Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Hepatic and Pancreatic Encephalopathy
Hepatic Encephalopathy
Definition
The term hepatic encephalopathy (HE) refers to any type of cerebral dysfunction that is due to liver insufficiency and/or portosystemic shunting and is detectable by clinical, neuropsychologic, or neurophysiologic means. Three types of HE are differentiated based on the underlying cause: type A occurs in patients with acute liver failure (ALF), type B in patients with portosystemic shunting in the absence of liver dysfunction, and type C in patients with cirrhosis. Episodic, recurrent, and chronic progressive forms have been described.
Clinical Features
HE is characterized by alterations of cognition, motor function, and consciousness in various combinations. The most commonly used grading system that distinguishes grades of HE (I–IV) based on the degree of alteration in consciousness is the West Haven system ( Table 12-1 ). Motor symptoms can be detected in all grades, but with increasing frequency and severity in grades II and III ( Fig. 12-1 ). The most characteristic motor findings are extrapyramidal and cerebellar symptoms, including hypomimia, hypo- and bradykinesia, rigidity, tremor, dysarthria, dysdiadochokinesia, and ataxia. Hyperreflexia and pyramidal signs are observed predominantly in patients with grades III and IV encephalopathy. Asterixis (flapping tremor), a form of negative myoclonus, may be present in the absence of any alteration of consciousness or cognition, but is observed most frequently in patients with grade II or III disease.
Table 12-1
West Haven Criteria for Grading of Clinically Overt Hepatic Encephalopathy
From Ferenci P, Lockwood A, Mullen K, et al: Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 35:716, 2002, with permission.
| Grade I | Trivial lack of awareness, shortened attention span, impaired performance of addition, euphoria or anxiety |
| Grade II | Lethargy or apathy, minimal disorientation for time and place, inappropriate behavior |
| Grade III | Somnolence to semistupor but responsiveness to verbal stimuli, confusion, gross disorientation |
| Grade IV | Coma |
Difficulties in writing and speech disturbances are some of the first symptoms of HE in patients with liver cirrhosis. In the early phases, tremulous writing, omission of single letters, reversal of order, and misspellings are common. With later stages of HE, letters become superimposed and lines of writing converge. Patients become unable to sign their names or to move the pencil from left to right. Speech, initially monotonous and slowed, becomes slurred and unintelligible with associated dysphasia in later stages of the illness.
Personality changes and alterations of mood may be the first symptoms of HE and are generally first observed by relatives or friends. As the disease progresses, patients may become uninhibited and bizarre due to increasing difficulties in visual perception and disorientation, illusions, and hallucinations. Mood alterations including euphoria and depression are common and may exhibit rapid fluctuations.
Chronic Progressive Hepatic Encephalopathy
The chronic progressive (or persistent) form of HE has predominantly been observed in patients with extensive portosystemic shunting that developed either spontaneously or after transjugular intrahepatic portosystemic stent shunting or other shunting procedures. Data regarding the prevalence of this subtype of HE are sparse. Cirrhosis-related parkinsonism and hepatic myelopathy are the best characterized manifestations of this form of HE. In a prospective study of 214 patients with cirrhosis awaiting liver transplantation, cirrhosis-related parkinsonism was found in 4 percent and hepatic myelopathy in 2 percent of patients. The parkinsonian patients show hypomimia, hypokinesia, tremor, and rigidity similar to patients with idiopathic Parkinson disease (PD), but typically they do not develop the characteristic shuffling gait of PD and have predominant involvement of their upper limbs. Moreover, symptoms develop faster and are symmetric more often. Tremor occurs predominantly with action; a parkinsonian rest tremor is observed less commonly. The extrapyramidal symptoms may be associated with cerebellar and corticospinal deficits.
Some patients present with a combination of cirrhosis-related parkinsonism and hepatic myelopathy. The myelopathy is characterized by a rapidly progressive spastic paraparesis without accompanying sensory deficits or disturbances of bladder or bowel functions. After only a few months of progressive disability, most patients with hepatic myelopathy either depend upon an assistive device or are confined to a wheelchair. For unknown reasons most patients with hepatic myelopathy are men, whereas cirrhosis-related parkinsonism is equally prevalent in men and women.
Minimal Hepatic Encephalopathy
Minimal HE is considered the mildest form of HE and is defined as cerebral dysfunction detectable only by neuropsychologic or neurophysiologic means in the absence of clinically overt symptoms of encephalopathy. The concept of minimal HE was developed in the 1970s when it became obvious that some patients who were considered unimpaired clinically nevertheless had significant deficits in attention, visual perception, and motor speed and accuracy on neuropsychometric tests; some only showed slowing of the electroencephalogram (EEG). These observations led to the addition of this early stage of HE to established grading systems.
