Intrathecal dexamethasone therapy for febrile infection-related epilepsy syndrome

Ann Clin Transl Neurol. 2021 Mar;8(3):645-655. doi: 10.1002/acn3.51308. Epub 2021 Feb 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Child
  • Child, Preschool
  • Cytokines / cerebrospinal fluid
  • Cytokines / drug effects*
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology*
  • Electroencephalography
  • Epileptic Syndromes / cerebrospinal fluid
  • Epileptic Syndromes / drug therapy*
  • Epileptic Syndromes / etiology
  • Epileptic Syndromes / physiopathology
  • Female
  • Fever / complications
  • Humans
  • Infections / complications
  • Inflammation / cerebrospinal fluid
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Inflammation / physiopathology
  • Injections, Spinal
  • Male
  • Outcome Assessment, Health Care*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Dexamethasone

Grant support

This work was funded by JSPS KAKENHI grant 19K08311; MHLW Research program on rare and intractable diseases grant JPMH20FC1039.