Pallidal Hyperintensity Research Articles

Welder's lung and brain MRI findings in manganese-exposed welders.

Biomarkers of manganese (Mn) exposure and manganism are poorly understood. Blood Mn levels are often used to assess exposure, while brain Mn accumulation may be demonstrated by pallidal hyperintensity at magnetic resonance imaging (MRI). Mn-containing electrodes used in manual metal arc welding may be associated with the welder's lungs. A cross-sectional study was set up to compare T1 intensity in basal ganglia at MRI and Mn blood levels in subjects with or without pneumoconiosis. Clinical, radiological, pulmonary function and laboratory parameters were assessed among 154 welders referred to our hospital for suspected pulmonary pathology. The study group included 123 male welders with pneumoconiosis (79.9%) and 31 welders without pulmonary damage (20.1%). The cases without pneumoconiosis were younger (38.5±6.6 vs 42.1±7.1, p=0.012). Cases with pneumoconiosis had blood lower Mn levels [13.5 (10-21)] as compared to those without pneumoconiosis [18.5 (7.8- 34)], p=0.035. In the same groups, the cases with high blood Mn levels were 49 (39.8%) and 18 (58.1%) p= 0.052, respectively. Brain MRI hyperintensity was found in 86 (55.8%) subjects with welder's lung 63 (51.2) but also in 23 (74.2) individuals without welder's lung. MRI hyperintensity in basal ganglia was significantly related to high blood Mn (p<0.005). This is the first study evaluating blood Mn levels of welders and their correlation with pulmonary and neurological effects. Poor working conditions may be associated with exposure to Mn and fibrogenic fumes leading to chronic lung diseases and hyperintensity in brain MRI suggesting Mn accumulation.

S2570 Elevated Manganese Levels: A Case Report of an Unusual Presentation in a Patient With Cirrhosis and Iron-Deficiency Anemia

INTRODUCTION: Manganese (Mn) is an essential element for human health found in nuts, grains, and legumes. Toxic levels can result in parkinsonian features, due to damage to the dopaminergic neurons of the basal ganglia and gliosis. Common causes for toxicity include occupational hazards such as welding, steel industry and ingestion of contaminated water. CASE DESCRIPTION/METHODS: A 55 year old woman with a history of decompensated alcohol related cirrhosis, presented to the ER with a three week history of worsening neck pain and generalized weakness. Physical examination revealed bradykinesia, dysarthria, and dystonia of the neck. She had severe motor weakness and was unable to feed herself or ambulate independently. She denied any hematemesis, hematochezia or melena. The patient had been started by her PCP on Levodopa-Carbidopa 2 weeks prior to admission for these Parkinson like symptoms. Her labs showed anemia with hemoglobin of 7.4 g/dL, ferritin was 5 ng/mL and 20% transferrin saturation. Folate, thiamine and vitamin B12 levels were normal. MRI of the brain revealed T1-weighted signal hyperintensity of the globus pallidus bilaterally. EGD showed small varices and mild PHG, colonoscopy showed internal hemorrhoids and 2 small polyps, no active GI bleeding was seen. Multiple heavy metal levels were checked and blood Mn was elevated to 24.1 ug/L (normal 4.2-16.5). The patient’s symptoms improved following the two week course of Levodopa-Carbidopa prior to discharge. DISCUSSION: Pallidal signal hyperintensity on T1-weighted MRI has been well described in patients with Parkinson’s disease and in patients with Mn toxicity. Increased Mn levels have been reported in patients with cirrhosis and may result from decreased uptake by the liver and increased portosystemic shunting. Although hepatic encephalopathy can present with a large array of neurologic symptoms, the severity of our patient’s neck pain that brought her to the ED and her profound weakness had prompted more thorough workup. Furthermore, Mn and iron share similar mechanisms of absorption and transport, which allows for Mn to influence iron homeostasis and vice versa. Some studies have shown that iron deficiency can lead to accumulation of Mn in the blood and reduce enzymatic protective effect from Mn-induced oxidative stress. It is possible that the concurrent iron deficiency anemia in our patient has led to increased levels of Mn. Early recognition of these findings especially in presence of iron deficiency may warrant evaluation for Mn toxicity.Figure 1.: Hyperintense globi pallidi on T1-weighted magnetic resonance imaging.

