Hypercapnic arousal responses in Prader-Willi syndrome

Study objective: Prader-Willi syndrome (PWS) is characterized by a number of abnormalities of hypothalamic function, such as hyperphagia, short stature, temperature instability, hypogonadotropic hypogonadism, and neurosecretory growth hormone deficiency. Patients with PWS are reported to have sleep-disordered breathing and have blunted hypercapnic ventilatory responses secondary to abnormal peripheral chemoreceptor function. Thus, we hypothesized that hypercapnic arousal responses would be abnormal in PWS. Design: Hypercapnic arousal responses were tested in ten nonobese children and adults with PWS, aged 17.7±2.5 (SEM) years, 70% female, and nine control subjects, aged 14.2±2.6 years, 67% female. Hypercapnic challenges were performed during stage 3/4 non-rapid eye movement sleep. Results: The PWS subjects had a significantly higher arousal threshold to hypercapnia compared with the controls (53±1.0 vs 46±1.7 mm Hg; p<0.01). The PWS subjects had significantly higher baseline end-tidalCO₂ levels (42±0.8 vs 38±1.1 mm Hg; p<0.01) and more central apneas greater than 15 s/h of sleep (1.5±0.3 vs 0.1±0.1; p<0.01). Conclusions: Elevated hypercapnic arousal thresholds during sleep are found in PWS subjects; these may be a manifestation of abnormal peripheral chemoreceptor function and may further contribute to sleep-disordered breathing in PWS patients.