Abstract
Epilepsy is one of the neurological diseases of complex etiology that affects around 50 million people worldwide and is characterized by abnormal electrical activity and recurrent seizures. Uncontrolled generalized repetitive tonic-clonic seizures (GTCS) are the main causes of unexpected sudden death in epilepsy (SUDEP). Hypoxic stress induced by seizure results in neurocardiogenic dysfunctions, including iron overload and cardiomyopathy (IOC) which is related to severe lipid peroxidation caused by the production of reactive oxygen species (ROS). ROS induces recurrent seizure activity, favoring the overexpression of P glycoprotein (P-gp) in the heart. P-gp plays a depolarizing role in cardiomyocyte membranes and potassium (Kir) channels control cellular excitability regarding the repolarization of the cardiac action potential. All these events result in a possible appearance of severe bradycardia and fatal arrhythmia. Several studies have sought evidence for different possible biomarkers for potential prediction of the risk of SUDEP avoiding its fatal outcome.
Highlights
Epilepsy is a chronic neurological disorder characterized by abnormal electrical activity of the brain with a permanent predisposition to generate epileptic seizures[1]
Sudden and unexpected death in epilepsy (SUDEP) may be related to heart failure due to high hypoxic stress and sympathetic over-stimulation that results in neurocardiogenic injury, since it affects the electrical properties of the heart, this favors the possible appearance of severe bradycardia and fatal arrhythmia[20]
The subsequent response to this stress is the activation of hypoxia-inducible factor 1 (HIF1), which is involved in cellular homeostasis, with its targets directed at vasomotor control, angiogenesis, erythropoiesis, iron metabolism and cell death 21 and regulation positive expression of responsive genes such as P glycoprotein (P-gp) and erythropoietin EPO receptor[22]
Summary
Epilepsy is a chronic neurological disorder characterized by abnormal electrical activity of the brain with a permanent predisposition to generate epileptic seizures[1]. Other lines of research point to terminal cardiac arrhythmia due to hypoxic stress triggered by frequent seizures associated with sympathetic overstimulation that leads to neurocardiogenic injury compromising the electrical properties of the myocardium, resulting in severe bradycardia and fatal cardiac arrhythmia[6,7]. Ferroptosis and iron metabolism in epilepsy Much has been said about the various forms of cell death that are involved in the pathogenesis of diseases[8].
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