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Presynaptic dopamine depletion determines the timing of levodopa-induced dyskinesia onset in Parkinson’s disease

  • Han Soo Yoo
  • Seok Jong Chung
  • Su Jin Chung
  • Hyojeong Moon
  • Jung Su Oh
  • Jae Seung Kim
  • Jin Yong Hong
  • Byoung Seok Ye
  • Young Ho Sohn
  • Phil Hyu Lee
Original Article

Abstract

Purpose

Reduced presynaptic dopaminergic activity plays an important role in the development of levodopa-induced dyskinesia (LID) in Parkinson’s disease (PD). In this study, we investigated whether dopaminergic function in the nigrostriatal system is associated with the timing of LID onset.

Methods

From among 412 drug-naive PD patients who underwent a dopamine transporter (DAT) PET scan during their baseline evaluation, we enrolled 65 patients who developed LID during a follow-up period of >2 years. Based on the time from PD onset, LID was classified as early, intermediate or late onset. We then compared DAT availability in the striatal subregions of the patients in the three groups.

Results

The demographic characteristics did not differ among the three patient groups except for earlier intervention of levodopa therapy in the early LID onset group (p = 0.001). After adjusting for age at PD onset, gender, timing of levodopa therapy from PD onset, and the severity of PD motor symptoms, DAT activity in the posterior putamen was found to be significantly lower in the early LID onset group than in the late LID onset group (p = 0.017). Multivariate linear regression analysis showed that low DAT activity in the posterior putamen was significantly associated with the early appearance of LID in the early LID onset group (β = 16.039, p = 0.033).

Conclusion

This study demonstrated that low DAT activity in the posterior putamen at baseline is a major risk factor for the early onset of LID in patients with PD, suggesting that the degree of presynaptic dopaminergic denervation plays an important role in determining the timing of LID onset.

Keywords

Dopamine transporter PET Parkinson’s disease Levodopa-induced dyskinesia 

Notes

Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and welfare, Republic of Korea (grant number: HI16C1118).

Compliance with ethical standards

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Supplementary material

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ESM 1 (PDF 19 kb)
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ESM 3

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Han Soo Yoo
    • 1
  • Seok Jong Chung
    • 1
  • Su Jin Chung
    • 1
  • Hyojeong Moon
    • 2
  • Jung Su Oh
    • 2
  • Jae Seung Kim
    • 2
  • Jin Yong Hong
    • 3
  • Byoung Seok Ye
    • 1
  • Young Ho Sohn
    • 1
  • Phil Hyu Lee
    • 1
  1. 1.Department of NeurologyYonsei University College of MedicineSeoulSouth Korea
  2. 2.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  3. 3.Yonsei University Wonju College of MedicineWonjuSouth Korea

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