Ventral Capsule/Ventral Striatum Stimulation in Obsessive-Compulsive Disorder: Toward a Unified Connectomic Target for Deep Brain Stimulation?

INTRODUCTION: Obsessive-compulsive disorder (OCD) is among the most disabling chronic psychiatric disorders and has a significant negative impact on multiple domains of quality of life. Deep brain stimulation (DBS) is a treatment option for severe therapy-resistant OCD. OBJECTIVE: To provide a detailed clinical description and treatment outcome analysis in a cohort of eight refractory OCD patients receiving ventral capsule/ventral striatum (VC/VS) stimulation with the intention to validate discriminating fiber bundles previously associated with clinical response. MATERIALS AND METHODS: The primary outcome measure (the Yale-Brown Obsessive Compulsive Scale [Y-BOCS]) and secondary outcomes depressive symptoms, anxiety, and quality of life were retrospectively analyzed. DBS leads were warped into standard stereotactic space. A normative connectome was used to identify the neural network associated with clinical outcome. RESULTS: With a median stimulation duration of 26 months, patients exhibited a mean Y-BOCS reduction of 10.5 resulting in a response rate of 63%. Modulation of a fiber bundle traversing the anterior limb of the internal capsule (ALIC) was associated with Y-BOCS reduction. This fiber bundle connected the frontal regions to the subthalamic nucleus (STN) and was functionally identified as the hyperdirect pathway of the basal ganglia circuitry. CONCLUSION: Our findings show that in VC/VS stimulation, the neural network associated with clinical outcome shows overlap with that of previously described for other targets namely the anterior limb of the internal capsula, the nucleus accumbens, or the STN, which supports the evolvement from the concept of an optimal gray matter target to conceiving the target as part of a symptom modulating network.

A brief demonstration of frontostriatal connectivity in OCD patients with intracranial electrodes.

Closed-loop neuromodulation is presumed to be the logical evolution for improving the effectiveness of deep brain stimulation (DBS) treatment protocols (Widge et al., 2018). Identifying symptom-relevant biomarkers that provide meaningful feedback to stimulator devices is an important initial step in this direction. This report demonstrates a technique for assaying neural circuitry hypothesized to contribute to OCD and DBS treatment outcomes. We computed phase-lag connectivity between LFPs and EEGs in thirteen treatment-refractory OCD patients. Simultaneous recordings from scalp EEG and externalized DBS electrodes in the ventral capsule/ventral striatum (VC/VS) were collected at rest during the perioperative treatment stage. Connectivity strength between midfrontal EEG sensors and VC/VS electrodes correlated with baseline OCD symptoms and 12-month posttreatment OCD symptoms. Results are qualified by a relatively small sample size, and limitations regarding the conclusiveness of VS and mPFC as neural generators given some concerns about volume conduction. Nonetheless, findings are consistent with treatment-relevant tractography findings and theories that link frontostriatal hyperconnectivity to the etiopathogenesis of OCD. Findings support the continued investigation of connectivity-based assays for aiding in determination of optimal stimulation location, and are an initial step towards the identification of biomarkers that can guide closed-loop neuromodulation systems.

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation.

The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson's disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

Opening the debate on deep brain stimulation for Alzheimer disease - a critical evaluation of rationale, shortcomings, and ethical justification.

