Abstracts

Rationale: Refractory epilepsy occurs in over 50% of individuals with tuberous sclerosis complex (TSC), making it about 1.5 times more common than in the general epilepsy population. This study explores cannabidiol (CBD) as a possible treatment of refractory epilepsy in TSC. Methods: Under an expanded access IND from the FDA, we are conducting a trial to determine the safety, tolerability, as well as efficacy of CBD (Epidiolex, GW Pharma) as an adjunct treatment in children and young adults with drug resistant epilepsy. Our 25 patients are a subset of a group presented in another abstract of all subjects by Devinsky, et al. (2014). Five of our 25 patients have TSC as the cause of their epilepsy. Data collected from the study were reviewed for demographics, epilepsy history, genetic analysis, and behavioral and cognitive issues. Cognitive impairment was defined by an IQ of <70. Cognitive and behavioral changes were based on parental report and/or clinician observation. Subjects were classified as responders if they showed greater than 50% decrease in seizure frequency after 16 weeks of treatment (including a 5 week titration of 5 mg/kg/day up to 25 mg/kg/day). Baseline seizure frequencies were measured for four weeks immediately preceding initiation of CBD treatment, during which they had two or more seizures per week, meeting study inclusion criteria. Results: The 5 TSC patients ranged in age from 5-14 years old. Four had previous genetic testing, 2 were found to have a TSC1 mutation, 2 a TSC2 mutation. Three of five were cognitively impaired; two had behavioral problems. They were on 2-4 concurrent anti-epileptic drugs (AEDs) and had previously been on 7-9 AEDs. Three had a VNS, three were on or had tried dietary treatment (low-glycemic index treatment (LGIT) or ketogenic diet), and four had undergone epilepsy surgery. Of the five patients, three were responders with 77% (n=1) and 97% (n=2) decreases in seizure frequencies. One non-responder showed a decrease in seizure frequency of 40%; the other showed little change, with seizures increasing 5%. All five had focal onset seizures. Additional seizure types included focal dyscognitive with secondary generalization, tonic, atypical absence, and atonic; all types responded to CBD treatment, including in overall non-responders. No patients became seizure free; however, atypical absence and complex partial seizures were eliminated in one patient who still experiences tonic seizures. All three patients with cognitive impairment experienced cognitive gains, including improved alertness, comprehension, maintained eye contact, engagement, and responsiveness; this group included both nonresponders. One of the two subjects with behavioral problems showed improvements. No subjects experienced side effects or adverse events that were thought to be related to CBD. Conclusions: Refractory epilepsy occurs frequently in TSC. In this small population, CBD appears to be a safe and effective treatment option. Although additional studies are needed, it appears that CBD may be an effective treatment for refractory epilepsy in TSC.