Hepatic encephalopathy (HE) reflects a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction. Previously, neurological disorders were considered only for cases of acute hepatic failure. However, in past 70 years, it was shown that neurological changes may occur also in chronic hepatic failure and cranial lesions may accompany in these cases (1).
In hepatic encephalopathy, magnetic resonance imaging (MRI) reveals T1 hyperintensities involving bilateral putamen, globus pallidus, lentiform nucleus, internal capsule and cerebral peduncles. There are few studies about MRI revealing cortical laminar intensities (2,3).
Our case was considered as a subclinic hepatic encephalopathy, presented with progressive cognitive impairment accompanied by cortical and subcortical cranial lesions with underlying asymptomatic liver disease.
A 62 year old male was admitted to our neurology out-patient clinic with progressive forgetfulness and social withdrawal lasting for a year. He could not recognize his relatives and had disorientation to place for the last 3 days. He had used an antipsychotic drug before his complaints began. He did not have a history of any disease or extra drug usage. In his neurological examination, he was disoriented to time. His detailed neuropsychiatric management revealed severe cognitive impairment involving mean-advanced verbal-nonverbal memory, visuospatial dysfunction with impairments related to frontal axe findings. Laboratory data showed thrombocytopenia (80000), hypoalbuminemia (3.1g/dl), elevated liver enzymes (AST (36 IU/L), GGT (151 U/L)), hyperammonemia (326.7 ug/dl) and elevated INR level (1.4). Other laboratory tests were in normal ranges including urea and creatinine levels (24 mg/dL, 0.76 mg/dL). His cranial MRI demonstrated high signal intensity in the bilateral globus pallidus on T1- weighted images and high signal intensity along the hemispheric white matter on FLAIR-T2- weighted images. Also diffusion restriction was seen in bilateral centrum semiovale. In his electroencephalogram (EEG), there was a gradual slowing of the frequency with the appearance of theta (5-7 Hz) and delta (1-2 Hz) waves. He had splenomegaly detected by abdominal ultrasonography and cirrhotic liver findings in abdominal tomography. He was consultated to gastroenterology clinic and biopsy was not necessarilly required. Hepatamine and propronolol therapies and policlinic controls were proposed. According to these findings, our case was considered as hepatic encephalopathy secondary to chronic liver disease.
HE, is a neuropsychiatric syndrome with motor and mental changes. The mental changes range to mild cognitive impairment to deep coma (4,5). HE is classified as episodic, chronic, sub clinic/latent according to its duration and clinical findings. Subclinic HE is identified in cirrhotic patients with mild cognitive dysfunction and it is hardly detected by standard clinical examination (6). Our patient also had progressive social withdrawal, autism and mild memory loss for about one year and he had a confusional state for lasting 3 days. His detailed neuropsychiatric examination could manifest his cognitive impairment.
The relationship between the neurological dysfunction and liver diseases is known. But it was suggested that neurological disorders were just due to acute hepatic failure. But now we know that neurological damage also continues in chronic disease due to high ammonia level in portal veins and high ammonia levels lead to Alzheimer like changes in Type 2 astrocytes (7). Also in our patient blood ammonia level was two-fold higher and it was thought to be the reason of cognitive dysfunction.
HE represents acute episodes in case of precipitating factors like gastrointestinal bleeding, uremia, constipation, infections and antipsychotic usage. Except these episodes there could be no sign of cognitive disorder (8). Also, there was an antipsychotic drug usage in the history of our patient before his confusional state.
Patients with HE have little changes on MRI’s. In severe cases we see white matter changes. The characteristic signs of chronic HE, are the T1 hyperintensities in bilateral globus pallidus and substantia nigra and white matter hyperintensities in T2 and FLAIR-weighted images (9). T2 hyperintensities in white matter reflect the myelin and axon loss due to edema of HE (10). Our patient had no sign of a liver disease till his cognitive dysfunction began. But his MRI findings showed signs of a chronic hepatic failure, his abdominal CT revealed cirrhotic changes. The laboratory abnormalities lead us to investigate HE. Also the MRI findings were typical for the disease.
On the other hand in a 62 year old patient the white matter changes can be due to microvascular disease. The localization and the size of the lesions can mimic chronic ischemic changes. In cirrhotic patients the lesions disappear as HE is cured, however vascular lesions remain (11). Also our patient had no risk factor for a vascular disease and he had abnormal laboratory findings that supports hepatic dysfunction.
Diffusion restriction in the white matter is also seen in HE. The probable reason of this is the elevated levels of ammonia leading to an interstitial edema by increasing the capillary permeability. And the cognitive dysfunction is the result of these changes (12). Also our patient’s MRI showed diffusion restriction in bilateral centrum semiovales. That’s why the white matter changes were not thought to be ischemic lesions.
There was a gradual slowing of the frequency with the appearance of theta and delta waves in our patient’s EEG. There were no triphasic waves. But the high levels of ammonia, elevated liver enzymes, hypoalbuminenia, and elevated INR level supported hepatic cell damage.
In conclusion, the laboratory and MRI findings lead us to investigate HE in a 62 year old man who had a progressive cognitive dysfunction without any signs of a systemic disease. A severe cognitive dysfunction just managed by a detailed neuropsychiatric test or rich MRI findings are not always due to a symptomatic liver disease. Thus, with this case report, we aimed to keep it in mind that HE may cause progressive cognitive impairment as a subclinic entity especially in elderly people.
1. Akın P, Erten B. Hepatik ensefalopati. İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Etkinlikleri 2002; 28:111-120 (Article in Turkish).
2. Khan F, Ashalatha R. Acquired (Non-Wilsonian) hepatocerebral degeneration. Neurology India 2004; 52:527.
3. Arnold SM, Els T, Spreer J, Schumacher M. Acute hepatic encephalopathy with diffuse cortical lesions. Neuroradiology 2001; 43:551-554.
4. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Bleir A. Hepatic encephalopathy: definition, nomenclature, diagnosis and quantification-final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 2002; 35:716-721.
5. Weissenborn K. Diagnosis of encephalopathy. Digestion 1998; 59:22-24.
6. Ortiz M, Jacas C, Cordoba J. Minimal hepatic encephalopathy: diagnosis, clinical significance and recommendations. J Hepatol 2005; 42:45-53.
7. Norenberg MD. Astroglial dysfunction in hepatic encephalopathy. Metab Brain Dis 1998; 13:319-335.
8. Rovira A. MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol 2008; 29:1612-1621.
9. Brunberg JA, Kanal E, Hirsch W, Van Thiel DH. Chronic acquired hepatic failure: MR imaging of the brain at 1.5 T. AJNR Am J Neuroradiol 1991; 12:909-914.
10. Matsusue E, Kinoshita T, Ohama E, Ogawa T. Cerebral cortical and white matter lesions in chronic hepatic encephalopathy: MR-pathologic correlations. AJNR Am J Neuroradiol 2005; 26:347-351.
11. Rovira A, Mínguez B, Córdoba J, Aymerich FX. Decreased white matter lesion volume and improved cognitive function following liver transplantation. Hepatology 2007; 46:1485-1490.
12. Ziylan YZ, Uzum G, Bernard G, Diler AS, Bourre JM. Changes in the permeability of the blood-brain barrier in acute hyperammonemia: Effect of dexamethasone. Mol Chem Neuropathol 1993; 20:203-218.