Dataset Information

Brain volume is related to neurological impairment and to copper overload in Wilson's disease.

ABSTRACT:

Introduction

To determine whether brain volume was associated with functional and neurological impairments and with copper overload markers in patients with Wilson's disease.

Methods

In 48 treatment-naïve patients, we assessed functional and neurological impairments with the Unified Wilson's Disease Rating Scale, measured normalized brain volumes based on magnetic resonance images, and assessed concentration of non-ceruloplasmin-bound copper. We correlated brain volume measures with functional and neurological impairment scores and copper overload indices.

Results

Functional and neurological impairments correlated with all brain volume measures, including the total brain volume and the volumes of white matter and gray matter (both peripheral gray matter and deep brain nuclei). Higher non-ceruloplasmin-bound copper concentrations were associated with greater functional and neurological impairments and lower brain volumes.

Conclusions

Our findings provided the first in vivo evidence that the severity of brain atrophy is a correlate of functional and neurological impairments in patients with Wilson's disease and that brain volume could serve as a marker of neurodegeneration induced by copper.

SUBMITTER: Smolinski L

PROVIDER: S-EPMC6745045 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Brain volume is related to neurological impairment and to copper overload in Wilson's disease.

Smolinski Lukasz L Litwin Tomasz T Redzia-Ogrodnik Barbara B Dziezyc Karolina K Kurkowska-Jastrzebska Iwona I Czlonkowska Anna A

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 20190530 10

<h4>Introduction</h4>To determine whether brain volume was associated with functional and neurological impairments and with copper overload markers in patients with Wilson's disease.<h4>Methods</h4>In 48 treatment-naïve patients, we assessed functional and neurological impairments with the Unified Wilson's Disease Rating Scale, measured normalized brain volumes based on magnetic resonance images, and assessed concentration of non-ceruloplasmin-bound copper. We correlated brain volume measures wi ...[more]

PMID: 31147855

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Project description:Background and purposeWilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.Materials and methodsA combination of 1HNMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the urine and blood serum samples collected from the copper-laden rat model of WD with PA treatment.ResultsCopper accumulation in the copper-laden rats is associated with increased lactate, creatinine, valine and leucine, as well as decreased levels of glucose and taurine in the blood serum. There were also significant changes in p-hydroxyphenylacetate (p-HPA), creatinine, alpha-ketoglutarate (α-KG), dimethylamine, N-acetylglutamate (NAG), N-acetylglycoprotein (NAC) in the urine of these rats. Notably, the changes in p-HPA, glucose, lactate, taurine, valine, leucine, and NAG were found reversed following PA treatment. Nevertheless, there were no changes for dimethylamine, α-KG, and NAC as a result of the treatment. Compared with the controls, the concentrations of hippurate, formate, alanine, and lactate were changed when PA was applied and this is probably due to its side effect. A tool named SMPDB (Small Molecule Pathway Database) is introduced to identify the metabolic pathway influenced by the copper-laden diet.ConclusionThe study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the molecular mechanism underlying disorder due to WD.

Dataset Information

Brain volume is related to neurological impairment and to copper overload in Wilson's disease.

Introduction

Methods

Results

Conclusions

Publications

Brain volume is related to neurological impairment and to copper overload in Wilson's disease.

Similar Datasets

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