FATAL SUPER-REFRACTORY STATUS EPILEPTICUS IN ADULT-ONSET FEBRILE INFECTION-RELATED EPILEPSY SYNDROME (FIRES): A CASE REPORT OF PHARMACOKINETIC CHALLENGES AND EARLY IMMUNOMODULATION
DOI:
https://doi.org/10.22159/ijpps.2026v18i5.58418Keywords:
Febril infection-related epilepsy syndrome, New-onset refractory status epilepticus, Super-refractory status epilepticus, Carbapenem–valproate interaction, Tocilizumab, Multidrug-resistant sepsisAbstract
Febrile Infection-Related Epilepsy Syndrome (FIRES), a subcategory of New-Onset Refractory Status Epilepticus (NORSE), is a catastrophic epileptic encephalopathy that is rarely described in adults. This report describes a fatal case of a 25-year-old woman who developed explosive-onset generalized seizures following a mild febrile prodrome. She rapidly progressed to refractory status epilepticus and met criteria for adult-onset FIRES after exclusion of infectious, structural, toxic, and antibody-mediated autoimmune etiologies. Despite aggressive escalation to super-refractory status epilepticus (SRSE) management with quadruple continuous intravenous anesthetics (propofol, midazolam, ketamine, thiopentone) and multiple antiseizure medications, seizure control remained unstable. The clinical course was critically destabilized by a preventable pharmacokinetic interaction: the initiation of meropenem for multidrug-resistant sepsis in a patient receiving valproic acid resulted in a rapid decline in serum valproate exposure and breakthrough seizures. Advanced immunomodulatory strategies including plasmapheresis, rituximab, and interleukin-6 (IL-6) receptor blockade with tocilizumab were instituted. Tocilizumab achieved transient seizure cessation (48 hours) and permitted partial anesthetic weaning but was followed by profound neutropenia and worsening septic shock. The patient ultimately succumbed to multidrug-resistant sepsis and multiple organ dysfunction syndrome (MODS) on day 39. This case highlights the high mortality of adult FIRES, the absolute contraindication of concurrent carbapenem–valproate therapy, and the potential value of earlier cytokine-targeted immunotherapy.
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