BACKGROUND: Deep brain stimulation (DBS) as investigational intervention for symptomatic relief from Alzheimer disease (AD) has generated big expectations. Our aim is to discuss the ethical justification of this research agenda by examining the underlying research rationale as well as potential methodological pitfalls. The shortcomings we address are of high ethical importance because only scientifically valid research has the potential to be ethical. METHOD: We performed a systematic search on MEDLINE and EMBASE. We included 166 publications about DBS for AD into the analysis of research rationale, risks and ethical aspects. Fifty-eight patients were reported in peer-reviewed journals with very mixed results. A grey literature search revealed hints for 75 yet to be published, potentially enrolled patients. RESULTS: The results of our systematic review indicate methodological shortcomings in the literature that are both scientific and ethical in nature. According to our analysis, research with human subjects was performed before decisive preclinical research was published examining the specific research question at stake. We also raise the concern that conclusions on the potential safety and efficacy have been reported in the literature that seem premature given the design of the feasibility studies from which they were drawn. In addition, some publications report that DBS for AD was performed without written informed consent from some patients, but from surrogates only. Furthermore, registered ongoing trials plan to enroll severely demented patients. We provide reasons that this would violate Art. 28 of the Declaration of Helsinki, because DBS for AD involves more than minimal risks and burdens, and because its efficacy and safety are not yet empirically established to be likely. CONCLUSION: Based on our empirical analysis, we argue that clinical research on interventions of risk class III (Food and Drug Administration and European Medicines Agency) should not be exploratory but grounded on sound, preclinically tested, and disease-specific a posteriori hypotheses. This also applies to DBS for dementia as long as therapeutic benefits are uncertain, and especially when research subjects with cognitive deficits are involved, who may foreseeably progress to full incapacity to provide informed consent during the required follow-up period.

Exploring the brain through posterior hypothalamus surgery for aggressive behavior.

Neurological surgery offers an opportunity to study brain functions, through either resection or implanted neuromodulation devices. Pathological aggressive behavior in patients with intellectual disability is a frequent condition that is difficult to treat using either supportive care or pharmacological therapy. The bulk of the laboratory studies performed throughout the 19th century enabled the formulation of hypotheses on brain circuits involved in the generation of emotions. Aggressive behavior was also studied extensively. Lesional radiofrequency surgery of the posterior hypothalamus, which peaked in the 1970s, was shown to be an effective therapy in many reported series. As with other surgical procedures for the treatment of psychiatric disorders, however, this therapy was abandoned for many reasons, including the risk of its misuse. Deep brain stimulation (DBS) offers the possibility of treating neurological and psychoaffective disorders through relatively reversible and adaptable therapy. Deep brain stimulation of the posterior hypothalamus was proposed and performed successfully in 2005 as a treatment for aggressive behavior. Other groups reported positive outcomes using target and parameter settings similar to those of the original study. Both the lesional and DBS approaches enabled researchers to explore the role of the posterior hypothalamus (or posterior hypothalamic area) in the autonomic and emotional systems.

Smile without euphoria induced by deep brain stimulation: a case report.

Poststroke central pain (PSCP) can be a debilitating medication-refractory disorder. We report a single case where right unilateral ventral capsule/ventral striatum (VC/VS) deep brain stimulation was used to treat PSCP and inadvertently induced a smile without euphoria. The patient was a 69 year-old woman who had a stroke with resultant dysesthesia and allodynia in her left hemibody and also a painful left hemibody dystonia. In her case, VC/VS stimulation induced a smile phenomenon, but without a euphoric sensation. This phenomenon was different from the typical smile responses we have observed in obsessive-compulsive disorder cases. This difference was considered to be possibly attributable to impairment in the emotional smile pathway.

Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

Deep brain stimulation for psychiatric disorders: where we are now.

Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

Surgical neuroanatomy and programming in deep brain stimulation for obsessive compulsive disorder.

