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.

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.

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.

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.

Long-term hardware-related complications of deep brain stimulation.

OBJECTIVE: To determine the incidence of long-term hardware-related complications of deep brain stimulation (DBS). METHODS: The study design is a retrospective chart review of a single-surgeon, single-institution experience with DBS in 84 consecutive cases from 1993 to 1999. Only patients with a minimum follow-up of 1 year were considered. Five patients were excluded because trial stimulation failed to achieve pain relief (n = 4) or because the procedure was aborted owing to hemorrhage (n = 1). Seventy-nine patients received 124 permanent DBS electrode implants. RESULTS: The mean follow-up period was 33 months, and the cumulative follow-up time was 217 patient-years or 310 electrode-years. Overall, 20 patients (25.3%) had 26 hardware-related complications involving 23 (18.5%) of the electrodes. There were 4 lead fractures, 4 lead migrations, 3 short or open circuits, 12 erosions and/or infections, 2 foreign body reactions, and one cerebrospinal fluid leak. The hardware-related complication rate per electrode-year was 8.4%. The most common complications were related to the electrode connectors. A significant finding was a high number of complications involving erosions or infections, which occurred in 7 of 12 instances as a late complication (beyond 12 mo). CONCLUSION: Long-term follow-up reveals that hardware-related complications occur in a significant number of patients. Factors that lead to such complications must be identified and addressed to maximize the important benefits of DBS therapy.