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Aim: To evaluate i) the relationship between epilepsy and inflammation by analyzing the levels of thymus activation-regulated chemokine (TARC), and interferon regulatory factor 5 (IRF5) in healthy controls, patients with epilepsy on monotherapy and polytherapy, ii) the levels of sICAM5, chemokine (c-x3-c motif) ligand 1 (CX3CL1), and septin 7 (SEPT7) which are important in both inflammation and synaptic formation. Methods: Patients who were seizure-free with monotherapy (epilepsy group-1), patients with drug-resistant epilepsy (epilepsy group-2), and healthy controls were included. Demographical data, disease durations, and medications were noted. Measurements were made by commercial ELISA kits. Results: The numbers of epilepsy group-1, epilepsy group-2, and healthy controls were 23, 20, and 21, respectively. TARC levels were significantly lower in healthy controls than in both epilepsy groups. Higher TARC levels than 0.58 pg/ml indicated epilepsy with a sensitivity of 81.8% and specificity of 84.0%. SEPT7 levels were significantly higher in epilepsy group-1 than in those epilepsy group-2. A negative correlation was found between SEPT7 levels and disease duration as is the case for the correlation between SEPT7 and average seizure duration. A positive correlation was found between IRF5 and CX3CL1 levels, SEPT7 and IRF5 levels, and IRF5 and sICAM5 levels. Conclusions: We suggest that TARC is a promising biomarker, even in a heterogeneous epilepsy group not only for drug-resistance epilepsy but also for seizure-free epilepsy with monotherapy. Additionally, drug resistance, longer disease, and longer seizure durations are related to lower levels of SEPT7, which has an essential role in immunological functions and dendritic morphology.

Epilepsy is a common affliction that involves inflammatory processes. There are currently no definitive chemical diagnostic biomarkers in the blood, so diagnosis is based on a sometimes expensive synthesis of clinical observation, radiology, neuro-psychological testing and interictal and ictal EEG studies. Soluble ICAM5 (sICAM5), also known as telencephalin, is an anti-inflammatory protein of strictly CNS-origin that is also found in blood. Here we have tested the hypothesis that plasma concentrations of select inflammatory cytokines, including sICAM5, might serve as biomarkers for epilepsy diagnosis. To test this hypothesis, we developed a highly sensitive and accurate electrochemiluminescent ELISA assay to measure sICAM5 levels, and measured levels of sICAM5 and 18 other inflammatory mediators in epilepsy patient plasma and controls. Patient samples were drawn from in-patients undergoing video-EEG monitoring, without regard to timing of seizures. Differences were defined by t-test, and Receiver Operating Condition (ROC) curves determined the ability of these tests to distinguish between the two populations. In epilepsy patient plasmas, we found that concentrations of anti-inflammatory sICAM5 are reduced (p=0.002) and pro-inflammatory IL-1β, IL-2 and IL-8 are elevated. TARC (thymus and activation regulated chemokine, CCL17) concentrations trend high. In contrast, levels of BDNF and a variety of other proinflammatory mediators are not altered. Based on p-value and ROC analysis, we find that the ratio of TARC/sICAM5 discriminates accurately between patients and controls, with an ROC Area Under the Curve (AUC) of 1.0 (p=0.034). In conclusion, we find that the ratio of TARC to sICAM5 accurately distinguishes between the two populations and provides a statistically and mechanistically compelling candidate blood biomarker for drug resistant epilepsy.