Abstract
BackgroundNeuropathological studies have revealed copper and iron accumulation in the deep gray matter (DGM) nuclei of patients with Wilson’s disease (WD). However, the association between metal accumulation and neurodegeneration in WD has not been well studied in vivo. The study was aimed to investigate whether metal accumulation in the DGM was associated with the structural and functional changes of DGM in neurological WD patients.MethodsSeventeen neurological WD patients and 20 healthy controls were recruited for the study. Mean bulk susceptibility values and volumes of DGM were obtained from quantitative susceptibility mapping (QSM). Regions of interest including the head of the caudate nucleus, globus pallidus, putamen, thalamus, substantia nigra, red nucleus, and dentate nucleus were manually segmented. The susceptibility values and volumes of DGM in different groups were compared using a linear regression model. Correlations between susceptibility values and volumes of DGM and Unified Wilson’s Disease Rating Scale (UWDRS) neurological subscores were investigated.ResultsThe susceptibility values of all examined DGM in WD patients were higher than those in healthy controls (P < 0.05). Volume reductions were observed in the head of the caudate nucleus, globus pallidus, putamen, thalamus, and substantia nigra of WD patients (P < 0.001). Susceptibility values were negatively correlated with the volumes of the head of the caudate nucleus (rp = −0.657, P = 0.037), putamen (rp = −0.667, P = 0.037), and thalamus (rp = −0.613, P = 0.046) in WD patients. UWDRS neurological subscores were positively correlated with the susceptibility values of all examined DGM. The susceptibility values of putamen, head of the caudate nucleus, and dentate nucleus could well predict UWDRS neurological subscores.ConclusionOur study provided in vivo evidence that paramagnetic metal accumulation in the DGM was associated with DGM atrophy and neurological impairment. The susceptibility of DGM could be used as a biomarker to assess the severity of neurodegeneration in WD.
Highlights
Wilson’s disease (WD), known as hepatolenticular degeneration, is a copper-overload inherited disease caused by ATP7B mutations on chromosome 13
Four WD patients were treated with D-penicillamine and 13 WD patients were treated with dimercaptosuccinic acid (DMSA)
The results of our study were consistent with the theory that iron and copper accumulation in deep gray matter (DGM) was a character of neuropathology in neurological WD patients
Summary
Wilson’s disease (WD), known as hepatolenticular degeneration, is a copper-overload inherited disease caused by ATP7B mutations on chromosome 13. Liver disease and neurological symptoms are the most common clinical features of WD. Copper chelators can effectively improve the hepatic symptoms of WD patients, but they are less effective in improving neurological symptoms and even cause neurological deterioration in initial treatment (Li et al, 2016; Czlonkowska and Litwin, 2017). Neuropathological studies have revealed copper and iron accumulation in the deep gray matter (DGM) nuclei of patients with Wilson’s disease (WD). The association between metal accumulation and neurodegeneration in WD has not been well studied in vivo. The study was aimed to investigate whether metal accumulation in the DGM was associated with the structural and functional changes of DGM in neurological WD patients
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