Abstract
PurposeInflammation plays a crucial role in epileptogenesis. We analyzed inflammatory cytokines in plasma and saliva from children with seizures and healthy controls and measured their associations with HHV6 and EBV infection. MethodsWe analyzed plasma from 36 children within 24 h of 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 PCR for viral DNA. Primary outcome was cytokine levels in cases vs. controls. Secondary outcomes included detection of HHV-6 and EBV viral DNA in cases vs. controls and viral loads in cases vs. controls. Statistical analysis included the Wilcoxon Rank Sum test, Fisher's exact test, ANOVA, and Spearman correlation. ResultsCompared to controls, patients had higher levels of CCL11 (p = 0.0018), CCL26 (p<0.001), IL10 (p = 0.044), IL6 (p<0.001), IL8 (p = 0.018), and MIP1β (p = 0.0012). CCL11 was higher with 3 or more seizures (p = 0.01), seizures longer than 10 min (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 a correlation. The frequency of HHV-6 and EBV detection was similar across groups and not different than controls. We found no correlation between viral load and cytokine levels. ConclusionsWe showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to viral infection.
Highlights
Experimental and clinical findings suggest a crucial role of inflammation in epileptogenesis
We showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to human herpesvirus (HHV)-6 infection
An emerging hypothesis is that various brain insults, including viral infections, from herpesviruses such as human herpesvirus (HHV)-63 can contribute to epileptogenesis by inducing a cascade of chronic central nervous system (CNS) inflammatory processes and increased blood–brain barrier permeability, leading to enhanced neuronal excitability.[4,5]
Summary
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. Current antiepileptic drugs target seizures symptomatically but not underlying pathophysiological mechanisms.[1] Experimental and clinical findings suggest a crucial role of inflammation in epileptogenesis.[2] New therapeutic strategies are necessary to improve seizure control and quality of life for people with epilepsy. An emerging hypothesis is that various brain insults, including viral infections, from herpesviruses such as human herpesvirus (HHV)-63 can contribute to epileptogenesis by inducing a cascade of chronic central nervous system (CNS) inflammatory processes and increased blood–brain barrier permeability, leading to enhanced neuronal excitability.[4,5] Previous studies highlighted the role of glial cells (astrocytes and microglia) and neurons in production of inflammatory cytokines.[6]
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