Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study

Abstract

Despite optimal pharmacotherapy and cognitive-behavioral treatments, a proportion of patients with obsessive-compulsive disorder (OCD) remain refractory to treatment. Neurosurgical ablative or nondestructive stimulation procedures to treat these refractory patients have been investigated. However, despite the potential benefits of these surgical procedures, patients show significant surgery-related complications. This preliminary study investigated the use of bilateral thermal capsulotomy for patients with treatment-refractory OCD using magnetic resonance-guided focused ultrasound (MRgFUS) as a novel, minimally invasive, non-cranium-opening surgical technique. Between February and May 2013, four patients with medically refractory OCD were treated with MRgFUS to ablate the anterior limb of the internal capsule. Patients underwent comprehensive neuropsychological evaluations and imaging at baseline, 1 week, 1 month and 6 months following treatment. Outcomes were measured with the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A), and treatment-related adverse events were evaluated. The results showed gradual improvements in Y-BOCS scores (a mean improvement of 33%) over the 6-month follow-up period, and all patients showed almost immediate and sustained improvements in depression (a mean reduction of 61.1%) and anxiety (a mean reduction of 69.4%). No patients demonstrated any side effects (physical or neuropsychological) in relation to the procedure. In addition, there were no significant differences found in the comprehensive neuropsychological test scores between the baseline and 6-month time points. This study demonstrates that bilateral thermal capsulotomy with MRgFUS can be used without inducing side effects to treat patients with medically refractory OCD. If larger trials validate the safety, effectiveness and long-term durability of this new approach, this procedure could considerably change the clinical management of treatment-refractory OCD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE . Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62: 617–627.

    PubMed  PubMed Central  Google Scholar 

  2. Kondziolka D, Flickinger JC, Hudak R . Results following gamma knife radiosurgical anterior capsulotomies for obsessive compulsive disorder. Neurosurgery 2011; 68: 28–32.

    Article  PubMed  Google Scholar 

  3. Lipsman N, Gerretsen P, Torres C, Lozano AM, Giacobbe P . A psychiatric primer for the functional neurosurgeon. J Neurosurg Sci 2012; 56: 209–220.

    CAS  PubMed  Google Scholar 

  4. Greenberg BD, Price LH, Rauch SL, Friehs G, Noren G, Malone D et al. Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues. Neurosurg Clin N Am 2003; 14: 199–212.

    Article  PubMed  Google Scholar 

  5. Blomstedt P, Sjoberg RL, Hansson M, Bodlund O, Hariz MI . Deep brain stimulation in the treatment of obsessive-compulsive disorder. World Neurosurg 2013; 80: e245–e253.

    Article  PubMed  Google Scholar 

  6. Edman G, Nyman H, Meyerson B, Mindus P . Capsulotomy as a last way out as far as no other alternative is available. Lakartidningen 1998; 95: 5008–5012.

    CAS  PubMed  Google Scholar 

  7. D'Astous M, Cottin S, Roy M, Picard C, Cantin L . Bilateral stereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up. J Neurol Neurosurg Psychiatry 2013; 84: 1208–1213.

    Article  PubMed  Google Scholar 

  8. Liu K, Zhang H, Liu C, Guan Y, Lang L, Cheng Y et al. Stereotactic treatment of refractory obsessive compulsive disorder by bilateral capsulotomy with 3 years follow-up. J Clin Neurosci 2008; 15: 622–629.

    Article  PubMed  Google Scholar 

  9. Ruck C, Karlsson A, Steele JD, Edman G, Meyerson BA, Ericson K et al. Capsulotomy for obsessive-compulsive disorder: long-term follow-up of 25 patients. Arch Gen Psychiatry 2008; 65: 914–921.

    Article  PubMed  Google Scholar 

  10. Fenoy AJ, Simpson RK Jr . Risks of common complications in deep brain stimulation surgery: management and avoidance. J Neurosurg 2014; 120: 132–139.

    Article  PubMed  Google Scholar 

  11. Baizabal Carvallo JF, Mostile G, Almaguer M, Davidson A, Simpson R, Jankovic J . Deep brain stimulation hardware complications in patients with movement disorders: risk factors and clinical correlations. Stereotact Funct Neurosurg 2012; 90: 300–306.

    Article  PubMed  Google Scholar 

  12. Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M et al. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol 2013; 12: 462–468.

    Article  PubMed  Google Scholar 

  13. Jeanmonod D, Werner B, Morel A, Michels L, Zadicario E, Schiff G et al. Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus 2012; 32: E1.

    Article  PubMed  Google Scholar 

  14. Rasmussen SA, Eisen JL . The epidemiology and clinical features of obsessive compulsive disorder. Psychiatr Clin North Am 1992; 15: 743–758.

    Article  CAS  PubMed  Google Scholar 

  15. Jenike MA, Rauch SL . Managing the patient with treatment-resistant obsessive compulsive disorder: current strategies. J Clin Psychiatry 1994; 55: 11–17.

