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Meta-Analysis
. 2023;101(4):244-253.
doi: 10.1159/000531089. Epub 2023 Jul 10.

Spinal Cord Stimulation for Parkinson's Disease: A Systematic Review and Meta-Analysis of Pain and Motor Outcomes

Can Sarica  1   2 , Ajmal Zemmar  3   4 , Omid Yousefi  5 , Andrew C Yang  6 , Ayse Uzuner  7 , Zhiyuan Sheng  3 , Brendan Santyr  6 , Nardin Samuel  6 , Michael Colditz  6 , Artur Vetkas  6 , Jürgen Germann  6 , Cletus Cheyuo  6 , Mohammadmahdi Sabahi  8 , Raja Niranjan Jani  4 , Ghazaleh Darmani  9 , Kazuaki Yamamoto  10 , David H Aguirre-Padilla  11 , Joseph S Neimat  4 , Suneil K Kalia  6   9   12 , Robert Chen  9   13 , Alfonso A Fasano  9   12   13 , Andres M Lozano  6   9
Affiliations
Meta-Analysis

Spinal Cord Stimulation for Parkinson's Disease: A Systematic Review and Meta-Analysis of Pain and Motor Outcomes

Can Sarica et al. Stereotact Funct Neurosurg. 2023.

Abstract

Background: Spinal cord stimulation (SCS) has been investigated as a potential therapeutic option for managing refractory symptoms in patients with Parkinson's disease (PD).

Objective: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of SCS in PD.

Method: A comprehensive literature search was conducted on PubMed and Web of Science to identify SCS studies reporting Unified Parkinson Disease Rating Scale-III (UPDRS-III) or Visual Analogue Scale (VAS) score changes in PD cohorts with at least 3 patients and a follow-up period of at least 1 month. Treatment effect was measured as the mean change in outcome scores and analyzed using an inverse variance random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale and funnel plots.

Results: A total of 11 studies comprising 76 patients were included. Nine studies involving 72 patients reported an estimated decrease of 4.43 points (95% confidence interval [CI]: 2.11; 6.75, p < 0.01) in UPDRS-III score, equivalent to a 14% reduction. The axial subscores in 48 patients decreased by 2.35 points (95% CI: 1.26; 3.45, p < 0.01, 20% reduction). The pooled effect size of five studies on back and leg pain VAS scores was calculated as 4.38 (95% CI: 2.67; 6.09, p < 0.001), equivalent to a 59% reduction.

Conclusions: Our analysis suggests that SCS may provide significant motor and pain benefits for patients with PD, although the results should be interpreted with caution due to several potential limitations including study heterogeneity, open-label designs, small sample sizes, and the possibility of publication bias. Further research using larger sample sizes and placebo-/sham-controlled designs is needed to confirm effectiveness.

Keywords: Gait improvement; Motor outcomes; Pain; Parkinson’s disease; Spinal cord stimulation.

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Conflict of interest statement

O.Y., A.C.Y., A.U., Z.S., B.S., N.S., M.C., A.V., J.G., C.C., M.S., R.J., G.D., K.Y., D.H.A.‐P., J.N., and R.C. report no disclosures relevant to the manuscript. C.S. has been receiving fellowship grants from the Michael and Amira Dan Foundation and Turkish Neurosurgical Society. A.Z. was supported by the Henan Provincial People’s Hospital Outstanding Talents Founding Grant Project. A.M.L. is scientific director for Functional Neuromodulation and a consultant to Medtronic, Abbott, Boston Scientific, Insightec, and the Focused Ultrasound Foundation. A.F. reports the following: consultancies from AbbVie, Medtronic, Boston Scientific, Sunovion, Chiesi Farmaceutici, UCB, and Ipsen; membership in advisory boards of AbbVie, Boston Scientific, and Ipsen; receiving honoraria from AbbVie, Medtronic, Boston Scientific, Sunovion, Chiesi Farmaceutici, UCB, and Ipsen; and receiving grants from the University of Toronto, Weston Foundation, AbbVie, Medtronic, and Boston Scientific. S.K.K. receives honoraria, consulting, and/or speaker fees from Abbott, Boston Scientific, inBrain, Medtronic, Novo Nordisk, Parkinson Canada, and Movement Disorders Society; and research support from Parkinson Canada, CIHR, MJFF, FUS Foundation, MitoO2, Toronto Western Hospital Foundation, Weston Foundation, and RR Tasker Chair in Stereotactic and Functional Neurosurgery.

Figures

Fig. 1.
Fig. 1.
Effect of tonic or burst stimulation on UPDRS-III score. Tonic stimulation in 43 patients from seven cohorts resulted in an estimated reduction of 4.52 points on the UPDRS-III score (95% CI: 1.35; 7.68, p < 0.05), and burst stimulation in 29 patients from four cohorts resulted in an estimated reduction of 4.2 points (95% CI: −2.53; 10.92, p = 0.14) when comparing the latest follow-up to baseline in the stimulation-ON/medication-ON state. Overall, 72 patients from eleven cohorts experienced an estimated decrease of 4.43 points (95% CI: 2.11; 6.75, p < 0.01) on the UPDRS-III score, equivalent to a 14% (6.6–21.3%) reduction. The exception was a report by Pinto de Souza et al. that used medication-OFF results for comparison. Total refers to the total number of patients; MD: mean difference (positive values indicate favorable outcomes); CI: confidence interval; df: degrees of freedom.
Fig. 2.
Fig. 2.
Effect of stimulation on: pain (VAS/NRS), freezing of gait (FOG-Q score), mobility (TUG and SWS scores), and quality of life (PDQ-39 or PDQ-8 scores). a In 56 patients with low back or leg pain, the VAS/NRS was reduced by an estimated 4.38 (95% CI: 2.67; 6.09, p < 0.001), equivalent to a 59% (36–82%) reduction. Heterogeneity testing revealed excess variation in the data (Q = 36.57, df = 6, p <0.001) with an I2 value of 84% (95% CI: 68–92%). b The FOG-Q scores were reduced by an estimated 4.6 points in 14 patients across three studies (95% CI: −9.07; 18.28, p = 0.28) with significant heterogeneity among studies (Q = 27.92, df = 2, p <0.001, I2 = 93% [95% CI: 82–97%]). Data from Hubsch et al., which did not provide exact values, were excluded from the analysis. c The TUG and SWS scores were reduced by a standardized mean difference of 0.46 (95% CI: −0.33; 1.26, p = 0.19) in 37 patients. In the study by Chakravarthy et al., group 1 consisted of patients receiving continuous burst stimulation, while group 2 received cycling burst stimulation. Hubsch et al. used the SWS score, while other studies used the TUG score. d Quality of life, as assessed by PDQ-39 or PDQ-8, was reduced by an estimated 0.49 (95% CI: −0.29; 1.27, p = 0.13) in 19 patients across four studies. All assessments were conducted in the medication-ON state, except for the study by Pinto de Souza et al., which reported results in the medication-OFF state. Total refers to the total number of patients; (S)MD: (standardized) mean difference (positive values indicate favorable outcomes); CI: confidence interval; df: degrees of freedom.
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