Effect of Eye Opening on Single-Unit Activity and Local Field Potentials in the Subthalamic Nucleus.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment in Parkinson's disease (PD). We investigate the effect of eye opening on neuronal activity and local field potentials (LFPs) in the STN. METHODS: We prospectively enrolled 25 PD patients undergoing STN DBS in our institution. During DBS, single-unit activity (SUA) and LFPs were measured when eyes were open and closed. As movement is known to result in changes in LFPs, we tested response to eye opening in the presence and absence of movement. RESULTS: Neither eye state nor arm movement has a significant influence on SUA recordings. There is a statistically significant interaction between eye state and arm movement (p < 0.05). In the presence of movement, STN SUA increase when eyes open (p < 0.05). When eyes are closed, STN SUA decrease with movement (p < 0.05). STN theta LFP oscillations decrease when eyes are open compared to closed, irrespective of movement status (p < 0.05). DISCUSSION: STN activity is influenced by eye state and arm movement. It is unclear whether this is attributed to a change in the STN's role in oculomotor control or from a change in attentional state. Understanding how physiologic normal activity alters neural activity is critical for the optimization of DBS therapy, particularly in closed-loop neuromodulation.

The Use of Preoperative Psychological Evaluations to Predict Spinal Cord Stimulation Success: Our Experience and a Review of the Literature.

BACKGROUND: Pre-operative psychological assessment is commonly used to assess patients for spinal cord stimulation (SCS). Though often times mandated by insurance, its value is frequently questioned. METHODS: We review the literature on the predictive value of psychological testing prior to SCS and retrospectively examine our prospective database of SCS patients. We examine associations of Minnesota Multiphasic Personality Inventory (MMPI), Beck Depression Inventory (BDI), and Pain Catastrophizing Scale (PCS) findings and outcomes on the visual analog scale (VAS), McGill Pain Questionnaire - Short Form (MPQ), and Oswestry Disability Index (ODI) at 6 and 12 months post-implantation. RESULTS: The nine studies examining psychological predictors of SCS outcomes collectively showed that substance abuse or feelings of demoralization or less joy correlated with worse outcomes. Though not statistically significant, our data show that at one year follow-up, patients without psychiatric disorders improved 1.5 times as much on ODI and 2.4 times as much on PCS as compared to patients with psychiatric disorders. Further, depressed patients concurrently treated with anti-depressants had greater improvement in BDI than non-medicated depressed patients (p = 0.009). We develop a tool for pain psychologists based on the existing literature to aid in identifying possible concerns and treating these patients peri-operatively. DISCUSSION: The predictive value of psychological testing depends on which psychiatric factors are used and which outcomes are measured. The predictive capacity of psychological indications can be used to holistically treat patients, specifically to recommend psychiatric medication and consulting to supplement SCS treatment as needed.

The effects of subthalamic deep brain stimulation on mechanical and thermal thresholds in 6OHDA-lesioned rats.

Chronic pain is a major complaint for up to 85% of Parkinson's disease patients; however, it often not identified as a symptom of Parkinson's disease. Adequate treatment of motor symptoms often provides analgesic effects in Parkinson's patients but how this occurs remains unclear. Studies have shown both Parkinson's patients and 6-hydroxydopamine-lesioned rats exhibit decreased sensory thresholds. In humans, some show improvements in these deficits after subthalamic deep brain stimulation, while others report no change. Differing methods of testing and response criteria may explain these varying results. We examined this effect in 6-hydroxydopamine-lesioned rats. Sprague-Dawley rats were unilaterally implanted with subthalamic stimulating electrodes in the lesioned right hemisphere and sensory thresholds were tested using von Frey, tail-flick and hot-plate tests. Tests were done during and off subthalamic stimulation at 50 and 150 Hz to assess its effects on sensory thresholds. The 6-hydroxydopamine-lesioned animals exhibited lower mechanical (left paw, P < 0.01) and thermal thresholds than shams (hot plate, P < 0.05). Both 50 and 150 Hz increased mechanical (left paw; P < 0.01) and thermal thresholds in 6-hydroxydopamine-lesioned rats (hot-plate test: 150 Hz, P < 0.05, 50 Hz, P < 0.01). Interestingly, during von Frey testing, low-frequency stimulation provided a more robust improvement in some 6OHDA lesioned rats, while in others, the magnitude of improvement on high-frequency stimulation was greater. This study shows that subthalamic deep brain stimulation improves mechanical allodynia and thermal hyperalgesia in 6-hydroxydopamine-lesioned animals at both high and low frequencies. Furthermore, we suggest considering using low-frequency stimulation when treating Parkinson's patients where pain remains the predominant complaint.

