Cryptogenic New Onset Refractory Status Epilepticus (NORSE) in adults-Infectious or not?

INTRODUCTION: In the majority of cases of New Onset Refractory Status Epilepticus (NORSE) in adults, a cause is discovered. However, some cases of NORSE remain undiagnosed, i.e. cryptogenic. They are usually presumed to be due to infectious encephalitis and typically have devastating consequences. We describe our experience with six adults who presented with NORSE and raise the possibility of non-infectious causes.
METHODS: Retrospective case series from an epilepsy service in a tertiary care urban hospital. We compare the clinical features of these cases with patients who develop NORSE in the setting of clinically-defined encephalitis from the California Encephalitis Project (most of whom are etiologically cryptogenic) as well as with patients who develop NORSE in the setting of proven infectious encephalitis.
RESULTS: We describe 6 previously-normal adults with NORSE where a cause was not established despite an exhaustive search. With an average duration of 36 days (range 6-68), the in-hospital and long-term morbidities were high; one patient died of the propofol infusion syndrome. In contradistinction to NORSE in the setting of etiologically-proven infectious encephalitis, these patients were afebrile and the abnormalities evident during their evaluation could be attributed to the ictal activity itself. Neuropathological examination revealed non-specific findings in 4 patients.
CONCLUSIONS: Though an underlying etiology remains unproven in these patients, we contend that NORSE is etiologically heterogeneous, with a proportion of cases due to non-infectious causes. Further study of this poorly understood form of status epilepticus is needed.