Peer-Review ReportDeep Brain Stimulation of the Nucleus Accumbens and Bed Nucleus of Stria Terminalis for Obsessive-Compulsive Disorder: A Case Series
Introduction
OCD is defined by the presence of obsessions, compulsions, or both. Obsessions are recurrent and persistent thoughts, impulses, or images that are experienced as intrusive and inappropriate; compulsions are repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession or according to rules that must be applied rigidly (2). OCD was classified as an anxiety disorder in the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM); the DSM-V has included a new chapter on obsessive-compulsive spectrum disorders, reflecting the fact that OCD is a separate category from anxiety disorders and forms a spectrum together with hoarding disorder, trichotillomania, and other OCD-related disorders. Compared with other psychiatric conditions, such as affective or psychotic disorders, OCD may appear in full-blown form early in life. It has a lifetime and 12-month prevalence estimates of approximately 2.3% and 1.2% respectively 13, 19, 37, and causes significant impairment in work and social functioning, as well as reduced quality of life, making it a significant cause of disability 15, 25. Although some patients may present acute or episodic OCD, it is usually a chronic disorder: patients with chronic OCD may experience periods of exacerbation and remission or progressive worsening over time with deterioration of global functioning.
First-line treatments include cognitive behavioral therapy (CBT) with fear exposure and response prevention 1, 11, 33, 35, as well as pharmacotherapy, namely selective serotonin-reuptake inhibitors (SSRIs). Patients who have not responded to at least 2 adequate trials of first-line medications may benefit from clomipramine or from an augmentation strategy, that is, lithium, clonazepam, atypical antipsychotics, or electroconvulsive therapy (ECT) 5, 7, 9, 38. A combination of pharmacotherapy and CBT is often used 10, 14.
It is a well-accepted fact that many patients with OCD do not respond to traditional medication or CBT. Different factors may influence response to treatment: for instance, symptoms such as hoarding compulsions, and obsessions focused on sexual or religious themes, are predictive of poorer outcome. Severity of illness, as measured with the Yale Brown Obsessive-Compulsive Scale (Y-BOCS), is also related to poor treatment response, as is the copresence of depressive or anxiety symptoms 3, 20, 35, 42. Up to 10% of patients with OCD are considered to be treatment resistant, meaning that, despite appropriate treatment, they still display severe symptoms 3, 7, 21, 22. In pharmacologic trials, treatment resistance is defined as a failure to respond (a response is considered a decrease of 35% in Y-BOCS scale's score) to 3 first-line medications (SSRIs or clomipramine), 2 second-line medications (augmentation strategies), and at least 6 months of CBT.
The neurobiological underpinnings of OCD include widespread abnormalities in the basal ganglia and frontal regions (32). Imaging studies suggest that in patients with OCD, there is abnormal metabolic activity in the orbitofrontal cortex, the anterior cingulate/caudal medial prefrontal cortex, and the caudate nucleus 34, 39, 43, 44.
Electrical stimulation of the brain was used to map cortical function in the 1930s (30), but it was only later that neurosurgeons began investigating the effects of stimulating deeper structures (17). Deep brain stimulation (DBS) originally was used for the treatment of movement disorders, namely essential tremor and Parkinson's disease (31). Surgical treatment for psychiatric disorders (psychosurgery) has been used since the 1940s and includes lesional procedures such as capsulotomy 23, 27, 36, subcaudate tractotomy, and limbic leucotomy (a combination of subcaudate tractotomy and anterior cingulotomy) (18) for the treatment of OCD. In early 2009, the U.S. Food and Drug Administration granted limited humanitarian approval for DBS for otherwise-intractable OCD (18).
Not all patients with OCD can be considered candidates for DBS. From a psychiatric standpoint, potential candidates have to satisfy the following conditions: chronicity (duration of illness, usually over 5 years), severity (usually cut-off is a Y-BOCS score of 28 or greater), and treatment resistance, as previously described. Careful screening of candidates is crucial. In this report we present a series of 8 patients who underwent DBS of different surgical targets for OCD between 2009 and 2014 at Istituto Neurologico “Carlo Besta” in Milan.
Section snippets
Patients and Methods
Written informed consent was obtained from all patients for publication of this case series. Copies of the written consent and CARE checklist are available.
Methods
T1, T2, and fluid-attenuated inversion recovery magnetic resonance brain images were obtained preoperatively for all patients; the morning of surgery, after general anesthesia, a Leksell G-frame was applied and a computed tomography scan performed. After adequate merging of the 2 examination results in a neuronavigation system (Medtronic, Minneapolis, Minnesota, USA) and use of direct and indirect targeting techniques (performed on a separate computer), the 2 methods were compared with the
Results
In the postoperative period, a volumetric brain computed tomography scan was obtained for all patients and merged with preoperative brain magnetic resonance scan; in both cases the correct positioning of the intracerebral electrodes was confirmed. Clinical outcome at 5-year follow-up for Patients 1, 2, 3, and 4 are available. Changes in OCD symptoms are shown in Figures 1 and 2 for all patients. Patients 1 and 2 presented a slow but evident clinical improvement of both obsessive–compulsive and
Discussion
Since DBS was approved for treatment-resistant OCD, there have been many trials that have used DBS for the treatment of chronic, severe, treatment-resistant OCD, and many surgical targets have been proposed, including the NACC, the anterior limb of the internal capsule, the subthalamic nucleus, the globus pallidus pars interna, and the BNST. Before that, the only options for patients who did not respond to traditional first- and second-line treatments consisted of stereotactic ablation. The
Conclusions
DBS of the NACC core nucleus and of the BNST seems a promising treatment for OCD. Advantages compared with lesional treatments are the less invasiveness and its reversibility and modularity. Further studies are warranted to help identify clinical predictors of outcome, and a crucial issue is still appropriate screening of potential candidates, ensuring that patients are selected according to stringent inclusion and exclusion criteria. Overall, DBS seems a safe, reversible. and adaptable
Acknowledgments
Dr. Rebecca Ranieri actively screened and assessed 2 patients for the present study. Dr. Michele Rizzi assisted Dr. Messina and Dr. Franzini in several surgeries.
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Conflict of interest statement: Dr. Lucrezia Islam and Prof. Orsola Gambini have previously participated as associate and principal investigator, respectively, in clinical trials sponsored by Medtronic. The remaining authors have no conflicts to report.