Abstracts

Rationale:
Dravet Syndrome (DS) is a rare cause of severe and pharmacoresistant epileptic encephalopathy. Stiripentol (STP) has a significant therapeutic benefit in the pediatric DS population. However, STP effects on adult patients have not been well studied. In our adult-STP-naïve DS patient population, STP initiation was associated with encephalopathy, despite decreases in valproate and clobazam dosages. Here we explored the cause and treatment of encephalopathic manifestations associated with STP in adults.
Method:
A total of 28 patients with a confirmed genetic diagnosis of Dravet Syndrome who attended the Adult Epilepsy Genetics Clinic were identified retrospectively. Patients who declined or discontinued STP after less than three months of use, patients who were deceased or seizure-free when the genetic diagnosis was confirmed, and those who started STP before leaving the pediatric system (< 18 years of age) were excluded. Levels of ammonia, carnitine and other anti-epileptic drugs (AEDs) were regularly checked for patients receiving STP.
Results:
We observed hyperammonemic encephalopathy in 77% of patients treated with STP (Figure 1). A statistically significant decline in ammonia levels was reached in patients supplemented with carnitine (p= 0.004). Five of the patients whose ammonia levels normalized were also offered an increase in Stiripentol dose and they were able to tolerate higher doses of this medication with improvement in side effects. Despite such adjustments, the mean maximum STP dose reached was 14.89+/-8.72 mg/kg/day (Table 1), which is lower than what is typically recommended in children (50 mg/kg/day).
Conclusion:
We report hyperammonemia in Stiripentol-naïve adult patients who were on valproate and clobazam, despite dose reduction of the latter drugs. We also report that treatment with carnitine improved hyperammonemia, allowing the continuation of STP.
Funding:
:This research was partly funded by Dravet Syndrome Foundation.