Deep Brain Stimulation for Obsessive-Compulsive Disorder

Internally Produced & Endorsed

Sponsors: Congress of Neurological Surgeons (CNS) and the American Society of Stereotactic and Functional Neurosurgery

Endorsement: Reviewed for evidence-based integrity and endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons

Specialty: Stereotactic & Functional

Original text of the guideline was edited to reflect the update. Please click here for the original publication.

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Neurosurgery, 2020

Authors

Michael D. Staudt, MD, MSc^1,2, Nader Pouratian, MD, PhD³, Jonathan P. Miller, MD⁴, Clement Hamani, MD, PhD⁵, Nataly Raviv, MD⁶, Guy M. McKhann, MD⁷, Jorge A. Gonzalez-Martinez, MD, PhD⁸, Julie G. Pilitsis, MD, PhD⁶

Affiliations

¹Department of Neurosurgery, Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA

²Michigan Head and Spine Institute, Southfield, Michigan, USA

³Department of Neurosurgery, University of California, Los Angeles, CA, USA

⁴Department of Neurosurgery, Case Western Reserve University, Cleveland, OH, USA

⁵Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada

⁶Department of Neurosurgery, Albany Medical College, Albany, NY, USA

⁷Department of Neurological Surgery, Columbia University Irving Medical Center, New York, NY, USA

⁸Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA

Correspondence

Julie G. Pilitsis MD, PhD

Department of Neurosurgery

Albany Medical College

47 New Scotland Ave, MC-10

Albany, NY 12208

Tel (518)262-0739

Fax (518)262-1017

Email: jpilitsis@yahoo.com

 

Keywords: bed nucleus of stria terminalis, deep brain stimulation, nucleus accumbens, obsessive-compulsive disorder, subthalamic nucleus

Abbreviations: AANS, American Association of Neurological Surgeons; ALIC, anterior limb of internal capsule ; BNST, bed nucleus of stria terminalis; CNS, Congress of Neurological Surgeons; DBS, deep brain stimulation; FDA, Food and Drug Administration; HDE, humanitarian device exemption; NAc, nucleus accumbens; OCD, obsessive-compulsive disorder; STN, subthalamic nucleus; VC/VS, ventral capsule/ventral striatum; Y-BOCS, Yale and Brown OCD Scale

ABSTRACT

Background: In 2020, the Guidelines Task Force conducted another systematic review of the relevant literature on deep brain stimulation for obsessive compulsive disorder to update the original 2014 guidelines to ensure timeliness and accuracy for clinical practice.

Objective: To conduct a systematic review of the literature and update the evidence-based guidelines on DBS for OCD.

Methods: The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies used to search PubMed and Embase for relevant literature.  The updated search included studies published between 1966 and December 2019. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed and relevant full text articles were retrieved and graded. Of 864 articles, 10 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update.

Results: Seven studies were included in the original guideline, reporting the use of bilateral DBS as more effective in improving OCD symptoms than sham treatment. An additional 10 studies were included in this update: 1 Class II and 9 Class III.

Conclusions: Based on the data published in the literature, the following recommendation can be made: 1) It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD (Level I). 2) Clinicians may use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patients with medically refractory OCD (Level II). There is insufficient evidence to make a recommendation for the identification of the most effective target.

RECOMMENDATIONS

1. It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD. (Level I)
2. Clinicians may use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patients with medically refractory OCD. (Level II)

INTRODUCTION

Rationale

In 2014, guidelines for the treatment of obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS) were established by the American Society for Stereotactic and Functional Neurosurgery and the Congress of Neurological Surgeons.¹ These guidelines were based on a literature review performed between 1966 and October 2012. The current article is a 5-year review of the medical literature in accordance with the standard operating procedures and methodology of the Congress of Neurological Surgeons for developing clinical practice guidelines.

