Exchangeable copper: a reflection of the neurological severity in Wilson's disease.

BACKGROUND AND PURPOSE: The severity of Wilson's disease (WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (CuEXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. METHODS: Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging (MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. CuEXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. RESULTS: Extra-hepatic patients had significantly higher CuEXC values than those with the hepatic form (P < 0.0001). The overall ability of CuEXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 µmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, CuEXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score (r = 0.45, P = 0.016), the Kayser-Fleischer ring score (r = 0.46, P = 0.014) and the brain MRI score (r = 0.38, P = 0.048), but it was not correlated with the hepatic score. CONCLUSIONS: Exchangeable copper determination is useful when diagnosing WD as a value >2.08 µmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes.

Cognitive profile in Wilson's disease: a case series of 31 patients.

BACKGROUND: Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients. METHODS: Patients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N(-)) (n=13), and WD patients with neurological signs (WD-N(+)) (n=18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities. RESULTS: Both groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N(+) group performed less well than the WD-N(-) group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control. CONCLUSIONS: Cognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease.

Wilson's disease, 100 years later .

Texts published, in 1912, 100 years ago, by Sir K. Wilson on his eponymous disease in Brain, The Lancet and La Revue Neurologique highlight the relevance of his descriptions in the light of the current knowledge. Wilson's invocation of an "unknown toxin" appears today as a prophetic intuition as the presence of excess copper in the liver was mentioned for the first time a year later whereas the role of copper in this disease was not described until 1929. Progress has been made to better understand the physiology of Wilson's disease (WD). The ATP7B gene implicated in WD is located on chromosome 13 and more than 500 mutations and 100 polymorphisms have been to date identified. The phenotypic expression is highly variable, even within a family. This can partly be explained by environmental factors as nutrition. Modulator genes are also involved in the phenotypic expression of the disease. Most of symptoms observed in WD have already been described in detail by Wilson in 1912, but subsequent progress was made over the following 100 years, helping the physician diagnose WD. Hepatic and neurological symptoms are the most frequent expressions of the disease. Other extrahepatic features include renal manifestations, osteoarticular disorders, myocardial abnormalities, endocrine disturbances, realizing a multisystemic disease. The diagnosis of the disease is based on a combination of clinical symptoms, biological, radiological and genetic data and new tools (Brain MRI, relative exchangeable copper…) allow reducing delay to diagnosis. Therapeutic findings have also changed the disease prognosis. Treatment is based on the use of copper chelators to promote copper excretion from the body (D-penicillamine and Triethylenetetramine) and zinc salts to reduce copper absorption. Tetratiomolybdate appears to be a promising treatment. While significant progress has been made during this century, many physiological aspects of this disease remain unknown and require further research to find answers in the next 100 years.

[Compliance with treatment in Wilson's disease: On the interest of a multidisciplinary closer follow-up]. / L'observance dans la maladie de Wilson : intérêt d'un suivi rapproché au long cours.

BACKGROUND: Compliance with treatment is very important for patients who suffer from Wilson's disease, a rare genetic disorder. They can benefit a long-life and effective treatment. The purpose of our study is to identify the level of compliance in Wilson's disease patients and features associated with compliance as well. METHODS: This is a prospective study carried out in the National Reference Center for Wilson Disease (based in Paris and Lyon) over a 8 months period. Patients were evaluated on the first (M0) and last month (M8) with a questionnaire evaluating the number of missed treatment doses, a self-questionnaire collecting the reasons for non-compliance, and analogic scales analyzing the doctor-patient relationship and their behavior towards the treatment. The severity of depression symptoms was investigated by the Beck Depression Inventory (BDI). A detailed phone call interview was conducted by a psychologist every two months to evaluate their compliance and feeling. RESULTS: Thirty-nine patients were included. The mean age of patients was 34 years (±9.9). At M0, 84.6% had a poor compliance with treatment. They were diagnosed more recently (P=0.049) with a higher proportion involving neurological disorders (P=0.007). Age, the type of treatment and the quality of the doctor-patient relationship were not associated with the outcome; 38.5% suffered from depressive symptoms. At M8, 56.8% of patients were poor compliants and 21.6% presented depressive symptoms. CONCLUSION: Wilsons's disease patients have important problems with compliance, without necessary being depressed. A close follow-up may help them become compliant, particularly those with neurological symptoms.