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

Rani K Singh; Rajdeep Singh; Alejandra Stewart; Katherine Van Poppel; Sarah Klinger; Joseph Hulihan; Heather Van Heusen; Henrikas Vaitkevicius; Maciej Gasior

doi:10.1016/j.ebr.2022.100567

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

Epilepsy Behav Rep. 2022 Oct 6:20:100567. doi: 10.1016/j.ebr.2022.100567. eCollection 2022.

Authors

Rani K Singh¹, Rajdeep Singh¹, Alejandra Stewart¹, Katherine Van Poppel¹, Sarah Klinger¹, Joseph Hulihan¹, Heather Van Heusen¹, Henrikas Vaitkevicius¹, Maciej Gasior¹

Affiliation

¹ Department of Pediatrics, Atrium Health/Levine Children's Pediatric Neurology Care, 100 Medical Park Drive Suite 310 E, Concord, NC 28025, USA.

Abstract

Synaptic GABA_A receptor (GABA_AR) 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.

Keywords: AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid; ASMs, anti-seizure medications; E-IND, emergency investigational new drug; FIRES, fever-induced refractory epilepsy syndrome; GABAAR, GABAA receptors; GNX, ganaxolone; KA, kainate; NMDA, N-methyl-d-aspartate; NORSE, new onset refractory status epilepticus; Neurosteroids; Pediatric; SE, status epilepticus; SRSE, super-refractory status epilepticus; Status epilepticus; Super-refractory status epilepticus.

Publication types

Case Reports