In the original 2014 guidelines, 7 articles were included for analysis, with 3 studies having a double-blind phase in which active stimulation was compared with sham treatment. One of these studies fulfilled criteria for Class I evidence,² whereas the other 2 were classified as Class II.^3,4 Four additional studies were classified as Class III evidence,^5-8 with the 2 studies by Greenberg et al. reporting the results of the same patient cohort at different follow-ups.^6,7

Objectives

The use of bilateral anterior limb of internal capsule (ALIC) DBS for OCD was approved by the US Food and Drug Administration (FDA) under a humanitarian device exemption (HDE) in 2009.⁹ Following this HDE approval and publication of the 2014 guidelines, there have been additional published studies reporting the use of DBS for OCD, although most do not meet criteria to be included in this guidelines update. The purpose of this update is to review the literature following publication of the original guidelines and to update the recommendations as appropriate. Based on the availability of new literature, the current article is a major update resulting in modification and update of prior recommendations (see Table 1) as well as an updated discussion.

METHODS

Writing Group and question Establishment

The Guidelines Task Force initiated an update of the original systematic review of the literature and evidence-based guideline relevant to the use of deep brain stimulation for the treatment of patients with obsessive compulsive disorder. This guideline update was developed for educational purposes to assist practitioners in their clinical decision-making processes. Additional information about the methods utilized in this systematic review is provided via the Congress of Neurological Surgeons Methodology.

Literature Search

The PubMed and Embase databases were searched using the terms “deep brain stimulation” and “obsessive compulsive disorder”, or “electrical stimulation” and “obsessive compulsive disorder”. Articles published between 1966 and December 2019 were screened via the inclusion and exclusion criteria established in the previous guidelines publication (Table 2).¹ A total of 748 and 175 articles were identified through the PubMed and Embase database searches, respectively. As the original guidelines did not include an Embase database search, the search was repeated for both databases from 1966. After removal of 59 duplicate entries, 864 articles underwent title and abstract review by 2 independent investigators (Figure 1). A total of 93 articles underwent full review and 17 met inclusion criteria. Seven of these 17 articles were analyzed in the original guidelines, and 10 new articles were selected for inclusion in this update. A total of 76 articles were excluded for the following reasons: the DBS target was ambiguous in 7 studies, 4 reported on non-DBS interventions, 27 had less than 6 patients, 4 had a follow-up period of less than 6 months, 13 reported a non-clinical outcome of interest, and 21 reported on the same patient population that was detailed in a separate article (i.e. clinical results in one article, and imaging studies in another).

Study Selection and Eligibility Criteria

A total of 93 citations underwent a full text, double blind review by the task force using the same inclusion and exclusion criteria as the original guideline.¹ The authors did not include systematic reviews, guidelines, or meta-analyses conducted by others. Those documents were developed using different inclusion criteria than those specified in this guideline. Therefore, those documents may include studies that do not meet the inclusion criteria specified above. See PRISMA Article Flow Chart (Figure 1).

Data Collection Process

The abstracts that met the selection criteria mentioned above were retrieved in full-text form. Each article’s adherence to the selection criteria was assessed. To determine how the data could be classified, the information in the full-text articles was then evaluated to determine whether they were providing results of therapy or were more centered on diagnostic or prognostic information. Agreement on these assessments and on the salient points regarding the type of study design and objectives, and the conclusions and data classification was then reached by exchanging drafts and comments among authors. The information was then used for construction of the evidence tables.

Rating Quality of Evidence

The quality of evidence was rated using an evidence hierarchy for therapeutic studies. Demonstrating the highest degree of clinical certainty, Class I evidence is used to support recommendations of the strongest type, defined as Level I recommendations. Level II recommendations reflect a moderate degree of clinical certainty and are supported by Class II evidence. Level III recommendations denote clinical uncertainty supported by Class III evidence. This hierarchy is shown in Table 3. Additional information regarding the hierarchy classification of evidence is found on the CNS Guidelines Procedures and Policies page.

Revision Plans

In accordance with the National Academy of Medicine’s standards for developing clinical practice guidelines the task force will monitor related publications following the release of this document and will revise the entire document and/or specific sections “if new evidence shows that a recommended intervention causes previously unknown substantial harm; that a new intervention is significantly superior to a previously recommended intervention from an efficacy or harms perspective; or that a recommendation can be applied to new populations.”¹⁰ In addition, the task force will confirm within 5 years from the date of publication that the content reflects current clinical practice and the available technologies regarding DBS for OCD.

