ObjectiveTo elucidate factors associated with epilepsy in children with septo-optic dysplasia (SOD).MethodPatients (<21 years) diagnosed with SOD (2013-2023) were identified. Multivariate binomial regression predicted seizures in patients with SOD.ResultsWe identified 107 children (M:F = 46:61) with SOD. Among those, 103 had seizure data. Fifty-two (52/103; 50.5%) experienced seizures. Median age of seizure onset was 9 months (IQR: 4 months -2 years 5 months). Abnormal neurologic examinations were seen in 82.6% with seizures (P = .002). Global developmental delay was noted in 46 (43.0%) and associated with seizures (P = .004). Of 24 patients with autism spectrum disorder, 75% had seizures (P = .01). Ventriculomegaly and schizencephaly were associated with seizures (P = .015, P = .004). No significant associations were found between seizures and SOD diagnostic criteria combinations.InterpretationSeizures are highly prevalent in SOD patients. Diagnostic criteria for SOD do not predict seizures, underscoring the need for comprehensive screening in all SOD patients, irrespective of phenotype.

BACKGROUND:Deep brain stimulation (DBS) is an increasingly promising approach for patients with drug-resistant epilepsy (DRE). However, there are limited studies characterizing patient complications from DBS placement. MATERIALS AND METHODS:Using reports from the Manufacturer and User Facility Device Experience (MAUDE) database from January 2018 through March 2024, we systematically analyzed available data on patient complications/complaints, management strategies, and clinical outcomes. Only data from DBS implantations specifically to treat DRE were collected and analyzed. RESULTS:A total of 151 reports involving DBS treatment of DRE were analyzed. The most common DBS complications were device-related problems (DRPs, 95/151 [62.9%]) and patient complaints (PCs, 66/151 [43.7%]). The percentages exceed 100% because the categories overlap; some cases may fall into both categories, indicating that items in one category can also be included in another. The most prevalent DBS device-related complications included impedance issues (34/95 DRPs, 35.8%), device failure (32/95 DRPs, 33.7%), inadequate simulation (14/95 DRPs, 14.7%), and lead breaks (13/95 DRPs, 13.7%). The most prevalent patient complaints were worsening of seizure activity (20/66 PCs, 30.3%), psychiatric changes (9/66 PCs, 13.6%), and neurocognitive behavioral changes (8/66, 12.1%). Of the 151 reports, surgical intervention occurred for 20 (13.2%) patients; device failure had a surgical intervention rate of 9/32 (28%) while impedance issues had a rate of 7/34 (21%). Infections resulted in resolved outcomes in 6/13 (46.2%) of reports, most commonly treated with device removal (9/13, 69.2%). CONCLUSIONS:The MAUDE database helps to more clearly define the risks and complications arising from DBS implantation to treat DRE. These results will help in assessing the risks, treatment alternatives, and outcomes associated with DBS device therapy for DRE. This will facilitate enhancements in the effectiveness of the device, better management of complications, and provide more comprehensive information to ensure patients can give informed consent.

BACKGROUND:To elucidate the clinical profiles and surgical outcomes of patients with generalized tonic seizures (GTSs) undergoing corpus callosotomy (CC) or focal surgery (FS). METHODS:Subjects with GTS undergoing CC or FS were identified using the Pediatric Epilepsy Research Consortium surgery database. Between-group comparisons were performed to assess differences in presurgical epilepsy characteristics and postsurgical seizure outcomes. RESULTS:Fifty-four patients (CC: 40 and FS: 14) included. Patients in the CC group had seizure onset at an older age (median = 1 year vs 0.4 years; P = 0.022), and were older at referral for phase-1 evaluation (median = 11.2 years vs 4.85 years; P = 0.026), and at time of surgery (median = 14 years vs 5.6 years; P = 0.008). The CC group showed higher rates of developmental delay (90% vs 57%; P = 0.013) and greater number of antiseizure medications attempted before surgery (median = 6 vs 4; P = 0.049). Electroencephalography localization also differed (P = 0.002), being most commonly generalized (64%, CC group) and multifocal (45%, FS group). Structural magnetic resonance imaging abnormalities were more common in FS group (92% vs 48%, P = 0.008). Median follow-up duration was 13.2 months (interquartile range = 5-24) in the CC group and 13.5 months in the FS group (interquartile range = 8-18). At last follow-up, FS group had a higher rate of seizure freedom (80% vs 19%; P = 0.0006). CONCLUSIONS:Our findings demonstrate differences in baseline characteristics and postsurgical outcomes of patients with GTS referred for FS and CC. FS yielded high seizure-freedom rates in focal cases. For patients with no discernible seizure focus, CC was often delayed, though outcomes were generally favorable and delays likely unwarranted.

