PDF(Pubmed)
Abstract：
While early-onset Parkinson\'s disease (EOPD) caused by mutations in the parkin gene (PRKN) tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between PRKN-EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with PRKN-EOPD and 16 with GU-EOPD who accepted both 11C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose PET were enrolled. The 11C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with PRKN-EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with PRKN-EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in patients with GU-EOPD only. Patients with PRKN-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with PRKN-EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, PRKN-EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in PRKN-EOPD.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s43657-022-00077-8.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s43657-022-00077-8.
摘要：
虽然由parkin基因突变（PRKN）引起的早发性帕金森病（EOPD）与遗传不确定（GU）-EOPD相比，往往具有相对良性的病程，确切的潜在机制仍然难以捉摸。我们旨在通过多巴胺转运蛋白（DAT）和葡萄糖代谢正电子发射断层扫描（PET）成像来搜索PRKN-EOPD和GU-EOPD之间的差异。纳入12名PRKN-EOPD患者和16名GU-EOPD患者，他们同时接受了11C-2b-碳甲氧基-3b-（4-三甲基锡烷基苯基）托烷（11C-CFT）和18F-氟脱氧葡萄糖PET。11C-CFT吸收在区域和体素水平上进行了分析，而葡萄糖代谢以体素方式评估。DAT与糖代谢显像的相关性,DAT成像和临床严重程度，以及糖代谢成像和临床严重程度进行了探讨。PRKN-EOPD患者的后壳核的临床症状和DAT结合模式高度对称，PRKN-EOPD患者的同侧壳核多巴胺能功能障碍比GU-EOPD严重。同时,DAT结合仅与GU-EOPD患者的运动功能障碍严重程度相关.PRKN-EOPD患者显示对侧内侧额回（辅助运动区（SMA））葡萄糖代谢增加，对侧黑质,对侧丘脑,和对侧小脑。值得注意的是,对侧内侧额回的葡萄糖代谢活性与双侧壳核的局部DAT结合呈负相关。PRKN-EOPD患者双侧壳核内代谢连接增强，同侧中央旁和中央前小叶，和同侧SMA。总的来说，与GU-EOPD相比，PRKN-EOPD的特点是对称，更严重的多巴胺能功能障碍和相对增加的葡萄糖代谢。同时,具有升高的葡萄糖代谢和增强的连通性的SMA可能在PRKN-EOPD中起补偿机制的作用。
UNASSIGNED：在线版本包含补充材料，可在10.1007/s43657-022-00077-8获得。
UNASSIGNED：在线版本包含补充材料，可在10.1007/s43657-022-00077-8获得。