OBJECTIVES: Deep brain stimulation (DBS) has been established as a safe, effective therapy for movement disorders (Parkinson's disease, essential tremor, etc.), and its application is expanding to the treatment of other intractable neuropsychiatric disorders including depression and obsessive-compulsive disorder (OCD). Several published studies have supported the efficacy of DBS for severely debilitating OCD. However, questions remain regarding the optimal anatomic target and the lack of a bedside programming paradigm for OCD DBS. Management of OCD DBS can be highly variable and is typically guided by each center's individual expertise. In this paper, we review the various approaches to targeting and programming for OCD DBS. We also review the clinical experience for each proposed target and discuss the relevant neuroanatomy. MATERIALS AND METHODS: A PubMed review was performed searching for literature on OCD DBS and included all articles published before March 2012. We included all available studies with a clear description of the anatomic targets, programming details, and the outcomes. RESULTS: Six different DBS approaches were identified. High-frequency stimulation with high voltage was applied in most cases, and predictive factors for favorable outcomes were discussed in the literature. CONCLUSION: DBS remains an experimental treatment for medication refractory OCD. Target selection and programming paradigms are not yet standardized, though an improved understanding of the relationship between the DBS lead and the surrounding neuroanatomic structures will aid in the selection of targets and the approach to programming. We propose to form a registry to track OCD DBS cases for future clinical study design.

Intracranial electrical stimulation of corticolimbic sites modulates arousal in humans.

BACKGROUND: Humans routinely shift their sleepiness and wakefulness levels in response to emotional factors. The diversity of emotional factors that modulates sleep-wake levels suggests that the ascending arousal network may be intimately linked with networks that mediate mood. Indeed, while animal studies have identified select limbic structures that play a role in sleep-wake regulation, the breadth of corticolimbic structures that directly modulates arousal in humans remains unknown. OBJECTIVE: We investigated whether select regional activation of the corticolimbic network through direct electrical stimulation can modulate sleep-wake levels in humans, as measured by subjective experience and behavior. METHODS: We performed intensive inpatient stimulation mapping in two human participants with treatment resistant depression, who underwent intracranial implantation with multi-site, bilateral depth electrodes. Stimulation responses of sleep-wake levels were measured by subjective surveys (i.e. Stanford Sleepiness Scale and visual-analog scale of energy) and a behavioral arousal score. Biomarker analyses of sleep-wake levels were performed by assessing spectral power features of resting-state electrophysiology. RESULTS: Our findings demonstrated three regions whereby direct stimulation modulated arousal, including the orbitofrontal cortex (OFC), subgenual cingulate (SGC), and, most robustly, ventral capsule (VC). Modulation of sleep-wake levels was frequency-specific: 100Hz OFC, SGC, and VC stimulation promoted wakefulness, whereas 1Hz OFC stimulation increased sleepiness. Sleep-wake levels were correlated with gamma activity across broad brain regions. CONCLUSIONS: Our findings provide evidence for the overlapping circuitry between arousal and mood regulation in humans. Furthermore, our findings open the door to new treatment targets and the consideration of therapeutic neurostimulation for sleep-wake disorders.

Prefrontal network engagement by deep brain stimulation in limbic hubs.

Prefrontal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders. However, the detailed neurophysiological effects of stimulation to these hubs are largely unknown. Here, we performed intracranial recordings across prefrontal networks while delivering electrical stimulation to two well-established white matter hubs involved in cognitive regulation and depression: the subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS). We demonstrate a shared frontotemporal circuit consisting of the ventromedial prefrontal cortex, amygdala, and lateral orbitofrontal cortex where gamma oscillations are differentially modulated by stimulation target. Additionally, we found participant-specific responses to stimulation in the dorsal anterior cingulate cortex and demonstrate the capacity for further tuning of neural activity using current-steered stimulation. Our findings indicate a potential neurophysiological mechanism for the dissociable therapeutic effects seen across the SCC and VC/VS targets for psychiatric neuromodulation and our results lay the groundwork for personalized, network-guided neurostimulation therapy.

Deep brain stimulation for treatment-resistant depression: a safe and effective option.

