MicroRNAs and SUDEP: news in small matters

Abstract

In approximately 30% of patients with temporal lobe epilepsy (TLE), seizures are refractory to medical therapy, and 9 in 1000 of these intractable patients will die yearly from sudden unexpected death in epilepsy (SUDEP) [1]. Importantly, several authors have emphasized the search of possible physiological biomarkers of SUDEP risk in animal models of acquired human TLE [1, 2]. With these considerations in mind, we enjoyed reading the recent article entitled, “MicroRNAs in temporal lobe epilepsy: a systematic review” by Asadi-Pooya and colleagues published in your esteemed journal [3]. In brief, the authors made clear some evidence on the potential applications of circulating serum microRNAs (specially microRNA-153) as biomarkers in people with drug-resistant TLE [3]. Thus, as neuroscientists are still unaware of the real involvement of circulating microRNAs in epilepsy [3], we applaud the authors for pursuing this topic. Furthermore, the possible role of microRNAs on SUDEP also deserves further reflections. Over the past 10 years, we are witnessing an illuminating period in SUDEP research [1]. In this view, it is common sense that epilepsy is the most common severe chronic neurological disease, that it affects millions of people globally, and that epidemiological studies have shown that it is accompanied by an increased risk of premature death compared to the general population [1, 2]. SUDEP is the most important direct epilepsy-related causes of death, accounting for 10–50% of all deaths [1, 2]. By far, the generalized tonic–clonic seizures (GTCS) frequency are the leading risk factor for SUDEP [1, 2]. In the current perspective, it is already known that seizure-induced cardiogenic SUDEP [1, 2]. For that, several studies have point out pathophysiological changes in both cardiac and brain tissue in SUDEP patients, which could act to generate arrhythmias [2]. Therefore, since a new class of specific circulating microRNAs has been recognized as potential biomarkers for cardiovascular disorders, it has also been considered the possibility that these same molecules could also be useful in the investigation of epilepsy and SUDEP [2–5]. In fact, the insight about the roles that microRNAs influence in epileptogenesis and biology of several cardiovascular diseases might be the key to explicate novel biomarkers for diagnosis and prognosis of possible SUDEP cases [2–5]. Thus, our research group recently evaluated the impact of the number of seizures on expression of microRNAs in the hearts of rats with epilepsy [2]. Importantly, we clearly found an increased in microRNA-21 and decreased in microRNA-320 expression in ventricles of rats with epilepsy, suggesting that the numbers of seizures impair cardiac function and morphology, probably through microRNA modulation [2]. Currently, there are no minimally invasive tests available in clinical practice to accurately diagnose possible SUDEP cases. Certainly, it is very probable that prospective * Fulvio A. Scorza [email protected]