Objective: To establish a personalized gait signature assay to inform on progression, phenotype and effects of intervention of gait abnormalities in PD.

Background: Gait signatures are defined as the relation between spatial or temporal foot fall metrics and gait speed. They represent a precise readout of gait metrics even when speed changes, as is typical in PD. In cross-sectional studies gait signatures differ between groups of subjects with PD and controls. However, walking problems among PD patients are heterogeneous. This raises the question of whether personalized gait signatures capture patient-specific features. In a validation cohort of healthy young adults we found that gait signatures were stable, allowing us to establish criteria for shifts in PD. Here, we set out to determine whether gait signatures of PD subjects shift over time, when shifts occur, which metrics shift, and if patterns of shifts are heterogeneous among patients.

Method: We performed a gait assessment in PD subjects and age- matched controls at baseline and follow-up intervals of at least 1 year. A retest was performed within 60 days of one of these visits. After a pause due to the COVID-19 pandemic, a subset completed a longitudinal visit 6-7 years after baseline. We used a Protokinetics Zeno walkway to measure gait parameters (stride length, swing time, stance time, stride velocity) at 5 walking speeds.

Results: At baseline, gait signatures of subjects with PD were highly individual. At test and retest, gait signatures within PD subjects remained stable. Over 7 years, one or more gait signatures of all PD subjects shifted. However, the combination of gait signatures that shifted was heterogeneous. Swing time was most prone to shifts, followed by stride length. Stance time shifts were seen only in a minority of patients. Shifts represented shorter stride length, swing time and/or stance time for a given velocity. Gait signatures could be stable for years before shifts developed and shifts were noted to progress over several years.

Conclusion: Longitudinal monitoring captured patient-specific features of progression in gait impairment.  Type, timing and magnitude of shifts were heterogeneous among PD subjects. Gait signatures are a promising, sensitive tool to monitor progression of gait impairment in PD and may also be employed to monitor efficacy of interventions and study underlying pathophysiology.

References: Broom L., Ellison B. A., Worley A., Wagenaar L., Sorberg E., Ashton C., et al. (2017). A translational approach to capture gait signatures of neurological disorders in mice and humans. Sci Rep 7 3225. 10.1038/s41598-017-03336-1

Broom L., Worley A., Gao F., Hernandez L. D., Ashton C. E., Shih L. C., et al. (2019). Translational methods to detect asymmetries in temporal and spatial walking metrics in parkinsonian mouse models and human subjects with Parkinson’s disease. Sci Rep 9 2437. 10.1038/s41598-019-38623-6

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-personalized-gait-signature-assay-in-parkinsons-disease/