4.7 Article

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

Journal

NEUROLOGY
Volume 76, Issue 15, Pages 1296-1301

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e3182152830

Keywords

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Funding

  1. Michael J. Fox Foundation
  2. NIH [R01 ES013743, K24 ES017765, KL2 RR024994, P42ES04696, 5T32NS007205-27, RO1 NS41509, RO1 NS058714]
  3. NCRR [UL1 RR024992]
  4. Neuroscience Blueprint [NS057105]
  5. American Parkinson Disease Association (APDA) Advanced Research Center at Washington University
  6. Greater St. Louis Chapter of the APDA
  7. McDonnell Center for Higher Brain Function
  8. Barnes-Jewish Hospital Foundation
  9. Merck Serono
  10. Chiltern International
  11. Teva Pharmaceutical Industries Ltd.
  12. Medivation, Inc.
  13. NIH
  14. American Parkinson Disease Association
  15. Medtronic, Inc.
  16. Huntington Disease Society of American Center of Excellence
  17. CHDI (formerly HiQ Foundation)
  18. Greater St. Louis Chapter of the American Parkinson Disease Association
  19. Bander Foundation for Medical Ethics and Advanced PD Research Center at Washington University
  20. Barnes Jewish Hospital Foundation
  21. NIH/NINDS
  22. Eisai Inc.,
  23. Solvay Pharmaceuticals, Inc.
  24. SCHWARZ PHARMA
  25. Solstice Neurosciences, Inc.
  26. Allergan, Inc.
  27. Neurogen Corporation
  28. NIH (NIEHS)
  29. 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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