Detection of HHV-6 and EBV and cytokine levels in saliva from children with seizures: Results of a multi-center cross-sectional study

Luca Bartolini, Eleonora Piras, Kathryn Sullivan, Sean Gillen, Adrian Bumbut, Cheng Te Major Lin, Emily C. Leibovitch, Jennifer S. Graves, Emmanuelle L. Waubant, James M. Chamberlain, William D. Gaillard, Steven Jacobson

Research output: Contribution to journalArticlepeer-review


Background and Objective: One third of children with epilepsy are refractory to medications. Growing data support a role of common childhood infections with neurotropic viruses and inflammation in epileptogenesis. Our objective was to determine the frequency of Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) infection and cytokine levels in saliva from children with seizures compared to healthy controls and to controls with a febrile illness without seizures. Methods: In this cross-sectional multi-center study, we collected saliva from 115 consecutive children with acute seizures (cases), 51 children with a fever and no seizures or underlying neurological disease (fever controls) and 46 healthy children (healthy controls). Specimens were analyzed by a novel droplet digital PCR for HHV-6 and EBV viral DNA and a bead-based immunoassay for neuroinflammatory cytokines. Results: Cases included febrile seizures (n = 30), acute seizures without (n = 53) and with fever (n = 4) in chronic epilepsy, new onset epilepsy (n = 13), febrile status epilepticus (n = 3), and first lifetime seizure (n = 12). HHV-6 DNA was found in 40% of cases vs. 37% fever controls and 35% healthy controls, with no statistically significant differences. EBV DNA was also detected with no differences in 17% cases, 16% fever controls, and 28% healthy controls. IL-8 and IL-1β were increased in saliva of 32 random samples from cases compared with 30 fever controls: IL-8 cases mean (SD): 1158.07 pg/mL (1427.41); controls 604.92 (754.04); p = 0.02. IL-1β 185.76 (230.57); controls 86.99 (187.39); p = 0.0002. IL-1β level correlated with HHV6 viral load (p = 0.007). Conclusion: Increase in inflammatory cytokines may play a role in the onset of acute seizures and saliva could represent an inexpensive and non-invasive method for detection of viral DNA and cytokines.

Original languageEnglish
Article number834
JournalFrontiers in Neurology
Issue numberOCT
Publication statusPublished - Oct 5 2018


  • Epilepsy
  • Epstein-Barr virus
  • Herpesvirus 6
  • Human
  • Inflammation
  • Interleukin-1
  • Pediatric
  • Saliva

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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