OBJECTIVE: The objective of this study is to report the results of the genetic analysis in a large and well-characterized population with pediatric-onset epilepsies and to identify those who could benefit from precision medicine treatments.
METHODS: In this retrospective observational study, we consecutively recruited patients with pediatric-onset epilepsy observed at a tertiary neurological center over a time span of 7 years, collecting clinical and laboratory findings. Following in-depth diagnostic process to exclude possible structural and metabolic causes of the disease, patients with a suspected genetically determined etiology underwent next-generation sequencing (NGS) screening with panels for the analysis of target genes causative of epilepsy.
RESULTS: We detected likely pathogenic or pathogenic variants (classes IV and V) in 24% of the 562 patients who underwent genetic investigations. By the evaluation of patients\' data, we observed that some features (onset of epilepsy before one year old, presence of neurological deficits, psychomotor delay/cognitive disability, and malformative aspects at brain MRI) were significantly associated with class IV or V variants. Moreover, statistical analysis showed that the diagnostic yield resulted higher for patients affected by Progressive Myoclonic Epilepsy (PME) and with early onset developmental and epileptic encephalopathies (DEE), compared with focal epilepsies, genetic generalized epilepsies, DEE with onset at/after 1 y.o., and unclassified epileptic syndromes. According to the results of the genetic screening, up to 33% of patients carrying class IV or V variants resulted potentially eligible for precision medicine treatments.
CONCLUSIONS: The large-scale application of NGS multigene panels of analysis is a useful tool for the molecular diagnosis of patients with pediatric-onset epilepsies, allowing the identification of those who could benefit from a personalized therapeutic approach.
CONCLUSIONS: The analysis of patients with pediatric-onset epilepsy using advanced technologies for the screening of all the implicated genes allows the identification of the cause of diseases in an ever-increasing number of cases. Understanding the pathogenic mechanisms could, in some cases, guide the selection and optimization of appropriate treatment approaches for patients.

Population-based data on drug-resistant epilepsy (DRE) are lacking. This retrospective study aimed to determine the prevalence and incidence of pediatric epilepsy and DRE in South Korea using health insurance claims data from the Health Insurance Review and Assessment Service (2013-2022). Epilepsy and DRE prevalence and incidence in children <18 years old were estimated over time and by age and sex. Results showed that the age-standardized prevalence and incidence rates of epilepsy increased. The age-standardized prevalence rate of DRE increased, while the age-standardized incidence rate remained unchanged. The standardized prevalence rate of DRE was 0.26 per 1000 persons, and the average standardized incidence rate of DRE was 0.06 per 1000 persons. The prevalence rate of DRE gradually increased with age, with age 0 demonstrating the highest incidence rate. The prevalence of generalized DRE was the highest across all ages, and incidence was the highest at 0 years. Conversely, the incidence of focal DRE did not change with age. Our study revealed a stable incidence rate of DRE in Korea, despite increased prevalence. DRE incidence was the highest in the first year of life, with the generalized type being the most prevalent.

Pediatric patients with epilepsy often have psychosocial and cognitive difficulties. Physical activity has emerged as a lifestyle modification that may reduce seizure burden, enhance brain plasticity, and improve cognitive and psychosocial comorbidities. We systematically reviewed published studies examining the effect of physical activity on cognitive and psychosocial function in children and adolescents with epilepsy. Studies were identified with PubMed and Emory Library databases. Eleven studies met inclusion criteria. Six of 10 studies related to psychosocial outcomes showed benefits of physical activity in children and adolescents with epilepsy, including improvements in internalizing symptoms, relationships, self-esteem, and psychological well-being, but four of the 10 studies showed no psychosocial benefits. Of the six studies evaluating cognitive outcomes, all six indicated that physical activity was associated with cognitive improvements in pediatric epilepsy, including areas of attention, processing speed, executive function, and memory. Our review was limited by the paucity of published studies on this topic, and the use of different measurement tools limited our ability to make direct comparisons between studies. Additional studies that compare pediatric epilepsy populations to non-epilepsy control groups are needed to better understand how physical activity affects seizure control and epilepsy-related comorbidities.

In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors\' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy.

Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1-3 was defined as good and 4-6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.