RESULTS

Of the 10 studies evaluated to update the guidelines, no study fulfilled criteria to be classified as a Class I study. One study was classified as Class II, which was a trial of ALIC or bed nucleus of stria terminalis (BNST) DBS.¹¹ Nine additional studies were classified as Class III.^12-20 Table 4 outlines those studies included for consideration in the updated guidelines.

The first recommendation from the 2014 guidelines indicated that there is Level I evidence, based on a single Class I study,² for the use of bilateral subthalamic nucleus (STN) DBS for the treatment of medically refractory OCD. In the interim, the STN was the DBS target in two additional Class III studies.^15,16 No additional Class I studies have been performed in the interim to justify additional recommendations. The verbiage of the recommendation was updated with respect to formatting only.  The recommendation now reads: It is recommended that clinicians utilize bilateral STN DBS over best medical management for the treatment of patients with medically refractory OCD.

The second original recommendation indicated that there is Level II evidence, based on a single Class II study,³ for the use of bilateral nucleus accumbens (NAc) DBS for the treatment of medically refractory OCD. In the interim, the DBS of NAc was studied in 5 additional Class III studies.^12-14,18,19 An additional Class II study was reported by Luyten et al.,¹¹ with implantation of bilateral DBS electrodes into the BNST and/or ALIC; overall improved therapeutic effects were seen with BNST stimulation compared to ALIC stimulation. As such, this recommendation has been expanded: Clinicians may use bilateral NAc or BNST DBS for the treatment of patients with medically refractory OCD (Level II).

The third original recommendation indicated that there is insufficient evidence to make a recommendation for the use of unilateral DBS for the treatment of medically refractory OCD. At the time of initial guideline publication, only 1 Class II study performed unilateral NAc DBS for the treatment of medically refractory OCD.⁴ No additional studies of unilateral DBS have been performed in the interim. As such, this recommendation has been removed.

DISCUSSION

Since the publication of the original DBS for OCD guidelines in 2014, multiple new studies have been published. Although it is encouraging that additional studies have been performed, there continues to be a lack of high-quality randomized controlled trials to support Level I recommendations. Whereas 1 Class II study was performed in the interim, the additional published trials were lower quality Class III studies. The majority of published studies continue to have low recruitment and short length of follow-up that preclude inclusion in these updated guidelines. However, based on the availability of new literature, a major update is required resulting in modification of the original recommendations (Table 4).

The trial reported by Luyten et al.¹¹ was well-designed, however was not classified as Class I due to certain limitations. This study included a randomized sham-controlled 3-month blinded crossover trial followed by open-label observation of up to 14 years, and was classified as Class II because only a subset of enrolled subjects (17 of 24) participated in the randomized phase. The trial reported by Tyagi et al.¹⁶ was downgraded primarily due to the indirectness of the evidence. In this study, 6 patients were implanted with bilateral electrodes separately targeting the STN and ventral capsule/ventral striatum (VC/VS), with the latter leads traversing the ALIC and NAc. Patients then underwent a randomized 3-month blinded stimulation phase of one target, followed by an additional 3-month cross-over phase stimulating the other target. This was followed by 3 subsequent open phases with combined stimulation of both targets, stimulation with optimized settings, and finally stimulation with concurrent cognitive-behavioral therapy. Although this study had a novel design, there was no comparison of active stimulation vs. sham treatment and no washout period. Furthermore, interpretation of the data is limited by the use of combined stimulation of two separate targets. The remainder of studies classified as Class III were case or case-control series, and did not include a blinded phase in which active stimulation was compared to sham treatment.^12-15,17-20

Key Issues for Future Investigation

The use of bilateral ALIC DBS for OCD was approved by the US FDA under a HDE in 2009.⁹ This approval was based on data generated from the multicenter study of 26 patients reported by Greenberg et al.⁷ As such, the ALIC continues to be the most commonly implanted target, and is also necessary for insurance coverage. Despite the publication of additional high quality studies since the initial HDE approval, clinical practice is largely unchanged. Indeed, it has been suggested that approval of the HDE would create challenges regarding patient recruitment for larger clinical trials or different targets.^21,22