BACKGROUND AND OBJECTIVES:Despite its proven effectiveness, epilepsy surgery for drug-resistant epilepsy (DRE) remains underutilized and frequently delayed. Previous studies of epilepsy duration before surgery-using variable delay thresholds (2-20 years)-were small, single-center cohorts focused mainly on temporal/frontal lobe epilepsy, showed better seizure freedom with earlier surgery, but did not distinguish total epilepsy duration from DRE duration. As contemporary epilepsy surgery now includes broader indications and emphasizes faster evaluation, the timing and impact of evaluation across this wider population remain unclear. We examined factors associated with evaluation timing from DRE diagnosis and its effect on surgical outcomes in a large multicenter cohort. METHODS:Using a prospective database across 29 US centers, we analyzed associations between patient and epilepsy factors and DRE-to-evaluation interval-defined as the interval from DRE diagnosis to phase 1 video-EEG admission, categorized as shorter (<1 year) or longer (≥1 year)-and compared seizure freedom between groups using multivariable logistic regression adjusted for etiology, seizure type, neuroimaging, and surgical factors. RESULTS:Among 1,310 children, 720 (55%) had shorter and 590 (45%) longer DRE-to-evaluation intervals. Shorter interval was associated with lesional epilepsy (OR 1.65, 95% CI 1.30-2.08), focal seizures (2.80, 2.13-3.70), and normal neurologic exams (1.86, 1.49-2.33). Structural congenital and acquired etiologies were linked to shorter interval, while genetic etiologies (1.73, 1.30-2.32) were linked to longer interval. Among 624 surgical patients (357 shorter, 267 longer), seizure freedom occurred in 53% vs 27% (3.04, 2.17-4.29; p < 0.01). After adjustment, longer interval remained independently associated with lower seizure freedom (0.59, 0.35-1.00; p = 0.0497). DRE-to-evaluation interval, not total epilepsy duration, predicted outcomes. DISCUSION:In this first large multicenter study across diverse epilepsy types applying a 1-year benchmark, nearly half of pediatric patients experienced delays, particularly those with MRI-negative, generalized, or genetic epilepsies. Delays from DRE diagnosis were independently associated with reduced seizure freedom, supporting presurgical evaluation within 1 year as an evidence-based quality benchmark.

In Lennox-Gastaut Syndrome (LGS), a severe developmental and epileptic encephalopathy, the absence of validated biomarkers limits our ability to detect disease early, predict outcomes, and guide treatment strategies. This review synthesizes advances in biomarker research spanning electrophysiological, genetic, neuroimaging, and neuroinflammatory domains. Interictal electroencephalography (EEG) patterns such as slow spike-wave (SSW) and generalized paroxysmal fast activity (GPFA) remain diagnostic hallmarks and show potential as markers of disease progression and treatment response, though further standardization and validation are needed. Genetic testing reveals pathogenic variants in a substantial subset of patients, creating opportunities for precision medicine guided by disease mechanisms. Neuroimaging approaches, including diffusion magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), and EEG-functional magnetic resonance imaging (EEG-fMRI), demonstrate widespread network abnormalities that may provide prognostic or treatment-relevant insights. Circulating molecular and inflammatory markers, such as microRNAs and cytokines, also show promise but remain in early stages of investigation. Overall, the development of reliable biomarkers in LGS will require multimodal integration, multicenter validation, and the application of artificial intelligence to advance toward predictive, preventive, and personalized care.

