The Brain in Sleep-disordered Breathing
Authors: David Gozal
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

public health problem. Indeed, several studies suggest that 2–3% of children between 2 and 8 years of age, 5–7% of stuttering or speech impediments from childhood. The mechmale middle-aged adults, and more than 15% of all people anism(s) by which such specific and localized regional taraged 65 years or older are affected (1), even when rather geting was achieved are unclear but direct the search for restrictive diagnostic criteria are used. Although substantial origins of SDB to an earlier stage of life (4), thereby raising research over the last two decades has provided invaluable the possibility of developmental contributions or neural ininsights on the pathophysiology of SDB, it is becoming in- sults as major pathophysiologic issues underlying the SDB creasingly clear that a single mechanism cannot explain the syndrome. presence or absence of the condition in the average patient. Is there any evidence to support such a heretic possibility? Several putative mechanisms would appear to be operative Most of the now well-established occurrences of neural defiat the same time to induce the decompensation of naturally cits in SDB patients would suggest otherwise. For example, occurring and system-embedded redundancies that routinely aberrant sensory processing of stimulation to the upper airpreserve upper airway patency. In other words, none of the way (5, 6), impaired autonomic responses (7), or the recent increased mass effect secondary to obesity, reduced upper demonstration of a reduction in apnea by atrial pacing (8) airway dilator motor tone during sleep, altered chemosensi- implicates deficits in central neural mechanisms. These neural tivity, and reduced mandibular and nasopharyngeal size can deficits have thus far been justifiably assumed to represent singly explain the occurrence and progression of SDB. There- a consequence of SDB rather than to precede the syndrome. fore, interactions between these pathophysiologic factors, to Perhaps the time has come to reverse our thinking. name just a few, need to occur. Coincidentally, initial genetic An additional important implication of this study relates population linkage studies suggest the occurrence of multiple to the potential location of brain regions affected by the genes as being involved in SDB and further reinforce the typical alterations that accompany SDB, namely, episodic concept of cross interactions between multiple genetically hypoxemia, hypercapnia, and arousal from sleep. These afdetermined elements in SDB (2). fected regions most likely underlie the prominent neurobeIs it then possible that genetically related alterations leading havioral deficits that occur in both pediatric and adult patients to abnormal neuronal proliferation or to premature neuronal with SDB and involve a wide range of behavioral, language, cell loss within particular brain regions mediating sleep, up- and cognitive skills. The anatomic findings reported by Macey per airway motor control, and/or cardiorespiratory regulation and coworkers (3) suggest dysfunction in Broca’s language could be implicated in SDB? Could primary abnormalities area, the hippocampus, a structure implicated in recent memoccurring in brain organogenesis or during postnatal develop- ory functions, the frontal and cerebellar cortices, associated ment lead to specific alterations in the functional characteris- with a range of cognitive aspects and processes involved tics of the “upper airway patency module” and provide a in selective inhibition of motor expression, important for unifying link between a primary central nervous system ab- Attention Deficit Disorder, and limbic structures, such as the normality and the generation of the SDB phenotype?