Deep brain stimulation of ventral internal capsule for refractory obsessive-compulsive disorder.

The main objective of this study is to assess the effectiveness of deep brain stimulation (DBS) of the ventral striatum (VS) of the anterior limb of internal capsule for patients suffering from refractory obsessive-compulsive disorder (OCD) and to compare its result with traditional anterior capsulotomy. The present study consisted of two patients subjected to stimulation of ventral capsule (VC)/VS region of internal capsule for refractory OCD. Leads were implanted on both sides stereotactically using fused images of magnetic resonance imaging and computed tomography scan brain and connected to pulse generator (Medtronic). Outcome of both the patients was measured by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory (BDI), and Mini-Mental Status Examination. The first case was followed for 4 years and 6 months, while the second case was followed for 2 years and 6 months. Both the patients responded very well to stimulation with reduction of Y-BOCS from 38 to 12 (68.42% improvement) in the first patient and 38 to 10 (78.68% improvement) in the second patient after 1 year. BDI also improved in both the patients with no significant change in mental state. No adverse effect was seen in any of the patient. The beneficial effect of DBS persisted in both the patients till follow-up and was much superior to the beneficial effect of anterior capsulotomy. We conclude that DBS of VC/VS complex is very safe and effective in refractory OCD and shows considerable promise for the future. The result of two treated patients was much better as compared to lesioning (anterior capsulotomy) and the beneficial effect persisted for long time. Copyright:

INTRODUCTION

Obsessive–compulsive disorder (OCD) is generally believed to be one of the most distressing of all anxiety disorders. Clinical experience with patients suggests that it affects the quality of life in many ways in the form of troubled relationship, work distraction. Patient feels bonded by obsession and compulsions, and they spent lot of time on compulsive rituals.[1] OCD patients are more likely to have divorce then non-OCD individual.[2]

Both pharmacological and cognitive behavioral therapy (CBT) has proven to be effective treatment in OCD.[3] However, full or partial remission is seen in 60%–80% patients and the remaining patients experience only a minimum or no response.

Despite medications and CBT, some OCD patients remain refractory and run a chronic deteriorating course.[4] In a follow-up of patients who have never undergone surgical intervention for different reason, their condition remained the same and some of them committed suicide.[5]

Therapeutic option in this group was initially limited to ablative surgeries such as anterior capsulotomy[6] or anterior cingulotomy.[7] The observation that lesion effect can be achieved by electrical current delivered at that level led to the development of implantable stimulation system to treat neurological disorder. Since deep brain stimulation (DBS) system consists of delivering high-frequency current at the target region without resulting in any neuronal injury led to the initiation of its use for patients who need capsulotomy for OCD. The effectiveness of DBS for OCD was established in various publications[891011] where anterior limb of internal capsule (ALIC) was used for stimulation. They used stimulation of ALIC 3–4 mm anterior to anterior commissure. A more posterior and ventral target was found to be more effective for controlling symptoms of OCD.[12] In a review article published in 2014, the effectiveness of various target for OCD was compared. The study was sponsored by the American Society of Stereotactic and Functional Neurosurgery and Congress of Neurological Surgeon and endorsed by the American Association of Neurological Surgeon. They found significant improvement after bilateral nucleus accumbens stimulation for medically refractive OCD and recommended it a reasonable therapeutic option in patient with severe treatment-refractory OCD.[13]

The current study is aimed to see the effect of DBS of posterior or and ventral part of internal capsule on severity of OCD symptoms after 3 months, 6 months, and then yearly follow-ups.

MATERIALS AND METHODS

Present series consisted of two patients having intractable OCD. This small sample size was because of unwillingness of patients/attendants to give consent for surgery. The study was approved by respective hospital's ethical committee. Two psychiatrists independently assessed each patient. Both the patients fulfilled the criteria for OCD (33.30) according to the Diagnostic and Statistical Manual of Psychiatric Disorders 4th edition (DSM-IV).[14] The enrolment required their agreement on diagnosis and refractiveness of OCD symptoms. Inclusion criteria were: diagnosis of OCD with a documented duration of at least 5 years, age between 18 and 60 years, OCD rated as severe or extreme illness, failed to improve following treatment with at least three selective serotonin reuptake inhibitors (SSRIs), completed or tried to complete CBT, no serious psychiatric disorder in addition to OCD (e.g., comorbid personality disorder) or substance abuse issues, and no other neurological disorders, including dementia.