OBJECTIVE:Despite being safe and effective, surgery for pediatric epilepsy is underutilized. Social determinants of health (SDoH) are important to consider when examining this treatment gap. This study examined the potential systemic inequities at three different stages in the journey toward epilepsy surgery across the Pediatric Epilepsy Research Consortium (PERC). METHODS:Any youth in the PERC prospective surgery database (≤18 years) was eligible and included if sociodemographic factors were also available. We examined if there were differences in disparity factors in: (1) referral to Phase I evaluation, (2) offering of surgery, and (3) completion of surgery. RESULTS:Of 1309 patients, the majority were male (53%, p = .04), White (82.2%, p < .001), not Hispanic or Latino (84.3%, p < .001), and privately insured (56.3%, p < .001). Of the youth who were offered surgical treatment (n = 1103, 84.3%), there were no significant differences in race/ethnicity or sex. Those with a structural lesion were more likely to be offered surgery, and historically marginalized youth were more likely to have a lesion. Of patients who completed surgery (n = 927, 84.0%), White patients were 1.88 times (95% confidence interval [CI]: 1.14-3.04) more likely than Black patients to complete surgery (p = .01). SIGNIFICANCE:Youth who began surgery evaluation are not representative of the demographics of those with epilepsy in the United States, with greater representation of White, non-Hispanic male individuals. In addition, youth who began surgery evaluation disproportionally have private insurance. At the next stage of offering surgery, there were no differences based on SDoH. However, there is evidence that underrepresented youth that were magnetic resonance negative were less likely to be referred for surgical workup and that Black youth were less likely to undergo surgery. Therefore, efforts to provide equitable opportunity for all youth with refractory epilepsy should be concentrated at the referral for surgery evaluation point of care; however, additional efforts are also needed at later stages.

OBJECTIVE:Surgery is an effective, yet underutilized treatment for children with drug-resistant epilepsy. Although predictors of surgical outcomes are well described, the decision to recommend surgery varies by institution. We aim to evaluate the rates of not recommending surgery, identify associated patient characteristics, and quantify variability across centers. METHODS:We queried the Pediatric Epilepsy Research Consortium Surgery database, a prospective multicenter cohort of children (0-18 years) undergoing initial evaluation for epilepsy surgery. Patients with documented surgical decisions were included. Demographic, clinical, and presurgical evaluation variables were compared by surgical recommendation status. Logistic regression identified factors associated with not recommending surgery. Mixed-effects models quantified between-center variability. RESULTS:Among 2480 patients across 29 centers, 532 (21%) were not recommended epilepsy surgery (median center rate 17%, interquartile range [IQR] 10%-28%). After accounting for patient characteristics associated with surgical candidacy, substantial variation in decision-making remained across centers, with a median twofold difference in the odds of not recommending surgery between otherwise similar patients evaluated at different institutions (Median Odds Ratio = 2.25; Intraclass Correlation Coefficient = .18). The clinical characteristics most strongly associated with not recommending surgery included monthly or less frequent seizures (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.75-2.69), non-structural etiology (OR 2.02, 95% CI 1.56-2.61), and taking ≤2 anti-seizure medications (ASMs) (OR 1.67, 95% CI 1.34-2.08, all p's < .01). These characteristics showed minimal clustering across centers (ICCs < .05). SIGNIFICANCE:One in five children evaluated for epilepsy surgery are not recommended to pursue surgical treatment. Although clinical factors influence decision-making, they do not explain the substantial variation in recommendations across pediatric epilepsy centers. Similar children evaluated at different institutions had significant differences in the odds of not being recommended surgery, suggesting that institutional decision-making contributes importantly to surgical candidacy.

