New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES)

New-onset refractory status epilepticus (NORSE) and its subcategory, febrile infection-related epilepsy syndrome (FIRES), are rare clinical presentations characterized by the sudden onset of drug-resistant seizures in individuals without prior epilepsy. These conditions typically follow a biphasic course, beginning with a catastrophic acute phase of status epilepticus followed by a chronic phase of refractory epilepsy and significant cognitive impairment, and are increasingly viewed as immune-inflammatory-mediated encephalopathies involving innate immunity dysfunction. While acute management initially follows traditional protocols for refractory status epilepticus, expert consensus recommends the rapid initiation of first-line immunotherapies, specifically intravenous methylprednisolone, intravenous immunoglobulins (IVIG), or plasma exchange, ideally within the first 72 hours of onset. If there is an inadequate response to these initial interventions, management typically escalates within the first week to second-line treatments, which include the ketogenic diet and targeted immunotherapies such as anakinra (an IL-1 antagonist), tocilizumab (an IL-6 antagonist), or rituximab. Despite extensive diagnostic evaluations, including MRI, EEG, and cerebrospinal fluid analysis, approximately 50% of adult cases and nearly all pediatric FIRES cases remain cryptogenic (of unknown cause). Outcomes are frequently unfavorable, with survivors often experiencing long-term functional disability and mortality rates estimated at 12% in children and 16–27% in adults.