Rationale: While status epilepticus (SE) is commonly associated with a known diagnosis of epilepsy, there is growing recognition of SE presenting without a prior history of seizure. New Onset Refractory Status Epilepticus (NORSE) is diagnosed in people without pre-existing epilepsy, any other neurological disorder, structural abnormality or toxic/metabolic disturbance. Cause is often unknown but is treated as an autoimmune process, so empiric immunotherapy such as steroids, intravenous immunoglobulin (IVIG), or agents like rituximab, is common. In our case, a patient with cryptogenic NORSE, failing multiple therapies, was treated with the IL-6 blocker tocilizumab. Methods: A 26-year-old woman presented with no prior seizure history presented in status epilepticus. Initial therapy with Levetiracetam, Lacosamide and anesthetic infusions failed. Magnetic resonance imaging (MRI) of her brain and cerebrospinal fluid (CSF) studies were unremarkable. Multiple medications were tried: phenytoin, phenobarbital, valproic acid, and clobazam. Two cycles of Steroids, IVIG, plasmapheresis and rituximab were given, and electroconvulsive therapy was attempted, all without benefit. Subtraction analysis of single photon emission computerized tomography (SPECT) showed multiregional activations, with no target for surgery. Brain biopsy showed microvasculopathy. Perampanel, Felbamate, Oxcarbazepine and Epidiolex were added without effect. Ketogenic diet was contraindicated due to hyperammonemia. After nine weeks of continued seizures, tocilizumab 300 mg IV was given. Results: Within 48 hours of tocilizumab, periodic epileptiform discharges resolved. Off anesthetics, the patient was alert and interactive. A few weeks later, there was psychomotor regression, and repeat EEG showed subclinical ictal discharges, so another 300 mg tocilizumab was given, resulting in resolution of the EEG changes. The patient was discharged to rehab for critical illness myopathy. Two months after discharge, her neurological examination demonstrated recovering cognitive and motor function, although she needed a walker. There were no further seizures reported. Conclusions: Although practice varies between institutions, no immunotherapy has been proven to be consistently effective for NORSE. Many recent studies have identified cytokines associated with poorly controlled epilepsy. Recent research has shown that uncontrolled seizures lead to an inflammatory cascade, with rising IL-6 levels, blood-brain barrier disruption and seizure propagation. This may explain why typical antiseizure measures fail to treat NORSE and why therapy aimed at breaking the inflammatory cycle could be more useful. In our patient, tocilizumab succeeded where numerous other treatments failed. This case demonstrates the need to further study the role that inflammation plays in the pathogenesis of NORSE, and the importance of identifying specific therapies, like tocilizumab, that could provide a more successful treatment for these patients. Funding: Please list any funding that was received in support of this abstract.: None