© 2008 American Thoracic Society doi: 10.1164/rccm.200808-1214ED
Matters of the HeartThe Brain in Pediatric Sleep Apnea
Kosair Children's Hospital Research Institute
The heart is the chief feature of a functioning mind. In the last decade, the increased awareness of the high prevalence of obstructive sleep apnea (OSA) in children has led to a remarkable expansion in our knowledge of the pathophysiology and morbidity associated with this condition. As in adults afflicted with the disease, OSA in children is associated with substantial neurobehavioral and cardiovascular consequences (1, 2). Although a dose-dependent relationship between the severity of OSA, as we currently measure it, and the magnitude of end-organ dysfunction has emerged, the strength of such relationships is rather modest, whereby only approximately 40% of the variance in cognitive function can be explained by the alterations in polysomnographic measures (3). In other words, at any given level of OSA severity, there will be children with a spectrum of cognitive function ranging from normal to severe dysfunction (2). The obvious question for such disparate findings is "Why?" In this issue of the Journal (pp. 870–875), Abou Khadra and colleagues examine some of the factors that adversely affect regional cerebral oxygenation (rSO2) in sleeping children who habitually snore by conducting simultaneous recordings of rSO2 with near-infrared spectroscopy in conjunction with standard polygraphic and beat-to-beat blood pressure measurements (4). One of their major findings is that, during stable sleep patterns in the absence of ongoing respiratory events, habitually snoring children without OSA are more likely to display reduced rSO2 than are control subjects or children with OSA (4). Opposite findings may have been reported if rSO2 had been measured during the respiratory events (5, 6). Rather surprisingly, when considering the important role played by CO2 in rSO2 (7), Abou Khadra and colleagues fail to incorporate end-tidal CO2 into their analyses (4). On the basis of the assigned role of CO2 in cerebral blood flow and oxygenation, we could postulate that increased mean end-tidal CO2 during stable sleep patterns without obvious respiratory events in OSA may have contributed to the ameliorated and normalized rSO2 in OSA patients and that the absence of such events in habitually snoring children may have prevented improved rSO2 during sleep. However, Abou Khadra and colleagues report that the mean end-tidal CO2 was actually lower in children with OSA (4), so that there seems to be a contradiction between the anticipated effect of CO2 on rSO2 and the findings reported by these investigators. The major elements identified in the multivariate modeling analyses as being detrimental to the stability of rSO2 were male sex, non-REM sleep, and increasing arousal index (4). Sex differences in cerebral blood flow have previously been described and could have played a role in the relatively older cohort of children studied (mean age of 10 yr) even though Tanner sexual development stages were not reported. However, in normal individuals, REM sleep has been traditionally associated with more variable and greater fluctuations in rSO2 patterns than in deeper non-REM stages, whereas clear reductions in rSO2 were recorded in the transition from wakefulness to non-REM sleep (8). Similarly, increased arousals would theoretically allow for adjustments and corrections in the underlying rSO2, so that one would have expected improved, rather than lower, rSO2 in the context of increased arousal index (9). The autoregulatory mechanisms that govern brain perfusion would predict that increased blood pressure (mean arterial pressure [MAP]) operates as an important component of rSO2 levels. Thus, the association between higher MAP and corresponding increases in rSO2 in the study by Abou Khadra and colleagues (4) was anticipated. However, cortical hemodynamic and rSO2 responses to MAP oscillations follow specific phase relationships due to cerebral autoregulatory action and circulatory transit times (10), such that alterations in microvascular properties and overall endothelial functioning may impose substantial disruption of autoregulatory mechanisms, particularly during obstructive apneic events (11), and ultimately underlie the adverse cognitive consequence of sleep-disordered breathing in children. Although we are unaware of any studies specifically addressing vascular reactivity responses in snoring children with and without OSA, such tests should provide more reliable estimates of rSO2 trajectories during transient states such as those occurring during the nocturnal evolution of both normal and diseased sleep (12). Furthermore, endothelial dysfunction clearly occurs in children with OSA (13), and both the magnitude of middle cerebral artery velocity (an indicator of cerebral autoregulatory vasomotor activity), brain metabolic function, and systemic inflammatory responses in the context of pediatric OSA have recently emerged as important determinants of cognitive outcomes in pediatric OSA (14–16). Studies like that of Abou Khadra and colleagues (4), which aim to integrate characteristics of cardiovascular functional responses and tissue oxygen delivery in the context of sleep-disordered breathing, may provide a better understanding of whether the poet Jean Ingelow was indeed correct when she wrote "The brain runs away with the heart's best blood." FOOTNOTES Conflict of Interest Statement: D.G. serves on the National Speaker Bureau for Merck Company and received $6,000 in 2006 and $8,000 in 2007 for lectures sponsored by the company. REFERENCES
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