Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2019 Oct;90(10):1078-1090.
doi: 10.1136/jnnp-2019-320379. Epub 2019 May 25.

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

Kara A Johnson  1   2 , P Thomas Fletcher  1   3 , Domenico Servello  4 , Alberto Bona  4 , Mauro Porta  5 , Jill L Ostrem  6 , Eric Bardinet  7 , Marie-Laure Welter  8 , Andres M Lozano  9 , Juan Carlos Baldermann  10 , Jens Kuhn  10 , Daniel Huys  10 , Thomas Foltynie  11 , Marwan Hariz  11 , Eileen M Joyce  11 , Ludvic Zrinzo  11 , Zinovia Kefalopoulou  11 , Jian-Guo Zhang  12 , Fan-Gang Meng  12 , ChenCheng Zhang  13 , Zhipei Ling  14 , Xin Xu  14 , Xinguang Yu  14 , Anouk Yjm Smeets  15 , Linda Ackermans  15 , Veerle Visser-Vandewalle  16 , Alon Y Mogilner  17 , Michael H Pourfar  17 , Leonardo Almeida  18 , Aysegul Gunduz  18   19 , Wei Hu  18 , Kelly D Foote  18 , Michael S Okun  18 , Christopher R Butson  20   2   21
Affiliations
Multicenter Study

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

Kara A Johnson et al. J Neurol Neurosurg Psychiatry. 2019 Oct.

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: JLO has received research grant support from the Michael J Fox Foundation, Boston Scientific, Cala Health, NIH, DARPA, PCORI and Biogen, and she has also received training grant support from Boston Scientific and Medtronic, and has served as a consultant for Acadia Pharmaceuticals and Medtronic. AL serves as a consultant for Boston Scientific and holds intellectual property in the field of DBS. JK has received financial support for investigator-initiated trials from Medtronic and grants from the German Research Foundation (KU2665/1-2) and the Marga and Walter Boll Foundation. CZ has received honoraria and travel expenses from the deep brain stimulation industry (Medtronic, PINS, SceneRay). MSO serves as a consultant for the National Parkinson Foundation, and has received research grants from NIH, NPF, the Michael J Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MSO DBS research is supported by R01 NR014852 and R01NS096008. MSO has previously received honoraria, but in the past >60 months has received no support from the industry. MSO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients and Cambridge (movement disorders books). MSO is an associate editor for New England Journal of Medicine Journal Watch Neurology. MSO has participated in CME and educational activities on movement disorders (in the last 36 months) sponsored by PeerView, Prime, QuantiaMD, WebMD, Medicus, MedNet, Henry Stewart and by Vanderbilt University. The institution and not MSO receives grants from Medtronic, AbbVie, Allergan and ANS/St Jude, and the PI has no financial interest in these grants. MSO has participated as a site PI and/or co-I for several NIH, foundation and industry sponsored trials over the years but has not received honoraria. CRB has served as a consultant for NeuroPace, Advanced Bionics, Boston Scientific, Intelect Medical, St Jude Medical and Functional Neuromodulation, and he holds intellectual property related to DBS.

Figures

Figure 1
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
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
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
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
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.
See this image and copyright information in PMC

Comment in

References

    1. Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain 2000;123:425–62. 10.1093/brain/123.3.425 - DOI - PubMed
    1. Freeman RD, Fast DK, Burd L, et al. . An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries. Dev Med Child Neurol 2000;42:436–47. 10.1017/S0012162200000839 - DOI - PubMed
    1. Leckman JF. Tourette's syndrome. Lancet 2002;360:1577–86. 10.1016/S0140-6736(02)11526-1 - DOI - PubMed
    1. Hirschtritt ME, Lee PC, Pauls DL, et al. . Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry 2015;72:325–33. 10.1001/jamapsychiatry.2014.2650 - DOI - PMC - PubMed
    1. Groth C, Mol Debes N, Rask CU, et al. . Course of Tourette syndrome and comorbidities in a large prospective clinical study. J Am Acad Child Adolesc Psychiatry 2017;56:304–12. 10.1016/j.jaac.2017.01.010 - DOI - PubMed

Publication types

MeSH terms