are seen, magnetic resonance imaging of the brain is usually performed; this shows hyperintensities in the part of the brain called the basal ganglia in the t2 setting. mri may also demonstrate the characteristic "face of the giant panda" pattern. no totally reliable test for wilson's disease is known, but levels of ceruloplasmin and copper in the blood, as well of the amount of copper excreted in urine during a 24-hour period, are together used to form an impression of the amount of copper in the body. the gold standard—or most ideal test—is a liver biopsy. ceruloplasmin ceruloplasmin levels of ceruloplasmin are abnormally low (<0.2 g/l) in 80–95% of cases. it can be present at normal levels, though, in people with ongoing inflammation, as it is an acute phase protein. low ceruloplasmin is also found in menkes disease and aceruloplasminemia, which are related to, but much rarer than wilson's disease. the combination of neurological symptoms, eye signs, and a low ceruloplasmin level is considered sufficient for the diagnosis of wilson's disease. in many cases, however, further tests are needed. serum and urine copper serum copper is low, which may seem paradoxical given that wilson's disease is a disease of copper excess. however, 95% of plasma copper is carried by ceruloplasmin, which is often low in wilson's disease. urine copper is elevated in wilson's disease and is collected for 24 hours in a bottle with a copper-free liner. levels above 100 μg/24h (1.6 μmol/24h) confirm wilson's disease, and levels above 40 μg/24h (0.6 μmol/24h) are strongly indicative. high urine copper levels are not unique to wilson's disease; they are sometimes observed in autoimmune hepatitis and in cholestasis (any disease obstructing the flow of bile from the liver to the small bowel). in children, the penicillamine test may be used. a 500 mg oral dose of penicillamine is administered, and urine collected for 24 hours. if this contains more than 1600 μg (25 μmol), it is a reliable indicator of wilson's disease. this test has not been validated in adults. slit-lamp examination the eyes of the patient are examined using a slit lamp to look for kayser–fleischer rings, which are strongly associated with wilson's disease and are caused by copper deposition on the inner cornea in descemet's membrane. liver biopsy once other investigations have indicated wilson's disease, the ideal test is the removal of a small amount of liver tissue through a liver biopsy. this is assessed microscopically for the degree of steatosis and cirrhosis, and histochemistry and quantification of copper are used to measure the severity of the copper accumulation. a level of 250 μg of copper per gram of dried liver tissue confirms wilson's disease. occasionally, lower levels of copper are found; in that case, the combination of the biopsy findings with all other tests could still lead to a formal diagnosis of wilson's. in the earlier stages of the disease, the biopsy typically shows steatosis (deposition of fatty material), increased glycogen in the nucleus, and areas of necrosis (cell death). in more advanced disease, the changes observed are quite similar to those seen in autoimmune hepatitis, such as infiltration by inflammatory cells, piecemeal necrosis, and fibrosis (scar tissue). in advanced disease, finally, cirrhosis is the main finding. in acute liver failure, degeneration of the liver cells and collapse of the liver tissue architecture is seen, typically on a background of cirrhotic changes. histochemical methods for detecting copper are inconsistent and unreliable, and taken alone are regarded as insufficient to establish a diagnosis. genetic testing mutation analysis of the atp7b gene, as well as other genes linked to copper accumulation in the liver, may be performed. once a mutation is confirmed, family members can be screened for the disease as part of clinical genetics family counseling. regional distributions of genes associated with wilson's disease are important to follow, as this can help clinicians design appropriate screening strategies. since mutations of the atp7b gene vary between populations, research and genetic testing done in countries such as the usa or united kingdom can pose problems, as they tend to have more mixed populations. treatment diet in general, a diet low in copper-containing foods is recommended with the avoidance of mushrooms, nuts, chocolate, dried fruit, liver, sesame seeds and sesame oil, and shellfish. medication medical treatments are available for wilson's disease. some increase the removal of copper from the body, while others prevent the absorption of copper from the diet. generally, penicillamine is the first treatment used. this binds copper (chelation) and leads to excretion of copper in the urine. hence, monitoring of the amount of copper in the urine can be done to ensure a sufficiently high dose is taken. penicillamine is not without problems; about 20% experience a side effect or complication of penicillamine treatment, such as drug-induced lupus (causing joint pains and a skin rash) or myasthenia (a nerve condition leading to