Abstracts

Rationale: Epileptic spasms (ES, also called infantile spasms) are most often encountered in the setting of West syndrome, a potentially devastating form of epileptic encephalopathy. With inadequate enduring response to established first-line therapies—namely ACTH, corticosteroids, and vigabatrin—there is a large unmet need for other safe and effective therapies. Limited and conflicting data suggest that felbamate (FBM) may be an effective treatment for ES. To a great extent, use of FBM has been curtailed by small and idiosyncratic risks of hepatic failure and aplastic anemia.  Using a large cohort of children with ES, we set out to evaluate the potential efficacy of FBM in treatment of ES. Methods: We conducted a retrospective cohort study in which we identified all children with ES at our center who were treated with FBM. For each patient we recorded baseline clinical and demographic characteristics, including the burden of other seizure-types, and calculated metrics of FBM exposure, including peak and weighted-average dosage. As we were chiefly interested in prompt response to FBM, we only considered exposure and response within 3 months of FBM initiation. “Clinical response” was defined as parent-reported resolution of ES for at least one month. “Complete response” required video-EEG verification of freedom from ES and hypsarrhythmia. With regard to adverse events, we screened medical records for transaminitis, leukopenia, insomnia, weight-loss and sedation. Results: We identified 62 children (29 female) with ES who were treated with FBM. At the time of FBM initiation, the median age was 39 months (IQR 22, 77) and median duration of ES was 27 months (IQR 12, 62), with the majority of patients already having failed hormonal therapy and vigabatrin. The median number of treatment failures prior to FBM initiation was 5 (IQR 3, 8). Among 54 patients with detailed exposure data available, the median peak and weighted-average FBM doses were 47 mg/kg/d (IQR 38, 64) and 40 mg/kg/d (IQR 27, 56). Among five (8%) clinical responders, two exhibited video-EEG-confirmed response, of whom one remained free of ES until last follow-up and one relapsed 7 months after initial response. The three clinical responders (without video-EEG evaluation) all transitioned to Lennox-Gastaut syndrome. Of note, in considering only the 17 patients with latency from ES onset to FBM treatment less than 1 year, the clinical response rate was 24% (4/17). Notable side effects included weight loss (11%), insomnia (15%), sedation (13%), transaminitis (2%), and leukopenia (2%). There were no deaths and no cases of hepatic failure or aplastic anemia. Conclusions: In this highly-refractory cohort of children with ES—often with years of ES prior to FBM initiation—FBM did not exhibit robust efficacy. FBM was generally well tolerated. Of note, this study is methodologically limited on multiple fronts, and we must emphasize the retrospective design, lack of randomization, and lack of control group. Further study in a less refractory population, with more rigorous experimental design—and perhaps higher dosage—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.