Blood-brain barrier-associated serum proteins as potential diagnostic biomarkers of epilepsy aetiology.

Abstract

Aim of study: We aimed to assess serum levels of proteins associated with the blood-brain barrier (BBB) in two aetiological populations of patients with epilepsy in the interictal period: genetic and structural-metabolic epilepsy.

Clinical rationale for study: Proteins associated with the BBB are emerging as potential indicators and/or inducers of pro-epileptogenic changes within the central nervous system (CNS). Dysfunction of BBB is known to contribute to the development of epilepsy, while on the other hand dysregulated BBB might be the result of seizures.

Material and methods: Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 100 patients who were seizure-free for a minimum of seven days and analysed by ELISA.

Results: Serum level of TSP-2 was higher in patients with genetic epilepsy compared to structural-metabolic epilepsy (p < 0.05), while P-selectin was higher in patients with structural-metabolic epilepsy (p < 0.05). Additionally, generalised linear mixed models showed higher levels of MMP-9 and MMP-2 in patients with structural-metabolic epilepsy, and higher levels of TSP-2 in patients with genetic epilepsy. Levels of S100B, CCL-2, ICAM-1, TIMP-1 and TIMP-2 did not differ between the two groups.

Conclusions and clinical implications: Serum levels of MMP-9, MMP-2, and P-selectin are elevated in patients with structural-metabolic epilepsy in the interictal period, which may indicate persistent impairment of the vascular part of the BBB. Serum level of TSP-2 was elevated in patients with genetic epilepsy, which may suggest its impact on synaptogenesis. Our study underlines the complexity of epilepsy, and indicates that different molecules participate in BBB disruption/restoration and neuroinflammation in different aetiological subgroups of epilepsy.