Children with Drug Resistant Epilepsy Referred for Resective Surgery: Characteristics Delaying Surgical Referral and Advanced Neuroimaging in Improving Outcome

Abstract

Research Question: Two questions will be addressed: “Are there certain characteristics in children with DRE in the US that delay their evaluation for epilepsy surgery despite failing three or more ASMs?” and “In children with DRE, does information derived from magnetoencephalography (MEG) advance presurgical localization of the epileptogenic zone (EZ) and improve the surgical outcome in those who have failed prior epilepsy surgery?”

Background, Significance, and Rationale: Anti-seizure medications (ASM) do not achieve seizure control in 30% of children with epilepsy. For these patients, epilepsy surgery is considered the best treatment. Children are considered to have drug resistant epilepsy (DRE) once they have failed two ASMs and should be referred for surgical evaluation. However, many patients fail more than two ASMs before referral. The characteristics of these children compared to children failing less than two AMSs have not been thoroughly investigated. These characteristics are critical to better understand variables that may interfere with surgical referral. Patients evaluated for surgery undergo an evaluation procedure which involves several neuroimaging techniques. The goal of this process is to identify the EZ. However, oftentimes the localization of this area is unsuccessful or inconclusive. In these cases, intracranial electroencephalography (iEEG) recordings are required which presents limitations due to invasiveness. The utility of MEG in guiding a second surgical workup after previous iEEG-guided surgery has failed has not been investigated. By determining the utility of MEG in aiding in seizure freedom, we would improve surgical management of patients.

Materials and Methods: We prospectively enrolled children = 18 years of age undergoing epilepsy surgery evaluation at 21 US pediatric epilepsy centers participating in the Pediatric Epilepsy Research Consortium Epilepsy Surgery Database. We compared sociodemographic and epilepsy variables of patients failing = and >2 ASMs at the time of epilepsy surgery evaluation. For characteristics of significance, we compared seizure outcome (Favorable: Engel 1 or 2; Unfavorable: Engel 3 or 4) after surgery between those failing =2 and >2 ASMs prior to referral. Statistical analyses was performed with SPSS. For the second question, a group of patients who had an unsuccessful prior iEEG-directed epilepsy surgery followed by a MEG-augmented surgery will be identified. MEG data from these children will be analyzed and the two areas of surgical resection will be compared to the dipoles identified from the MEG data. We will compare the localization findings between the two surgeries to assess how MEG augments the surgical outcome.

Results and Conclusion: Additional ASM trials prior to surgical referral are associated with younger age at seizure onset and delay to evaluation. Patients failing >2 ASMs more often have abnormal neurological exam and daily seizures, while also failing treatments other than ASMs prior to surgical referral. Importantly, abnormal exam and seizure frequency do not predict outcome, suggesting delay of surgical evaluation because of these characteristics may be unnecessary. Similarly, children less likely to be rendered seizure free from surgery more often trial >2 ASMs, despite palliative surgical outcomes superior to that expected with additional ASM trials. Recognizing patient characteristics which lead to delayed surgical referral may shorten the duration to surgical therapy with potential for improved outcomes. Finally, MEG seems to augment the surgical workup and aid in favorable outcomes after a previously unsuccessful iEEG-directed surgery.