Exploratory analysis of cell-free miRNA expression changes in patients with isolated first seizure and new-onset epilepsy

One in ten individuals will experience a seizure in their lives, but only 43%–61% will be diagnosed with new-onset epilepsy (NOE). Existing methods to distinguish between a first unprovoked seizure and a diagnosis of epilepsy are inadequate and often lead to unnecessary treatment with antiseizure medications. To uncover potential targets associated with NOE, we analyzed cell-free circulating miRNA expression in plasma samples obtained from 20 patients who presented with a first unprovoked seizure. Patients were monitored for 2 years following their initial seizure, and a total of 7 patients experienced a second seizure within the follow-up period. Analysis of the miRNA expression levels revealed 15 differentially expressed miRNAs between patients who experienced only a first unprovoked seizure versus those who had a second seizure. These 15 miRNAs were experimentally linked as regulators to 160 genes related to epilepsy, including genes involved in the mTOR and WNT signaling pathways. These findings highlight a number of key circulating miRNA targets that may be further developed as a biomarker signature in larger cohorts and may offer insights into factors associated with epileptogenesis.