Restoration of locomotive function in Parkinson’s disease by spinal cord stimulation: mechanistic approach

摘要

Specific motor symptoms of Parkinson’s disease (PD) can be treated effectively using direct electrical stimulation of deep nuclei in the brain. However, this is an invasive procedure, and the fraction of eligible patients is rather low according to currently used criterion. Spinal cord stimulation (SCS), a minimally invasive method, has more recently been proposed as a therapeutic approach to alleviate PD akinesia, in light of its proven ability to rescue locomotion in rodent models of PD. The mechanisms accounting for this effect are unknown but from accumulated experience using SCS in the management of chronic pain, it is known that the pathways most likely activated by SCS are the superficial fibers of the dorsal columns. We suggest that the prokinetic effect of SCS is due to direct activation of ascending pathways reaching thalamic nuclei and the cerebral cortex. The afferent stimulation may, in addition, activate brain stem nuclei contributing to initiation of locomotion. Based on the striking change in the cortico-striatal oscillatory mode of neuronal activity induced by SCS, we propose that through activation of lemniscal and brainstem pathways, the locomotive increase is achieved by disruption of antikinetic low frequency (< 30 Hz) oscillatory synchronization in the cortico-basal ganglia circuits.