Gaps and roadmap of novel neuromodulation targets for treatment of gait in Parkinson’s disease

Abstract

Gait issues in Parkinson’s disease (PD) are common and can be highly disabling. Although levodopa and deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus internus have been established therapies for addressing the motor symptoms of PD, their effects on gait are less predictable and not well sustained with disease progression. Given the high prevalence of gait impairment in PD and the limitations in currently approved therapies, there has been considerable interest in alternative neuromodulation targets and techniques. These have included DBS of pedunculopontine nucleus and substantia nigra pars reticulata, spinal cord stimulation, non-invasive modulation of cortical regions and, more recently, vagus nerve stimulation. However, successes and failures have also emerged with these approaches. Current gaps and controversies are related to patient selection, optimal electrode placement within the target, placebo effects and the optimal programming parameters. Additionally, recent advances in pathophysiology of oscillation dynamics have driven new models of closed-loop DBS systems that may or may not be applicable to gait issues. Our aim is to describe approaches, especially neuromodulation procedures, and emerging challenges to address PD gait issues beyond subthalamic nucleus and the globus pallidus internus stimulation.

Why Does Tardive Dyskinesia Have Oro-facial Predominance? A Network Analysis

“…However, consistent with our results, some stages utilize more diffuse connectivity, in which each microchannel connects with all others typically at the level of to GPi/SNr (Shipp 2017). Clinical studies on Parkinson's disease (PD) patients has shown that deep brain stimulation (DBS) of the SNr but not of the Subthalamic nucleus (STN) was better at controlling anticipatory postural adjustments and gait control, and DBS has been shown to be feasible in PD patients with dyskinesia as well (Cury et al 2022). The implications of our result are that specifically focused therapeutic improvements towards the SNr, perhaps through the STN (Lagière et al 2020) could help in the plastic reorganization of the network to decrease the induction of repetitive oro-facial movements.…”

“…Clinical studies on Parkinson’s disease (PD) patients has shown that deep brain stimulation (DBS) of the SNr but not of the Subthalamic nucleus (STN) was better at controlling anticipatory postural adjustments and gait control, and DBS has been shown to be feasible in PD patients with dyskinesia as well (Cury et al. 2022 ). The implications of our result are that specifically focused therapeutic improvements towards the SNr, perhaps through the STN (Lagière et al.…”

Current Rehabilitation Therapies in Parkinson’s Disease

“…As for anxiety, Parkinson's anxiety scale (PAS) and a PD-specific anxiety scale have higher specificity and sensitivity for their use as a screening tools than other scales [27]. Non-pharmacologic approaches in Non-motor features in PD [25].…”

Deep brain stimulation in Parkinson’s disease: state of the art and future perspectives

“…Despite good results of SCS in treating gait problems, only a small number of PD patients were evaluated so far, with variable study populations. Furthermore, the stimulation produces tangible sensations which might be responsible for a placebo effect, which should be addressed in newer trials 69 . Double-blind approaches designed with an amplitude subthreshold for paresthesia, very high frequencies (below the sensory threshold), or new paradigms such as burst stimulation, will hopefully guide these future trials to avoid placebo effects 70 .…”