Anakinra in the treatment of new-onset refractory status epilepticus: Our experience from a clinical case

ABSTRACT

Background and aims: Recent studies have associated functional and genetic defects in interleukin-1 pathway with New-Onset Refractory Status Epilepticus (NORSE), supporting the use of anakinra in the treatment of this disease;however, the evidence is limited. Methods: Case-report. Results: A 23-year-old male, with history of a cousin with epileptic encephalopathy, presented refractory convulsive status epilepticus (SE), preceded by febrile episodes, requiring non-barbituric sedation and admission to intensive care unit (ICU). Blood tests and brain-MRI were normal. CSF analysis showed mild mononuclear pleocytosis, elevated proteins and negative microbiological study. Antineuronal and anti-neuropil antibodies in serum/CSF were negative. Initial video-EEG showed diffuse slowing. Fullbody CT-scan and testicular ultrasound showed no findings. Nosocomial SARS-CoV-2 infection was diagnosed. Patient presented torpid evolution, persisting fever and seizures, despite anti-seizure drugs and barbituric sedation. Successive video-EEGs showed burst-suppression pattern alternating with multifocal seizures with left frontotemporal predominance, progressing to continuous SE when sedation was reduced. Methylprednisolone, IVIg, plasma exchange and tocilizumab were administered without response. Anakinra 5mg/kg/dose was started with dramatic improvement in level of consciousness and EEG, reverting SE pattern and withdrawing sedation;however, focal and focal to bilateral tonic-clonic seizures persisted daily. Anakinra was removed after four weeks due to neutropenia without aggravation. The frequency/intensity of seizures kept improving until two-per-week. He is currently on third month in ICU and under valproate, brivaracetam, zonisamide, perampanel, ketogenic diet and cannabidiol. Conclusion: Given the proposed pathophysiology for NORSE, anakinra is an interesting treatment option. We report a positive, although incomplete, response to anakinra. More evidence is required to support this indication.