Target-Specific Effects of Deep Brain Stimulation for Tourette Syndrome: A Systematic Review and Meta-Analysis

Abstract

Background: Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus-nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus-parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and commonalities between those targets need to be compared systematically. Objective: Therefore, we evaluated whether DBS is effective in reducing TS symptoms and target-specific differences. Methods: A PubMed literature search was conducted according to the PRISMA guidelines. Eligible literature was used to conduct a systematic review and meta-analysis. Results: In total, 65 studies with 376 patients were included. Overall, Yale Global Tic Severity Scale (YGTSS) scores were reduced by more than 50 in 69% of the patients. DBS also resulted in significant reductions of secondary outcome measures, including the total YGTSS, modified Rush Video-Based Tic Rating Scale (mRVRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Becks Depression Inventory (BDI). All targets resulted in significant reductions of YGTSS scores and, with the exception of the CM-Pf, also in reduced YBOCS scores. Interestingly, DBS of pallidal targets showed increased YGTSS and YBOCS reductions compared to thalamic targets. Also, the meta-analysis including six randomized controlled and double-blinded trials demonstrated clinical efficacy of DBS for TS, that remained significant for GPi but not thalamic stimulation in two separate meta-analyses. Conclusion: We conclude that DBS is a clinically effective treatment option for patients with treatment-refractory TS, with all targets showing comparable improvement rates. Future research might focus on personalized and symptom-specific target selection.

Keywords: DBS; Tourette syndrome; deep brain stimulation; meta-analysis; neuromodulation; systematic review; tic disorders.

Figure 1

Adapted PRISMA 2020 flow diagram (44).

Figure 2

Simplified visualization of DBS electrodes of the different targets. Shown are the target regions: green = CM; purple = Pf; turquoise = Voi; red = pvlGPi; orange = amGPi. For illustration purposes targets are displayed unilateral only. (A) Thalamic targets: left electrode = CM-Pf; right electrode = CM-Voi. Background shows the coronal section of a brain MRI. (B) Pallidal targets: left electrode = pvlGPi; right electrode = amGPi. Background shows the horizontal section of a brain MRI. Graphics were generated using the DISTAL atlas (120) and MNI PD25 atlas (121). S, superior; A, anterior; L, left; R, right.

Figure 3

Scatterplots of global YGTSS scores for all targets combined at different postoperative time points (T0: baseline; T1: ≤ 6 months; T2: ≤ 12 months; T3: >12 months). Circles represent individual studies; color-filled circles represent more heavily weighted studies (more participants). Horizontal bars show the median values for each target. Significant differences between time points are indicated with asterisks (p < 0.05).

Figure 4

Scatterplots of global YGTSS percentage change scores for the different targets at T2 (6–12 months after DBS surgery). Circles represent individual studies; color-filled circles represent more heavily weighted studies (more participants). Horizontal bars show the median values for each target. Significant differences between targets are indicated with asterisks (p < 0.05).

Figure 5

Scatterplots of YBOCS absolute change scores for the different targets at maximum follow-up. Circles represent individual studies; color-filled circles represent more heavily weighted studies (more participants). Horizontal bars show the median values for each target. Significant differences between targets are indicated with asterisks (p < 0.05).

Figure 6

Forest plots of RCTs. Mean YGTSS total tic scores were compared between experimental conditions (DBS ON) vs. control conditions (DBS OFF). (A) General effect of DBS for both thalamic and pallidal targets. (B) Effect of DBS for thalamic targets. (C) Effect of DBS for pallidal targets. Targets were not further specified. Graphics were created with the Review Manager 5.4.1. (48). GPi, globus pallidus internus; Tha, thalamus; CI, confidence interval.