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The Medial Forebrain Bundle As a Target for Deep Brain Stimulation for Obsessive-Compulsive Disorder

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The Medial Forebrain Bundle As a Target for Deep Brain Stimulation for Obsessive-Compulsive Disorder CNS Spectrums (2017), 22, 282–289. © Cambridge University Press 2016. The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/4.0/>. The written permission of Cambridge University Press must be obtained for commercial re-use. doi:10.1017/S1092852916000286 ORIGINAL RESEARCH The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder Volker A. Coenen,1*ThomasE.Schlaepfer,2 Peter Goll,3 Peter C. Reinacher,1 Ulrich Voderholzer,4 Ludger Tebartz van Elst,3 Horst Urbach,5 and Tobias Freyer3 1 Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Germany 2 Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany 3 Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany 4 Schön Klinik Roseneck, Prien am Chiemsee, Germany 5 Department of Neuroradiology, Freiburg University Medical Center, Freiburg, Germany Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale–Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS < 14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico–striato–thalamo–cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease. Received 7 March 2016; Accepted 16 April 2016; First published online 8 June 2016 Key words: Deep brain stimulation (DBS), depression, functional neurosurgery, obsessive-compulsive disorder (OCD), medial forebrain bundle (MFB), Yale–Brown Obsessive Compulsive Scale (YBOCS). Introduction therapeutic effects remain unclear.3,4 Targets under investigation are the anterior limb of the internal capsule Over the last 15 years, deep brain stimulation (DBS) has (ALIC; often also ventral capsule = vc), the ventral been demonstrated to be a promising putative therapy for stiatum (vs), the medial subthalamic nucleus (mSTN), the patients with treatment-refractory obsessive-compulsive inferior thalamic peduncle, and the nucleus accumbens ’ disorder (OCD). This is because of the procedure s (NAC).5 These structures have been selected because reversibility and adjustability, and its comparable efficacy they have been considered as genuine parts of the OCD 1,2 to ablative surgeries that were used previously. Several circuitry,6 and they have previously been used as stereo- meta-analyses and reviews summarize the potential of tactic lesions targets or were correlated with improve- DBS in OCD; however, the mechanisms underlying its ments of comorbid OCD symptoms in patients undergoing DBS surgery for other indications (eg, the STN in * Address for correspondence: Volker A. Coenen, M.D., Department Parkinson disease). Recently, convincing antidepressant of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Breisacher Str. 64, 79106 Freiburg (i.Br.), Germany. effects of stimulation of the supero-lateral branch of the (Email: [email protected]) medial forebrain bundle (slMFB) in severely depressed Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.234, on 28 Sep 2021 at 06:01:07, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S1092852916000286 DBS OF MEDIAL FOREBRAIN BUNDLE FOR OCD 283 patients (ie, those with major depressive disorder [MDD]) CO, USA). Rendition of the individual slMFB with have been reported.7 It was hypothesized that the possible, deterministic tractography was performed as described more rapid onset of clinical improvement, the possible low before with a single region of interest.7,10 rate of side-effects, and the low current needed were all due to the more direct stimulation of the crucial white matter Surgery tract connecting the structures involved in the pathology of depression, namely the medial forebrain bundle Stereotactic implantation of bilateral DBS electrodes was – (MFB).8 10 Moreover, some of the established target performed under mild analgesia with the patient regions for DBS in OCD are interconnected through the responsive using a Leksell G-Frame (Elekta, Sweden) MFB,8,10,11 supporting the notion that direct stimulation using typical coronal entry points. The DTI tracto- of the reward system (and its main regulating structure, the graphic rendition of the slMFB served to determine the MFB) could—as in depression—result in strong clinical individual target regions (inferior borders of slMFB). effects in OCD patients. Here, we present 2 cases with Microelectrode recording on 3 trajectories (anterior, treatment-refractory OCD with a significant and sustained lateral, and central) was applied to electrophysiologically therapeutic benefit after DBS of the slMFB. We also verify the corridor between the red nucleus (poster- discuss a mode of action that might explain the proposed omedially) and the subthalamic region (laterally) and efficacy of this approach in the context of reward system more inferior the substantia nigra (laterally, see Figure modulation. 1). After a macrostimulation test to search for anti- aversive (anti-OCD) effects of stimulation and the Materials and Methods oculomotor threshold, the final DBS electrodes (model 3389, Medtronic) were implanted under lateral x-ray DBS of the anterior limb of the internal capsule (ventral control. In a second step and under general anesthesia, capsule) and the ventral striatum (vc/vs) for therapy the DBS electrodes were subcutaneously connected to an refractory OCD is an established therapy in Europe and internal pulse generator that was located abdominally has received a (preliminary) CE-mark. The use of the (ACTIVA PC, Medtronic). slMFB as target for DBS is a compassionate use along this line of argumentation and was brought to the attention of Case descriptions the local ethics committee of Freiburg University before the implantations in both cases. The patients gave Patient 1 written informed consent especially with respect to the Patient 1 was a 32-year-old man who had suffered from experimental nature of the treatment. OCD since the age of 10. His family first sought professional help when the patient was 13. Since then Imaging and tractographic approach he had been treated by several psychiatrists and Anatomical and diffusion tensor imaging was performed psychotherapists, including cognitive behavioral therapy on a clinical 3 Tesla MRI system (Siemens Magnetom with exposure and response prevention (CBT with ERP) Trio Tim System 3T, Erlangen, Germany) a few days and numerous medications administered at adequate before surgery under mild sedation. Specifications were dosages and for adequate durations (clomipramine, as follows: anatomical sequences: 12-channel head coil, SSRIs, augmentation with second-generation antipsy- 3D magnetization prepared rapid gradient echo chotics). Neither inpatient nor outpatient treatment had (MPRAGE): TR 1 390 ms, TE 2.15 ms, TI 800 ms, flip a substantial effect on the course of his OCD, with angle 15°, voxel size 1.0 × 1.0 × 1.0 mm3, acquisition symptoms steadily deteriorating over time. Despite the time 3:15 min; 3D T2 SPACE-sequence: TR 2 500 ms, rather slow but successful completion of training as a TE 231 ms, echo train length 141, flip angle variable, baker and as an office administrator, he was never able to voxel size 1.0 × 1.0 × 1.0 mm3, acquisition time 6:42 min; work in these professions due to the severity of his OCD. diffusion tensor imaging: single shot 2D SE EPI, At the time of assessment, he had been receiving TR 10 000 ms, TE 94 ms, diffusion values b = 0 s/mm2, invalidity pension for 4 years and had significant b = 1000 s/mm2, diffusions directions 61, slice count functional and social impairment. Baseline evaluation 69, voxel size 2.0 × 2.0 × 2.0 mm3, acquisition time revealed severe contamination obsessions with asso- 11:40 min. Deformation correction
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