Long-term improvement in obsessions and compulsions with subthalamic stimulation

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Article

Reference

Long-term improvement in obsessions and compulsions with subthalamic stimulation

POLOSAN, Mircea, et al.

POLOSAN, Mircea, et al . Long-term improvement in obsessions and compulsions with subthalamic stimulation. Neurology , 2016, vol. 87, no. 17, p. 1843-1844

DOI : 10.1212/WNL.0000000000003248 PMID : 27655738

Available at:

http://archive-ouverte.unige.ch/unige:95975

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Clinical/Scientific Notes

Mircea Polosan, MD, PhD

Stephan Chabardes, MD, PhD

Thierry Bougerol, MD, PhD

Claire Ardouin, MS Pierre Pollak, MD, PhD Alim Louis Benabid, MD,

PhD

Paul Krack, MD, PhD

Supplemental data at Neurology.org.

LONG-TERM IMPROVEMENT IN OBSESSIONS AND COMPULSIONS WITH SUBTHALAMIC STIMULATION

Obsessive-compulsive disorder (OCD) may be con- ceptualized as a disorder of self-control and behavioral inhibition.¹ Recent studies^2,3 suggested interest in deep brain stimulation (DBS) of different subcortical brain targets such as the nucleus accumbens, anterior internal capsule/ventral striatum, and subthalamic nucleus (STN) in severe, resistant OCD. STN is a crit- ical node of the indirect and hyperdirect basal ganglia– thalamocortical circuit. STN-DBS may release its function as a brake on behavioral programs, disinhibit- ing habitual responses and enabling more flexible goal- directed behavior control in OCD.^4,5Little is known about long-term outcome of STN-DBS in OCD.

Based on experience in Parkinson disease, STN-DBS can induce a change from apathetic to disinhibited behavior.⁶This target has also a potential impact on addictions.^4,6

The study is listed on clinical trials.gov (NCT00169377).

Case report. A 49-year-old man had chronic, severe OCD starting at age 21 preceded by hyperactivity in childhood and multiple simple and complex motor tics and vocal tics starting as late as age 20 years after being enrolled into military service. Tics and OCD worsened in parallel and the patient was initially diagnosed with Tourette syndrome.⁷Over time, the simple motor tics virtually disappeared, while OCD eventually dominated the clinical picture. Some of the rituals followed a complex evolution: while at the early phases of the illness they appeared as simple involuntary motor tics, they evolved into complex tics and then, over time, were integrated into deliberate rituals and executed in a compulsive manner, in response to obsessions, such as the licking ritual shown on the video at Neurology.org.

Obsessions were centered on imminent catastro- phe, with fatal accidents occurring to his wife and chil- dren. Compulsions consisted primarily of neutralizing mental operations by mental superimposition of sce- narios of accidents with positive images of situations of well-being of his family members.“Just right”compulsions included repetitive throat clearing and touch- ing or licking objects, based on the initial simple tics.

His medical history revealed traumatic biographi- cal events, influencing his OCD theme: his mother’s death from a car accident when he was 10 years old, witnessing a terrorist bomb explosion at age 20 years, and, finally, seeing his beloved grandmother’s dead body the day before his marriage, which eventually triggered the onset of his OCD, without constituting a real posttraumatic stress disorder.

Despite adequate therapeutic trials of psychotherapy (dynamic psychotherapy, cognitive behavioral therapy) and pharmacotherapy (4 selective serotonin reuptake inhibitors, 1 serotonin and norepinephrine reuptake inhibitor, clomipramine, 2 antipsychotics; clonidine, in different combinations), OCD induced major dis- ability, with socioprofessional withdrawal. Alcohol intake, used as a daily sedative after 33 years of age, contributed to emotional lability and several impulsive suicide attempts (benzodiazepines). Clinical assessment eliminated cluster A or B personality disorders.

By age 39 years, considering this disabling chronic and treatment-resistant OCD, the patient underwent neurosurgery for DBS of the associative-limbic part of the STN, as the first Grenoble participant in a French national multicenter study.²

STN-DBS rapidly led to major improvement in OCD (see video) at low voltage (1.3 V/60ms/130 Hz monopolar stimulation bilaterally), paralleled by acute mild hypomania on discharge, which progressively worsened up to full-blown mania at 1.5 V bilaterally. This state improved within less than 30 minutes after a reduc- tion of 0.2 V bilaterally, not requiring hospitalization.

