The Patient Lived-Experience of Ventral Capsulotomy for Obsessive-Compulsive Disorder: An Interpretive Phenomenological Analysis of Neuroablative Psychiatric Neurosurgery.

Ventral Capsulotomy (VC) is a surgical intervention for treatment-resistant Obsessive-Compulsive Disorder (OCD). Despite clinical studies, little is known about patient perception and lived experience after neurosurgery for severe OCD. To examine the lived experiences of patients who have undergone VC for severe, treatment-resistant OCD through qualitative analysis. We conducted semi-structured interviews with six participants treated with VC for OCD. Interviews were analyzed using Interpretive Phenomenological Analysis. The following themes emerged: (1) After years of conventional treatments, patients felt neurosurgery was their "last hope" and described themselves as "desperate," (2) While some described the surgery as a "supernatural experience," patients also demonstrated understanding of the scientific procedure, its risks and potential benefits, (3) The surgical experience itself was positive or neutral, which was linked to trust in the clinical team, (4) Post-surgery, participants described months of heightened fear as they awaited lesion formation and functional improvement. (5) Patients consistently contextualized outcome in the context of their own life goals. Patients undergoing VC have positive views of this neurosurgical intervention, but psychiatric neurosurgical teams should anticipate patient discomfort with the time needed to achieve behavioral improvement following surgery and emphasize the importance of post-operative psychiatric care.

Differential assessment of frontally-mediated behaviors between self- and informant-report in patients with obsessive-compulsive disorder following gamma ventral capsulotomy.

Obsessive-Compulsive Disorder (OCD) is a debilitating disorder causing marked distress and functional impairment. While advances in behavioral and pharmacotherapies have been effective for a majority of patients with OCD, 10-30% remain treatment refractory and severely impaired. For a subset of treatment-resistant individuals with the most severe and disabling (intractable) illness, gamma ventral capsulotomy (GVC) appears effective in reducing OCD symptoms and functional impairment. However, the effects of the ventral internal capsule lesion via GVC surgery on executive function in everyday life have been minimally investigated. Examining behavioral outcomes of GVC also provides a rare opportunity to probe the functional importance of the ventral prefrontal-subcortical connections of the internal capsule white matter tract in a relatively homogenous sample of patients with comparable white matter lesions. The present study investigated changes in frontally-mediated behaviors, measured by the Frontal Systems Behavior Scale (FrSBe), following GVC in 45 individuals with severe and otherwise intractable OCD, as rated by patients themselves and family members. Linear mixed effects models revealed a significant improvement in patient self-ratings on the FrSBe after surgery, while family ratings did not significantly change. Interestingly, improvement on the FrSBe for both self and family raters was significantly correlated with improvement in OCD symptomatology post-surgery, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). At the group level, we found no evidence of decline in frontally-mediated behaviors assessed by the FrSBe as a result of focal white matter disconnection via GVC. However, we cannot rule out the possibility that placebo effects or compromised patient self-awareness or insight contributed to the significant improvement in self ratings. Our measures may also have limited sensitivity to more selective impairments that could result from a small lesion to the ventral internal capsule. The present study demonstrates the need for detailed investigation of cognitive and behavioral changes as important factors when considering GVC as a viable treatment option for patients with refractory OCD.

The prefrontal cortex and neurosurgical treatment for intractable OCD.

Over the past two decades, circuit-based neurosurgical procedures have gained increasing acceptance as a safe and efficacious approach to the treatment of the intractable obsessive-compulsive disorder (OCD). Lesions and deep brain stimulation (DBS) of the longitudinal corticofugal white matter tracts connecting the prefrontal cortex with the striatum, thalamus, subthalamic nucleus (STN), and brainstem implicate orbitofrontal, medial prefrontal, frontopolar, and ventrolateral cortical networks in the symptoms underlying OCD. The highly parallel distributed nature of these networks may explain the relative lack of adverse effects observed following surgery. Additional pre-post studies of cognitive tasks in more surgical patients are needed to confirm the role of these networks in OCD and to define therapeutic responses to surgical intervention.

Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration. OBJECTIVE: To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo. METHODS: A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies. RESULTS: A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery. CONCLUSION: LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.

Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.

BACKGROUND: Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. METHODS: Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. RESULTS: Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. CONCLUSIONS: Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.

Personality measures after gamma ventral capsulotomy in intractable OCD.

BACKGROUND: Neurosurgeries such as gamma ventral capsulotomy (GVC) are an option for otherwise intractable obsessive-compulsive disorder (OCD) patients. In general, clinical and neuropsychological status both improve after GVC. However, its consequences on personality traits are not well-studied. The objective of this study was to investigate personality changes after one year of GVC in intractable OCD patients. METHODS: The personality assessment was conducted using the Revised NEO Personality Inventory (NEO PI-R) and Cloninger's Temperament and Character Inventory (TCI) in 14 intractable OCD patients before and one year after GVC. Comparisons of personality features between treatment responders (n=5) and non-responders (n=9) were performed. Multiple linear regression was also used for predicting changes in clinical and global functioning variables. RESULTS: Overall, no deleterious effect was found in personality after GVC. Responders had a reduction in neuroticism (p=0.043) and an increase in extraversion (p=0.043). No significant changes were observed in non-responders. Increases in novelty seeking and self-directedness, and decreases in persistence and cooperativiness predicted OCD symptom improvement. Similary, improvement in functioning was also predicted by hgher novelty seeking and self-directedness after GVC, whereas better functioning was also associated with lower reward dependence and cooperativeness after surgery. CONCLUSIONS: The pattern of changes in personality traits after GVC was generally towards that observed in nonclinical population, and does not raise safety concerns.

Integrating evolutionary and regulatory information with a multispecies approach implicates genes and pathways in obsessive-compulsive disorder.

Obsessive-compulsive disorder is a severe psychiatric disorder linked to abnormalities in glutamate signaling and the cortico-striatal circuit. We sequenced coding and regulatory elements for 608 genes potentially involved in obsessive-compulsive disorder in human, dog, and mouse. Using a new method that prioritizes likely functional variants, we compared 592 cases to 560 controls and found four strongly associated genes, validated in a larger cohort. NRXN1 and HTR2A are enriched for coding variants altering postsynaptic protein-binding domains. CTTNBP2 (synapse maintenance) and REEP3 (vesicle trafficking) are enriched for regulatory variants, of which at least six (35%) alter transcription factor-DNA binding in neuroblastoma cells. NRXN1 achieves genome-wide significance (p = 6.37 × 10-11) when we include 33,370 population-matched controls. Our findings suggest synaptic adhesion as a key component in compulsive behaviors, and show that targeted sequencing plus functional annotation can identify potentially causative variants, even when genomic data are limited.Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with symptoms including intrusive thoughts and time-consuming repetitive behaviors. Here Noh and colleagues identify genes enriched for functional variants associated with increased risk of OCD.

Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial.

