Clinical History
A young patient presented with acute onset of expressive and receptive dysphasia with associated personality changes. There was no relevant past clinical history, no infective features, no known metabolic or hereditary diseases and no history of any toxic exposure like carbon monoxide or methanol poisoning.
Imaging Findings
MRI brain revealed bilateral symmetrical T2 hyperintensity (Fig. 1 and 2) and T1 hypointensity (Fig. 3) of the putamen, globus pallidus and caudate nuclei. Gradient-echo images (T2* GRE sequence) demonstrated low signal foci within the basal ganglia, suggesting iron or copper deposition (Fig. 4). The T2-fluid attenuated inversion recovery (Flair) images showed central hypointensity, suggesting presence of fluid content (Fig. 5). Thalamus showed very subtle T2-hyperintensity at the ventrolateral aspect (Fig. 1). The diffusion-weighted imaging, post-contrast sequences and MR venogram did not reveal any abnormalities. The mesencephalon, pons, cerebellar hemispheres and cerebral cortex were not involved. Considering the clinical history and MR findings with dominant finding of symmetrical bilateral basal ganglia involvement, the most likely possibility of metabolic disorder was considered. Other differentials which were felt less likely included: hypoxia, ischaemia, infection and primary CNS lymphoma. The diagnosis of Wilson’s disease was subsequently confirmed after biochemical investigations.
Discussion
Wilson’s disease is a rare genetic disorder characterized by deficiency of ceruloplasmin affecting copper metabolism, leading to excessive systemic copper deposition, particularly in liver and brain. The most frequent abnormalities reported in brain imaging are bilateral symmetrical T2-hyperintensity of the putamen and globus pallidus, followed by caudate nuclei, thalami, pons, midbrain, cerebellum and cerebral subcortical regions respectively [1-4]. The T2-weighted high signal changes represent oedema, gliosis, necrosis or spongiform cystic degeneration [2, 3]. Reversal of T2 signal changes can occur following copper chelating treatment [2]. Deposition of copper or iron ferritin can contribute to reduced signal on T2-weighted images. Kim et al reported that T1-weighted hyperintensity of the basal ganglia was the most common MR imaging finding in children which reflect hepatic involvement of the disease [2]. Diffusion restriction is generally seen in the early stages of the disease [1]. MR imaging can reveal a characteristic appearance of the mid brain called “face of the giant panda sign” due to high T2-signal in the tegmentum and normal signal of red nuclei [2, 3]. A similar sign is seen in the pons, albeit slightly smaller, aptly named the “face of the miniature panda” sign [3].
Bilateral symmetrical T2 hyperintensity of the basal ganglia in Wilson disease is most frequently associated with signal changes within the thalami, followed by the brain stem [1-4], however, our case demonstrated dominant symmetric involvement of the basal ganglia only. This type of presentation with bilateral symmetrical hyperintensity of basal ganglia most likely suggests: neurotoxicity due to carbon monoxide, methanol or cyanide poisoning, hypoglycaemia or hyperglycaemia, extrapontine myelinolysis due to rapid correction of hyponatraemia, Wilson disease and other liver diseases, lymphoma, ischaemia and other rare genetic causes like mitochondria diseases, Leigh disease [1-4]. The association of symmetric thalamic involvement widens the differentials with conditions like stroke, primary CNS lymphoma and infections. Addition of T2* GRE sequence can help in limiting the differentials with demonstration of hypointensities in basal ganglia which suggest deposition of iron or copper.
To conclude, the MRI features of bilateral T2 hyperintensity of basal ganglia as initial acute presentation of Wilson disease may not be typically diagnostic due to wide differentials. However, in the absence of toxic exposure or blood sugar disorder, no history of rapid electrolyte correction and presence of susceptibility changes at T2* GRE MR imaging, raises the likelihood of Wilson disease.
Differential Diagnosis List
Wilson disease
Carbon monoxide poisoning
Extrapontine myelinolysis
