Abstract
Introduction
Wilson’s disease (WD) is an autosomal recessive that can lead to high copper concentrations and copper accumulation in bodily organs, specifically the liver, nervous system, and cornea of the eye. Previous meta-analysis studies have evaluated literature reports of diffusion tensor imaging (DTI) to characterize brain microstructural abnormalities in specific neurological diseases, but there have been no systematic reviews of DTI findings in Wilson’s disease (WD). Therefore, this study aimed to systematically review studies reporting DTI findings in patients with WD.
Methods
This systematic review was conducted according to the PRISMA 2020 guidelines. PubMed, Scopus, and Embase databases were searched on May 6th, 2021. We then performed a two-step screening process comprising title/abstract and full-text screening phases. Data from the included studies were then extracted.
Results
We found 10 eligible studies. Most of the included studies identified altered DTI metrics. Affected brain regions included the basal ganglia, thalamus, brainstem, cerebellum, corpus callosum, projection and association fibers. DTI alterations were also observed in patients clinically presenting with hepatic-only WD without neurological symptoms. DTI alterations preceded structural magnetic resonance imaging findings in studies of the thalamus and frontal and occipital lobe white matter changes. The extent of DTI alterations correlated with disease severity and clinical disability, cognitive memory declines, and asymmetry in motor symptoms in several studies.
Conclusions
DTI allows early detection of brain abnormalities associated with WD, prior to the occurrence of morphological brain changes by MRI. Correlations with treatment outcomes and clinical severity may provide objective and quantitative assessment of early and ongoing treatment response. Future studies are required to elucidate the role of DTI in WD clinical practice and find the most consistent DTI markers that may improve clinical outcome.
Similar content being viewed by others
Availability of data and materials
All data that is not included in the manuscript or the supplementary material is available upon request.
References
Ala, A., Walker, A. P., Ashkan, K., Dooley, J. S., & Schilsky, M. L. (2007). Wilson’s disease. Lancet (London, England), 369(9559), 397–408.
Alexander, A. L., Hurley, S. A., Samsonov, A. A., Adluru, N., Hosseinbor, A. P., Mossahebi, P., et al. (2011). Characterization of cerebral white matter properties using quantitative magnetic resonance imaging stains. Brain Connectivity, 1(6), 423–446.
Beaulieu, C. (2002). The basis of anisotropic water diffusion in the nervous system - a technical review. NMR in Biomedicine, 15(7–8), 435–455.
Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., & Cox, D. W. (1993). The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nature Genetics, 5(4), 327–337.
Chang, I. J., & Hahn, S. H. (2017). The genetics of Wilson disease. Handbook of Clinical Neurology, 142, 19–34.
Członkowska, A., Litwin, T., & Chabik, G. (2017). Wilson disease: Neurologic features. Handbook of Clinical Neurology, 142, 101–119.
Degirmenci, C., Palamar, M. (2020). Evaluation and grading of Kayser-Fleischer ring in Wilson disease by Scheimpflug camera. European Journal of Ophthalmology. 1120672120931025.
Dong, T., Yang, W. M., Wu, M. C., Zhang, J., Huang, P., Xu, C. S., et al. (2019). Microstructure changes in whiter matter relate to cognitive impairment in Wilson's disease. Bioscience Reports, 39(3).
Dusek, P., Litwin, T., & Członkowska, A. (2019). Neurologic impairment in Wilson disease. Annals of Translational Medicine, 7(Suppl 2), S64.
Dusek, P., Smolinski, L., Redzia-Ogrodnik, B., Golebiowski, M., Skowronska, M., Poujois, A., et al. (2020). Semiquantitative scale for assessing brain MRI abnormalities in Wilson disease: A validation study. Movement Disorders, 35(6), 994–1001.
Feldman, H. M., Yeatman, J. D., Lee, E. S., Barde, L. H., & Gaman-Bean, S. (2010). Diffusion tensor imaging: A review for pediatric researchers and clinicians. Journal of Developmental and Behavioral Pediatrics : JDBP, 31(4), 346–356.
Forbes, J. R., & Cox, D. W. (2000). Copper-dependent trafficking of Wilson disease mutant ATP7B proteins. Human Molecular Genetics, 9(13), 1927–1935.
García-García, R., Cruz-Gómez, Á. J., Mangas-Losada, A., Urios, A., Forn, C., Escudero-García, D., et al. (2017). Reduced resting state connectivity and gray matter volume correlate with cognitive impairment in minimal hepatic encephalopathy. PLoS ONE, 12(10), e0186463.
Ghazi Sherbaf, F., Aarabi, M. H., Hosein Yazdi, M., & Haghshomar, M. (2019). White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies. Human Brain Mapping, 40(3), 1017–1036.
Hegde, A. N., Mohan, S., Lath, N., & Lim, C. C. (2011). Differential diagnosis for bilateral abnormalities of the basal ganglia and thalamus. Radiographics, 31(1), 5–30.
