Increased cerebral blood flow velocity in children with mild sleep-disordered breathing: a possible association with abnormal neuropsychological function.

Abstract

SLEEP-DISORDERED BREATHING (SDB) encompasses a spectrum of upper airway obstruction in sleep from simple primary snoring, through the upper airways resistance syndrome, to obstructive sleep apnea (OSA). Primary snoring is estimated to affect on average 10% of preschool children1-3 at a time when adenotonsillar size is maximal relative to the airway.4 Emerging evidence has challenged previous assumptions that primary snoring is benign. A recent report identified reduced attention and higher levels of social problems and anxiety/depressive symptoms in snoring children compared with controls.5 Furthermore, a population-based survey identified that habitual snoring was associated with hyperactive and inattentive behavior independent of measures of nocturnal hypoxia.6 Uncertainty persists regarding clinical thresholds for medical or surgical intervention in SDB,7 underlining the need to better understand the pathophysiology of this condition. The causative pathway from SDB to neurocognitive dysfunction in children is poorly understood. Beebe and Gozal8 proposed a model of prefrontal cortical dysfunction resulting from the intermittent hypoxia and sleep fragmentation characteristic of OSA and recommended study of executive function domains in future pediatric research. There is emerging evidence for an executive function deficit in children with SDB.9,10 Systematic review11 and a recent population study12 have supported the hypothesis that intermittent hypoxia may be an important mediator of neurocognitive deficits. The lack of consistent strong correlations between polysomnographic variables and measurable neurocognitive outcomes in studies of childhood SDB9,13 suggests a complex relationship between clinically measurable pathophysiological processes and behavioral abnormality. One possibility is that there are structural and functional adaptations in the brain and its vasculature that obscure any direct effect of exposure to hypoxia or arousals but eventually have deleterious effects. The association between OSA and stroke risk14 in adults has prompted researchers to look for evidence of cerebrovascular disease. Ultrasonography has revealed increased carotid intima-media thickness in adults with OSA.15 Transcranial Doppler (TCD) cerebral blood flow velocity (CBFV)16 measurement in the intracranial arteries17 has demonstrated significant sleep apnea-related fluctuations in CBFV in adult OSA,18 as well as reduced daytime cerebrovascular reactivity to hypercapnia.19 There has been little focus on cerebrovascular function in children with SDB, partly reflecting the need for sedation in neuroimaging of young children and the ethical constraints on using these techniques in research. However, this would seem an important line of investigation, because studies have identified abnormalities of the systemic vasculature.20-22 Amin et al23 demonstrated that increased mean blood pressure variability in children correlated with polysomnographic indices of SDB severity. Increased systemic blood pressure variability in adult populations is associated with cerebrovascular disease and brain atrophy in adults.24 There are advantages to studying cardiovascular morbidity in children who lack the comorbid atherogenic disease that complicates adult clinical research.25 Furthermore, increased CBFV has been associated with deficits on measures of intelligence26,27 and attention28 in children with sickle cell disease, a condition associated with chronic hypoxemia in childhood, suggesting that it is a marker for vulnerable brain tissue with reduced function. We aimed to determine whether CBFV differed between children with mild SDB, below the conventional threshold for surgical intervention, and age and socioeconomically similar controls. Secondary aims were twofold: (1) to explore a possible relationship between polysomnographic indices of SDB (eg, apnea/hypopnea index and pulse oxygen saturation [Spo2]) and CBFV and (2) to explore the extent to which CBFV is associated with SDB and neuropsychological/behavioral scores.