Suk Hwan Kim

High signal intensity on magnetic resonance imaging is a better predictor of neurobehavioral performances than blood manganese in asymptomatic welders

OBJECTIVES The aim of the study was to evaluate subclinical neurological effects in welders, using an extensive list of neurobehavioral batteries and determine if there is a link between pallidal index (PI) and subclinical neurobehavioral effects in the spectrum of manganese (Mn) symptomatology. METHODS A total of 43 asymptomatic male welders and 29 age- and sex-matched healthy control individuals completed questionnaires, and underwent blood examinations, brain magnetic resonance imaging (MRI) scans, and a wide range of neurobehavioral examinations. RESULTS Digit symbol, auditory verbal learning test (delayed recall), complex figure test (copy and immediate recall), digit span, verbal fluency test, Stroop test, grooved pegboard, finger tapping, frequency dispersion and harmonic index of tremor, and maximum frequency of hand coordination showed differences between welders and control individuals. No differences were noted for simple reaction time, postural sway, smell test, and profile of mood states (POMS). Blood Mn levels were shown to be significantly associated with grooved pegboard (dominant hand) and complex figure test (copy) results. PI was significantly associated with digit symbol, digit span backward, Stroop Word and Stroop error index, and grooved pegboard (dominant hand) results. CONCLUSIONS The present findings that there were significant correlations between several neurobehavioral deficits and PI as well as blood Mn suggest that they may be attributed to Mn exposure in welding fumes. The present study also shows that PI is a better predictor of neurobehavioral performance than blood Mn levels in asymptomatic welders.

A case of generalized argyria after ingestion of colloidal silver solution

A 58-year-old woman was referred to our hospital due to progressive skin darkening, which began 5 months previously. The patient had strikingly diffuse blue-gray discoloration of the skin, most prominent in sun-exposed areas, especially her face and hands. The oral mucosa, tongue, gums, eye conjunctiva, ears, nail beds, and trunk were also involved. Bluish-gray discoloration of all nails was aggravated by cold weather. She had ingested 1 L of colloidal silver solution daily for approximately 16 months as a traditional remedy. Her serum silver concentration was 381 ng/ml which was a very high (reference level: <15 ng/ml). Light microscopic examination of a punch biopsy specimen from her nose revealed fine, minute, round, and brown-black granules deposited in the basement membrane of hair follicular epithelium. Scanning electron microscopic examination showed electron-dense granules deposited in the intercellular space of sweat glands. Energy disperse X-ray spectrometry analysis demonstrated peaks for silver and sulfur in the dense black deposits. The ingestion of colloidal silver appears to be an increasing practice among patients using alternative health practices. All silver-containing products including colloidal silver should be labeled with a clear warning to prevent argyria, especially in alternative health practices.

Altered working memory process in the manganese-exposed brain.

Chronic manganese (Mn) exposure often leads to impairments in fine motor and cognitive functions, particularly memory. However, the neural correlates of Mn-induced alterations in memory remain unclear. In the present study, we performed functional MRI (fMRI) with 2-back memory tests to assess the neural correlates of Mn-induced memory impairment in response to subclinical dysfunction in the working memory networks in welders exposed to Mn for extended periods of time. Within-group and between-group analyses revealed that brain activity in working memory networks was increased in welders with chronic Mn exposure during the 2-back verbal working memory task compared to healthy control individuals. Therefore, our fMRI findings indicate that welders might require more neural resources in working memory networks to compensate for subtle deficits in working memory and altered working memory processes, even if they performed the tasks at the same level as healthy control individuals.

Altered white matter microstructural integrity revealed by voxel-wise analysis of diffusion tensor imaging in welders with manganese exposure.

