Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: Outcomes after one year

Abstract

Objective

To investigate the effects of unilateral deep brain stimulation (DBS) in the right nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Predominantly bilateral stimulation of the anterior limb of the internal capsule was utilized.

Methods

The study was designed as a double-blind sham-controlled crossover study. Patients received 3 months of deep brain stimulation followed by 3 months of sham stimulation, or vice versa. Subsequently, stimulation was continued unblinded for all patients. The primary outcome measure was the severity level of OCD, measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Secondary outcome measures were depressive symptoms, anxiety, psychological symptom severity, global functioning, quality of life, and cognitive function.

Results

The mean Y-BOCS scores decreased significantly from 32.2 (±4.0) at baseline to 25.4 (±6.7) after 12 months (p = 0.012). Five out of ten patients showed a decrease of more than 25%, indicating at least a partial response. One patient showed a decrease in Y-BOCS severity greater than 35%. Similarly, depression, global functioning and quality of life improved within one year. In contrast, anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well-tolerated.

Conclusions

DBS of the unilateral right nucleus accumbens showed encouraging results in patients with treatment-resistant OCD. Five out of ten patients reached at least a partial response after the first year.

Introduction

Obsessive-compulsive disorder (OCD) is a chronic and widespread psychiatric disorder with a worldwide prevalence of about 2%. For most patients, cognitive-behavioral therapy (involving exposure to and prevention of rituals) and medications such as clomipramine and serotonin reuptake inhibitors have proven efficacy. Nonetheless, an estimated 10% of patients remain resistant to treatment and thus are markedly affected by OCD. For this group, neurosurgical interventions can be considered as a last-resort treatment option. So far, the most effective interventions, such as anterior capsulotomy or anterior cingulotomy, all include methods of ablative surgery [1].

In the late 1990 s, Nuttin and Cosyns published the first case series of patients with treatment-resistant OCD undergoing deep brain stimulation (DBS) [2]. This stereotactical method involves surgically implanted electrodes. It has been used mainly for the treatment of Parkinson's disease and tremor. Besides the work of Nuttin's group with case series of up to six patients [3], [4] and several case reports [5], [6], a sham stimulation controlled study of four patients [7] and an open-label case series of ten patients including outcomes of up to three years in patients with treatment-resistant OCD receiving DBS [8] have recently been published. In almost all reported cases, a bilateral stimulation was applied in the anterior limb of the internal capsule (ALIC), similar to the target region of the anterior capsulotomy. But the electrode designs varied between the groups, and in some cases the stimulation area was extended to the adjacent ventral striatal regions including the nucleus accumbens (NAC).

Cortico-striato-thalamo-cortical (CSTC) circuits and their different physiologic functions were first described by Alexander et al. [9]. They support the idea that dysfunctions in these loops also implicate the pathogenesis underlying OCD, which is caused by a failure of inhibition of the ventral striatum [10]. The nucleus accumbens is part of the ventral striatum, along with other parts of the tuberculum olfactorium, ventromedial parts of the nucleus caudatus, and the putamen. We consider the NAC to be a promising target location for DBS, because of its predominant role in modulating these circuits [11]. In addition, the NAC borders ventrally on the anterior limb of the internal capsule, and the lateral subventricular fundus of the nucleus accumbens is even permeated in rostral sections by numerous internal capsule fiber bundles. We therefore expected that the electrode trajectories and stimulation target that we selected would have an additional effect on the fiber systems of the internal capsule. The NAC was introduced as a primary target for DBS in treatment-resistant OCD by Sturm and co-workers. A pilot series showed that the right stimulation of the NAC yielded the best results; whereas, bilateral stimulation showed no additional benefit [12].