of life as measured by the quality of life in childhood epilepsy (QOLCE-55) questionnaire. Secondary end points included the change in the serum levels of high-mobility group box1 protein (HMGB1), interleukin-1β (IL-1β), homocysteine (Hcy), and NLR family pyrin domain-containing 3 (NLRP3). After 6 months and relative to the control group, the probiotic (Lactobacillus acidophilus) group experienced a significant decline in seizure frequency (p = 0.04) and a significant improvement in the QOLCE-55 total score (p < 0.0001). Additionally, the probiotic group exhibited significant decreases in the serum levels of HMGB1 (p = 0.0005), NLRP3 (p = 0.002), Hcy (p = 0.001), and IL-1β (p = 0.05) compared with the control group. Lactobacillus acidophilus supplementation appears to enhance the effectiveness of conventional antiepileptic drugs, reduce systemic inflammation, improve quality of life, and reduce seizure frequency in children with DRE. However, further validation is necessary. NCT05539287.

The latest European Medicines Agency (EMA) guideline on the clinical investigation of medicines to treat epileptic disorders was adopted by the EMA Committee for Medicinal Products for Human Use in 2025. We compared this guideline with the previous version (2010), highlighting areas where significant revisions were introduced. The 2025 and 2010 versions of the guideline were systematically analyzed to identify significant modifications. The latest EMA guideline incorporated terminology from the 2017 International League Against Epilepsy (ILAE) classification of seizures and epilepsy and the 2022 classification of syndromes and replaced the older term "antiepileptic drug (AED)" with "antiseizure medication (ASM)." Recommendations for add-on studies in common epilepsies have remained substantially unchanged, the main revision being the acceptability of the time-to-event design also for confirmatory trials, provided it is not the only design in the clinical development plan. A major novelty is the feasibility of extrapolating data from add-on trials to the monotherapy indication, provided specific conditions are met. Guidance on pediatric ASM development has been expanded, addressing extrapolation of efficacy from data in adults and older children and options for studies in developmental and epileptic encephalopathies and other rare epilepsies. Compared with the previous guideline, greater emphasis is placed on nonseizure outcomes, including functional, quality of life, and patient-reported outcomes. Two new sections have been introduced, addressing studies in neonates and clinical trials in status epilepticus and other seizure emergencies. Options for innovative designs, including registry-based studies, are also discussed insituations where randomized controlled trials are unfeasible. The updated guideline reflects the changing scenario in epilepsy treatment development, with a greater focus on pediatric epilepsies, rare epilepsies, and other indications with high unmet needs. The updates also reflect the contribution during the consultation process by a wide range of stakeholders, including the ILAE Task Force on Regulatory Affairs.

Pediatric functional seizures: Demographics, clinical and psychological characteristics and risk factors.

Prevalence of Epilepsy in Children With Autism Spectrum Disorder Referred to the Autism Clinic in a Tertiary Care Hospital in Bangladesh

Abstract The mammalian target of rapamycin (mTOR) pathway orchestrates neuronal proliferation, migration, and synaptic regulation. Dysregulation of this pathway through germline or somatic mutations underlies a spectrum of cortical malformations collectively termed “mTORopathies,” including tuberous sclerosis complex (TSC), focal cortical dysplasia (FCD) type II, and hemimegalencephaly (HME). These conditions are major causes of drug-resistant epilepsy (DRE) in childhood. Since the early 1990s, neurosurgical approaches have evolved from open lesionectomies toward network-based resections, functional disconnections, and minimally invasive laser interstitial thermal therapy (LITT). This narrative review synthesizes evidence on presurgical evaluation, operative strategies, outcomes, and molecular integration in the modern era of precision neurosurgery.

Multidisciplinary clinics (MDCs) improve care for patients with complex, comorbid conditions through coordinated, team-based care. Despite their potential, MDCs remain underutilized and understudied in pediatric neurology, particularly for individuals with rare, chronic epilepsies. The subject of MDCs in pediatric epilepsy was explored through two workshops and surveys of caregivers and clinicians. MDC models vary widely-from general clinics (e.g., neurology, genetics, and neuropsychology) to disorder-specific clinics with multisystemic specialists. Caregivers identified key barriers, including geographical distance, personal expense, and insurance prior authorization requirements, yet overall reported positive experiences-citing valuable opportunities to participate in research and meaningful changes to clinical care. Although the findings reflect responses from a predominantly white, higher-income, English-speaking group of caregivers recruited through patient advocacy networks-and may therefore carry certain biases-their perspectives remain broadly generalizable to prospective patients across diverse socioeconomic settings. Similarly, physicians identified funding and space as the primary barriers to establishing multidisciplinary clinics, yet a majority recognized the importance of advancing research, translational studies, and clinical trials. MDCs can improve care for patients with medically complex rare epilepsies by integrating the management of comorbidities. These clinics bring value to both rare patients and physicians by providing a setting for synergistic activities between clinical care, clinical trials, and research. To expand their impact, we recommend: (1) establishing more MDCs using sustainable models; (2) improving access to extend the reach of MDCs; (3) including key specialists for integrated care; (4) sharing disorder-specific expertise through collaboration and training; and (5) tracking standardized success measures to validate and scale these efforts.

Expert consensus on the diagnosis and treatment of pediatric febrile infection-related epilepsy syndrome (2026)

Febrile infection-related epilepsy syndrome (FIRES) often requires prolonged gamma-aminobutyric acid (GABA)-ergic anesthesia for super-refractory status epilepticus; however, the neurocognitive impact of propofol, independent of disease severity, remains unclear. This study aimed to distinguish practice-driven propofol administration from illness severity-driven necessity and to evaluate the dose-dependent association of propofol with long-term cognitive outcomes in children. This retrospective cohort study included 74 FIRES survivors (median age: 7.2 years) who were admitted from 2014 to 2022. We developed the metabolism-corrected propofol exposure intensity (MC-PEI) metric, which standardizes cumulative propofol dose (mg/kg) to ideal body weight and adjusts for organ dysfunction. A generalized additive model linked MC-PEI to illness severity markers to derive dose residuals (DR), reflecting variation in clinical practice. The median MC-PEI was 2,180 mg/kg. After applying inverse probability of treatment weighting (IPTW), each 100 mg/kg increase in DR was independently associated with a decrease of 0.41 points in the Full-Scale Intelligence Quotient (FSIQ) (p = 0.003). The high DR tertile had a mean FSIQ score of 63.7, which is below the intellectual disability threshold (<70). A significant inflection point was observed at MC-PEI = 2,000 mg/kg: above this level, the FSIQ declined by 0.55 points per 100 mg/kg (p < 0.001). High DR was associated with a 79% rate of intellectual disability, compared to 44% in the low DR group (p = 0.009). Additionally, the rate of school re-entry dropped to 21%. Practice-driven propofol exposure significantly impairs long-term cognition in a dose-dependent manner in FIRES, with accelerated neurotoxicity beyond 2,000 mg/kg. This threshold should prompt a mandatory multidisciplinary review and consideration of alternative treatment options.

Parameter-efficient convolutional neural network for drug treatment outcome studies of pediatric epilepsy.