Perampanel was used as the last anti-epileptic drug (AED) in two patients with NCSE who were on maximal doses of three other AEDs including levetiracetam, phenytoin and lacosamide, in addition to midazolam infusion.

Case 1: A 73-year-old woman with a history of multiple cryptogenic embolic strokes presented with new onset SE. SE was initially controlled with levetiracetam, phenytoin and lacosamide on admission. On Day 6, long-term video EEG showed right frontal lobe NCSE.  Midazolam infusion was started, with resolution of SE.  After a loading dose of 12mg, Perampanel was adjusted to 8mg daily.  Midazolam was weaned within 72 hours and the patient remained seizure free, clinically and electrographically, for the next 11 days until discharge.

Case 2: A 40-year-old man with a right thalamic hemorrhage on admission, developed focal seizures from the right posterior quadrant on Day 4, initially controlled with levetiracetam. However, on Day 16, he was found to be in NCSE resistant to the addition of phenytoin and lacosamide.  High dose Perampanel (36mg loading dose, 12mg daily), along with midazolam infusion terminated his refractory NCSE. Midazolam was successfully weaned over the next 96 hours.

Patients with RSE who fail first-line AEDs may require an intravenous anesthetic agent. Both our patients with RSE were successfully weaned off the anesthetic drug with introduction of Perampanel. The use of Perampanel in this manner deserves further study to determine its efficacy and safety, more quantitatively as an adjunctive therapy for RSE.