Neurology and Neurosurgery

July 21, 2023

Cryptogenic drug-resistant seizure disorders may involve inflammatory processes that traditional anti-seizure medications don't target. Mayo Clinic researchers found that febrile infection-related epilepsy syndrome (FIRES) might be associated with hyperinflammatory monocytic responses to normally banal bacterial pathogens.

The researchers isolated peripheral blood mononuclear cells (PBMCs) from blood drawn from a 9-year-old child with FIRES both before and after successful treatment with intrathecal dexamethasone. As described in a case report published in the May 2023 issue of Annals of Clinical and Translational Neurology, the previously healthy boy had presented with seizures following streptococcal pharyngitis.

The PBMCs were stimulated ex vivo with bacterial or viral ligands. Cytokine release from the stimulated cells and the levels of inflammatory factors in blood and cerebrospinal fluid were measured and compared with those of healthy pediatric controls.

Key findings

• The patient's blood and cerebral spinal fluid had high levels of inflammatory factors despite treatment with conventional therapies, including intravenous immune globulin, plasma exchange, systemic methylprednisolone and anakinra.
• Ex vivo stimulation of the patient's PBMCs revealed exaggerated interleukin-6 and CXCL8 release in response to bacterial exposure.
• The hyperinflammatory phenotype resolved after the initiation of intrathecal dexamethasone, with the patient experiencing profound recovery.

The researchers note that the mechanism by which dexamethasone mediated these effects is unclear. "It may be that the locus of corticosteroid delivery matters more than the specific identity of the drug," says Charles L. Howe, Ph.D., director of the Translational Neuroimmunology Laboratory at Mayo Clinic in Rochester, Minnesota.

While more research is needed, the Mayo Clinic study offers potential guidance for clinicians managing individuals with FIRES.

"There may be diagnostic relevance in profiling the ex vivo responses of innate immune cells, in addition to performing rapid, serial profiling of inflammatory factors in serum and cerebral spinal fluid," Dr. Howe says.

For more information

Howe CL, et al. Drug-resistant seizures associated with hyperinflammatory monocytes in FIRES. Annals of Clinical and Translational Neurology. 2023;10:719.

Translational Neuroimmunology Laboratory. Mayo Clinic.

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