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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic encephalopathy (HE) is a major neuropsychiatric complication of cirrhosis. HE develops slowly in cirrhotic patients, starting with altered sleep patterns and eventually progressing through asterixis to stupor and coma. Precipitating factors are common and include an oral protein load, gastrointestinal bleeding and the use of sedatives. HE is common following transjugular intrahepatic portosystemic stent shunts (TIPS). Neuropathologically, HE in cirrhotic patients is characterized by astrocytic (rather than neuronal) changes known as Alzheimer type II astrocytosis and in altered expression of key astrocytic proteins. Magnetic resonance imaging in cirrhotic patients reveals bilateral signal hyperintensities particularly in globus pallidus on T1-weighted imaging, a phenomenon which may result from manganese deposition. Proton (1H) magnetic resonance spectroscopy shows increases in the glutamine resonance in brain, a finding which confirms previous biochemical studies and results no doubt from increased brain ammonia removal (glutamine synthesis). Additional evidence for increased brain ammonia uptake and removal in cirrhotic patients is provided by studies using positron emission tomography and 13NH3. Recent molecular biological studies demonstrate increased expression of genes coding for neurotransmitter-related proteins in chronic liver failure. Such genes include monoamine oxidase (MAO-A isoform), the peripheral-type benzodiazepine receptor and nitric oxide synthase (nNOS isoform). Activation of these systems has the potential to lead to alterations of monoamine and amino acid neurotransmitter function as well as modified cerebral perfusion in chronic liver failure. Prevention and treatment of HE in cirrhotic patients continues to rely on ammonia-lowering strategies which include assessment of dietary protein intake and the use of lactulose, neomycin, sodium benzoate and L-ornithine-aspartate. The benzodiazepine receptor antagonist flumazenil may be effective in certain cases. A more widespread use of central nervous system-acting drugs awaits a more complete understanding of the precise neurotransmitter systems involved in the pathogenesis of HE in chronic liver failure.
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PMID:Complications of cirrhosis III. Hepatic encephalopathy. 1072 3

Exposure to thioacetamide is associated with the development of liver cirrhosis in experimental animals. In addition to liver, thioacetamide toxicity has been observed in other organs. In this study, the toxic effect of thioacetamide on the spleen was investigated at 0, 4, 8 and 12 weeks post-treatment durations. The level of tissue copper and selenium increased until the eighth week when a significant drop was observed. The zinc level was also increased but returned back to normal by week 8, thereafter it showed further increase. Calculation of the copper/zinc ratio showed an increase, but, recovered and returned to normal value by week 12. The level of manganese fluctuated until the eighth week. It then increased rapidly. Histological studies of the spleen tissue showed a significant increase in extramedullary haematopoiesis in the red pulp region and marked hyperplasia in the marginal zone and follicles. The results of this study, demonstrate an intimate association between trace element levels and spleen pathology, as observed in studies of other organs.
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PMID:Thioacetamide toxicity and the spleen: histological and biochemical analysis. 1082 Aug 95

We describe a case of Wilson's disease with late psychiatric onset. Major depressive disorder was the first clinical manifestation at the age of 38 years. After pharmacotherapy with antidepressive agents, a manic episode was observed. Extrapyramidal hand tremor and micrography were the first neurological signs. Emotional lability occurred during worsening of extrapyramidal signs. Diagnosis was based on urinary and serum copper levels, ceruloplasmin serum level, Kayser-Fleischer ring, and liver biopsy that detected cirrhosis. Magnetic resonance imaging revealed basal ganglia hyperintensity on T1-weighted images, and hypodensity in the central part and hyperintensity in the peripheral part of the lentiform nucleus on T2-weighted images. Hyperintensity on T2-weighted images was also observed in the dorsal part of the midbrain. 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT) detected a normal distribution of the drug in the brain, with better signal in the right side and deficit of D2-dopaminergic receptors in the basal ganglia. Abnormal manganese erythrocyte level was observed. Treatment was based on penicillamine, zinc salts, low-copper diet, antidepressant agents, interpersonal psychotherapy and neurorehabilitation.
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PMID:Psychiatric symptoms as late onset of Wilson's disease: neuroradiological findings, clinical features and treatment. 1093 85

