Kempster Peter A
Monash Medical Centre, Clayton, Victoria, Australia.
BMJ Neurol Open. 2025 Sep 8;7(2):e001215. doi: 10.1136/bmjno-2025-001215. eCollection 2025.
Over the long term, Parkinson's disease (PD) appears to progress, in a linear fashion, at an annual rate of about 2% of the maximum motor disability score. This figure aligns quite well with pathological research on the rate that substantia nigra dopaminergic neurons are lost. An unexpected finding from cohort studies and clinical trials is that progression is twice as fast in prodromal PD, leading up to clinical diagnosis, and in recently diagnosed PD prior to the commencement of dopaminergic therapy. Levodopa initiation reduces motor disability by 40% of the pretreatment level. This benefit is composed of the short duration response, which is easily measured as the difference between and states, and the long duration response, which is comparable in size though not directly observable. Despite clinical impressions to the contrary, there is little evidence that the response to levodopa wanes over time or that axial motor deficits affecting speech, gait and balance become increasingly resistant to treatment. While not revealed by prospective longitudinal studies, the advanced PD phase, accompanied by visual hallucinations and cognitive decline, may show an exponential rate of change. Serial motor scale assessment, informed by a knowledge of symptomatic dopaminergic treatment effects, is probably still the best way to measure the underlying rate of progression of PD in clinical trials.
从长期来看,帕金森病(PD)似乎呈线性进展,每年的进展速度约为最大运动残疾评分的2%。这一数字与黑质多巴胺能神经元丢失率的病理学研究结果相当吻合。队列研究和临床试验的一个意外发现是,在临床诊断前的前驱期帕金森病以及多巴胺能治疗开始前最近诊断的帕金森病中,进展速度是原来的两倍。左旋多巴的起始治疗可使运动残疾程度降低至治疗前水平的40%。这种益处包括短期反应,可轻松测量为[具体状态1]和[具体状态2]之间的差异,以及长期反应,其大小相当但无法直接观察到。尽管临床印象相反,但几乎没有证据表明对左旋多巴的反应会随着时间减弱,或者影响言语、步态和平衡的轴性运动缺陷对治疗的抵抗性会越来越强。虽然前瞻性纵向研究未揭示这一点,但伴有视幻觉和认知衰退的晚期帕金森病阶段可能呈现指数级变化。结合对有症状的多巴胺能治疗效果的了解进行连续运动量表评估,可能仍然是在临床试验中衡量帕金森病潜在进展速度的最佳方法。