Schröter Nils, Rijntjes Michel, Urbach Horst, Weiller Cornelius, Treppner Martin, Kellner Elias, Jost Wolfgang H, Sajonz Bastian E A, Reisert Marco, Hosp Jonas A, Rau Alexander
Department of Neurology and Clinical Neuroscience, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Neuroradiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
NPJ Parkinsons Dis. 2022 Oct 14;8(1):132. doi: 10.1038/s41531-022-00401-z.
The extent to which the degeneration of the substantia nigra (SN) and putamen each contribute to motor impairment in Parkinson's disease (PD) is unclear, as they are usually investigated using different imaging modalities. To examine the pathophysiological significance of the SN and putamen in both motor impairment and the levodopa response in PD using diffusion microstructure imaging (DMI). In this monocentric retrospective cross-sectional study, DMI parameters from 108 patients with PD and 35 healthy controls (HC) were analyzed using a voxel- and region-based approach. Linear models were applied to investigate the association between individual DMI parameters and Movement Disorder Society Unified Parkinson's Disease Rating Scale-Part 3 performance in ON- and OFF-states, as well as the levodopa response, controlling for age and sex. Voxel- and region-based group comparisons of DMI parameters between PD and HC revealed significant differences in the SN and putamen. In PD, a poorer MDS-UPDRS-III performance in the ON-state was associated with increased free fluid in the SN (b-weight = 65.79, p = 0.004) and putamen (b-weight = 86.00, p = 0.006), and contrariwise with the demise of cells in both structures. The levodopa response was inversely associated with free fluid both in the SN (b-weight = -83.61, p = 0.009) and putamen (b-weight = -176.56, p < 0.001). Interestingly, when the two structures were assessed together, the integrity of the putamen, but not the SN, served as a predictor for the levodopa response (b-weight = -158.03, p < 0.001). Structural alterations in the SN and putamen can be measured by diffusion microstructure imaging in PD. They are associated with poorer motor performance in the ON-state, as well as a reduced response to levodopa. While both nigral and putaminal integrity are required for good performance in the ON-state, it is putaminal integrity alone that determines the levodopa response. Therefore, the structural integrity of the putamen is crucial for the improvement of motor symptoms to dopaminergic medication, and might therefore serve as a promising biomarker for motor staging.
黑质（SN）和壳核各自对帕金森病（PD）运动功能障碍的影响程度尚不清楚，因为它们通常使用不同的成像方式进行研究。本研究旨在使用扩散微观结构成像（DMI）来探究SN和壳核在PD运动功能障碍及左旋多巴反应中的病理生理意义。在这项单中心回顾性横断面研究中，采用基于体素和区域的方法分析了108例PD患者和35名健康对照（HC）的DMI参数。应用线性模型研究个体DMI参数与运动障碍协会统一帕金森病评定量表第3部分在开期和关期表现以及左旋多巴反应之间的关联，并对年龄和性别进行控制。基于体素和区域的PD与HC之间DMI参数的组间比较显示，SN和壳核存在显著差异。在PD中，开期较差的MDS-UPDRS-III表现与SN（b值 = 65.79，p = 0.004）和壳核（b值 = 86.00，p = 0.00）中自由液体增加相关，反之与这两个结构中细胞的减少相关。左旋多巴反应与SN（b值 = -83.61，p = 0.009）和壳核（b值 = -176.56，p < 0.001）中的自由液体均呈负相关。有趣的是，当同时评估这两个结构时，壳核而非SN的完整性可作为左旋多巴反应的预测指标（b值 = -158.03，p < 0.001）。PD中SN和壳核的结构改变可通过扩散微观结构成像来测量。它们与开期较差的运动表现以及对左旋多巴反应降低相关。虽然在开期良好表现需要黑质和壳核的完整性，但仅壳核的完整性决定左旋多巴反应。因此，壳核的结构完整性对于多巴胺能药物改善运动症状至关重要，因此可能作为运动分期的一个有前景的生物标志物。
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