Hermann, W. (2014). Morphological and functional imaging in neurological and non-neurological Wilson’s patients. Annals of the New York Academy of Sciences, 1315, 24–29.
Hu, S., Xu, C., Dong, T., Wu, H., Wang, Y., Wang, A., et al. (2021). Structural and functional changes are related to cognitive status in Wilson’s disease. Frontiers in Human Neuroscience, 15, 610947.
Jacobs, D. A., Markowitz, C. E., Liebeskind, D. S., & Galetta, S. L. (2003). The “double panda sign” in Wilson’s disease. Neurology, 61(7), 969.
Jadav, R., Saini, J., Sinha, S., Bagepally, B., Rao, S., & Taly, A. B. (2013). Diffusion tensor imaging (DTI) and its clinical correlates in drug naïve Wilson’s disease. Metabolic Brain Disease, 28(3), 455–462.
Jeurissen, B., Leemans, A., Tournier, J. D., Jones, D. K., & Sijbers, J. (2013). Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Human Brain Mapping, 34(11), 2747–2766.
Kim, T. J., Kim, I. O., Kim, W. S., Cheon, J. E., Moon, S. G., Kwon, J. W., et al. (2006). MR imaging of the brain in Wilson disease of childhood: Findings before and after treatment with clinical correlation. AJNR American Journal of Neuroradiology, 27(6), 1373–1378.
King, A. D., Walshe, J. M., Kendall, B. E., Chinn, R. J., Paley, M. N., Wilkinson, I. D., et al. (1996). Cranial MR imaging in Wilson’s disease. AJR American Journal of Roentgenology, 167(6), 1579–1584.
Lawrence, A., Saini, J., Sinha, S., Rao, S., Naggappa, M., Bindu, P. S., et al. (2016). Improvement of Diffusion Tensor Imaging (DTI) parameters with decoppering treatment in Wilson’s disease. JIMD Reports, 25, 31–37.
Letelier, M. E., Lepe, A. M., Faúndez, M., Salazar, J., Marín, R., Aracena, P., et al. (2005). Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity. Chemico-Biological Interactions, 151(2), 71–82.
Li, G., Zhou, X., Xu, P., Pan, X., & Chen, Y. (2014). Microstructure assessment of the thalamus in Wilson’s disease using diffusion tensor imaging. Clinical Radiology, 69(3), 294–298.
Litwin, T., Gromadzka, G., & Członkowska, A. (2012). Gender differences in Wilson’s disease. Journal of the Neurological Sciences, 312(1–2), 31–35.
Lorincz, M. T. (2010). Neurologic Wilson’s disease. Annals of the New York Academy of Sciences, 1184, 173–187.
Momtazmanesh, S., Aarabi, M. H., SanjariMoghaddam, H., Delavari, F., Shafie, M., Abbasi-Feijani, F., et al. (2021). Brain microstructural abnormalities in 22q11.2 deletion syndrome: A systematic review of diffusion tensor imaging studies. European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology., 52, 96–135.
Mosher, V., Swain, M., Pang, J., Kaplan, G., Sharkey, K., MacQueen, G., et al. (2019). Primary biliary cholangitis patients exhibit MRI changes in structure and function of interoceptive brain regions. PLoS ONE, 14(2), e0211906.
Partridge, S. C., Mukherjee, P., Henry, R. G., Miller, S. P., Berman, J. I., Jin, H., et al. (2004). Diffusion tensor imaging: Serial quantitation of white matter tract maturity in premature newborns. NeuroImage, 22(3), 1302–1314.
Parvez, S., Fatima, G., Al-Awaida, W., Hussien, Y. A., Tamam, S. A., & Hadi, N. R. (2021). Vitamin D: Implications in COVID-19. Latin American Journal of Pharmacy, 40(Special Issue), 23–6.
Pierpaoli, C., & Basser, P. J. (1996). Toward a quantitative assessment of diffusion anisotropy. Magnetic Resonance in Medicine, 36(6), 893–906.
PRISMA 2020 checklist, last accessed: 2 Oct 2022, available online at: https://www.prisma-statement.org/
Reddy, P. V., Rao, K. V., & Norenberg, M. D. (2008). The mitochondrial permeability transition, and oxidative and nitrosative stress in the mechanism of copper toxicity in cultured neurons and astrocytes. Laboratory Investigation: a Journal of Technical Methods and Pathology., 88(8), 816–30.
Rędzia-Ogrodnik, B., Członkowska, A., Bembenek, J., Antos, A., Kurkowska-Jastrzębska, I., Skowrońska, M., et al. (2022). Brain magnetic resonance imaging and severity of neurological disease in Wilson’s disease - the neuroradiological correlations. Neurological Sciences, 43(7), 4405–4412.
Sanjari Moghaddam, H., Ghazi Sherbaf, F., & Aarabi, M. H. (2019). Brain microstructural abnormalities in type 2 diabetes mellitus: A systematic review of diffusion tensor imaging studies. Frontiers in Neuroendocrinology, 55, 100782.
