Coryell, J.

Abstract 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.

Abstract Background Genetic testing is increasingly used in presurgical evaluation, but the yield of resection across germline genetic epilepsies remains uncertain. Methods We conducted a systematic review of MEDLINE (PubMed) and Scopus and added cases from three institutional cohorts and the Pediatric Epilepsy Research Consortium (PERC) databases, including individuals with pathogenic/likely pathogenic germline variants besides tuberous sclerosis and neurofibromatosis who underwent resection or laser ablation. Etiologies were grouped into biologically informed categories (GATORopathies, vascular, overgrowth, CNVs, channelopathies, synaptopathies, other). Primary outcome was seizure freedom (Engel I) at last follow-up. Group comparisons used Fisher’s exact and Kruskal–Wallis tests (α=0.05; Bonferroni when applicable). Prespecified sensitivity analyses stratified by lesional status, excluded GATORopathies, and restricted to literature-only cases. Results We included 223 literature cases (64 studies), 35 institutional cases, and 11 PERC cases (n=269). Median follow-up was 24 months (IQR 12–48.0). Seizure freedom was achieved in: vascular disorders 14/19 (73.6%), GATORopathies 79/120 (67.5%), CNVs 18/31 (66.7%), overgrowth 7/13 (53.8%), other 16/25 (41.7%), channelopathies 13/43 (33.3%), and synaptopathies 4/18 (22.2%) (overall p<0.001). Among cases with known imaging, 208/253 (82.2%) had epileptogenic MRI lesions, including 64% of channelopathies and 80% of the synaptopathies. In univariate contrasts (each category vs all others), odds of seizure freedom were higher for vascular disorders (2.66-fold, 95% CI 0.87–9.72) and GATORopathies (2.46-fold, 95% CI 1.46–4.18), and lower for synaptopathies (∼4.2-fold lower, OR 0.24, 95% CI 0.05– 0.78) and channelopathies (∼4.5-fold lower, OR 0.22, 95% CI 0.09–0.48). Direction and magnitude were consistent across prespecified sensitivity analyses (lesional-only, literature-only, exclusion of GATORopathies). Conclusions Resective surgeries can be effective in germline genetic epilepsies, but outcomes vary by pathway. Disorders with discrete, lesional substrates (GATORopathies, vascular) show the highest likelihood of seizure freedom, whereas channelopathies and synaptopathies, despite the presence of MRI lesions, have substantially lower yields even in lesional cases. Prospective, genotype-aware surgical registries with standardized reporting (EEG, imaging, pathology) and time-to-event outcomes are needed to refine the selection of surgical candidates and quantify seizure and non-seizure-related outcomes.