Symptomatic management of NORSE/FIRES: Acute and chronic anti-seizure treatment

The treatment paradigm in new onset refractory status epilepticus (NORSE) and its subtype febrile infection-related epilepsy syndrome (FIRES) is generally multimodal, including treatments that target the underlying etiology (immunotherapy) and symptomatic treatment of seizures (anti-seizure medications (ASMs), ketogenic diet, and neuromodulation/epilepsy surgery). In the acute phase, treatment with escalating ASMs and anesthetic agents ensues as per other etiologies of refractory status epilepticus (RSE), with prompt initiation of ketogenic diet and first and second line, targeted immunotherapy. After resolution of RSE, treatment in the chronic phase consists of de-escalating ASM polypharmacy, acute immunotherapy, and often ketogenic diet while continuously considering side effect profile, seizure burden, and quality of life to find an appropriate balance. No single ASM is considered superior and treatment is tailored to the individual patient and side effect/comorbid disease profiles. Importantly, we lack high level evidence to guide symptomatic or targeted treatment in both the acute and post-acute phases, and further research is needed to identify the best treatment strategy.