Cardiac and Autonomic Mechanisms Contributing to SUDEP

Abstract

Sudden unexpected death in epilepsy is likely caused by a cascade of events affecting the vegetative nervous system leading to cardiorespiratory failure and death. Multiple genetic, electrophysiological, neurochemical, and pharmacological cardiac alterations have been associated with epilepsy, which can affect autonomic regulation of the heart and predispose patients to sudden unexpected death in epilepsy. These cardiac and autonomic changes are more frequently seen in patients with longstanding and medication refractory epilepsy and may be a prerequisite for sudden unexpected death in epilepsy. Cardiac changes are also observed within the immediate periictal period in patients with and without preexisting cardiac pathology and could be the tipping point in the cascade of events compromising autonomic, respiratory, and cardiac function during an epileptic convulsion. Better understanding if and how these cardiac alterations can make a particular individual with epilepsy more susceptible to sudden unexpected death in epilepsy will hopefully lead us to more effective preventative strategies.

The yield of long‐term electrocardiographic recordings in refractory focal epilepsy

“…The absence of postictal arrhythmias in our study, despite the recording of thousands of seizures in a high-risk group, suggests that the demonstration of postictal arrhythmias is not sensitive enough to evaluate SUDEP risk. [16][17][18] The first of two previous studies reported that one-fifth of people had a clinically relevant bradycardia or asystole with subsequent permanent pacemaker insertion. Subject 9 was excluded from analysis due to newly diagnosed dissociative seizures.…”

“…Accordingly, most periods of ictal asystole (80%) were found to be symptomatic 15 ; loss of tone and falls during a typical focal seizure with impaired awareness provide an important diagnostic clue for ictal asystole. [16][17][18] The first of two previous studies reported that one-fifth of people had a clinically relevant bradycardia or asystole with subsequent permanent pacemaker insertion. 9 Although no special attention was given to exact timing of the arrhythmias, all events coincided with typical focal seizures and likely resemble ictal asystole.…”

Exploring novel AEDs from drugs used for treatment of non-epileptic disorders

“…Moreover, uncontrolled seizures themselves can increase the risk of severe cardiovascular events, such as sudden unexpected death [68]. To ensure the safe use of COX-2 inhibitors in the treatment of epilepsy, we may need to take some additional measures, such as shortening the time of COX-2 inhibitor use, using smaller or even subclinical dosages, or developing drugs that act downstream of the COX-2 pathway or its other targets such as prostaglandin E2 receptor subtype (EP2) which had been demonstrated to have beneficial effects in mouse SE model and lack the cardiovascular side effects [69].…”

Heart Conduction and Rhythm Disorders in Iktal Epilepsy Period: The Prevalence and Predictors

“…Большая часть публикаций о нарушениях ритма сердца при эпилепсии, встречаемых в отечественной и зарубежной литературе, посвящена роли сердечных аритмий в патогенезе внезапной необъяснимой смерти при эпилепсии (SUDEP), поскольку, по мнению большинства исследователей, нарушения сердечного ритма и проводимости являются ведущим фактором в возникновении SUDEP [1][2][3][4].…”

“…Данные литературы нередко противоречивы, что подтверждает актуальность дальнейшего изучения патогенетических механизмов, факторов риска, частоты встречаемости, характера изменений сердечного ритма и роли противоэпилептической терапии в возникновении нарушений ритма и проводимости сердца у пациентов с фокальной эпилепсией в период развития эпилептических приступов [2][3][4][5].…”