Prevention of Implant-Associated Infection in Neuromodulation: Review of the Literature and Prototype of a Novel Protective Implant Coating.

Background: Implanting hardware into surgical sites increases the rate of infection associated with these sites. Without novel efforts to reduce this rate of infection, we can expect to see an increase in the number of hardware-associated infections as more patients are implanted with these devices. These infections often necessitate the removal of these devices resulting in a significant financial and clinical burden to patients. We developed a prototype antibiotic coating using products that are both low cost and that can be sourced easily. Our study aims to test the effectiveness of this coating against bacteria commonly observed in hospital-associated infections. Methods: The antibiotic coating was prepared by combining one gram of vancomycin and 500 mg of ciprofloxacin in 50 mL of glycerol. The coating was examined for inhibition of growth of Pseudomonas aeruginosa PA14 and Staphylococcus aureus AH2486 and compared with the bacterial growth of the above bacteria in glycerol alone. The growth curves were plotted measuring the bacterial growth at 5 h intervals. Results: The results of the growth curves clearly demonstrate a lack of bacterial growth when these bacteria are combined with glycerol combined with our selected antibiotic agents. Conclusion: There appears to be a limited interest from device companies in developing new strategies for infection prevention associated with neurosurgical hardware, and we propose that this prototype will be an effective and low-cost solution to a large problem.

Deep Brain Stimulation of the Hypothalamus Leads to Increased Metabolic Rate in Refractory Obesity.

OBJECTIVE: Obesity has become a worldwide epidemic, with very few long-term successful treatment options for refractory disease. Deep brain stimulation (DBS) of the bilateral lateral hypothalamus (LH) in refractory obesity has been performed safely. However, questions remain regarding the optimal settings and its effects on metabolic rate. The goals of our experiment were to determine the optimal DBS settings and the actual effect of optimal stimulation on energy expenditure. METHODS: After bilateral LH DBS implantation, 2 subjects with treatment refractory obesity underwent 4 days of metabolic testing. The subjects slept overnight in a respiratory chamber to measure their baseline sleep energy expenditure, followed by 4 consecutive days of resting metabolic rate (RMR) testing at different stimulation settings. On day 4, the optimized DBS settings were used, and sleep energy expenditure was measured again overnight in the room calorimeter. RESULTS: During daily testing, the RMR fluctuated acutely with changes in stimulation settings and returned to baseline immediately after turning off the stimulation. Optimal stimulation settings selected for participants showed a 20% and 16% increase in RMR for the 2 participants. Overnight sleep energy expenditure measurements at these optimized settings on day 4 yielded a 10.4% and 4.8% increase over the baseline measurements for the 2 participants. CONCLUSIONS: These findings have demonstrated the efficacy of optimized DBS of the LH on increasing the RMR acutely and maintaining this increase during overnight sleep. These promising preliminary findings have laid the groundwork for the possible treatment of refractory obesity with DBS.

Deep brain stimulation for appetite disorders: a review.

The mechanisms of appetite disorders, such as refractory obesity and anorexia nervosa, have been vigorously studied over the last century, and these studies have shown that the central nervous system has significant involvement with, and responsibility for, the pathology associated with these diseases. Because deep brain stimulation has been shown to be a safe, efficacious, and adjustable treatment modality for a variety of other neurological disorders, it has also been studied as a possible treatment for appetite disorders. In studies of refractory obesity in animal models, the ventromedial hypothalamus, the lateral hypothalamus, and the nucleus accumbens have all demonstrated elements of success as deep brain stimulation targets. Multiple targets for deep brain stimulation have been proposed for anorexia nervosa, with research predominantly focusing on the subcallosal cingulate, the nucleus accumbens, and the stria terminalis and medial forebrain bundle. Human deep brain stimulation studies that focus specifically on refractory obesity and anorexia nervosa have been performed but with limited numbers of patients. In these studies, the target for refractory obesity has been the lateral hypothalamus, ventromedial hypothalamus, and nucleus accumbens, and the target for anorexia nervosa has been the subcallosal cingulate. These studies have shown promising findings, but further research is needed to elucidate the long-term efficacy of deep brain stimulation for the treatment of appetite disorders.