Home video-only recordings (HVR) of seizures are an important adjunct in diagnosing and managing epilepsy alongside video-EEG (vEEG) monitoring. HVR demonstrate high levels of accuracy, sensitivity, and specificity, making them useful for distinguishing between epileptic seizures and non-epileptic spells. HVR effectively monitors patients experiencing spells (such as movement abnormalities like tics and benign sleep myoclonus, syncope, or breath holding) that may resemble seizures. These recordings help determine seizure frequency, quantify seizure burden, and analyze seizure semiology. Additionally, HVR offers lower costs, greater accessibility, and faster diagnosis of epilepsy. They are particularly beneficial for patients in underserved areas lacking access to specialized epilepsy centers. In this review, we discuss the available epilepsy-specific platforms for home monitoring, clinical applications of HVR, benefits and limitations of HVR without EEG, technical and practical considerations, the role of artificial intelligence in HRV with the detection of seizures, and future prospects for HVR. HVR provides a practical option for epilepsy care that improves diagnostic accuracy and accessibility. With artificial intelligence integration in epilepsy diagnosis and management, HVR may see widespread adoption in clinical practice, alleviating the burden of this common condition for patients, caregivers, and healthcare providers.

Drug-resistant epilepsy (DRE) remains challenging to treat, and seizure control often fluctuates over time. Responsive neurostimulation (RNS) is increasingly used in pediatric and young adult populations, yet long-term effectiveness and safety data are limited. We evaluated longitudinal seizure control trajectories and safety of RNS in children, adolescents, and young adults treated at our center. Seizure frequency was assessed at approximately 6-month intervals from serial follow-up visits through the most recent follow-up, with each sampled visit categorized by ≥ 50 % (all-responder, AR) or ≥90 % (super-responder, SR) seizure reduction. We examined the persistence and durability of seizure control and used recurrent-event regression to identify clinical modifiers of sustained response. Responder rates improved over time, with 57 % and 75 % of patients achieving AR status at 24 and 47 mean months post-implantation, respectively; corresponding SR rates were 22 % and 33 %. Once achieved, seizure control was typically maintained: the probability of remaining an AR for 24 months was 70 %, and the median proportion of follow-up with sustained response exceeded 85 % across age groups. Concurrent epilepsy surgery favored maintenance of AR status (HR 1.83, p = 0.02), while syndrome-related epilepsies reduced the likelihood of sustained SR status (HR 0.30, p = 0.03). Age at implantation and responder status at 24 months both associated with long-term seizure control. Serious (0.032 events/person-year) and non-serious (0.038 events/person-year) adverse effects were infrequent. RNS provided durable benefit for most, though not all, patients, reflecting the dynamic nature of seizure control. The favorable effectiveness and safety profile support use of RNS in young patients with DRE.

OBJECTIVE:Epilepsy duration is a modifiable risk factor in the outcome of definitive epilepsy surgery; however, an analogous effect in palliative procedures has not been shown. We reviewed the Pediatric Epilepsy Surgery Database data for an association between epilepsy duration and seizure reduction in palliative procedures. METHODS:Patients enrolled between January 2018 and April 2025 who underwent their first epilepsy surgery with palliative intent with 6 months of follow-up were included. Procedures included neuromodulation, corpus callosotomy, hemispherotomy, lesionectomy, and lobectomy where surgical intent was not seizure freedom. Outcomes of seizure freedom, 90% seizure reduction, and 50% seizure reduction were considered at 6-12 months and >12 months from surgery. Duration from epilepsy onset to surgery was compared for patients above and below each outcome threshold at each time point. Logistic regression analysis for the association between epilepsy duration and seizure reduction adjusted for potential confounders including procedure type, etiology, and other clinical factors. Logistic regression analysis was performed on the overall cohort and subgroups of patients with each procedure. RESULTS:A total of 588 patients were included. Initial univariate analysis suggested that epilepsy duration at time of surgery was significantly associated with seizure freedom and 90% seizure reduction at both 6-12 months and >12 months. After adjusting for confounders, only seizure freedom at >12 months was significantly associated with duration of epilepsy. When individual procedures were considered, only lobectomy was sensitive to duration of epilepsy in multivariate analysis, with significant impacts on >50% and >90% seizure reduction at >12 months. Lesional epilepsy predicted seizure freedom at >12 months. Neuromodulation and corpus callosotomy were less likely to achieve seizure reduction than other procedures. SIGNIFICANCE:We did not find an association between early epilepsy surgery and seizure reduction. This reflects the heterogeneity of our population, including different types of surgical procedures and lesional and nonlesional epilepsies.