Volume changes of subcortical structures in patients with post-hepatitis B cirrhosis: A magnetic resonance imaging study.

To investigate volume changes of subcortical structures in patients with post-hepatitis B cirrhosis. Thirty patients with post-hepatitis B cirrhosis (the cirrhosis group) and 24 age- and sex-matched healthy controls (the control group) were enrolled in this prospective study. All subjects underwent neuropsychological tests, blood biochemical determinations, and cerebral MRI. Volumes of 18 selected subcortical structures were automatically segmented and analyzed by the FreeSurfer. In the cirrhosis group, the relationships between abnormal subcortical volumes and clinical index or neurocognitive performance were investigated. The relationships between globus pallidus volumes and pallidal hyperintensity were also examined. Compared with the healthy controls, patients with post-hepatitis B cirrhosis displayed smaller bilateral putamen, amygdala, and nucleus accumbens volumes and larger bilateral globus pallidus volumes (P<0.001 or P=0.001). In the cirrhosis group, the volumes of left putamen and amygdala were negatively correlated with the number connection test-A (NCT-A)(left putamen r=-0.410, P=0.034; left amygdala r=-0.439, P=0.022), and the volumes of bilateral globus pallidus were positively correlated with pallidal index (PI) (left globus pallidus r=0.889, P<0.001; right globus pallidus r=0.900, P<0.001). Abnormalities of subcortical volumes appear bilaterally symmetrical in patients with post-hepatitis B cirrhosis. Atrophy of left putamen and amygdala might contribute to poor neurocognitive performance, and the manganese deposition might contribute to the increased globus pallidus volumes in patients with post-hepatitis B cirrhosis.

Deep gray matter iron measurement in patients with liver cirrhosis using quantitative susceptibility mapping: Relationship with pallidal T1 hyperintensity.

The liver is a central organ for the metabolism of iron and manganese and the places where those metals are commonly deposited overlap in the brain. To elucidate the relationship between pallidal T1 hyperintensity and iron deposition in the deep gray matter of liver cirrhosis patients using quantitative susceptibility mapping (QSM). Retrospective case-control study SUBJECTS: In all, 38 consecutive liver cirrhosis patients who received brain magnetic resonance imaging (MRI) as pretransplant evaluation. QSM was reconstructed from 3D multi- or single-echo phase images at 3T. T1 -weighted images were used for the assessment of pallidal hyperintensity and pallidal index (PI). Patients were divided into two groups according to the presence of pallidal hyperintensity by consensus of two radiologists. Susceptibility values were acquired for five deep gray matter structures. QSM measures were compared between two groups using the t-test. We also calculated Pearson correlations between QSM measures and PI. In all, 26 patients showed pallidal hyperintensity (T1 h group) and 12 did not (T1 n group). The susceptibility of the globus pallidus (GP) in the T1 h group (120.6 ± 38.1 ppb) was significantly lower than that in the T1 n group (150.0 ± 35.2, P = 0.030). The susceptibility of the dentate nucleus (DN) in the T1 h group (88.1 ± 31.0) was significantly lower than that in the T1 n group (125.6 ± 30.6, P = 0.001). Negative correlation between the susceptibility of GP (r = -0.37, P = 0.022) and the PI, and between DN (r = -0.43, P < 0.001) and the PI was found. Liver cirrhosis patients with pallidal T1 hyperintensity had lower susceptibility values in the GP and DN than those without it. This suggests a possible interaction between iron and manganese in the brains of liver cirrhosis patients. 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1342-1349.

Bilirubin-Induced Neurological Dysfunction: A Clinico-Radiological-Neurophysiological Correlation in 30 Consecutive Children.

