Abstracts

Rationale: Epileptic spasms (ES) are most often encountered in the setting of infantile spasms, a severe form of epileptic encephalopathy characterized by ES alongside hypsarrhythmia and developmental impairment. There is a significant unmet need for new therapies given inadequate enduring effectiveness of first-line therapy (prednisolone, adrenocorticotropic hormone, and vigabatrin). The use of clobazam (CLB) for treatment of ES is supported only by uncontrolled open-label experience and anecdotal report. We set out to explore the efficacy and safety of clobazam in a large cohort of children with refractory ES. Methods: We conducted a retrospective cohort study in which we identified all children with IS at our center who were treated with CLB. For each patient, we recorded baseline clinical and demographic characteristics, and calculated metrics of CLB exposure, including and weighted-average weight-based dosage. Response was defined by video-EEG confirmed freedom from ES and hypsarrhythmia, without relapse for at least 1 month, with response achieved within 3 months of CLB initiation, and not better explained by an alternative treatment (i.e., prednisolone, ACTH, vigabatrin, or respective surgery). Results: We identified 145 children with ES who were treated with CLB. Age of onset of ES was 7.5 months (interquartile range [IQR] 4.9, 15.6). CLB was consistently used as a very late treatment after prior failure of a median of 5 (IQR 3, 8) other therapies. Median weighted-average weight-based CLB dose was 0.8 mg/kg/day (IQR 0.4, 1.1). Although CLB accompanied at least subjective reduction in ES frequency in numerous cases, there were only three (2.1%) patients with video-EEG confirmed freedom from ES and hypsarrhythmia, within 3 months of treatment inititaion. Conclusions: This study suggests that CLB exhibits rather modest efficacy in the treatment of ES, 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.