Chronic exposure to manganese (Mn), which can be an occupational hazard or can result from liver failure, is associated with adverse motor and cognitive outcomes. Evidence from previous neuroimaging and magnetic resonance spectroscopy studies suggested alteration of function in Mn-exposed brains. However, the effect of chronic exposure of the human brain to Mn on white matter (WM) structure has not yet been determined. In the present study, we used diffusion tensor imaging (DTI) to investigate whether welders exposed to Mn demonstrate differences in WM integrity, compared with control subjects. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on a voxel-wise basis in 30 male welders with exposure to Mn and in 19 age- and gender-matched control subjects. Direct comparison between welders and controls using investigator-independent Statistical Parametric Mapping (SPM) voxel-wise analysis of DTI metrics revealed a reduction of FA in the corpus callosum (CC) and frontal WM in Mn-exposed welders. Further, marked increases in RD and negligible changes in AD suggested that the microstructural changes in the CC and frontal WM result from compromised radial directionality of fibers in these areas, caused primarily by demyelination. Correlation analysis with neurobehavioral performance also suggested that the microstructural abnormalities were associated with subtle motor and cognitive differences in welders.

Pallidal index measured with three-dimensional T1-weighted gradient echo sequence is a good predictor of manganese exposure in welders.

To evaluate which T1‐wieghted technique between 3D gradient‐echo (FSPGR) and conventional spin‐echo (SE) sequence is more sensitive predictor of neurobehavioral dysfunction found in welders with chronic manganese (Mn) acquired at 3 Tesla.

Neurochemical changes in welders revealed by proton magnetic resonance spectroscopy

BACKGROUND Occupational and environmental exposure to manganese (Mn) is associated with various neurobehavioral and movement dysfunctions. However, few studies have systemically examined the neurochemical effects of Mn exposure. OBJECTIVES We examined typical changes in cerebral metabolite ratios in welders chronically exposed to Mn, compared with control individuals, using proton magnetic resonance spectroscopy (MRS), investigated whether an abnormality in brain metabolism is associated with neurobehavioral changes, and assessed possible implications of chronic Mn exposure. METHODS Thirty-five welders chronically exposed to Mn and 20 age-matched healthy subjects underwent single-voxel MRS at short echo time to assess the N-acetylaspartate (NAA), myoinositol (mI), total choline (tCho), and glutamine plus glutamate (Glx) levels, each of which was expressed as a ratio to total creatine (tCr). Neurobehavioral tests were also performed to define cognitive status. RESULTS NAA/tCr, Glx/tCr, and tCho/tCr ratios in the frontal gray matter (anterior cingulate cortex; ACC) and parietal white matter did not differ significantly between welders and control subjects. These metabolite ratios did not correlate significantly with blood Mn concentration or neurobehavioral parameters. However, mI levels in the ACC, but not in the parietal white matter, were significantly reduced in welders compared with control individuals (P<0.01). Furthermore, in the frontal lobe of the brain, the mI/tCr ratio was significantly correlated with verbal memory scores as well as blood Mn concentration (P<0.05). CONCLUSIONS The cognitive decline observed in welders exposed to Mn was associated with a decreased mI/tCr ratio in the ACC. The depletion of mI in welders may reflect possible glial cell swelling and/or detoxification processes associated with long-term exposure to Mn.

Decreased brain volumes in manganese-exposed welders

BACKGROUND A great deal of research has been devoted to identifying subclinical functional brain abnormalities in manganese (Mn)-exposed welders. However, no previous study has investigated morphological brain abnormalities, such as changes in brain volume, in welders. This study evaluates morphological changes in brain volume among welders, and investigates the relationship between structural brain abnormalities and subclinical dysfunction in this population. METHODS We used voxel-based morphometry (VBM) to assess differences in gray and white matter brain volumes between 40 welders with chronic Mn exposure and 26 age-matched control subjects. Correlation analyses were used to investigate the relationship between brain volume changes and decreased performance on neurobehavioral tests. RESULTS Brain volumes in the globus pallidus and cerebellar regions were significantly diminished in welders with chronic Mn exposure compared to controls (FDR-corrected P<0.05). These changes in brain volume were negatively correlated with cognitive performance and grooved pegboard scores. CONCLUSION There are measurable brain volume reductions in the globus pallidus and cerebellum of welders chronically exposed to Mn, and these volume reductions correlate with cognitive and motor neurobehavioral deficits. Our findings therefore indicate that volumetric measurement could be a useful subclinical marker among welders that show no signs of manganism.

