Diagnostic value of matrix metalloproteinase-2 and high mobility group box 1 in patients with refractory epilepsy

Abstract

Introduction There are large numbers of inflammatory molecules and humoral mediators that can be involved in the epileptogenesis such as cytokines, matrix metalloproteinases (MMP), and high mobility group box-1 (HMGB1). We aimed to evaluate serum levels and the diagnostic value of MMP-2 and HMGB1 in Iraqi patients with epilepsy. Methods One hundred epileptic patients comprised 60 controlled epileptics and 40 refractory patients to treatment with multi antiepileptic drugs (AEDs). Other 50 family-unrelated age- and sex-matched healthy subjects were selected to represent the control group. Serum levels of MMP-2 and HMGB1 were estimated using ELISA. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of these markers when required. Results MMP-2 level was significantly higher in controls than epileptic patients in general (controlled and refractory patients). ROC curve, showed poor diagnostic value of MMP-2 in discriminating epileptics into responsive or refractory to treatment from controls (AUC = 0.679 (95% CI = 0.536-0.823), and AUC = 0.77 (95% CI = 0.637-902), respectively). Serum HMGB1 level in epileptic patients and controls was in close approximation to each other. Conclusions MMP-2 is significantly decreased in patients particularly those with refractory epilepsy (RE); however, it has poor diagnostic value. No difference in the serum HMGB1 level between epileptic patients and controls.

Diagnostic Value of High Mobility Group Box-1 (HMGB1) in Children with Refractory Epilepsy

“…When compared to a control group of healthy individuals, both factors were notably elevated in epileptic patients. In agreement with us, there was no statistically remarkable variation in age, weight, and sex between the case and control groups [4].…”

“…Walker et al [17] found a similar increase in the total HMGB1 serum concentration following seizures in epilepsy patients who had been seizurefree for more than six months (8.6 3.5 against 1.25 0.71, p 0.0001) and in those who were resistant to AED treatment (8.6 3.5 versus 0.7 0.3, p 0.002). In contrast, the Salih study found no statistically significant variation in serum HMGB1 levels between epilepsy patients who were controlled and those who were refractory to treatment [4].…”

“…Numerous inflammatory compounds and humoral mediators, such as matrix metalloproteinases (MMP) cytokines, and high mobility group box-1, can contribute to epileptogenesis (HMGB1) [4].…”

Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction

“…In this study, we chose molecules whose levels are not only known to be affected in epilepsy but also which can be measured in serum (MMP-9, MMP-2, CCL-2, S100B, TIMP-1, TIMP-2, ICAM-1, TSP-2, P-selectin) [ 4 , 9 , 11 , 18 , 27 , 28 ]. The aim of the study was to assess if the examined molecules can be considered biomarkers of seizure prediction.…”