The therapeutic window of DBS between OCD improvement and hypomania remained narrow over years. As a satisfying compromise, some residual OCD were accepted to avoid behavioral disorder.^2,4,5Chronic stimulation with these parameters led to marked improvement in OCD (Yale-Brown Obsessive Compul- sive Disorder Scale [Y-BOCS] decrease from 37 to 9/40 within 3 months), anxiety, and mood. The patient’s social and family lives markedly improved and profes- sional reinsertion became possible. He has been able to reduce his use of alcohol and had major improvement in suicidal ideas, despite 2 suicidal attempts committed in a context of short, partial relapses following self-decided medication discontinuation during the first postoperative years. His overall state has been relatively stable over

Neurology 87 October 25, 2016 1843

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2016 American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

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recent years, requiring only small DBS adjustments.

Currently, after 10 years of follow-up, the Y-BOCS is improved by 43% (current treatment: fluvoxamine 200 mg/d; lorazepam 4 mg/d; 2 V/60ms/130 Hz).

The patient subjectively estimates his improvement at 80%, paralleled by a quality of life better than ever achieved on conventional treatment.

Discussion. We highlight this case as it illustrates rapid onset of improvement and long-term efficacy of STN-DBS in OCD. Initial limbic side effects were transient. The small therapeutic window required cautious DBS management for optimizing outcome.

Future studies will have to confirm the long-term efficacy of STN-DBS in OCD illustrated in this single case report, compare different DBS targets, and identify responder profiles.

From CHU Grenoble (M.P., S.C., T.B., C.A., P.K.); Grenoble In- stitut des Neurosciences–Inserm U1216 (M.P., S.C., T.B., P.K.), University Grenoble Alpes, France; University Hospital Geneva and University of Geneva (P.P., P.K.), Switzerland; and Clinatec (A.L.B.), Grenoble, France.

Author contributions: M.P. and P.K. contributed to drafting of the manuscript. M.P., P.K., A.L.B., C.A., P.P., S.C., and T.B. were involved in the pluridisciplinary management (evaluation, surgical intervention, postoperative adaptation of DBS and medications, as well as 10-year follow-up of this historical first patient treated by STN-DBS for OCD in the multidisciplinary team). These authors all critically read and revised the manuscript.

Study funding: The patient took part in the STOC study (ClinicalTrials.gov NCT00169377), funded by grants from the Programme Hospitalier de la Recherche Clinique Assistance Pub- lique–Hôpitaux de Paris (AOM 03141) and the Agence Nationale de la Recherche Program for Young Researchers (R05121DS).

Medtronic purchased the stimulators.

Disclosure: M. Polosan has received reimbursement for traveling costs for participation in scientific meetings by Medtronic. S. Chabardes, T. Bougerol, C. Ardouin, P. Pollak, and A. Benabid report no disclosures relevant to the manuscript. P. Krack has received research grants and reimbursement for traveling costs for participation in scientific meetings by Medtronic, St Jude, and Boston Scientific: all 3 companies manufacture neurostimulators. Go to Neurology.org for full disclosures.

Received November 21, 2015. Accepted in final form July 11, 2016.

Correspondence to Dr. Krack: [email protected]

1. Robbins TW, Gillan CM, Smith DG, de Wit S, Ersche KD. Neurocognitive endophenotypes of impulsivity and compulsivity: towards dimensional psychiatry. Trends Cogn Sci 2012;16:81–91.

2. Mallet L, Polosan M, Jaafari N, et al; STOC Study Group.

Subthalamic nucleus stimulation in severe obsessive- compulsive disorder [erratum 2009;361:1027]. N Engl J Med 2008;359:2121–2134.

3. Denys D, Mantione M, Figee M, et al. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 2010;

67:1061–1068.

4. Krack P, Hariz MI, Baunez C, Guridi J, Obeso JA. Deep brain stimulation: from neurology to psychiatry? Trends Neurosci 2010;33:474–484.

5. Jahanshahi M, Obeso I, Baunez C, Alegre M, Krack P.

Parkinson’s disease, the subthalamic nucleus, inhibition, and impulsivity. Mov Disord 2015;30:128–140.

6. Castrioto A, Lhommée E, Moro E, Krack P. Mood and behavioural effects of subthalamic stimulation in Parkinson’s disease. Lancet Neurol 2014;13:287–305.

7. Cavanna AE, Servo S, Monaco F, Robertson MM. The behavioral spectrum of Gilles de la Tourette syndrome.

J Neuropsychiatry Clin Neurosci 2009;21:13–23.

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DOI 10.1212/WNL.0000000000003248

2016;87;1843-1844 Published Online before print September 21, 2016 Neurology

Mircea Polosan, Stephan Chabardes, Thierry Bougerol, et al.

Long-term improvement in obsessions and compulsions with subthalamic stimulation

This information is current as of September 21, 2016

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http://www.neurology.org//cgi/collection/tics Tics

http://www.neurology.org//cgi/collection/all_psychiatric_disorders All Psychiatric disorders

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