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Presynaptic dopamine depletion predicts levodopa-induced dyskinesia in de novo Parkinson disease

 Jin Yong Hong  ;  Jungsu S. Oh  ;  Injoo Lee  ;  Mun Kyung Sunwoo  ;  Jee Hyun Ham  ;  Ji E. Lee  ;  Young H. Sohn  ;  Jae Seung Kim  ;  Phil Hyu Lee 
 NEUROLOGY, Vol.82(18) : 1597-1604, 2014 
Journal Title
Issue Date
Aged ; Antiparkinson Agents/adverse effects* ; Chi-Square Distribution ; Cohort Studies ; Corpus Striatum/diagnostic imaging ; Corpus Striatum/pathology ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Dyskinesia, Drug-Induced/diagnostic imaging ; Dyskinesia, Drug-Induced/etiology* ; Dyskinesia, Drug-Induced/pathology* ; Female ; Humans ; Levodopa/adverse effects* ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/drug therapy ; Positron-Emission Tomography ; Predictive Value of Tests ; Proportional Hazards Models ; Tropanes
Objective: To investigate whether the magnitude of presynaptic dopamine depletion is a risk factor for the development of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) by quantitatively analyzing 18F-FP-CIT PET data.

Methods: This retrospective cohort study enrolled a total of 127 drug-naive de novo patients with PD who completed 18F-FP-CIT PET scanning at their initial evaluation. The patients visited our outpatient clinic every 3–6 months and had been followed for a minimum of 2 years since beginning dopaminergic medication. The predictive power of the quantitatively analyzed 18F-FP-CIT uptake of striatal subregions and other clinical factors for the development of LID was evaluated using Cox proportional hazard models.

Results: During a mean follow-up period of 3.4 years, 35 patients with PD (27.6%) developed LID. Patients with LID showed less dopamine transporter (DAT) activity in the putamen than did those without LID. Multivariate Cox proportional hazard models revealed that the DAT uptakes of the anterior putamen (hazard ratio [HR] 0.530; p = 0.032), posterior putamen (HR 0.302; p = 0.024), and whole putamen (HR 0.386; p = 0.022) were significant predictors of the development of LID, whereas DAT activities in the caudate and ventral striatum were not significantly correlated with the development of LID. In addition, younger age at onset of PD and higher dose of levodopa were also significant predictors of the development of LID.

Conclusions: The present results provide convincing evidence that presynaptic dopaminergic denervation in PD plays a crucial role in the development of LID.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Sunwoo, Mun Kyung(선우문경)
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Lee, Ji Eun(이지은)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Ham, Jee Hyun(함지현)
Hong, Jin Yong(홍진용)
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