Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study

Abstract

Background: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.

Methods: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.

Results: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.

Conclusion: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Keywords: globus pallidus; neuromodulation; obsessive-compulsive behavior; thalamus; tics.

Figure 1

Tic severity and obsessive–compulsive behaviour over time. (A) YGTSS total scores over time grouped by DBS target. (B–D) YGTSS subscores (motor, phonic and impairment) over time grouped by DBS target. (E) Y-BOCS total scores over time grouped by DBS target. YGTSS subscores and Y-BOCS scores were collected for only a subset of the targets. The number of patients in each group is annotated above each boxplot and is coloured according to the legend. ALIC, anterior limb of the internal capsule; amGPi, anteromedial globus pallidus internus; DBS, deep brain stimulation; CM, centromedial; NA, nucleus accumbens; pvGPi, posteroventral globus pallidus internus; Y-BOCS, Yale-Brown Obsessive Compulsive Scale; YGTSS, Yale Global Tic Severity Scale.

Figure 2

Median time to response across the TS DBS cohort and subgroups. (A) Cumulative probability of response for all patients in the cohort (N=110). (B) Cumulative probability of response for patients implanted in the GPi and CM thalamus. (C) Cumulative probability of response in patients with TS and OCB and patients with TS only. (D) Cumulative probability of response in patients grouped by age at DBS implantation. The shaded regions are 95% CIs. The numbers of patients and the median times to response (in months) are listed in the legends. CM, centromedial; DBS, deep brain stimulation; GPi, globus pallidus internus; OCB, obsessive–compulsive behaviour; TS, Tourette syndrome; YGTSS, Yale Global Tic Severity Scale.

Figure 3

Variability of bilateral active DBS contact locations in the cohort atlas space. (A) Three-dimensional superior view of the locations of the active contacts in the cohort atlas space for n=70 patients relative to nuclei segmentations. Each sphere represents an active DBS contact and is coloured by intended DBS target region as listed in the legend in (B). (B) Sagittal (x), coronal (y) and axial (z) coordinates in mean (SD) mm relative to the mid-commissural point of the cohort atlas. DBS, deep brain stimulation.

Figure 4

PSAs of clinical outcomes in GPi DBS patients. (A) PSA of the proportion of the total number of patients stimulated at each voxel. The region with the greatest number of overlapping VTA across GPi DBS patients was located within the amGPi and the regions inferior of the amGPi. (B) PSA of the mean per cent improvement in YGTSS total score. (C) Regions stimulated in nonresponders, responders and the regions where they overlapped. There was substantial overlap of effective regions and regions that were associated with little to no therapeutic benefit. (D) PSA of the mean per cent improvement in the Y-BOCS total score showed that the VTA of patients who did not reach a 25% improvement extended below the GPi. The VTA of patients who reached a >25% improvement were located within the pallidum and/or medial or superior to the pallidum and did not extend below the GPi. Segmentation outlines of nuclei are overlaid for reference (GPi, yellow; GPe, white). For axial and sagittal views, see online supplementary figures 1-4. amGPi, anteromedial globus pallidus internus; DBS, deep brain stimulation; GPe, globus pallidus externus; GPi, globus pallidus internus; PSA, probabilistic stimulation atlas.

Figure 5

PSAs of clinical outcomes in CM thalamus DBS patients. (A) PSA of the proportion of the total number of patients stimulated at each voxel. The region with the greatest number of overlapping VTA across the CM thalamus DBS patients was located at the intersection of the CMn-Pf complex-Voi. (B) PSA of the mean per cent improvement in YGTSS total score. (C) Regions stimulated in nonresponders, responders and the regions where they overlapped. There were regions associated with improvement and overlapping regions associated with little to no therapeutic benefit. (D) PSA of the mean per cent improvement in the Y-BOCS total score. Segmentation outlines of the nuclei are overlaid for reference (thalamus, white; CM nucleus, light blue; PF complex, dark green; Voi, yellow-green). For axial and sagittal views, see online supplementary figures 6-9. CM, centromedial; CMn-Pf, centromedian nucleus-parafascicular; DBS, deep brain stimulation; PSAs, probabilistic stimulation atlases; Voi, ventro-oralis internus.