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Background: The ventral intermediate (VIM) thalamic nucleus is the main target for the surgical treatment of refractory tremor. Initial targeting traditionally relies on atlas-based stereotactic targeting formulas, which only minimally account for individual anatomy. Alternative approaches have been proposed, including direct targeting of the dentato-rubro-thalamic tract (DRTT), which, in clinical settings, is generally reconstructed with deterministic tracking. Whether more advanced probabilistic techniques are feasible on clinical-grade magnetic resonance acquisitions and lead to enhanced reconstructions is poorly understood., Objective: To compare DRTT reconstructed with deterministic vs probabilistic tracking., Methods: This is a retrospective study of 19 patients with essential tremor who underwent deep brain stimulation (DBS) with intraoperative neurophysiology and stimulation testing. We assessed the proximity of the DRTT to the DBS lead and to the active contact chosen based on clinical response., Results: In the commissural plane, the deterministic DRTT was anterior (P < 10-4) and lateral (P < 10-4) to the DBS lead. By contrast, although the probabilistic DRTT was also anterior to the lead (P < 10-4), there was no difference in the mediolateral dimension (P = .5). Moreover, the 3-dimensional Euclidean distance from the active contact to the probabilistic DRTT was smaller vs the distance to the deterministic DRTT (3.32 ± 1.70 mm vs 5.01 ± 2.12 mm; P < 10-4)., Conclusion: DRTT reconstructed with probabilistic fiber tracking was superior in spatial proximity to the physiology-guided DBS lead and to the empirically chosen active contact. These data inform strategies for surgical targeting of the VIM., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant depression (TRD) that has shown variable efficacy. This report describes long-term outcomes of DBS for TRD., Methods: A consecutive series of 8 patients with TRD were implanted with ventral capsule/ventral striatum (VC/VS) DBS systems as part of the Reclaim clinical trial. Outcomes from 2009 to 2020 were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Demographic information, MADRS scores, and data on adverse events were collected via retrospective chart review. MADRS scores were integrated over time using an area-under-the-curve technique., Results: This cohort of patients had severe TRD-all had failed trials of ECT, and all had failed a minimum of 4 adequate medication trials. Mean ± SD follow-up for patients who continued to receive stimulation was 11.0 ± 0.4 years (7.8 ± 4.3 years for the entire cohort). At last follow-up, mean improvement in MADRS scores was 44.9% ± 42.7%. Response (≥ 50% improvement) and remission (MADRS score ≤ 10) rates at last follow-up were 50% and 25%, respectively. Two patients discontinued stimulation due to lack of efficacy, and another patient committed suicide after stimulation was discontinued due to recurrent mania. The majority of the cohort (63%) continued to receive stimulation through the end of the study., Conclusions: While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this small open-label study demonstrates that some patients achieve meaningful and sustained clinical benefit. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including patient selection, integrative outcome measures, and long-term observation is essential for future trial design., Trial Registration: ClinicalTrials.gov identifier: NCT00837486., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Background: In deep brain stimulation (DBS) for essential tremor, the primary target ventrointermedius (VIM) nucleus cannot be clearly visualized with structural imaging. As such, there has been much interest in the dentatorubrothalamic tract (DRTT) for target localization, but evidence for the DRTT as a putative stimulation target in tremor suppression is lacking. We evaluated proximity of the DRTT in relation to DBS stimulation parameters., Methods: This is a retrospective analysis of 26 consecutive patients who underwent DBS with microelectrode recordings (46 leads). Fiber tracking was performed with a published deterministic technique. Clinically optimized stimulation parameters were obtained in all patients at the time of most recent follow-up (6.2 months). Volume of tissue activated (VTA) around contacts was calculated from a published model., Results: Tremor severity was reduced in all treated hemispheres, with 70% improvement in the treated hand score of the Clinical Rating Scale for Tremor. At the level of the active contact (2.9 ± 2.0 mm superior to the commissural plane), the center of the DRTT was lateral to the contacts (5.1 ± 2.1 mm). The nearest fibers of the DRTT were 2.4 ± 1.7 mm from the contacts, whereas the radius of the VTA was 2.9 ± 0.7 mm. The VTA overlapped with the DRTT in 77% of active contacts. The distance from active contact to the DRTT was positively correlated with stimulation voltage requirements (Kendall τ = 0.33, P = 0.006), whereas distance to the atlas-based VIM coordinates was not., Conclusions: Active contacts in proximity to the DRTT had lower voltage requirements. Data from a large cohort provide support for the DRTT as an effective stimulation target for tremor control., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Deep brain stimulation (DBS) has revolutionized the treatment of neurological disease, but its therapeutic efficacy is limited by the lifetime of the implantable pulse generator (IPG) batteries. At the end of the battery life, IPG replacement surgery is required. New IPGs with rechargeable batteries (RC-IPGs) have recently been introduced and allow for decreased reoperation rates for IPG replacements. The authors aimed to examine the merits and limitations of these devices., Methods: The authors reviewed the medical records of patients who underwent DBS implantation at their institution. RC-IPGs were placed either during initial DBS implantation or during an IPG change. A cost analysis was performed that compared RC-IPGs with standard IPGs, and telephone patient surveys were conducted to assess patient satisfaction., Results: The authors identified 206 consecutive patients from 2011 to 2016 who underwent RC-IPG placement (mean age 61 years; 67 women, 33%). Parkinson's disease was the most common indication for DBS (n = 144, 70%), followed by essential tremor (n = 41, 20%), dystonia (n = 13, 6%), depression (n = 5, 2%), multiple sclerosis tremor (n = 2, 1%), and epilepsy (n = 1, 0.5%). DBS leads were typically placed bilaterally (n = 192, 93%) and targeted the subthalamic nucleus (n = 136, 66%), ventral intermediate nucleus of the thalamus (n = 43, 21%), internal globus pallidus (n = 21, 10%), ventral striatum (n = 5, 2%), or anterior nucleus of the thalamus (n = 1, 0.5%). RC-IPGs were inserted at initial DBS implantation in 123 patients (60%), while 83 patients (40%) were converted to RC-IPGs during an IPG replacement surgery. The authors found that RC-IPG implantation resulted in $60,900 of cost savings over the course of 9 years. Furthermore, patient satisfaction was high with RC-IPG implantation. Overall, 87.3% of patients who responded to the survey were satisfied with their device, and only 6.7% found the rechargeable component difficult to use. In patients who were switched from a standard IPG to RC-IPG, the majority who responded (70.3%) preferred the rechargeable IPG., Conclusions: RC-IPGs can provide DBS patients with long-term therapeutic benefit while minimizing the need for battery replacement surgery. The authors have implanted rechargeable stimulators in 206 patients undergoing DBS surgery, and here they demonstrate the cost-effectiveness and high patient satisfaction associated with this procedure.