muscle weakness). in those who presented with neurological symptoms, almost half experience a paradoxical worsening in their symptoms. while this phenomenon is observed in other treatments for wilson's, it is usually taken as an indication for discontinuing penicillamine and commencing second-line treatment. those intolerant to penicillamine may instead be commenced on trientine hydrochloride, which also has chelating properties. some recommend trientine as first-line treatment, but experience with penicillamine is more extensive. a further agent, under clinical investigation by wilson therapeutics, with known activity in wilson's disease is tetrathiomolybdate. this is regarded as experimental, though some studies have shown a beneficial effect. once all results have returned to normal, zinc (usually in the form of a zinc acetate prescription called galzin) may be used instead of chelators to maintain stable copper levels in the body. zinc stimulates metallothionein, a protein in gut cells that binds copper and prevents its absorption and transport to the liver. zinc therapy is continued unless symptoms recur or if the urinary excretion of copper increases. in rare cases where none of the oral treatments is effective, especially in severe neurological disease, dimercaprol (british anti-lewisite) is occasionally necessary. this treatment is injected intramuscularly (into a muscle) every few weeks and has unpleasant side effects such as pain. people who are asymptomatic (for instance, those diagnosed through family screening or only as a result of abnormal test results) are generally treated, as the copper accumulation may cause long-term damage in the future. whether these people are best treated with penicillamine or zinc acetate is unclear. physical and occupational therapies physiotherapy and occupational therapy are beneficial for patients with the neurological form of the disease. the copper-chelating treatment may take up to six months to start working, and these therapies can assist in coping with ataxia, dystonia, and tremors, as well as preventing the development of contractures that can result from dystonia. transplantation liver transplantation is an effective cure for wilson's disease, but is used only in particular scenarios because of the risks and complications associated with the procedure. it is used mainly in people with fulminant liver failure who fail to respond to medical treatment or in those with advanced chronic liver disease. liver transplantation is avoided in severe neuropsychiatric illnesses, in which its benefit has not been demonstrated. prognosis left untreated, wilson's disease tends to become progressively worse and is eventually fatal. serious complications include liver cirrhosis, acute kidney failure, and psychosis. with early detection and treatment, most of those affected can live relatively normal lives. liver and neurologic damage that occurs prior to treatment may improve, but it is often permanent. history the disease bears the name of british physician samuel alexander kinnier wilson (1878–1937), a neurologist who described the condition, including the pathological changes in the brain and liver, in 1912. wilson's work had been predated by, and drew on, reports from german neurologist karl westphal (in 1883), who termed it "pseudo-sclerosis"; by the british neurologist william gowers (in 1888); by the finnish neuropathologist ernst alexander homén (in 1889–1892), who noted the hereditary nature of the disease; and by adolph strümpell (in 1898), who noted hepatic cirrhosis. neuropathologist john nathaniel cumings made the link with copper accumulation in both the liver and the brain in 1948. the occurrence of hemolysis was noted in 1967. in 1951, cumings, and new zealand neurologist derek denny-brown, working in the united states, simultaneously reported the first effective treatment, using metal chelator british anti-lewisite . this treatment had to be injected, but was one of the first therapies available in the field of neurology, a field that classically was able to observe and diagnose, but had few treatments to offer. the first effective oral chelation agent, penicillamine, was discovered in 1956 by british neurologist john walshe. in 1982, walshe also introduced trientine, and was the first to develop tetra-thiomolybdate for clinical use. zinc acetate therapy initially made its appearance in the netherlands, where physicians schouwink and hoogenraad used it in 1961 and in the 1970s, respectively, but it was further developed later by brewer and colleagues at the university of michigan. the genetic basis of wilson's disease, and its link to atp7b mutations, was elucidated by several research groups in the 1980s and 1990s. in other animals hereditary copper accumulation has been described in bedlington terriers, where it generally only affects the liver. it is due to mutations in the commd1 (or murr1) gene. despite this findings, commd1 mutations could not be detected in humans with non-wilsonian copper accumulation states (such as indian childhood cirrhosis) to explain their genetic origin.