Neuropathology of New-Onset Refractory Status Epilepticus (NORSE)

Abstract

New-Onset Refractory Status Epilepticus (NORSE), including its subtype with a preceding febrile illness known as FIRES (Febrile Infection-Related Epilepsy Syndrome), is one of the most severe forms of status epilepticus. Despite an extensive workup (clinical evaluation, EEG, imaging, biological tests), the majority of NORSE cases remain unexplained (i.e., "cryptogenic NORSE"). Understanding the pathophysiological mechanisms underlying cryptogenic NORSE and the related long-term consequences is crucial to improve patient management and preventing secondary neuronal injury and drug-resistant post-NORSE epilepsy. Previously, neuropathological evaluations conducted on biopsies or autopsies have been found helpful for identifying the etiologies of some cases that were previously of unknown cause. Here, we summarize the findings of studies reporting neuropathology findings in patients with NORSE, including FIRES. We identified 64 cryptogenic cases and 66 neuropathology tissue samples, including 37 biopsies, 18 autopsies, and seven epilepsy surgeries (the type of tissue sample was not detailed for 4 cases). We describe the main neuropathology findings and place a particular emphasis on cases for which neuropathology findings helped establish a diagnosis or elucidate the pathophysiology of cryptogenic NORSE, or on described cases in which neuropathology findings supported the selection of specific treatments for patients with NORSE.

Keywords: Autopsy; Biopsy; Epilepsy surgery; Febrile Infection-Related Epilepsy Syndrome (FIRES); Neuropathology; New-Onset Refractory Status Epilepticus (NORSE).