In the original guidelines, an important focus of discussion was the clarification of the most effective DBS target. No recommendation was made due to the lack of data. As the literature has expanded, the most commonly targeted regions include the VC/VS and NAc; however, it is important to recognize that the VC/VS is a region, not a defined structure, with the NAc as its most ventral extension. In the literature, the description of DBS targets for OCD can be inconsistent or ambiguous when comparing results between studies or even within the same study. Overlap has been observed with the reporting of coordinates for striatal region targets, which includes the VC/VS, NAc, ALIC and BNST.²³ For example, some of the studies included in the updated guidelines describe targeting both the ALIC and NAc along the same electrode trajectory.^12,16,18,19 Furthermore, in the study which led to HDE approval, improved results were seen with refinement of the implantation target more posteriorly, with distal contacts in the caudal NAc or traversing the BNST;⁷ however, bilateral ALIC DBS continues to be the only FDA approved target. Future guideline updates may consider the recommendation of a “striatal target” based on pooled evidence from these striatal subregions.

It is possible that DBS results in stimulation of multiple targets, or that an optimal target can be stimulated with different electrode trajectories. As such, it is not possible to conclusively propose a single “most effective” target, and improving DBS outcomes may depend on identifying patient- or disease-specific commonalities. An additional area in need of further study is identification of patient- or disease-specific phenotypes in order to determine which candidates will respond best to DBS. OCD is a markedly heterogeneous disorder, and the variations in treatment response observed in the literature may be explained by diversity in phenotype. Therefore, there remains insufficient evidence to make a recommendation for the identification of the most effective target. Furthermore, the analysis performed in this guideline does not compare the efficacy or quality of data for DBS compared to other established or novel surgical therapies for OCD, including stereotactic radiosurgery, radiofrequency thermocoagulation, or focused ultrasound.

CONCLUSION

DBS is being increasingly used in the treatment of medically refractory OCD with overall good results, resulting in the publication of multiple new reports since the original guidelines were introduced in 2014. Although the overall level of evidence remains low, a major update to the original recommendations can be made due to the availability of new evidence. Additional research is necessary to identify which patient-specific characteristics and surgical target(s) are most likely to benefit patients with OCD.

Conflicts of Interest

All Guideline Task Force members were required to disclose all potential COIs prior to beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Review Committee. The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guideline Task Force Chair may approve nominations of task force members with possible conflicts and restrict the writing, reviewing, and/or voting privileges of that person to topics that are unrelated to the possible COIs. See Table 5 for a complete list of disclosures.

Funding

This evidence-based clinical practice guidelines were funded exclusively by the Congress of Neurological Surgeons, which received no funding from outside commercial sources to support the development of this document.

Disclaimer of Liability

This clinical, systematic, evidence-based clinical practice guideline was developed by a multi-disciplinary physician volunteer taskforce and is provided as an educational tool based on an assessment of the current scientific and clinical information regarding deep brain stimulation for the treatment of patients with obsessive-compulsive disorder. These guidelines are disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in their development are not meant to replace the individualized care and treatment advice from a patient's physician(s). If medical advice or assistance is required, the services of a physician should be sought. The proposals contained in these guidelines may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in these guidelines must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.

Acknowledgments

The guidelines task force would like to acknowledge the Congress of Neurological Surgeons Guidelines Committee for their contributions throughout the development of the guideline, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Review Committee for their review, comments, and suggestions throughout peer review, as well as the contributions of Trish Rehring, MPH, CHES, Associate Director of Evidence-Based Practice Initiatives for the CNS. Throughout the review process, the reviewers and authors were blinded from one another. At this time the guidelines task force would like to acknowledge the following individual peer reviewers for their contributions: Jennifer Sweet, MD, Kimon Bekelis, MD, Jeffrey Olson, MD, Jon T. Willie, MD, Sharona Ben-Haim, MD.

Figure 1.  Flowchart showing the process involved in identifying relevant literature for the 2020 Update.

