Understanding new-onset refractory status epilepticus from an immunological point of view.

New-onset refractory status epilepticus (NORSE) is unexpected onset of refractory status epilepticus in individuals with no preexisting relevant neurologic condition. The etiologies remain largely cryptogenic; treatment is challenging after failure to control seizures despite use of multiple antiepileptic drugs and anesthetic agents. Frequent fever and other infectious prodromes, elevated proinflammatory cytokine/chemokine levels, and limbic or multifocal brain lesions indicate active inflammation in NORSE. Among identified causes, autoimmune encephalitis is the most common and accounts for more than one-third of all known NORSE cases, followed by infection-related etiologies. Although more evidence is needed, anti-cytokine therapies with tocilizumab and anakinra along with other immunotherapeutic agents used in autoimmune encephalitis can aid in alleviating or hindering the inflammatory cascade and controlling seizures.