Introduction: Major depressive disorder (MDD) is the leading cause of years lost to disability worldwide. Pharmacotherapy and psychotherapy are effective treatments in most depressive episodes; but, about 30% of MDD patients remain symptomatic, and relapse is a common event. Recently, deep brain stimulation (DBS) has emerged as a valid therapeutic option in treatment-resistant depression (TRD) patients.Areas covered: In this paper, the authors summarize the findings of studies focused on these pathophysiologic phenomena and specifically on the role of DBS as a therapeutic option in TRD patients. The authors simply reviewed RCTs, open-label studies, neurophysiological mechanisms of DBS in MDD, and the possible role of different targets. Finally, we suggest possible future options.Expert opinion: Depression is a systems-level disorder, involving several brain structures. Neuroimaging studies demonstrate multiple interconnected regions that modulate different neural networks. DBS can modulate different targets, and others are under investigation. Among these subcallosal cingulate gyrus (SCG), ventral capsule and ventral striatum (VC/VS) seems to be the most relevant targets. We believe that, in the next future, DBS for TRD might become a first-line of treatment, especially using directional leads, that may help us to improve therapeutic effects.

Improving long term patient outcomes from deep brain stimulation for treatment-refractory obsessive-compulsive disorder.

Introduction: Deep brain stimulation (DBS) has emerged as an effective treatment for patients with severe treatment-refractory obsessive-compulsive disorder (OCD). Over the past two decades, several clinical trials with multiple years of follow-up have shown that DBS offers long-term symptom relief for individuals with severe OCD, though a portion of patients do not achieve an adequate response.Areas covered: This review sought to summarize the literature on the efficacy and long-term effectiveness of DBS for OCD, and to identify strategies that have the potential to improve treatment outcomes.Expert opinion: Although this literature is just emerging, a small number of DBS enhancement strategies have shown promising initial results. More posterior targets along the striatal axis and at the bed nucleus of the stria terminalis appear to offer greater symptom relief than more anterior targets. Research is also beginning to demonstrate the feasibility of maximizing treatment outcomes with target selection based on neural activation patterns during symptom provocation and clinical presentation. Finally, integrating DBS with post-surgery exposure and response prevention therapy appears to be another promising approach. Definitive conclusions about these strategies are limited by a low number of studies with small sample sizes that will require multi-site replication.

Case Report of Dual-Site Neurostimulation and Chronic Recording of Cortico-Striatal Circuitry in a Patient With Treatment Refractory Obsessive Compulsive Disorder.

Psychiatric disorders are increasingly understood as dysfunctions of hyper- or hypoconnectivity in distributed brain circuits. A prototypical example is obsessive compulsive disorder (OCD), which has been repeatedly linked to hyper-connectivity of cortico-striatal-thalamo-cortical (CSTC) loops. Deep brain stimulation (DBS) and lesions of CSTC structures have shown promise for treating both OCD and related disorders involving over-expression of automatic/habitual behaviors. Physiologically, we propose that this CSTC hyper-connectivity may be reflected in high synchrony of neural firing between loop structures, which could be measured as coherent oscillations in the local field potential (LFP). Here we report the results from the pilot patient in an Early Feasibility study (https://clinicaltrials.gov/ct2/show/NCT03184454) in which we use the Medtronic Activa PC+ S device to simultaneously record and stimulate in the supplementary motor area (SMA) and ventral capsule/ventral striatum (VC/VS). We hypothesized that frequency-mismatched stimulation should disrupt coherence and reduce compulsive symptoms. The patient reported subjective improvement in OCD symptoms and showed evidence of improved cognitive control with the addition of cortical stimulation, but these changes were not reflected in primary rating scales specific to OCD and depression, or during blinded cortical stimulation. This subjective improvement was correlated with increased SMA and VC/VS coherence in the alpha, beta, and gamma bands, signals which persisted after correcting for stimulation artifacts. We discuss the implications of this research, and propose future directions for research in network modulation in OCD and more broadly across psychiatric disorders.

Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression.