The clinical expression of bilirubin-induced neurological dysfunction varies according to severity and location of the disease. Definitions have been proposed to describe different bilirubin-induced neurological dysfunction subtypes. Our objective was to describe the severity and clinico-radiological-neurophysiological correlation in 30 consecutive children with bilirubin-induced neurological dysfunction seen over a period of 5 years. Thirty children exposed to acute neonatal bilirubin encephalopathy were included in the study. The mean peak total serum bilirubin level was 625 μmol/L (range 480-900 μmol/L). Acoustic brainstem responses were abnormal in 73% (n = 22). Pallidal hyperintensity was observed on magnetic resonance imaging in 20 children. Peak total serum bilirubin levels correlated with motor severity (P = .03). Children with severe motor impairment were likely to manifest severe auditory neuropathy (P < .01). We found that in a resource-constrained setting, classical kernicterus was the most common bilirubin-induced neurological dysfunction subtype, and the majority of children had abnormal acoustic brainstem responses and magnetic resonance imaging.

Chronic acquired hepatocerebral degeneration, pallidal T1 MRI hyperintensity and manganese in a series of cirrhotic patients

Chronic acquired hepatocerebral degeneration (CAHD) is a rare neurological disorder of cirrhotic patients, characterized by parkinsonism and cognitive impairment. A T1 hyperintensity on the globus pallidum due to an accumulation of manganese (Mn) is found in these patients. The aim of the study was to investigate CAHD, Mn and the MRI pallidal signal in a series of cirrhotic patients. The association between pallidal T1 hyperintensity, CAHD, and blood levels of Mn, the effect of orthotopic liver transplantation (OLT) on the MRI signal and neurological findings, and the role of the pallidal signal as a predictor of CAHD were evaluated. Twenty-six out of 90 patients with cirrhosis had pallidal T1 hyperintensity. Seven patients had CAHD. OLT was followed by the disappearance of CAHD and MRI signal in 2/2 patients. The MRI signal disappeared after OLT in 8/13 patients after a median follow-up time of 24months. In the patients who did not undergo OLT, CAHD did not present after a median follow-up time of 18months. The cause of cirrhosis, episodes of acute hepatic encephalopathy and signal intensity were not correlated with CAHD. The blood levels of Mn did not reflect either the MRI signal or CAHD. In conclusion, the pallidal T1 hyperintensity is a prerequisite for the clinical manifestations of CAHD but is not sufficient. The blood levels of Mn as routinely monitored are not a useful marker of Mn burden. The MRI pallidal signal is not a predictor of CAHD.

Basal ganglia hyperintensity on T1‐weighted MRI in rendu–osler–weber disease

The purpose of this study was to evaluate possible central nervous system (CNS) involvement in Rendu-Osler-Weber (ROW) disease in magnetic resonance imaging (MRI). Three patients with symptomatic ROW disease underwent brain MRI. Brain MRI depicted in all three of them increased signal intensity on T1-weighted images involving the globus pallidus and cerebral crura bilaterally. Laboratory studies of the two men showed iron deficiency anemia, while all three of them had normal liver function tests and increased manganese blood concentration. Gastroscopy and colonoscopy revealed a gastric and a cecal arteriovenous malformation (AVM) in the first one, while pulmonary and hepatic computed tomography (CT) angiography did not detect any intrahepatic shunts. Liver ultrasound in the second one revealed dilatation of intrahepatic artery branches consistent with intrahepatic shunts, while it was normal in the third patient. Chest radiographs were normal in all three patients. Pallidal T1 hyperintensity on T1-weighted imaging may be a biomarker of manganese overload in ROW disease.

