Surgery for Obsessive-Compulsive Disorder

Introduction

Obsessive-compulsive disorder (OCD) is one of the most common neuropsychiatric disorders, affecting about 2% to 3% of the population. OCD is the 10th leading cause of disability worldwide and affects both genders equally. ^, OCD is the key example of the obsessive-compulsive and related disorders, a group of conditions that are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). According to the DSM-5, OCD is characterized by persistent obsessions with intrusive thoughts that lead to severe generalized anxiety or compulsions in the form of repetitive tasks to relieve this distress. ^, These compulsions are severe enough and last long enough (>1 h/day) to interfere with one’s routine activities, performance at work, family and social interactions. ^, In addition to these symptoms, patients with OCD are twice as likely to report suicide attempts as those with other psychiatric disorders. Pharmacotherapy such as the use of selective serotonin reuptake inhibitors (SSRIs) and cognitive behavior therapy (CBT) are the first-line treatment option for patients with OCD. ^, These therapeutic measures provide a 40% to 60% reduction in OCD symptoms in 50% of patients. However, despite aggressive pharmacotherapy and CBT, 10% to 25% of patients remain treatment resistant, leading to significant morbidity. ^{, , ,}

Surgical management is an option for patients with medically refractory OCD ( Fig. 122.1 ). The surgical treatment of various psychiatric disorders can be dated back to the origin of neurological surgery; however, surgery fell out of favor because of a poor understanding of the pathophysiology of psychiatric disorders and the high surgical morbidity and mortality associated with frontal lobotomy. Furthermore, variable reporting of surgical outcomes, high complication rates, and the development of effective medications made surgical therapy obsolete. Neuroscience advances and evolution in brain imaging techniques not only improved our understanding of the pathophysiology of psychiatric disorders but also led to a renewed interest in the surgical treatment of refractory psychiatric disorders, including OCD. Various surgical targets have been explored with deep brain stimulation (DBS) and ablation approaches with good clinical results.

The success of DBS surgery for a variety of movement disorders has led to the exploration of this treatment modality for medically refractory OCD. Both the minimally invasive nature of DBS surgery and its excellent safety profile make it a favorable technique for treating functional brain disorders. Worldwide, more than 160,000 patients have received DBS implants for a variety of disorders, including OCD. Currently more than 300 patients have undergone DBS surgery for medically refractory OCD, and it was approved by the US Food and Drug Administration (FDA) in 2009 under Humanitarian Device Exemption (HDE) status. This chapter focuses on the surgical management of OCD, with an overview of the pertinent literature, historical aspects of psychosurgery, pathophysiology, involved circuits, different anatomic targets, ethical considerations, current challenges with DBS systems, and recent advances in DBS surgery. We also discuss the use of MR-guided focused ultrasound (MRgFUS) as an evolving noninvasive ablative neurosurgical tool.

History of Psychosurgery

The current role of neurosurgery in the treatment of OCD and other psychiatric conditions has evolved significantly from its troubled past. Surgical techniques have transformed from simple trephination used to treat madness in the Neolithic and Renaissance eras, to ablative surgery as early as the 1890s, to sophisticated modern-day stereotactic DBS surgery, ^{, ,} and recently to incisionless transcranial MRgFUS ablation. ^,

