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Updated: Aug 6, 2025
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A Behavioral Screen for Heat-Induced Seizures in Mouse Models of Epilepsy
Published on: July 12, 2021
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Drug-resistant seizures associated with hyperinflammatory monocytes in FIRES
Charles L Howe1,2,3,4, Renee K Johnson1, Brittany L Overlee1
1Translational Neuroimmunology Lab, Mayo Clinic, Rochester, Minnesota, USA.
Annals of Clinical and Translational Neurology
|March 16, 2023
Summary
Febrile infection-related epilepsy syndrome (FIRES) involves a hyperinflammatory response. Intrathecal dexamethasone (dexamethasone delivered into the cerebrospinal fluid) may resolve seizures by normalizing this immune overreaction.
Area of Science:
- Neuroscience
- Immunology
- Pediatric Neurology
Background:
- Therapies for Febrile Infection-Related Epilepsy Syndrome (FIRES) are limited and often ineffective.
- Inflammation is a key driver of FIRES pathogenesis.
- Investigating the monocytic response profile in FIRES is crucial for understanding disease mechanisms.
Observation:
- Peripheral blood mononuclear cells (PBMCs) from a child with FIRES exhibited hyperinflammatory cytokine release (IL6, CXCL8) upon bacterial stimulation during refractory status epilepticus (RSE).
- Elevated serum inflammatory markers (IL6, CXCL8, HMGB1, S100A8/A9, CRP) and CSF IL6 were observed during RSE.
- Following intrathecal dexamethasone therapy, RSE resolved, inflammatory markers normalized, and the ex vivo PBMC hyperinflammatory response renormalized.
Findings:
- FIRES is associated with a hyperinflammatory monocytic response to bacterial pathogens.
- This inflammatory response may lead to increased neutrophils and exacerbate neuroinflammation.
- Ex vivo analysis of PBMCs provides insights into the immune dysregulation in FIRES.
Implications:
- Intrathecal dexamethasone may resolve RSE by modulating the inflammatory feedback loop.
- Understanding the monocytic response in FIRES can guide the development of targeted therapies.
- This study highlights the potential of immunomodulatory treatments for FIRES.
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