Abstracts

Rationale: Rufinamide (RUF) is an FDA-approved new anticonvulsant licensed as an orphan drug for patients with Lennox-Gastaut-Syndrome (LGS) in Europe. In this retrospective European multicenter study we evaluated the efficacy of RUF in patients with Dravet syndrome (DS) and refractory seizures. Methods: 20 patients (17 male, age 3-23 years, mean 12.2 years) in whom RUF was started before February 2010 were included. All of them showed mental retardation (7 mild, 9 moderate, 4 severe).We analyzed the responder rate (defined as a 50% seizure reduction), tolerability and retention rate after 6 and 12 months. In 16 patients an SCN1A mutation was detected. Before the RUF trial patients had been treated with 2-15 (mean: 7) antiepileptic drugs. The most frequent antiepileptic co-medication at the beginning of RUF was valproic acid (10 patients). Results: The responder rate after 6 months was 20% (4 of 20). In all of them seizure reduction was observed within the first 3 months of treatment. The responder rate after 12 months was 5% (1 of 20). The retention rate was 35% (7 /20) after 6 months and 25% (5/20) after 12 months. RUF treatment was stopped due to aggravation of seizures in 6 patients, no effect (45%; 9 of 20) or side effects (10%; 2 of 20). Side effects were fatigue, gait disorders, decreased appetite, nausea, vomiting, abdominal pain and aggressive behaviour. The duration of treatment was between 9 days and 30 months (mean 9.2 months), only 2 patients still continue, since 29 and 32 months. One of the responders had to stop the medication with RUF due to side effects. The mean dose of the patients treated with RUF longer than 3 months was 32.9 mg/kg/d (range from 9.5 mg/kg/d to 72 mg/kg/d). Conclusions: The efficacy and long-term retention rate in our patients with DS and refractory seizures is far less than in our patients with LGS and Doose syndrome. One third of our patients experienced a seizure aggravation. RUF does not seem to be a suitable option for the long-term treatment in patients with DS.