Functional Brain Imaging in Glucocerebrosidase Mutation Carriers With and Without Parkinsonism
Functional Brain Imaging in Glucocerebrosidase Mutation Carriers With and Without Parkinsonism
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DOI：
10.1002/mds.23213
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发表时间：
2010-09-15
影响因子：
8.6
通讯作者：
Miyajima, Hiroaki
中科院分区：
文献类型：
--
作者：
Kono, Satoshi;Ouchi, Yasuomi;Miyajima, Hiroaki
葡萄糖脑苷酶基因（GBA）的突变增加了帕金森病的风险，并且还与疾病的早期发病和动态帕金森表型有关。为了研究这种疾病的潜在发病机制，我们使用正电子发射断层扫描（PET）评估了伴有和不伴有帕金森病的GBA突变携带者的脑代谢。[(18)F]采用三维立体定向表面投影分析方法-氟脱氧葡萄糖(FDG)-PET测量了1例帕金森病加戈谢病（GD）患者和5例GBA杂合突变患者（包括3例帕金森病患者和3例无症状携带者）与10例同年龄段健康对照者的脑葡萄糖代谢率（CMRGlc）。用[(11)C] cft和[(11)C] raclopride-PET研究多巴胺能神经元的活性。所有GBA突变携带者在补充运动区（SMA）表现出显著的CMRGlc下降。帕金森病患者在顶枕皮层表现出额外的低代谢。无症状携带者的CFT和raclopride PET图像显示，壳核的CFT结合在正常范围内，尾状核的CFT结合明显增加，而纹状体的raclopride结合在正常范围内。晚期帕金森病携带者在纹状体中显示CFT结合减少和raclopride结合增加。SMA中CMRGlc的降低是GBA突变携带者的特征。因此，当携带者表现出帕金森时，SMA的低代谢可能与GBA突变相关的帕金森病的临床特征有关。(C) 2010运动障碍学会
Mutations in the glucocerebrosidase gene (GBA) increase the risk for Parkinson's disease and are also associated with an earlier onset of the disease and an akinetic parkinsonian phenotype. To investigate the underlying pathogenesis of this condition, we assessed cerebral metabolism using positron emission tomography (PET) in GBA mutation carriers with and without parkinsonism. [(18)F]-fluorodeoxyglucose (FDG)-PET using a three-dimensional stereotactic surface projection analysis was used to measure the cerebral metabolic rates of glucose (CMRGlc) in a patient with parkinsonism and Gaucher disease (GD) and five subjects with a heterozygous GBA mutation, including three patients with parkinsonism and three asymptomatic carriers in comparison to 10 healthy controls in the same age range. Dopaminergic neuronal activity was investigated using [(11)C] CFT-and [(11)C] raclopride-PET. All GBA mutation carriers displayed a significant CMRGlc decrease in the supplemental motor area (SMA). The carriers with parkinsonism showed additional hypometabolism in the parietooccipital cortices. The CFT and raclopride PET images in the asymptomatic carriers demonstrated the CFT binding to be within normal values in the putamen and a significant increase was observed in the caudate nucleus while raclopride binding in the striatum was in the normal range. An advanced parkinsonian carrier showed decreased CFT binding and increased raclopride binding in the striatum. The decreased CMRGlc in the SMA was characteristic of the GBA mutation carriers. The hypometabolism in the SMA may, therefore, be involved in the clinical characteristics of parkinsonism associated with GBA mutations when the carriers manifest parkinsonism. (C) 2010 Movement Disorder Society