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Intrathecal dexamethasone in FIRES
Wai Dic Foong1, Zhibin Tan1, Sarah Hasnor Abu Hassan1
1Department of Neurology, National Neuroscience Institute (NNI) @ Singapore General Hospital (SGH), 1 Hospital Blvd., Singapore, 168581, Singapore; Neuroscience Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, 8 College Rd., Singapore, 169857, Singapore.
Background:
New-onset refractory status epilepticus (NORSE) and its subset, febrile infection-related epilepsy syndrome (FIRES), are rare but severe neurological disorders. Conventional systemic immunotherapies such as intravenous methylprednisolone, intravenous immunoglobulin, and biologic agents often yield suboptimal outcomes. Intrathecal dexamethasone (IT-DEX) has emerged as a potential therapeutic option. Here, we review existing literature on the use of IT-DEX in patients with FIRES.
Methods:
Searches of PubMed and Google Scholar (1 January 2010-31 December 2025) was performed, and reports of NORSE/FIRES treated with IT-DEX were reviewed. Demographical data, ancillary test findings, cytokine profiles, IT-DEX regimen, and treatment outcomes were extracted and analysed.
Results:
Two case series and six case reports were identified, comprising 24 patients with FIRES. The median age was 7 years (IQR 6-12). Prior to receiving IT-DEX, all were treated with systemic immunotherapy and anaesthetic agents. IT-DEX was initiated a median of 19.5 days (IQR 10.5-39.5) from onset, with a median dose and cumulative dose of 0.20 mg/kg/dose (IQR 0.19-0.25) and 1.12 mg/kg (IQR 0.90-1.29) respectively, administered at a median of 72-hour intervals. Patients received a median of 5 doses (IQR 4.5-6). No adverse events were reported. 87.5% showed clinical improvement, and anaesthetic agents were discontinued in nearly all. 39.1% achieved favourable functional outcomes, especially in those receiving cumulative doses of ≥ 1 mg/kg (p = 0.048). However, improvement in cytokine levels and the time to commencing IT-DEX did not influence treatment outcomes.
Conclusion:
IT-DEX may represent a promising therapeutic option for FIRES, particularly in children and adolescents. Our findings provide preliminary evidence supporting its potential use, with administration at 72-hour intervals to a cumulative dose of 1 mg/kg emerging as a potentially reasonable approach. However, further studies are required to determine its optimal dosing, safety and efficacy.
