Introduction

Super refractory status epilepticus (SRSE) carries significant risk of morbidity and mortality. It is defined as status epilepticus (SE) after 24 hours of third line agents (TLAs). Ganaxolone is an allosteric modulator of GABA-A receptors with favorable phase II safety data. High dose ganaxolone has been shown to reduce use of TLAs, but has not previously been evaluated among SRSE patients. Here we describe our experience with high dose IV ganaxolone in a SRSE patient. 

Case Summary

A woman in her 60’s was admitted for elective aortic endarterectomy. She developed SRSE and ultimately failed multiple TLA wean attempts. The etiology of her New Onset Refractory Status Epilepticus (NORSE) was unclear despite an exhaustive evaluation. On hospital day 30, ganaxalone IV was obtained from Marinus Pharmacueticals, Inc under emergency authorization from the FDA. The patient was in electrographic SE with 2.5 Hz near continuous generalized discharges. Initial loading dose resulted in burst suppression within 1.5 minutes, lasting 24 hours without any hemodynamic changes from the infusion. The patient’s EEG ultimately returned to 2-2.5 Hz generalized periodic discharges.

Discussion

Patients with SRSE are in need of better treatment strategies. Ganaxolone IV revealed a robust initial EEG response in this patient, but did not achieve a durable suppression. Outcomes in NORSE and SRSE is closely linked to underlying etiology, [2,3] more effective treatment strategies may offer greater hope for reducing morbidity and mortality among these patients.

Conclusions

High dose ganaxolone may be effective in achieving burst suppression. However long-term burst suppression was not achieved, and clinical benefit of the drug remains unclear. Usage of high dose ganaxolone in SRSE, with greater focus on safe dosing parameters warrants further study.

Sponsorship: Drug supplied by Marinus Pharmaceuticals. Dr. Fehnel and Dr. Merical received no compensation.

1. 1. PMID:28779545
2. 2. PMID:8814099
3. 3. PMID: 20008655