The prevalence of minimal HE ranges between 30 and 60 percent of patients with liver cirrhosis. Variations in prevalence estimates are due to differences in methods used for diagnosis and population differences regarding underlying liver diseases.
It has been suggested that minimal and grade I HE should be merged into a new class termed “covert HE” as grade I HE may only be apparent to clinicians with experience in neurologic assessment. More detailed clinical examination of HE patients yields a higher number with grade I HE and fewer with minimal HE. In one study, among patients initially thought to be clinically unimpaired, bradykinesia, tremor, and hyperactive muscle stretch reflexes were detected in about 30 percent when examined in detail, and 50 percent of these patients showed eye movement abnormalities indicating cerebellar dysfunction.
Encephalopathy in Acute Liver Failure
The presence of HE is a prerequisite for diagnosing ALF in patients with jaundice, coagulopathy, and no pre-existing liver disease. Thus, HE is present by definition in all patients with ALF. In contrast, clinically overt HE is prevalent in 10 to 14 percent of all cirrhotic patients, and in about 20 percent of patients with decompensated cirrhosis. The risk of HE recurrence is 40 percent within 1 year.
In contrast to HE in patients with liver cirrhosis, HE with ALF may be complicated by significant brain edema (25 to 35% in grade III; 65 to 75% in grade IV). Currently, the prevalence of brain edema in patients with ALF seems to be decreasing, though for unclear reasons. An analysis of the case records of 3,305 patients with ALF or acute liver injury from King’s College Hospital, London, between 1973 and 2008 showed that the proportion of patients with intracranial hypertension fell from 76 percent in the period from 1984 to 1988 to 20 percent in 2004 to 2008. Multivariate analysis showed an association of intracranial hypertension with younger age, female sex, and elevated international normalized ratio.
While restlessness, agitation, and irritability are characteristic of the initial phase of ALF, HE in patients with cirrhosis usually begins with psychomotor slowing. With increasing grade of HE, clinical presentations are more similar, as depressed consciousness predominates. Extrapyramidal symptoms are not typically observed in patients with ALF, but signs of corticospinal tract dysfunction are present. Seizures are a frequent complication of ALF, but occur only rarely in patients with cirrhosis.
Diagnosis of Forms of Hepatic Encephalopathy
The diagnosis of HE can only be made after exclusion of other possible causes of brain dysfunction, as the symptoms are not specific. Hyponatremia, hypo- or hyperglycemia, uremia, diabetes mellitus, and renal dysfunction are frequent in patients with cirrhosis and may resemble HE. Other important disorders to distinguish are septic encephalopathy and Wernicke encephalopathy. In a neuropathologic study of the brains of 32 patients with cirrhosis who died with HE, cerebellar lesions suggestive of Wernicke encephalopathy were observed in 50 percent. The diagnosis of Wernicke encephalopathy was made in nine patients, whereas it had been made based on clinical findings in only two patients.
Due to altered coagulation, intracranial hemorrhage must be considered in the differential diagnosis of HE, and brain imaging should be obtained in all patients, usually with noncontrast computed tomography (CT). Magnetic resonance imaging (MRI) requires much more cooperation than CT, and thus is not practical in agitated patients.
Cirrhosis-Related Parkinsonism
In patients with cirrhosis who develop clinical signs of extrapyramidal motor dysfunction, the differential diagnosis includes acquired hepatocerebral degeneration or an independent neurodegenerative disease. The course of the disease and the symptom combination may help to differentiate between these entities.
The clinical features of cirrhosis-related parkinsonism resemble those of patients with PD. As discussed earlier, however, symptoms in PD are more often asymmetric, develop more slowly, may be associated with early gait abnormalities, are not accompanied by cerebellar or corticospinal deficits, and respond well to dopaminergic drugs.
More difficult is the distinction from multiple system atrophy (MSA), which combines extrapyramidal symptoms with cerebellar and pyramidal deficits and thereby can resemble cirrhosis-related parkinsonism. MSA likewise shows rapid progression and often a poor response to dopaminergic agents. In contrast to patients with cirrhosis-related parkinsonism, however, patients with MSA characteristically show severe autonomic dysfunction and many show alterations of the basal ganglia, midbrain, and cerebellum on MRI. Single-photon emission computed tomography (SPECT) in patients with cirrhosis-related parkinsonism shows a decreased binding capacity of striatal dopamine receptors and the dopamine transporter similar to the findings in MSA but different from those in PD, in which there is decreased availability of the transporter but not of the receptors.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here