Manganism and idiopathic parkinsonism

Abstract

From the comparison we have made between PD and manganism, we draw the following conclusions: 1. There are similarities between PD and manganism, notably the presence of (a) generalized bradykinesia and (b) widespread rigidity. 2. There are also dissimilarities between PD and manganism, notably the following in manganism: (a) less-frequent resting tremor, (b) more frequent dystonia, (c) a particular propensity to fall backward, (d) failure to achieve a sustained therapeutic response to levodopa, and (e) failure to detect a reduction in fluorodopa uptake by PET. Further studies are likely to yield more discriminants between PD and manganism. For example, PET with raclopride may be useful in early cases of manganism, and MRI may be helpful in patients with advanced manganism.

Manganese transport in eukaryotes: The role of DMT1

“…While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson's disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia (Calne et al, 1994;Dobson et al, 2004).…”

“…While Mn deficiency is uncommon in humans, Mn toxicity is known to be readily prevalent due to occupational overexposure in miners, smelters and possibly welders. Excessive exposure to Mn can cause Parkinson's disease-like syndrome; patients typically exhibit extrapyramidal symptoms that include tremor, rigidity and hypokinesia (Calne et al, 1994;Dobson et al, 2004).Mn-induced motor neuron diseases have been the subjects of numerous studies; however, this review is not intended to discuss its neurotoxic potential or its role in the etiology of motor neuron disorders. Rather, it will focus on Mn uptake and transport via the orthologues of the divalent metal transporter (DMT1) and its possible implications to Mn toxicity in various categories of eukaryotic systems, such as in vitro cell lines, in vivo rodents, the fruitfly, Drosophila melanogaster, the honeybee, Apis mellifera L., the nematode, Caenorhabditis elegans, and the baker's yeast, Saccharomyces cerevisiae.…”

“…Occupational exposure to Mn for periods from 6 months to 2 years can cause extrapyramidal symptoms that resemble idiopathic Parkinson's Disease, a disease known as manganism. Patients suffering from manganism exhibit a signature biphasic mode of physical decline, which comprises of an initial phase of psychiatric disturbance and neurological deficits which are followed by motor defects such as akinetic rigidity, dystonia and bradyskinesia (Calne et al, 1994;Olanow, 2004). …”

Postnatal manganese exposure alters dopamine transporter function in adult rats: Potential impact on nonassociative and associative processes

“…Humans exposed to excess Mn for prolonged periods often exhibit extrapyramidal motor impairments similar to Parkinson's Disease (Calne et al, 1994;Mergler, 1999;Aschner, 2000), as well as cognitive deficits and psychiatric disturbances (Mergler et al, 1994;Aschner, 2000). Although Mn impacts multiple neurotransmitter systems (Fitsanakis et al, 2006b), the complex symptomology characteristic of Mn toxicity suggests that both the mesocorticolimbic and nigrostriatal dopamine systems might be affected.…”

Direct effects of manganese compounds on dopamine and its metabolite Dopac: An in vitro study

“…The symptoms that these miners developed were termed locally as "locura manganica" or manganic madness (Mena et al, 1967). Following exposure, the main areas of the mammalian brain targeted by excessive Mn neurotoxicity are the basal ganglia (caudate, putamen, globus pallidus, substantia nigra, and subthalamic nucleus; Calne et al, 1994;Eriksson et al, 1992;Nagatomo et al, 1999;Brenneman et al, 1999). Of these regions, the globus pallidus appears to be affected the most, a feature of Mn neurotoxicity that is distinct from Parkinsonism (Verity, 1999).…”