Decreased cortical thickness in central hypoventilation syndrome

Central hypoventilation syndrome (CHS) is a rare condition characterized by hypoventilation during sleep, reduced ventilatory responsiveness to CO(2) and O(2), impaired perception of air hunger, and autonomic abnormalities. Neural impairments accompany the condition, including structural injury, impaired cerebral autoregulation, and dysfunctional autonomic control. The hypoventilation may induce cortical hypoxic injury, additional to consequences of maldevelopment from PHOX2B mutations present in most CHS subjects. We assessed cortical injury in clinically diagnosed CHS using high-resolution magnetic resonance imaging scans, collected from 14 CHS (mean age ± standard deviation [SD] 17.7 ± 5.0 years; 6 female) and 29 control (mean age ± SD, 17.9 ± 4.3 years; 12 female) subjects. We measured group differences in mean cortical thickness and age-thickness correlations using FreeSurfer software, accounting for age and sex (0.1 false discovery rate). Reduced thickness in CHS appeared in the dorsomedial frontal cortex and anterior cingulate; medial prefrontal, parietal, and posterior cingulate cortices; the insular cortex; anterior and lateral temporal lobes; and mid- and accessory motor strips. Normal age-related cortical thinning in multiple regions did not appear in CHS. The cortical thinning may contribute to CHS cardiovascular and memory deficits and may impair affect and perception of breathlessness. Extensive axonal injury in CHS is paralleled by reduced cortical tissue and absence of normal developmental patterns.