LAUSR

RATIONALE Congenital Central Hypoventilation Syndrome (CCHS) is a rare autonomic disorder with altered regulation of breathing, heart rate (HR), and blood pressure (BP). Aberrant cerebral oxygenation in response to hypercapnia/hypoxia in CCHS raises concern that altered cerebral autoregulation may contribute to CCHS-related, variably impaired neurodevelopment. OBJECTIVES Evaluate cerebral autoregulation in response to orthostatic challenge in CCHS cases vs. controls. METHODS CCHS and age- and sex-matched control subjects were studied with head-up tilt (HUT) testing to induce orthostatic stress. 50 CCHS and 100 control HUT recordings were included. HR, BP, and cerebral oxygen saturation (rSO2) were continuously monitored. Cerebral oximetry index (COx), a real-time measure of cerebral autoregulation based on these measures, was calculated. MAIN RESULTS HUT resulted in greater mean BP decrease from baseline in CCHS vs. controls (11% vs. 6%; p<0.05) and a diminished increase in HR in CCHS vs. controls (11% vs. 18%; p<0.01) in the 5 minutes after tilt-up. Despite a similar COx at baseline, orthostatic provocation within 5 minutes of tilt-up caused a 50% greater increase in COx (p<0.01) and a 29% increase in minutes of impaired autoregulation (p<0.02) in CCHS vs. controls (4.0 vs. 3.1 min). CONCLUSIONS Cerebral autoregulatory mechanisms appear intact in CCHS, but the greater hypotension observed in CCHS consequent to orthostatic provocation is associated with greater values of COx/impaired autoregulation when BP is below lower limits of autoregulation. Effects of repeated orthostatic challenges in everyday living in CCHS necessitate further study to determine their influence on neurodevelopmental disease burden.