Abstracts

Rationale: Background : Status epilepticus (SE) is deemed refractory (RSE) when there is no response to both first and second line anti convulsants and seizures continue for more than 48 hrs. SE usually develops in individuals with established epilepsy or in setting of acute structural lesion of the brain; rarely it can present de novo without obvious underlying cause, identified recently as NORSE. NORSE was first described in 2005 in a series of 7 female patients and since then has been recognized as a separate clinical entity which responds poorly to aggressive medical management. It has been speculated that NORSE stems from an infectious or autoimmune process and its histopathology is not well described Methods: We retrospectively reviewed 115 patients who presented with SE to the WSU/DMC Epilepsy Program from 2007 to 2013. Out of 115,13 patients were classified as RSE, of which 8 underwent either surgical resection of the epileptogenic zone or biopsy during the acute phase. 5 of the 8 patients were identified as NORSE and 3 had a previous history of epilepsy. A detailed review of clinical, imaging and laboratory findings was done. A neuropathologist reviewed all samples. Results: Of the 5 patients who were classified as NORSE, 3 were female with a median age of 30.6 years (22 to 39 years). One patient had a previous diagnosis of systemic lupus erythematosus (SLE), whereas the others were previously healthy. All of them had a prolonged ICU stay, received multiple antiepileptic medications including IV anesthetics and underwent extensive evaluation to look for a structural lesion, immunological or infectious process. Average duration of NORSE was 48.4 days (range 3-141). MRI studies revealed diffuse T2 hyperintensity in 4 of the 5 patients, which were considered consistent with peri-ictal changes, whereas 1 had diffusion weighted changes consistent with acute infarcts in an area far removed from the seizure focus. Serological workup revealed positive anti-GAD antibodies in the serum in one patient but was negative in others. Due to failed medical management, 4 out of 5 patients had acute palliative surgery for removal of epileptogenic zone while one had brain biopsy done as part of the workup. Histopathological evaluation revealed evidence of autoimmune CNS inflammation with vasculitis in 1 and necrotizing vasculopathy in another patient. The patient with anti-GAD antibodies in the serum had inflammation with T cell infiltration in limbic structures while the remaining 2 had an array of diffuse gliosis and neuronal loss, which was not considered specific for any etiology. On the other hand, 3 patients with previous history of epilepsy who underwent cortical resection for treatment of RSE uniformly had diffuse gliosis, atrocytosis and neuronal loss on pathology. Conclusions: Histopathological examination of brain obtained acutely during course of NORSE reveals a mixed bag of pathology with a slight predisposition towards an autoimmune inflammatory process without apparent infectious agent. Sign of active inflammatory process is usually absent in patients with known history of epilepsy acutely operated for RSE.