Prince of Wales Medical Research Institute, University of New South Wales, Randwick, Australia.
Mov Disord. 2009 Oct 30;24(14):2128-35. doi: 10.1002/mds.22747.
To determine whether variable thalamic degeneration in Parkinson's disease (PD) contributes to less drug responsive clinical features. Formalin-fixed thalami from longitudinally followed patients with PD and early dystonia (N = 6), early falls (N = 5) or no dystonia or falls (N = 6) and age-matched controls without neuropathology (N = 10) were serially sectioned, stained, and analyzed. Neurons in the centromedian parafascicular (CM-Pf) nucleus were quantified using the optical disector method and analysis of variance with post hoc testing used to determine variability in neurodegeneration between groups. Patients with PD were confirmed to have significant neurodegeneration in the CM-Pf complex, with no difference in the degree of neurodegeneration between patients with PD with early falls compared with patients with no history of falls or dystonia. In contrast, patients with PD with early dystonia had significantly less neurodegeneration of the CM but not the Pf than patients without this feature. Preservation of the CM in patients with PD with early dystonia would result in a relative increase in CM activity through the direct basal ganglia pathway and increased primary motor cortex activity. Overall this data provides evidence for pathway-specific neurodegeneration as an underlying feature of the clinical variability observed in patients with PD.
为了确定帕金森病(PD)患者丘脑变性的可变性是否导致药物反应性临床特征减少。从纵向随访的 PD 患者和早期肌张力障碍(N=6)、早期跌倒(N=5)或无肌张力障碍或跌倒(N=6)以及年龄匹配无神经病理学对照(N=10)中获取福尔马林固定的丘脑,进行连续切片、染色和分析。使用光学分割器方法对中央旁正中(CM-Pf)核中的神经元进行定量,并使用方差分析和事后检验来确定组间神经退行性变的变异性。PD 患者的 CM-Pf 复合体确实存在明显的神经退行性变,与无跌倒或肌张力障碍病史的患者相比,早期跌倒的 PD 患者的神经退行性变程度没有差异。相比之下,与无此特征的患者相比,早期肌张力障碍的 PD 患者的 CM 神经退行性变明显减少,但 Pf 没有。在早期有肌张力障碍的 PD 患者中,CM 的保留将导致通过直接基底节途径增加 CM 活动,并增加初级运动皮层活动。总的来说,这些数据为特定途径的神经退行性变作为 PD 患者观察到的临床变异性的潜在特征提供了证据。