Functional Brain MRI as a Diagnostic Tool for Detecting Neurological Changes in Children with Wilson’s Disease

Abstract

Background: Wilson's disease (WD) is a rare genetic disorder marked by copper buildup, causing hepatic and neurological issues. Objective: This study aimed to thoroughly evaluate clinical, biochemical, and neuroimaging aspects of WD, highlighting the diagnostic potential of magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) for detecting neurological involvement. Patients and methods: The study included 40 children divided into two groups: 20 healthy children (group 1) and 20 with Wilson's disease (group 2). Various MRI techniques, including T1, T2, FLAIR, diffusion imaging, and MRS, were used. For WD patients, comprehensive clinical examinations, lab tests, and MRS were performed to understand their neurochemical profile. The analysis involved assessing clinical features (hepatomegaly prevalence) and lab parameters (24-hour urine copper excretion, albumin, alkaline phosphatase, bilirubin, and ceruloplasmin). MRS provided insights into metabolites like N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr). The diagnostic accuracy of neurochemical ratios (NAA/Cr, NAA/Cho, Cho/Cr) for predicting neurological manifestations was evaluated, alongside conventional brain MRI and diffusion MRI for neurological status assessment. Results: The study found hepatomegaly in 70% of WD patients, a significant range of 24-hour urine copper excretion was from 10 to 4699 µg/24h and a median of 122.5 µg/24h (IQR=27.5-309) and distinct neurochemical shifts in NAA, Cho, and Cr. Brain MRI detected neurological abnormalities in 80% of patients. Cho showed promise (P-value: 0.038) in predicting neurological issues, while caution was urged against relying solely on Cr due to lower specificity (p-value: 0.777). The NAA/Cr ratio proved a robust predictor (P-value: 0.006), surpassing NAA/Cho (P-value: 0.925). Conclusion: Our study underscored the clinical significance of hepatomegaly, elevated 24-hour urine copper excretion, and distinctive neurochemical shifts in WD. Neuroimaging findings, especially using diffusion-weighted imaging, contributed valuable insights into neurological manifestations. The diagnostic potential of MRS-derived ratios, notably the NAA/Cr ratio, hold promise for predicting neurological involvement in Wilson's disease.