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Research paper
Early-onset drug-induced parkinsonism after exposure to offenders implies nigrostriatal dopaminergic dysfunction
  1. Seok Jong Chung1,
  2. Han Soo Yoo1,
  3. Hyojeong Moon2,
  4. Jungsu S Oh2,
  5. Jae Seung Kim2,
  6. Yong Hee Park3,
  7. Jin Yong Hong3,
  8. Byoung Seok Ye1,
  9. Young H Sohn1,
  10. Phil Hyu Lee1,4
  1. 1 Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea
  2. 2 Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  3. 3 Department of Neurology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
  4. 4 Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
  1. Correspondence to Professor Phil Hyu Lee, Department of Neurology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea; phlee{at}


Objectives The onset of parkinsonism in patients with drug-induced parkinsonism (DIP) exhibits extensive individual variability following exposure to offending drugs. We investigated whether the individual variations in the onset time of parkinsonism reflected the underlying subtle dopaminergic dysfunction in DIP.

Methods We enrolled 71 patients with DIP who had visually normal striatal dopamine transporter (DAT) availability in 18F-FP-CIT positron emission tomography scans. According to their exposure durations to the offending drugs prior to onset of the parkinsonism, the patients were divided into the early-onset group (duration ≤6 months; n=35) and delayed-onset group (duration >6 months; n=36). We performed the quantitative analysis of the DAT availability in each striatal subregion between the groups.

Results No patients with DIP had DAT availability that was more than 2 SD below the normal mean of DAT availability. Compared with the delayed-onset group, the early-onset DIP group had decreased DAT availability in the striatal subregions including the posterior putamen (p=0.018), anterior putamen (p=0.011), caudate (p=0.035) and ventral striatum (p=0.027). After adjusting for age, sex and cross-cultural smell identification test scores, a multivariate analysis revealed that the DAT availability in the striatal subregions of the patients with DIP was significantly and positively associated with the natural logarithm of the duration of drug exposure.

Conclusions These results suggest that a short exposure to the offending drugs before the development of parkinsonism would be associated with subtle nigrostriatal dopaminergic dysfunction in patients with DIP.

  • drug-induced parkinsonism
  • dopamine transporter
  • Parkinson’s disease

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  • Contributors The study was conceived and planned by SJC and PHL. SJC, HSY, YHP and JYH collected the data. SJC, HM, JSO, JSK and PHL analysed and interpreted the data, and were involved in the initial drafting of the manuscript. HSY, JYH, BSY and YHS revised the paper. PHL was involved in the final approval of the version to be published, and takes responsibility for the integrity and accuracy of the data analyses.

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

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study was approved by Yonsei University Severance Hospital ethical standards committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement We can share raw data of DAT availability and demographic characteristics of patients with DIP if asked. Anyone who is interested in this study can contact the first author (SJC, or the corresponding author (PHL,