Subthalamic deep brain stimulation alleviates the gait sequence effect and freezing of gait in Parkinson's disease.

Background: The sequence effect in gait-progressive shortening of strides-contributes to freezing of gait (FOG), a debilitating symptom of Parkinson's disease (PD). The sequence effect is refractory to dopaminergic medications and attentional strategies, with improvement observed only through external cueing. While subthalamic nucleus (STN) deep brain stimulation (DBS) is a standard treatment for PD, its efficacy for gait and FOG remains debated.

Objective: To characterize the sequence effect in spatiotemporal gait parameters in PD and to investigate the effects of STN-DBS.

Methods: Eighteen individuals with PD with bilateral STN-DBS and fourteen age-matched healthy controls performed a harnessed Stepping-In-Place task, validated to elicit FOG. PD participants were assessed OFF and ON DBS in the off-medication state. Gait kinematics were measured using shank IMU sensors. The sequence effect was quantified by fitting an exponential decay function to each spatiotemporal gait parameter prior to freezing.

Results: The sequence effect was evident in PD participants but not in healthy controls. It manifested as a progressive reduction in swing angular velocity and angular range over time, with variable trends in swing time. The severity of the sequence effect significantly correlated with percent time spent freezing off therapy (p < 0.001). STN-DBS significantly alleviated the sequence effect (p = 0.002) and reduced percent time freezing (p = 0.01).

Conclusions: The Stepping-In-Place task elicited the sequence effect in PD, revealing progressive deterioration in both spatial and velocity aspects of gait, which contributed to the severity of FOG. STN-DBS effectively reduced the sequence effect, thereby improving FOG.