STN STIMULATION--DA TRANSPORTERS & OUTCOME IN PARKINSON'

本研究的具体目的将包括用神经成像技术量化接受辅助丘脑下核（STN）刺激治疗的帕金森病患者多巴胺能神经系统张力的纵向变化。研究结果将与单纯接受苍白球切开术或常规药物治疗的患者进行比较。每一组的长期结果将通过神经心理学测试、由神经科研究人员管理的临床评定量表和反复测量多巴胺转运体浓度来评估。转运蛋白浓度将用一种获奖的锝-99m标记显像剂进行估计，这种显像剂可以准确地将帕金森病患者与匹配的对照组区分开来。适当的不对称可以在年轻的、最近被诊断患有哈密-帕金森氏症的患者中检测到。在每毫升的成本只有几美分的情况下，数据清楚地表明[Tc-99m]TRODAT-1的摄取值与患者和对照组中多巴胺部分介导的几种神经心理任务表现得分显著相关。该研究被设计为一项多组临床试验。在患者中，在手术前两周，盲法研究者将同时测量转运蛋白浓度和神经心理学测试表现，然后在接下来的三(3)年内每隔六(6)个月重复一次。在匹配的对照组中，同样的方案将每隔两周进行一次，每年一次，持续三年。全自动统计参数映射和严格的MRI共配准图像分析技术将用于将生理与行为联系起来，同时控制f9r衰老作为混杂协变量。由于几个原因，该结果可能具有临床相关性。帕金森氏症仍然是一个相对常见且具有潜在破坏性的问题。对某些患者来说，丘脑下核刺激似乎是一种特别有前途的方法。长期抑制从下丘脑投射的谷氨酰胺能神经元可能保护多巴胺能神经元，如果实际上不是拯救的话。虽然它的有效性已经得到了一些强有力的支持，但它并非没有风险，而且反映人脑对慢性丘脑下核刺激反应的相关生理学的客观测量尚未报道。这项研究将提供这些数据，同时追求开发一种更有效、更经济的方法来客观评估一种新疗法的结果的长期目标。

The specific aims Of this study will include quantifying longitudinal changes in the tone Of the dopaminergic nervous system with neuroimaging techniques in patients with Parkinson's disease who are treated with adjunctive subthalamic nucleus (STN) stimulation. The findings will be compared to outcome in patients treated with pallidotomy Or conventional medications alone. Long-term outcome in each of these groups will be assessed with neuropsychological tests, clinical rating scales administered by research neurologists, and repeated measurements of dopamine transporter concentrations. Transporter concentrations will be estimated with an award-winning, technetium-99m labeled imaging agent that can accurately distinguish patients with Parkinson's disease from matched controls. Appropriate asymmetries can be detected in young, recently diagnosed patients with Hami-Parkinson's. At a cost of only pennies per milliCurie, the data clearly demonstrate that the uptake values of [Tc-99m]TRODAT-1 are significantly related to several neuropsychological task performance scores that are known to be partially mediated by dopamine in both patients and controls. The study has been designed as a multi-arm clinical trial. In patients, simultaneous measurements of transporter concentrations and neuropsychological test performance will be performed by blinded investigators two weeks before surgery, and then repeated at six (6) month intervals over the next three (3) years. In matched controls, the same protocol will be performed at two-week intervals once each year for three years. Both fully automated statistical parametric mapping and rigorous MRI coregistration image analysis techniques will be used to correlate physiology with behavior while controlling f9r aging as a confounding covariate. The results may be clinically relevant for several reasons. Parkinson's disease remains a relatively common and potentially devastating problem. Subthalamic nucleus stimulation seems to be a particularly promising approach in some patients. Chronic inhibition of the glutaminergic neurons projecting from the subthalamus may protect, if not actually rescue, dopaminergic neurons. While there is already some strong support for its effectiveness, it is not risk-free, and an objective measure of relevant physiology that reflects the response of the human brain to chronic subthalamic nucleus stimulation has not been reported. This study will provide that data while pursuing a long-term goal of developing a more effective and economical method for objectively assessing the outcome of an new treatment.