The current state, challenges, and future directions of deep brain stimulation for obsessive compulsive disorder.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is clinically and pathologically heterogenous, with symptoms often refractory to first-line treatments. Deep brain stimulation (DBS) for the treatment of refractory OCD provides an opportunity to adjust and individualize neuromodulation targeting aberrant circuitry underlying OCD. The tailoring of DBS therapy may allow precision in symptom control based on patient-specific pathology. Progress has been made in understanding the potential targets for DBS intervention; however, a consensus on an optimal target has not been agreed upon. AREAS COVERED: A literature review of DBS for OCD was performed by querying the PubMed database. The following topics were covered: the evolution of DBS targeting in OCD, the concept of an underlying unified connectomic network, current DBS targets, challenges facing the field, and future directions which could advance personalized DBS in this challenging population. EXPERT OPINION: To continue the increasing efficacy of DBS for OCD, we must further explore the optimal DBS response across clinical profiles and neuropsychiatric domains of OCD as well as how interventions targeting multiple points in an aberrant circuit, multiple aberrant circuits, or a connectivity hub impact clinical response. Additionally, biomarkers would be invaluable in programming adjustments and creating a closed-loop paradigm to address symptom fluctuation in daily life.

Olanzapine in ED patients: differential effects on oxygenation in patients with alcohol intoxication.

INTRODUCTION: Agitation has significant consequences for patients and staff. When verbal techniques fail, expert guidelines recommend the use of second-generation antipsychotics (SGAs). Perhaps out of familiarity with haloperidol and benzodiazepines, emergency department (ED) clinicians often pair SGAs with benzodiazepines as well. Use of SGAs such as olanzapine in alcohol-intoxicated (ETOH+) patients or with benzodiazepines is not well studied and may be associated with vital sign abnormalities. METHODS: This is a structured chart review of all patient visits who received either oral or intramuscular (i.m.) olanzapine in an academic ED from 2004 to 2010 and who had systolic blood pressure, heart rate, and oxygen saturation documented before medication administration and within 4 hours afterwards. RESULTS: Four hundred eighty-two patient visits received olanzapine; 275 patient visits (225 oral, 50 i.m.) had vital signs documented. Neither route of administration, concurrent benzodiazepines, nor ingestion of ETOH were associated with significant decreases in systolic BP or heart rate (P = ns for all comparisons). Decreases in oxygen saturations, however, were significantly larger in ETOH+ patients who received i.m. olanzapine or i.m. olanzapine + benzodiazepines. Route of administration, concurrent benzodiazepines, nor ingestion of ETOH was associated with significant decreases in systolic blood pressure or heart rate (p = ns for all comparisons). Decreases in oxygen saturations, however, were significantly larger in ETOH+ patients who received i.m. olanzapine or i.m. olanzapine + benzodiazepines. CONCLUSIONS: Oral olanzapine was not associated with significant vital sign changes in ED patients. Intramuscular olanzapine also was not associated with vital sign changes in ETOH- patients. In ETOH+ patients, i.m. olanzapine was associated with significant oxygen desaturations. In ETOH+ ED patients, oral olanzapine (with or without benzodiazepines) or haloperidol may be safer choices. ETOH+ patients may have differential effects with the use of i.m. SGAs such as olanzapine and should be studied separately in drug trials.

The Effects of Topical Vancomycin on Mesenchymal Stem Cells: More May Not Be Better.

