Intrathecal Dexamethasone as a FIRES Extinguisher: A 12-Patient Clinical Experience with Usage of Intrathecal Dexamethasone for Febrile Infection-Related Epilepsy Syndrome

Abstract

Background: New-onset refractory status epilepticus (NORSE) is a devastating condition with high mortality and poor long-term outcomes. Febrile infection-related epilepsy syndrome (FIRES) is a subset of NORSE, preceded by fever. Intrathecal dexamethasone (IT-DEX) has emerged as a potential treatment, but few cases have been reported. This study aims to describe the use of IT-DEX in NORSE/FIRES, focusing on treatment logistics, dosing strategies, and patient outcomes.

Methods: We conducted a retrospective analysis of 12 patients (10 children and 2 adults) with NORSE (including FIRES) enrolled in an international multicenter clinical biorepository who received IT-DEX as part of their treatment. Demographic and clinical data were extracted. IT-DEX pharmacological details and administration logistics were collected by contacting the primary investigators. A descriptive analysis was performed to evaluate treatment timing, dosage, and concurrent management, as well as clinical outcomes and cytokine profiles.

Results: All patients qualified as FIRES. Patients were treated with a median of five doses of IT-DEX, starting a median of 20 days after refractory status epilepticus onset, with a median dose per infusion of 5 mg (0.21 mg/kg/dose). Clinicians reported a perceived favorable effect on seizure control in 83% of cases, with a median delay of 5 days to wean off continuous infusions after the last IT-DEX administration. Cytokine analysis (based on data from four patients with serial cerebrospinal fluid measurements and two patients with serial blood measurements) revealed persistently elevated levels of proinflammatory markers in most patients, with no significant changes following IT-DEX administration. No adverse effects were reported.

Conclusions: Most clinicians perceived a favorable effect of IT-DEX in refractory status epilepticus termination, and its use appears to be safe in patients with FIRES. This study provides a detailed description of administration logistics and dosing strategies from an international multicenter cohort. Additional studies are needed to confirm the safety and efficacy of IT-DEX and determine its impact on long-term outcomes including epilepsy prevention and functional recovery.

Keywords: Febrile infection-related epilepsy syndrome; Intrathecal dexamethasone; New-onset refractory status epilepticus; Outcomes.