IMPORTANCE: Select cases of intractable obsessive-compulsive disorder (OCD) have undergone neurosurgical ablation for more than half a century. However, to our knowledge, there have been no randomized clinical trials of such procedures for the treatment of any psychiatric disorder. OBJECTIVE: To determine the efficacy and safety of a radiosurgery (gamma ventral capsulotomy [GVC]) for intractable OCD. DESIGN, SETTING, AND PARTICIPANTS: In a double-blind, placebo-controlled, randomized clinical trial, 16 patients with intractable OCD were randomized to active (n = 8) or sham (n = 8) GVC. Blinding was maintained for 12 months. After unblinding, sham-group patients were offered active GVC. INTERVENTIONS: Patients randomized to active GVC had 2 distinct isocenters on each side irradiated at the ventral border of the anterior limb of the internal capsule. The patients randomized to sham GVC received simulated radiosurgery using the same equipment. MAIN OUTCOMES AND MEASURES: Scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Clinical Global Impression-Improvement (CGI-I) Scale. Response was defined as a 35% or greater reduction in Y-BOCS severity and "improved" or "much improved" CGI-I ratings. RESULTS: Three of 8 patients randomized to active treatment responded at 12 months, while none of the 8 sham-GVC patients responded (absolute risk reduction, 0.375; 95% CI, 0.04-0.71). At 12 months, OCD symptom improvement was significantly higher in the active-GVC group than in the sham group (Y-BOCS, P = .046; Dimensional Y-BOCS, P = .01). At 54 months, 2 additional patients in the active group had become responders. Of the 4 sham-GVC patients who later received active GVC, 2 responded by post-GVC month 12. The most serious adverse event was an asymptomatic radiation-induced cyst in 1 patient. CONCLUSIONS AND RELEVANCE: Gamma ventral capsulotomy benefitted patients with otherwise intractable OCD and thus appears to be an alternative to deep-brain stimulation in selected cases. Given the risks inherent in any psychiatric neurosurgery, such procedures should be conducted at specialized centers. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01004302.

OCD behavior therapy before and after gamma ventral capsulotomy: case report.

We report the case of a patient requiring gamma ventral capsulotomy (GVC), a neurosurgical intervention to address severe refractory obsessive-compulsive disorder (OCD). GVC involves stereotactic lesions in the ventral anterior limb of the internal capsule and adjacent ventral striatum. This study details the course of an extinction-based behavioral therapy, namely exposure and response prevention (ERP). The patient experienced significant changes in motivation and ability to tolerate ERP post-surgery. Furthermore, he was better able to absorb and remember exposure sessions. GVC surgery may affect the neural mechanisms involved in the extinction learning process, the same process implicated in ERP treatment.

Treatment of resistant obsessive-compulsive disorder with ventral capsular/ventral striatal gamma capsulotomy: a pilot prospective study.

A subgroup of obsessive-compulsive disorder (OCD) patients remains refractory to conventional treatments. For them, a new stereotactic radiosurgery has been recently developed: the ventral capsular/ventral striatal (VC/VS) gamma capsulotomy. The authors aim to report efficacy and adverse events of VC/VS gamma capsulotomy. Five refractory OCD patients were selected. The authors assessed OCD, anxiety and depressive symptoms, and side effects pre- and postoperatively. Three patients (60%) met response criteria 48 months after surgery. Adverse effects were episodic and transient. Ventral capsular/ventral striatal gamma capsulotomy holds therapeutic promise, with few adverse effects.

Neuropsychological outcome of ventral capsular/ventral striatal gamma capsulotomy for refractory obsessive-compulsive disorder: a pilot study.

Five refractory obsessive-compulsive patients were assessed using a neuropsychological battery after a modified gamma knife capsulotomy. The surgical technique was not associated with profound cognitive deficits. The authors found improvements in attention, vocabulary, learning, abstract reasoning, and memory.

Perforation rates for nonsterile examination gloves in routine dermatologic procedures.

BACKGROUND: Low cost, nonsterile examination gloves are used routinely to perform various dermatologic procedures. OBJECTIVE: To evaluate the perforation rate of nonsterile examination gloves in routine dermatologic procedures. METHODS: Three hundred fifty nonsterile latex examination gloves used to perform shave biopsies were evaluated for perforations using an air inflation/water submersion method. Ninety gloves, which were intentionally perforated with a 30-gauge needle, were used as controls to assess our evaluation method. RESULTS: Eight of the 350 gloves were found to have a perforation, which corresponds to a 2.3% perforation rate. Seven of the eight perforations were found in the web space between the second and third finger sleeves, with one being an obvious manufacturing error. All 90 perforations of the control group were correctly identified. CONCLUSION: There appears to be a very low risk of glove perforation when nonsterile examination gloves are used in routine dermatologic procedures.