Table 1: Recommendations

2014 Guideline Recommendations
There is Level I evidence, based on a single Class I study, for the use of bilateral subthalamic nucleus DBS for the treatment of medically refractory OCD
There is Level II evidence, based on a single Class II study, for the use of bilateral nucleus accumbens DBS for the treatment of medically refractory OCD
There is insufficient evidence to make a recommendation for the use of unilateral DBS for the treatment of medically refractory OCD
Updated Recommendations
Clinicians should consider bilateral subthalamic nucleus DBS for the treatment of patients with medically refractory OCD as effective (Level I)
Clinicians may use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patients with medically refractory OCD (Level II)

Table 2. Study Selection Criteria

Inclusion Criteria	Exclusion Criteria
Clinical series with 6 or more patients treated with DBS	Clinical series with fewer than 6 patients
Clinical series with a minimum postoperative follow-up of 6 months	Clinical series with a follow-up shorter than 6 months
	Articles reporting on patient populations other than those with OCD
	Clinical series in which ablative surgery was used instead of DBS
	Reports that mainly addressed aspects related to surgical technique
	Studies including only preclinical data, review articles, and letters to the editor

Table 3. Rating Evidence Quality

Classification of Evidence on Therapeutic Effectiveness 

Class I Evidence Level I (or A) Recommendation	Evidence from one or more-well designed, randomized controlled clinical trial, including overviews of such trials.
Class II Evidence Level II (or B) Recommendation	Evidence from one or more well-designed comparative clinical studies, such as non-randomized cohort studies, case-control studies, and other comparable studies, including less well-designed randomized controlled trials.
Class III Evidence Level III (or C) Recommendation	Evidence from case series, comparative studies with historical controls, case reports, and expert opinion, as well as significantly flawed randomized controlled trials.

