Sirolimus for epileptic seizures associated with focal cortical dysplasia type II

OBJECTIVE: To determine whether sirolimus, a mechanistic target of rapamycin (mTOR) inhibitor, reduces epileptic seizures associated with focal cortical dysplasia (FCD) type II. METHODS: Sixteen patients (aged 6–57 years) with FCD type II received sirolimus at an initial dose of 1 or 2 mg/day based on body weight (FCDS‐01). In 15 patients, the dose was adjusted to achieve target trough ranges of 5–15 ng/mL, followed by a 12‐week maintenance therapy period. The primary endpoint was a lower focal seizure frequency during the maintenance therapy period. Further, we also conducted a prospective cohort study (RES‐FCD) in which 60 patients with FCD type II were included as an external control group. RESULTS: The focal seizure frequency reduced by 25% in all patients during the maintenance therapy period and by a median value of 17%, 28%, and 23% during the 1–4‐, 5–8‐, and 9–12‐week periods. The response rate was 33%. The focal seizure frequency in the external control group reduced by 0.5%. However, the background characteristics of external and sirolimus‐treated groups differed. Adverse events were consistent with those of mTOR inhibitors reported previously. The blood KL‐6 level was elevated over time. INTERPRETATION: The reduction of focal seizures did not meet the predetermined level of statistical significance. The safety profile of the drug was tolerable. The potential for a reduction of focal seizures over time merit further investigations.