Journal
NEUROLOGY
Volume 76, Issue 15, Pages 1296-1301Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182152830
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Funding
- Michael J. Fox Foundation
- NIH [R01 ES013743, K24 ES017765, KL2 RR024994, P42ES04696, 5T32NS007205-27, RO1 NS41509, RO1 NS058714]
- NCRR [UL1 RR024992]
- Neuroscience Blueprint [NS057105]
- American Parkinson Disease Association (APDA) Advanced Research Center at Washington University
- Greater St. Louis Chapter of the APDA
- McDonnell Center for Higher Brain Function
- Barnes-Jewish Hospital Foundation
- Merck Serono
- Chiltern International
- Teva Pharmaceutical Industries Ltd.
- Medivation, Inc.
- NIH
- American Parkinson Disease Association
- Medtronic, Inc.
- Huntington Disease Society of American Center of Excellence
- CHDI (formerly HiQ Foundation)
- Greater St. Louis Chapter of the American Parkinson Disease Association
- Bander Foundation for Medical Ethics and Advanced PD Research Center at Washington University
- Barnes Jewish Hospital Foundation
- NIH/NINDS
- Eisai Inc.,
- Solvay Pharmaceuticals, Inc.
- SCHWARZ PHARMA
- Solstice Neurosciences, Inc.
- Allergan, Inc.
- Neurogen Corporation
- NIH (NIEHS)
- BJHF/ICTS
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Background: Welding exposes workers to manganese (Mn) fumes, but it is unclear if this exposure damages dopaminergic neurons in the basal ganglia and predisposes individuals to develop parkinsonism. PET imaging with 6-[F-18]fluoro-L-dopa (FDOPA) is a noninvasive measure of nigrostriatal dopaminergic neuron integrity. The purpose of this study is to determine whether welding exposure is associated with damage to nigrostriatal neurons in asymptomatic workers. Methods: We imaged 20 asymptomatic welders exposed to Mn fumes, 20 subjects with idiopathic Parkinson disease (IPD), and 20 normal controls using FDOPA PET. All subjects were examined by a movement disorders specialist. Basal ganglia volumes of interest were identified for each subject. The specific uptake of FDOPA, K-i, was generated for each region using graphical analysis method. Results: Repeated measures general linear model (GLM) analysis demonstrated a strong interaction between diagnostic group and region (F-4,F-112 = 15.36, p < 0.001). Caudate K(i)s were lower in asymptomatic welders (0.0098 + 0.0013 minutes(-1)) compared to control subjects (0.0111 + 0.0012 minutes(-1), p = 0.002). The regional pattern of uptake in welders was most affected in the caudate > anterior putamen > posterior putamen. This uptake pattern was anatomically reversed from the pattern found in subjects with IPD. Conclusions: Active, asymptomatic welders with Mn exposure demonstrate reduced FDOPA PET uptake indicating dysfunction in the nigrostriatal dopamine system. The caudate K-i reduction in welders may represent an early (asymptomatic) marker of Mn neurotoxicity and appears to be distinct from the pattern of dysfunction found in symptomatic IPD. Neurology (R) 2011;76:1296-1301
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