Progressive myelopathy is a rare complication of chronic hepatic disease which has never been reported in the paediatric age group. We describe the 11 year course of an adolescent male with hepatic myelopathy caused by cryptogenic micronodular cirrhosis. His condition has been associated with persistent polycythaemia and extraordinary increases of whole blood manganese, with magnetic resonance imaging evidence of manganese deposition within the basal ganglia and other regions of the brain. The patient has developed neither liver failure nor parkinsonism. The pathophysiological bases of this multiorgan system disorder are described.
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PMID:Paraparesis, hypermanganesaemia, and polycythaemia: a novel presentation of cirrhosis. 1104 Jan 56

Relaxometry revealed changes in the basal ganglia in T(1) and T(2) relaxation times due to liver disease. Manganese is probably responsible for T(1) and T(2) shortening (as the concentration is known to be higher in both the liver and blood due to hepatic cirrhosis). The aim of this study was to follow possible recovery after liver transplantation by MR relaxometry. Together with a group of 20 healthy volunteers we scanned 53 patients before and after liver transplantation (some of them repeatedly). Both T(1) and T(2) values were evaluated in the basal ganglia, thalamus, and frontal white matter. T(1) relaxation time was shortened by approx. 20-25% compared to the control group, probably the result of manganese deposition in the brain caused by hepatic cirrhosis. After liver transplantation the relaxation time recovered gradually with almost normal values reached approx. 2 years after surgery. T(1) recovery was observed in all evaluated structures. Similar results were observed with T(2) relaxation in the basal ganglia and thalamus. In the white matter T(2) remained low even 2 years after surgery.
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PMID:Chronic liver disease: relaxometry in the brain after liver transplantation. 1125 87

Cirrhotic patients tend to accumulate manganese in their brain, especially in basal ganglia. Manganese is a well-known neurotoxic metal, however, its effect in a condition such as liver damage has not been explored deeply due to the lack of a suitable experimental model. A method to induce manganese accumulation in the brain of the cirrhotic rat is described. Cirrhosis was induced by obstruction of biliary duct and simultaneous treatment with manganese in the drinking water (0.5 or 1 mg/ml) during 4 weeks. Metal brain accumulation was low in sham-operated rats with both of the Mn concentrations used. In contrast, manganese treatment to bile obstructed rats resulted in fourfold and eightfold metal increments in the 0.5 and 1 mg/ml Mn2+ concentrations, respectively. This method is useful to induce brain manganese deposition and to study its consequences.
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PMID:A method to induce manganese accumulation in the brain of the cirrhotic rat and its evaluation. 1185 65

Pallidal hyperintensity at magnetic resonance imaging (MRI) correlates to blood manganese (Mn) levels and parkinsonian signs in patients with cirrhosis. Similarly, metabolite changes in the basal ganglia (BG) at proton spectroscopy are related to these neurological signs. The evolution of these abnormalities after liver transplantation (OLT) is incompletely described. We evaluated 14 unselected consecutive patients with cirrhosis (minimal hepatic encephalopathy [HE] n=8, no HE n=6) before and 4 months after successful OLT for the evolution of parkinsonism using a validated scale (the United Parkinson's Disease Rating Scale, or UPDRS). Pallidal intensity at MRI, spectroscopic changes in the BG at magnetic resonance spectroscopy (MRS), and whole blood manganese concentrations were measured. After OLT in patients with preoperative minimal HE, the UPDRS scores improved, but mild parkinsonism persisted (16.1+/-3.6 to 6.2+/-4.8, P<0.05). Pallidal hyperintensity remained abnormal in 5/8 of cases, but spectroscopic changes normalized in all patients. Blood Mn remained elevated in 4/6 patients. In patients without HE, UPDRS values remained negligible (2.42+/-1.5 to 2.5+/-1.4). Pallidal hyperintensity normalized in 7/8 patients and spectroscopic changes normalized in all patients. Blood Mn remained elevated in 5/6 patients. Four months after successful OLT, patients with preoperative minimal HE and severe pallidal hyperintensity showed persistent mild parkinsonism. The role of blood manganese determination appears limited in the monitoring of MRI and parkinsonian signs changes after OLT.
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PMID:Persistence of mild parkinsonism 4 months after liver transplantation in patients with preoperative minimal hepatic encephalopathy: a study on neuroradiological and blood manganese changes. 1197 41

