Plasticity induced loss of apnea alarm through repeated apneas: A proposed mechanism for respiratory sudden death

Abstract

We are inspired by two observations and questions. 1) In most cases of sudden unexpected death in epilepsy (SUDEP) patients experience a fatal failure to breathe which onsets a few minutes after a seizure, suggested to be of neural (not mechanical) origin. If respiration is such a critical behavior, then how could the architecture of the respiratory neural circuit ever allow an extended apnea to persist until it is fatal, especially in low-risk cases (first lifetime seizure) in which the patient’s brain is not measurably impaired in any way? 2) Emerging data continue to support the theory that there are often concrete, measurable physiological changes in a patient prior to SUDEP, particularly in their respiratory reflexes and apnea drive. If this theory is true, then how could the architecture of the respiratory neural circuit acquire increased risk of fatal extended apnea? In this article we focus on the supposed “suffocation alarm” in the respiratory neural circuit, the balance of apnea and breathing, and how the balance can shift in both healthy controls and several disorders. The variations in suffocation alarm presentation suggest that the respiratory neural network can permit extended apnea without inducing alarm, arousal, or significant compensatory hyperpnea, even in healthy subjects. This apnea comfort can be induced with existing, healthy plasticity in apnea training (swimming and diving), pathologies which might mimic apnea training (repeated apneas in epilepsy, obstructive sleep apnea), or pathologies which modify the stability and feedback of the system (carotid body resection, neurodegeneration). These similarities, along with emerging data about the fundamental dynamics of the respiratory brainstem, suggest a network structure in which apnea can become a “steady state” and persist until death unless there is an outside stimulus like cardiopulmonary resuscitation.