Background: Deep brain stimulation (DBS) has emerged as a safe and efficacious surgical intervention for several movement disorders; however, the 30-day all-cause readmission rate associated with this procedure has not previously been documented., Object: To perform a retrospective cohort study to estimate the 30-day all-cause readmission rate associated with DBS., Methods: We reviewed medical records of patients over the age of 18 who underwent DBS surgery at Pennsylvania Hospital of the University of Pennsylvania between 2009 and 2014. We identified patients who were readmitted to an inpatient medical facility within 30 days from their initial discharge., Results: Over the study period, 23 (6.6%) of 347 DBS procedures resulted in a readmission to the hospital within 30 days. Causes of readmission were broadly categorized into surgery-related (3.7%): intracranial lead infection (0.6%), battery-site infection (0.6%), intracranial hematoma along the electrode tract (0.6%), battery-site hematoma (0.9%), and seizures (1.2%); and nonsurgery-related (2.9%): altered mental status (1.8%), nonsurgical-site infections (0.6%), malnutrition and poor wound healing (0.3%), and a pulse generator malfunction requiring reprogramming (0.3%). Readmissions could be predicted by the presence of medical comorbidities ( P < .001), but not by age, gender, or length of stay ( P s > .15)., Conclusion: All-cause 30-day readmission for DBS is 6.6%. This compares favorably to previously studied neurosurgical procedures. Readmissions frequently resulted from surgery-related complications, particularly infection, seizures, and hematomas, and were significantly associated with the presence of medical comorbidities ( P < .001)., (Copyright © 2017 by the Congress of Neurological Surgeons)

