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.
Neurology. 2014 May 6;82(18):1597-604. doi: 10.1212/WNL.0000000000000385. Epub 2014 Apr 9.
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.
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.
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.
The present results provide convincing evidence that presynaptic dopaminergic denervation in PD plays a crucial role in the development of LID.
通过定量分析 18F-FP-CIT PET 数据，探讨帕金森病（PD）患者纹状体突触前多巴胺耗竭程度是否为左旋多巴诱导运动障碍（LID）发生的危险因素。
本回顾性队列研究共纳入 127 例初诊的、未经药物治疗的新发 PD 患者，这些患者在初始评估时均完成了 18F-FP-CIT PET 扫描。患者每 3-6 个月到我院门诊就诊，自开始使用多巴胺能药物后至少随访 2 年。采用 Cox 比例风险模型评估定量分析的纹状体亚区 18F-FP-CIT 摄取和其他临床因素对 LID 发生的预测能力。
在平均 3.4 年的随访期间，35 例 PD 患者（27.6%）出现 LID。与无 LID 的患者相比，有 LID 的患者纹状体的多巴胺转运体（DAT）活性较低。多变量 Cox 比例风险模型显示，前纹状体（危险比 [HR] 0.530；p = 0.032）、后纹状体（HR 0.302；p = 0.024）和整个纹状体（HR 0.386；p = 0.022）的 DAT 摄取量是 LID 发生的显著预测因子，而尾状核和腹侧纹状体的 DAT 活性与 LID 的发生无显著相关性。此外，PD 发病年龄较小和左旋多巴剂量较高也是 LID 发生的显著预测因子。
本研究结果提供了令人信服的证据，表明 PD 患者的突触前多巴胺能神经退行性变在 LID 的发生中起着关键作用。