Significant Volume Reduction and Shape Abnormalities of the Basal Ganglia in Cases of Chronic Liver Cirrhosis

Chronic liver disease frequently includes cognitive and movement disorders, suggesting an alteration of the striatum. With the exception of hyperintensities evident on T1-weighted images indicative of Mn deposition, radiographic findings of the BG are nonspecific. Volumetric and morphometric analysis of DGM is limited. Whether DGM undergoes degeneration and whether this change is associated with pallidal hyperintensity and cognitive performance are currently unknown in patients with cirrhosis. The DGM volumes of 28 patients with chronic cirrhosis and 28 control patients were compared. Using 3D high-resolution MR images, the volume and shape of each structure were automatically analyzed by the FSL. Correlations between the DGM volume and other clinical variables, including the pallidal signal intensity, were assessed by multiple regression analysis. Patients with Child B and Child C liver disease had significantly smaller bilateral putaminal volumes than control patients, and patients with Child C also demonstrated smaller left caudate nucleus and left amygdala volumes than control patients. Pallidal hyperintensity correlated with smaller striatum volume, which was linearly related to worse cognitive performance. The nonuniform distributed shape abnormalities in the striatum further support the ascending spiral interconnecting theory of the striatum. These findings strongly suggest lower DGM volume develops according to the severity of the liver cirrhosis. The Mn deposition might contribute the striatum deficit. These findings support the value of additional psychomotor research associated with liver cirrhosis.

Pallidal hyperintensities - a coincidental finding of clinical relevance in Miller Fisher syndrome

Pallidal hyperintensities - a coincidental finding of clinical relevance in Miller Fisher syndrome

A Preliminary Study Revealing a New Association in Patients Undergoing Maintenance Hemodialysis: Manganism Symptoms and T1 Hyperintense Changes in the Basal Ganglia

Patients undergoing parenteral nutrition and those with portosystemic encephalopathy secondary to chronic liver disease and acquired and congenital portosystemic venous shunts frequently present manganese deposition in the basal ganglia, detected by MR imaging as hyperintense areas on T1-weighted sequences. We also observed similar abnormalities in the basal ganglia of patients with chronic renal failure undergoing maintenance hemodialysis. Our aim was to evaluate the pallidal signal intensity on T1-weighted images in a series of patients undergoing hemodialysis, with further evaluation of serum manganese levels and neurologic correlation, comparing them with patients with chronic renal failure without dialytic treatment. We performed MR imaging examinations in 9 patients with chronic renal failure, 5 of whom were undergoing hemodialysis. An experienced neuroradiologist scrutinized the presence of symmetric hyperintensities in the basal ganglia on T1-weighted sequences. We also determined the serum manganese levels and performed the neurologic evaluations in all patients. All patients undergoing hemodialysis presented elevated serum manganese levels and symmetric hyperintensities within the globus pallidus. In this group, 4 patients presented with parkinsonian symptoms, myoclonus, and syndromes with vestibular and vestibular-auditory symptoms. The patients without dialytic treatment presented with neither bilaterally increased T1 MR imaging signal intensity within the globus pallidus nor symptoms of manganism. Our preliminary results demonstrated the occurrence of bilateral pallidal hyperintensity on T1-weighted images in all patients undergoing hemodialysis associated with high serum manganese levels, revealing a new association.

Brain metal concentrations in chronic liver failure patients with pallidal T1 MRI hyperintensity

Chronic liver failure may be associated with pallidal MRI T1 hyperintensity and heterogeneous neurologic syndromes, including parkinsonism, cognitive impairment, and others. Manganese accumulation may be responsible for the imaging and clinical findings. To measure manganese plus other metal concentrations in pallidum and additional brain regions and to examine the corresponding neuropathology in cases of chronic liver failure. Regional brain metal concentrations were measured in seven chronic liver failure cases, four with pallidal T1 hyperintensity and three with normal MRI, plus five controls. Neuropathologic examination employed alpha-synuclein and tau immunohistochemistry. In patients with pallidal T1 hyperintensity, pallidal manganese concentrations were increased sevenfold over controls and over fourfold vs liver patients with normal MRI; manganese concentrations were also significantly elevated in all other brain regions. Copper was additionally increased in all brain regions, whereas other metal concentrations were similar to control values. Neuropathology revealed mild to moderate Alzheimer type II gliosis in the liver failure groups and negative alpha-synuclein and tau immunostaining except for one case (intermediate Alzheimer disease pathology). In chronic liver failure, manganese accumulation is responsible for the pallidal MRI T1 hyperintensity. Pallidal copper was also elevated in affected cases, but copper does not have the paramagnetic properties to generate isolated T1 hyperintensity. Basal ganglia manganese or copper accumulation may be responsible for the parkinsonism sometimes seen in chronic liver failure. Pallidal MRI T1 hyperintensity is a biomarker of manganese overload.

