Intrathecal dexamethasone therapy for febrile infection‐related epilepsy syndrome

Abstract

Objective Increasing reports suggest a role for immunological mechanisms in febrile infection‐related epilepsy syndrome (FIRES). The objective of this study was to elucidate the efficacy and safety of intrathecal dexamethasone therapy (IT‐DEX). Methods We assessed six pediatric patients with FIRES who were administered add‐on IT‐DEX in the acute (n = 5) and chronic (n = 1) phases. We evaluated clinical courses and prognosis. We measured cytokines/chemokines in cerebrospinal fluid (CSF) from FIRES patients at several points, including pre‐ and post‐IT‐DEX, and compared them with control patients with chronic epilepsy (n = 12, for cytokines/chemokines) or with noninflammatory neurological disease (NIND, n = 13, for neopterin). Results Anesthesia was weaned after a median of 5.5 days from IT‐DEX initiation (n = 6). There was a positive correlation between the duration from the disease onset to the introduction of IT‐DEX and the length of ICU stay and the duration of mechanical ventilation. No patient experienced severe adverse events. Seizure spreading and background activities on electroencephalography were improved after IT‐DEX in all patients. The levels of CXCL10, CXCL9, IFN‐γ, and neopterin at pre‐IT‐DEX were significantly elevated compared to levels in epilepsy controls, and CXCL10 and neopterin were significantly decreased post‐IT‐DEX, but were still higher compared to patients with chronic epilepsy. IL‐6, IL‐8, and IL‐1β were significantly elevated before IT‐DEX compared to epilepsy controls, though there was no significant decrease post‐treatment. Interpretation IT‐DEX represents a therapeutic option for patients with FIRES that could shorten the duration of the critical stage of the disease. The effect of IT‐DEX on FIRES might include cytokine‐independent mechanisms.

Cytokines inNew‐OnsetRefractory Status Epilepticus Predict Outcomes

“…However, a decrease in CSF pro-inflammatory cytokine levels was found to be associated with clinical improvement after intrathecal dexamethasone or anakinra therapies. 10,16 The CSF IL-6 and CXCL8 levels were found positively associated to an up-proteomic score that has been suggested as a promising indicator for assessment of the severity of NORSE in a cohort of 11 patients. 15 Proinflammatory cytokines may enhance seizure recurrence and subsequent sequelae.…”

Drug‐resistant seizures associated with hyperinflammatory monocytes in FIRES

“…During the complicated therapeutic odyssey in this child we collected repeated PBMCs and biofluids in an effort to characterize changes in inflammatory response associated with treatment. Remarkably, this patient responded to intrathecal dexamethasone 28 with a profound recovery and resolution of both inflammation and RSE.…”

Review and standard operating procedures for collection of biospecimens and analysis of biomarkers innew onsetrefractory status epilepticus

“…3 Those studies aimed to compare data from patients with NORSE to healthy donors or patients with febrile SE (defined by the emergence of fever within 24 h before SE onset, but not present earlier). [22][23][24][25][26][27] Two other studies were conducted in 2015 and 2016 to compare pediatric patients with FIRES to healthy controls or patients with noninflammatory neurological disorders. 28,29 Both of those studies used the original definition of FIRES proposed in 2010: a non-encephalitic encephalopathy defined by the occurrence of recurrent seizures or SE, which was not necessarily refractory, and was preceded by febrile infection in previously healthy children.…”