Abstracts

New-onset refractory status epilepticus (NORSE) is a neurologic emergency involving continuous seizures in a previously healthy patient. Despite extensive workup, no specific etiology is found in over half of NORSE cases, a presentation termed Cryptogenic NORSE. Prolonged seizures in NORSE are believed to internalize synaptic GABAA receptors, partly explaining the increased resistance of seizures to treatments targeting neural inhibitory pathways. While intrasynaptic GABAA receptors are internalized in status epilepticus, extrasynaptic GABAA receptors are conserved and may be targeted.

Both electroconvulsive therapy (ECT) and Ganaxolone target these alternative neural pathways and have shown efficacy as novel treatments for drug-resistant and cryptogenic NORSE. ECT delivers an electric current through the cerebral cortex, aiming to induce a generalized seizure. ECT is believed to assist with refractory seizures by producing neurotrophic effects, promoting neuroplasticity, increasing GABAergic transmission, and elevating the seizure threshold. Ganaxolone is a neuroactive steroid that works as a positive allosteric modulator, enhancing inhibitory signaling through both intrasynaptic and extrasynaptic GABAA receptors. To our knowledge, no study has evaluated the efficacy of combining ECT with Ganaxolone in treating cryptogenic NORSE.

The patient is a 23-year-old female with no prior seizure history who presented in status epilepticus after a weeklong prodrome of fever, cough, headache, and vomiting. She developed multiple consecutive seizures that were refractory to medical management, with an unrevealing extensive workup. Seizure activity was suppressed after she was placed into a Pentobarbital-induced coma. Attempts to wean her off Pentobarbital failed despite multiple anti-epileptic drugs, immunotherapies, and non-pharmacologic strategies. A combination therapy involving Ganaxolone and ECT was then explored. Starting on day 116 of hospitalization, the patient underwent 12 ECT sessions over 20 days. Each session utilized bitemporal electrode placement with a 800 mAmp stimulus and 120 Hz pulse frequency. A continuous infusion of Ganaxolone was initiated after ECT session three. After ECT session eight, the patient transitioned from intravenous to enteral Ganaxolone, which was maintained for the remainder of ECT.

Continuous infusion of Pentobarbital was gradually reduced from 5.75 mg/kg/hr after ECT session one. Electroencephalogram (EEG) changes were detected after ECT sessions one and two, prior to Ganaxolone initiation. After ECT session nine, visible tonic-clonic seizures were observed. After 12 ECT sessions, the EEG showed significant improvements, allowing for complete titration of Pentobarbital.

In patients with cryptogenic NORSE refractory to conventional treatments, combination therapy with ECT and Ganaxolone demonstrates potential in reducing seizure activity. This combined approach shows promise in safely tapering patients off anti-epileptic medications and managing cryptogenic NORSE.