Clinical research on alterations of brain MRI and 1H-MRS in chronic hepatic disease

目的 采用MRI和MR氢质子波谱(1H-MRS)的方法,研究慢性肝病脑部的异常信号及代谢改变,探讨苍白球T1WI异常高信号的临床意义及MRI和1H-MRS在肝性脑病诊断和治疗中的应用价值.方法 选择50例经临床和(或)手术病理确诊为慢性肝病的患者和健康志愿者20例进行MRI和1H-MRS检查.测量苍白球指数(PI)和1H-MRS中观察到的谷氨酰胺及谷氨酸复合物(Glx)的峰高.对各组PI值和Glx峰高进行分析,并对MR信号改变和代谢物的变化与肝功能Child Pugh积分和血氨之间的关系进行相关性分析.对5例并发慢性肝性脑病(CHE)患者(其中3例行肝移植)进行治疗前、后的对比研究.结果 PI值在正常对照组、慢性肝炎组和肝硬化组中逐渐增高,分别为1.01±0.04、1.06±0.09、1.18±0.09,各组间差异有统计学意义(F=22.294,P＜0.01﹚.1H-MRS分析显示Glx峰在对照组、慢性肝炎组、肝硬化组、CHE组峰高平均秩次分别为25.25±0.04、25.85±0.07、39.47±1.10、57.77±2.17,差异有统计学意义(Kruskal-Wallis t值＝30.21,P＜0.01﹚.相关性分析显示PI值与Child Pugh积分及Glx间呈正相关(r值分别为0.768、0.545),而与血氨无明显相关性(r=0.314).慢性肝病治疗前、后对比研究显示,苍白球T1WI高信号随肝功能改善而减轻,于肝移植成功后5～6个月完全消失.脑内代谢物异常的恢复要早于信号改变,移植后1～3个月可恢复到正常水平.结论 PI指数可作为评估肝功能衰竭程度的一项参考指标,1H-MRS Glx峰能较血氨更好地反映脑损害严重程度,MRI和1H-MRS在肝性脑病诊断和治疗中有肯定的临床应用价值。

Progressive motor syndrome in a welder with pallidal T1 hyperintensity on MRI: A two‐year follow‐up

Chronic exposure to manganese (Mn) fume during welding may lead to mainly extrapyramidal syndrome that is resistant to treatment. We present a 32-year-old patient who developed severe postural instability, Parkinsonism, dystonia, and pyramidal signs in the 10th year of welding. The neurological condition of the patient worsened markedly in the following 3 years, resulting in severe disability rendering him to be assisted in all his daily activities and he did not benefit from any dopaminergic agent. T1 sequences of the MRI of the brain showed pallidal hyperintensity symmetrically. Welders in our country often protect their eyes but ignore to use tools that protect them from inhalation of the fume. Since chronic Mn toxicity may cause serious disability and irreversible neurological disturbances, we strongly believe that it is necessary to inform welders and their employers about this potential hazard.

Reversible Parkinsonism and T1W pallidal hyperintensities in acute liver failure

We report on a young woman who survived acute liver failure (ALF) without liver transplant. During the ALF, she developed a disabling, levodopa-unresponsive, symmetrical Parkinsonism. This was characterized by severe bradykinesia, mild rigidity, mutism, and prominent gait impairment. Magnetic resonance imaging (MRI) showed bilateral T1W pallidal hyperintensities. Parkinsonism and MRI changes remitted in parallel with normalization of hepatic function. We implicate excessive pallidal manganese deposition secondary to ALF in the pathogenesis of this neuroradiological syndrome. Though hitherto unreported, we propose that Parkinsonism with T1W pallidal hyperintensities may not be uncommon in ALF.

