Brooks D J
MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Trends Neurosci. 2000 Oct;23(10 Suppl):S101-8. doi: 10.1016/s1471-1931(00)00016-1.
Parkinson's disease (PD) patients with motor complications show a greater reduction in putamen [18F]dopa uptake on positron emission tomography (PET) compared with sustained responders to L-dopa, although individual ranges overlap considerably. This implies that, although loss of putamen dopamine storage predisposes motor complications in PD, it cannot be the only factor determining timing of onset. Additional PET studies suggest that loss of striatal dopamine storage capacity along with pulsatile exposure to exogenous L-dopa results in pathologically raised synaptic dopamine levels and deranged basal ganglia opioid transmission.This, rather than altered dopamine receptor binding, then causes inappropriate overactivity of basal ganglia-frontal projections, resulting in breakthrough involuntary movements.
与对左旋多巴持续有反应的患者相比,患有运动并发症的帕金森病(PD)患者在正电子发射断层扫描(PET)上壳核[18F]多巴摄取量的降低更为明显,尽管个体范围有相当大的重叠。这意味着,虽然壳核多巴胺储存的丧失易使PD患者出现运动并发症,但它不可能是决定发病时间的唯一因素。其他PET研究表明,纹状体多巴胺储存能力的丧失以及对外源性左旋多巴的脉冲式暴露导致突触多巴胺水平病理性升高和基底神经节阿片类物质传递紊乱。这而非多巴胺受体结合的改变,进而导致基底神经节-额叶投射的不适当过度活跃,从而引发突破性不自主运动。