Scheiber, I. F., Brůha, R., & Dušek, P. (2017). Pathogenesis of Wilson disease. Handbook of Clinical Neurology, 142, 43–55.
Sener, R. N. (2003). Diffusion MRI findings in Wilson’s disease. Computerized Medical Imaging and Graphics : The Official Journal of the Computerized Medical Imaging Society, 27(1), 17–21.
Shribman, S., Heller, C., Burrows, M., Heslegrave, A., Swift, I., Foiani, M. S., et al. (2021). Plasma neurofilament light as a biomarker of neurological involvement in Wilson’s disease. Movement Disorders, 36(2), 503–508.
Shribman, S., Burrows, M., Convery, R., Bocchetta, M., Sudre, C. H., Acosta-Cabronero, J., et al. (2022). Neuroimaging correlates of cognitive deficits in Wilson’s disease. Movement Disorders, 37(8), 1728–1738.
Smolinski, L., Litwin, T., Redzia-Ogrodnik, B., Dziezyc, K., Kurkowska-Jastrzebska, I., & Czlonkowska, A. (2019). Brain volume is related to neurological impairment and to copper overload in Wilson’s disease. Neurological Sciences, 40(10), 2089–2095.
Song, Y. K., Li, X. B., Huang, X. L., Zhao, J., Zhou, X. X., Wang, Y. L., et al. (2018). A study of neurite orientation dispersion and density imaging in wilson’s disease. Journal of Magnetic Resonance Imaging : JMRI, 48(2), 423–430.
Tinaz, S., Arora, J., Nalamada, K., Vives-Rodriguez, A., Sezgin, M., Robakis, D., et al. (2020). Structural and functional brain changes in hepatic and neurological Wilson disease. Brain imaging and behavior.
Viswanathan, M., Ansari, M. T., Berkman, N. D., et al. (2008). Assessing the risk of bias of individual studies in systematic reviews of health care interventions. 2012 Mar 8. In: Methods Guide for Effectiveness and Comparative Effectiveness Reviews [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US). Available from: https://www.ncbi.nlm.nih.gov/books/NBK91433/
Walshe, J. M., & Yealland, M. (1992). Wilson’s disease: The problem of delayed diagnosis. Journal of Neurology, Neurosurgery, and Psychiatry, 55(8), 692–696.
Wang, A., Wu, H., Xu, C., Tang, L., Lee, J., Wang, M., et al. (2017). Study on lesion assessment of Cerebello-Thalamo-Cortical Network in Wilson’s disease with diffusion tensor imaging. Neural Plasticity, 2017, 7323121.
Wu, P., Zheng, Y., Fan, X., Wang, H., Deng, X., Sun, B., et al. (2020). Predictors of caregiver burden in patients with neurologic Wilson disease. Journal of International Medical Research, 48(6), 300060520930156-.
Yu, X. E., Gao, S., Yang, R. M., & Han, Y. Z. (2019). MR imaging of the brain in neurologic Wilson disease. AJNR American Journal of Neuroradiology, 40(1), 178–183.
Zhou, X. X., Li, X. H., Qin, H., Li, G. D., Huang, H. W., Liang, Y. Y., et al. (2016). Diffusion tensor imaging of the extracorticospinal network in the brains of patients with Wilson disease. Journal of the Neurological Sciences, 362, 292–298.
Zhou, X. X., Li, X. H., Chen, D. B., Wu, C., Feng, L., Chu, J. P., et al. (2018). The asymmetry of neural symptoms in Wilson’s disease patients detecting by diffusion tensor imaging, resting-state functional MRI, and susceptibility-weighted imaging. Brain and Behavior, 8(5), e00930.
Ziemssen, T., Akgun, K., Członkowska, A., Antos, A., Bembenek, J., Kurkowska-Jastrzębska, I., et al. (2022). Serum neurofilament light chain as a biomarker of brain injury in Wilson’s disease: Clinical and neuroradiological correlations. Movement Disorders, 37(5), 1074–1079.
Author information
Authors and Affiliations
Contributions
Author contributions included conception and study design (Soheil Mohammadi and Mohammad Amin Salehi), data collection or acquisition (Soheil Mohammadi and Mohammad Amin Salehi), statistical analysis (Soheil Mohammadi), interpretation of results (Amirali Karimi), drafting the manuscript work or revising it critically for important intellectual content (Amirali Karimi, Soheil Mohammad, and Mohammad Amin Salehi) 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).
Corresponding author
Ethics declarations
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
We declare that the authors have no competing interests as defined by Springer, or other interests that might be perceived to influence the results and/or discussion reported in this paper.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Karimi, A., Mohammadi, S., Salehi, M.A. et al. Brain microstructural abnormalities in patients with Wilson’s disease: A systematic review of diffusion tenor imaging studies. Brain Imaging and Behavior 16, 2809–2840 (2022). https://doi.org/10.1007/s11682-022-00733-7
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11682-022-00733-7