Evaluating the effectiveness of medical therapy in infantile epileptic spasms syndrome due to surgically-remediable lesions.

Abstract

Objective: This single-center retrospective study examined the response to initial standard therapy in children with infantile epileptic spasms syndrome (IESS) associated with surgically-remediable lesion and evaluated the risk factors for drug resistance. We assessed whether the failure of the first standard therapy for surgically-remediable IESS predicted eventual drug resistance.

Methods: New-onset IESS with surgically-remediable lesions was included. Regression analysis was performed to identify risk factors for drug resistance. Kaplan-Meier survival analysis stratified by the response to first standard therapy was conducted to explore if earlier recognition of drug-resistant epilepsy (DRE) was possible.

Results: We identified 61 patients (57% female) with IESS and surgically-remediable lesion (median follow-up of 52 months). First standard treatment started at a median of 15 days after IESS onset resulted in favorable initial response in 31%. Response rate to second standard therapy among those who failed first treatment was 53%, with an overall response rate to sequential standard therapy of 63.8%. Relapses (epileptic spasms/focal seizures) were frequent (59%). At last follow-up, 41% (n = 25) remained drug responsive. The cumulative proportion of survival free of drug resistance was 57% at 2 months, dropping to 38% at 36 months after IESS diagnosis. The odds for DRE increased with extensive magnetic resonance imaging (MRI) abnormality (odds ratio [OR] = 38.5) and congenital-structural abnormality (OR = 23.3) and decreased with older age at IESS onset (OR = 0.68). Kaplan-Meier survival curve differed significantly between responders and non-responders to first standard therapy (p = .02). In the drug-resistant group (n = 36), 34 underwent surgery with Engel class I outcome in 76.5%.

Significance: Although two-thirds of surgically-remediable IESS exhibited an initial response to medical therapy, relapses were frequent. The majority progressed to DRE during follow-up, particularly those with younger age at IESS onset, congenital-structural etiology, or extensive MRI abnormalities. Patients at risk for DRE can be recognized early by the lack of response to first standard therapy (OR 4.15). Our findings can help reduce delays for surgical referral in patients with surgically-remediable IESS.