Department of Neurology, H2-225, Academic Medical Center, University of Amsterdam, PO Box 22660, Amsterdam 1100 DD, The Netherlands.
EJNMMI Res. 2013 Jun 5;3(1):44. doi: 10.1186/2191-219X-3-44.
Although the treatment of Parkinson's disease (PD) is very effective, in the course of the disease, 40% to 60% of patients develop dyskinesias. The pathophysiology of dyskinesias is still unclear. Results of preclinical research suggest that uptake and uncontrolled release of dopamine by serotonergic neurons is an important factor. Based on this model, we hypothesized that dyskinesias will develop predominantly in PD patients with a relatively preserved serotonergic system.
Between 1995 and 1998, 50 patients with early-stage untreated PD, diagnosed according to clinical criteria, and reduced striatal [123I]β-carboxymethyoxy-3-beta-(4-iodophenyl) tropane (CIT) single-photon emission computed tomography (SPECT) binding were recruited. To test our hypothesis, we retrospectively assessed baseline [123I]β-CIT SPECT scans for striatal dopamine transporter (DAT) and midbrain serotonin transporter (SERT) availability as well as the SERT-to-DAT ratios. We compared these data between patients that developed dyskinesias and patients that did not develop dyskinesias during a mean follow-up of 14.2 years.
Approximately half of the PD patients developed dyskinesias. No differences in baseline [123I]β-CIT DAT availability, SERT availability, or SERT-to-DAT ratios were found between the dyskinetic and non-dyskinetic group. The development of dyskinesias was most strongly associated with the age of onset (P = 0.002).
SERT-to-DAT ratios in early-stage untreated PD do not correlate with the future development of dyskinesias. However, our study does not exclude the possibility that SERT-to-DAT ratios increase with disease progression in patients that develop dyskinesias because of a slower rate of degeneration of the serotonergic system.
尽管帕金森病（PD）的治疗非常有效，但在疾病过程中，40%至 60%的患者会出现运动障碍。运动障碍的病理生理学仍不清楚。临床前研究结果表明，5-羟色胺能神经元对多巴胺的摄取和不受控制的释放是一个重要因素。基于该模型，我们假设运动障碍将主要发生在多巴胺能系统相对保留的 PD 患者中。
1995 年至 1998 年间，我们招募了 50 名未经治疗的早期 PD 患者，这些患者根据临床标准诊断，并进行了纹状体[123I]β-羧甲氧基-3-β-（4-碘苯基）托烷（CIT）单光子发射计算机断层扫描（SPECT）结合。为了验证我们的假设，我们回顾性评估了基线[123I]β-CIT SPECT 扫描以获取纹状体多巴胺转运体（DAT）和中脑 5-羟色胺转运体（SERT）的可用性以及 SERT-to-DAT 比值。我们将这些数据与在平均 14.2 年的随访期间出现运动障碍和未出现运动障碍的患者进行了比较。
大约一半的 PD 患者出现了运动障碍。在运动障碍组和非运动障碍组之间，基线[123I]β-CIT DAT 可用性、SERT 可用性或 SERT-to-DAT 比值均无差异。运动障碍的发生与发病年龄（P=0.002）关系最为密切。
在未经治疗的早期 PD 中，SERT-to-DAT 比值与未来运动障碍的发展无关。然而，我们的研究并不排除 SERT-to-DAT 比值随着出现运动障碍的患者疾病进展而增加的可能性，因为 5-羟色胺能系统的退化速度较慢。
