Retrospective multicenter study on cryptogenic NORSE/FIRES patients treated with anakinra

Abstract

Purpose: Refractory status epilepticus (RSE) is a neurological emergency characterized by persistent seizures despite two appropriate antiseizure medications. It is defined as new-onset RSE (NORSE) when occurring in previously healthy people. NORSE is defined as cryptogenic (cNORSE) when no cause is found. Febrile-infection related epilepsy syndrome (FIRES) is now defined as the cNORSE variant preceded by fever. In 2016 anakinra was reported effective in an anecdotal case. After this experience, second-line immunotherapy has been increasingly used, being incorporated in cNORSE recommendations in 2022.

Methods: We conducted a retrospective study in an Italian case series of 14 patients with cNORSE (including FIRES cases) treated with anakinra in Italy before implementation of the international recommendations, that could serve as historical reference for futures studies based on the shared recommendations.

Results: In our population higher duration of intensive care stay period was associated with later time of anakinra use, although no evidence of efficacy on the long-term neurological outcome was demonstrated.

Conclusion: There is an urgent need for well-designed head-to-head multicenter prospective clinical trials to clarify the benefits of available treatments and the role of biomarkers to guide choices.

Keywords: Cryptogenic NORSE (cNORSE); Febrile infection-related epilepsy syndrome (FIRES); Interleukin-1 inhibitor; New-onset refractory status epilepticus (NORSE); Refractory status epilepticus (RSE).