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Neurological syndromes commonly occur in patients with liver disease. A neurological syndrome associated with a liver disease may be a complication of the disease, it may be induced by a factor that also contributes to the disease
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Neurological syndromes commonly occur in patients with liver disease. A neurological syndrome associated with a liver disease may be a complication of the disease, it may be induced by a factor that also contributes to the disease—for example, alcohol—or it may have no relation to the presence of the liver disease. Neurological deficits associated with liver disease may affect the CNS, the peripheral nervous system, or both. This review focuses on syndromes characterised by altered CNS function associated with structural liver diseases. Space does not permit consideration of peripheral neuropathies associated with liver disease (for example, xanthomatous peripheral neuropathy), diseases of childhood that affect the liver and CNS (for example, Reye’s syndrome), or neurological consequences of hepatic lesions characterised by specific enzyme deficiencies (for example, congenital hyperammonaemias, the porphyrias, kernicterus, galactosaemia, and Zellweger’s syndrome (cerebrohepatorenal syndrome)).
That there is a relationship between the functional status of the liver and that of the brain has been known for centuries.1 The most widely recognised aspect of this relation is that hepatocellular failure may be complicated by the behavioural syndrome of hepatic encephalopathy, in which neurotransmission in the brain is altered.2 3 Recently, it has been suggested that two other behavioural complications of liver disease, scratching due to pruritus in cholestatic patients4 5 and profound fatigue in patients with chronic cholestasis,6 7 may also be associated with altered neurotransmission in the brain.
DEFINITIONS AND CLASSIFICATION
The term hepatic encephalopathy refers to the syndrome of neuropsychiatric disturbances that may arise as a complication of acute, subacute, or chronic hepatocellular failure. The syndrome is associated with increased portal-systemic shunting of gut derived constituents of portal venous blood, due to their impaired extraction by the failing liver and, in most instances, their passage through intrahepatic and/or extrahepatic portal-systemic venous collateral channels.
The term portal-systemic encephalopathy is often used interchangeably with hepatic encephalopathy, but portal-systemic encephalopathy can be defined to include encephalopathy associated with increased portal-systemic shunting in the absence of unequivocal evidence of hepatocellular insufficiency—for example, shunting secondary to a congenital portal-systemic shunt, extrahepatic portal hypertension or portal hypertension due to hepatic fibrosis (for example, schistosomiasis).
Subclinical hepatic encephalopathy is the term applied to a patient with chronic liver disease (for example, cirrhosis) when routine neurological examination is normal, but application of psychometric or electrophysiological tests discloses abnormal brain function that can be reversed by effective treatment for hepatic encephalopathy.8
Fulminant hepatic failure and subfulminant (or late onset) hepatic failure are terms used when the syndrome of acute liver failure is complicated by hepatic encephalopathy within one to several weeks of the first evidence of liver disease or the development of jaundice.9 10
Hepatic encephalopathy occurring in a patient with cirrhosis may be either acute or chronic. The acute form in such a patient is usually associated with a clearly identifiable precipitating factor and usually resolves when the precipitating factor is removed or corrected. Failure to find a precipitating factor may imply that a decrease in overall hepatocellular function has taken place. The term chronic hepatic encephalopathy (or chronic portal-systemic encephalopathy) is often applied to a patient with cirrhosis and substantial portal-systemic shunting, who has hepatic encephalopathy that is persistent or episodic, with or without complete resolution of encephalopathy between episodes.
It has been conventional to classify hepatic encephalopathy as a reversible metabolic encephalopathy. This definition excludes rare neurodegenerative disorders associated with chronic liver disease and extensive portal systemic shunting (see Degenerative disorders section). However, this widely accepted classification of hepatic encephalopathy may need reappraisal.11 12 It is probably useful to classify cerebral oedema and raised intracranial pressure (ICP) occurring in patients with fulminant hepatic failure separately from hepatic encephalopathy. However, these complications of fulminant hepatic failure contribute to encephalopathy, occur together with hepatic encephalopathy, and may share pathogenic factors with hepatic encephalopathy (for example, raised ammonia concentrations) (see Fulminant hepatic failure section).
The term encephalopathy covers a wide range of neuropsychiatric disturbances ranging from minimal changes in personality or altered sleep pattern to deep coma13 (table 1). The earliest clinical signs of hepatic encephalopathy (stage 1) are often subtle psychiatric and behavioural changes that m