Whole brain volume and cortical thickness abnormalities in Wilson's disease: a clinical correlation study

Wilson's disease (WD) is an inherited autosomal recessive disorder of copper metabolism, and its neurological and neuropsychiatric manifestations are associated with copper accumulation in brain. A few neuroimaging studies have shown that gray matter atrophy in WD affects both subcortical structures and cortex. This study aims to quantitatively evaluate the morphometric brain abnormalities in patients with WD in terms of whole brain volume and cortical thickness and their associations with clinical severity of WD. Thirty patients clinically diagnosed as WD with neurological manifestations and 25 healthy controls (HC) were recruited. 3D T1-weighted images were segmented into 276 whole-brain regions of interest (ROIs) and 68 cortical ROIs. WD-vs-HC group comparisons were then conducted for each ROI. The associations between those morphometric measurements and the Global Assessment Scale (GAS) score for WD were analyzed. Compared with HC, significant WD-related volumetric decreases were found in the bilateral subcortical nuclei (putamen, globus pallidus, caudate nucleus, substantia nigra, red nucleus and thalamus), diffuse white matter and several gray matter regions. WD patients showed reduced cortical thickness in the left precentral gyrus and the left insula. Further, the volumes of the right globus pallidus, bilateral putamen, right external capsule and left superior longitudinal fasciculus were negatively correlated with GAS. Our results indicated that significant WD-related morphometric abnormalities were quantified in terms of whole-brain volumes and cortical thicknesses, some of which correlated significantly to the clinical severity of WD. Those morphometrics may provide a potentially effective biomarker of WD.