Abstracts

Rationale: Approximately 80% of individuals with Tuberous Sclerosis Complex (TSC) will have epilepsy during their lives, and the epilepsy is often medically refractory. Levetiracetam (LEV) has been reported to be useful as an adjunctive treatment in TSC and epilepsy. However, there is only one case report demonstrating benefit from LEV monotherapy. We report our experience with LEV monotherapy and adjunctive therapy in a large cohort of children with TSC and epilepsy.Methods: We conducted a retrospective chart review of patients aged 1 – 19 years with a diagnosis of TSC and epilepsy treated with LEV in monotherapy or as an adjunctive therapy. Detailed analysis was performed on children who had completed 6 months of treatment. Seizure frequency and incidence of side effects were recorded from parental reports. LEV initial target dose was 20 mg/kg/day, and was titrated as necessary until a maximum response was achieved or intolerable side effects occurred. Response to treatment was defined as a ≥50% reduction in baseline seizure frequency. We analyzed patient’s complete epilepsy history, including age at onset, seizure types, EEG and previous/concurrent treatments, as well as details about their TSC (genotype, cognitive status, and comorbid psycho-behavioral disorders).Results: Detailed analysis was performed on charts of 43 children (21 female). Four additional patients were on LEV for 5 weeks or less, and were not included in this study. The majority (39) had complex partial seizures, and 30 had refractory epilepsy. LEV was used in monotherapy in 11 (4 as the initial medication), and as an adjunctive antiepileptic drug in 32. A reduction ≥50% in seizure frequency was observed in 28 (65%), 24 had a decrease ≥75%, and 15 (35%) children experienced a reduction ≥95%. In the monotherapy subgroup, which included 4 patients with intractable epilepsy, 9/11 were responders, 8 with 97% or more decrease in seizure frequency. The average LEV dose was 43 mg/kg/day (range, 10 – 106) for responders, and 54 (range, 21 – 91) for non-responders. The mean baseline seizure frequency was the only characteristic associated with the response to LEV: non-responders had 189 ± 132 seizures/month, responders overall had 68 ± 73, and monotherapy responders had 29 ± 45. There was no other significant difference between groups. Side effects occurred in 23 patients, most commonly psycho-behavioral (14) and sleep disturbances (13). Only 6 children stopped LEV due to lack of efficacy and/or side effects.Conclusions: Levetiracetam in monotherapy or as an adjunctive treatment appears to be effective and reasonably well tolerated in managing epilepsy in children with TSC, including those with intractable seizures. Baseline seizure frequency appears to be associated with the degree of response to levetiracetam. (Dr. Carranza was supported by a restricted grant from the Young Investigator Research Program of UCB, Inc.)