Movement Disorders Section, Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Neurotherapeutics. 2020 Oct;17(4):1331-1338. doi: 10.1007/s13311-020-00924-4. Epub 2020 Sep 15.
Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the middle stage of the disorder pathologically, when 50% or more of the dopaminergic neurons have degenerated in the substantia nigra. This discrepancy between the early stage clinically and that pathologically has, in part, spurred the debate as to when it is best to initiate symptomatic therapy. The most well-studied monotherapeutic agents for PD in its early course include levodopa (the cornerstone of PD therapy), dopamine agonists, and monoamine oxidase inhibitors (MAOIs). With several options for initiating pharmacologic therapy, along with the heterogenous presentation of the disorder, an individualized approach is warranted. Careful deliberation must be done to optimize risk reduction while providing effective symptom control, taking the chronological age, comorbidities, social and financial disposition, work status, and both immediate- and long-term goals into consideration. Generally, treatment can be delayed in patients with mild symptoms and minimal functional impairment at any age. If treatment must be initiated, dopamine agonists and monoamine oxidase type B inhibitors can be used, especially in younger patients with milder disease. However, for older patients, those with moderate to severe PD symptoms, regardless of age, or for patients with greater comorbidities, levodopa generally remains the better choice. Eventually, regardless of initial therapy, studies have shown that most will eventually require levodopa therapy when symptoms become more disabling.
帕金森病（PD）是一种进行性神经退行性疾病，经历六个病理阶段。最早的临床症状出现在疾病的中期，此时黑质中 50%或更多的多巴胺能神经元已经退化。这种临床早期和病理晚期之间的差异，在一定程度上引发了关于何时开始症状治疗最佳的争论。在疾病的早期，研究最充分的 PD 单药治疗包括左旋多巴（PD 治疗的基石）、多巴胺激动剂和单胺氧化酶抑制剂（MAOIs）。有几种药物可以开始进行药物治疗，再加上疾病的异质性表现，因此需要个体化治疗。必须仔细考虑，在提供有效的症状控制的同时，尽量降低风险，同时考虑患者的年龄、合并症、社会和经济状况、工作状况以及近期和长期目标。一般来说，在任何年龄，只要患者有轻度症状和最小的功能障碍，可以延迟治疗。如果必须开始治疗，可以使用多巴胺激动剂和单胺氧化酶 B 抑制剂，特别是对于轻度疾病的年轻患者。然而，对于老年患者、中重度 PD 症状的患者，无论年龄大小，或对于合并症较多的患者，左旋多巴通常仍然是更好的选择。最终，无论初始治疗如何，研究表明，当症状变得更加致残时，大多数患者最终都需要左旋多巴治疗。