Background: We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS)., Methods: Participants were randomised to active (n=12) versus sham (n=13) DBS for 16 weeks. Data were analysed at the individual and group levels. Group differences were analysed using repeated measures ANOVAs. Relationships between depression severity and cognition were examined using partial correlations. The false discovery rate method controlled for multiple analyses., Results: No significant interactions comparing active versus sham stimulation over time were evident. Change in depression was unrelated to change in neuropsychological measures. Twenty patients declined by ≥1 SD on at least one measure (41.3% of declines occurred in active group participants; 63.0% in older participants regardless of stimulation status). Twenty-two patients exhibited improvements >1 SD on neuropsychological measures (47.7% in the active group; 63.1% in younger participants)., Conclusions: These data suggest that VC/VS DBS in patients with TRD does not significantly affect neuropsychological function. Age at surgery, regardless of stimulation status, may be related to cognitive outcome at the individual patient level., Trial Registration Number: NCT00837486; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 ( clinicaltrials.gov ).

Background: Multiple open-label trials of deep brain stimulation (DBS) for treatment-resistant depression (TRD), including those targeting the ventral capsule/ventral striatum target, have shown encouraging response rates. However, no randomized controlled trials of DBS for TRD have been published., Methods: Thirty patients with TRD participated in a sham-controlled trial of DBS at the ventral capsule/ventral striatum target for TRD. Patients were randomized to active versus sham DBS treatment in a blinded fashion for 16 weeks, followed by an open-label continuation phase. The primary outcome measure was response, defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline., Results: There was no significant difference in response rates between the active (3 of 15 subjects; 20%) and control (2 of 14 subjects; 14.3%) treatment arms and no significant difference between change in Montgomery-Åsberg Depression Rating Scale scores as a continuous measure upon completion of the 16-week controlled phase of the trial. The response rates at 12, 18, and 24 months during the open-label continuation phase were 20%, 26.7%, and 23.3%, respectively., Conclusion: The results of this first randomized controlled study of DBS for the treatment of TRD did not demonstrate a significant difference in response rates between the active and control groups at the end of the 16-week controlled phase. However, a range of 20% to 26.7% of patients did achieve response at any time during the open-label continuation phase. Future studies, perhaps utilizing alternative study designs and stimulation parameters, are needed., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Studies of deep brain stimulation (DBS) in mice are rare due to their small size, agility, aversion to handling, and high anxiety compared to larger species. Studying DBS modulation of neural circuitry in murine models of human behavior may ensure safety, guide stimulatory parameters for clinical trials in humans, and inform a long-eluded mechanism., Methods: Stereotactic deep brain electrode implantation in a mouse is performed. Mechanical etching of the skull with a high-speed drill is used with placement of cyanoacrylate glue and molding of dental acrylate to affix the electrode in place. Stimulation experiments are conducted in the home cage after a habituation period. After testing is complete, electrode placement is verified in fixed tissue., Results: Electrodes can be safely and accurately implanted in mice for DBS experimentation. Previous findings demonstrated accuracy in placement within the nucleus accumbens shell of 93 % [14]. In this study, there were no hardware malfunctions that required interrupting experimentation., Conclusions: Stereotactic DBS studies may be safely and effectively performed in mice to investigate neuropsychiatric disorders. In addition, examining the biochemical and molecular mechanisms underlying these disorders may be facilitated by widely available transgenic mouse lines and the Cre-Lox recombination system.

Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation., (Copyright © 2013. Published by Elsevier Ltd.)

Purpose: Based on the success of deep brain stimulation (DBS) in the treatment of adult disorders, it is reasonable to assume that the application of DBS in the pediatric population is an emerging area worthy of study. The purpose of this paper is to outline the current movement disorder indications for DBS in the pediatric population, and to describe areas of investigation, including possible medically refractory psychiatric indications., Methods: We performed a structured review of the English language literature from 1990 to 2011 related to studies of DBS in pediatrics using Medline and PubMed search results., Results: Twenty-four reports of DBS in the pediatric population were found. Based on published data on the use of DBS for pediatric indications, there is a spectrum of clinical evidence for the use of DBS to treat different disorders. Dystonia, a disease associated with a low rate of remission and significant disability, is routinely treated with DBS and is currently the most promising pediatric application of DBS. We caution the application of DBS to conditions associated with a high remission rate later in adulthood, like obsessive-compulsive disorder and Tourette's syndrome. Moreover, epilepsy and obesity are currently being investigated as indications for DBS in the adult population; however, both are associated with significant morbidity in pediatrics., Conclusion: While currently dystonia is the most promising application of DBS in the pediatric population, multiple conditions currently being investigated in adults also afflict children and adolescents, and thus warrant further research.

