Abstracts

Rationale: Experimental and clinical findings suggest a crucial role of inflammation in epileptogenesis. An emerging hypothesis is that various brain insults, including viral infections, can induce a cascade of chronic inflammatory processes in the CNS as well as increased permeability of the blood–brain barrier, leading to enhanced neuronal excitability which may contribute to epileptogenesis. Previous studies detected Human Herpesvirus-6B (HHV-6B) in blood from patients with febrile seizures and febrile status epilepticus and in resected epileptogenic tissue from temporal lobe epilepsy cases.Aim of this study was to determine the frequency of HHV6 and EBV infection and cytokine expression in saliva from children with seizures compared with children with a febrile illness without seizures. Methods: We analyzed saliva from 115 children with acute seizures (cases) and 51 children with a fever and no seizures or underlying neurological disease (controls) by means of a novel droplet digital PCR for HHV-6A, HHV-6B and Epstein-Barr Virus (EBV) and a bead-based immunoassay for neuroinflammatory cytokines that included interleukin-8 (IL-8), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor (TNF), and interleukin-12p70 (IL-12p70). Statistical analysis included Pearson Chi-squared, Mann-Whitney U test, one-way analysis of variance on ranks and Spearman’s correlation. Results: Cases had a mean age of 6.3 years (standard deviation [SD] 5.1) and included febrile seizures (n=30), acute seizures without (n=53) and with fever (n=4) in chronic epilepsy, new onset epilepsy (n=8), febrile status epilepticus (n=3) and first lifetime seizure (n=17). Mean age of controls was 5.9 years (SD 5.5). We observed no difference in HHV-6 and EBV detection and viral loads across groups. IL-8 and IL-1β were upregulated in saliva of 32 children with seizures of any etiology compared with 30 controls (p=0.02 and p=0.0002, respectively). We found a positive correlation between age and IL-8 (r=0.335, p=0.007) and IL-1β (r=0.343, p=0.006) but no correlation between fever grade, single/multiple seizures or short/long seizures and cytokine expression.  Conclusions: We demonstrated upregulation of inflammatory cytokines in saliva of children with seizures, and found no differences in HHV-6 or EBV detection frequency in several groups of children with seizures, including febrile seizures, compared with children with acute febrile illness. Funding: The study did not receive financial support.