Update in new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome

New-onset refractory status epileptics (NORSE) and a subset, febrile infection-related epilepsy syndrome (FIRES), are rare clinical presentations with rapid onset, cryptogenic etiology, unpredictable course, and long-standing neurologic sequalae. International consensus recommendations were published in 2022 to aid in diagnosis, treatment, and research of NORSE/FIRES. Subsequently, there have been advances in understanding both the pathophysiology and the efficacy of immunotherapies.

There is growing evidence of immune dysregulation in NORSE/FIRES. Cytokine/chemokine profiles may serve as biomarkers to guide diagnosis and management. The treatment landscape for NORSE/FIRES is evolving, with increasing use of second-line immunotherapies such as anakinra and tocilizumab. Intrathecal dexamethasone is an emerging treatment. Additionally, studies are investigating more targeted immunotherapies based on immunologic profiles. Despite treatment, outcomes remain poor, with high morbidity and mortality. Neurologic sequalae includes intractable epilepsy, functional impairment, mood disorders, and behavioral disturbances. Many patients report poor quality of life.

NORSE/FIRES is a severe neurologic entity. Research is underway to determine pathogenesis, develop biomarkers, and provide more targeted immunotherapies with hopes of improving patient outcomes.