STN STIMULATION--DA TRANSPORTERS & OUTCOME IN PARKINSON'

这项研究的具体目标将包括使用神经成像技术量化帕金森病患者在接受辅助丘脑底核(STN)刺激治疗后多巴胺能神经系统音调的纵向变化。这一发现将与单纯接受苍白球切开术或常规药物治疗的患者的结果进行比较。每一组的长期结果将通过神经心理测试、研究神经科医生实施的临床评定量表和重复测量多巴胺转运体浓度来评估。转运体浓度将使用获奖的~(99)Tm标记显像剂进行估计，该显像剂可以准确地区分帕金森氏病患者和匹配的对照组。在年轻的、最近确诊的哈米帕金森氏症患者中可以检测到适当的不对称性。以每毫居里仅几美分的成本，数据清楚地表明，[TC-99m]TRODAT-1的摄取值与几个神经心理学任务表现评分显著相关，这些评分在患者和对照组中都被认为是部分受多巴胺调节的。这项研究被设计为一项多臂临床试验。在患者中，转运蛋白浓度和神经心理测试性能的同步测量将由盲目调查人员在手术前两周进行，然后在接下来的三(3)年中每隔6个月重复一次。在配对的对照组中，同样的方案将在三年内每年一次，每两周执行一次。全自动统计参数映射和严格的磁共振图像配准图像分析技术将被用于将生理和行为关联起来，同时将F9R老化作为一个混杂的协变量进行控制。出于几个原因，这一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。在某些患者中，丘脑底核刺激似乎是一种特别有希望的方法。长期抑制从丘脑下部投射的谷氨酸能神经元可能会保护多巴胺能神经元，如果不是实际上拯救的话。虽然已经有一些强有力的支持其有效性，但它并不是无风险的，反映人类大脑对慢性丘脑底核刺激反应的相关生理学的客观指标尚未见报道。这项研究将提供这些数据，同时追求开发一种更有效和更经济的方法来客观评估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.