Abstract
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.
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Acknowledgements
We thank Zhuoyi Peng, Xinbei Li, Yuliang Wang, and Yisu Tian for their research assistance, and all participants involved in this study.
Funding
This work was supported by the National Key R&D Program of China (2017YFC0112404), the National Natural Science Foundation of China (NSFC 81501546 and NSFC 81201074), and the Science and Technology Program of Guangdong Province (201508020121) and the Natural Science Foundation of Guangdong Province (2017A030313676).
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Conception and study design (SYK, CJP and TXY), data collection or acquisition (SYK, ZL, HXQ, QHS and ZJ), statistical analysis (SYK, ZL), interpretation of results (SYK, ZL, HYQ, QHS, TXY and CJP), drafting the manuscript work or revising it critically for important intellectual content (SYK, ZL, TXY and CJP) and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (All authors).
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Appendices
Appendices
Subjects
There were significant group differences in HAMD score (WD: 10.90 ± 5.71, HC: 1.88 ± 2.20) and HAM-A score (WD: 13.93 ± 7.35, HC: 1.32 ± 1.70) between WD and HC (P < 0.05). No significant differences were found in gender (P = 0.608, χ2 test), age (P = 0.900, Student’s t test), years of education (P = 0.270, Student’s t test) nor MMSE score (P = 0.133 for Student’s t test, P = 0.135 for χ2 test) between WD and HC. For the patients with WD, the mean total disease duration time was 43.87 ± 19.51 months (range: 12–84 months) and the mean GAS score was 15.64 ± 6.64 (range: 5–30). A higher GAS score indicates a more severe clinical symptom. (Table 1)
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Song, Y., Zou, L., Zhao, J. et al. Whole brain volume and cortical thickness abnormalities in Wilson’s disease: a clinical correlation study. Brain Imaging and Behavior 15, 1778–1787 (2021). https://doi.org/10.1007/s11682-020-00373-9
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DOI: https://doi.org/10.1007/s11682-020-00373-9