OBJECTIVE:Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to open resection for pediatric drug-resistant epilepsy (DRE). This systematic review and individual participant data meta-analysis aimed to identify independent predictors of seizure outcomes and operative and neurological complications following MRgLITT. METHODS:Uni- and multivariable mixed-effects Cox proportional-hazards regressions models were used to identify independent predictors of time to seizure recurrence following MRgLITT. Among patients with at least 12 months of follow-up, uni- and multivariable mixed-effects logistic regression analyses were conducted to ascertain the independent risk factors associated with seizure recurrence at last follow-up, operative complications, and postoperative neurological complications. RESULTS:A literature review identified 354 pediatric patients with a mean epilepsy duration of 7.5 (SD 5.3) years prior to MRgLITT. The mean age at seizure onset was 4.52 (SD 4.69) years, and focal seizures were more common (85.5%) than generalized seizures (14.5%). Lesions were detected on MRI in 82.1% of cases. The most common epilepsy etiologies were hypothalamic hamartoma (HH; 23.7%) and malformations of cortical development (23.7%). The mean follow-up duration after MRgLITT was 16.02 (SD 11.63) months. Engel class I outcomes were achieved in 57% of patients. In 205 cases where information was available regarding postoperative neurological complications, 35 patients (17.1%) experienced postoperative neurological complications, with hemiparesis as the most frequent complication (n = 16 patients). Of the 354 total patients who underwent MRgLITT, 8.2% underwent revision epilepsy surgery. No operative or clinical characteristics were associated with seizure recurrence. Seizure freedom probability was significantly higher among patients with HH compared to those with nonlesional MRI (p = 0.012). Patients with mesial temporal sclerosis experienced earlier seizure recurrence (p = 0.023), and an extratemporal surgical location was associated with longer seizure freedom probability (p = 0.034). Lesional MRI was associated with reduced odds of postoperative neurological complications (p = 0.031). CONCLUSIONS:MRgLITT may be a safe and effective alternative option for pediatric DRE. Further prospective studies are warranted to elucidate MRgLITT strategies in pediatric DRE.

ABSTRACT Rationale Longer duration of epilepsy before surgery is a predictor of poor outcome. While referral delays of surgical candidates are well documented, factors causing delay during the presurgical evaluation remain unclear and may vary depending on institutional characteristics. By benchmarking the duration of presurgical evaluation across multiple centers and identifying patient and evaluation characteristics contributing to duration, we can ascertain best practices and address modifiable contributors to reduce delays. Methods We queried the Pediatric Epilepsy Research Consortium Surgery Database, a prospective, observational multicenter study enrolling children 0–18 years at 27 US pediatric epilepsy centers, for all patients undergoing initial presurgical evaluation for drug‐resistant epilepsy (DRE). We included patients with completed evaluations and data on duration from initiation of presurgical evaluation to final surgical decision. We compared patient characteristics and evaluation components between those with long duration evaluations (> 75% quartile) and those with short evaluations (< 25% quartile). Akaike information criteria selection identified variables associated with longer duration. From these, we developed a logistic prediction model for evaluation duration, using a random 80/20 training/testing split of the entire cohort. The model was tested among institutions with ≥ 10 patients in the cohort to assess its accuracy in predicting long durations. Linear models for each site assessed each variable's impact on duration. Variables with < 10% of the patient population at each site were excluded. Beta values were compared to identify intra‐ and inter‐institution variability and to delineate institutions with the shortest added duration for each variable. Results Of 2318 patients undergoing surgical evaluation, 1655 (71%) from 23 sites had complete data. Median evaluation duration was 8 weeks (interquartile range 3–22); 453 (27%) were short‐duration evaluations and 414 (25%) were long‐duration evaluations. Multiple patient and evaluation characteristics were associated with duration (Table 1). Table 6 provides the average duration each variable contributes to evaluation by site, highlighting the shortest durations compared with other groups. Conclusions Duration of presurgical evaluation for DRE can be accurately modeled using multiple patient characteristics and testing strategies commonly employed in epilepsy surgery evaluations. This predictive model can not only estimate evaluation duration but also identify opportunities to improve systemic efficiency. Institution‐level modeling identifies specific program strengths, providing an opportunity to learn from successful processes. Subsequent research will focus on institutional process mapping to better understand systemic practices that lead to improved efficiencies, then sharing these processes across the consortium to shorten evaluation durations.

Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, specific electroencephalogram (EEG) patterns, and significant cognitive and behavioral impairments. To date, eight anti-seizure medications (ASMs) have been specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of LGS: clonazepam, felbamate, lamotrigine, topiramate, rufinamide, clobazam, cannabidiol, and fenfluramine. Additionally, several other ASMs, including valproate, are frequently used off-label for LGS management. As the therapeutic landscape for LGS expands, clinicians are increasingly faced with complex decisions regarding optimal ASM selection. This narrative review explores evolving treatment strategies, offering a consensus-based treatment algorithm designed by a panel of U.S.- based experts. We analyze both FDA-approved and off-label ASMs, drawing on data from randomized controlled trials, open-label extensions, and real-world studies to assess each drug's efficacy and safety profile. A key challenge in comparing ASMs lies in the heterogeneity of study designs and outcome measures. This review addresses these limitations and considers crucial factors influencing ASM selection, such as seizure outcomes, safety profiles, cognitive and behavioral outcomes, drug-drug interactions, and rational polypharmacy. Barriers to access, including economic and regulatory hurdles, are also discussed. The proposed treatment algorithm emphasizes a personalized approach to LGS management, recommending valproate or clobazam as first-line treatments, followed by individualized combinations based on the specific patient profile and associated comorbidities.

OBJECTIVES:To evaluate the extent and content of transition of care (TOC) documentation in a pediatric neurology clinic, specifically evaluating adherence to the eight common principles established by the Child Neurology Foundation (CNF). METHODS:A retrospective chart review was conducted of patients 16-21 years of age seen in a pediatric neurology clinic between February-March 2024. Demographics and clinical data, including TOC documentation elements, were extracted and analyzed. Documentation practices were assessed based on the CNF-TOC principles and compared across sex and presence of intellectual disability (ID). RESULTS:The study included 193 patients: 54 % female and 58 % aged 16-17 years. Individual TOC elements were documented in 0-21 % of cases. Patients with ID had a higher number of antiseizure medications trialed (median:2 [IQR:2-4] vs. 2 [IQR:1-3], p = 0.006), were seen later in pediatric neurology follow-up (median age: 18 [IQR:17-19] vs. 17 [IQR:16-18], p < 0.001), and had earlier seizure onset (median age: 9 [IQR:6-14] vs. 13 [IQR:9-15], p = 0.012). Documentation of anticipated living situation was less in patients with ID (1 % vs. 10 %, p = 0.034), whereas documentation of guardianship prior to age 18 was higher among those with ID (16 % vs. 1 %, p = 0.034). CONCLUSIONS:Despite the recognized importance of TOC, most documentation elements including transition readiness, anticipated barriers, and referral plans were present in only 0-21 % of records. These gaps were evident across both ID and non-ID groups, underscoring the need for systematic approaches to TOC documentation to support effective care transitions for adolescents with epilepsy.

