de la Fuente-Fernández R, Lu J Q, Sossi V, Jivan S, Schulzer M, Holden J E, Lee C S, Ruth T J, Calne D B, Stoessl A J
Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, BC, Canada.
Ann Neurol. 2001 Mar;49(3):298-303. doi: 10.1002/ana.65.abs.
Motor fluctuations are a major disabling complication in the treatment of Parkinson's disease. To investigate whether such oscillations in mobility can be attributed to changes in the synaptic levels of dopamine, we studied prospectively patients in the early stages of Parkinson's disease with a follow-up after at least 3 years of levodopa treatment. At baseline, 3 positron emission tomography (PET) scans using [11C]raclopride before and after (1 hour and 4 hours) orally administered levodopa were performed on the same day for each patient. Patients who developed "wearing-off" fluctuations during the follow-up period had a different pattern of levodopa-induced changes in [11C]raclopride binding potential (BP) from that observed in patients who were still stable by the end of the follow-up. Thus, 1 hour post-levodopa the estimated increase in the synaptic level of dopamine was 3 times higher in fluctuators than in stable responders. By contrast, only stable responders maintained increased levels of synaptic dopamine in the PET scan performed after 4 hours. These results indicate that fluctuations in the synaptic concentration of dopamine precede clinically apparent "wearing-off" phenomena. The rapid increase in synaptic levels of dopamine observed in fluctuators suggests that increased dopamine turnover might play a relevant role in levodopa-related motor complications.
运动波动是帕金森病治疗中一种严重的致残性并发症。为了研究这种运动波动是否可归因于多巴胺突触水平的变化，我们对帕金森病早期患者进行了前瞻性研究，并在左旋多巴治疗至少3年后进行随访。在基线时，为每位患者在同一天进行3次正电子发射断层扫描（PET），使用[11C]雷氯必利，分别在口服左旋多巴前以及口服后1小时和4小时进行扫描。在随访期间出现“剂末”波动的患者，其左旋多巴诱导的[11C]雷氯必利结合电位（BP）变化模式与随访结束时仍保持稳定的患者不同。因此，左旋多巴给药后1小时，波动患者突触多巴胺水平的估计升高幅度比稳定反应者高3倍。相比之下，只有稳定反应者在4小时后进行的PET扫描中保持突触多巴胺水平升高。这些结果表明，多巴胺突触浓度的波动先于临床上明显的“剂末”现象出现。波动患者中观察到的突触多巴胺水平的快速升高表明，多巴胺周转增加可能在左旋多巴相关的运动并发症中起相关作用。