Major depressive disorder (MDD) is a leading cause of disability and a significant cause of mortality worldwide. Approximately 30-40% of patients fail to achieve clinical remission with available pharmacological treatments, a clinical course termed treatment-resistant depression (TRD). Numerous studies have investigated deep brain stimulation (DBS) as a therapy for TRD. We performed a meta-analysis to determine efficacy and a meta-regression to compare stimulation targets. We identified and screened 1397 studies. We included 125 citations in the qualitative review and considered 26 for quantitative analysis. Only blinded studies that compared active DBS to sham stimulation (k = 12) were included in the meta-analysis. The random-effects model supported the efficacy of DBS for TRD (standardized mean difference = -0.75, <0 favors active stimulation; p = 0.0001). The meta-regression did not demonstrate a statistically significant difference between stimulation targets (p = 0.45). While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this meta-analysis reveals a significant effect of DBS for the treatment of TRD. Additionally, the majority of trials have demonstrated the safety and efficacy of DBS for this indication. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including electrode placement technique, patient selection, and long-term follow-up is essential for future trial design.

Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: Towards an Individualized Approach.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder featuring repetitive intrusive thoughts and behaviors associated with a significant handicap. Of patients, 20% are refractory to medication and cognitive behavioral therapy. Refractory OCD is associated with suicidal behavior and significant degradation of social and professional functioning, with high health costs. Deep brain stimulation (DBS) has been proposed as a reversible and controllable method to treat refractory patients, with meta-analyses showing 60% response rate following DBS, whatever the target: anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), nucleus accumbens (NAcc), anteromedial subthalamic nucleus (amSTN), or inferior thalamic peduncle (ITP). But how do we choose the "best" target? Functional neuroimaging studies have shown that ALIC-DBS requires the modulation of the fiber tract within the ventral ALIC via the ventral striatum, bordering the bed nucleus of the stria terminalis and connecting the medial prefrontal cortex with the thalamus to be successful. VC/VS effective sites of stimulation were found within the VC and primarily connected to the medial orbitofrontal cortex (OFC) dorsomedial thalamus, amygdala, and the habenula. NAcc-DBS has been found to reduce OCD symptoms by decreasing excessive fronto-striatal connectivity between NAcc and the lateral and medial prefrontal cortex. The amSTN effective stimulation sites are located at the inferior medial border of the STN, primarily connected to lateral OFC, dorsal anterior cingulate, and dorsolateral prefrontal cortex. Finally, ITP-DBS recruits a bidirectional fiber pathway between the OFC and the thalamus. Thus, these functional connectivity studies show that the various DBS targets lie within the same diseased neural network. They share similar efficacy profiles on OCD symptoms as estimated on the Y-BOCS, the amSTN being the target supported by the strongest evidence in the literature. VC/VS-DBS, amSTN-DBS, and ALIC-DBS were also found to improve mood, behavioral adaptability and potentially both, respectively. Because OCD is such a heterogeneous disease with many different symptom dimensions, the ultimate aim should be to find the most appropriate DBS target for a given refractory patient. This quest will benefit from further investigation and understanding of the individual functional connectivity of OCD patients.

Current and future directions of deep brain stimulation for neurological and psychiatric disorders.

Deep brain stimulation (DBS) has evolved considerably over the past 4 decades. Although it has primarily been used to treat movement disorders such as Parkinson's disease, essential tremor, and dystonia, recently it has been approved to treat obsessive-compulsive disorder and epilepsy. Novel potential indications in both neurological and psychiatric disorders are undergoing active study. There have been significant advances in DBS technology, including preoperative and intraoperative imaging, surgical approaches and techniques, and device improvements. In addition to providing significant clinical benefits and improving quality of life, DBS has also increased the understanding of human electrophysiology and network interactions. Despite the value of DBS, future developments should be aimed at developing less invasive techniques and attaining not just symptom improvement but curative disease modification.

Successful deep brain stimulation for central post-stroke pain and dystonia in a single operation.

