CSF high-mobility group box 1 is associated with drug-resistance and symptomatic etiology in adult patients with epilepsy

Abstract

Purpose: Extracellular high-mobility group box 1 (HMGB1) is considered a proinflammatory mediator and is involved in various neurological disorders. This study aims to determine the expression profiles of HMGB1 in cerebrospinal fluid (CSF) and paired serum, and to explore whether there is a relationship between CSF HMGB1 concentrations with seizure parameters in adult patients with epilepsy.

Methods: CSF and paired serum HMGB1 concentrations were measured in patients with drug-refractory epilepsy (DRE, n = 27), newly diagnosed epilepsy (NDE, n = 56), and other non-inflammatory neurological disorders (ONNDs, n = 22). The correlations in HMGB1 levels between CSF and blood were performed. The associations between HMGB1 levels and seizure parameters were analyzed.

Results: Mean (± SD) CSF HMGB1 concentrations were 5.08 ± 3.06, 3.03 ± 2.25, 0.83 ± 0.77 ng/mL in patients with DRE, NDE, and ONNDs, respectively. Corresponding mean (± SD) serum concentrations were 4.53 ± 2.81, 2.32 ± 1.54, 1.56 ± 0.84 ng/mL. The CSF HMGB1 concentrations were significantly higher in the DRE and NDE groups compared with the ONNDs group (p < 0.001). There were no correlations in HMGB1 levels between CSF and serum in the DRE, NDE, and ONNDs groups. Furthermore, patients with symptomatic etiology showed significantly high levels of CSF HMGB1. Patients without remission expressed elevated levels of CSF HMGB1 at one-year follow-up. Additionally, the CSF HMGB1 levels were positively associated with seizure frequency.

Conclusion: Our study shows that HMGB1 may be a critical player in seizure mechanisms and CSF HMGB1 might be predictive in determining epilepsy etiology and prognosis.

Keywords: Biomarker; Brain inflammation; Cerebrospinal fluid; Epilepsy; High-mobility group box 1.