Antiseizure Medication Trials Before Referral in Pediatric Patients Undergoing Epilepsy Surgery

Drug-resistant epilepsy is defined as failure of 2 appropriately chosen and tolerated antiseizure medications (ASMs), after which referral for surgical evaluation is recommended. However, many children undergo additional ASM trials before referral. We aimed to identify preoperative factors associated with a higher number of ASM trials before referral in a nationwide, population-based pediatric epilepsy surgery cohort.

We conducted a retrospective study of all children (younger than19 years) undergoing resective epilepsy surgery at the national pediatric epilepsy surgery center in Finland between 2002 and 2022. Patients were identified from a prospective surgical registry. Preoperative clinical characteristics, including etiology, seizure frequency, and resection location, were analyzed. Patients were categorized according to ≤3 vs >3 ASM trials before referral. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of referral after >3 ASM trials. Seizure outcomes 2 years after the final surgery were classified using the Engel classification.

Among 239 children, the median number of ASM trials before referral was 4.0 (IQR, 3.0); 68% were referred after >3 ASMs. Younger age at epilepsy onset, daily seizures, and extratemporal, multilobar, or hemispheric resections were independently associated with referral after >3 ASM trials. Compared with patients referred after ≤3 ASMs, those referred after >3 ASMs had longer onset-to-referral intervals and were less likely to achieve Engel class 1 (odds ratio 2.0, 95% CI 1.0-3.9, P = .047) and more likely to require reoperation (20.9% vs 5.3%, P = .002). The number of prereferral ASM trials decreased over time.

In this population-based cohort, most children underwent more ASM trials than recommended before referral for epilepsy surgery. Greater ASM exposure was associated with more severe epilepsy phenotypes. These findings reinforce the importance of timely recognition of drug-resistant epilepsy and consideration of surgical evaluation alongside escalation of ASM trials.