课件：瑞金医院帕金森病.ppt

* This slide shows the changes in the basal ganglia cortical circuitry after substantia nigra compacta damage. The main features are the reduced dopaminergic impulses from substantia nigra to the striatum, enhanced excitation of the subthalamic nucleus and the globus pallidus internus, and increased inhibition of the thalamus. Thus surgical lesion or electrode implantation to facilitate a depolarizing conduction block of subthalamic nucleus and globus pallidus internus would produce symptomatic benefit in Parkinson’s disease. * 目前认为帕金森病是因纹状体内多巴胺缺乏导致的，主要病变在黑质－纹状体多巴胺能神经通路。正常状态下，中枢神经系统中的乙酰胆碱及多巴胺两种系统的作用保持平衡，而在帕金森病的患者中，由于多巴胺的减少，使乙酰胆碱系统的作用相对占优势，从而破坏了神经生化反应的平衡。 * Levodopa: Advantages After more than thirty years of clinical use, levodopa remains the cornerstone treatment of PD. Compared with the pre-levodopa era, the amount of disability and mortality associated with PD is markedly reduced, and levodopa has had a major impact on the natural history of PD. The life expectancy with PD now approaches that of the normal population. Levodopa remains the most effective symptomatic PD treatment. Consequently, regardless of where levodopa is administered in the course of therapy, all patients will, at some point, require levodopa therapy. Importantly, levodopa continues to provide antiparkinsonian benefits over the entire course of the disease. Decades of clinical experience with levodopa has shown it to be generally well tolerated. Agid et al. Lancet 2002; 360: 575. Agid et al. Movement Disord 1999; 14: 911–913. Hoehn. Neurological Clin 1992; 10: 331–339. Olanow et al. Neurology 2001; 56: S1–86. * 下面我们来关注一下帕金森病的病程进展。如图所示，在疾病初发后到5年左右的一段时间内，患者会经历一段“蜜月期”，在这一时期内，传统的药物治疗能够获得比较满意的疗效；但在“蜜月期”过后，由于长期应用抗帕金森药物，患者在发病5到12年期间将会出现不同程度的药物导致的运动并发症；病程进展到12年后患者出现认知功能障碍，部分患者在发病15年后死亡。 * Long-term challenges: Changes in levodopa response In the early stages of PD there is a large therapeutic window, and the response to levodopa is excellent. The benefits of levodopa therapy persist for many