Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity
Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity
复制标题
DOI：
10.1001/archneur.62.3.378
复制
发表时间：
2005-03-01
影响因子：
--
通讯作者：
Heiss, WD
中科院分区：
文献类型：
--
作者：
Hilker, R;Schweitzer, K;Heiss, WD
背景：疾病进展的研究提供了有关帕金森病 (PD) 细胞死亡动态的重要信息。目的：利用正电子发射断层扫描 (PET) 确定 PD 中多巴胺能损伤的进展。设计：随访期为 64.5 +/- 22.6 个月（平均值 +/- SD）的纵向前瞻性队列研究。地点：大学医院患者：PD 患者的连续样本（N = 31；年龄）症状发作时（53.6 +/- 11.3 岁），在研究进入时症状持续时间和严重程度有很大差异。干预措施：通过连续氟多巴 F 18 ([F-18] 氟多巴) PET 进行调查，作为纹状体多巴胺能功能的标记。主要结果指标：尾状核和壳核 [F-18] 氟多巴流入常数的变化结果：在PD患者中，壳核[F-18]氟多巴Ki的下降率与研究纳入前的病程呈负相关（r=-0.46，P=.01），与基线Ki值呈正相关（r=0.44，P=.01），表明多巴胺神经元呈负指数损失。年疾病进展率从尾状核的 4.4% 到壳核的 6.3% 不等。根据对照组的壳核 Ki 阈值 69% 出现症状，计算出平均临床前期为 5.6 +/- 3.2 年。假设非线性进展动力学，发现使用 [F-18] 氟多巴 PET 证明神经保护所需的样本量随着研究对象先前症状持续时间的增加而强烈增加。结论：这些数据表明 PD 的神经退行性过程遵循负指数过程，并随着症状持续时间的增加而减慢，这与 PD 的长潜伏期假设相矛盾。
Background: The investigation of disease progression provides important information on the dynamics of cell death in Parkinson disease (PD).Objective: To determine the progression of dopaminergic impairment in PD with the use of positron emission tomography (PET).Design: Longitudinal prospective cohort study with a follow-up period of 64.5 +/- 22.6 months (mean +/- SD).Setting: University hospitalPatients: A consecutive sample of patients with PD (N = 31; age at symptom onset, 53.6 +/- 11.3 years) with a wide range of symptom duration and severity at the time of study entry.Interventions: Investigation by serial fluorodopa F 18 ([F-18] fluorodopa) PET as a marker for striatal dopaminergic function.Main Outcome Measures: Changes in caudate and putaminal [F-18] fluorodopa influx constant (K-i) values.Results: In patients with PD, the decline rate of putaminal [F-18] fluorodopa Ki correlated inversely with disease duration before study inclusion (r=-0.46, P=.01) and positively with baseline Ki values (r=0.44, P=.01),indicating a negative exponential loss of dopamine neurons. Annual disease progression rates ranged from 4.4% in the caudate nucleus to 6.3% in the putamen. A mean preclinical period of 5.6 +/- 3.2 years was calculated with symptom onset at a putaminal Ki threshold of 69% from controls. Assuming nonlinear progression kinetics, the required sample size to prove neuroprotection with the use of [F-18] fluorodopa PET was found to increase strongly with the preceding symptom duration of study subjects.Conclusion: These data suggest that the neurodegenerative process in PD follows a negative exponential course and slows down with increasing symptom duration, contradicting the long-latency hypothesis of PD.