Potential mechanisms of sudden unexpected death in epilepsy

• Published in: Epilepsy & behavior Vol. 26; no. 3; pp. 410 - 414
• Main Authors: Tolstykh, Gleb P., Cavazos, José E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2013
• Subjects: Animals; Autonomic Nervous System Diseases - etiology; Cell Death - physiology; Death, Sudden - epidemiology; Death, Sudden - etiology; Disease Models, Animal; Epilepsy - complications; Epilepsy - epidemiology; Humans; KCNK channels; Neurology; Neuron loss; Neurons - pathology; NTS; Nucleus of the solitary tract; Rats; Solitary Nucleus - pathology; Solitary Nucleus - physiopathology; SUDEP; Nucleus of the solitary tract; Neuron loss; SUDEP; NTS; KCNK channels
• ISSN: 1525-5050; 1525-5069; 1525-5069
• DOI: 10.1016/j.yebeh.2012.09.017

Sudden unexpected death in epilepsy (SUDEP) accounts for 15% of all deaths in people with epilepsy and 50% in refractory epilepsy. The underlying mechanisms are not well understood, but seizure-induced cardiac and respiratory arrests are involved. The cardiovascular and respiratory systems are subject to precise reflex regulation to ensure appropriate oxygen supply under a wide range of circumstances. Barosensory and chemosensory afferents project into the nucleus tractus solitarius (NTS), which relays systemic data to higher brain centers for integration of homeostatic responses in heart rate, peripheral resistance, respiration, and other autonomic reactions. Being the afferent autonomic gatekeeper, NTS plays a critical role in cardiovascular and respiratory regulation. In the course of studying the kainic acid model, we became aware of progressive neuronal loss in the NTS and noted SUDEP-like deaths in rats with frequent convulsions. Increased autonomic susceptibility with inhalation anesthetics was also observed, often seen after impairment of baroreceptor and chemoreceptor reflex loops. Seizure-induced neuron loss in NTS may play a role impairing the integrative functions of NTS resulting in poor homeostatic responses during seizures and leading to SUDEP. This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”. ► The definition and risk factors for SUDEP are discussed. ► Descriptions of homeostatic cardiorespiratory reflexes mediated by chemo- and baro-receptors inputs into the nucleus of the solitary tract (NTS) are presented. ► KCNQ channel physiology is discussed in the setting of the integrative function of the NTS. ► Disruption of this integrative function may play a role in SUDEP.