Increased Blood Manganese in Cirrhotic Patients: Relationship to Pallidal Magnetic Resonance Signal Hyperintensity and Neurological Symptoms

Abstract

1 long-term parenteral nutrition, 3 and after occupational manIncreasing evidence suggests that manganese deposiganese exposure sufficient to cause Parkinson's-like extrapytion is responsible for the T 1 -weighted magnetic resoramidal symptoms. 4 MRI signal hyperintensities may disapnance imaging (MRI) signal hyperintensity consistently pear after the cessation of manganese administration during observed in pallidum of cirrhotic patients. However, the parenteral nutrition 5 or after liver transplantation. 1 More relationship between blood manganese and the etiology recently, we demonstrated that pallidal manganese concenor severity of liver disease, as well as the neurological trations were markedly elevated in cirrhotic patients who symptomatology in these patients, has not been well esdied in hepatic coma. tablished. In the present study, blood manganese conHepatic encephalopathy (HE) is a spectrum of neuropsychicentrations were measured by atomic absorption specatric disturbances occurring in patients with chronic liver trometry together with MRI and neurological evaluation disease. Variable degrees of impairment of mental function in 57 cirrhotic patients with various etiologies and seare observed, and close clinical examination may disclose exverity of liver disease. Blood manganese concentrations trapyramidal signs. Recent reports evaluating the relationwere elevated in 67% of cirrhotic patients and were sigship between pallidal hyperintensity and neurological sympnificantly higher in patients with previous portacaval toms provide conflicting results. 7-12 Because manganese anastomoses or transjugular intrahepatic portosystemic toxicity may result in both pallidal hyperintensity and in shunt (TIPS). Pallidal signal hyperintensity was ob-Parkinson's-like extrapyramidal symptoms, and because served in 88% of patients, and significant correlations similar symptoms have been described in patients with were demonstrated between blood manganese and palchronic liver disease, we evaluated and attempted to correlidal index (PI) (a measure of pallidal signal hyperintenlate, in the same cirrhotic patients, neurological status, T 1 -sity), as well as Child-Pugh score. Assessment of extrapyweighted pallidal MRI signal intensity, and blood manganese ramidal symptoms using the Columbia rating scale concentrations. revealed a significant incidence of tremor, rigidity, or akinesia in up to 89% of cirrhotic patients. However, PATIENTS AND METHODSthere was no significant correlation between blood manPatients. Fifty-seven patients with biopsy-proven cirrhosis were ganese and extrapyramidal symptoms, although severincluded in the present study. None of them had clinically overt ity of akinesia was significantly greater in Child-Pugh encephalopathy. Clinical and biochemical characteristics are shown C patients. Extrapyramidal symptoms could result from in Table 1. a toxic effect of manganese on basal ganglia dopaminerNeurological evaluation was performed by the same neurologist gic function. These findings further support a rol...

Association of neurobehavioral performance with R2* in the caudate nucleus of asymptomatic welders

“…This result is consistent with previous studies suggesting whole blood metal levels may be a better exposure biomarker than plasma or serum metal levels (Costa and Aschner, 2014; Spahr et al, 1996), especially when exposure is relatively low. This is probably because the majority of Fe in the body (~ 80%) is bound to hemoglobin in red blood cells (RBC) and only a fraction is found in plasma (Collings et al, 2013).…”

Magnetic Resonance Imaging of Brain in Patients with Cirrhotic and Non-Cirrhotic Portal Hypertension

“…It could be because of impaired hepatic excretion or because of increased bioavailability or altered volume of distribution because of porto-systemic shunting. Although many studies have implicated porto-systemic shunting as a cause [1,13,22,23,32,33], this could not explain the lack of T1 W MRI hyperintensities in our EHPVO patients and their presence in NCPF patients. Our EHPVO and NCPF patients were equally matched with respect to duration of portal hypertension, absence of any overt/biochemical liver disease during almost 15 years of follow-up, and severity of portal hypertension (according to the grade of gastroesophageal varices) at the time of the MRI study.…”

“…Since in cirrhosis (human or animal) both mechanisms are operative, it has been difficult to dissect out the exact culprit. However, several authors have implicated shunting as the major mechanism of Mn accumulation in the brain [1,13,22,23].…”

Fatigue and primary biliary cirrhosis: association of globus pallidus magnetisation transfer ratio measurements with fatigue severity and blood manganese levels

“…47 The major route of excretion is biliary and this serves as the main homeostatic mechanism. Elevated blood manganese concentrations occur in cirrhosis 15 16 and have also been reported in chronic hepatitis. 48 Brain concentrations of manganese are relatively low and tightly regulated.…”