In the pediatric population, epilepsy is one of the most common neurological disorders that often results in cognitive dysfunction. It affects patients\' life quality by limiting academic performance and self-esteem and increasing social rejection. There are several interventions for the neurohabilitation of cognitive impairment, including LEGO®-based therapy (LEGO® B-T), which promotes neuronal connectivity and cortical plasticity through the use of assembly sets and robotic programming. Therefore, the aim of this study was to analyze the effect of LEGO® B-T on cognitive processes in pediatric patients with epilepsy. Eligible patients were identified; in the treatment group, an initial evaluation was performed with the NEUROPSI and BANFE-2 neuropsychological tests. Then, the interventions were performed once a week, and a final test was performed. In the control group, after the initial evaluation, the final evaluation was performed. An overall improvement was observed in the LEGO® B-T patients, with a significant increase in BANFE-2 scores in the orbitomedial, anterior prefrontal, and dorsolateral areas. In addition, in the gain score analysis, the orbitomedial and memory scores were significantly different from the control group. LEGO® B-T neurohabilitation is a remarkable option for epilepsy patients, who are motivated when they observe improvements.

BACKGROUND: Approximately 10% to 20% of children with epilepsy experience status epilepticus (SE), and children with seizure clustering are at higher risk. Ketamine is growing in use for SE. This study examines the efficacy and safety of enteral ketamine in the treatment of convulsive status epilepticus (CSE) characterized by refractory seizure clusters and nonconvulsive status epilepticus (NCSE) in children with epilepsy.
METHODS: Patient charts were reviewed retrospectively. Children with epilepsy aged one to 21 years presenting in SE and treated with enteral ketamine between September 1, 2021 and September 1, 2022 at a pediatric tertiary care center were identified. Resolution or reduction in seizure frequency within 48 hours, clinical presentation, endotracheal intubation, hospitalization duration, side effects, and readmission were assessed.
RESULTS: Nine patients aged two to 21 years were identified. Six patients presented in CSE characterized by recurrent seizures, and three patients presented in NCSE. Five patients had genetic epilepsies, including PCDH19- and MECP2-related epilepsy. Seven patients had resolution or reduction in seizures within 48 hours of ketamine initiation. Two patients were intubated. Hospitalization duration ranged from one to 34 days. Three patients reported side effects. Three patient readmissions with early ketamine treatment had equal or shorter hospitalizations.
CONCLUSIONS: Enteral ketamine may prove an effective, well-tolerated option for treatment of convulsive and nonconvulsive SE in children with epilepsy, including genetic epilepsies, and may prevent intubation and shorten hospitalization time.

OBJECTIVE: A surgical \"treatment gap\" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts.
METHODS: In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for -DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight-adjusted quantile regression analysis, and categorical variables were analyzed by weight-adjusted counts with percentages and compared with weight-adjusted chi-square test results.
RESULTS: These data indicate an increase in epilepsy surgeries over a 22-year period, primarily due to a statistically significant increase in open surgery and a non-significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed.
CONCLUSIONS: An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical \"treatment gap.\"

Epilepsy is a disorder characterized by abnormal brain neuron activity, predisposing individuals to seizures. The International League Against Epilepsy (ILAE) categorizes epilepsy into the following groups: focal, generalized, generalized and focal, and unknown. Infants are the most vulnerable pediatric group to the condition, with the cause of epilepsy development being attributed to congenital brain developmental defects, white matter damage, intraventricular hemorrhage, perinatal hypoxic-ischemic injury, perinatal stroke, or genetic factors such as mutations in the Sodium Channel Protein Type 1 Subunit Alpha (SCN1A) gene. Due to the risks associated with this condition, we have investigated how the latest pharmacological treatments for epilepsy in children impact the reduction or complete elimination of seizures. We reviewed literature from 2018 to 2024, focusing on the age group from 1 month to 18 years old, with some studies including this age group as well as older individuals. The significance of this review is to present and compile research findings on the latest antiseizure drugs (ASDs), their effectiveness, dosing, and adverse effects in the pediatric population, which can contribute to selecting the best drug for a particular patient. The medications described in this review have shown significant efficacy and safety in the studied patient group, outweighing the observed adverse effects. The main aim of this review is to provide a comprehensive summary of the current state of knowledge regarding the newest pharmacotherapy for childhood epilepsy.

BACKGROUND: Epilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a \"last resort\" compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database.
METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired.
RESULTS: Six hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group.
CONCLUSIONS: Patients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications.