Unité de Neuroimagerie Fonctionelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Quebec, Canada.
PLoS One. 2009 Dec 10;4(12):e8247. doi: 10.1371/journal.pone.0008247.
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia). Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC) matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution) and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3) in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.
特发性帕金森病(PD)是一种神经退行性疾病,其特征为多巴胺能依赖的皮质-基底节环路功能障碍,并根据运动症状(震颤和/或僵硬和运动迟缓)进行诊断。尸检研究倾向于表明,黑质中的多巴胺能神经元的破坏构成了更广泛的神经退行性过程的中间步骤,而不是帕金森病的独特特征,因为存在从延髓/脑桥被盖到脑桥的一致进展模式。迄今为止,神经影像学技术还无法描述 PD 的无症状前阶段。然而,如果存在这样一种有规律的神经退行性模式,即使在疾病的早期阶段,脑干也会发现一致的损伤。我们招募了 23 名 Hoenn 和 Yahr 疾病 I 至 II 期的 PD 患者和 18 名年龄匹配的健康对照者(HC)。采集 T1 加权解剖扫描(MPRAGE,分辨率为 1mm3),并使用优化的 VBM 方案进行分析,以在没有空间先验的情况下检测白质和灰质体积减少。当将 HC 组与 PD 组进行比较时,脑干中单个簇在统计学上存在差异(p<0.05,假发现率校正,4287mm3),位于脑桥和延髓之间。本研究提供了体内证据,表明脑干损伤可能是 PD 神经病理学的第一个可识别阶段,并且随着其他因素的识别,这可能有助于未来的早期诊断。这种损伤也可以解释 PD 中的一些非运动症状,这些症状通常在诊断之前出现,例如自主功能障碍和睡眠障碍。