Rodriguez-Oroz Maria C, Jahanshahi Marjan, Krack Paul, Litvan Irene, Macias Raúl, Bezard Erwan, Obeso José A
Department of Neurology, Clinica Universitaria and Medical School and Neuroscience, CIMA, University of Navarra, Pamplona, Spain.
Lancet Neurol. 2009 Dec;8(12):1128-39. doi: 10.1016/S1474-4422(09)70293-5.
A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
帕金森病（PD）患者的多巴胺能缺乏会导致运动、行为、学习和情绪异常。主要运动特征（即震颤、僵硬和运动不能）与壳核后部和运动回路中多巴胺缺乏有关。运动减少和运动迟缓可能有双重解剖功能基础：运动减少由脑干机制介导，运动迟缓由皮质机制介导。PD的经典病理生理模型（即苍白球内侧部和黑质网状部活动亢进）无法解释僵硬和震颤，这可能是由初级运动皮层活动变化引起的。执行功能（即计划和解决问题）在早期PD中也会受损，但通常在临床上未被注意到。这些损害与尾状核中多巴胺缺乏以及联合和其他非运动回路功能障碍有关。冷漠、焦虑和抑郁是未经治疗的PD的主要精神表现，这可能是由腹侧纹状体多巴胺能缺乏以及血清素和去甲肾上腺素耗竭引起的。在本综述中，我们讨论了帕金森状态早期与多巴胺能缺乏相关的运动、认知和精神表现以及涉及的不同回路，并提出了不同的机制来解释PD诊断时广泛的临床症状。
