Comparative Evaluation of Signal Hyperintensity in Pallidal Structures of Patients with Liver Cirrhosis

Clinical, laboratorial, morphologic and magnetic resonance imaging (MRI) observations indicate accumulation of paramagnetic substance (manganese - Mn and/or copper - Cu) in the brain of patients with hepatoencephalopathy (HE). Pallidal index (PI) - semi-quantitative indicator of brain manganese concentration in vivo is calculated as a ratio of globus pallidus to subcortical frontal white matter signal intensity in sagittal T1-weighted MRI planes multiplied by 100. Signal intensity in other regions of the brain (putamen, subthalamic area, amygdala etc.) also represents an area of interest. Significant correlations have been shown between blood Mn content, liver enzyme activity, brain MRI changes and signs of parkinsonism in cirrhotic patients. Recently it has been showed that in the diagnostics of HE psychometric tests are as valuable as neuroimaging. The goal of our study was to reveal correlations between signal intensity and severity of HE measured by number connection test part - A. The signal intensity was defined in the areas of globus pallidus, putamen and prefrontal white matter. Some correlations were calculated between PI, HE degree and in blood and 24 hour urine manganese and copper contents. The study covered 17 patients suffering from HE. Hyperintense T1 signal was revealed in all 17 cases. Maximal signal intensity was obtained in the pallidal area, less - in putamen and very low - in the prefrontal white matter. The brain manganese deposition is explained by the following hypothesis: hyperammonemia and lack of substrate - glutamate leads to the saturation and decrease of glutaminesynthetase activity. Imbalance in the distribution of metal co-enzyme Mn ions in mitochondria and cytosol occurs. Needless and thus unused free manganese ions released from mitochondria in cytosol, accumulate and create paramagnetic deposits. epatoencephalopathy (HE) presents partially reversible neuro-psychiatric syndrome which develops in the patients with damaged liver function. Etiopathogenetic factors and mechanisms have not been defined yet, though recently two toxic substances have been detected: ammonium and manganese metabolic abnormality of which is considered to be the cause of HE (5,10). The disturbance of ammonia metabolism in inflicted by decreased detoxifying function of liver and bile secretion. Resulted hyperammoniemia contributes to the entrance of ammonium to the brain where it will be converted into glutamate due to the glutaminsynthetase. This process takes place only in astrocytes. They are mainly located in the basal ganglia. After the introduction of magnetic resonance imaging it become known that liver disfunction leads to the T1-signal hyperintensity in the brain, particularly, in pallidal area in 50-75% of patients (4,11,12). The same can be noticed in the brain MRI of patients chronically intoxicated by Mn (13), long-term parenteral nutrition (14), and among manganic mine workers (15). Excess amount of Mn and Cu was defined in the brain, pallidal area, putamen and white-matter areas of the patients who died from HE. On the bases of the above-mentioned data, it was proposed that disturbances in the metabolism of Mn plays significant role in HE pathogenesis. The aim of our study was to tie up the given theories with the view to explain pathogenesis of HE (ammonia, Mn, edema etc.).