Hypercapneic arousal responses in children with congenital central hypoventilation syndrome

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is generally thought to be due to insensitivity of the central chemoreceptors to carbon dioxide. Children with CCHS have absent ventilatory responses to both hypercapnea and hypoxia, suggesting either abnormal central and peripheral chemoreceptor function or abnormal central integration of chemoreceptor input. Because ventilatory and arousal responses to respiratory stimuli are distinct from each other, if children with CCHS have complete chemoreceptor dysfunction, one would predict that both ventilatory and arousal responses to respiratory stimuli would be abnormal. However, if they have abnormal central integration of chemoreceptor input for ventilation, they may still arouse to respiratory stimuli despite the absence of a ventilatory response. Hypercapneic arousal responses were tested in eight children with CCHS, aged 5.8 +/- 1.2 (SEM) years, and seven healthy control subjects, aged 4.4 +/- 1.1 years. Children were studied during sleep while normal ventilation was maintained using their home ventilators. Hypercapneic challenges were performed by rapidly increasing the inspired carbon dioxide tension to 60 mm Hg and maintaining this level until the child aroused or for a maximum of 3 minutes. Of children with CCHS, 87.5% aroused to hypercapnea, compared with 100% of control children. There was no significant difference in arousal between children with CCHS and normal control subjects. It is concluded that most children with CCHS arouse to hypercapnea, indicating the presence of some central chemoreceptor function. It is speculated that because these children do respond to hypercapnea, the most probable mechanism for CCHS is a brainstem lesion in the area where input from both chemoreceptors is integrated.