A Systematic Review of Deep Brain Stimulation Targets for Obsessive Compulsive Disorder.

BACKGROUND: Obsessive compulsive disorder (OCD) is a complex neuropsychiatric disease characterized by obsessions and compulsions. Deep brain stimulation (DBS) has demonstrated efficacy in improving symptoms in medically refractory patients. Multiple targets have been investigated. OBJECTIVE: To systematically review the current level and quality of evidence supporting OCD-DBS by target region with the goal of establishing a common nomenclature. METHODS: A systematic literature review was performed using the PubMed database and a patient/problem, intervention, comparison, outcome search with the terms "DBS" and "OCD." Of 86 eligible articles that underwent full-text review, 28 were included for review. Articles were excluded if the target was not specified, the focus on nonclinical outcomes, the follow-up period shorter than 3 mo, or the sample size smaller than 3 subjects. Level of evidence was assigned according to the American Association of Neurological Surgeons/Congress of Neurological Surgeons joint guideline committee recommendations. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Selected publications included 9 randomized controlled trials, 1 cohort study, 1 case-control study, 1 cross-sectional study, and 16 case series. Striatal region targets such as the anterior limb of the internal capsule, ventral capsule/ventral striatum, and nucleus accumbens were identified, but stereotactic coordinates were similar despite differing structural names. Only 15 of 28 articles included coordinates. CONCLUSION: The striatal area is the most commonly targeted region for OCD-DBS. We recommend a common nomenclature based on this review. To move the field forward to individualized therapy, active contact location relative to stereotactic coordinates and patient specific anatomical and clinical variances need to be reported.

Correlations Between Family History of Psychiatric Illnesses and Outcomes of Spinal Cord Stimulation.

OBJECTIVES: Spinal cord stimulation (SCS) is a well-established procedure for chronic neuropathic pain. Research has established patients with personal psychiatric history do not fare as well as their correspondents following SCS surgery. We explored whether a documented psychiatric family history (PFH) correlated with worse outcomes following SCS surgery. MATERIALS AND METHODS: We retrospectively reviewed our single-center, prospectively collected database of patients who received permanent SCS implants over the past eight years. Subjects were separated into those with documented PFH and those without. Subjects completed validated scales at preoperative, 6 ± 2 postoperative, and 12 ± 3 months postoperative visits. The percent change in scores from preoperative to postoperative timepoints was compared between subjects with PFH vs. controls. RESULTS: SCS subjects reporting a PFH demonstrated significantly worse 6-month outcomes on Pain Catastrophizing Scale-rumination subscale (p = 0.02), numeric rating scale (NRS) scores on "pain at its least" (p = 0.04) and NRS "pain right now" (p = 0.02). This group also endorsed greater disability as measured by the Oswestry Disability Index (ODI) throughout the follow-up period (p = 0.04 at 6 ± 2 months, p = 0.001 at 12 ± 3 months). CONCLUSIONS: Subjects with PFH may experience less improvement in disability following SCS as compared to subjects without PFH. They may take longer to achieve the same outcomes, including pain relief and decrease in pain rumination. Our findings show that improvements in the PFH cohort are equivalent to that of the no PFH cohort on all measures except ODI at 12-month follow-up. Thus obtaining a detailed PFH prior to performing SCS is important in order to implement pre-operative coping training for PFH patients, rather than exclusion from SCS.

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson's Disease and Essential Tremor Patients.

BACKGROUND: Newer generation deep brain stimulation (DBS) systems have recently become available in the United States. Data on real-life experience are limited. We present our initial experience incorporating newer generation DBS with Parkinson's disease (PD) and essential tremor (ET) patients. Newer systems allow for smart energy delivery and more intuitive programming and hardware modifications including constant current and directional segmented contacts. METHODS: We compared six-month outcomes between 42 newer generation and legacy leads implanted in 28 patients. Two cohorts each included 7 PD patients with bilateral subthalamic nucleus (STN) stimulation and 7 ET patients with unilateral ventral intermediate nucleus (VIM) stimulation of the thalamus. All directional leads included 6172 Infinity 8-Channel Directional leads and Infinity internal pulse generators (Abbott Neuromodulation, Plano, TX, USA) and nondirectional leads included lead 3389 with Activa SC for VIM and PC for STN (Medtronic, Minneapolis, MN, USA). RESULTS: Six-month outcomes for medication reduction and motor score improvements between new and legacy DBS systems in PD and ET patients were similar. Directionality was employed in 1/3 of patients. Therapeutic window (difference between amplitude when initial symptom relief was obtained and when intolerable side effects appeared with the contact being used) was significantly greater in new DBS systems in both PD (p = 0.005) and ET (p = 0.035) patients. The windows for new and legacy systems were 3.60 V ± 0.42 and 2.00 V ± 0.32 for STN and 3.06 V ± 0.44 and 1.85 V ± 0.28 for VIM, respectively. DISCUSSION: The therapeutic window of newer systems, whether or not directionality was used, was significantly greater than that of the legacy system, which suggests increased benefit and programming options. Improvements in hardware and programming interfaces in the newer systems may also contribute to wider therapeutic windows. We expect that as we alter workflow associated with newer technology, more patients will use directionality, and amplitudes will become lower.