BACKGROUND: Central post-stroke pain is known to be refractory to medications and difficult to manage. We present a case of central post-stroke pain associated with dystonia. Both conditions were successfully treated with a single deep brain stimulation (DBS) operation. CASE DESCRIPTION: A 60-year-old female suffered a right posterior cerebral artery stroke following emergent clipping of a ruptured posterior cerebral artery aneurysm resulting in central post-stroke pain. This manifested as delayed left face and hemibody allodynia and hyperesthesia. The patient also developed marked left-sided dystonia. These progressive symptoms were disabling and refractory to conservative management. The patient underwent a single-stage DBS surgery with stereotactic targeting and implantation of two leads. One lead was placed in the right-sided ventral capsule/ventral striatum for treatment of pain and a second lead in the right-sided globus pallidus interna for treatment of dystonia. The surgical implantation proceeded without complication. The patient's dystonia markedly improved following surgery. While her pain improved, she required multiple, meticulous programing sessions to achieve significant pain relief and decrease in pain medication use. Overall, the patient was satisfied with the results of her intervention. She did, however, have occasional intermittent spells of severe pain on top of her residual discomfort throughout her treatment course. Unfortunately, she died from small cell lung carcinoma a year after her DBS surgery. CONCLUSIONS: Deep brain stimulation targeting multiple brain networks in one operation is feasible and safe. Deep brain stimulation may be considered in some refractory cases of central post-stroke pain; however, it requires meticulous programming.

Deep brain stimulation hardware-related infections: 10-year experience at a single institution.

OBJECTIVEDeep brain stimulation is an effective surgical treatment for managing some neurological and psychiatric disorders. Infection related to the deep brain stimulator (DBS) hardware causes significant morbidity: hardware explantation may be required; initial disease symptoms such as tremor, rigidity, and bradykinesia may recur; and the medication requirements for adequate disease management may increase. These morbidities are of particular concern given that published DBS-related infection rates have been as high as 23%. To date, however, the key risk factors for and the potential preventive measures against these infections remain largely uncharacterized. In this study, the authors endeavored to identify possible risk factors for DBS-related infection and analyze the efficacy of prophylactic intrawound vancomycin powder (VP).METHODSThe authors performed a retrospective cohort study of patients who had undergone primary DBS implantation at a single institution in the period from December 2005 through September 2015 to identify possible risk factors for surgical site infection (SSI) and to assess the impact of perioperative (before, during, and after surgery) prophylactic antibiotics on the SSI rate. They also evaluated the effect of a change in the National Healthcare Safety Network's definition of SSI on the number of infections detected. Statistical analyses were performed using the 2-sample t-test, the Wilcoxon rank-sum test, the chi-square test, Fisher's exact test, or logistic regression, as appropriate for the variables examined.RESULTSFour hundred sixty-four electrodes were placed in 242 adults during 245 primary procedures over approximately 10.5 years; most patients underwent bilateral electrode implantation. Among the 245 procedures, 9 SSIs (3.7%) occurred within 90 days and 16 (6.5%) occurred within 1 year of DBS placement. Gram-positive bacteria were the most common etiological agents. Most patient- and procedure-related characteristics did not differ between those who had acquired an SSI and those who had not. The rate of SSIs among patients who had received intrawound VP was only 3.3% compared with 9.7% among those who had not received topical VP (OR 0.32, 95% CI 0.10-1.02, p = 0.04). After controlling for patient sex, the association between VP and decreased SSI risk did not reach the predetermined level of significance (adjusted OR 0.32, 95% CI 0.10-1.03, p = 0.06). The SSI rates were similar after staged and unstaged implantations.CONCLUSIONSWhile most patient-related and procedure-related factors assessed in this study were not associated with the risk for an SSI, the data did suggest that intrawound VP may help to reduce the SSI risk after DBS implantation. Furthermore, given the implications of SSI after DBS surgery and the frequency of infections occurring more than 90 days after implantation, continued follow-up for at least 1 year after such a procedure is prudent to establish the true burden of these infections and to properly treat them when they do occur.