Psychosurgery was popularized in 1935 with the introduction of frontal leucotomy/lobotomy by Portuguese neurologist Egaz Moniz and neurosurgeon Pedro Almeida. Their clinical work was based on the success of frontal ablative procedures in primates by American neuroscientists John Fulton and Carlyle Jacobsen. Moniz and Almeida treated their first seven patients with ethanol injection into the centrum semiovale through a lateral trepanation in the skull. After finding that they needed to repeat the procedure multiple times, they altered their technique, employing a leucotome (a cannulated instrument that produced a 1-cm lesion in the white matter) to lesion the brain, typically producing six lesions in each of the frontal lobes. ^, In 1949 Moniz was awarded the Nobel Prize in Physiology or Medicine for “the discovery of the therapeutic value of leucotomy in certain psychoses. ^, Neurologist Walter Freeman and neurosurgeon James Watts popularized Moniz’s technique in the United States. In 1942, they communicated their initial findings in 200 frontal lobotomy patients, reporting that 63% showed symptomatic improvement. Although effective, prefrontal leucotomy was associated with significant complications such as uncontrolled hemorrhage, seizures, apathy, and death. Later, Freeman developed and popularized bilateral transorbital frontal leucotomy, in which a sharp leucotome (orbitoclast) was introduced into the frontal lobes through the thin orbital roof. This procedure was performed in an outpatient setting, with electroconvulsive therapy used as general anesthesia. The technique was used liberally for a variety of psychiatric illnesses, and more than 60,000 transorbital leucotomies were performed by 1956. ^, The widespread and indiscriminate use of this crude surgical technique with a relative paucity of appropriate assessment tools and controlled studies led to disastrous outcomes. Both the medical community and the public viewed the procedure as inhumane and called for an end to the practice of psychosurgery. Furthermore, the advent of more effective pharmacotherapies ended this era of psychosurgery. ^{, ,}

Although there was a significant decline in the practice of psychosurgery, there was still an impetus for research into possible surgical treatment modalities for severe psychiatric disorders. Introduction of a stereotactic coordinate system by French neurosurgeon Jean Talairach and Cartesian stereotactic systems developed by Spiegel and Wycis and by Leksell in late 1940s coupled with neuroscience development enabled neurosurgeons to perform stereotactic neurosurgery and also psychosurgery with greater precision and safety, thereby minimizing the complications associated with cruder frontal leucotomies. ^{, ,} Stereotactic ablative procedures such as cingulotomy, anterior capsulotomy, subcaudate tractotomy, and anterior callosotomy replaced frontal leucotomies and lobotomies for refractory psychiatric disorders. ^{, ,} Various lesioning techniques such as radiofrequency thermocoagulation and radioisotope (yttrium 90) implantation or stereotactic radiosurgery were used to perform these ablative procedures. ^, There has been a recent increased interest in ablative procedures with the introduction of the MRgFUS technique, which does not require an incision or hardware. MRgFUS is an FDA- and CE marking–approved treatment for essential tremor and tremor-dominant Parkinson disease, and has been demonstrated to be safe and effective in the treatment of tremor. ^, The initial experience of MRgFUS capsulotomy in OCD is encouraging. There is a renewed interest in ablative treatment, and recent review and meta-analysis have suggested a relatively better outcome with ablative procedures than with DBS. ^{, ,} The widespread use of DBS for movement disorders has provided a reversible and adjustable surgical option for the treatment of OCD. There are pros and cons to both approaches, and the decision to use lesioning or DBS is often determined by the expertise and choice of a center and patient preference.

Neural Circuits and Pathophysiology

The functional organization of neural circuits implicated in the pathophysiology of psychiatric disorders is increasingly better understood with the evolution in neuroscience and neuroimaging. Multiple parallel basal ganglia–thalamocortical loops (cortical-striatal-pallidal-thalamic-cortical loops) were identified by Alexander and colleagues that process cortical inputs from the motor, oculomotor, dorsolateral prefrontal, lateral orbitofrontal, and anterior cingulate regions ( Fig. 122.2 ). Each of these circuits includes functionally and anatomically discrete regions of the striatum, globus pallidus and substantia nigra, thalamus, and cortex. Although these circuits are anatomically and functionally segregated, there is connectivity between them, so limbic, cognitive, and motor pathways are integrated.

