Tyagi, Himanshu; (2022) A comprehensive investigation of outcomes with deep brain stimulation of ventral capsule/ventral striatum and subthalamic nucleus in obsessive-compulsive disorder. Doctoral thesis (Ph.D), University College London (UCL).

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Abstract

Summary: Background Deep brain stimulation (DBS) is an emerging treatment for severe OCD. Previous studies implicate two principal brain targets: ventral internal capsule/ventral striatum (VC/VS) and anteromedial subthalamic nucleus (amSTN). Symptom response during DBS is variable with no clear indication of which site is optimal. We undertook the first pilot trial comparing VC/VS and amSTN DBS in the same patients with severe OCD. Methods: Six patients with treatment-refractory OCD were recruited from NHS OCD Specialist Services (5 males; 38-62yrs; illness duration ≥20 years; Yale Brown Obsessive Compulsive Scale (YBOCS) > 32). Patients entered randomised, double-blind, counterbalanced phases of 12 weeks amSTN or VC/VS DBS, followed by open phases when amSTN and VC/VS were stimulated together, optimal stimulation parameters achieved, and adjunctive inpatient CBT delivered. OCD symptoms, mood and disability were assessed with standardised scales and cognition with tests sensitive to OCD. Response was defined as ≥35% reduction in the YBOCS. Findings: Responder status during each DBS phase was: amSTN 3/6; VC/VS 5/6; amSTN + VC/VS 5/6; optimal stimulation 6/6; adjunctive CBT 6/6. At study end, YBOCS scores were subclinical (≤ 8) in three patients, mild in two and moderate in one. DBS at each site significantly reduced OCD symptoms, the magnitude of change being equivalent between them and with little additional gain after concurrent stimulation at both sites. Significant differential effects were found with amSTN improving cognitive flexibility and VC/VS improving mood. Volumes of tissue activation showed that the effective VC/VS site was the ventral aspect of the anterior limb of the internal capsule not the nucleus accumbens. Himanshu Tyagi PhD Thesis. Student Number: 12085079 Interpretation: DBS of VC/VS and amSTN are effective targets for amelioration of severe treatmentrefractory OCD. Effects on mood and cognition differ between sites, implicating separate neural circuits contributing to different aspects of the disorder. Long term data indicates that DBS is safe and conferred a long-term benefit in reduction of obsessive-compulsive symptoms, however reintegrating into normal life was problematic. Burden of ongoing maintenance of implanted hardware and lifelong follow up with super specialist team probably counterbalances the gains offered by this treatment. However, this could be a safe alternative to patients who do not respond to any other form of OCD treatment and do not want to undergo ablation surgery.

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