Abstracts

Rationale: Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome is characterized by frequent, intractable seizures, almost uniform neurodevelopmental delay, and increased risk of mortality. There is emerging evidence that stiripentol, a new antiepileptic (AED) not currently available in the US, is an effective adjunctive treatment for Dravet syndrome. Methods: This is a retrospective cohort analysis of patients at a single US tertiary care children s hospital with a clinical diagnosis of Dravet syndrome who received treatment with stiripentol from 2008 until 2013. Dravet syndrome was defined as children having a documented sodium channel, voltage-gated, type I, alpha subunit (SCN1A) mutation or clinical confirmation by two pediatric neurologists. Children were required to have documented treatment failure of at least two therapeutic anticonvulsants, excluding Na+ channel blockers. Seizure frequency, concurrent medications and adverse events (AEs) were monitored over a 6-month period. Data were analyzed with a mixed model analysis to account for repeated measures. Results: There were 16 patients who had received stiripentol, of which 14 had at least 3 months of follow up to enable evaluation. Of the 14 patients treated with stiripentol, 11 (78%) were responders ( 50% reduction in the number of seizures) after 1 month of treatment. The overall seizure frequency was not statistically significantly reduced at 1, 3, and 6 months (42.0%, 37.8% and 26.9% respectively (p=0.181)). However, the combined frequency of atonic, tonic, tonic-clonic and focal seizures nearly reached significant reduction to 27% of baseline seizures (p=0.054). The number of concurrent AEDs significantly decreased from an average of 3.2 to 2.3 (p 0.025). There were no serious AEs. The most common AEs were drowsiness, decreased appetite, and aggression or behavior changes. Conclusions: Stiripentol appears to be effective adjuvant anti-epileptic treatment for patients with Dravet syndrome in this short-term study. This study further demonstrates that stiripentol is safe in these children. While there was only a trend towards overall seizure reduction, this is most likely due to the small sample size and wide variation in the number of seizures between patients. Further studies are needed to confirm the safety of stiripentol and find the most effective combination of AEDs for Dravet syndrome in a larger cohort; however, less restricted use of stiripentol should be allowed given the severity of Dravet syndrome.