Annual Meeting Abstracts: View
(Abst. 2.234), 2019
Risk of Epileptic Spasms Induction by Voltage-Gated Sodium Channel Blockade
Authors: Jaeden Heesch, UCLA; Julius Weng, UCLA; Rajsekar Rajaraman, UCLA; Divya Nadkarni, UCLA; Adam Numis, UCSF; Raman Sankar, UCLA; Shaun A. Hussain, UCLA
Content: Rationale: Epileptic spasms (ES, also called infantile spasms) are most often encountered in the setting of West syndrome. Several case reports have suggested that voltage-gated sodium channel blockade by carbamazepine (CBZ) or oxcarbazepine (OXC) may induce epileptic spasms (Mutoh 1993; Veerapandiyan 2012). Given that voltage-gated sodium channel blockers (SCB), and especially OXC, are among the most common treatments for focal seizures among infants, and the potentially devastating impact of ES, we set out to rigorously evaluate whether SCB exposure is associated with higher risk of subsequent ES and/or earlier onset of ES. Methods: We conducted a nested and matched case-control study. Cases were defined as children with nonsyndromic epilepsy, with focal or multifocal seizures, who subsequently developed video-EEG confirmed ES. Controls were children with nonsyndromic epilepsy who did not develop ES. Cases and controls were matched on the basis of age of onset of epilepsy. For each patient, a reviewer blinded to case/control status recorded all medication exposures and seizure-frequency at each neurology encounter from the onset of nonsyndromic epilepsy to the onset of ES (cases) or a predefined censorship date (controls) so as to ensure equal opportunity to be exposed to any given anti-seizure drug. Cox proportional hazards regression, with time-varying covariates to account for dynamic exposure to specific anti-seizure drugs, was used to determine whether time to onset of ES was associated with exposure to any voltage-gated sodium channel blocker, namely CBZ, OXC, lacosamide (LAC), and phenytoin (PHT). We hypothesized that shorter latency to ES would be associated with SCB exposure, etiology, and seizure-frequency. Results: We identified 50 cases and 50 matched controls. In multivariate time-to-event analysis, there was an interaction between SCB exposure and 'high-risk' etiology (namely HIE/stroke/hemorrage, TSC, FCD, trisomy 21, CDKL5, Aicardi, Dup15q) as follows: Although latency to onset of ES was not associated with SCB exposure alone (hazard ratio 2.0; 95%CI 0.6 - 7.0; P = 0.3), shorter latency was associated with high-risk etiology alone (hazard ratio 2.6; 95%CI 1.4 - 5.1; P = 0.004), as well as the combination of high-risk etiology and SCB exposure (hazard ratio 7.0; 95%CI 2.5 - 19.8; P < 0.001). Of note, latency to onset of ES was not associated with seizure-frequency. Conclusions: This study suggests that SCB exposure may substantially elevate the risk of ES among children already at high risk for ES on the basis of etiology. However, these results should be interpreted in the context of the limitations of the study design-especially the lack of randomization. Further study is warranted. Funding: This study was accomplished with support from the Elsie and Isaac Fogelman Endowment, the Hughes Family Foundation, and the UCLA Children’s Discovery and Innovation Institute.