Service de neurologie et centre de référence atrophie multisystématisée, CHU de Bordeaux, avenue Magellan, Pessac cedex, France.
Rev Neurol (Paris). 2012 Nov;168(11):809-14. doi: 10.1016/j.neurol.2012.07.004. Epub 2012 Sep 13.
Cardinal motor features of Parkinson's disease (PD) appear when about half of the nigral dopamine neurons have disappeared. Based on extrapolations from post-mortem and imaging studies, the delay between the onset of dopamine denervation and the appearance of motor signs ranges from 5 to 20years. According to Braak and co-workers, motor symptoms only appear at stage III of PD, while the neurodegenerative process begins earlier in the olfactory bulb and lower brain stem. In addition to the cardinal motor features, non-motor signs are increasingly being recognized in PD. Some of them, mainly olfactory disturbances, rapid-eye-movement sleep behaviour disorder and autonomic dysfunction, are already present in the early disease stages and may precede the onset of motor signs by up to four decades. These non-motor signs are related to widespread extranigral and even extracerebral degeneration, and have been considered risk factors for many years. Indeed, recent evidence suggests that they may be prodromal manifestations of PD. From the perspective of future disease-modifying or neuroprotective treatments, combining prodromal non-motor signs and paraclinical investigations may help to further develop reliable tools for early diagnosis of PD before the onset of its cardinal motor features.
帕金森病（PD）的主要运动特征出现在大约一半黑质多巴胺神经元消失后。根据死后和影像学研究的推断，多巴胺神经支配丧失和运动症状出现之间的延迟时间范围为 5 到 20 年。根据 Braak 及其同事的研究，运动症状仅出现在 PD 的第三阶段，而神经退行性过程在嗅球和下脑干中更早开始。除了主要的运动特征外，PD 中越来越多地认识到非运动症状。其中一些，主要是嗅觉障碍、快速眼动睡眠行为障碍和自主神经功能障碍，已经存在于疾病早期阶段，并且可能在运动症状出现前长达四十年。这些非运动症状与广泛的非黑质甚至脑外退化有关，多年来一直被认为是危险因素。事实上，最近的证据表明，它们可能是 PD 的前驱表现。从未来疾病修饰或神经保护治疗的角度来看，结合前驱非运动症状和临床前研究，可能有助于在 PD 主要运动特征出现之前，进一步开发可靠的早期诊断 PD 的工具。
