Abstracts

Rationale: Although vigabatrin (VGB) is a first-line treatment for infantile spasms (IS) and particularly effective among children with tuberous sclerosis complex (TSC), there is substantial risk of relapse. We previously demonstrated that higher post-response VGB dosage is associated with lower risk of relapse among children with TSC (Hussain, 2018). However, it is not clear that this potential benefit extends to children without TSC, especially as VGB seems to exhibit lower efficacy among children without TSC. Using a large cohort of children with IS, we set out to determine whether relapse varies as a function of post-response VGB dosage among children without TSC. Methods: Patients with IS who exhibited video-EEG confirmed response (freedom from epileptic spasms and hypsarrhythmia) during treatment with VGB (not necessarily monotherapy) were retrospectively identified. For each patient we recorded the dates of IS onset, response, and relapse (if any). We then quantified VGB exposure by recording VGB dosage and patient weight at all sequential neurology encounters, to enable calculation of peak and weighted-average weight-based dosage. Time to relapse was evaluated using Kaplan-Meier plots and Cox proportional hazards regression. Results: We identified 53 patients with video-EEG confirmed response during VGB treatment, who were followed for a median of 16.5 months (interquartile range [IQR] 8.4, 40.5). Seventeen (32%) children were also treated with hormonal therapy (prednisolone or ACTH) at the time of response. Median peak VGB dosage was 140 mg/kg/day (IQR 108, 176), and median weighted-average dosage was 121 mg/kg/day (IQR 98, 148). Twenty-one (40%) children relapsed with a median latency of 2.1 months (IQR 0.8, 6.6). Time to relapse was not associated with peak VGB dosage (P = 0.1), weighted-average VGB dosage (P = 0.2; Figure 1), persistence or emergence of other seizure-types (other than epileptic spasms, P = 0.2), or concomitant hormonal therapy at the time of initial response (P = 1.0). Conclusions: In contrast to prior data suggesting that high post-response VGB dosage may reduce risk of IS relapse, this study suggests that the potential for VGB to reduce risk of relapse does not extend to children without TSC. Importantly, this study is limited by the retrospective design and relatively small sample size. Further study is warranted to replicate these findings. 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.