Dementia in hepatic and renal failure
by Kurt Jellinger
Among metabolic and toxic disorders leading to cognitive impairment, both acute and chronic hepatic and renal failure may have adverse effects on the CNS with serious repercussions for cerebral function causing both neurological and psychiatric signs and symptoms.
They result in metabolic encephalopathies, a series of disorders that, although potentially reversible following appropriate therapy or organ transplantation, may ultimately lead to CNS changes. The best characterised of these disorders include those associated with liver and kidney failure.
Hepatic or portal-systemic encephalopathy; uremic encephalopathy.
Symptoms and course
Fulminant hepatic failure results from severe inflammatory or necrotic liver disease of rapid onset and progressive neurological signs from altered mental status, stupor and coma, often within hours or days. It is also seen in failed liver transplants.
Porto-systemic encephalopathy (PSE) is the most commonly encountered form of CNS disorder associated with hepatic failure. It accompanies the development of portal-systemic collaterals arising as a result of portal hypertension in liver cirrhosis.
Neurologically, it develops slowly, the onset is insidious starting with anxiety, restlessness, and altered sleep patterns. These symptoms are followed by shortened attention span and muscular incoordination, asterixis, and lethargy, progressing to stupor and coma.
Multiple episodes of PSE are not uncommon. In uremic encephalopathy, occurring when the glomerular filtrating rate declines below 10% of normal, neurological symptoms tend to fluctuate, and although, variable include disturbances of memory and cognition. They may progress to delirium, convulsions, stupor and coma.
Acute hepatic encephalopathy shows a rapidly progressing course and death results in 70-80% of the patients, which reach grade IV (deep) coma. Clinical signs of increased intracranial pressure include increased muscle tone in the arms and legs, progressing to full decerebrate posture, marked hyperventilation and dilated pupils with final deep coma or brain death.
PSE shows a chronic progressive course, which may be lethal due to severe hepatic failure. The same applies for uremic encephalopathy.
Causes and risk factors
Acute hepatic encephalopathy results from acute hepatic failure with severe brain swelling which varies according to the aetiology of liver disease, with patients with hepatitis B or non-A, non-B hepatitis having the highest incidence of this complication.
PSE frequently results from a precipitating factor, such as dietary protein overload, constipation or gastrointestinal bleeding. Other conditions are hypoglycaemia, hypoxia, or the use of sedative drugs, particulary benzodiazepines, may also precipitate PSE in cirrhosis patients.
The pathophysiology of uremic encephalopathy is complex and is considered a multifactorial process, and may initially reflect a neurotransmitter deficit. There is evidence that parathyroid hormone (PTH) plays a role (Fraser, 1993), since, in uremic patients, both the EEG abnormalities and the neuropsychiatric symptoms are improved by either parathyroidectomy or medical suppression of PTH (Cogan et al. 1978). The mechanism whereby parathyroid hormone disturbs CNS function is unknown but could relate to facilitation of Ca2+ entry into the cell and consequent cell death.
Continuous monitoring of liver and kidney functions.
Care and treatment
Treatment would be best in a potentially reversible stage with urgent liver and /or kidney tranplantation. Treatment of PSE is prevention of variceal bleeding in cirrhotic patients, use of transjugular intrahepatic portal-systemic shunts (TIPS) which are safer and less expensive to perform than portocaval anastomosis surgery. However, a major complication of TIPS is PSE, which occurs in over 30% of patiens, particularly those over 60 years of age (Conn, 1993).
Treatment of uremic encephalopathy, except kidney tranplantation, is dialysis that may be associated with various clinical disorders of the CNS: dialysis disequilibrium syndrome resulting as a consequence of an osmotic gradient which develops between plasma and the brain during rapid dialysis, progressive intellectual dysfunction, and dialysis dementia that may be related to aluminium neurotoxicity. The frequency of dialysis dementia has been reduced with the use of aluminium-free dialysate (Burn & Bates, 1998).
Liver and kidney transplant services and dialysis services in many hospitals all over Europe.
Last Updated: vendredi 09 octobre 2009