Differential Activation of Neuroinflammatory Pathways in Children with Seizures
Abstract number :
1.081
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2019
Submission ID :
2421077
Source :
www.aesnet.org
Presentation date :
12/7/2019 6:00:00 PM
Published date :
Nov 25, 2019, 12:14 PM
Authors :
Luca Bartolini, National Institutes of Health; Michael P. Moran, National Institutes of Health; Gina Norato, National Institutes of Health; Bobbe Thomas, Children's National Medical Center; Alexander D. Dick, Children's National Medical Center; Elizabeth
Rationale: Experimental and clinical findings suggest a crucial role of inflammation in epileptogenesis. We measured levels of inflammatory cytokines in plasma and saliva from children with acute seizures and healthy controls and measured their associations with HHV6 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 immunoassay (Meso Scale Discovery) including: IFNgamma, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, TNFalpha, CCL2, CCL3, CCL4, CCL11, CCL17, CCL22, CCL26, CXCL10. Saliva from all controls and 6 cases and blood from 26 controls and 16 cases were analyzed by ddPCR for HHV6 and EBV 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 than controls in children with three or more seizures (p=0.01), in those with seizures longer than 10 minutes (p=0.001) and when EEG showed focal slowing (p=0.02). Cytokine levels were not associated with the height of fever.In saliva, we observed higher levels of IL-1beta in febrile seizures (n=7, p=0.04) and IL-6 in new onset seizures (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: Children with febrile seizures had activation of the IFNg/CXCL10/IL-10 pathway, highlighting a potential link with viral infection, possibly other than HHV-6 or EBV. Children with new onset of seizures had higher levels of CCL11, a cytokine that can enhance microglial neuroinflammation and reduce hippocampal neurogenesis. CCL11 was even higher in children with chronic epilepsy, perhaps suggesting that its production by resident CNS cells may contribute to epileptogenesis. Funding: This study was funded by the American Epilepsy Society, the NINDS Division of Intramural Research and by WBCARN U03MC00006 Children’s National PECARN site
Translational Research