A rare condition that presents with refractory and many times super-refractory status epilepticus, NORSE, including its subtype febrile infection related epilepsy syndrome (FIRES), is heterogeneous without one single etiology.
Researchers of a new paper have outlined an in-hospital approach to managing new-onset refractory status epilepticus (NORSE), a clinical presentation in patients without active epilepsy or another relevant pre-existing neurological disorder.
A rare condition that presents with refractory and many times super-refractory status epilepticus, NORSE, including its subtype febrile infection related epilepsy syndrome (FIRES), is heterogeneous with no single etiology.
“Attempts at controlling status epilepticus should run parallel with disease modification efforts of the presumed disease, even when the etiology is unknown,” the authors wrote. “Acute treatment of seizures should be similar to treatment of RSE in any situation. However, in patients without a clear explanation for SE in the first day or two, one should strongly consider first-line immunotherapy in the form of steroids, IVIG, or plasmapheresis; the consensus recommendations are to start these within the first 72 h of the onset of RSE.”
The group explained that response to first-line methylprednisolone is often incomplete, and second-line treatment should be initiated within 7 days of RSE onset, though outcomes may still improve if administered several weeks after onset. Guidance on second-line treatment relies on anecdotal experience, rather than high-quality data.
Approaches for seizure suppression—guided by local or institutional guidelines—include antiseizure medications, with benzodiazepines as first-line treatment for convulsive status epilepticus. Data has supported levetiracetam, valproate, and fosphenytoin as effective second-line options. The group noted that treatments should be discontinued if a patient does not respond in order to reduce antiseizure medication burden.
Anesthetics can also be considered and, according to the researchers, should be used similarly to that of RSE in other conditions in the first 48 hours. With no preference of one agent over another, options include midazolam, propofol, pentobarbital, thiopental, and ketamine; the latter 3 should be used with caution in the context of mitochondrial disorders, as they are associated with liver dysfunction.
“The Neurocritical Care Society guideline for evaluating and managing status epilepticus discusses the dosing considerations for the above-described anesthetic agents. There are no high-quality data to support the intensity and duration of anesthetic agents. The titration of the anesthetic agent is guided by continuous EEG, with the goal being the suppression of seizures or a background pattern of burst suppression,” the researchers explained.
“Titration to suppression-burst was associated with a lower frequency of seizure recurrence than titration to suppression of seizures; however, it was also associated with a significantly higher frequency of hypotension in a meta-analysis. Neither the choice of the anesthetic agent nor the titration goal was associated with differences in the overall outcome.”
Outside of drug treatment, following the ketogenic diet is recommended within the first week of hospitalization in children and should be considered in all prolonged and severe cases among all ages. In a retrospective study of 77 children with NORSE, the ketogenic diet was the only treatment to shorten the acute phase of presentation. Other data supported the efficacy of the approach while showing mild side effects.
Sheikh Z, Hirsch L. A practical approach to in-hospital management of new-onset refractory status epilepticus/ febrile infection related epilepsy syndrome. Front Neurol. Published online May 12, 2023. doi: 10.3389/fneur.2023.1150496