Simultaneous development of quantitative tests for context dependent Parkinsonian gait abnormalities and next generation DBS technology
Elizabeth C. Hardin1, Sinem Balta Beylergil2, Cameron McIntyre2, Aasef G. Shaikh 1,3
1Motion Study Lab & Human Performance Virtual Reality Lab, Cleveland FES Center, Cleveland VA Medical Center, 2Dept. of Biomedical Engineering, Case Western Reserve Univ., 3Dept. of Neurology, Cleveland VA Medical Center and Dept. of Neurology, University Hospitals, Cleveland, OH
Background: Seven to 10 million people in the world live with neurodegeneration from Parkinson’s disease (PD). Gait impairments include abnormal navigation and lateral drifts. They can’t process sensory information to update orientation to spatial landmarks causing falls, common in ~68% of those with PD. Conventional pharmacotherapy does not produce predictable gait and balance responses. Alternatively, although high-frequency subthalamic deep brain stimulation (DBS) improves many motor symptoms, gait improvement is variable.
Aims: 1) Test the feasibility of discordant optic-flow (DOF) to determine PD gait function. 2) Determine the effects of subthalamic DBS on gait function. 3) Simulate a patient-specific DBS model in a PD patient whose gait function responded to subthalamic DBS to optimize DBS placement and stimulation parameters.
Methods: We tested the feasibility of imposing DOF (Aim 1) to determine PD gait function via virtual reality. The patient walked at their preferred speed for 2 minutes while anatomical kinematics were measured. DOF was imposed (10x normal); this was repeated with DBS on and off to determine DBS effects on gait function (Aim 2). For Aim 3, we simulated a patient-specific DBS model in a PD patient (a subthalamic DBS responder). Structural MR images were segmented to 3-D volume representations of patient-specific anatomy and the activated pathway was measured.
Results: During DOF, step time and step length decreased (30% and 38%, Aim 1) (ANOVA, p<0.001). The subthalamic DBS effects (Aim 2) were increased step time and step length (35% and 53%) (ANOVA, p<0.01) suggesting gait function improvement. Subthalamic DBS also affected gait impairment development during DOF with a minimal change in step time, step length, and walking speed (ANOVA p>0.05). These findings suggest subthalamic DBS improved gait function. The modeled optimal therapeutic stimulation pattern (Aim 3) resulted in prominent activation of cerebellothalamic tract bilaterally, followed by pallidothalamic and subthalamopallidal stimulation. These results suggest that subthalamic DBS influences gait function by stimulation of the pallidothalamic projections, also influencing the cerebellothalamic tract downstream from the subthalamo-cerebellar projections.
Conclusion: Imposing DOF to determine gait function in a PD patient was feasible. We also found that subthalamic DBS influenced gait function during DOF. Lastly, the DBS patient-specific model suggested that subthalamic DBS influences gait function by stimulation of the pallidothalamic projections. Next, we will implement a therapeutic strategy to optimize DBS placement and stimulation parameters to improve gait function in PD, and develop quantitative tests for gait abnormalities.