New-onset refractory
status epilepticus (NORSE) is "a clinical presentation, not a specific diagnosis, in a patient without active
epilepsy or other preexisting relevant
neurological disorder, with new onset of refractory
status epilepticus without a clear acute or active structural, toxic, or metabolic cause." Febrile
infection related
epilepsy syndrome (FIRES) is "a subcategory of NORSE that requires a prior febrile
infection, with
fever starting between 2 weeks and 24 h before the onset of refractory
status epilepticus, with or without
fever at the onset of
status epilepticus." These apply to all ages. Extensive testing of blood and CSF for infectious, rheumatologic, and metabolic conditions, neuroimaging, EEG, autoimmune/paraneoplastic antibody evaluations,
malignancy screen, genetic testing, and CSF metagenomics may reveal the etiology in some patients, while a significant proportion of patients' disease remains unexplained, known as NORSE of unknown etiology or cryptogenic NORSE.
Seizures are refractory and usually super-refractory (i.e., persist despite 24 h of
anesthesia), requiring a prolonged intensive care unit stay, often (but not always) with fair to poor outcomes. Management of
seizures in the initial 24-48 h should be like any case of refractory
status epilepticus. However, based on the published consensus recommendations, the first-line
immunotherapy should begin within 72 h using
steroids,
intravenous immunoglobulins, or
plasmapheresis. If there is no improvement, the
ketogenic diet and second-line
immunotherapy should start within seven days.
Rituximab is recommended as the second-line treatment if there is a strong suggestion or proof of an antibody-mediated disease, while
anakinra or
tocilizumab are recommended for cryptogenic cases. Intensive motor and cognitive rehab are usually necessary after a prolonged
hospital stay. Many patients will have pharmacoresistant
epilepsy at discharge, and some may need continued immunologic treatments and an
epilepsy surgery evaluation. Extensive research is in progress now via multinational consortia relating to the specific type(s) of
inflammation involved, whether age and prior febrile illness affect this, and whether measuring and following serum and/or CSF
cytokines can help determine the best treatment.