Reduced uptake of [
            <sup>18</sup>
            F]FDOPA PET in asymptomatic welders with occupational manganese exposure

Criswell, Susan R.; Perlmutter, Joel S.; Videen, Tom O.; Moerlein, Stephen M.; Flores, Hubert; Birke, Angela; Racette, Brad A.

doi:10.1212/wnl.0b013e3182152830

Cited by 82 publications

(88 citation statements)

References 35 publications

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“…Similarly, neuropathological examinations in humans with symptomatic clinical Mn toxicity reveal degeneration of the medial segment of the globus pallidus with less severe degeneration of the putamen and caudate 13. Additional evidence that welding affects non-pallidal basal ganglia structures comes from the observation that PET measured uptake of [ 18 F]FDOPA is reduced in the caudate of asymptomatic welders 14. Together these findings suggest that extra-pallidal hyperintensities are likely present in occupationally exposed welders.…”

Section: Introductionmentioning

confidence: 96%

Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

et al. 2012

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Objectives Manganese exposure leads to diffuse cerebral metal deposition with the highest concentration in the globus pallidus associated with increased T1-weighted MRI signal. T1 signal intensity in extra-pallidal basal ganglia (caudate and putamen) has not been studied in occupationally exposed workers. Diffusion weighted imaging is a non-invasive measure of neuronal damage and may provide a quantification of neurotoxicity associated with welding and manganese exposure. This study investigated extra-pallidal T1 basal ganglia signal intensity as a marker of manganese exposure and basal ganglia diffusion weighted imaging abnormalities as a potential marker of neurotoxicity. Methods A 3T MR case:control imaging study was performed on 18 welders and 18 age- and gender-matched controls. Basal ganglia regions of interest were identified for each subject. T1-weighted intensity indices and apparent diffusion coefficients were generated for each region. Results All regional indices were higher in welders than controls (p≤0.05). Combined basal ganglia (ρ=0.610), caudate (ρ=0.645), anterior (ρ=0.595) and posterior putamen (ρ=0.511) indices were more correlated with exposure than pallidal (ρ=0.484) index. Welder apparent diffusion coefficient values were lower than controls for globus pallidus (p=0.03) and anterior putamen (p=0.004). Conclusions Welders demonstrated elevated T1 indices throughout the basal ganglia. Combined basal ganglia, caudate and putamen indices were more correlated with exposure than pallidal index suggesting more inclusive basal ganglia sampling results in better exposure markers. Elevated indices were associated with diffusion weighted abnormalities in the pallidum and anterior putamen suggesting neurotoxicity in these regions.

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Section: Introductionmentioning

confidence: 96%

Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

et al. 2012

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“…The largest molecular imaging study of the presynaptic dopaminergic system (the pathway primarily affected in PD) demonstrated dopaminergic dysfunction in Mn-exposed welders. 40,41 Although the pattern of dopaminergic dysfunction was different from that seen in PD, findings from molecular imaging of the dopaminergic system in patients with Mn toxicity secondary to liver failure suggest that the pattern of dopaminergic dysfunction may be more typical of PD. 42,43 Much of the epidemiological research conducted to date suffers from severe limitations.…”

Section: Discussionmentioning

confidence: 99%

Epidemiological Studies of Parkinsonism in Welders

Checkoway¹,

Nielsen²,

Racette³

2014

Manganese in Health and Disease

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Welders have been the focus of numerous epidemiological studies addressing possible etiologic relations between manganese (Mn) and Parkinson disease (PD). These include investigations of defined cohorts of welders, which we regard as most informative, general population surveys of welding occupations, and population-based case-control studies. With a few notable exceptions among the studies of defined cohorts of welders, there is little evidence that welders are at increased risk of PD. However, most prior research has suffered from severe limitations due to incomplete ascertainment of incident cases, questionable diagnostic accuracy, and non-specific Mn exposure assessment that precludes quantitative dose–response estimation. A potential etiologic relation between environmental Mn exposure and PD continues to be an important scientific and public health topic, given the ubiquitous nature of Mn exposure. Investigations of welders, who experience some of the highest Mn doses in the population, should remain a priority. Recommended future epidemiological research should involve longitudinal assessments of risk, severity, and progression of clinically diagnosed PD among well-characterized cohorts of welders, whose exposures to Mn and potential confounders can be assessed quantitatively.

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“…This could explain the clinical phenotype associated with Mn neurotoxicity in which neuropsychiatric symptoms, including cognitive impairment, depression, and hallucinations, are often present before or concurrent with motor symptomatology, which would be unusual in early IPD. [125][126][127] The differences between early PET studies by Wolters et al 116 and subsequent studies may be related to differences in the method of Mn exposure, upgrades in scanner resolution, or more likely sample size, because these studies were not powered to detect the approximately 10% difference in [ 18 F]-fluoro-L-dopa uptake identified by Criswell et al 123 While these [ 18 F]-fluoro-L-dopa PET studies demonstrate evidence of presynaptic dopaminergic dysfunction, [ 18 F]-fluoro-L-dopa measurements alone cannot distinguish a neurotoxic effect on nigrostriatal neurons from a dysfunctional process causing a regulatory effect on presynaptic decarboxylase activity. In combination with the non-human primate studies by Guilarte et al,112 these findings support the hypothesis that chronic Mn exposure produces clinical neurotoxicity through presynaptic dopamine terminal dysfunction.…”

Section: Pet Studies In Human Subjectsmentioning

confidence: 99%

Imaging Modalities for Manganese Toxicity

Dydak¹,

Criswell²

2014

Manganese in Health and Disease

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Rapidly advancing imaging technology has been essential to the study of manganese (Mn) toxicity in vivo. Over the past few decades, imaging techniques have been effectively utilized as markers of Mn exposure and to investigate the biological effects of Mn neurotoxicity. This chapter will review several of the imaging modalities that have made an impact in Mn neurotoxicity research. The scope of this chapter will include discussions of magnetic resonance imaging (MRI), including magnetic resonance spectroscopy (MRS), diffusion weighted imaging (DWI), and functional MRI (fMRI), as well as positron emission tomography (PET), single photon emission computed tomography (SPECT), and X-ray fluorescence imaging. For each modality, the basic principle of the imaging technique will be briefly described to facilitate proper data interpretation and understanding of limitations. This will be followed by a discussion on the main research findings using that modality, and how they have shaped our understanding of Mn toxicity.

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Reduced uptake of [ ¹⁸ F]FDOPA PET in asymptomatic welders with occupational manganese exposure

Abstract: Background: Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure

Cited by 82 publications

References 35 publications

Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

Epidemiological Studies of Parkinsonism in Welders

Imaging Modalities for Manganese Toxicity

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Reduced uptake of [ 18 F]FDOPA PET in asymptomatic welders with occupational manganese exposure

Abstract: Background: Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure

Cited by 82 publications

References 35 publications

Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

Basal ganglia intensity indices and diffusion weighted imaging in manganese-exposed welders

Epidemiological Studies of Parkinsonism in Welders

Imaging Modalities for Manganese Toxicity

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Product

Resources

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Reduced uptake of [ ¹⁸ F]FDOPA PET in asymptomatic welders with occupational manganese exposure