Progression of nigrostriatal dysfunction in a parkin kindred:: an [18F] dopa PET and clinical study
Progression of nigrostriatal dysfunction in a parkin kindred:: an [18F] dopa PET and clinical study
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DOI：
10.1093/brain/awf237
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发表时间：
2002-10-01
期刊：
影响因子：
14.5
通讯作者：
Piccini, P
中科院分区：
文献类型：
--
作者：
Khan, NL;Brooks, DJ;Piccini, P
帕金森相关性帕金森综合征的分子和临床特征得到了很好的描述;然而，没有关于帕金森相关性疾病中多巴胺终末功能障碍进展的数据。我们已经使用[F-18]多巴PET系列研究一个家庭的成员与帕金森病发作谁是复合杂合子突变parkin基因，有一个外显子缺失和一个新的内含子剪接位点突变。4名患者进行了两次研究，间隔10年，以评估疾病进展。此外，我们还研究了5个无症状的家庭成员，其中4人携带单一帕金突变，1人具有正常基因型。两名携带者和一名基因型正常的个体有重复的[F-18]多巴PET。与一组具有与parkin组相似的基线壳核[F-18]多巴摄取和疾病严重程度的特发性帕金森病（IPD）患者相比，parkin组患者显示壳核[F-18]多巴摄取的损失显著较慢（P = 0.0008）。这些结果表明，帕金突变患者的疾病进展比IPD患者慢。无症状帕金携带者组也表现出明显的纹状体多巴胺能功能障碍，其中3人出现轻微的锥体外系体征。然而，两名携带者扫描了两次，显示在7年内没有进展。帕金森病患者的疾病进展速度较慢，这可能解释了这些年轻发作的帕金森综合征患者接近正常的寿命。
Molecular and clinical characterization of parkin-associated parkinsonism is well described; however, there are no data available on progression of dopamine terminal dysfunction in parkin-associated disease. We have used [F-18]dopa PET serially to study members of a family with young-onset parkinsonism who are compound heterozygous for mutations in the parkin gene, having an exonic deletion and a novel intronic splice site mutation. Four patients have been studied twice, 10 years apart, to assess disease progression. Additionally, we have studied five asymptomatic family members, four of whom carry a single parkin mutation and one individual who has a normal genotype. Two of the carriers and the individual with the normal genotype had repeat [F-18]dopa PET. The group of parkin patients showed a significantly slower loss of putamen [F-18]dopa uptake (P = 0.0008) compared with a group of idiopathic Parkinson's disease (IPD) patients who had baseline putamen [F-18]dopa uptake and disease severity similar to the parkin group. These results indicate that disease progression in patients with parkin mutations is slower than that of IPD patients. The group of asymptomatic parkin carriers also showed significant striatal dopaminergic dysfunction, and three of them developed subtle extrapyramidal signs. However, the two carriers scanned twice showed no progression over a 7-year period. The slower rate of disease progression in parkin patients may explain the near normal longevity of these patients with young onset parkinsonism.