BACKGROUND: The use of topical vancomycin is increasingly popular in spine surgery. Large retrospective reviews suggest that topical vancomycin provides a cost-effective decrease in post-operative infection. Currently, there is little that is known about the maximum dose that can be applied locally. When 1 gram of vancomycin is mixed into the bone graft and another 1 gram applied freely in a spine wound, the local concentration of antibiotic ranges from 260-2900 µg/mL in the immediate post-op period and 50-730 µg/mL by the second post-operative day. We hypothesized that exuberant doses of vancomycin would be toxic to mesenchymal stem cells (MSCs). METHODS: Bone marrow was obtained from the femoral canal of patients undergoing routine elective total hip arthroplasty. Mesenchymal stem cells were isolated using plastic adhesion. Cells were exposed to a wide range of doses of vancomycin for 24 hours and then assessed for viability. Osteogenic potential was assessed with alizarin red staining. RESULTS: There was dose-dependent cell death with vancomycin use. MSC death was 9.43% at 400 µg/mL (p=0.047), 13.79% at 1600 µg/mL (p=0.0047), 19.35% at 3200 µg/mL (p<0.0001), 24.82% at 6400 µg/mL (p<0.0001) and 51.83% at 12800 µg/mL of vancomycin (p<0.0001) in comparison to the control group containing no vancomycin. CONCLUSIONS: Our in vitro study suggests that vancomycin has toxic effects on hMSCs, a cell population particularly important for bone formation. In the absence of any clinical evidence suggesting that "more vancomycin is better," and our data suggesting that more vancomycin is harmful in vitro, surgeons electing to use topical vancomycin in spine surgery should restrict their use to the doses currently reported in the available published studies unless specific reasons exist otherwise. This study does not establish a contraindication to the use of topical vancomycin, nor does it suggest that pseudarthroses are attributable to vancomycin use.

Treatment of Allodynia by Occipital Nerve Stimulation in Chronic Migraine Rodent.

BACKGROUND: Occipital nerve stimulation (ONS) is a therapy that benefits one-third of medically refractory chronic migraine (CM) patients. How ONS affects sensory thresholds and whether modulation of thresholds could predict which patients respond to the therapy remains unclear. OBJECTIVE: To examine the effects of ONS on mechanical and thermal thresholds in a rodent CM model to better elucidate its mechanism of action. METHODS: Male Sprague-Dawley rats were implanted bilaterally with electrodes to produce ONS. The CM cohort was infused with inflammatory media epidurally based on a validated model, whereas shams were not. Thresholds were evaluated with von Frey filaments and hot plate and thermode tests. RESULTS: No baseline differences in sensory thresholds were found between the sham (n = 16) and CM (n = 16) groups. After headache induction, CM animals demonstrated mechanical allodynia in the occiput, periorbital region, forepaws, and hind paws (P < .05). In CM animals, ONS increased mechanical thresholds in all regions (P < .001), whereas in shams, it did not. ONS did not affect thermal thresholds in either group. CONCLUSION: We show that ONS improves mechanical thresholds in a rodent CM model, but not in shams. Our finding that mechanical but not thermal thresholds are altered with ONS suggests a more significant modulation of A-α/ß fibers than of C fibers. Assessing the ability of ONS to reduce mechanical thresholds during a trial period could potentially be used to predict which patients respond.

Place conditioning to apomorphine in rat models of Parkinson's disease: differences by dose and side-effect expression.

One potential complication of treating Parkinson's Disease (PD) with dopaminergic drugs is dopamine dysregulation syndrome, an addiction-like response to the drug therapy. Here, we assessed whether rats given parkinsonian-like symptoms with a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle (6-OHDA-MFB), exhibit similar behavior. To examine this, we injected these rats or sham-lesioned rats subcutaneously (sc) with apomorphine (APO) at low (0.05mg/kg) and high (1mg/kg) dosage and monitored their conditioned place preference Saline was administered on alternating days. After 4 and 8 conditioned pairings, both rat groups underwent post-conditioning tests in a drug-free state 6-OHDA rats exhibited positive place conditioning to the low dose of APO after 4 and 8 pairings whereas sham-lesioned rats did not (p<0.01). At the high APO dose, sham-lesioned rats showed consistent positive place conditioning, but preferences in 6-OHDA rats were more variable although they all exhibited rotation behavior. Upon further inspection, we noted that contraversive rotation increased over time and this negatively correlated with place conditioning scores. While the absolute number of rotations did not negatively affect preference for the APO-paired chamber, an increase in rotation numbers between pairings did (r=-0.634, p=0.027). Taken together, 6-OHDA rats were more sensitive to the rewarding aspects of APO, but the adverse consequence of rotation diminished this response This model may be ideal to study addiction-like responses in PD.