Factors Associated With More Medication Trials Before Surgical Evaluation and Postsurgical Outcomes in Pediatric Drug-Resistant Epilepsy

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.