MicroRNAs (miRNAs) are key regulators of gene expression and are involved in the pathomechanisms of epilepsy. MiRNAs may also serve as peripheral biomarkers of epilepsy. We investigated the miRNA profile in the blood serum of patients suffering from mesial temporal lobe epilepsy (mTLE) following a single focal seizure evolving to a bilateral convulsive seizure (BCS) during video-EEG monitoring. Data of 15 patients were included in the final analysis. MiRNA expression was determined using Real Time-PCR followed by thorough bioinformatical analysis of expression levels. We found that more than 200 miRNAs were differentially expressed in the serum of patients within 30 min after a single seizure. Validation of the 20 top miRNA candidates confirmed that 4 miRNAs (miR-143, miR-145, miR-532, miR-365a) were significantly deregulated. Interestingly, in a sub-group of patients with seizures occurring during sleep, we found 10 miRNAs to be deregulated up to 20-28 h after the seizure. In this group of patients, miR-663b was significantly deregulated. We conclude that single seizures are associated with detectable transient miRNA alterations in blood serum in the early postictal phase. The significant upregulation of miR-663b following BCS arising during sleep indicates potential suitability of this miRNA as a potential biomarker for seizure diagnostics. (C) 2016 Elsevier Inc. All rights reserved.