We aimed to determine whether our targeting method for the subthalamic nucleus (STN) in Parkinson's disease informs the initial programming sequence. We evaluated 100 STN-lead pairs from 50 patients who underwent bilateral STN-deep brain stimulation operations. All patients had at least one year of follow-up. In each patient, we measured coordinates of the STN borders and determined the center from special T2-weighted MRI. We then measured the postoperative location of the lead tip by MRI registered to preoperative images. Finally, we determined the mode and active contact(s). Programming was monopolar 71% of the time. A total of 52% of left and 72% of right STN active contacts were located posterolateral to the STN center. In z, only 14% of the active contact(s) were >1mm below the STN center. Contacts 1 or 2 were active 90% of the time. The consistent location of active contacts suggests that initial programming began with contact 1 or 2., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Prevention of surgical site infections is critical in deep brain stimulation (DBS). In the present study, we tested the ability of a self-administered preoperative alcohol-based (70% ethyl alcohol) preparation to reduce the rate of postoperative infection after DBS surgery., Methods: This Institutional Review Board-approved retrospective review was conducted at our institution between January 2005 and October 2007 (mean follow-up, 23 months). The participants comprised a consecutive sample of 172 patients with movement disorders who underwent DBS surgery at our institution. Starting in January 2007, all patients were required to use the alcohol-based preparation. These patients (n = 48) were instructed to self-administer the wash on the night before surgery and the morning of surgery. Before this time, no self-administered wash was used (n = 122)., Results: There was no difference in preoperative skin cleansing between the 2 groups, and all patients received intravenous antibiotics immediately before and after surgery for 24 hours. We compared the rate of postoperative infection in the 2 groups and reviewed other possible factors underlying infection. We found 11 cases of infection (6.47%), all in the group without the preoperative antiseptic wash. The infection rate was 9.02% in the group without the preoperative wash and 0 in the group with the preoperative wash (P < .029). There was no difference between the 2 groups in terms of mean age, duration of operative procedure, or number of microelectrode tracts attempted., Conclusions: Our results support the incorporation of this self-administered antiseptic wash into our standard antiseptic protocol for patients undergoing DBS surgery., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Aims: To determine the success threshold at which a theoretical course of deep brain stimulation (DBS) would provide the same quality of life (QoL) and cost-effectiveness for heroin dependence as methadone maintenance treatment (MMT)., Design: We constructed a decision analysis model to calculate QoL after 6 months of MMT and compared it to a theoretical course of DBS. We also performed a cost-effectiveness analysis using societal costs of heroin dependence, MMT and DBS., Setting: Systematic literature review and meta-analysis., Participants: Patients (n = 1191) from 15 trials administering 6 months of MMT and patients (n = 2937) from 45 trials of DBS for movement disorders., Measurements: Data on QoL before and after MMT, retention in MMT at 6 months, as well as complications of DBS and their impact on QoL in movement disorders., Findings: We found a QoL of 0.633 (perfect health = 1) in heroin addicts initiating MMT. Sixty-six per cent of patients completed MMT, but only 47% of them had opiate-free urine samples, resulting in an average QoL of 0.7148 (0.3574 quality-adjusted life years (QALYs) over 6 months). A trial of DBS is less expensive ($81,000) than untreated (or relapsed) heroin dependence ($100,000), but more expensive than MMT ($58,000). A theoretical course of DBS would need a success rate of 36.5% to match MMT, but a success rate of 49% to be cost-effective., Conclusions: The success rate, defined as the percentage of patients remaining heroin-free after 6 months of treatment, at which deep brain stimulation would be similarly cost-effective in treating opiate addiction to methadone maintenance treatment, is estimated at 49%., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

