Abstracts

Rationale: Infantile spasms (IS) is an often catastrophic form of epileptic encephalopathy. IS tends to be highly refractory and treatment is frequently complicated by relapse, which is in turn linked to high morbidity and poor neurodevelopmental outcomes. Prior studies have estimated a cumulative risk of relapse of 40-50% (Hiyashi et al 2016; Rajaraman et al 2016). There are no established clinical predictors of relapse and no known effective strategy to reduce the risk of relapse. Using a large cohort of children with IS, we set out to describe the epidemiology of IS relapse and identify clinical and etiologic factors which may modify risk. Methods: Patients with IS were identified using a database of all patients with video-EEG confirmed IS at UCLA. We then identified the subset of patients with response to therapy observed at UCLA and recorded dates of relapse and most recent follow-up, as well as relevant clinical and etiologic data. Response was defined as complete resolution of epileptic spasms, without relapse for at least one month. Relapse was defined as the return of epileptic spasms at least one month after initial response. Relapse data were right-censored at 6 years. Time to relapse was evaluated with the Kaplan-Meier procedure and multivariate Cox proportional hazards regression. Results: We identified 227 patients with IS who responded to treatment administered at UCLA. Among these 227 patients, with median follow-up of 38.6 months (interquartile range [IQR] 16.3 - 80.5), there were 68 cases of relapse, which occurred a median of 6.3 months (IQR, 2.6 - 12.0) after initial response. Latency to relapse was independently associated with response to medical therapy (rather than surgical resection; HR = 7.7; 95%CI 1.8 - 31.9; P = 0.005), history of prior response (and relapse) at other centers (HR = 2.1; 95%CI 1.3 - 3.4; P = 0.005), and identified genetic etiology (HR = 1.8, 95%CI 1.1 - 2.9; P = 0.02). There were no other demographic, etiologic, or treatment-associated factors which predicted response. Conclusions: This study demonstrates that relapse is common after initial response to therapy for IS, and that risk is higher with identified genetic etiology, and lower among patients who respond to surgical resection. However, these identified risk factors are not modifiable by treatment, and together they explain only a small fraction of observed relapse. The factors which most drive relapse risk remain unknown, and may hold the key to the development of superior therapies to not only prevent relapse, but improve initial treatment. 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.