Abstracts

Rationale: NMDA receptor auto-antibodies are increasingly recognized as a cause of limbic encephalitis with seizures. Although originally described in association with ovarian teratoma, they are now recognized to occur in association with other neoplasms and even without an identifiable tumor. New Onset Refractory Status Epilepticus (NORSE) is a syndrome first identified in Singapore in which previously healthy young women present in status epilepticus. We describe a young woman presenting with NORSE associated with NMDA receptor autoantibodies but without tumor, who was successfully treated with cyclophosphamide. Methods: Case report and review of the literature. Results: A 19 year-old Korean woman presented to the emergency room for a generalized convulsion. The patient had been in excellent health and normal cognitive status until the week previously, then developed emotional lability, echolalia and personality changes over the 3-4 days prior to her first seizure. She received workup and treatment for presumed meningoencephalitis with LP (WBC 15, otherwise normal), MRI, and 2 courses of acyclovir and empiric antibiotics. CT of Chest/Abdomen/Pelvis with and without contrast was normal. Extensive laboratory workup was negative for meningoencephalitis panel, porphyria, and paraneoplastic panel. She progressively declined in terms of her neurological function, and after 3 weeks was only intermittently verbal, non-ambulatory, unable to take POs, and demonstrated a fluctuating mental status with clinical suggestion of subtle seizures. Continuous EEG monitoring revealed non-convulsive status epilepticus. The patient was treated with up to 7 anti-epileptics agents and three anesthetic agents (ketamine, propofol and pentobarbital), which initially resulted in burst suppression with generalized periodic epileptiform discharges. Empiric treatment with several courses of IVIG, corticosteroids, and plasmapheresis yielded no improvement. The ketogenic diet was started and a VNS was placed. Nonetheless, she remained in tenuous burst-suppression with occasional breakthrough electrographic seizures for 5 months. NMDA receptor antibody testing returned as positive. As IVIG, corticosteroids and plasmapheresis yielded no clinical improvement, four pulses of cylcophosphamide were administered. This gradually yielded resolution of epileptiform discharges. The patient improved dramatically over the next month, and is now speaking, eating, ambulating independently with a wheelchair, and participating in rehabilitation after a 9-month acute illness. Conclusions: In most descriptions of NMDA receptor encephalitis, seizures are responsive to conventional anti-epileptic treatment. In our case, the seizures were extremely refractory to treatment including NMDA antagonist Ketamine, and only resolved when the underlying auto-antibody condition was treated. As such, we propose that some cases previously described as NORSE may in fact be severe, but treatable, cases of NMDA Receptor encephalitis.