Dopaminergic neuronal integrity in parkinsonism associated with liver cirrhosis.

OBJECTIVE To investigate the nature of parkinsonism associated with liver cirrhosis, which entails examination of the integrity of the nigrostriatal dopaminergic system. METHODS Consecutive patients who had concurrent liver cirrhosis and parkinsonism were investigated with MRI and dopamine transporter (DAT) single-photon emission computerized tomography (SPECT) using iodine I 123 [(123)I]-radiolabeled fluoropropyl (FP) 2-carbomethoxy-3-(4-iodophenyl) tropane (CIT). RESULTS Five patients with liver cirrhosis were identified and confirmed to have concurrent parkinsonism. In all patients, MRI showed increased T1 signals, affecting basal ganglia bilaterally. DAT density was normal in four patients, and these patients had relatively non-progressive, levodopa-unresponsive parkinsonism. In one patient, striatal [(123)I]FP-CIT uptake was reduced, similar to the pattern of idiopathic Parkinsons disease (PD). This patient showed sustained response to levodopa treatment. CONCLUSIONS Our patients showed two different patterns of clinical and neuroradiological features, that is, atypical parkinsonism with normal DAT density, which is clearly differentiated from PD versus levodopa-responsive parkinsonism with reduced DAT density (classical PD). Further investigations using other markers of dopaminergic transmission and histopathological studies should be conducted to elucidate whether damage to the nigrostriatal dopaminergic system occurs in parkinsonism associated with liver cirrhosis.

Gender difference in blood cadmium concentration in the general population: can it be explained by iron deficiency?

INTRODUCTION Gender differences in blood cadmium concentrations and the effect of iron deficiency on blood cadmium levels were analyzed in a representative sample of Koreans assessed in the Korean National Health and Nutritional Examination Survey (KNHANES) 2008-2011. METHODS A rolling sampling design was used to perform a complex, stratified, multistage probability cluster survey of a representative sample of the non-institutionalized civilian population in South Korea. Serum ferritin was categorized as low (<15.0 μg/L), low normal (15.0-<30.0 μg/L for females and 15.0-<50.0 μg/L for males), and normal (≥30.0 μg/L for females and ≥50.0 μg/L for males), and its association with blood cadmium levels was assessed after adjustment for various demographic and lifestyle factors. RESULTS The geometric mean (GM) of the blood cadmium level was significantly higher in females than in males, and significantly higher in older individuals for both genders. After controlling for covariates, multiple regression analysis with interaction terms showed that blood cadmium was correlated with serum ferritin levels only in pre-menopausal females. DISCUSSION Iron deficiency is associated with blood cadmium levels in a representative sample of pre-menopausal females, as evaluated in KNHANES. Gender differences in blood cadmium concentration may not be due solely to an iron deficiency-associated increase in blood cadmium.

High Pallidal T1 Signal is Rarely Observed in Obstructive Jaundice, but is Frequently Observed in Liver Cirrhosis

High Pallidal T1 Signal is Rarely Observed in Obstructive Jaundice, but is Frequently Observed in Liver Cirrhosis: Sung‐Jo Bang, et al. Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, South Korea—Although high signal intensities in the globus pallidus are frequently observed in T1‐weighted magnetic resonance images (MRI) of patients with liver cirrhosis, it is unclear whether these increases are due to portal‐systemic shunt or obstruction of biliary excretion. We therefore studied pallidal signals in 18 cancer patients with bile duct obstruction and marked jaundice (>10 mg/dl). Patients who had fever, leukocytosis or liver cirrhosis were excluded to ensure that jaundice was due to bile duct obstruction. All patients showed a dilated intrahepatic duct on computed tomography (CT) scan. A high pallidal signal was observed in one of 18 biliary obstructive patients whereas high signals were highly prevalent in liver cirrhosis. A portal‐systemic shunt rather than an obstruction of biliary excretion may be responsible for the increased blood manganese concentrations and pallidal T1 signals in chronic liver diseases.