Brain microstructural abnormalities in patients with Wilson's disease: A systematic review of diffusion tenor imaging studies

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 6^th, 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.