NORSE/FIRES: how can we advance our understanding of this devastating condition?

Abstract

Introduction: New onset refractory status epilepticus (NORSE) is a rare and devastating condition characterised by the sudden onset of refractory status epilepticus (RSE) without an identifiable acute or active structural, toxic, or metabolic cause in an individual without a pre-existing diagnosis of epilepsy. Febrile infection-related epilepsy syndrome (FIRES) is considered a subcategory of NORSE and presents following a febrile illness prior to seizure onset. NORSE/FIRES is associated with high morbidity and mortality in children and adults.

Methods and results: In this review we first briefly summarise the reported clinical, paraclinical, treatment and outcome data in the literature. We then report on existing knowledge of the underlying pathophysiology in relation to in vitro and in vivo pre-clinical seizure and epilepsy models of potential relevance to NORSE/FIRES.

Discussion: We highlight how pre-clinical models can enhance our understanding of FIRES/NORSE and propose future directions for research.

Keywords: FIRES; NORSE; animal models; autoantibodies; immunomodulation; status epilepticus.

Figure 1

Graphical representation of features of pre-existing epilepsy animal models that align with disease stages of NORSE/FIRES. No single model recapitulates the full disease course. (A) Animal models that reproduce the acute phase of Status Epilepticus. (B) Animal models that show features of acute seizures and cognitive impairment. (C) Animal models that show features of both refractory seizures and cognitive impairment. (D) Pre-clinical models that demonstrate refractory seizures in vitro. Figure created in Biorender.com.