Basal ganglia bilateral symmetric hyperintensity in T1-weighted sequences at magnetic resonance imaging (MRI) is recognized to be due to the presence of manganese deposits. This abnormal finding has been reported in occupational exposures, liver cirrhosis and total parenteral nutrition with unbalanced solutions. However, the same imaging is often observed "by chance" in brain MRIs of patients not belonging to these groups. In order to better understand which are the clinical conditions coexisting with such findings, we decided to study systematically patients which showed this kind of imaging, focusing on their manganese and iron status, as it is known that these two metals have similar properties and that iron-deficiency can competitively increase manganese absorption. The 20 patients studied underwent clinical evaluation and the following laboratory tests: whole blood iron and manganese, hemoglobin, plasma iron, transferrin and ferritin. The neuroradiologic evaluation was integrated by pallidal index calculation, in order to provide a semi-quantitative esteem of the hyperintensity. The patients could be classified into four subgroups: Parkinsonism, anemia, cirrhosis, central nervous system tumors. In 18 out of 20 cases, we found abnormalities in iron and/or manganese-related values. Particularly, iron-deficiency seems to be frequent among patients showing brain MRI abnormalities compatible with manganese deposits in basal ganglia. This observation suggests that iron-deficiency could be an important risk factor for manganese-induced neurotoxicity and should, therefore, be accurately considered and treated.
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PMID:T1-weighted hyperintensity in basal ganglia at brain magnetic resonance imaging: are different pathologies sharing a common mechanism? 1252 Jul 56

1H magnetic resonance (1H MR) studies of the brain in patients with liver diseases have shown several abnormalities that may be relevant for the pathogenesis of hepatic encephalopathy. 1H magnetic resonance imaging shows a typical pallidal hyperintensity on T1-weighted images. This abnormality appears to be secondary to the accumulation of manganese in basal ganglia because of portal-systemic shunting. No direct correlation between the magnitude of pallidal hyperintensity and the grade of hepatic encephalopathy has been found, but some studies have related pallidal hyperintensity to parkinsonism. 1H magnetic resonance spectroscopy shows relative to creatine an increase in glutamine/glutamate (Glx) signal and a decrease of choline containing compounds (Cho) and myo-inositol. Abnormalities in the Glx signal have been interpreted as an increase in brain glutamine secondary to the metabolism of ammonia in astrocytes. Disturbances of Cho and myo-inositol have been interpreted as a compensatory response to the increase in intracellular osmolality caused by the accumulation of glutamine in astrocytes. In addition, magnetization transfer imaging shows signs compatible with low-grade cerebral edema. Altogether, 1H MR studies suggest the accumulation of manganese and the development of osmotic abnormalities in the brain of patients with cirrhosis. These abnormalities appear to participate in some of the neurological manifestations of hepatic encephalopathy.
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PMID:1H magnetic resonance in the study of hepatic encephalopathy in humans. 1260 17

Cirrhosis promotes increases of both manganese and glutamine in brain. Manganese is a modulator and glutamine is the product of glutamine synthetase. This work studies the relationship between manganese and glutamine synthetase in a model of cirrhosis in the rat. We administered manganese (1 g/L) in the drinking water of sham-operated and bile-duct obstructed rats. We evaluated the manganese and glutamine accumulation and the glutamine synthetase activity in frontal cortex, striatum, and pallidum after 2, 4, and 6 weeks of biliary obstruction or sham surgery. Cirrhotic rats receiving manganese increased their brain content of metal about 400%-600% after 4 weeks of treatment (P < .05) and also remarkably accumulated glutamine through time in the three regions studied (P < .05 at week 6). Interestingly, bile-duct obstructed rats treated with manganese showed no effect on glutamine synthetase activity. Results from this study suggest that manganese induces increases of brain glutamine independently of its synthesis.
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PMID:Role of manganese accumulation in increased brain glutamine of the cirrhotic rat. 1271 45


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