Hepatic encephalopathy (HE) is a neuropsychiatric spectrum, mainly caused by cirrhosis, portosystemic shunt or portal hypertension.(1) It is associated with poor survival and high recurrence rate, unless the underlying cause is successfully treated.(2) In a middle-aged patient with rapid onset of symmetric Parkinsonism, hepato-cerebral Parkinsonism should be suspected.(3) Global hypokinesia and gait impairment are early Parkinsonian symptoms in cirrhosis, whereas dementia and resting tremors are uncommon symptoms.(3) It was reported that these symptoms are reversible once patient is treated with portosystemic shunting or liver transplant.(3)
Manganese and ammonia are two of many compounds that are metabolized by the liver.(4) They may enter the brain and induce disturbances in neurological function.(4) It is widely accepted that ammonia is the main cause of hepatic encephalopathy, where it is deposited into astrocyte and causes brain edema.(5) In turn, they will be converted into glutamine which causes neurological disturbance.(5) Manganese was already considered neurotoxic since 150 years ago, when industrial workers were exposed to black oxide manganese developed unsteady gait and muscle weakness.(4) In this case, they typically exhibit extrapyramidal symptoms such as hypokinesia, rigidity and tremors.(4) In cases of cirrhosis and portosystemic shunts, plasma manganese levels is increased and then transported to brain, causes neuronal loss in basal ganglia structures and reactive gliosis.(4) At toxic level, it affects mitochondria where it catalyzes dopamine oxidation mainly in globus pallidus, extending to substantia nigra (which has high concentration of neuromelanin).(6, 7) Excess manganese within brain is believed to be the cause for T1W hyperintensity on MRI, can be seen affecting bilateral globus pallidus and substantia nigra, which explains Parkinsonian manifestation.(3–5) It coincided with autopsied brain tissue, where it affects the post synaptic dopamine D2 binding sites, associated with high level of manganese.(8)
Although the diagnosis of hepatic encephalopathy almost always clinical, we can however appreciate the affected brain areas, in which different areas of distribution can be seen in acute and chronic hepatic encephalopathy.
MRI is an important modality in aiding diagnosis of hepatic encephalopathy. FLAIR sequence is sensitive to detect hyperintense white matter lesion which is a combination of reversible edema and irreversible neuronal damage. This can be seen along the hemispheric corticospinal tract and subcortical hemispheric white matter.(4) Meanwhile on DWI increased diffusion can be seen at hemispheric white matter, which suggests interstitial brain edema.7 On MR spectroscopy, increase glutamine/glutamate signal seen, caused by osmolar adaptation of intra-astrocystic accumulation of glutamine.(4) Diffuse cortical lesion involving cingulate gyrus and insula cortex, with sparing occipital and perirolandic cortices is highly specific of hepatic encephalopathy, which may be explained by susceptibility towards hyperammonemic-hyperglutaminergic encephalopathy.(1, 9) Other sites involved includes thalami, midbrain, and periventricular areas.(9) However, it is important to take note that any other hyperammonemic cause of encephalopathy also yield similar findings on MRI.(9)
Table 1
Comparison of acute and chronic hepatic encephalopathy. (4, 5, 8, 10)
Types of Hepatic Encephalopathy | Chronic Hepatic Encephalopathy | Acute Hepatic Encephalopathy |
Frequency | Common | Rare |
Etiology | Chronic severe liver disease (cirrhosis) | Varies – hyperammonemia, infections, drug toxicities, parenteral nutrition |
Imaging findings | T1WI hyperintensities involving: • Globus pallidus • Substantia nigra | FLAIR/DWI hyperintensities involving: • Mainly insula and cingulate gyri • Spares perirolandic and occipital regions • May involve basal ganglia, thalami, and periventricular regions MRS may show glutamate-glutamine peak |
Cause of imaging findings | Attributed to manganese deposits | Hyperammonemia |