Detection of HHV-6 and EBV and Cytokine Levels in Saliva From Children With Seizures: Results of a Multi-Center Cross-Sectional Study

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) infecti...

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Published in:Frontiers in neurology Vol. 9; p. 834
Main Authors: Bartolini, Luca, Piras, Eleonora, Sullivan, Kathryn, Gillen, Sean, Bumbut, Adrian, Lin, Cheng-Te Major, Leibovitch, Emily C., Graves, Jennifer S., Waubant, Emmanuelle L., Chamberlain, James M., Gaillard, William D., Jacobson, Steven
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 05.10.2018
Subjects:
epilepsy
herpesvirus 6
human
inflammation
interleukin-1
Neurology
saliva
epilepsy
herpesvirus 6
saliva
interleukin-1
Epstein-Barr Virus
inflammation
human
pediatric
ISSN:1664-2295, 1664-2295
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Summary: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. 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. Cases included febrile seizures ( = 30), acute seizures without ( = 53) and with fever ( = 4) in chronic epilepsy, new onset epilepsy ( = 13), febrile status epilepticus ( = 3), and first lifetime seizure ( = 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); = 0.02. IL-1β 185.76 (230.57); controls 86.99 (187.39); = 0.0002. IL-1β level correlated with HHV6 viral load ( = 0.007). 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.
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Edited by: Hong Ni, Children's Hospital of Suzhou University, China
Reviewed by: Joaquin Lugo, Baylor University, United States; Dinesh Upadhya, Manipal Academy of Higher Education, India
This article was submitted to Pediatric Neurology, a section of the journal Frontiers in Neurology
ISSN:1664-2295
1664-2295
DOI:10.3389/fneur.2018.00834