Both the patients provided informed consent from themselves and family members. Both the patients have tried at least two to three antiobsessional medications (SSRI, clomipramine, and antipsychotic). Both the patients have received CBT as well. Both the patients had stable medications at least 6 weeks before surgery. The outcome of both the patients was measured by Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) scale, Beck Depression Inventory (BDI), and Mini-Mental Status Examination (MMSE).

YBOC is a 40-item scale in which patients answer 20 questions related to obsessions and 20 related to compulsions. High score of YBOCS are related to more severe OCD symptoms. In most open-label studies, response to DBS in OCD is defined by 35% or greater improvement in YBOCS scores as compared to those recorded at baseline.[1516]

BDI is a self-related 21-item questionnaire. It is an instrument to measure behavioral manifestation of depression. The total scores 0–10: normal; 11–16: dysphoria; 17–20: borderline depressed; 21–30: moderately depressed; 31–40; severely depressed; 41–63: very severely depressed.[17]

MMSE is a tool for different mental abilities such as memory, attention, and language. It is a series of questions and tests, each of which scores point if answered correctly. The maximum score is 30. The response of the therapy can be assessed by the change in the score.[18]

The pre- and postoperative assessment was done by two clinical psychologists who independently assessed both the patients.

Target for stimulation was deep ventral at ALIC 0–1 mm posterior to anterior commissure 5–6 mm from the midline. Leads were implanted stereotactically on both sides under local anesthesia and sedation. Surgical trajectory planning used fused images of magnetic resonance imaging (MRI) and computed tomography scan brain. Quadripolar-stimulating electrodes (Model 3387 Medtronic)[6] were used on both sides, and they are connected to Pulse Generator (Medtronic) by connecting leads under general anesthesia. The electrode contact 0 was placed in the ventral striatum just below the axial plane defined by the anterior and posterior commissure, contact 1 and 2 in the ventral half of capsule and contact 3 at the dorsal margin of the capsule. In the first case, nonrechargeable pulse generator (Kinetra) was used, while in the second case, rechargeable pulse generator (Activa RC) was used. Postoperatively, MRI brain was done to check position of electrodes before connecting stimulating electrodes to pulse generator. Programming of the device was started after 6 weeks and continued for 6 to 8 months till the patient shows significant improvement. Medications were kept unchanged. Neuropsychiatric evaluation was done after 3 months and 6 months. Afterward, yearly follow-up was done.

Case 1

A 48-year-old homemaker and a mother of two children had symptoms of OCD for the last 20 years. She feels contaminated by drain water and seeks reassurance frequently from her husband. She had doubts that she might have touched drain water and frequently washed herself. Her husband had to open and close taps as she thought they would be contaminated. When her husband and son would go out of the house, she would sit immobile at home, she would not cook, eat, or even go to the toilet out of fear of contamination. Cooking was an elaborate ritual where she used to order her son to do the various chores and would make him wash any utensils she had touched. The family frequently would eat food from outside. She was treated with medication and CBT earlier. 8–9 years ago, she stopped medication; subsequently, she had recurrence of symptoms. She kept worsening despite use of SSRIs and augmenting them with various combination of medication. Clinically, she had obsessions of dirt and contamination, obsessional doubts, and compulsive washing. She was registered for the surgery on January 1, 2010.

Before surgery, her Y-BOCS was 38, BDI was 22, and MMSE was 29. She fulfilled the DSM-IV criteria for OCD. She was subjected to DBS on August 23, 2010. Ventral striatum and ALIC were targeted for stimulation and Medtronic 3387 lead along with Kinetra (nonrechargeable pulse generator) was implanted [Figures 1 and 2].

Figure 1

Magnetic resonance imaging axial image of Case 1 showing electrodes in ventral capsule/ventral striatum complex

Figure 2

Magnetic resonance imaging coronal image of Case 1 showing electrodes in ventral capsule/ventral striatum complex

She was evaluated and after 3 months her Y-BOCS reduced to 14, her BDI reduced to 16, and her MMSE remained unchanged at 29. She continued to have improvement in her symptoms of obsession and compulsion. She was followed up, and after 6 months, her Y-BOCS and BDI scores were reduced to 12 each [Table 1]. After 1 year of surgery, her scores were remain unchanged. She started cooking and all other household work, started going to market. Her obsession for cleanliness improved.

