No abstract

Wilson's disease is a disorder of biliary copper excretion that may result in severe neurological symptoms and advanced liver disease. The wide variation of phenotypic disease expression cannot be fully explained by the different mutations of the Wilson disease gene. In neurological disorders, such as Alzheimer's disease, temporal lobe epilepsy and cerebral trauma, the presence of the apolipoprotein E (ApoE) allele epsilon4 is associated with an increased vulnerability of the brain to the effects of the disease, whereas the presence of the ApoE genotype epsilon3/3 appears to provide moderate neuroprotection. We examined whether this hypothesis holds true for the development of neurological symptoms in patients with Wilson's disease. The ApoE genotype and the H1069Q mutation (the most common in Wilson's disease) status were determined by polymerase chain reaction-based mutation assays in 121 well-characterized, symptomatic index patients with Wilson's disease. An investigation profile was established in which the patients were grouped according to the clinical symptoms at presentation, the ApoE genotypes and the status of the H1069Q mutation. Fifty-nine per cent of the 121 patients had the allele combination ApoE epsilon3/3 (21% ApoE epsilon3/4, 19% ApoE epsilon3/2, 1% ApoE epsilon4/2). The distribution of ApoE genotypes did not deviate from known distributions in healthy European subjects. Within the group of 40 H1069Q-homozygous patients, the onset of symptoms was significantly delayed in patients with the ApoE epsilon3/3 genotype (25 +/- 6 years at presentation) compared with patients with the ApoE epsilon3/4 genotype (20 +/- 3 years at presentation). In this study, the ApoE genotype was established as an important factor delaying the onset of neurological and hepatic symptoms, but not modifying phenotypic disease expression in a homogeneous group of patients with Wilson's disease (all H1069Q-homozygotes, similar genetic background). The presence of ApoE epsilon3/3 attenuates clinical manifestations in Wilson's disease by mechanisms which might involve the antioxidant and membrane-stabilizing properties of the ApoE 3 protein.

Subarachnoid haemorrhage (SAH) has a high mortality and morbidity rate. Early SAH diagnosis allows the early treatment of a ruptured cerebral aneurysm, which improves the prognosis. Diagnostic cerebrospinal fluid (CSF) analyses may be performed after a negative computed tomography scan, but the precise analytical methods to be used have been debated. Here, we summarize the scientific evidence for different CSF methods for SAH diagnosis and describe their implementation in different countries. The principle literature search was conducted using PubMed and Scopus with the search items "cerebrospinal fluid", "subarachnoid haemorrhage", and "diagnosis". CSF analyses for SAH include visual examination, red blood cell counts, spectrophotometry for oxyhaemoglobin or bilirubin determination, CSF cytology, and ferritin measurement. The methods vary in availability and performance. There is a consensus that spectrophotometry has the highest diagnostic performance, but both oxyhaemoglobin and bilirubin determinations are susceptible to important confounding factors. Visual inspection of CSF for xanthochromia is still frequently used for diagnosis of SAH, but it is advised against because spectrophotometry has a superior diagnostic accuracy. A positive finding of CSF bilirubin is a strong indicator of an intracranial bleeding, whereas a positive finding of CSF oxyhaemoglobin may indicate an intracranial bleeding or a traumatic tap. Where spectrophotometry is not available, the combination of CSF cytology for erythrophages or siderophages and ferritin is a promising alternative.

No abstract

The drug of choice for the initial treatment of "decoppering" in Wilson's disease, an inherited disorder of copper metabolism, is the chelating agent D-penicillamine. In the case of harmful side-effects an alternative drug is triethylenetetramine dihydrocholoride (trien or trientine). Using the 24-h-urine excretion of copper and the oral copper loading test with copper-64, a double function for trien was found: trien increases the urine copper excretion and decreases the intestinal copper absorption respectively.