Epileptic encephalopathy: Can glial activity factors be used asbiomarkers?

Objectives: Epileptic encephalopathies (EE) is the name given to conditions that can be seen at any age, but mostly begin in infancy and early childhood, where cognitive and neurological functions worsen in relation to epileptic activity. Lennox-Gastaut Syndrome with a wide variety of resistant seizures and West Syndrome with epileptic spasms are among the most common epileptic encephalopathies, and it is thought that they may be related to immunological mechanisms with their response to immunotherapy. Therefore, it was planned to study these patients mainly. In this study, to investigate the presence of glial activity factors such as TREM2, RANKL, HMGB1, S100-B, GFAP, CHI3L1, CXCL-13, sIL-2R, sCD-163 in the blood of patients with idiopathic epileptic encephalopathy, especially in patients with West Syndrome and Lennox-Gastaut Syndrome. and according to the results, it is aimed to reach new information about the role of these factors as biomarkers in EE and to lay the groundwork for the development of diagnosis and treatment strategies. Materials and Methods: A total of 31 patients, including 18 idiopathic WS patients aged 0-18 years, 13 idiopathic LGS patients diagnosed with EE, and 31 age/sex-matched healthy controls were included in the study. To identify the contribution of glial activity in EE, serum levels of TREM2, RANKL, HMGB1, S100-B, GFAP, CHI3L1, CXCL-13, sIL-2R, sCD-163 were measured in all serum samples by immunohistochemical analysis or ELISA. Results: When patients' seizure onset age and duration of disease were evaluated, LGS patients were significantly older than WS patients and the disease duration was significantly longer. Patients with EE showed significantly higher levels of CHI3L1 than healthy controls. HMGB1, CHI3L1, sCD163 and TREM2 levels were higher in LGS patients compared to WS patients and/or healthy controls. One or more of the mediators investigated were associated with response to treatment, disease severity, and presence of pathological features on EEG. Conclusion: The findings of our study provide the first patient-based evidence that astrocyte- and microglia-mediated neuroinflammation may play a role in the pathogenesis of LGS and WS. Moreover, glial mediators may serve as prognostic biomarkers in patients with idiopathic IE. In summary, our results provide a "proof-of-concept" basis for the contribution of glial cells, particularly in LGS patients, thereby confirming the findings of previous animal model studies and patient-based immunohistochemistry reports. Keywords: Epileptic Encephalopathy; West syndrome; Lennox-Gastaut syndrome; chitinase-3-like protein 1; glia; neuroinflammation