Magnetic resonance images of the globus pallidus in patients with idiopathic portal hypertension: A quantitative analysis of the relationship between signal intensity and the grade of portosystemic shunt

To elucidate a quantitative relationship between hyperintensity of the globus pallidus on T1-weighted magnetic resonance images (MRI) and portosystemic shunt (PSS) in portal hypertension. Fifteen patients with idiopathic portal hypertension (IPH) and 44 patients with liver cirrhosis (LC) underwent brain MRI to asses signal intensity at the globus pallidus and Doppler sonography to examine the blood flow volume of PSS. Blood manganese (Mn) levels were examined in 36 patients and neuropsychological tests were performed in 15 patients without overt hepatic encephalopathy. Pallidal hyperintensity on MRI was more prominent in patients with IPH than in patients with LC. There was no correlation between MRI pallidal hyperintensity and the severity of liver dysfunction or hepatic encephalopathy. The grade of hyperintensity correlated well with the grade of PSS. The correlation was stronger in patients with IPH than in patients with LC. The plasma ammonia level and whole blood Mn level significantly correlated with MRI pallidal hyperintensity, but blood Mn level showed a stronger correlation than plasma ammonia. Hyperintensity of the globus pallidus on T1-weighted MRI correlated with the development of PSS independent of liver cell function. This brain image should be an index of the grade of PSS rather than a landmark of chronic liver failure.

Clinical heterogeneity in Hallervorden-Spatz syndrome: A clinicoradiological study in 13 patients from South India

Hallervorden-Spatz syndrome (HSS) is a rare autosomal recessive neurodegenerative disorder of childhood. Thirteen patients with this syndrome seen over a period of 7 years were reviewed. Two distinct groups were identified. The early onset childhood group had uniform presentation with developmental delay, recurrent falls, gait abnormalities, cognitive deterioration and dystonia. This group was also characterised by familial incidence, retinal involvement and absence of behavioural problems. Late onset group, included patients with different presentations such as behavioural changes, optic atrophy and dystonia. Consanguinity was prominent in this study, being present in 61.5% patients. MRI ( n=11) showed pallidal hyperintensity on T1-weighted images and hypointensity or ‘eye of the tiger’ sign on T2-weighted images. Two patients had acanthocytes in peripheral blood smear. This study emphasizes the phenotypic heterogeneity in HSS and as well brings out the common features shared by patients with early onset disease.

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.

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

Abstract 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.

Astrocytes and manganese neurotoxicity

Increasing evidence suggests that astrocytes are the site of early dysfunction and damage in manganese neurotoxicity. Astrocytes accumulate manganese by a high affinity, high capacity, specific transport system. Chronic exposure to manganese leads to increased pallidal signal hyperintensities on T1-weighted magnetic resonance images and selective neuronal loss in basal ganglia structures together with characteristic astrocytic changes known as Alzheimer type II astrocytosis. Manganese is sequestered in mitochondria where it inhibits oxidative phosphorylation. Exposure of astrocytes to manganese results in important changes including (i) decreased uptake of glutamate; (ii) increased densities of binding sites for the “peripheral-type” benzodiazepine receptor (PTBR), a class of receptor localized to mitochondria of astrocytes and involved in oxidative metabolism, mitochondrial proliferation, and neurosteroid synthesis; (iii) increased gene expression and activity of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), known to be associated with apoptosis; (iv) increased uptake of l-arginine, a precursor of nitric oxide, together with increased expression of the inducible form of nitric oxide synthase (iNOS). Potential consequences of these alterations in astrocytic gene expression include failure of energy metabolism, production of reactive oxygen species (ROS), increased extracellular glutamate concentration and excitotoxicity which could play a key role in manganese-induced neuronal cell death as a direct result of impaired astrocytic–neuronal interactions.

1H magnetic resonance in the study of hepatic encephalopathy in humans.

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.