CBF and Childhood OSAS
Condition: Obstructive Sleep Apnea Syndrome
MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Sleep Study; Neurocognitive Testing; CBF During Wakefulness; CBF During Sleep
Intervention type(s): Other; Other; Other; Other
Intervention description(s): Overnight, video-recorded sleep study will be performed in a dedicated pediatric sleep lab. Sleep architecture, apneas and hypopneas, arterial oxygen saturation and end-tidal carbon dioxide tension will be evaluated during the sleep study. Safety measures including arterial oxygen saturation using pulse oximetry, EEG and EKG will be continuously monitored during the study.; Cognitive and behavioral measures including intelligence, attention, working memory, and processing speed will be assessed by a trained psychologist.; Cerebral blood flow (CBF) will be measure using Diffuse optical and correlation spectroscopy (DOS/DCS), a non-significant risk device used to collect data for this study but not being tested as part of the protocol. Light sources and detectors which are embedded in a rubber pad will be attached to the subject's head in order to record right and left hemispheric cerebral blood flow, total hemoglobin concentration and tissue oxygen saturation. Measurements will be continuously recorded during the study and averaged for purposes of statistical analysis. With DOS/DCS in place, ventilatory response to hypercapnia will be determined using the rebreathing technique, a standard clinical test. While CBF is being measured, subjects will wear nose clips and sit comfortably breathing through a mouthpiece while the level of carbon dioxide is adjusted over a 3-4 minute period. Oxygen and carbon dioxide levels will be carefully monitored throughout the testing.; This is the same as the CBF testing during wakefulness/daytime except that it will be done during a sleep study performed with a continuous positive airway pressure (CPAP) mask not nose clips and a mouthpiece. With DOS/DCS in place, ventilatory response to hypercapnia will be determined using the rebreathing technique. While CBF is being measured, OSAS subjects will receive an individualized positive pressure aimed at treating obstructive sleep apnea and controls will receive a standard pressure. End-tidal carbon dioxide will be measured via a port in the mask. A constant flow of carbon dioxide will be introduced to the circuit, a slowly adjusted until the patient arouses or for a maximum of 3 minutes, whichever occurs first. One trial will be attempted in each sleep stage (slow-wave sleep and rapid-eye-movement) with a minimum of 15 minute of breathing room air between challenges. Oxygen and carbon dioxide levels will be carefully monitored throughout the testing.
Other intervention name(s): Polysomnography; Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Daytime/Wakefulness); Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Nighttime/Sleep)
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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.
      
Keywords: Obstructive Sleep Apnea Syndrome; Cerebral Blood Flow; Neurocognition