[F]FDOPA positron emission tomography in manganese-exposed workers

Susan R. Criswell, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: criswells@neuro.wustl.edu.
Susan Searles Nielsen, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Mark Warden, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Joel S. Perlmutter, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA; Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA; Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA.
Stephen M. Moerlein, Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
Hubert P. Flores, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
John Huang, Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA.
Lianne Sheppard, Department of Environmental and Occupational Health Sciences, University of Washington, School of Public Health, Seattle, WA, USA; Department of Biostatistics, University of Washington, School of Public Health, Seattle, WA, USA.
Noah Seixas, Department of Environmental and Occupational Health Sciences, University of Washington, School of Public Health, Seattle, WA, USA.
Harvey Checkoway, Department of Family Medicine and Public Health, UC San Diego School of Medicine, La Jolla, CA, USA.
Brad A. Racette, Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa.

Document Type

Article

Abstract

Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014min (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012min (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p≤0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism.

Medical Subject Headings

Adult; Corpus Striatum (diagnostic imaging, metabolism); Cross-Sectional Studies; Dihydroxyphenylalanine (analogs & derivatives); Female; Humans; Magnetic Resonance Imaging; Male; Manganese Poisoning (diagnostic imaging, metabolism); Middle Aged; Occupational Diseases (chemically induced, diagnostic imaging, metabolism); Occupational Exposure; Parkinsonian Disorders (chemically induced, diagnostic imaging, metabolism); Positron-Emission Tomography; Welding

Publication Date

1-1-2018

Publication Title

Neurotoxicology

E-ISSN

1872-9711

Volume

64

First Page

43

Last Page

49

PubMed ID

28694016

Digital Object Identifier (DOI)

10.1016/j.neuro.2017.07.004

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