ABSTRACT
Most case series of patients experiencing sudden death in the setting of epilepsy document a significant preponderance of cases occurring during sleep, especially nocturnal sleep (Kloster and Engelskjøn 1999; Langan et al. 2005). However, the mechanisms underlying this strong tendency have gone relatively unexplored when considering the etiology of sudden unexpected death in epilepsy (SUDEP). In general, three main mechanisms have been proposed to explain SUDEP: (1) a seizure poses an insurmountable autonomic stress to the heart resulting in an arrhythmia, (2) the epileptogenic process itself deranges central autonomic network function substantially, thus rendering the heart more vulnerable to arrhythmogenesis, and (3) a prolonged postictal apnea results in death. Of course, these are not mutually exclusive explanations, and they may all play a role in SUDEP, with potentially additive effects in a given patient. The first two mechanisms appear to be potentially highly synergistic. In this chapter, we will review aspects of the sleep-wake cycle and other circadian factors that are potentially relevant to the pathogenesis of SUDEP, with emphasis on the role of dysfunctional central autonomic cardiac regulation. Additionally, we will propose a unifying theory of the pathogenesis of SUDEP based on the reviewed evidence. Unfortunately, because of the very limited research in this area, much of our discussion will be speculative, but we hope it may stimulate much needed research.
