Abstracts

Rationale: Infantile spasms (IS, also called epileptic spasms) are most often encountered in the in the setting of West Syndrome, a potentially devastating form of epileptic encephalopathy. There is a significant unmet need for additional therapies as many patients lack enduring response to first-line therapies, namely prednisolone, ACTH, and vigabatrin. The use of zonisamide (ZNS) for treatment of IS is supported only by small, open-label case series. Using a large cohort of children with IS, we set out to evaluate the potential efficacy of ZNS for treatment of IS. Methods: We conducted a retrospective cohort study in which we identified all children with IS at our center who were treated with ZNS. For each patient we recorded baseline clinical and demographic characteristics, and calculated metrics of ZNS exposure, including peak and weighted-average dosage. We only considered response within 3 months of ZNS initiation. Response was defined separately as (1) parent-reported resolution of IS for at least 1 month, and (2) freedom from IS and hypsarrhythmia as verified by follow-up video-EEG, without relapse for at least one month. To evaluate ZNS tolerability, we screened medical records for notation of sedation, appetite reduction, weight-loss, hypohidrosis, and nephrolithiasis. Results: Results:  We identified 87 (35 female) children with video-EEG confirmed IS who were treated with ZNS. At the time of ZNS initiation, the median age of patients was 17.4 months (IQR 9.8, 35.9) and the median duration of IS before ZNS exposure was 9.1 months (IQR 1.7, 28.7). The majority of patients had failed prior treatment with prednisolone, ACTH, or vigabatrin. Median peak and weighted-average ZNS dosage was 7.1 mg/kg/d (IQR 3.6, 10.2) and 5.4 mg/kg/d (IQR 3.0, 8.9), respectively. Five (6%) were classified as clinical responders, and only two exhibited video-EEG confirmed response. Furthermore, among those clinical responders, two responded immediately following incomplete (albeit substantial) response to hormonal therapy. Of note, identified side effects included appetite reduction and/or weight loss (17%), and sedation (10%). We did not encounter any cases with documented hypohidrosis or nephrolithiasis. Conclusions: This study suggests that ZNS exhibits rather modest efficacy in the treatment of IS, at least in a relatively refractory population. Further study is warranted to confirm 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.