Presynaptic dopamine depletion predicts levodopa-induced dyskinesia in de novo Parkinson disease.
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 (18)F-FP-CIT PET data.


METHODS
This retrospective cohort study enrolled a total of 127 drug-naive de novo patients with PD who completed (18)F-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 (18)F-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.
From the Department of Neurology (J.Y.H.), Yonsei University Wonju College of Medicine, Wonju; the Department of Nuclear Medicine (J.S.O., I.L., J.S.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul; and the Department of Neurology and Brain Research Institute (J.Y.H., M.K.S., J.H.H., J.E.L., Y.H.S., P.H.L.) and Severance Biomedical Science Institute (P.H.L.), Yonsei University College of Medicine, Seoul, Korea.
Jin Yong
JY
Hong
Jungsu S
JS
Oh
Injoo
I
Lee
Mun Kyung
MK
Sunwoo
Jee Hyun
JH
Ham
Ji E
JE
Lee
Young H
YH
Sohn
Jae Seung
JS
Kim
Phil Hyu
PH
Lee
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D014326:Tropanes
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D007980:Levodopa