Sleep Apnea in Pediatric Neurological Conditions Gabor Szuhay, MD, and Josh Rotenberg, MD Corresponding author Gabor Szuhay, MD Department of Neurosciences and Behavioral Medicine, George Washington University of Medicine, Children’s National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010, USA. E-mail: gszuhay@cnmc.org Current Neurology and Neuroscience Reports 2009, 9: 145–152 Current Medicine Group LLC ISSN 1528-4042 Copyright © 2009 by Current Medicine Group LLC Sleep apnea in neurologically compromised children is common but underrecognized. It can be second- ary to diseases at all locations on the neuroaxis and may independently alter their presentation, severity, and course. As a primary and secondary illness, it is associated with signi ficant neurologi- cal morbidities. In its severe manifestation, it can cause life-threatening short- and long-term sys- temic morbidities. The authors review the most recent and relevant literature and provide the pedi- atric neurologist with a framework with which to identify children at risk. Introduction Disordered breathing in sleep is a common and treat- able condition affecting children of all ages. While the presentation has a spectrum of severity, sleep apnea (SA) syndrome implies the presence of markedly abnormal breathing in sleep with disruption in daytime function- ing, behavioral problems, and/or excessive daytime somnolence (EDS). Neurologically impaired children have additional unique and often multiple disease-speci fic risk factors for SA. Genetic susceptibility and treatment exposures also contribute to disease expression. SA can be dif ficult to appreciate in this group of children because patients and parents with cognitive limitations tend to underreport symptoms and signs. Furthermore, SA symptoms and signs may be falsely attributed to the underlying neurological disease. As SA is curable and its morbidities are at least partially reversible, pediatric neurologists must be able to identify patients at risk. Anatomy and Physiology Respiration Ef ficient breathing relies on three intact compartments: the central and peripheral nervous system, the respira- tory musculature, and the airway. The drive to breathe in sleep is largely automatic. Peripheral and central respira- tory chemoreceptors and pulmonary mechanoreceptors all project to the nucleus of the solitary tract. Respiratory rhythm is generated by the medulla’s ventral respiratory group and the pre-Botzinger complex. The carotid bodies are sensitive to hypoxia and project to the ventral respira- tory column’s and pre-Botzinger complex’s glutaminergic neurons via the nucleus of the solitary tract. The seroto- nergic neurons in the medullary raphe and ventral surface are sensitive to carbon dioxide and hydrogen ions. These neurons mainly project to the phrenic nerve. The arcuate nucleus is the equivalent of the central chemoreceptors in animals and perhaps in humans [1••]. Pousielle’s law describes the physics of laminar flow through a tube and speci fies the direct relationship between flow and the fourth power of the tube’s radius. As a result, a small decrease in airway diameter pro- foundly reduces the ef ficiency of breathing. The airway stays patent through tonic activation of the upper airway musculature. In brief, during stage 1 and 2 sleep, voluntary control of respiration persists; automatic breathing occurs in non–rapid eye movement (NREM) and REM sleep. In NREM sleep, respiratory drive depends on input from peripheral chemoreceptors, the diaphragm, and other respiratory muscle groups to stay active. In REM sleep, muscle atonia involves all respiratory muscles except the dia- phragm. Respiration depends more on central drive. In the progression to REM sleep, the activity of the tonic motor neurons is lowest; upper airway resistance (and therefore the risk of apnea) is highest. The amount and distribution of REM sleep and thus the apnea rate vary throughout the night in different age groups. Sleep Ef ficient sleep is important to protect vital functions of the developing brain such as memory consolidation and is maintained by minimizing sleep disruption from arousals. Arousal is necessary to resolve respiratory compromise by