Thalamic Deep Brain Stimulation.

The use of deep brain stimulation (DBS) of the thalamus has been proven to be a safe and efficacious treatment for the management of many diseases. The most common indication for thalamic DBS remains essential tremor (ET), one of the most common movement disorders in the world. ET patients should be considered for surgical intervention when their tremor has demonstrated to be refractory to medication, a characteristic estimated to be present in roughly 50% of ET cases. Advantages of DBS over thalamotomy include its reversibility, the ability to adjust stimulation settings to optimize efficacy and minimize side effects, the ability to perform bilateral procedures safely, and an association with a lower risk of postoperative cognitive problems. The most common target of DBS for ET is the ventralis intermedius (VIM) of the thalamus, and the optimal electrode location corresponds to the anterior margin of the VIM. Other indications for thalamic DBS include non-ET tremor, obsessive-compulsive disorder, neuropathic pain, traumatic brain injury, Tourette's syndrome, and drug-resistant epilepsy among others.

Cranial plate anchoring of spinal cord stimulation paddle leads: technical note.

BACKGROUND: Lead migration is a frequent complication of spinal cord stimulation (SCS) and requires revision surgery. The evolution of wider paddle leads has necessitated more extensive laminotomy and epidural adhesiolysis, which may increase the risk of lead migration. OBJECTIVE: We describe a novel anchoring technique for SCS paddle leads with use of a cranial "dogbone" plate. METHODS: We retrospectively reviewed a consecutive series of 11 patients who underwent placement of paddle lead spinal cord stimulators with titanium plate anchoring. Patients were followed for a mean of 29.5 months from SCS implantation (range, 5-65 months). A 4-hole linear titanium cranial plate and two 4-mm screws were used to tightly affix the proximal paddle lead wiring to the lamina below the laminotomy defect. RESULTS: All patients continue to have satisfactory spinal cord stimulation with no loss of efficacy or need for revision. No complications have been attributed to titanium plate anchoring, and there have been no cases of lead migration with this technique. Titanium plate anchoring added minimal time (approximately 3-5 minutes) to the operative case. CONCLUSION: We report a safe and effective anchoring technique for paddle lead SCS with the use of a cranial plate. Our experience has been that this technique, which anchors the proximal lead wiring to the remaining lamina at the inferior laminotomy defect, is superior to anchoring methods that rely on suturing of lead wiring.

Deep brain stimulation for obesity--from theoretical foundations to designing the first human pilot study.

Obesity is perhaps an evolutionary consequence of a species reared with intermittent caloric reward. Humans are hardwired to enjoy food, and our bodies voraciously extract and store energy from food as if each meal was the last. As an amalgam of behavioral and metabolic disturbance, obesity is an attractive target for deep brain stimulation (DBS) since neuromodulation may be able to influence both eating behavior and metabolism. The current pandemic proportions of obesity combined with the failures and morbidity of modern treatments remain the impetus behind the application of DBS to this complex disease. We review the rationale and scientific foundations for obesity DBS and explain how this preclinical evidence has helped sculpt the design of the first human pilot study.

Expanding applications of deep brain stimulation: a potential therapeutic role in obesity and addiction management.

