Hepatic parenchymal copper concentration
- Is the hallmark of Wilson’s disease.
It can cause fatty liver or cirrhosis of the liver.
It can be seen with sonography,
CT (Fig.4) or MRI of hepar.
- hepatic copper overload cannot be excluded by histochemical evaluation of a liver biopsy alone.
Therefore,
the measurement of hepatic parenchymal copper concentration is the method of choice for the diagnosis of Wilson’s disease
Liver histology
- Is only required if the clinical signs and noninvasive tests do not allow a final diagnosis or if there is suspicion of other or additional liver pathologies
- biopsies for quantitative copper determination should be placed dry in a copper-free container.
Shipment for quantitative copper determination does not require special precautions like freezing.
At least 1 cm of biopsy core length should be submitted for analysis.
- the earliest histologic abnormalities in the liver include mild steatosis (both microvesicular and macrovesicular),
glycogenated nuclei in hepatocytes,
and focal hepatocellular necrosis.
Frequently,
these changes are misdiagnosed as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
The liver biopsy may show classic histologic features of autoimmune hepatitis (the so-called “chronic active hepatitis” picture).
With progressive parenchymal damage,
fibrosis and subsequently cirrhosis develop.
About half of the patients have cirrhosis at the time of diagnosis.
Magnetic resonance imaging (MRI) or computed tomography of the brain
- In the brain may detect structural abnormalities in the basal ganglia,
and cortical atrophy.
- the most frequent findings are an increased density on computed tomography or hyperintensity on T2 MRI in the region of the basal ganglia.
- MRI may be more sensitive in detecting these lesions.
Abnormal findings are not limited to this region,
and other abnormalities have been described.
- a characteristic finding in Wilson’s disease is the “face of the giant panda” sign,
but is found only in a minority of patients.
Besides this sign,
hyperintensities in tectal-plate and central pons (CPM-like),
and simultaneous involvement of basal ganglia,
thalamus,
and brainstem are virtually pathognomonic of Wilson’s disease.
MRI findings in Wilson disease: 5 pattern
All the lesions are bilateral and have symetric involvement.
Some of the lesions due to medical treatment are reversible.
1.
T2–hyperintense lesion/T1-Hypointense
The high-signal-intensity lesions on T2-weighted image can be caused by edema,
gliosis,
demyelination,
neuronal necrosis,
or cystic degeneration.
T2 hyperintense lesion can be found in putamen,
globus pallidus,
thalamus,
nucleus caudatus,
midbrain and potine tegmentum,
in subcortical region (like frontal,
parietal and temporal),
cerebellar peduncle.
2.
T2-Hypoinstense center with peripheral hyperintense.
T2-weighted image can show hypointensity in the basal ganglia (globus pallidus) region may be as a result of deposition of iron in exchange for copper after chelation.
3.
T1-Hyperintense lesion/T2-Iso/Hypointense
High signal intensity abnormality on T1-weighted image showed bilateral and symetric distribution.
Sites of involvements are globus pallidus,
putamen,
midbrain and caudate nucleus.
Wilson disease can be categorized into 2 groups on the basis of MRI imaging finding:
A.
High-signal intensity lesions in the basal ganglia on T1-weighted images reflected hepatic involvement of Wilson disease.
B.
High-signal-intensity lesions on T2-weighted images reflected cerebral involvement of Wilson disease.
4.
Generalised brain atrophy is evident in 68% of neurologically symptomatic patients.
5.
Specific abnormal sign – Face of giant panda sign (Fig.1),
Face of miniature panda sign (Fig.2),
Bright claustrum sign (Fig.3).
Spectroscopy and single-photon emission computed tomography (SPECT).
- Might be useful in detecting early brain damage in Wilson’s disease,
not only in the perspective of assessing and treating motor impairment but also in better evaluating the less investigated disorders in the cognitive domain.
Transcranial brain parenchyma sonography (TCS).
- Detects lenticular nucleus hyperechogenicity even when in MRI no abnormalities are observed,
but it must be confirmed in further studies.
Others:
- In laboratory findings can be found coagulopathy,
elevation of liver enzymes,
decreased level of ceruloplasmin,
high levels of copper in urine,
urinary copper excretion with D-penicillamine
- neurologic findings
- genetic testing
Scoring system:
- Leipzig score is a scoring system based on typical clinical symptoms,
signs and tests (Fig.5).