Levodopa responsive gait dynamics in OFF- and ONOFF-state freezing of gait in Parkinson's disease.

Background: In people with Parkinson's disease (PwPD), Freezing of Gait (FOG) episodes can be levodopa responsive (OFF-FOG) or levodopa unresponsive (ONOFF-FOG). Steady-state gait abnormalities, outside of the freezing episodes themselves also exist and the response to levodopa in these different groups has not been previously documented.
Objectives: To define the levodopa responsiveness in steady-state gait in OFF-FOG and ONOFF-FOG individuals.
Methods: Steady-state gait was collected in both the effective levodopa OFF-state (doses withheld > 8 h) and ON-state (1 h after levodopa dosing) in 32 PwPD; 10 with OFF-FOG and 22 with ONOFF-FOG. Levodopa response was compared between the two groups in the mean and variability (CV) of 8 spatiotemporal gait parameters.
Results: Both OFF-FOG and ONOFF-FOG participants showed improvement in mean stride-length and stride-velocity with levodopa. Improvement was seen in the OFF-FOG but not the ONOFF-FOG groups in mean stride-width and CV Integrated pressure with levodopa.
Discussion: In this study we show that steady-state gait deficits improve with levodopa in PwPD with OFF-FOG and ONOFF-FOG, even though episodes of FOG did not resolve in the ONOFF-FOG group. Lowering levodopa in people with ONOFF-FOG, or levodopa-unresponsive freezing of gait, should be undertake with caution and objective gait titration at different levodopa doses may be beneficial. Further work is needed to elucidate the pathophysiologic mechanisms of these differences.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Virmani received salary support from the University of Arkansas for Medical Sciences (UAMS), salary from the UAMS clinician scientist program (UAMS CSP), salary from a grant from the Parkinson’s Foundation (PF-JFA-1935) and a pilot NIGMS award (GM110702). Ms. Glover and Ms. Pillai, received salary support from the UAMS CSP, PF and NIGMS pilot awards (to TV). Dr. Landes received salary support from NIH/NCATS and the PF grant. None of the authors have any financial disclosures or conflicts of interest related to the research covered in this manuscript.
(© 2023 The Author(s).)