Mechanisms of Gait and Balance Impairment in Progressive Supranuclear Palsy

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.

Grant Number: 5K23NS124688-04
NIH Institute/Center: NIH
Principal Investigator: Farwa Ali