Sudden unexpected death in epilepsy: Fatal post-ictal respiratory and arousal mechanisms

Abstract

Sudden unexplained death in epilepsy (SUDEP) is the cause of premature death of up to 17% of all patients with epilepsy and as many as 50% with chronic refractory epilepsy. However, SUDEP is not widely recognized to exist. The etiology of SUDEP remains unclear, but growing evidence points to peri-ictal respiratory, cardiac, or autonomic nervous system dysfunction. How seizures affect these systems remains uncertain. Here we focus on respiratory mechanisms believed to underlie SUDEP. We highlight clinical evidence that indicates peri-ictal hypoxemia occurs in a large percentage of patients due to central apnea, and identify the proposed anatomical regions of the brain governing these responses. In addition, we discuss animal models used to study peri-ictal respiratory depression. We highlight the role 5-HT neurons play in respiratory control, chemoreception, and arousal. Finally, we discuss the evidence that 5-HT deficits contribute to SUDEP and sudden infant death syndrome and the striking similarities between the two.

The Structural Connectome of the Human Central Homeostatic Network

“…Medullary-forebrain connectivity through the human LFB also provides a potential neuroanatomic basis for CHN disorders such as SUDEP (Engel et al, 2013;Richardson, 2012;Sowers et al, 2013), which is associated with temporal lobe epilepsy (Mueller et al, 2014;Schuele et al, 2011), as well as SIDS and SUDC, which are associated with hippocampal anomalies in infants and young children, respectively (Kinney et al, 2007(Kinney et al, , 2009(Kinney et al, , 2015. A paradoxical feature of the CHN is its marked susceptibility to generate and propagate seizures (Harper, 1986;Oliveira et al, 2011)-paradoxical in that a network so vital to survival is so prone to seizures that are inherently dangerous and potentially lethal.…”

Mechanisms of sudden unexpected death in epilepsy: the pathway to prevention

“…However, these numbers will likely change rapidly, because SUDEP is becoming more salient among patients and their families, and as they educate themselves doctors will become more aware. The pace of publications on SUDEP is rapidly increasing 6 , yet there remains a gap in our knowledge of the mechanisms involved, in part because the unpredictable occurrence of SUDEP has hindered the gathering of high quality data at the time of death. In particular, there have been human SUDEP cases in which the EKG was recorded and respiratory rate was estimated by visual observation, but no blood pressure or tidal volume data were obtained.…”

The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

“…Various neurological conditions are associated with severe breathing disturbances. These disorders include multiple system atrophy (Schwarzacher et al, 2011), Rett syndrome (Ramirez et al, 2013b; Weese-Mayer et al, 2006, 2008b), Familial Dysautonomia (Carroll et al, 2012; Weese-Mayer et al, 2008a), sudden infant death syndrome (Garcia et al, 2013; Kinney et al, 2009; Paterson, 2013), congenital central hypoventilation syndrome (Ramanantsoa and Gallego, 2013), sleep apnea (Gozal and Kheirandish-Gozal, 2008; Ramirez et al, 2013a), Pitt Hopkins Syndrome (Gallego, 2012), and sudden death of epilepsy (Kalume, 2013; Sowers et al, 2013). Thus, understanding how breathing is generated within the nervous system and how the CNS controls ventilatory functions is of great clinical interest.…”