Persistence of mild parkinsonism 4 months after liver transplantation in patients with preoperative minimal hepatic encephalopathy: a study on neuroradiological and blood manganese changes

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.

[1]  R. Butterworth.  Neurotransmitter Dysfunction in Hepatic Encephalopathy: New Approaches and New Findings , 2001, Metabolic Brain Disease.

[2]  G. P. Layrargues.  Movement Dysfunction and Hepatic Encephalopathy , 2001, Metabolic Brain Disease.

[3]  P. Davidson.  Hepatic Surgery , 1890, Pediatric Surgery International.

[4]  L. R. Ferraz,et al.  [Diagnosis of hepatic encephalopathy]. , 2004, Revista da Associacao Medica Brasileira.

[5]  H. Watanabe,et al.  Chronic manganese poisoning: A neuropathological study with determination of manganese distribution in the brain , 2004, Acta Neuropathologica.

[6]  K Weissenborn,et al.  Neuropsychological characterization of hepatic encephalopathy. , 2001, Journal of hepatology.

[7]  P. Ferenci.  Treatment of hepatic encephalopathy. , 2001, Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology.

[8]  F. Lazeyras,et al.  Magnetic resonance imaging and proton spectroscopic alterations correlate with parkinsonian signs in patients with cirrhosis. , 2000, Gastroenterology.

[9]  U. Klose,et al.  MR imaging and (1)H spectroscopy of brain metabolites in hepatic encephalopathy: time-course of renormalization after liver transplantation. , 2000, Radiology.

[10]  W. Bechstein,et al.  Neurotoxicity of calcineurin inhibitors: impact and clinical management , 2000, Transplant international : official journal of the European Society for Organ Transplantation.

[11]  Y. Yamashita,et al.  Manganese deposition in the globus pallidus in patients with biliary atresia. , 2000, Transplantation.

[12]  R Fischer,et al.  Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema? , 2000, Journal of hepatology.

[13]  A. Lockwood,et al.  "What's in a name?" Improving the care of cirrhotics. , 2000, Journal of hepatology.

[14]  R. Butterworth.  Complications of cirrhosis III. Hepatic encephalopathy. , 2000, Journal of hepatology.

[15]  R. Butterworth,et al.  Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. , 1999, Gastroenterology.

[16]  K. Kosaka,et al.  Cerebrospinal fluid manganese concentrations in patients with symmetric pallidal hyperintensities on T1 weighted MRI , 1999, Journal of neurology, neurosurgery, and psychiatry.

[17]  K. Weissenborn.  Diagnosis of Encephalopathy , 1998, Digestion.

[18]  M. Manns,et al.  The number connection tests A and B: interindividual variability and use for the assessment of early hepatic encephalopathy. , 1998, Journal of hepatology.

[19]  R. Butterworth,et al.  Diencephalic and cerebellar pathology in alcoholic and nonalcoholic patients with end‐stage liver disease , 1997, Hepatology.

[20]  D. Krieger,et al.  MRI findings in chronic hepatic encephalopathy depend on portosystemic shunt: results of a controlled prospective clinical investigation. , 1997, Journal of hepatology.

[21]  J. Hennig,et al.  Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. , 1997, Gastroenterology.

[22]  J. Schölmerich,et al.  Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging , 1997, Hepatology.

[23]  R. Butterworth,et al.  Increased blood manganese in cirrhotic patients: Relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms , 1996, Hepatology.

[24]  D. Krieger,et al.  Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis. , 1996, Gastroenterology.

[25]  A. Lang,et al.  Chronic acquired hepatocerebral degeneration: Case reports and new insights , 1995, Movement disorders : official journal of the Movement Disorder Society.

[26]  R. Moreau,et al.  Hemodynamics after orthotopic liver transplantation: Study of associated factors and long‐term effects , 1995, Hepatology.

[27]  D. Krieger,et al.  Manganese and chronic hepatic encephalopathy , 1995, The Lancet.

[28]  R. Butterworth,et al.  Increased manganese concentrations in pallidum of cirrhotic patients , 1995, The Lancet.

[29]  G. Fell,et al.  Manganese in long-term paediatric parenteral nutrition. , 1994, Archives of disease in childhood.

[30]  C. Martínez,et al.  Manganese intoxication and chronic liver failure , 1994, Annals of Neurology.

[31]  R. Sterzi,et al.  Neurologic complications following orthotopic liver transplantation. , 1994, Transplantation proceedings.

[32]  E. Kiely,et al.  Manganese in long term paediatric parenteral nutrition. , 1994, Archives of disease in childhood.

[33]  J Hennig,et al.  Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. , 1994, Gastroenterology.

[34]  E. Keeffe,et al.  Neurological complications of liver transplantation in adult versus pediatric patients. , 1994, Transplantation.

[35]  A. Mamourian,et al.  Dystonia, hyperintense basal ganglia, and high whole blood manganese levels in Alagille's syndrome. , 1994, Gastroenterology.

[36]  P. Martínez-Martín,et al.  Unified Parkinson's disease rating scale characteristics and structure , 1994, Movement disorders : official journal of the Movement Disorder Society.

[37]  M Richards,et al.  Interrater reliability of the unified Parkinson's disease rating scale motor examination , 1994, Movement disorders : official journal of the Movement Disorder Society.

[38]  D B Calne,et al.  Progression after chronic manganese exposure , 1993, Neurology.

[39]  E. Tolosa,et al.  Hyperintense globus pallidus on T1‐weighted MRI in cirrhotic patients is associated with severity of liver failure , 1993, Neurology.

[40]  J. Kulisevsky,et al.  Pallidal hyperintensity on magnetic resonance imaging in cirrhotic patients: Clinical correlations , 1992, Hepatology.

[41]  S. Mirowitz,et al.  Hyperintense basal ganglia on T1-weighted MR images in patients receiving parenteral nutrition. , 1991, Radiology.

[42]  W H Wong,et al.  Altered Cerebral Blood Flow and Glucose Metabolism in Patients with Liver Disease and Minimal Encephalopathy , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  D. V. van Thiel,et al.  Subclinical hepatic encephalopathy. Comparison before and after orthotopic liver transplantation. , 1990, Transplantation.

[44]  A. Seppäläinen,et al.  Tests for encephalopathy before and after liver transplantation. , 1990, Transplantation proceedings.

[45]  J. Chalk,et al.  Improvement in chronic hepatocerebral degeneration following liver transplantation. , 1990, Gastroenterology.

[46]  R. Shprintzen,et al.  What's in a name? , 1990, The Cleft palate journal.

[47]  G. Norquist,et al.  Cognitive function and quality of life in adult liver transplant recipients. , 1989, Transplantation proceedings.

[48]  T. Starzl,et al.  Neuropsychiatric status after liver transplantation. , 1984, The Journal of laboratory and clinical medicine.

[49]  J. Versieck,et al.  Determination of manganese in whole blood and serum. , 1980, Clinical chemistry.

[50]  L. Seeff,et al.  Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. , 1977, Gastroenterology.

[51]  M. Norenberg.  A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder. , 1977, Laboratory investigation; a journal of technical methods and pathology.

[52]  J. Versieck,et al.  Manganese, copper, and zinc concentrations in serum and packed blood cells during acute hepatitis, chronic hepatitis, and posthepatitic cirrhosis. , 1974, Clinical chemistry.

[53]  R. Pugh,et al.  Transection of the oesophagus for bleeding oesophageal varices , 1973, The British journal of surgery.