Mechanisms of Gait and Balance Impairment in Progressive Supranuclear Palsy

进行性核上性麻痹的步态和平衡障碍的机制

• 批准号: 10657768
• 负责人: Farwa Ali
• 金额: $ 19.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657768
• 关键词: 3-Dimensional; Accreditation; Address; Age; Calibration; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Collaborations; Controlled Environment; Data; Detection; Development; Devices; Diagnosis; Diagnostic tests; Diffusion Magnetic Resonance Imaging; Disease; Equilibrium; Evaluation; Frequencies; Future; Gait; Gait abnormality; Goals; Grant; Heterogeneity; Human; Image; Impairment; Knowledge; Laboratories; Locomotion; Magnetic Resonance Imaging; Measures; Mentorship; Methods; Minnesota; Monitor; Morbidity - disease rate; Motion; Movement Disorders; Nerve Degeneration; Neuroanatomy; Neurodegenerative Disorders; Outcome; Outcome Measure; Outcomes Research; Patients; Pattern; Phenotype; Positioning Attribute; Posture; Productivity; Progressive Supranuclear Palsy; Qualifying; Reporting; Research; Research Methodology; Research Project Grants; Research Proposals; Severity of illness; Standardization; Syndrome; System; Tauopathies; Technology; Testing; Training; Translations; Universities; Validation; Work; career; career development; clinical biomarkers; clinical examination; clinical heterogeneity; clinical outcome measures; clinical practice; clinical training; clinically significant; comparative; cost effective; diagnostic tool; disability; equilibration disorder; experience; fall risk; falls; human model; improved; innovation; mortality; motor control; multidisciplinary; multimodality; neurobiological mechanism; neuroimaging; normal aging; patient oriented research; patient population; portability; professor; prognostic assays; programs; sex; skills; statistics; structural imaging; three-dimensional modeling; tractography; treatment trial; trial planning; wearable device

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.

项目摘要/摘要 进行性核上麻痹（PSP）是一种致命的，进行的，无法治愈的神经退行性tauopathy。瀑布 步态和平衡障碍导致的是该疾病的基本特征，并且发生在所有PSP中 综合征。目前，这些异常检测依赖于主观的临床检查和 秤。没有标准化的方法来量化步态的特定特征和PSP中的平衡损伤。 诊断和预后测试重点是患者相关结果，例如与步态相关的残疾 需要。运动分析技术可用于步态和平衡变量的客观资格。这 提供了开发以患者为中心的诊断工具的机会，以测量步态障碍的功能 及其对跌倒风险的影响。基于实验室的视频运动捕获利用了多个高频摄像头 在经过良好校准的受控环境中，生成了人类运动的三维模型 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获，以确定最能表征PSP Richardson综合征的步态指标， PSP皮层和PSP毛皮综合征，并将PSP与正常对照区分开。但是，获得了认可 运动分析实验室不容易访问，需要精心设计的通常昂贵的设置。戴身体 运动传感设备提供了可行的替代方案。它们具有成本效益，便携式，易于使用 设置。但是，必须在特定患者中建立这些设备的可靠性和准确性 人群和评估捕获数据的临床意义。因此，在这个项目中，我们将采用 身体上戴的运动传感设备或惯性监控单元（IMU），以检测步态和平衡最佳指标 表征PSP。然后将来自IMU的数据与运动分析实验室进行比较，以建立其 准确性。步态指标有可能在PSP中作为以患者为中心的结果度量。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中的损害。我们将将确定的步态和平衡度量与体积磁性相关联 共振成像（MRI），扩散MRI（DMRI）和拖拉术，以确定皮质破坏模式 PSP中的皮层运动控制系统。性别作为生物学意义的变量的影响将是 评估。年龄将是一个协变量，以确定与疾病状态和 不是正常衰老的继发。该研究项目的结果将有助于患者的发展 以中心的结果度量，评估临床异质性和对步态机制的理解 PSP综合征的损害。未来的方向将包括纵向评估和比较 跨相关神经退行性疾病的分析，以提高以患者为中心的诊断和发展 临床试验的结果指标。