OBJECTIVE:Advances in the analysis and collation of radiographic datasets have enhanced presurgical planning for various neurosurgical procedures, including clipping of cerebral aneurysms, surgical resection of tumors, and arteriovenous malformation management. The surgical theater (ST) system converts radiographic datasets, traditionally interpreted as a series of two-dimensional images, into three-dimensional interactive models better allowing understanding of anatomy as well as the complex anatomic relationships between different diagnostic phase I datasets. METHODS:We reviewed the capabilities and impact of the ST system on patients treated by our pediatric epilepsy service at our institution. RESULTS:The ST system was used in the treatment of 85 patients in our pediatric epilepsy service. Multiple layers of phase I data were converted into a single, multi-layered 3D model which added precision to points of collaboration on creating Phase II plans, allowed for the collaborative creation of detailed surgical plans and facilitated VR practice of complex surigcal plans with intraoperative augmented reality navigation. We highlight both current and future applications and present 4 cases to illustrate how ST is applied in our clinical setting. SIGNIFICANCE:The multi-layered and 3D model of the ST system facilitates epilepsy decision-making for both diagnosis and treatment, enhances surgical navigation, and even allows, in a robust virtual reality (VR) environment, the practice of complex surgical procedures. PLAIN LANGUAGE SUMMARY:The surgical theater (ST) system converts two-dimensional imaging tests (eg MRI, MEG, CT and PET) into three-dimensional interactive models. This helps physicians understand complex Phase I datasets and make decisions for the diagnosis and treatment of pediatric epilepsy. These models also facilitate patient and family education, which may reduce their anxiety. In this article, we discuss the current and future applications of the ST system and how it is used to treat pediatric patients with epilepsy at our Institution. We also describe four of our patients to show how the ST system works in a clinical setting.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), have emerged as important treatment options for patients with LGS who do not respond adequately to antiseizure medications. This review, developed with input from the Pediatric Epilepsy Research Consortium (PERC) LGS Special Interest Group, provides practical guidance for clinicians on the use of these neuromodulation approaches in patients with LGS. We discuss patient selection criteria, expected seizure and non-seizure outcomes, potential complications, and device management considerations for each technique. The review also covers initiation and titration strategies, ongoing care requirements, and emerging data on combining multiple neuromodulation modalities. While all three approaches can reduce seizure frequency in patients with LGS, with commonly reported responder rates ranging from 50% to 60%, their impacts on cognition, behavior and quality of life are more variable. Careful patient selection, individualized programming, and long-term follow-up are essential to optimize outcomes with neuromodulation in this challenging patient population. Further research is needed to identify optimal candidates, determine the ideal timing during patients’ clinical course to consider neuromodulation, develop standardized outcome measures, and evaluate the comparative effectiveness and cost-effectiveness of different neuromodulation techniques for LGS.

BACKGROUND AND OBJECTIVES:CHD2 variants have been implicated in a spectrum of neurodevelopmental disorders, including early-onset developmental and epileptic encephalopathy. Despite growing interest in CHD2-related disorders, the full phenotypic spectrum, including epilepsy features and genotype-phenotype relationships, is not fully understood. This study aims to systematically review the literature and analyze data from a multicenter registry to independently describe phenotypic and genotypic features of CHD2-associated epilepsy. METHODS:A systematic literature review was conducted from inception to 7/2024 using EMBASE, Web of Science, and PubMed with the keywords "CHD2". Additional data was collected from a search of the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Genetics Database and the same parameters were used to gather relevant information about patients with both CHD2 variants and epilepsy. RESULTS:Of the 644 screened articles, 74 articles containing individual participant data were included for full-text review and analysis, focusing on parameters such as CHD2 variants, clinical characteristics, neuroimaging findings, and electroencephalography (EEG) results. Data from 236 individuals with epilepsy and CHD2 variants were included, including 12 previously unreported cases from the PERC Genetics database. Of the patients with available data, 53% (108/205) were male, and 95% (170/179) had confirmed de novo mutations. Seizure onset ranged from 1 day to 22 years, with 59% (80/136) of the cases exhibiting photosensitivity and 37% (33/90) fever sensitivity. Most common comorbidities included intellectual disability (86%, 121/141), developmental delay (88%, 156/177), and autism (45%, 68/150). EEG showed epileptiform abnormalities in 88% (122/138) of the cases. MRI findings were abnormal in 19% (22/116) of patients. DISCUSSION:CHD2-associated epilepsy presents with considerable phenotypic variability, including variable age of seizure onset, photosensitivity, and neurodevelopmental comorbidities. This review highlights the importance of comprehensive phenotypic-genotypic characterization to better understand the clinical spectrum of CHD2 variants, emphasizing the need for further investigation into the mechanisms driving phenotypic diversity.