The following is a summary of “Bridging the Gap: Tailoring an Approach to Treatment in Febrile Infection‐Related Epilepsy Syndrome,” published in the June 2023 issue of Neurology by Goh, et al.
For a study, researchers sought to highlight the potential benefit of personalized immunomonitoring and cytokine profiling in febrile infection-related epilepsy syndrome (FIRES) and to explore the use of tocilizumab, an interleukin-6 (IL-6) inhibitor, in the treatment of FIRES patients with elevated IL-6 levels.
An 18-year-old man presented with his first seizure following a febrile illness. He developed super-refractory status epilepticus and received various treatments, including pulsed methylprednisolone, plasma exchange, and a ketogenic diet. Initial investigations were unremarkable, including CSF analysis, autoantibody testing, and malignancy screening. Genetic testing revealed uncertain significance variants in the CNKSR2 and OPN1LW genes. Serum and CSF cytokine analysis revealed elevated levels of IL-6, IL-1RA, monocyte chemoattractant protein-1, macrophage inflammatory protein 1β, and interferon γ, indicating a cytokine release syndrome primarily in the central nervous system (CNS).
Tofacitinib, a Janus kinase inhibitor, was administered but did not result in clinical improvement, and IL-6 levels continued to rise. Tocilizumab, an IL-6 inhibitor, was administered, leading to significant clinical and electrographic improvement. Anakinra, an IL-1 receptor antagonist, was subsequently trialed but discontinued due to a poor response. Serial cytokine profiling showed improvement after multiple doses of tocilizumab, accompanied by improved seizure control.
The case demonstrated the potential utility of personalized immunomonitoring and cytokine profiling in managing FIRES, where proinflammatory cytokines are implicated in epileptogenesis. Close collaboration with immunologists and tocilizumab, particularly in patients with upregulated IL-6, is a treatment strategy for FIRES. Further research and larger studies were warranted to establish the effectiveness of cytokine-targeted therapies in FIRES management.