Portosystemic encephalopathy: causes, symptoms, diagnosis, treatment

Portosystemic encephalopathy is a reversible psychoneurological syndrome that develops in patients with portosystemic shunting. Symptoms of portosystemic encephalopathy are mainly psychoneurological (for example, confusion, "clapping" tremor, coma). The diagnosis is based on clinical signs. Treatment of portosystemic encephalopathy usually consists in the elimination of the acute cause, the restriction of the dietary protein and the administration of oral lactulose.

The term "portosystemic encephalopathy" better reflects the pathophysiology of a condition than hepatic encephalopathy or a hepatic coma, but all three terms are interchangeable.

[1], [2], [3], [4]

Causes of Portosystemic Encephalopathy

Portosystemic encephalopathy can develop with fulminant hepatitis caused by a viral infection, drugs or toxins, but this is more common for cirrhosis of the liver or other chronic diseases in which significant portosystemic collaterals are formed as a result of portal hypertension. Encephalopathy develops after portosystemic shunting, for example after the creation of anastomoses between the portal and hollow veins [portocaval anastomosis or transgular intrahepatic portosystemic shunting (TIPS)].

In patients with chronic liver disease, acute episodes of encephalopathy are usually provoked by causes that can be eliminated. The most common of these are metabolic stress (eg, infection, electrolyte imbalance, especially hypokalemia, dehydration, use of diuretics), conditions in which protein absorption from the intestine increases (eg, gastrointestinal bleeding, protein-rich diet) and nonspecific agents that depress CNS (eg, alcohol, sedatives, analgesics).

[5], [6], [7], [8]

Pathophysiology of Portosystemic Encephalopathy

Portosystemic shunting leads to the intake of metabolites in the bloodstream, which must be rendered harmless by the liver and toxic to the brain, especially the cortex. Which substances have a toxic effect on the brain, it is not known. An important role is played by ammonia, which is a product of protein digestion, but other factors [for example, changes in benzodiazepine receptors of the brain and neurotransmission by gamma-aminobutyric acid (GABA)] can also contribute. The level of aromatic amino acids in the serum is usually high, and the branched chain amino acids is low, but these ratios most likely do not cause encephalopathy.

Symptoms of Portosystemic Encephalopathy

Symptoms and manifestations of encephalopathy tend to progress. Until moderate malfunction of the brain occurs, signs of encephalopathy are usually implicit. Constructive apraxia, in which the patient can not reproduce a simple pattern (for example, a star), develops early. Excitation and manic syndrome may develop, but not necessarily. A characteristic "fluttering" tremor (asterixis) is revealed if the patient keeps his hands outstretched with wrists bent downward. Neurological disorders are usually symmetrical. Neurologic manifestations in coma usually reflect bilateral diffuse hemispheric dysfunction. Signs of brainstem dysfunction develop only with the progression of coma, often within a few hours or days before death. A musty, sweetish odor when breathing (liver odor from the mouth) can be observed regardless of the stage of encephalopathy.

Diagnosis of Portosystemic Encephalopathy

The diagnosis, as a rule, is based on clinical data, but an additional examination helps in its formulation. A psychometric study can reveal unexpressed neuropsychiatric disorders that will help verify early symptoms of encephalopathy. The level of ammonia as a whole serves as a laboratory marker of encephalopathy, but this analysis is neither specific nor highly sensitive and does not characterize the severity of encephalopathy. EEG usually demonstrates diffuse low-wave activity even with moderate encephalopathy and can be a fairly sensitive technique, but it is not specific for early stages of encephalopathy. CSF examination is usually not necessary; the only permanent pathological change is a moderate increase in protein.

In the case of differential diagnosis, other potentially potential disturbances that can cause such manifestations (eg, infection, subdural hematoma, hypoglycemia, intoxication) should be excluded. If portosystemic encephalopathy is confirmed, the cause of its progression should be specified.

[9], [10], [11], [12], [13]

Treatment of Portosystemic Encephalopathy

In mild cases, the elimination of the cause usually leads to the reverse development of encephalopathy. The second task of therapy is the elimination of toxic digestive products from the body, it is achieved through the use of a number of methods. The intestine should be cleaned with an enema or, more often, by ingestion of lactulose syrup, which can be used to feed through the probe in comatose patients. This synthetic disaccharide is an osmotic cleanser. It also lowers the pH in the colon, reducing the formation of ammonia in the fecal masses. The initial dosage (30-45 ml orally 3 times a day) should be adjusted so that the patient has two or three times a soft stool every day. Also, food protein must be eliminated (20-40 g per day for moderate manifestations), and the lack of calories is compensated by ingestion or intravenous carbohydrates.

Sedation aggravates encephalopathy, and, if possible, it should be avoided. With coma caused by fulminant hepatitis, careful care and a therapeutic diet along with prevention and treatment of complications increase the chance of survival. Glucorticoids in high doses, exchange blood transfusions, and a complex of other complex measures aimed at eliminating toxins circulating in the blood do not generally improve the result. Clinical deterioration is due to the rapid development of hepatic insufficiency, and patients can be saved only by liver transplantation.

Other treatments including levodopa, bromocriptine, flumazenil, sodium benzoate, branched chain amino acid transfusions, essential amino acid ketoanalys and prostaglandins have proved ineffective. The results of using complex blood plasma filtration systems (artificial liver) are encouraging, but they require further study.

Forecast of portosystemic encephalopathy

In chronic liver diseases, the elimination of the cause of encephalopathy usually leads to its reversal without permanent neurological consequences. Some patients, especially with portocaval shunting or TIPS, need constant drug therapy, irreversible extrapyramidal disorders or spastic paraparesis rarely develop. Coma (4th stage of encephalopathy) with fulminant hepatitis is fatal in 80% of patients, despite intensive therapy; a combination of progressive chronic liver failure and portosystemic encephalopathy is also often fatal.

Clinical stages of portosystemic encephalopathy

Stage	Cognitive Sphere and Behavior	Neuromuscular function
0 (subclinical)	Asymptomatic loss of cognitive abilities	Absent
1	Sleep disturbance; violation of concentration; depression; anxiety or irritability	A monotonous voice; tremor; bad handwriting; constructive apraxia
2	Drowsiness; disorientation; bad short-term memory; behavioral disorders	Ataxia; dysarthria; "Fluttering" tremor; automatism (yawning, blinking, sucking)
3	Drowsiness; confusion of consciousness; amnesia; anger; paranoia or other strange behavior	Nystagmus; stiff muscles; hyper- or hyporeflexia
4	Coma	Extended pupils; oculocephalic or oculovestibular reflexes; decerebral pose

[14], [15], [16], [17], [18]