Differential Activation of Neuroinflammatory Pathways in Children with Seizures: A Cross-Sectional Study

Abstract

Background: Experimental and clinical findings suggest a crucial role of inflammation in epileptogenesis. We aimed to analyze levels of inflammatory cytokines in plasma and saliva from children with acute seizures and healthy controls and measure their associations with HHV6 and EBV infection. Methods: We analyzed plasma from 36 children within 24 hours of acute seizures (cases) and 43 healthy controls and saliva from 44 cases and 44 controls with a multiplex immunoassay. Saliva from all controls and 65 cases and blood from 26 controls and 35 cases were also analyzed by ddPCR for viral DNA. Statistical analysis included Wilcoxon Rank Sum test, Fisher’s exact test, ANOVA and Spearman correlation. Results: Compared to controls, children with breakthrough seizures (n=18) had higher levels of CCL11 (p<0.001), CCL26 (p<0.001), IL-8 (p=0.03), CCL4 (p=0.02) in plasma. Children with new onset seizures (n=13) showed higher levels of CCL11 (p=0.05) and IL-6 (p=0.01). Patients with febrile seizures (n=5) had higher levels of IFNg (p<0.001), IL-6 (p<0.001), IL-10 (p<0.001), CXCL10 (p=0.001). CCL11 was higher with 3 or more seizures (p=0.01), seizures longer than 10 minutes (p=0.001) and when EEG showed focal slowing (p=0.02). In saliva, febrile seizures had higher levels of IL-1β (n=7, p=0.04) and new onset seizures had higher IL-6 (n=15, p=0.02). Plasma and saliva cytokine levels did not show correlation. Frequency of HHV-6 and EBV detection was similar across seizure types and not different than controls. We found no correlation between viral load and cytokine levels Conclusions: We showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to HHV-6 infection.