Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
Department of Neurology, Christian-Albrechts-University of Kiel, Kiel, Germany.
J Parkinsons Dis. 2021;11(4):1677-1687. doi: 10.3233/JPD-212761.
We have hypothesized that Parkinson's disease (PD) comprises two subtypes. Brain-first, where pathogenic α-synuclein initially forms unilaterally in one hemisphere leading to asymmetric nigrostriatal degeneration, and body-first with initial enteric pathology, which spreads through overlapping vagal innervation leading to more symmetric brainstem involvement and hence more symmetric nigrostriatal degeneration. Isolated REM sleep behaviour disorder has been identified as a strong marker of the body-first type.
To analyse striatal asymmetry in [18F]FDOPA PET and [123I]FP-CIT DaT SPECT data from iRBD patients, de novo PD patients with RBD (PD+RBD) and de novo PD patients without RBD (PD-RBD). These groups were defined as prodromal body-first, de novo body-first, and de novo brain-first, respectively.
We included [18F]FDOPA PET scans from 21 iRBD patients, 11 de novo PD+RBD, 22 de novo PD-RBD, and 18 controls subjects. Also, [123I]FP-CIT DaT SPECT data from iRBD and de novo PD patients with unknown RBD status from the PPPMI dataset was analysed. Lowest putamen specific binding ratio and putamen asymmetry index (AI) was defined.
Nigrostriatal degeneration was significantly more symmetric in patients with RBD versus patients without RBD or with unknown RBD status in both FDOPA (p = 0.001) and DaT SPECT (p = 0.001) datasets.
iRBD subjects and de novo PD+RBD patients present with significantly more symmetric nigrostriatal dopaminergic degeneration compared to de novo PD-RBD patients. The results support the hypothesis that body-first PD is characterized by more symmetric distribution most likely due to more symmetric propagation of pathogenic α-synuclein compared to brain-first PD.
我们假设帕金森病（PD）包括两种亚型。一种是脑先型，其中致病性α-突触核蛋白最初在一个半球单侧形成，导致不对称的黑质纹状体变性；另一种是体先型，最初存在肠道病理学，通过重叠的迷走神经支配传播，导致更对称的脑干受累，从而导致更对称的黑质纹状体变性。孤立性 REM 睡眠行为障碍已被确定为体先型的一个强烈标志物。
分析 iRBD 患者、有 REM 睡眠行为障碍的新发 PD 患者（PD+RBD）和无 REM 睡眠行为障碍的新发 PD 患者（PD-RBD）的[18F]FDOPA PET 和[123I]FP-CIT DaT SPECT 数据中的纹状体不对称性。这些组分别定义为前驱体先型、新发体先型和新发脑先型。
我们纳入了 21 名 iRBD 患者、11 名新发 PD+RBD、22 名新发 PD-RBD 和 18 名对照受试者的[18F]FDOPA PET 扫描。此外，还分析了 PPPMI 数据集的 iRBD 和新发 PD 患者中未知 RBD 状态的[123I]FP-CIT DaT SPECT 数据。定义了最低壳核特异性结合比和壳核不对称指数（AI）。
在 FDOPA（p=0.001）和 DaT SPECT（p=0.001）数据集，RBD 患者的黑质纹状体变性明显比无 RBD 患者或未知 RBD 状态的患者更对称。
iRBD 患者和新发 PD+RBD 患者的黑质纹状体多巴胺能变性明显比新发 PD-RBD 患者更对称。结果支持这样一种假设，即体先型 PD 的特征是更对称的分布，这很可能是由于致病性α-突触核蛋白的更对称传播，与脑先型 PD 相比。
