A Pragmatic Review on Spinal Cord Stimulation Therapy for Parkinson's Disease Gait Related Disorders: Gaps and Controversies

Abstract

Background: Parkinson's Disease (PD) is a progressive neurological disorder that results in potentially debilitating mobility deficits. Recently, spinal cord stimulation (SCS) has been proposed as a novel therapy for PD gait disorders. The highest levels of evidence remain limited for SCS.

Objectives: In this systematic review and narrative synthesis, the literature was searched using combinations of key phrases indicating spinal cord stimulation and PD.

Methods: We included pre-clinical studies and all published clinical trials, case reports, conference abstracts as well as protocols for ongoing clinical trials. Additionally, we included trials of SCS applied to atypical parkinsonism.

Results: A total of 45 human studies and trials met the inclusion criteria. Based on the narrative synthesis, a number of knowledge gaps and future avenues of potential research were identified. This review demonstrated that evidence for SCS is currently not sufficient to recommend it as an evidence-based therapy for PD related gait disorders. There remain challenges and significant barriers to widespread implementation, including issues regarding patient selection, effective outcome selection, stimulation location and mode, and in programming parameter optimization. Results of early randomized controlled trials are currently pending. SCS is prone to placebo, lessebo and nocebo as well as blinding effects which may impact interpretation of outcomes, particularly when studies are underpowered.

Conclusion: Therapies such as SCS may build on current evidence and be shown to improve specific gait features in PD. Early negative trials should be interpreted with caution, as more evidence will be required to develop effective methodologies in order to drive clinical outcomes.

Keywords: Parkinson's disease; falls; freezing of gait; gait disorder; neuromodulation; spinal cord stimulation.

Figure 1

Outcome improvement at best follow up on gait trials including gait speed, walking trials, and timed up and go tests improvement, Freezing of gait (FoG) questionnaires or episodes reduction and Unified Parkinson's disease rating scale part 3 (UPDRS III) scores reduction sorted by (A) study design (B) Lead type, (C) pain status and (D) lead level. Number of subjects per category highlighted.

Figure 2

Outcome improvement in percentage on best follow up discriminated by stimulation parameters. Bubble charts display improvement by color and average frequency and pulse width employed in the study, and subject number by bubble size. Frequency and pulse width ranges are represented by arrows and outcome improvement by dashes. (A). Timed up and go (TUG) or stand walk sit (SWS) test time reduction per parameters. (B) Linear gait speed increase per direct measure or linear walk trials, per parameters (C) Freezing of gait (FoG) questionnaire score or episodes count reduction per parameters. (D) Unified Parkinson's disease rating scale part 3 (UPDRS III) score reduction per parameters.