Impaired CO2-Induced Arousal in SIDS and SUDEP

• Published in: Trends in neurosciences (Regular ed.) 2019-04, Vol.42 (4), p.242-250
• Main Author: Buchanan, Gordon F.
• Format: Article
• Language: English
• Subjects: arousal; chemoreception; serotonin; sudden death
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/j.tins.2019.02.002

Premature, sudden death is devastating. Certain patient populations are at greater risk to succumb to sudden death. For instance, infants under 1year of age are at risk for sudden infant death syndrome (SIDS), and patients with epilepsy are at risk for sudden unexpected death in epilepsy (SUDEP). Deaths are attributed to these syndromic entities in these select populations when other diagnoses have been excluded. There are a number of similarities between these syndromes, and the commonalities suggest that the two syndromes may share certain etiological features. One such feature may be deficiency of arousal to CO2. Under normal conditions, CO2 is a potent arousal stimulus. Circumstances surrounding SIDS and SUDEP deaths often facilitate CO2 elevation, and faulty CO2 arousal mechanisms could, at least in part, contribute to death. SIDS and SUDEP are among the leading causes of death in their respective patient populations (i.e., infants under 1year of age and patients with refractory epilepsy), but their pathophysiology is poorly understood. Some common features of SIDS and SUDEP have been identified, including impaired cardiorespiratory function and dysfunctional serotonin signaling. A possible common pathophysiological mechanism is impaired arousal in response to elevated CO2. Individuals at risk for both conditions experience situations in which serum CO2 concentrations rise (e.g., due to physical airway obstruction, or as a consequence of a seizure). However, the physiological mechanisms of CO2-induced arousal from sleep are not fully understood, and whether a definitive link to SIDS or SUDEP exists remains to be validated. Better understanding of the mechanisms of CO2-induced arousal, and how these impaired mechanisms possibly contribute to death in SIDS and SUDEP, may help address the pressing need for effective prevention strategies in these conditions.