Successful Treatment of Cryptogenic NORSE Resistant to Immunosuppression With Intravenous Ganaxolone and Electroconvulsive Therapy

Introduction: New Onset Refractory Status Epilepticus (NORSE) occurs without an acute structural, toxic, or metabolic cause in individuals without known epilepsy or a related neurological disease. In about 50% of cases, NORSE is attributed to autoimmune or viral encephalitis; in the rest, it remains cryptogenic, posing significant treatment challenges and high risks of mortality and long-term neurological issues. Standard management often involves multiple antiseizure medications, and immunosuppressive therapies used even when an autoimmune cause is unproven.

Case Description: We report a 23-year-old woman with cryptogenic NORSE resistant to multiple antiseizure medications, intravenous anesthetics, and immunosuppression, requiring a 5-month barbiturate-induced coma. Attempts to reduce anesthetics triggered recurrent super-refractory status epilepticus. Extensive working up including neuroimaging, cerebrospinal fluid, and autoimmune testing revealed no clear etiology. High-dose steroids, IVIG, plasmapheresis, rituximab, tocilizumab, and anakinra were ineffective. An FDA authorization for emergency single-patient IND (eIND) approval allowed treatment with IV ganaxolone, a GABA_A receptor modulator, which was used alongside electroconvulsive therapy. Nine days after initiation of ganaxolone and 13 days after ECT was started, pentobarbital was successfully tapered, and seizures ceased. Consciousness and near-normal language function returned gradually, with residual cognitive deficits. After an 8-month hospitalization, she was discharged to inpatient rehabilitation and subsequently home. At 6 months post-discharge, her Glasgow Outcome Scale–Extended Score was 7.