Table 4. Evidence Tables for the 2020 Update

Author, year	Class of Evidence	Description of the Study	Conclusions
Luyten 201611	II	Bilateral BNST/ALIC DBS. 24 patients, 17 whom completed a double-blind randomized crossover trial (consisting of ON and OFF phases lasting 3 months each), 18 followed for >4 years. 48-171 month follow-up.	16/24 patients (67%) were responders. At last follow-up, median improvements in scores were as follows: 45% on Y-BOCS, 45% on HARS, 49% on HDRS, and 30 points on GAF. Y-BOCS score was highly correlated with the ON score during the crossover trial (R=0.83, p<0.001). Data interpreted as suggesting that BNST might be a better target for reducing obsessions and compulsions than ALIC.
Liebrand 201917	III	Bilateral ventral ALIC DBS. Case series involving 12 DBS patients. Tractography analysis of the supero-lateral branch of the medial forebrain bundle (MFB) and the anterior thalamic radiation (ATR) was performed in order to evaluate bundle-specific targeting. 12-month follow-up.	7 patients were responders (>35% improvement in Y-BOCS score), and 2 were partial responders (25-35% improvement). Active stimulation of the ventral ALIC closer to the MFB than to the ATR was associated with better treatment outcome as assessed by Y-BOCS scores at baseline and at one-year follow-up (p=0.04, r2=0.34).
Mantione 201513	III	Bilateral NAc DBS. Case-control study evaluating 16 patients treated with DBS and 14 control patients receiving standard medical management.  8 month follow up.	DBS group experienced a mean reduction of 15.7 ± 10.8 points in Y-BOCS score, as well as decreases of 10.7 ± 8.1 points on the HARS and 9.0 ± 6.2 points on the HDRS. OCD, anxiety and depressive symptoms remained unchanged in the control group. Of note, minor reduction in the performance of certain measures of executive functioning was noted in the DBS group, though overall cognitive functioning was unaffected.
Hartmann 201612	III	Bilateral NAc/ALIC DBS. Case series of six patients undergoing DBS. Computational models were created for each patient in order to assess fiber tract activation. 24-month follow-up.	Two patients were responders and 2 were partial responders. Modulation of the right anterior middle frontal gyrus was associated with good response. In contrast, non-responders demonstrated high activation in the orbital part of the right inferior frontal gyrus.
Huys 201918	III	Bilateral NAc/ALIC DBS. Case series with open-label design, involving 20 patients undergoing stimulation for one year. 12-month follow-up.	ALIC-NAc DBS significantly decreased OCD symptoms and improved global functioning. 40% of subjects were full responders, with a mean Y-BOCS score reduction of 33%. No loss of efficacy was noted over 1 year. No significant changes were found in depressive or anxiety symptoms. 35% of patients reported an increase in anxiety and anhedonia with acute cessation of stimulation.
Baldermann 201919	III	Bilateral NAc/ALIC DBS. Case series involving 22 patients undergoing DBS and the development of patient-specific models of connectivity. 12-month follow-up.	Y-BOCS scores decreased significantly by a mean of 30.4 ± 20.1%. Models of optimal connectivity successfully cross-predicted clinical outcomes. Degree of connectivity of stimulation sites to the medial and lateral prefrontal cortices significantly predicted clinical improvement.
Farrand 201714	III	Bilateral NAc or BNST DBS. Case series involving 7 patients who underwent DBS (3 bilateral BNST, 3 bilateral NAc, 1 with unilateral NAc [right] and unilateral BNST [left]). Mean follow-up of 31 month (range 8-54 months).	Three patients were responders, and the other 4 demonstrated between 7-20% improvement in Y-BOCS scores.
Polosan 201915	III	Bilateral STN DBS. Case series involving 12 patients implanted prior to study testing protocol. Duration of stimulation ranged 5-71 months. Ten patients underwent double-blind, randomized ON and OFF STN DBS over 2 successive days, and degrees of valence and arousal were assessed in response to images.	Post-operative Y-BOCS scores at the time of the study were reduced by 41±28% when compared to pre-operative scores. STN DBS increased positive ratings and decreased negative ratings in response to stimuli.
Tyagi 201916	III	Bilateral STN and/or VC/VS DBS. Six patients underwent double-blinded counterbalanced phases of 12-week STN or VC/VS stimulation, followed by stimulation of both targets during a 12-week open phase. Two additional 12-week open phases with optimal settings, with participants in the latter phase receiving adjunctive cognitive behavioral therapy.	DBS at each site significantly and equivalently reduced OCD symptoms with little additional gain with combined stimulation. Anteromedial STN significantly improved cognitive flexibility, whereas VC/VS had a greater effect on mood.
Menchόn 201920	III	Bilateral ALIC DBS. Open-label, multi-center study of safety and efficacy in 30 patients. Primary study objective was to characterize adverse events. 12-month follow-up.	Y-BOCS scores decreased significantly by a mean of 42 ± 27% from baseline at 12 months, with 57% of patients classified as responders. Improvements also seen in comorbid depression, GAF and EQ-5D. Adverse events were common, although most were classified as mild (52%) or moderate (37%), and were transient and related to programming.

Abbreviations: Randomized controlled trial (RCT); Yale-Brown Obsessive Compulsive Scale (Y-BOCS); Responders (≥35% Y-BOCS reduction); Partial responders (25-35% Y-BOCS reduction); EuroQol group-5 Dimensional (EQ-5D); Hamilton Depression Rating Scale (HDRS); Hamilton Anxiety Rating Scale (HARS); Global Assessment of Functioning (GAF) Scale.

Table 5. Conflict of Interest

Author	Conflict of Interest Disclosure
Michael D. Staudt, MD, MSc	No Disclosures
Nader Pouratian, MD, PhD	Consultant: Abbott and Boston Scientific
Jonathan P. Miller, MD	No Disclosures
Clement Hamani, MD, PhD	Advisory Board: Medtronic*
Nataly Raviv, MD	No Disclosures
Guy M. McKhann, MD	Consultant: Koh Young Inc. Grant Support: NIH
Jorge A. Gonzalez-Martinez, MD, PhD	No Disclosures
Julie G. Pilitsis, MD, PhD	Consultant: Boston Scientific, Nevro, TerSera, Medtronic, Saluda and Abbott Grant Support: Medtronic, Boston Scientific, Abbott, Nevro, TerSera, NIH 2R01CA166379-06 and NIH U44NS115111 Medical Advisor: Aim Medical Robotics and Karuna Stock: Karuna

*conflict not related to guideline topic

Abbreviations: NIH- National Institutes of Health

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