Sudden unexpected death in epilepsy (SUDEP) is defined as “sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in patients with epilepsy with or without evidence for a seizure, and excluding documented status epilepticus, in which postmortem examination does not reveal a structural or toxicological cause of death”
[14][15][42,43]. SUDEP is responsible for a total of about 8–17% of the causes of death in epilepsy patients. In adults, the prevalence of SUDEP is estimated at approximately 1.2 cases per 1000 people per year
[14][42]. The most probable, commonly known risk factors for SUDEP are early age of onset, male gender, long duration of the disease, generalized tonic-clonic seizures (GTCS), the underlying disease causing the epilepsy, polytherapy, and patient’s lack of cooperation in the treatment process. The structural brain abnormalities, abnormal neurological assessment and intellectual disability, and psychiatric comorbidities also predispose to SUDEP
[16][44]. In addition, the risk of SUDEP increases when seizures occur during sleep and at night
[14][17][18][42,45,46]. In 2015, Mostacci et al. found that patients with nocturnal frontal lobe epilepsy (the syndrome’s name has been changed from autosomal dominant nocturnal frontal lobe epilepsy to sleep-related hypermotor epilepsy) did not show a higher risk of SUDEP. They suggested the need for an additional risk factor for SUDEP, possibly the occurrence of GTCS
[19][47]. SUDEP pathomechanisms may result from arrhythmias, paroxysmal cardiomyopathy, dysfunction of the autonomic nervous system, and seizure-related respiratory failure. Nashef et al.
[15][43] indicated the possibility of a coexisting susceptibility to sudden cardiac death―independent of or related to the epilepsy―that becomes symptomatic in the presence of uncontrolled seizures. It is extremely important that there is a group of epilepsy patients with various types of cardiac repolarization abnormalities that also occur in the interictal period. The occurrence of these changes, regardless of epileptic seizures, may be associated with gene mutations (e.g., leading to long QT syndrome and catecholaminergic polymorphic ventricular tachycardia) and mutations of the sodium channel genes SCN1A, SCN5A, potassium KCNH2, etc., which may cause the clinical picture of the disease with seizures, epilepsy, and fatal arrhythmias. Genetically conditioned shortening of the QT complex may be associated with peri-paroxysmal tachyarrhythmia and an increased risk of SUDEP. The discovery of mutations in the KCNQ1 gene in laboratory animals is associated with their predisposition to the occurrence of long QT syndrome and epileptic seizures. Because long QT is associated with an increased risk of arrhythmias, it appears to be responsible for a certain percentage of SUDEP cases as well
[17][20][21][45,48,49].
Scorza et al.
[17][45] suggested, that modifications to the expression pattern of circulating miRNAs may be associated with abnormal underlying cardiovascular processes and may be identified and used as SUDEP biomarkers
[17][45]. De Matteis et al.
[22][50] conducted a study of patients with SUDEP compared with 10 autopsies of traumatic or asphyxia deaths. They analyzed the expression profiles of several miRNAs (miR-301a-3p, miR-194–5p, miR-30b-5p, mIR-342-5p, and miR-4446-3p) from the plasma and temporal lobe and identified upregulation of miR-301a-3p in the plasma (2.3-fold) and hippocampus (3.2-fold) for SUDEP vs. controls
[14][22][42,50]. Pansani et al.
[23][51], in animal models of epilepsy, found in the group of rats with epilepsy and five GTCS increased in microRNA-21 and decreased in microRNA-320 expression compared to the group of rats without epilepsy and the group of rats with epilepsy and ten GTCS. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation
[23][51].
A new class of specific circulating miRNAs has been identified as potential biomarkers of cardiovascular disorders, therefore there is a reasonable focus that the same molecules could also be useful in the investigation of SUDEP
[17][45]. However, most authors believe that this potential biomarker still needs to be confirmed with additional cases.