Cerebral Blood Flow and Childhood Obstructive Sleep Apnea

Obstructive sleep apnea syndrome (OSAS) causes hypoxemia and hypercapnia, which may impair cerebral blood flow and cause deficits in behavior. This is a case-control study designed to investigate cerebral blood flow and neurocognitive function in children with OSAS when compared to these findings from normal children. The study hypothesis is that children with OSAS have an impaired cerebral blood flow during wakefulness and sleep compared to normal controls, and that the degree of this impairment correlates with neurocognitive function.

OSAS is characterized by repetitive occlusion of the upper airway during sleep that results in hypoxemia, hypercapnia and arousal from sleep. Children with the obstructive sleep apnea syndrome (OSAS) have impaired behavior and cognition compared to normal controls. Previous studies in adults with OSAS have shown significant alterations of cerebral blood flow during wakefulness and sleep and our preliminary data showed blunted cerebral blood flow response to hypercapnia in children with OSAS during wakefulness. However, it is unknown whether children with OSAS also have impaired cerebral blood flow during sleep. It is also unknown whether the deficits in behavior and cognition in children are associated with cerebral blood flow dysregulation.

This study will investigate whether the changes in cerebral blood flow during wakefulness and sleep elicited by hypercapneic challenge, differ in children with OSAS compared to normal controls. Additionally the study will evaluate the changes in cerebral blood flow during wakefulness and sleep elicited by hypercapneic challenge in children with OSAS before and after treatment (adenotonsillectomy, adenoidectomy, or tonsillectomy). Finally, the study will investigate whether the changes in cerebral blood flow elicited by the aforementioned testing correlate with neurocognitive outcomes.

Children with OSAS aged 6-12 years will be recruited following a clinical polysomnogram. Normal age- and gender-matched controls will be recruited from the general community.

The primary interventions of this study for the two groups (OSAS and controls) are: sleep studies, neurocognitive testing, measurement of cerebral blood flow by near-infrared spectroscopy during hypercapnic challenges conducted during wakefulness and sleep. In addition, OSAS subjects will be re-tested after clinical treatment of OSAS to evaluate for resolution of OSAS, and all subjects will be re-tested at two separate time points after baseline to compare changes due to the treatment of OSAS versus those occurring secondary to normal development.

Eligibility Criteria:
Inclusion Criteria (OSAS subjects):

1. Age between 6 years and 12 years. The lower limit criterion was selected to include children who can understand and cooperate with testing. The upper limit criterion was selected to avoid overlap with the adult presentation of OSAS.
2. Absence of neurologic, cardiovascular, pulmonary, or any other chronic illness with the exception of well-controlled asthma
3. No prior surgery on the nose, palate or oropharynx including an adenotonsillectomy
4. No current drug intake that may interfere with testing such as sedatives or stimulants
5. No prior treatment of sleep-disordered breathing
6. Polysomnographic recording criteria: subjects with OSAS must have an obstructive apnea hypopnea index (AHI) ≥ 5/hour and be a candidate for clinically-indicated surgical treatment.
7. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria (OSAS Subjects)

1. Previous adenotonsillectomy
2. Previous use of CPAP
3. Craniofacial anomalies that can interfere with upper airway anatomy (e.g., Treacher-Collins syndrome)
4. Genetic syndromes (e.g., Trisomy 21, Prader-Willi)
5. Attention deficit hyperactivity disorder (ADHD) on medication
6. Developmental delay
7. Non-English speaking participants due to the nature of neurobehavioral testing

Inclusion Criteria (Control subjects)

1. Age between 6 years and 12 years. The lower limit criterion was selected to include children who can understand and cooperate with testing. The upper limit criterion was selected to avoid overlap with the adult presentation of OSAS.
2. Absence of neurologic, cardiovascular, pulmonary, or any other chronic illness with the exception of well-controlled asthma
3. No prior surgery on the nose, palate or oropharynx including an adenotonsillectomy
4. No current drug intake that may interfere with testing such as sedatives or stimulants
5. No prior treatment of sleep-disordered breathing
6. Polysomnographic recording criteria: Normal control subjects must have an AHI ≤ 1.5/hour.
7. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria (Control Subjects)

1. Previous adenotonsillectomy
2. Previous use of CPAP
3. Craniofacial anomalies that can interfere with upper airway anatomy (e.g., Treacher-Collins syndrome)
4. Genetic syndromes (e.g., Trisomy 21, Prader-Willi)
5. ADHD on medication
6. Developmental delay
7. Positive Pediatric Sleep Questionnaire
8. Non-English speaking participants due to the nature of neurobehavioral testing