Neurological diseases with cirrhosis

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

Wilson SAK Progressive lenticular degeneration a familial nervous disease associated with cirrhosis of the liver. Brain 34 295-509, 1912 Winther JF, Friis S, Bach FW, et al Neurological disease among women with silicone breast implants in Denmark. Acta Neurol Scand 103 93-96, 2001... 

Parenteral administration of iodinated contrast media to patients taking metformin may result in lactic acidosis. However, the problem is reported to occur only if the contrast media causes renal failure and metformin use is continued. This is because metformin is mainly excreted by the kidneys and in renal failure toxic levels may accumulate, which may result in lactic acidosis. A literature search identified 18 cases of lactic acidosis after the use of contrast media in patients taking metformin. Of these 18 cases, 14 or 15 were associated with pre-existing renal impairment and 2 cases with other contraindications to metformin (sepsis and cirrhosis). The remaining case was in an elderly woman with neurological disease. 

Interpretation of Wilson s disease on the basis of disrupted copper metabolism is far from complete. The accumulation of copper in tissues is generally considered responsible for the lesions of the liver (cirrhosis), renal tubules (amino aciduria), and basal ganglia (neurological disorder), but the special affinity of these various tissues for copper remains to be explained, as does the mechanism of copper toxicity in these organs. Penicillamine, a copper-chelating substance, has been administered for treatment of Wilson s disease with some degree of success. In fact, it has even been claimed that asymptomatic victims of Wilson s disease can be treated preventively [56]. 

In a fulminant course of Wilson s disease or an advanced stage of cirrhosis with complications or in cases where medication is not feasible, the only remaining alternative is liver transplantation. After successful transplantation, all clinical findings and laboratory parameters improve, and even neurological disorders become reversible. Transplantation is a causal therapy, which confirms that the primary metabolic defect of Wilson s disease is located in the liver. (348) This means that no copperreleasing medication is required following transplantation. (324, 352, 361, 363, 372, 375, 384)... 

Most patients with Wilson disease, whatever their clinical presentation, have some degree of liver disease. Chronic liver disease (if undiagnosed and untreated) may precede manifestation of neurological symptoms for more than 10 years. Patients can present with liver disease at any age. The most common age of hepatic manifestation is between 8 and 18 years, but cirrhosis may already be present in children below the age of 5. On the other hand, Wilson disease is diagnosed also in patients presenting with advanced chronic liver disease in their 50s or 60s, without neurological symptoms and without Kayser-Fleischer rings. 

Liver transplantation is the treatment of choice in patients with fulminant Wilson disease and in patients with decompensated cirrhosis. Besides improving survival, liver transplantation also corrects the biochemical defect underlying Wilson disease. However, the role of this procedure in the management of patients with neurological Wilson disease in the absence of hepatic insufficiency is still uncertain. 

Hyperammonemia may also result from congenital or acquired causes that are not related to inherited metabolic diseases. Examples of congenital causes include malformations such as portosystemic shunts, extrahepatic portal vein obstructions, and cirrhosis with portal hypertension. Transient hyperammonemia of the newborn (THAN) is typically identified in premature infants and does not appear to have a neurologic effect on those asymptomatic preterm infants [11]. Liver failure may also result in fulminant hyperammonemia. In severe liver failure, all of the enzymes expressed in the liver are deficient, resulting in complete impairment of the urea cycle as well as a deficiency of other important liver-specific enzymes snch as the glycine cleavage enzyme. 

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