LAUSR

Cytokine profiling prior to immunotherapy is increasingly prevalent in Febrile infection-related epilepsy syndrome (FIRES). In this case, an 18-year-old boy presented with first-onset seizure after a nonspecific febrile illness. He developed super refractory status epilepticus requiring multiple anti-seizure medications and general anesthetic infusions. He was treated with pulsed methylprednisolone, plasma exchange and ketogenic diet. Contrast-enhanced MRI brain revealed post-ictal changes. EEG showed multifocal ictal runs and generalized periodic epileptiform discharges. Cerebrospinal fluid analysis, autoantibody testing and malignancy screen were unremarkable. Genetic testing revealed variants of uncertain significance (VUS) in the CNKSR2 and OPN1LW genes.Initial serum and CSF cytokine analyses performed on days 6 and 21 revealed that IL-6, IL-1RA, MCP1, MIP1β and IFNγ were elevated predominantly in the CNS, a profile consistent with cytokine release syndrome. Tofacitinib was initially trialed on day 30 of admission. There was no clinical improvement and IL-6 continued to rise. Tocilizumab was given on day 51 with significant clinical and electrographic response. Anakinra was subsequently trialed from days 99 to 103, as clinical ictal activity re-emerged on weaning anesthetics, but stopped due to poor response.Serial cytokine profiles showed improvement after 7 doses of tocilizumab. There was corresponding improved seizure control.This case illustrates how personalized immunomonitoring may be helpful in cases of FIRES, where proinflammatory cytokines are postulated to act in epileptogenesis. There is an emerging role for cytokine profiling and close collaboration with immunologists for the treatment of FIRES. The use of tocilizumab may be considered in FIRES patients with upregulated IL-6.