Diffusion tensor imaging demonstrates brainstem and cerebellar abnormalities in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show reduced breathing drive during sleep, decreased hypoxic and hypercapnic ventilatory responses, and autonomic and affective deficits, suggesting both brainstem and forebrain injuries. Forebrain damage was previously described in CCHS, but methodological limitations precluded detection of brainstem injury, a concern because genetic mutations in CCHS target brainstem autonomic nuclei. To assess brainstem and cerebellar areas, we used diffusion tensor imaging-based measures, namely axial diffusivity, reflecting water diffusion parallel to fibers, and sensitive to axonal injury, and radial diffusivity, measuring diffusion perpendicular to fibers, and indicative of myelin injury. Diffusion tensor imaging was performed in 12 CCHS and 26 controls, and axial and radial diffusivity maps were compared between groups using analysis of covariance (covariates; age and gender). Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons. Cerebellar cortex and deep nuclei, and the superior and inferior cerebellar peduncles showed increased radial diffusivity. Midbrain, pontine, and lateral medullary structures, and the cerebellum and its fiber systems are injured in CCHS, likely contributing to the characteristics found in the syndrome.