Background: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus., Methods: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474., Findings: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups., Interpretation: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation., Funding: St Jude Medical Neuromodulation Division., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The use of checklists to reduce error rates in procedural literature has led our group to employ this strategy during deep brain stimulation (DBS) surgery., Objectives: We sought to examine the improvement in the number of errors made during DBS surgery after long-term use of a checklist., Methods: Our checklist has been used for all DBS cases at our institution since the beginning of this study's enrollment in 2008. The number of cases in which errors were detected after 1 year of routine use (group B, n = 11) was compared in one cohort of DBS subjects to that of an earlier cohort of patients (group A, n = 17), which underwent DBS exactly 1 year prior., Results: Eleven of the 14 cases where major errors were detected occurred in group A; 6 of the 9 cases where only minor errors were detected were also in group A; of the patients without any error, all 5 were in group B. We found a significant difference in these proportions between group A and group B [χ(2)(2) = 9.73; p < 0.008]., Conclusions: After 1 year of checklist use, the total number of major and minor errors made was reduced, indicating an improvement in error rate after long-term routine incorporation of this checklist., (Copyright © 2012 S. Karger AG, Basel.)

Background/aims: Microelectrode recording (MER) is necessary for precision localization of target structures such as the subthalamic nucleus during deep brain stimulation (DBS) surgery. Attempts to automate this process have produced quantitative temporal trends (feature activity vs. time) extracted from mobile MER data. Our goal was to evaluate computational methods of generating spatial profiles (feature activity vs. depth) from temporal trends that would decouple automated MER localization from the clinical procedure and enhance functional localization in DBS surgery., Methods: We evaluated two methods of interpolation (standard vs. kernel) that generated spatial profiles from temporal trends. We compared interpolated spatial profiles to true spatial profiles that were calculated with depth windows, using correlation coefficient analysis., Results: Excellent approximation of true spatial profiles is achieved by interpolation. Kernel-interpolated spatial profiles produced superior correlation coefficient values at optimal kernel widths (r = 0.932-0.940) compared to standard interpolation (r = 0.891). The choice of kernel function and kernel width resulted in trade-offs in smoothing and resolution., Conclusions: Interpolation of feature activity to create spatial profiles from temporal trends is accurate and can standardize and facilitate MER functional localization of subcortical structures. The methods are computationally efficient, enhancing localization without imposing additional constraints on the MER clinical procedure during DBS surgery., (Copyright © 2012 S. Karger AG, Basel.)

Background: Brain shift during deep brain stimulation (DBS) surgery may compromise target localization. Loss of cerebrospinal fluid is believed to be the underlying mechanism, thus an intraventricular trajectory during DBS surgery may be associated with increased shift, in addition to other complications, such as intraventricular hemorrhage., Objective: We set out to assess the effect of traversing the lateral ventricle on brain shift during DBS surgery., Methods: We performed a retrospective review of 65 pre- and postoperative MR images of patients who underwent bilateral subthalamic nucleus deep brain stimulator placement to treat advanced Parkinson's disease. Patients were separated into two groups: Group A (intraventricular trajectory, n = 46) and Group B (no intraventricular trajectory, n = 19). In these patients, we compared pre- and postoperative frame coordinates of the red nucleus (RN)., Results: Group B demonstrated significantly more posterior shift of the center of the RN (1.40 ± 1.32 mm) than Group A (0.64 ± 1.76 mm; p < 0.02). We found no increase in incidence of intraventricular hemorrhage or the number of microelectrode trajectory attempts., Conclusions: Intraventricular trajectories during DBS surgery do not appear to compromise safety or targeting accuracy., (Copyright © 2011 S. Karger AG, Basel.)

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 DBS—the hypothalamus and nucleus accumbens—in 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.

Objective: There continues to be debate about the surgical technique, electrophysiology, and hardware used in deep brain stimulation (DBS), despite its widespread use in medically intractable Parkinson's disease and essential tremor. This article is the first, to our knowledge, to compare the longevity of the available internal pulse generators (IPGs) of DBS (Kinetra and Soletra, Medtronics)., Methods: We compared the elapsed time from the initial surgery to the first replacement of IPGs in patients with bilateral Soletra IPGs to those with the unilateral Kinetra IPG and analyzed the various stimulation parameters of each device., Results: The battery life of the Soletra system was significantly longer than that of the Kinetra and also allowed for higher voltages, longer use of monopolar mode, and a greater number of electrode contacts., Conclusions: Our findings support superior battery life and a greater capacity for titration to symptom control with bilateral Soletra IPGs., (Copyright © 2010 S. Karger AG, Basel.)