Less Pain Relief, More Depression, and Female Sex Correlate With Spinal Cord Stimulation Explants.

BACKGROUND: Spinal cord stimulation (SCS) is a known therapy for a variety of chronic pain conditions, but over time a number of patients proceed to explants. OBJECTIVES: We compared explant rates based on degree of pain relief, diagnosis, lead location, gender, and age to determine possible predictors for SCS implant success. METHODS: First, we performed a single-center retrospective chart review of consecutive SCS-implanted subjects was to document internal explant rates. Rates of explants based on diagnosis, gender, age, and lead location were compared to determine potential trends. We then examined which thoracic SCS patients in our prospectively collected outcome measures data base who were explanted. RESULTS: A total of 63 of 671 thoracic SCS were explanted. Thoracic explants occurred in patients who were significantly younger (p = 0.03). Women who were explanted reported significantly more discomfort from the device (p = 0.05). When we looked at our data base of patients with a mean time implanted of 2.77 years and a minimum of one year follow-up, 11 of 114 thoracic SCS patients were explanted. All explants were women. There was no correlation with diagnosis or age. Those who were explanted reported more pain (p = 0.03) and depression (p < 0.01) at one year follow-up. CONCLUSIONS: Our data correlates explants with less pain relief and more depression. Women are more likely to have explants than men. The role of physiologic and psychosocial variables leading to this difference has yet to be elucidated.

Effects of subthalamic deep brain stimulation with gabapentin and morphine on mechanical and thermal thresholds in 6-hydroxydopamine lesioned rats.

Chronic pain is the most common non-motor symptom among Parkinson's disease (PD) patients, with 1.85 million estimated to be in debilitating pain by 2030. Subthalamic deep brain stimulation (STN DBS) programmed for treating PD motor symptoms has also been shown to significantly improve pain scores. However, even though most patients' pain symptoms improve or disappear, 74% of patients treated develop new pain symptoms within 8 years. Previously we have shown that duloxetine and STN high frequency stimulation (HFS) significantly increase mechanical thresholds more than either alone. The current project specifically investigates the effects of gabapentin and morphine alone and with high (150 Hz; HFS) and low (50 Hz; LFS) frequency stimulation in the 6-hydroxydopamine rat model for PD. We found that HFS, LFS, gabapentin 15 mg/kg and morphine 1 mg/kg all independently improve von Frey (VF) thresholds. Neither drug augments the HFS response significantly. Morphine at 1 mg/kg showed a trend to increasing thresholds compared to LFS alone (p = 0.062). Interestingly, gabapentin significantly reduced (p = 0.019) the improved VF thresholds and Randall Selitto thresholds seen with LFS. Thus, though neither drug augments DBS, we found effects of both compounds independently increase VF thresholds, informing use of our model of chronic pain in PD. Gabapentin's reversal of LFS effects warrants further exploration.

The motivation to behaviorally thermoregulate during passive heat exposure in humans is dependent on the magnitude of increases in skin temperature.

We tested the hypothesis that the motivation to behaviorally thermoregulate in humans is dependent on the magnitude of changes in mean skin temperature. Ten healthy subjects (22 ±â€¯3 y, 5 females) underwent 60 min of seated rest in a 32±1 °C or 42±1 °C environment (20% relative humidity). Trials were completed in a counterbalanced order. The motivation to behaviorally thermoregulate was measured using an operant behavior task on a fixed ratio schedule, in which subjects received thermal reinforcement after clicking a button 100 times. The reinforcer was 30 s of cooling on the dorsal aspect of the neck. The motivation to behave was defined as the cumulative number of button clicks over time and behavioral thermoregulation was defined as the change in neck skin temperature. Mean skin temperature was higher throughout the 42 °C versus the 32 °C trial (at 60 min: 36.3±0.5 °C vs. 34.5±0.5 °C, P < .01) and core temperature became higher in this trial 40 min into heat exposure (at 60 min: 37.2±0.2 °C vs. 37.1±0.1 °C, P ≤ .04), but did not differ from pre- heat exposure (P = .81). Neck skin temperature was lower in the 42 °C compared to the 32 °C trial starting at 30 min (33.7±0.8 °C vs. 35.3±0.5°C, P < .01), which was maintained thereafter (P ≤ .04). Cumulative responding for thermal reinforcement was greater in the 42 °C trial compared to the 32 °C trial at 20 min (180±155 clicks vs. 0±0 clicks, P < .01), which persisted thereafter (P < .01). These data indicate that the motivation to behaviorally thermoregulate during passive heat exposure in humans is dependent on the magnitude of increases in skin temperature.