Clissold Benjamin G, McColl Craig D, Reardon Katrina R, Shiff Mark, Kempster Peter A
Neurosciences Department, Monash Medical Centre, Melbourne, Australia.
Mov Disord. 2006 Dec;21(12):2116-21. doi: 10.1002/mds.21126.
In this prospective study of 34 patients with Parkinson's disease, measurements of the short duration levodopa motor response have been performed in defined off states at 3 yearly intervals over a mean period of 11.4 years from the point of commencement of levodopa treatment. Twenty-two patients were still available for study; 10 had died and 2 were lost to follow-up. The levodopa motor response amplitude increases over the first 5 years of treatment, and thereafter, on and off scores worsen in parallel with conservation of the response. Patients who developed motor fluctuations within the first 5 years of treatment had, on average, a stronger response to levodopa with significantly better on phase motor function (P = 0.003). Although the proportion of "midline" motor disability (affecting gait, balance, and cranial motor function) increases with time, these deficits do not actually become unresponsive to levodopa. Patients who developed dementia had a significantly more rapid decline in motor function. The latest graph of serial scores for the whole cohort shows an upward curving or exponential increase in motor disability after the first decade of treatment. Applying a notional untreated disability line to this graph--an estimate of the disability that would have accrued if drugs had never been given--we suggest that the long-duration response to levodopa eventually runs down with disease progression.
在这项针对34例帕金森病患者的前瞻性研究中，从左旋多巴治疗开始起，在长达11.4年的平均时间里，每隔3年在明确的“关”状态下对左旋多巴的短期运动反应进行测量。22例患者仍可供研究；10例患者死亡，2例失访。左旋多巴运动反应幅度在治疗的前5年增加，此后，“开”和“关”状态的评分随着反应的维持而平行恶化。在治疗的前5年内出现运动波动的患者，平均而言，对左旋多巴的反应更强，“开”期运动功能明显更好（P = 0.003）。尽管“中线”运动功能障碍（影响步态、平衡和颅部运动功能）的比例随时间增加，但这些功能障碍实际上对左旋多巴并非无反应。出现痴呆的患者运动功能下降明显更快。整个队列的系列评分最新图表显示，治疗第一个十年后运动功能障碍呈向上弯曲或指数增长。将一条假设的未治疗时的功能障碍线应用于此图表（这是对如果从未给予药物可能出现的功能障碍的估计），我们认为左旋多巴的长期反应最终会随着疾病进展而降低。