Object: Roux-en-Y gastric bypass is the gold standard treatment for morbid obesity, although failure rates may be high, particularly in patients with a BMI > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of obesity, deep brain stimulation (DBS) offers a less invasive and reversible alternative to available surgical treatments. In this decision analysis, the authors determined the success rate at which DBS would be equivalent to the two most common bariatric surgeries., Methods: Medline searches were performed for studies of laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB), and DBS for movement disorders. Bariatric surgery was considered successful if postoperative excess weight loss exceeded 45% at 1-year follow-up. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment by LAGB, LRYGB, DBS, or no surgical treatment. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used., Results: Fifteen studies involving 3489 and 3306 cases of LAGB and LRYGB, respectively, and 45 studies involving 2937 cases treated with DBS were included. The operative successes were 0.30 (95% CI 0.247-0.358) for LAGB and 0.968 (95% CI 0.967-0.969) for LRYGB. Sensitivity analysis revealed utility of surgical complications in LRYGB, probability of surgical complications in DBS, and success rate of DBS as having the greatest influence on outcomes. At no values did LAGB result in superior outcomes compared with other treatments., Conclusions: Deep brain stimulation must achieve a success rate of 83% to be equivalent to bariatric surgery. This high-threshold success rate is probably due to the reported success rate of LRYGB, despite its higher complication rate (33.4%) compared with DBS (19.4%). The results support further research into the role of DBS for the treatment of obesity.

Deep brain stimulation (DBS) is the treatment of choice for otherwise healthy patients with advanced Parkinson disease who are suffering from disabling dyskinesias and motor fluctuations related to dopaminergic therapy. As DBS is an elective procedure, it is essential to minimize the risk of morbidity. Further, precision in targeting deep brain structures is critical to optimize efficacy in controlling motor features. The authors have already established an operational checklist in an effort to minimize errors made during DBS surgery. Here, they set out to standardize a strict, step-by-step approach to the DBS surgery used at their institution, including preoperative evaluation, the day of surgery, and the postoperative course. They provide careful instruction on Leksell frame assembly and placement as well as the determination of indirect coordinates derived from MR images used to target deep brain structures. Detailed descriptions of the operative procedure are provided, outlining placement of the stereotactic arc as well as determination of the appropriate bur hole location, lead placement using electrophysiology, and placement of the internal pulse generator. The authors also include their approach to preventing postoperative morbidity. They believe that a strategic, step-by-step approach to DBS surgery combined with a standardized checklist will help to minimize operating room mistakes that can compromise targeting and increase the risk of complication.

Deep brain stimulation for epilepsy has garnered attention from epileptologists due to its well-documented success in treating movement disorders and the low morbidity associated with the implantation of electrodes. Given the large proportion of patients who fail medical therapy and are not candidates for surgical amelioration, as well as the suboptimal seizure control offered by vagus nerve stimulation, the search for appropriate brain structures to serve as targets for deep brain stimulation has generated a useful body of evidence to serve as the basis for larger investigations. Early results of the SANTE trial should lay the foundation for widespread implementation of DBS for epilepsy targeting the anterior thalamic nucleus. Other targets also offer promise, including the caudate nucleus, the subthalamic nucleus, the cerebellum, the centromedian nucleus of the thalamus, and the hippocampus. This paper reviews the logic which underlies these potential targets and recapitulates the current data from limited human trials supporting each one. It also provides a succinct overview of the surgical procedure used for electrode implantation.

