Exploring the effects of spinal cord stimulation for freezing of gait in parkinsonian patients
Abstract
Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is that mid-thoracic, dorsal SCS effectively reduces FOG by modulating the sensory processing system in gait and may have a dopaminergic effect in individuals with FOG. The primary objective was to understand the relationship between FOG reduction, improvements in upper limb visual-motor performance, modulation of cortical activity and striatal dopaminergic innervation in 7 PD participants. FOG reduction was associated with changes in upper limb reaction time, speed and accuracy measured using robotic target reaching choice tasks. Modulation of resting-state, sensorimotor cortical activity, recorded using electroencephalography, was significantly associated with FOG reduction while participants were OFF-levodopa. Thus, SCS may alleviate FOG by modulating cortical activity associated with motor planning and sensory perception. Changes to striatal dopaminergic innervation, measured using a dopamine transporter marker, were associated with visual-motor performance improvements. Axial and appendicular motor features may be mediated by non-dopaminergic and dopaminergic pathways, respectively. The secondary objective was to demonstrate the short- and long-term effects of SCS for alleviating dopaminergic-resistant FOG and gait dysfunction in 5 PD and 3 PSP-RS participants without back/leg pain. SCS programming was individualized based on which setting best improved gait and/or FOG responses per participant using objective gait analysis. Significant improvements in stride velocity, step length and reduced FOG frequency were observed in all PD participants with up to 3-years of SCS. Similar gait and FOG improvements were observed in all PSP-RS participants up to 6-months. SCS is a promising therapeutic option for parkinsonian patients with FOG by possibly influencing cortical and subcortical structures involved in locomotion physiology.