Scherfler Christoph, Khan Naheed L, Pavese Nicola, Eunson Louise, Graham Elizabeth, Lees Andrew J, Quinn Niall P, Wood Nicholas W, Brooks David J, Piccini Paola P
MRC Clinical Science Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Brain. 2004 Jun;127(Pt 6):1332-42. doi: 10.1093/brain/awh150. Epub 2004 Apr 16.
To investigate striatal and cortical pre- and postsynaptic dopaminergic function in parkin-linked parkinsonism, 13 unrelated patients homozygous or compound heterozygous for parkin mutations were studied with [(18)F]dopa and [(11)C]raclopride (RAC) PET. Data were compared with a young-onset Parkinson's disease (YOPD) cohort, matched for age, disease severity and duration, but negative for parkin mutations. Significant changes in [(18)F]dopa uptake and RAC binding potential (BP) were localized in striatum using regions of interest (ROIs) and throughout the entire brain volume with statistical parametric mapping (SPM). As expected, both YOPD and parkin patients showed significant decreases in striatal [(18)F]dopa uptake; however, in parkin patients, additional reductions in caudate and midbrain were localized with SPM. The RAC-BP was significantly decreased in striatal, thalamic and cortical areas (temporal, orbito-frontal and parietal cortex) in parkin compared with YOPD patients. Our [(18)F]dopa PET findings suggest that, compared with YOPD, parkin disease is associated with more severe and widespread presynaptic dopaminergic deficits. The global decreases in D2 binding found in parkin compared with YOPD patients could be a direct consequence of the parkin genetic defect itself or a greater susceptibility to receptor downregulation following long-term dopaminergic agent exposure. Cortical reductions in D2 binding may contribute to the behavioural problems reported in parkin patients.
为研究帕金森病相关帕金森综合征中纹状体和皮质突触前及突触后多巴胺能功能，我们对13名携带帕金森病基因（parkin）突变的纯合子或复合杂合子无关患者进行了[¹⁸F]多巴和[¹¹C]雷氯必利（RAC）PET研究。将数据与一组年龄、疾病严重程度和病程相匹配但无parkin基因突变的早发性帕金森病（YOPD）队列进行比较。使用感兴趣区域（ROI）在纹状体中定位[¹⁸F]多巴摄取和RAC结合潜能（BP）的显著变化，并通过统计参数映射（SPM）在整个脑体积中进行定位。正如预期的那样，YOPD患者和parkin患者的纹状体[¹⁸F]多巴摄取均显著降低；然而，在parkin患者中，通过SPM发现尾状核和中脑有额外的降低。与YOPD患者相比，parkin患者的纹状体、丘脑和皮质区域（颞叶、眶额皮质和顶叶皮质）的RAC-BP显著降低。我们的[¹⁸F]多巴PET研究结果表明，与YOPD相比，parkin病与更严重和广泛的突触前多巴胺能缺陷有关。与YOPD患者相比，parkin患者中发现的D2结合的整体降低可能是parkin基因缺陷本身的直接后果，或者是长期接触多巴胺能药物后对受体下调的更大易感性。皮质D2结合的减少可能导致parkin患者报告的行为问题。