The symptoms of OCD manifest as abnormalities in multiple interweaved neural circuits that form a complex network that regulates mood and anxiety ^, ( Fig. 122.3 ). The basal ganglia−thalamocortical loop implicated in the pathophysiology of OCD originates in the prefrontal cortex and orbitofrontal cortex (OFC) and projects to the ventral striatum through the ventral internal capsule. Specifically, these fibers reach the ventral aspect of the caudate and the nucleus accumbens (NAcc) and are excitatory in nature by means of glutamate and aspartate. ^, This area also receives inhibitory serotonergic input from the dorsal raphe nucleus of the midbrain. From the ventral striatum, the fibers then project to the ventral pallidum and are mediated by substance P, enkephalin, and γ-aminobutyric acid (GABA). ^, Inhibitory projections then reach the mediodorsal aspect of the thalamus. Finally, the thalamus projects fibers back to the OFC. The overall output of this pathway is inhibitory in nature and seeks to dampen the input to the cortex. ^{, ,} There also exists a parallel circuit originating in the anterior cingulate cortex (ACC), with projections to the ventral striatum and pallidum and termination in the mediodorsal aspect of the thalamus. This loop then projects back to the ACC. The anterior cingulate loop is believed to underlie the anxiety component of OCD, whereas the circuit originating in the OFC is thought to mediate the core symptoms of OCD. Moreover, although the basal ganglia−thalamocortical loop originating in the OFC is inhibitory in nature, the cortical-thalamic-cortical circuit originating in the orbitofrontal and prefrontal cortices is excitatory in nature. These loops are also referred to as the direct and inhibitory pathways, respectively. ^, The positive feedback loop originates in the orbitofrontal and prefrontal cortices and projects to the dorsomedial thalamic nucleus through the anterior limb of the internal capsule (see Fig. 122.3 ). In a normal state, this excitatory pathway is dampened by the net inhibitory output of the aforementioned basal ganglia−thalamocortical loop. There is also a net effect of decreased thalamic stimulation of the cortex through pallidothalamic connections, which are mediated by GABA. ^, It is believed that OCD symptoms arise when the equilibrium between these finely tuned pathways is lost. An additional loop involving the limbic and Papez circuits underlies the emotional aspects of OCD. Widespread connections between the ACC, OFC, dorsomedial thalamus, NAcc, and Papez circuit may mediate the limbic component of OCD. ^, Obsessive-compulsive symptoms are caused by either decreased activity in the basal ganglia−thalamocortical (striatal-pallidal-thalamic-cortical) loops or increased activity in the cortical-thalamic-cortical (orbital-frontal-thalamic) loops. In general, there is increased stimulation of OFC due to decreased modulation by the cortical-subcortical circuits, resulting in the OCD symptoms. Therefore modulating either of these pathways and the Papez circuit could possibly ameliorate the obsessive-compulsive, anxiety, and emotional symptoms associated with OCD.

One of the largest neuroimaging analyses to date in OCD, consisting of 16 pediatric data sets (501 patients with OCD and 439 healthy control subjects) and 30 adult data sets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-analysis) Consortium, noted asymmetry in the thalamus and pallidum, but only in pediatric OCD. This asymmetry was left hemispheric and was mainly due to increase in the volume of thalamus and decrease in the volume of pallidum. These subcortical changes are in agreement with the previous study and favors cortico-striato-thalamo-cortical circuitry involvement. The pathophysiologic basis of this asymmetry needs further evaluation, as this asymmetry was unrelated to the medication status, age at a disease onset, disease duration, current anxiety and depression comorbidity, or disease symptoms.

