Mechanisms of Gait and Balance Impairment in Progressive Supranuclear Palsy

项目摘要/摘要 进行性核上性麻痹(PSP)是一种致命的、进行性的、不可治愈的神经退行性变态反应。瀑布 步态和平衡障碍是该病的一个主要特征，在所有PSP中都会发生 综合症。目前，发现这些异常在很大程度上依赖于主观的临床检查和 比例。目前还没有标准化的方法来量化PSP中步态和平衡损害的具体特征。 侧重于患者相关结果的诊断和预后测试，如步态相关残疾 需要的。运动分析技术可以用来对步态和平衡变量进行客观的鉴定。这 提供了开发以患者为中心的诊断工具的机会，这些工具可以测量步态损伤的特征 以及它对跌倒风险的影响。基于实验室的视频运动捕获利用多个高频摄像机 在经过良好校准的受控环境中生成人体运动的三维模型 平衡。这被认为是最准确、最可靠的运动分析方法。我们的项目将利用 基于实验室的运动捕捉，以确定最能表征PSP Richardson综合征的步态指标， PSP-皮质和PSP-皮质下综合征，并与正常对照区分PSP。然而，经过认可的 运动分析实验室并不容易进入，并且需要复杂的、通常昂贵的设置。穿着上身 运动感应设备提供了一个可行的替代方案。它们性价比高，携带方便，便于在门诊使用 设置。然而，在特定的患者中建立这些设备的可靠性和准确性是至关重要的 并评估所捕获数据的临床意义。因此，在这个项目中，我们将雇用一名 身体佩戴的运动感应装置或惯性监测单元(IMU)，可检测最佳步态和平衡指标 描述PSP的特征。然后，来自IMU的数据将与运动分析实验室进行比较，以确定其 精确度。步态测量有可能在PSP中作为以患者为中心的结果测量。在这个项目中 我们还将使用这些变量来分析步态和平衡的神经生物学机制 PSP损害。我们将识别的步态和平衡度量值与体积磁场相关联 磁共振成像(MRI)、弥散磁共振成像(DMRI)和声带造影术确定皮质破坏的类型 以及PSP的皮质下运动控制系统。性别作为一个具有生物学意义的变量的影响将是 评估过了。年龄将成为识别步态异常的协变量，这些步态异常与疾病状态和 不会继发于正常衰老。本研究项目的成果将为患者的发展做出贡献 中心性结果测量、临床异质性评估和步态机制的理解 PSP综合征的损害。未来的方向将包括纵向评估和比较 分析相关神经退行性疾病，促进以患者为中心的诊断和发展 临床试验的结果衡量标准。

PROJECT SUMMARY/ABSTRACT Progressive supranuclear palsy (PSP) is a fatal, progressive, incurable neurodegenerative tauopathy. Falls resulting from gait and balance impairments are a cardinal feature of the disease and occur in all PSP syndromes. Currently, detection of these abnormalities relies on largely subjective clinical examination and scales. There are no standardized ways to quantify specific features of gait and balance impairments in PSP. Diagnostic, and prognostic tests focusing on patient relevant outcomes such as gait related disability are needed. Motion analysis technology can be used for objective qualification of gait and balance variables. This offers an opportunity to develop patient-centric diagnostic tools that can measure features of gait impairment and its impact on risk for falls. Laboratory-based video motion capture utilizes multiple high frequency cameras in a well calibrated controlled environment to generate a three-dimensional model of human locomotion and balance. This is considered the most accurate and reliable method of motion analysis. Our project will utilize laboratory-based motion capture to identify gait metrics that best characterize PSP Richardson syndrome, PSP-cortical and PSP-subcortical syndromes and distinguish PSP from normal controls. However, accredited motion analysis labs are not readily accessible, and require an elaborate usually expensive set-up. Body-worn motion-sensing devices offer a feasible alternative. They are cost-effective, portable, easy to use in ambulatory settings. However, it is essential to establish reliability and accuracy of these devices in specific patient populations and assess clinical significance of the data captured. Therefore, in this project we will employ a body-worn motion sensing device or inertial monitoring unit (IMU) to detect gait and balance metrics that best characterize PSP. The data from the IMU will then be compared to the motion analysis lab to establish its accuracy. Gait metrics have the potential to serve as patient-centric outcome measures in PSP. In this project we will also use these variables to analyze neurobiological mechanisms underlying gait and balance impairment in PSP. We will correlate the identified gait and balance metrics with volumetric magnetic resonance imaging (MRI), diffusion MRI (dMRI) and tractography to determine patterns of disruption of cortical and subcortical motor control systems in PSP. The effect of sex as a biologically significant variable will be assessed. Age will be a covariate to identify gait abnormalities that are specifically related to disease state and not secondary to normal aging. The outcomes of this research project will contribute to development of patient centric outcome measures, assessment of clinical heterogeneity and understanding of mechanisms of gait impairment in PSP syndromes. Future directions will include longitudinal assessment and comparative analyses across related neurodegenerative diseases to advance diagnosis and development of patient centric outcome measures for clinical trials.