BACKGROUND: The indications for deep brain stimulation (DBS) are expanding, and the feasibility and efficacy of this surgical procedure in various neurologic and neuropsychiatric disorders continue to be tested. This review attempts to provide background and rationale for applying this therapeutic option to obesity and addiction. We review neural targets currently under clinical investigation for DBS­the hypothalamus and nucleus accumbens­in conditions such as cluster headache and obsessive-compulsive disorder. These brain regions have also been strongly implicated in obesity and addiction. These disorders are frequently refractory, with very high rates of weight regain or relapse, respectively, despite the best available treatments. METHODS: We performed a structured literature review of the animal studies of DBS, which revealed attenuation of food intake, increased metabolism, or decreased drug seeking. We also review the available radiologic evidence in humans, implicating the hypothalamus and nucleus in obesity and addiction. RESULTS: The available evidence of the promise of DBS in these conditions combined with significant medical need, support pursuing pilot studies and clinical trials of DBS in order to decrease the risk of dietary and drug relapse. CONCLUSIONS: Well-designed pilot studies and clinical trials enrolling carefully selected patients with obesity or addiction should be initiated.

Randomized, prospective, and controlled clinical trial of pulsed electromagnetic field stimulation for cervical fusion.

BACKGROUND CONTEXT: Multilevel fusions, the use of allograft bone, and smoking have been associated with an increased risk of nonunion after anterior cervical discectomy and fusion (ACDF) procedures. Pulsed electromagnetic field (PEMF) stimulation has been shown to increase arthrodesis rates after lumbar spine fusion surgery, but there are minimal data concerning the effect of PEMF stimulation on cervical spine fusion. PURPOSE: To determine the efficacy and safety of PEMF stimulation as an adjunct to arthrodesis after ACDF in patients with potential risk factors for nonunion. STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial. PATIENT SAMPLE: Three hundred and twenty-three patients with radiographic evidence (computed tomography-myelogram [CT-myelo] or magnetic resonance imaging [MRI]) of a compressed cervical nerve root and symptomatic radiculopathy appropriate to the compressed root that had failed to respond to nonoperative management were enrolled in the study. The patients were either smokers (more than one pack per day) and/or were undergoing multilevel fusions. All patients underwent ACDF using the Smith-Robinson technique. Allograft bone and an anterior cervical plate were used in all cases. OUTCOME MEASURES: Measurements were obtained preoperatively and at each postoperative interval and included neurologic assessment, visual analog scale (VAS) scores for shoulder/arm pain at rest and with activity, SF-12 scores, the neck disability index (NDI), and radiographs (anteroposterior, lateral, and flexion-extension views). Two orthopedic surgeons not otherwise affiliated with the study and blinded to treatment group evaluated the radiographs, as did a blinded radiologist. Adverse events were reported by all patients throughout the study to determine device safety. METHODS: Patients were randomly assigned to one of two groups: those receiving PEMF stimulation after surgery (PEMF group, 163 patients) and those not receiving PEMF stimulation (control group, 160 patients). Postoperative care was otherwise identical. Follow-up was carried out at 1, 2, 3, 6, and 12 months postoperatively. RESULTS: The PEMF and control groups were comparable with regard to age, gender, race, past medical history, smoking status, and litigation status. Both groups were also comparable in terms of baseline diagnosis (herniated disc, spondylosis, or both) and number of levels operated (one, two, three, or four). At 6 months postoperatively, the PEMF group had a significantly higher fusion rate than the control group (83.6% vs. 68.6%, p=.0065). At 12 months after surgery, the stimulated group had a fusion rate of 92.8% compared with 86.7% for the control group (p=.1129). There were no significant differences between the PEMF and control groups with regard to VAS pain scores, NDI, or SF-12 scores at 6 or 12 months. No significant differences were found in the incidence of adverse events in the groups. CONCLUSIONS: This is the first randomized, controlled trial that analyzes the effects of PEMF stimulation on cervical spine fusion. PEMF stimulation significantly improved the fusion rate at 6 months postoperatively in patients undergoing ACDF with an allograft and an anterior cervical plate, the eligibility criteria being patients who were smokers or had undergone multilevel cervical fusion. At 12 months postoperatively, however, the fusion rate for PEMF patients was not significantly different from that of the control group. There were no differences in the incidence of adverse events in the two groups, indicating that the use of PEMF stimulation is safe in this clinical setting.