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Based on evidence that inflammation drives pathogenesis in FIRES, we used ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) to characterize the monocytic response profile before and after therapy in a child successfully treated with dexamethasone delivered intrathecally six times between hospital Day 23 and 40 at 0.25\u2009mg\/kg\/dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PBMCs were isolated from serial blood draws acquired during refractory status epilepticus (RSE) and following resolution associated with intrathecal dexamethasone therapy in a previously healthy 9\u2010year\u2010old male that presented with seizures following Streptococcal pharyngitis. Cells were stimulated with bacterial or viral ligands and cytokine release was measured and compared to responses in age\u2010matched healthy control PBMCs. Levels of inflammatory factors in the blood and CSF were also measured and compared to pediatric healthy control ranges.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During RSE, serum levels of IL6, CXCL8, HMGB1, S100A8\/A9, and CRP were significantly elevated. IL6 was elevated in CSF. Ex vivo stimulation of PBMCs collected during RSE revealed hyperinflammatory release of IL6 and CXCL8 in response to bacterial stimulation. Following intrathecal dexamethasone, RSE resolved, inflammatory levels normalized in serum and CSF, and the PBMC hyperinflammatory response renormalized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>FIRES may be associated with a hyperinflammatory monocytic response to normally banal bacterial pathogens. This hyperinflammatory response may induce a profound neutrophil burden and the consequent release of factors that further exacerbate inflammation and drive neuroinflammation. Intrathecal dexamethasone may resolve RSE by resetting this inflammatory feedback loop.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51755","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T08:21:05Z","timestamp":1678954865000},"page":"719-731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Drug\u2010resistant seizures associated with hyperinflammatory monocytes in <scp>FIRES<\/scp>"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-8739","authenticated-orcid":false,"given":"Charles L.","family":"Howe","sequence":"first","affiliation":[{"name":"Translational Neuroimmunology Lab Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota USA"},{"name":"Center for MS and Autoimmune Neurology Mayo Clinic  Rochester Minnesota USA"},{"name":"Division of Experimental Neurology Mayo Clinic  Rochester 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