Portosystemic Encephalopathy Workup

Updated: Sep 17, 2019
  • Author: Gagan K Sood, MD; Chief Editor: BS Anand, MD  more...
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Workup

Laboratory Studies

Laboratory studies include the following:

  • Serum calcium levels

  • Serum ammonia levels, preferably arterial: Elevated blood levels are not diagnostic of hepatic encephalopathy, and normal levels do not rule out hepatic encephalopathy. However, very high levels may suggest an unsuspected urea cycle enzyme deficiency. They are helpful to suggest a diagnosis of hepatic encephalopathy when the cause is obscure.

  • Serum glucose measurements

  • Serum aspartate aminotransferase (AST) levels: A very high AST and/or alanine aminotransferase (ALT) level (eg >1000 U/L) may suggest widespread hepatic necrosis as a consequence of acetaminophen toxicity and, accordingly, may help guide appropriate diagnostic evaluations and therapy (with acetaminophen levels and N-acetylcysteine). However, very high AST and ALT values may be observed in other settings (notably ischemic hepatitis and other causes of submassive or massive hepatic necrosis) and, therefore, are not specific.

  • Serum ALT levels: ALT is more specific for a liver origin because AST also may be released from muscle.

  • Serum bilirubin measurements

  • Complete blood cell (CBC) count

  • Blood and urine screen for drugs

  • Blood alcohol level

  • Serum electrolyte levels: Electrolytes may be disturbed for a variety of reasons in patients with advanced liver disease. Hyponatremia resulting from diuretic use, renal failure, water intoxication, or the syndrome of inappropriate secretion of antidiuretic hormone is particularly important to consider as a contributing cause of encephalopathy.

  • Prothrombin time, and levels of serum albumin and bilirubin: These measurements are true liver function tests that provide an estimate of the severity of liver damage. They also allow the clinician to anticipate certain potential complications (eg, bleeding) and adjust therapy appropriately.

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Imaging Studies

Computed tomography (CT) scanning of the head

The rationale for CT scanning is to exclude structural considerations in the differential diagnosis, including intracranial hemorrhage (epidural, subdural, subarachnoid, intraparenchymal), cerebral infarct, intracranial infections (brain abscess with mass effect, meningoencephalitis), and hydrocephalus.

CT scanning of the head may not be necessary in patients with well-documented liver disease and a typical history, especially if no focal or localizing signs are evident. However, if the circumstances leave any doubt, CT scanning is critical in helping exclude structural causes for encephalopathy.

This test is more widely available than magnetic resonance imaging (MRI) and generally can be performed more rapidly. Therefore, it is the imaging modality of first choice in most instances.

Patients may develop portosystemic encephalopathy and subsequently sustain head trauma. This is particularly common among patients with alcoholism, and the event may not be volunteered during history taking or may not be evident upon physical examination. However, in uncomplicated portosystemic encephalopathy, no characteristic clues or findings are present.

Magnetic resonance imaging (MRI)

The availability and speed with which CT scans can be performed make them preferable in most instances for helping exclude mass lesions and, especially, intracranial hemorrhage. However, MRI findings may be of particular value in cases in which a diagnosis is not clear, based on other clinical and laboratory data.

The presence of hyperintense-appearing regions on T1-weighted MRI studies of the brains of patients with cirrhosis is described as a characteristic feature. The increased MRI signal intensity may be the result of manganese (Mn) deposition in these structures.

The globus pallidus, putamen, and caudate nucleus of the basal ganglia and the frontal and occipital cortex of patients with cirrhosis who died with hepatic encephalopathy contain increased Mn concentrations when compared to matched control specimens. Pallidal hyperintensity on T1-weighted MRI does not appear to be present in well-compensated patients with cirrhosis who do not have hepatic encephalopathy. This finding appears to correlate with blood ammonia levels but not the severity of hepatic encephalopathy itself.

The amount of Mn deposition that can be identified at autopsy of patients with hepatic coma appears to be independent of the patient's age, etiology of cirrhosis, or the presence of chronic hepatic encephalopathy. In an experimental model using both cirrhotic and portacaval-shunted rats, Mn levels in the basal ganglia were significantly elevated above control values. These levels also were significantly higher in portacaval-shunted rats when compared to those with experimental cirrhosis; therefore, although the precise etiology responsible for Mn deposition is unclear, it is enhanced by portal hypertension.

