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Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

ABSTRACT: Gamma ventral capsulotomy (GVC) radiosurgery is intended to minimize side effects while maintaining the efficacy of traditional thermocoagulation techniques for the treatment of refractory obsessive-compulsive disorder (OCD). Neuropsychological outcomes are not clear based on previous studies and, therefore, we investigated the effects of GVC on cognitive and motor performance. A double-blind, randomized controlled trial (RCT) was conducted with 16 refractory OCD patients allocated to active treatment (n=8) and sham (n=8) groups. A comprehensive neuropsychological evaluation including intellectual functioning, attention, verbal and visuospatial learning and memory, visuospatial perception, inhibitory control, cognitive flexibility, and motor functioning was applied at baseline and one year after the procedure. Secondary analysis included all operated patients: eight from the active group, four from the sham group who were submitted to surgery after blind was broken, and five patients from a previous open pilot study (n=5), totaling 17 patients. In the RCT, visuospatial memory (VSM) performance significantly improved in the active group after GVC (p=0.008), and remained stable in the sham group. Considering all patients operated, there was no decline in cognitive or motor functioning after one year of follow-up. Our initial results after 1 year of follow-up suggests that GVC not only is a safe procedure in terms of neuropsychological functioning but in fact may actually improve certain neuropsychological domains, particularly VSM performance, in treatment refractory OCD patients.

SUBMITTER: Batistuzzo MC

PROVIDER: S-EPMC4839507 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

Batistuzzo Marcelo C MC Hoexter Marcelo Q MQ Taub Anita A Gentil André F AF Cesar Raony C C RC Joaquim Marinês A MA D'Alcante Carina Chaubet CC McLaughlin Nicole C NC Canteras Miguel M MM Shavitt Roseli G RG Savage Cary R CR Greenberg Benjamin D BD Norén Georg G Miguel Eurípedes C EC Lopes Antonio C AC

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150203 8

Gamma ventral capsulotomy (GVC) radiosurgery is intended to minimize side effects while maintaining the efficacy of traditional thermocoagulation techniques for the treatment of refractory obsessive-compulsive disorder (OCD). Neuropsychological outcomes are not clear based on previous studies and, therefore, we investigated the effects of GVC on cognitive and motor performance. A double-blind, randomized controlled trial (RCT) was conducted with 16 refractory OCD patients allocated to active tre ...[more]

PMID: 25645373

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Project description:For more than half a century, stereotactic neurosurgical procedures have been available to treat patients with severe, debilitating symptoms of obsessive-compulsive disorder (OCD) that have proven refractory to extensive, appropriate pharmacological, and psychological treatment. Although reliable predictors of outcome remain elusive, the establishment of narrower selection criteria for neurosurgical candidacy, together with a better understanding of the functional neuroanatomy implicated in OCD, has resulted in improved clinical efficacy for an array of ablative and non-ablative intervention techniques targeting the cingulum, internal capsule, and other limbic regions. It was against this backdrop that gamma knife capsulotomy (GKC) for OCD was developed. In this paper, we review the history of this stereotactic radiosurgical procedure, from its inception to recent advances. We perform a systematic review of the existing literature and also provide a narrative account of the evolution of the procedure, detailing how the procedure has changed over time, and has been shaped by forces of evidence and innovation. As the procedure has evolved and adverse events have decreased considerably, favorable response rates have remained attainable for approximately one-half to two-thirds of individuals treated at experienced centers. A reduction in obsessive-compulsive symptom severity may result not only from direct modulation of OCD neural pathways but also from enhanced efficacy of pharmacological and psychological therapies working in a synergistic fashion with GKC. Possible complications include frontal lobe edema and even the rare formation of delayed radionecrotic cysts. These adverse events have become much less common with new radiation dose and targeting strategies. Detailed neuropsychological assessments from recent studies suggest that cognitive function is not impaired, and in some domains may even improve following treatment. We conclude this review with discussions covering topics essential for further progress of this therapy, including suggestions for future trial design given the unique features of GKC therapy, considerations for optimizing stereotactic targeting and dose planning using biophysical models, and the use of advanced imaging techniques to understand circuitry and predict response. GKC, and in particular its modern variant, gamma ventral capsulotomy, continues to be a reliable treatment option for selected cases of otherwise highly refractory OCD.

Project description: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.

Project description:BACKGROUND:Recently, a new thermal lesioning approach using magnetic resonance-guided focused ultrasound (MRgFUS) was introduced for the treatment of neurologic disorders. However, only 2 studies have used this approach for treatment-refractory obsessive-compulsive disorder (OCD), and follow-up was short-term. We investigated the efficacy and safety of bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS in patients with treatment-refractory OCD and followed them for 2 years. METHODS:Eleven patients with treatment-refractory OCD were included in the study. Clinical outcomes were evaluated using the Yale-Brown Obsessive Compulsive Scale, the Clinical Global Impression scale (including improvement and severity), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A) at 1 week and 1, 3, 6, 12 and 24 months following MRgFUS. Neuropsychological functioning, Global Assessment of Functioning and adverse events were also assessed. RESULTS:After MRgFUS, Yale-Brown Obsessive Compulsive Scale scores decreased significantly across the 24-month follow-up period (mean ± standard deviation, 34.4 ± 2.3 at baseline v. 21.3 ± 6.2 at 24 months, p < 0.001). Scores on the Hamilton rating scales for depression and anxiety also significantly decreased from baseline to 24 months (HAM-D, 19.0 ± 5.3 v. 7.6 ± 5.3, p < 0.001; HAM-A, 22.4 ± 5.9 v. 7.9 ± 3.9, p < 0.001). Global Assessment of Functioning scores improved significantly (35.8 ± 4.9 at baseline v. 56.0 ± 10.3 at 24 months, p < 0.001) and Memory Quotient significantly improved, but other neuropsychological functions were unchanged. The side effects of MRgFUS included headache and vestibular symptoms, but these were mild and transient. LIMITATIONS:The main limitations of this study were the small sample size and the open-label design. CONCLUSION:Bilateral thermal lesioning of the anterior limb of the internal capsule using MRgFUS may improve obsessive-compulsive, depressive and anxiety symptoms in patients with treatment-refractory OCD, without serious adverse effects.

Dataset Information

Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

Publications

Visuospatial Memory Improvement after Gamma Ventral Capsulotomy in Treatment Refractory Obsessive-Compulsive Disorder Patients.

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