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Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience

Molecular Psychiatry volume 15, pages 64–79 (2010)Cite this article

Abstract

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a ‘learning curve’ both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior–posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

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Acknowledgements

We acknowledge the following individuals for their contributions to this multidisciplinary effort (listed by research team). Butler/Brown (BH): Richard Marsland, William Wong, M Evans, Norman Moore, Ronald Gaertner, Robert Bumgartner, Robert Gross, for management of study patients; Rouba Youssef, Katherine Rowinski, Erin Einbinder and Kathleen Barreiro for data management and administrative support. Leuven/Antwerp (LV): Kris van Kuyck, Marleen Welkenhuysen, Laura Luyten and John Das for their parallel animal research and technical support; Paul De Sutter, Bjorn Meyerson, Sergej, Andréewitch and Christian Rück, for contributing their neurosurgical and psychiatric experience; Cleveland Clinic (CC): Deborah Vegh RN, Natalie Sykuta RN for management of study patients; University of Florida (UF): Russell M Bauer, Gary Geffken, Candy L Hill, Chuck Jacobson, Nikki Ricciuti, Eric A Storch for clinical, technical and administrative support; Medtronic Inc. (MT): Keith Mullett, Frans Gielen, Roy Testerman for technical advice.

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Author notes

  1. B D Greenberg and L A Gabriels: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry and Human Behavior, Division of Neurosurgery, Butler Hospital, Brown Medical School, Providence, RI, USA

    B D Greenberg, G M Friehs, P F Malloy, S P Salloway & S A Rasmussen

  2. Department of Clinical Neurosciences, Division of Neurosurgery, Butler Hospital, Brown Medical School, Providence, RI, USA

    B D Greenberg, G M Friehs, P F Malloy, S P Salloway & S A Rasmussen

  3. Department of Neurosurgery, Catholic University of Leuven, Leuven, Belgium

    L A Gabriels, P R Cosyns & B J Nuttin

  4. Department of Psychiatry, University of Antwerp, Antwerp, Belgium

    L A Gabriels, P R Cosyns & B J Nuttin

  5. Center for Neurological Restoration, Cleveland Clinic Foundation, Cleveland, OH, USA

    D A Malone Jr, A R Rezai, C S Kubu, A G Machado & K B Baker

  6. Department of Psychiatry, University of Florida, Gainesville, FL, USA

    M S Okun, N A Shapira, K D Foote & W K Goodman

  7. Department of Neurology, University of Florida, Gainesville, FL, USA

    M S Okun, N A Shapira, K D Foote & W K Goodman

  8. Movement Disorders Center, University of Florida, Gainesville, FL, USA

    M S Okun, N A Shapira, K D Foote & W K Goodman

  9. Medtronic Neurological Inc., Minneapolis, MN, USA

    J E Giftakis, M T Rise & P H Stypulkowski

Authors
  1. B D Greenberg
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  2. L A Gabriels
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  3. D A Malone Jr
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  6. M S Okun
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  7. N A Shapira
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  8. K D Foote
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  9. P R Cosyns
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  10. C S Kubu
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  14. M T Rise
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  15. A G Machado
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  16. K B Baker
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  18. W K Goodman
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  19. S A Rasmussen
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  20. B J Nuttin
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Corresponding author

Correspondence to B D Greenberg.

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Disclosures

Financial support and other disclosures (listed by center): Butler Hospital/Brown (BH): Medtronic Inc. (investigator-initiated research) and by a NARSAD Independent Investigator Award (BDG). Cleveland Clinic (CC): Medtronic Inc. (investigator-initiated research). Leuven/Antwerp (LV): Research Fund KU Leuven (projects OT-98-31, VIS-02-007 and OT-03-57), the Institute for the Promotion of Innovation by Science and Technology in Flanders (SBO50151); the Fonds voor Wetenschappelijk Onderzoek - Vlaanderen (G.0598.06 and G.0273.97.N) (BN); the Verkennende Internationale Samenwerking (VIS ZKB1159) and the Research Mandate of the University of Antwerp (LAG). Stimulation devices provided by Medtronic Inc. (QUEST program, L1170). University of Florida (UF): Funded by NIMH 5R21MH064161-03 (WKG, PI) and by General Clinical Research Center MO1-RR00082. UF has a contract with Medtronic for DBS fellowship training and programming training for physicians focusing on DBS in Movement Disorders. Individual Authors: BDG, SAR and DAM were unpaid consultants to Medtronic Inc.; DAM and LAG became paid MDT consultants after these data were collected. Medtronic personnel roles: PHS and MTR focused on DBS technology, targeting and data analysis; JEG performed statistical analysis of the data. BJN has received research and teaching grants from Medtronic, and is co-holder of a patent for the use of DBS for OCD.

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Greenberg, B., Gabriels, L., Malone, D. et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry 15, 64–79 (2010). https://doi.org/10.1038/mp.2008.55

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