Therefore, signs of extrapyramidal toxicity in hepatic encephalopathy conceivably may result from Mn deposition. The neurologic and radiologic changes may resolve gradually with time following liver transplantation. Deposition of Mn also may potentiate the effects of benzodiazepines (BZPs), natural or otherwise, by increasing the number of available peripheral-type BZP binding sites (possibly by promoting receptor expression).

These intriguing issues unveiled by the advent of MRI are complemented by the metabolic data derived from the application of magnetic resonance spectroscopy (MRS). This technique has demonstrated findings of altered glutamine metabolism. Its role in clinical evaluation and management of hepatic encephalopathy is unclear. In one series, MRS findings (ie, decreased myoinositol, increased glutamine) correlated poorly with neurologic status. These markers were suggested to be more representative of the underlying chronic hepatic dysfunction.

Positron emission tomography (PET) scanning

PET scanning has demonstrated reduced metabolic activity for glucose utilization in the parietal cortex of patients with cirrhosis with mild hepatic encephalopathy. At present, this technique is best reserved for research applications because no clear clinical guidelines are available for its use, and moreover its availability is limited.

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Other Tests

Psychometric testing

Psychometric evaluations are of value for establishing the diagnosis and perhaps for monitoring the response to therapy in subclinical portosystemic encephalopathy. The number-connection test and the trail-making test are pragmatic approaches, and they are used widely at the bedside.

More formal testing may not be feasible with many patients, in part due to the length of time taken to administer the tests and also because of patient uncooperativeness. However, the results of psychometric testing in subclinical portosystemic encephalopathy may be of prognostic value independent of the Child-Pugh score of disease severity.

Patients with alcohol-induced liver disease exhibit poorer test scores than those with liver disease from other causes, presumably due to cerebral toxicity intrinsic to chronic alcohol use and independent of the hepatic insufficiency.

A grading scheme that incorporates the level of consciousness, personality and intellect, neurologic signs, and electroencephalographic (EEG) abnormalities has been proposed for hepatic encephalopathy. The clinical portion of this grading approach has the advantage of being easily administered at the bedside, and it is helpful as a guide to progress.

Electroencephalography

EEG studies of patients in portosystemic encephalopathy grades 1-3 may demonstrate high voltage and low-frequency triphasic waves of 1-3 Hz. These also may be seen in uremia but are characteristic of hepatic encephalopathy. With progression to coma, the EEG typically shows delta-wave activity, representing a generalized slowing of the cortex, a nonspecific pattern seen in toxic and metabolic encephalopathies.

The EEG is most helpful in excluding the presence of other causes for encephalopathy, such as status epilepticus and akinetic seizures, or the demonstration of postictal slowing with or without focal spike and wave activity that suggests prior seizures.

EEG monitoring frequently is useful in assisting with the diagnosis of hepatic encephalopathy, especially subclinical hepatic encephalopathy. Computer-assisted or spectral EEG analysis may demonstrate characteristic abnormalities, but the incremental benefit over conventional EEG is unclear.

Evoked potentials

Further electrophysiologic assessment may be performed with evoked-potential studies, but whether this approach is of value remains unclear, except when significant doubt exists with respect to the underlying diagnosis of portosystemic encephalopathy as the cause for neuropsychiatric dysfunction. This is rarely the case in practice.

These studies include visual-evoked potentials, somatosensory-evoked potentials, or brainstem auditory–evoked potentials, and they represent the externally recorded voltage from synchronous firing of neurons in a network response to specific stimuli.

The chief value of this approach may be to document abnormal cortical function in subclinical portosystemic encephalopathy and to establish the diagnosis. Brainstem auditory–evoked responses appear particularly sensitive as a marker of perturbed cortical function. Evoked-potential studies in acute hepatic encephalopathy conceivably may be useful for monitoring clinical response to treatment; however, the use of these electrophysiologic diagnostic modalities is not widespread.

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Histologic Findings

In neuropathologic studies of hepatic encephalopathy, Alzheimer type II astrocytosis is typical and likely represents the end result of these mechanisms. The astrocytes demonstrate swollen nuclei, margination of the chromatin, and a prominent nucleolus.

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