Table 1

Outcomes of Case 1

	Y-BOCS (percentage improvement)	BDI (percentage improvement)	MMSE
Preoperative	38	22	29
After 3 months	14 (63.15)	16 (27.27)	29
After 6 months	12 (68.42)	12 (45.45)	29
After 1 year	12 (68.42)	12 (45.45)	29

Y-BOCS – Yale-Brown Obsessive-Compulsive Scale; BDI – Beck Depression Inventory; MMSE – Mini-Mental Status Examination

She started having reoccurrence of signs and symptoms from January 2013 due to battery depletion of her pulse generator. She was operated again, and new Kinetra (nonrechargeable pulse generator) was replaced on March 8, 2013. Her symptoms improved again. In January 2015, her Y-BOCS, BDI, and MMSE scores were 12, 12, and 29, respectively.

Case 2

A 45-year-old married female had intractable OCD. Her symptoms started when she was 19 years old. She was registered to OPD on December 15, 2012. Her main obsession was for dirt, germs, and white liquid. She was frequently washing herself and had checking compulsion also. Her illness gradually progressed. Initially, she responded to medications but slowly response to medications declined. These symptoms were progressed gradually to indecisiveness, there was frequent fight in family and she used to remain in toilet for many hours. She tried to commit suicide but was revived. After her marriage, there was frequent argument with her husband and her symptoms worsened after delivery. She fulfilled DSM-IV criteria for OCD. She could not get benefit with anti-obsession medications and cognitive and behavioral therapy.

Before surgery, her Y-BOCS was 38, her BDI was 24, and her MMSE was 28.

She was operated on July 12, 2013. DBS in ventral striatum and ALIC were done. Medtronic 3387 leads along with Activa RC (Rechargeable Impulse Generator) were implanted.

She responded very well to stimulation. Her symptoms of obsession for cleanliness have improved, and after follow-up of 2 years and 6 months, her Y-BOCS reduced to 10. Her BDI was 07 and her MMSE remained at 28 [Table 2].

Table 2

Outcomes of Case 2

	Y BOCS (percentage improvement)	BDI (percentage improvement)	MMSE
Preoperative	38	24	28
After 3 months	12 (68.42)	10 (58.33)	28
After 6 months	10 (73.68)	07 (70.83)	28
After 1 year	10 (78.68)	07 (70.83)	28

Y-BOCS – Yale-Brown Obsessive-Compulsive Scale; BDI – Beck Depression Inventory; MMSE – Mini-Mental Status Examination

DISCUSSION AND RESULTS

The primary aim of this study is to determine the efficacy of DBS for OCD and to compare its result to traditional anterior capsulotomy, for which its potential replacement and to know the effectiveness of present target for stimulation. As the quality of life improvement is well-established finding after DBS, the current study examined the effect of DBS of ventroposterior part of ALIC in a nonrandomized way for ethical reasons. The literature[5] indicates that anterior capsulotomy produces a 35% improvement in OCD symptoms in about 45% of operated patients.

The present series of two patients showed very significant improvement in both cases. Our first case reported 68.42% improvement in her Y-BOCS, 45.45% of improvement in BDI score after 1 year. Similar finding was observed in the second patient where Y-BOCS reduced from 38 to 10 (73.68% improvement) and BDI improved to 70.83%. There was no change in MMSE score in both cases that signifies no adverse effect on mental status. Both the patients showed more than 35% improvement that was much superior to results achieved by bilateral capsulotomy. Very significant improvements in the present series relate to the placement of leads that were more posterior and ventral. The worldwide collaborative study also showed more effectiveness of ventral and posterior target as compared to anterior target. One hypothesis for better outcome in posterior and ventral location is the more compact organization of cortico-striatal-thalamo-cortical network in that region.[13]

DBS was tolerated very well by both the patients as no adverse effect related to placement of electrodes or stimulation was observed.

There was recurrence of symptoms of OCD in the first patient after 19 months related to depletion of battery that improved after replacement with newer one. This problem was rectified in the second patient where rechargeable DBS system was used that has long battery life.

CONCLUSION

We conclude that DBS of ventral capsule/ventral striatum complex is very safe and effective in refractory OCD. The long-term result of this small controlled study is much better as compared to lesioning (capsulotomy). By virtue of its reversibility and potential larger area of stimulation, it opens window on neurocircuitry involved in pathophysiology of OCD. A search for ideal target sites within the brain, which may allow better results with less current, is also clearly needed. More research work with larger sample size and long-term follow-up would be needed to evaluate whether therapeutic benefit persists for long time with disease progression.

For this therapy, collaborative relationship between psychiatrist and neurosurgeon is essential. The neurosurgeon should have extensive experience in stereotactic skill and surgery and psychiatrist should have expertise in managing advanced cases of OCD.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.