Investigators in functional neuroimaging (positron emission tomography [PET] and functional MRI [fMRI]) studies have reported abnormally increased metabolic activity of the prefrontal cortex, ACC, OFC, caudate, and thalamus in OCD patients in both neutral and provoked states as compared with healthy individuals. ^{, ,} Studies have also reported decreased levels of N -acetyl aspartate (a marker of neuronal density) in the medial prefrontal cortex and its correlation with symptom severity in patients with OCD as compared with healthy controls. A decrease in metabolic activity in the pathologic cortical-subcortical loop (OFC, bilateral caudate, and cingulate gyri) has been shown in patients with OCD after successful treatment with either medications (SSRIs) or behavior therapy. ^{, , , ,} In addition, the ventral and anterior striatum, which receives cortical afferents from the ACC and OFC, has a high concentration of striosomes compared with other regions. ^{, ,} These striosomes are specialized to influence negative feedback inhibition on the frontal-subcortical circuits by inhibiting dopaminergic input to the region. When there is dysfunction in the striosomes, there is hyperactivity in the caudate nucleus, which is thought to lead to inhibition of negative feedback on the frontal cortices. This allows for the higher-than-normal levels of stimulation of the frontal cortex and deficits in cognitive and emotional functioning that are central to OCD. These neuroimaging, anatomic, and physiologic studies provide insight into the pathophysiology of OCD that may identify new nodes for surgical intervention.

To simplify neural circuits for surgical treatment, a “three-circuit” frontal lobe model can be considered:

• 1.

  The dorsolateral circuit, anatomically originating in the dorsolateral aspect of the frontal lobe with projections to the head of caudate and medial putamen

• 2.

  The orbitofrontal circuit, anatomically originating in the inferolateral prefrontal cortex with projections to the medial caudate and NAcc

• 3.

  The anterior cingulate circuit, anatomically originating in the anterior cingulate gyrus with projections to the ventromedial striatum

It is of importance to highlight that the basal ganglia are the initial target for all three frontal lobe circuits, and modern functional neurosurgery for OCD focuses mainly on targeting these three circuits.

Patient Selection, and Team Approach

Given the challenging history of psychosurgery, it is crucial to follow strict ethical guidelines to ensure appropriate application of this treatment in patients with OCD. To avoid inadvertent use of psychosurgery in this and other vulnerable populations, the National Research Act laid the foundation for a National Commission for the Protection of Human Subjects in 1977. This commission delineated recommendations regarding the application of psychosurgery in both research and clinical practice. According to these recommendations, all patients should meet criteria for chronic, severe, and treatment-refractory OCD as defined by the DSM-5 as a prerequisite for any surgical intervention. Patient selection should be determined by a multidisciplinary team composed of a psychiatrist, psychologists, and functional neurosurgeon ^, ( Table 122.1 ). Preoperative and postoperative assessments should include quantitative scales such as the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), administered by an experienced psychiatrist, to assess results objectively. The FDA has approved DBS therapy to treat refractory OCD in patients with a Y-BOCS score ≥30 ; however, neurosurgical intervention also has been found to be effective for moderate treatment-refractory OCD. ^,

Patients and families/caretakers need to be educated and counseled regarding the details of the surgical procedure, as well as potential benefits and complications. Patients and families need to demonstrate realistic expectations about the surgical outcome, and must be compliant with follow-up visits and participation in overall treatment by the team. There are pros and cons to both ablative and DBS procedures, and the decision to use lesioning or DBS is determined by the expertise and choice of the team at a particular center and the patient’s preference after clear understanding of the details of each procedure and the potential benefits and complications. Overall, DBS is more popular worldwide than ablative procedures because of its nondestructive and reversible nature. With evolution of MRgFUS technology, ablative procedures may get another boost in coming years.

Surgical Management of Obsessive-Compulsive Disorder

The advent of stereotaxy made it possible to target subcortical structures with millimeter accuracy, thereby increasing surgical safety while maintaining the efficacy of earlier surgical procedures for OCD. ^, Most (but not all) reports regarding surgical outcomes represent uncontrolled or nonblinded studies that need to be cautiously interpreted. Nevertheless, surgical treatment can provide hope to patients with severe and medically refractory OCD. All of the procedures thus far employed tend to modulate activity within the OFC, dorsolateral frontal cortex, and ACC, and their interactions with the basal ganglia and thalamus. Surgical procedures such as DBS, stereotactic ablation, vagus nerve stimulation (VNS) and recently MRgFUS ablation have been shown to improve OCD symptoms in various studies, as discussed later.