Intravenous ganaxolone in pediatric super-refractory status epilepticus: A single hospital experience

Synaptic GABA(A) receptor (GABA(A)R) internalization contributes to the drug resistant nature of super-refractory status epilepticus (SRSE). Ganaxolone is a 3β-methylated synthetic analog of the endogenous neuroactive steroid, allopregnanolone, that has positive allosteric modulatory activity on synaptic and extrasynaptic GABA(A) receptors. Ganaxolone is currently in clinical trials to treat rare pediatric seizure disorders and established and refractory SE. Two pediatric patients with SRSE (age 17 and age 7) were treated under emergency investigational new drug (E-IND) applications with intravenous (IV) ganaxolone administered as an initial bolus and a maintenance infusion for up to 4.5 days with intermittent IV boluses as-needed followed by taper on day 5 and transitioned to chronic treatment using ganaxolone suspension. Adjunctive ganaxolone was effective in terminating SRSE in both patients, safely permitting IV anesthetics to be weaned. Seizure control has been maintained after transitioning to enteric ganaxolone. Further investigation of ganaxolone as a safe and effective treatment for SRSE is warranted.