Radiological imaging of intracranial manifestation of Wilson Disease.

Dr/ ABD ALLAH NAZEER. MD.

Wilson disease is an inborn (autosomal recessive) error of copper metabolism characterized by inability of the liver to excrete copper into the bile, with excessive deposition of copper primarily in the liver and in the brain. Wilson disease occurs in 1 to 4 per 100,000 people and symptoms usually appear between the ages of 6 and 20 years. In Wilson disease, ceruloplasmin, the serum transport protein for copper, is deficient. Copper accumulates in the tissues of patients primarily in the liver and later in the brain. Accordingly these patients present with either hepatic or neuropsychiatric symptoms. The severity of the liver damage varies from a simple fatty infiltration to advanced cirrhosis with porto systemic shunts. The brain damage can be present even without a severe hepatic damage. In the brain there is a predilection for the extrapyramidal system. The initial neurological presentations frequently include dysarthria and tremors, with later manifestations of personality and psychiatric problems, and neurologic abnormalities like Parkinsonian tremors, ataxia, dystonia, and chorea.

Clinical presentationClinical presentation is non-specific and varied:weakening of hands and dysarthria are often the earliest symptomsdystoniapseudo-parkinsonian and cerebellar symptomspsychiatric symptomsliver disease (more so in children and young adults)Kayser-Fleischer rings are seen in the cornea and are a characteristic feature.PathologyIt is a disorder that results from abnormal ceruloplasmin metabolism; a result of a variety of mutations in the ATP7B gene. Total body copper is elevated with deposition and resultant damage to a variety of organs, e.g. liver and brain.Three pathways affected mostly:dentatorubrothalamic tractpontocerebellar tractcorticospinal tract

Computed Tomography:CT is much less sensitive than MRI in cases of Wilson's disease, may be normal or show only a mild generalized atrophy and ventricular dilatation.The most frequent findings are putamina bilateral hypodensity.CT can be improved by using thin slices (1 or 2 mm) in the levels of the basal ganglia.It is important that the radiologist when faced with a CT scan showing signs of brain atrophy, especially in young patients, make the correlation with clinical data, which may include Wilson's disease as a diagnostic possibility, requiring further research imaging, indicating the MRI.

On MRI study, the brain lesions are usually bilateral and often symmetrical. Lesions are usually hyperintense on T2-weighted images. The high signal intensity of gray matter nuclei on T2 weighted images can be caused by edema, gliosis, necrosis or cystic degeneration. Diffusion-weighted images can show areas of restricted diffusion early in the disease process due to cytotoxic edema or inflammation due to excessive copper deposition. However, this restricted diffusion is not seen in chronic cases. Hypointensity on T2-weighted images can be seen sometimes, secondary to copper deposition or iron deposition. The cause of hyperintensity on T1-weighted images in some patients remains elusive. It has previously been suggested that these abnormalities result from the toxic effect of copper overload in the brain and indirectly from liver failure as a result of copper intoxication. In this exhibit we will describe the diverse spectrum of intracranial magnetic resonance imaging (MRI) manifestation of Wilson disease in adult as well as pediatric population.

Wilson disease in a 13-year-old boy with abdominal distention.A and B, T1-weighted axial MR images show bilateral increased signal intensity in the globus pallidus (arrows) and midbrain (arrowhead).

High-signal-intensity lesions on T2-weighted MR images.A, Wilson disease in a 12-year-old girl with dysarthria. T2-weighted axial MR image shows bilateral high signal intensity with central dark signal intensity in the putamen (arrows) and caudate nuclei (arrowheads).B, Wilson disease in a 13-year-old girl with dysarthria. T2-weighted axial MR image shows bilateral symmetric high signal intensity in the putamen (black arrows) and caudate nuclei (white arrows). Slightly increased signal intensity in both thalami (black arrowheads) and globus pallidi (white arrowheads) is also noted.

Wilson disease in a 14-year-old girl with dystonia.A, Initial T2-weighted axial MR image shows increased signal intensity in both caudate nuclei (arrowheads) and putamen (arrows).B and C, Follow-up T2-weighted axial MR images obtained after 3 years show aggravated lesions, especially in the thalamus (white arrows) and midbrain (arrowheads). Clinically, the patient’s neurologic symptoms, including dystonia, were deteriorated, despite adequate treatment.

Brain MRI (axial flair images) showing zones of impaired signal at the level of mesencephalon (A) and thalami (B) in a 21-year-old patient presenting Wilson’s disease. In the left panel, note the relative sparing of red nuclei and part of pars reticulata (giving a typical aspect called the “Panda sign”). In the right panel, the simultaneous hyposignals of basal ganglia (blue arrows) and the hypersignals in thalamic nuclei and internal capsule (red arrows) are very suggestive.

Wilson disease with low and high non-enhanced signal in the basal ganglia. Signs of cerebral atrophy and mild dilatation of the ventricular system

T2 AXIAL: areas of hyperintensity lenticular nuclei and thalamus bilaterally.

Areas of hyperintensity in the basal ganglia and the cerebral peduncles bilaterally.

IR AXIAL: Hypointensity in the brain stem (pontocerebellar tract: anterior pontine fibers, pontine tegmental reticular nucleus and middle cerebellar peduncles).

IR AXIAL: Hypointense signal in the basal ganglia bilaterally. Note also the cortical sulci, suggesting signs of cerebral atrophy.

Acquisitions axial T2 (right) and T1 (IR) with foci of hyperintensity on T2 and hypointense on T1 (IR) in the cerebral peduncles. Furthermore, there was moderate dilatation of IVo. ventricle.

Sign of "Face of the Giant Panda" in the midbrain.

Restricted diffusion observed in caudate and lenticular nuclei bilaterally.

Serial T2-weighted MRI of Wilson’s disease over a six month period illustrating evolution of the characteristic “face of the giant panda” in the midbrain (A, C, and E) and face of her cub in the dorsal pons (B, D, and F).

Panda with "Bright eyes" in Wilson's disease.

Wilson disease. A, Proton density–weighted image reveals bilateral high signal intensity in the putamina and in the heads of the caudate nuclei.B, Heavily diffusion-weighted (b = 1000 s/mm2) image reveals high signal intensity changes (restricted diffusion). This probably reflects accumulated copper.C, Corresponding ADC map shows low ADC values, 0.49, 0.47, and 0.54 × 10−3mm2/s, in the corresponding regions, compared with a normal ADC value from the parenchyma, 0.82 × 10−3 mm2/s.

Thank You.