Progressive Gray Matter Changes in Patients with Congenital Central Hypoventilation Syndrome

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) patients show brain injury in areas that control chemosensory, autonomic, motor, cognitive, and emotion functions, which are deficient in the condition. Many of these abnormal characteristics are present from the neonatal period; however, it is unclear if tissue injury underlying the characteristics progressively worsens with time. We hypothesized that several brain areas in CCHS subjects would show increased gray matter volume loss over time. METHODS: We collected high-resolution T1-weighted images twice (four years apart) from 7 CCHS (age at first study, 16.1±2.7 years; 4 males) and 3 control subjects (15.9±2.1 years; 3 males) using a 3.0-Tesla MRI scanner, and evaluated regional gray matter volume changes with voxel-based-morphometry procedures. RESULTS: Multiple brain sites in CCHS, including frontal, prefrontal, insular and cingulate cortices, caudate nuclei and putamen, ventral temporal and parietal cortices, and cerebellar cortices showed significantly reduced gray matter volume over time. Only limited brain areas, including sensory, temporal, and medullary regions emerged with increased gray matter at the later age. CONCLUSIONS: CCHS patients show reduced gray matter volume with age progression in autonomic, respiratory, and cognitive regulatory areas, an outcome that may contribute to deterioration of functions found in the syndrome with increasing age.