Chronic manganese poisoning: A neuropathological study with determination of manganese distribution in the brain

Abstract

An autopsy case of a 52-year-old man suffering from chronic manganese poisoning (CMP) is reported with determination of the manganese distribution in the brain. The patient had been working in a manganese ore crushing plant since 1965. In 1967 he began to complain of difficulties in walking and diminished libido. Later, he developed various neuropsychiatric symptoms including euphoria, emotional incontinence, masked face, monotonous speech, "cock-walk", increased muscle tone, weakness of upper and lower extremities, tremor of the eye lids, and exaggeration of knee jerks. The major neuropathological change was degeneration of the basal ganglia, in which the pallidum was severely affected. The pallidum disclosed a loss and degeneration of nerve cells, which was especially marked in the medial segment, a prominent decrease of myelinated fibers, and moderate astrocytic proliferation. The substantia nigra was intact. Distribution of manganese in the brain of the present case of CMP was determined using flameless atomic absorption spectrometry and compared with control cases and also a case of Parkinson's disease (PD). There was no significant difference between the control cases and the case of PD in average concentration of manganese and its distribution in the brain. The present case of CMP showed no elevation in average concentration of manganese in the brain. However, there were some changes in its distribution. Thus, the continuance of neurological disorders in CMP is not linked to an elevated manganese concentration itself in the brain. CMP appears to be different from PD in neuropathology and manganese behavior in brain.

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“…Manganese neurotoxicity had previously been reported in miners after a prolonged exposure to manganese dust, resulting in extrapyramidal symptoms resembling Parkinson's disease (Yamada et al, 1986). In cirrhotic patients a high incidence of extrapyramidal symptoms is observed when a detailed and careful neurological evaluation is performed (Spahr et al, 1996).…”

Methylcyclopentadienyl manganese tricarbonyl: health risk uncertainties and research directions.

“…Some speculation has suggested that the difference in neurobehavioral sensitivity of rodents and primates may be related to the fact that, unlike primates, rodents do not have pigmented substantia nigra, which is a brain region of relatively high Mn uptake. However, it appears that other nuclei of the basal ganglia are more likely to be target sites of Mn neurotoxicity (29 For improvement of the exposure assessment, the U.S. EPA has recommended obtaining personal exposure measurements using a probabilistic sampling design in areas where MMT is used in gasoline (96). At the time this recommendation was made, Canada was the only country where MMT was used in unleaded gasoline, and thus it was presumed that such studies would have to be conducted in Canada.…”

“…Postmortem examinations of Mn-exposed humans and experimental studies of Mnexposed laboratory animals indicate that Mn is distributed preferentially to nuclei of the basal ganglia, particularly the caudate, putamen, globus pallidus, subthalamic nucleus, and substantia nigra, and to a lesser extent to other regions of the brain, including the cerebellum and pituitary (29)(30)(31). Generally the primary sites of neuropathologic changes associated with Mn toxicity in humans and experimental animals are the basal ganglia, particularly the globus pallidus, caudate, and putamen.…”

“…Generally the primary sites of neuropathologic changes associated with Mn toxicity in humans and experimental animals are the basal ganglia, particularly the globus pallidus, caudate, and putamen. There is little or no involvement of the substantia nigra (29)(30)(31)(32)(33). Investigation of the mechanisms of Mn neurotoxicity has focused on the oxidative properties of Mn (especially Mn3+) and its interactions with the dopaminergic system, including biphasic increases and decreases in dopamine levels associated with Mn exposure (34).…”

Dietary modulation of age-related changes in cerebral pro-oxidant status

“…Manganese-induced brain lesions tend to occur in regions of intense oxygen consumption (Yamada et al, 1986), and are marked by enhanced auto-oxidation and turnover of dopamine, losses of neurons and demyelination (Cotzias et al, 1971;Donaldson et al, 1984;Gerlach et al, 1994;Erikson et al, 1987). The site-specificity of the pathology and the selective targeting of dopamine have led to the comparison of manganese-induced neurodegeneration to that of other transition metals, iron and copper (Triggs and Willmore, 1984;Rauhala and Chiueh, 2000;Sengstock et al, 1993), i.e.…”