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DC Field | Value | Language |
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dc.contributor.author | Shribman, S | - |
dc.contributor.author | Bocchetta, M | - |
dc.contributor.author | Sudre, CH | - |
dc.contributor.author | Acosta-Cabronero, J | - |
dc.contributor.author | Burrows, M | - |
dc.contributor.author | Cook, P | - |
dc.contributor.author | Thomas, DL | - |
dc.contributor.author | Gillett, GT | - |
dc.contributor.author | Tsochatzis, EA | - |
dc.contributor.author | Bandmann, O | - |
dc.contributor.author | Rohrer, JD | - |
dc.contributor.author | Warner, TT | - |
dc.date.accessioned | 2023-01-04T21:47:50Z | - |
dc.date.available | 2021-07-21 | - |
dc.date.available | 2023-01-04T21:47:50Z | - |
dc.date.issued | 2021-07-21 | - |
dc.identifier | ORCID iD: Martina Bocchetta https://orcid.org/0000-0003-1814-5024 | - |
dc.identifier.citation | Shribman, S. et al. (2022) 'Neuroimaging correlates of brain injury in Wilson's disease: a multimodal, whole-brain MRI study', Brain, 2021, 145 (1), pp. 263 - 275. doi: 10.1093/brain/awab274. | en_US |
dc.identifier.issn | 0006-8950 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/25722 | - |
dc.description | Supplementary material: Supplementary material is available at Brain online at https://academic.oup.com/brain/article/145/1/263/6325019#supplementary-data . | en_US |
dc.description.abstract | Copyright © The Author(s) (2021). Wilson’s disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to ‘de-copper’ patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focused on specific sequences or regions of interest, often stratifying chronically treated patients according to persisting symptoms as opposed to initial presentation. In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively recruited patients with Wilson’s disease (age range 16–68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding 6 months as having ‘active’ disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically treated, stable patients. Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound (‘free’) copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically treated patients. Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson’s disease. | en_US |
dc.description.sponsorship | The study was funded by a fellowship awarded to S.S. by the Guarantors of Brain and Association of British Neurologists. The Reta Lila Weston Institute and Wilson’s Disease Support Group UK provided additional financial support for MRI and participant-related costs, respectively. M.B. is supported by a Fellowship award from the Alzheimer’s Society (AS-JF-19a-004–517) and the UK Dementia Research Institute, which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. D.L.T. was supported by the UCL Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575). J.D.R. is an MRC Clinician Scientist (MR/M008525/1) and has received funding from the NIHR Rare Diseases Translational Research Collaboration (BRC149/NS/MH), the Bluefield Project and the Association for Frontotemporal Degeneration. | en_US |
dc.format.extent | 263 - 275 | - |
dc.format.medium | Print-Electronic | - |
dc.language | English | - |
dc.language.iso | en_US | en_US |
dc.publisher | Oxford University Press on behalf of the Guarantors of Brain | en_US |
dc.rights | Copyright © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | - |
dc.subject | Wilson’s disease | en_US |
dc.subject | MRI | en_US |
dc.subject | biomarker | en_US |
dc.subject | atrophy | en_US |
dc.subject | diffusion | en_US |
dc.title | Neuroimaging correlates of brain injury in Wilson's disease: a multimodal, whole-brain MRI study | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1093/brain/awab274 | - |
dc.relation.isPartOf | Brain | - |
pubs.issue | 1 | - |
pubs.publication-status | Published | - |
pubs.volume | 145 | - |
dc.identifier.eissn | 1460-2156 | - |
dc.rights.license | https://creativecommons.org/licenses/by/4.0/ | - |
dc.rights.holder | The Author(s) | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | 1.24 MB | Adobe PDF | View/Open |
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