Objective: To identify white-matter (WM) correlates of physical therapy (PT)-measures in Parkinson’s disease (PD) patients with freezing of gait (FOG).

Background: Significant gap remains in understanding the pathophysiology of FOG in PD. FOG is determined clinically by consensus between experienced physical therapists and neurologists. However, whether these clinical measures are influenced by WM disorganization remains poorly understood. In this study, we examined correlation between PT-measures and WM organization by conventional single tensor diffusion tensor imaging (DTI) and free-water corrected DTI (FW-DTI) measures.

Method: Thirty-eight individuals with PD were recruited at our center. Each participant underwent a comprehensive clinical examination including Unified Parkinson’s Disease Rating Scale score, disease duration, FOG questionnaire, and Levodopa Equivalent Dose in a clinically defined “OFF” state. PD patients were classified as PD-FOG through physical therapy evaluation by a trained physical therapist (JL) and were verified by the neurologists (AR and ZM). 17 PD-FOG and 21 PD-nFOG patients were identified in our cohort. Detailed demographics are shown in Table.1. We collected high spatial (1.5mm³) and high angular (71 unique directions) resolution diffusion MRI (dMRI) each at three shells (b=500s/mm², b=1000s/mm², and b=2500s/mm²) using HCP-like sequence on a 3T Siemens Skyra. Both DTI and FW-DTI metrics were estimated in each voxel using in-house scripts. Correlation between the PT-measures and various dMRI-derived voxelwise measures at the center of the WM tracts was conducted using non-parametric statistics and significance was established at family-wise error correction of p_corr<0.05.

Results: Significant correlations were observed between DTI measures such as fractional anisotropy (FA), radial diffusivity (RD), and mean diffusivity (MD) and PT-measures such as total FOG scores (Total-FOG) and change in motor performance under dual-task conditions (motor-DTE). However, the group-dependent correlation disappeared after the correction of FW. Additionally, a significantly higher correlation was obtained between FW and Total-FOG and between FW and motor-DTE in PD-FOG as compared to PD-nFOG.

Conclusion: Our analysis suggests that FW-DTI is capable to fill the gap in our understanding of the pathophysiology of PD-FOG through understanding differences in WM organization as compared to PD-nFOG.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/white-matter-correlates-of-physical-therapy-measures-in-parkinsons-disease-patients-with-freezing-of-gait/