    PubMed  Google Scholar 

  16. Mindus P, Edman G, Andreewitch S . A prospective, long-term study of personality traits in patients with intractable obsessional illness treated by capsulotomy. Acta Psychiatr Scand 1999; 99: 40–50.

    Article  CAS  PubMed  Google Scholar 

  17. Leveque M, Carron R, Regis J . Radiosurgery for the treatment of psychiatric disorders: a review. World Neurosurg 2013; 80: S32 e31–S32, e39.

    Article  Google Scholar 

  18. Sheehan JP, Patterson G, Schlesinger D, Xu Z . Gamma Knife surgery anterior capsulotomy for severe and refractory obsessive-compulsive disorder. J Neurosurg 2013; 119: 1112–1118.

    Article  PubMed  Google Scholar 

  19. Lopes AC, Greenberg BD, Noren G, Canteras MM, Busatto GF, de Mathis ME et al. Treatment of resistant obsessive-compulsive disorder with ventral capsular/ventral striatal gamma capsulotomy: a pilot prospective study. J Neuropsychiatry Clin Neurosci 2009; 21: 381–392.

    Article  CAS  PubMed  Google Scholar 

  20. Glover PM, Cavin I, Qian W, Bowtell R, Gowland PA . Magnetic-field-induced vertigo: a theoretical and experimental investigation. Bioelectromagnetics 2007; 28: 349–361.

    Article  CAS  PubMed  Google Scholar 

  21. Lippitz BE, Mindus P, Meyerson BA, Kihlstrom L, Lindquist C . Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere. Neurosurgery 1999; 44: 452–458.

    Article  CAS  PubMed  Google Scholar 

  22. Falowski S, Ooi YC, Smith A, Verhargen Metman L, Bakay RA . An evaluation of hardware and surgical complications with deep brain stimulation based on diagnosis and lead location. Stereotact Funct Neurosurg 2012; 90: 173–180.

    Article  PubMed  Google Scholar 

  23. Denys D, Mantione M, Figee M, van den Munckhof P, Koerselman F, Westenberg H et al. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2010; 67: 1061–1068.

    Article  PubMed  Google Scholar 

  24. Greenberg BD, Gabriels LA, Malone DA Jr, Rezai AR, Friehs GM, Okun MS et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry 2010; 15: 64–79.

    Article  CAS  PubMed  Google Scholar 

  25. Taub A, Lopes AC, Fuentes D, D'Alcante CC, de Mathis ME, Canteras MM et al. Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study. J Neuropsychiatry Clin Neurosci 2009; 21: 393–397.

    Article  PubMed  Google Scholar 

  26. Nuttin BJ, Gabriels LA, Cosyns PR, Meyerson BA, Andreewitch S, Sunaert SG et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 2003; 52: 1263–1272

    Article  PubMed  Google Scholar 

  27. Roh D, Chang WS, Chang JW, Kim CH . Long-term follow-up of deep brain stimulation for refractory obsessive-compulsive disorder. Psychiatry Res 2012; 200: 1067–1070.

    Article  PubMed  Google Scholar 

  28. Colen RR, Jolesz FA . Future potential of MRI-guided focused ultrasound brain surgery. Neuroimaging Clin N Am 2010; 20: 355–366.

    Article  PubMed  Google Scholar 

  29. Wintermark M, Druzgal J, Huss DS, Khaled MA, Monteith S, Raghavan P et al. Imaging findings in MR imaging-guided focused ultrasound treatment for patients with essential tremor. AJNR Am J Neuroradiol 2014; 35: 891–896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW . Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry, advance online publication, 29 May 2014; doi:10.1136/jnnp-2014-307642 (e-pub ahead of print).

  31. Gabriels L, Nuttin B, Cosyns P . Applicants for stereotactic neurosurgery for psychiatric disorders: role of the Flemish advisory board. Acta Psychiatr Scand 2008; 117: 381–389.

    Article  CAS  PubMed  Google Scholar 

  32. Garnaat SL, Greenberg BD, Sibrava NJ, Goodman WK, Mancebo MC, Eisen JL et al. Who qualifies for deep brain stimulation for OCD? Data from a naturalistic clinical sample. J Neuropsychiatry Clin Neurosci 2014; 26: 81–86.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by a faculty research grant from Yonsei University College of Medicine (6-2009-0063, Seoul, Korea) and Insightec (1-2012-0032, Haifa, Israel). We thank Eyal Zadicario, Itay Rachmilevitch and other employees of InSightec for excellent assistance in the technical aspects of the procedures.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to C-H Kim or J W Chang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jung, H., Kim, S., Roh, D. et al. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry 20, 1205–1211 (2015). https://doi.org/10.1038/mp.2014.154

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2014.154

This article is cited by

Search

Quick links