AUTHOR=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 

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

JOURNAL=Frontiers in Neurology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00834

DOI=10.3389/fneur.2018.00834

ISSN=1664-2295

ABSTRACT=<p><bold>Background and Objective:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Cases included febrile seizures (<italic>n</italic> = 30), acute seizures without (<italic>n</italic> = 53) and with fever (<italic>n</italic> = 4) in chronic epilepsy, new onset epilepsy (<italic>n</italic> = 13), febrile status epilepticus (<italic>n</italic> = 3), and first lifetime seizure (<italic>n</italic> = 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); <italic>p</italic> = 0.02. IL-1β 185.76 (230.57); controls 86.99 (187.39); <italic>p</italic> = 0.0002. IL-1β level correlated with HHV6 viral load (<italic>p</italic> = 0.007).</p><p><bold>Conclusion:</bold> 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.</p>