Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear palsy has been assessed using MRI. Degeneration of white matter tracts is evident with diffusion tensor imaging and PET methods have been used to assess brain metabolism or presence of tau protein deposits. Patients with progressive supranuclear palsy present with a variety of clinical syndromes; however early onset of gait impairments and postural instability are common features. In this study we assessed the relationship between multimodal imaging biomarkers (i.e., MRI atrophy, white matter tracts degeneration, flortaucipir-PET uptake) and laboratory-based measures of gait and balance abnormalities in a cohort of nineteen patients with progressive supranuclear palsy, using univariate and multivariate statistical analyses. The PSP rating scale and its gait midline sub-score were strongly correlated to gait abnormalities but not to postural imbalance. Principal component analysis on gait variables identified velocity, stride length, gait stability ratio, length of gait phases and dynamic stability as the main contributors to the first component, which was associated with diffusion tensor imaging measures in the posterior thalamic radiation, external capsule, superior cerebellar peduncle, superior fronto-occipital fasciculus, body and splenium of the corpus callosum and sagittal stratum, with MRI volumes in frontal and precentral regions and with flortaucipir-PET uptake in the precentral gyrus. The main contributor to the second principal component was cadence, which was higher in patients presenting more abnormalities on mean diffusivity: this unexpected finding might be related to compensatory gait strategies adopted in progressive supranuclear palsy. Postural imbalance was the main contributor to the third principal component, which was related to flortaucipir-PET uptake in the left paracentral lobule and supplementary motor area and white matter disruption in the superior cerebellar peduncle, putamen, pontine crossing tract and corticospinal tract. A partial least square model identified flortaucipir-PET uptake in midbrain, basal ganglia and thalamus as the main correlate of speed and dynamic component of gait in progressive supranuclear palsy. Although causality cannot be established in this analysis, our study sheds light on neurodegeneration of brain regions and white matter tracts that underlies gait and balance impairment in progressive supranuclear palsy.

进行性核上性麻痹是一种神经退行性疾病，其主要特征是中脑、基底节、丘脑、前运动和额叶皮层的 tau 蛋白包涵体和神经退行性变。进行性核上性麻痹的神经退行性变化已使用 MRI 进行了评估。弥散张量成像可以明显看出白质束的退化，PET 方法已被用于评估脑代谢或 tau 蛋白沉积物的存在。进行性核上性麻痹患者出现多种临床综合征；然而，早期出现的步态障碍和姿势不稳定是常见的特征。在这项研究中，我们评估了多模式成像生物标志物（即 MRI 萎缩、白质束变性、flortaucipir-PET 摄取）和基于实验室的步态和平衡异常测量在 19 名进行性核上性麻痹患者的队列中，使用单变量和多变量统计分析。PSP 评分量表及其步态中线子评分与步态异常密切相关，但与姿势不平衡无关。对步态变量的主成分分析确定了速度、步幅长度、步态稳定性比、步态相位长度和动态稳定性是第一个成分的主要贡献者，这与后丘脑辐射、外囊、优越的扩散张量成像测量相关小脑脚、额枕上束、胼胝体体和压部及矢状层，在额叶和中央前区有 MRI 体积，在中央前回有 flortaucipir-PET 摄取。第二个主要成分的主要贡献者是节奏，在表现出更多平均扩散率异常的患者中节奏更高：这一意外发现可能与进行性核上性麻痹中采用的代偿步态策略有关。姿势不平衡是第三个主要成分的主要原因，这与左侧旁中央小叶和辅助运动区的 flortaucipir-PET 摄取以及小脑上脚、壳核、脑桥交叉束和皮质脊髓束的白质破坏有关。偏最小二乘模型确定了 flortaucipir-PET 在中脑的摄取，基底节和丘脑是进行性核上性麻痹中速度和步态动态成分的主要相关因素。尽管在该分析中无法确定因果关系，但我们的研究揭示了进行性核上性麻痹中步态和平衡障碍的大脑区域和白质束的神经变性。