Objective: The addition of subcutaneous heparin (SQH) to mechanical prophylaxis for venous thromboembolism (VTE) involves a balance between the benefit of greater protection from VTE and the added risk of intracranial hemorrhage. There is evidence that the hemorrhage risk outweighs the benefits for patients undergoing craniotomy. We investigated the safety of SQH in patients undergoing deep brain stimulation (DBS) surgery., Methods: A retrospective analysis was performed of all patients with movement disorders (n = 254) undergoing DBS surgery at our institution from 2003 to 2007. Before September 2005, none of the patients undergoing DBS received SQH (non-SQH group) (n = 121). Thereafter, all patients were administered SQH perioperatively (SQH group) (n = 133). All patients wore graduated compression stockings and pneumatic compression boots postoperatively in bed. A postoperative brain magnetic resonance imaging scan was obtained on the day of surgery., Results: Five (3.8%) of 133 SQH patients and 1 (0.8%) of 121 non-SQH patients developed asymptomatic intracranial hemorrhage. None of the SQH patients developed clinically significant VTE, whereas 3 (2.5%) non-SQH patients developed VTE (1 deep venous thrombosis, 2 pulmonary embolisms). Using a decision-analysis model, we have shown that the use of SQH plus mechanical prophylaxis together yielded outcomes at least as good as mechanical prophylaxis alone., Conclusion: Our findings suggest that SQH for VTE prophylaxis in patients with movement disorders undergoing DBS surgery is safe. SQH protects against VTE in this patient population and merits further investigation.

Objective: Parkinson's disease (PD) is a neurodegenerative disorder characterized by significant motor dysfunction and various non-motor disturbances, including cognitive alterations. Deep brain stimulation (DBS) is an increasingly utilized therapeutic option for patients with PD that yields remarkable success in alleviating disabling motor symptoms. DBS has additionally been associated with changes in cognition, yet the evidence is not consistent across studies. The following review sought to provide a clearer understanding of the various cognitive sequelae of bilateral subthalamic nucleus (STN) DBS while taking into account corresponding neuroanatomy and potential confounding variables., Design: A literature search was performed using the following inclusion criteria: (1) at least five subjects followed for a mean of at least 3 months after surgery; (2) pre- and postoperative cognitive data using at least one standardized measure; (3) adequate report of study results using means and standard deviations., Results: Two recent meta-analyses found mild post-operative impairments in verbal learning and executive function in patients who underwent DBS surgery. However, studies have revealed improved working memory and psychomotor speed in the 'on' vs 'off' stimulation state. A deficit in language may be a consequence of the surgical procedure., Conclusions: While cognitive decline has been observed in some domains, our review of the data suggests that STN DBS is a worthwhile and safe method to treat PD., ((c) 2008 John Wiley & Sons, Ltd.)

Despite the clinical success of deep brain stimulation (DBS), it remains to be elucidated where within the work process the surgical result could diverge from the surgical plan. We sought to determine this. We implemented a standardized checklist to detect and remediate procedural errors. A consecutive series of 13 patients was studied. Revisions, explantations and thermal lesions were excluded. We tabulated the number and type of errors that could occur when implementing a surgical plan. Errors were categorized as minor or major. The elapsed time was also assessed. A mean of two errors per case were identified: 1.15 major errors/case and 0.85 minor errors per case. The total number of errors identified per case did not change significantly over the course of the series. Time to complete the checklist decreased monotonically from 4 min 5 s to 1 min 10 s. The checklist applied in this scenario is a useful tool to identify and remediate errors during DBS, adding minimal additional operative time and consistently identifying errors., ((c) 2009 S. Karger AG, Basel.)

Objective: Tremor resulting from damage to midbrain structures is poorly understood and often difficult to treat. The authors report a case of cystic degeneration of the brainstem with resultant Holmes-like tremor which was successfully treated using a stimulating electrode placed in the contralateral ventralis intermedius nucleus (VIM) of the thalamus., Clinical Presentation: A 31-year-old man presented with a multilobulated, multiseptated lesion of the upper brainstem diagnosed after subacute onset of headaches. The patient subsequently developed an incapacitating left-upper-extremity tremor refractory to medical treatment., Intervention: The patient underwent implantation of a deep brain stimulator in the VIM with symptomatic and functional improvement., Conclusions: Deep brain stimulation is an effective and safe intervention for tremor of unusual etiology. Electrode placement should be based on an understanding of the structure-function relationships underlying the various and distinct types of tremor., ((c) 2009 S. Karger AG, Basel.)

Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.

Microelectrode recording during deep brain stimulation surgery is a useful adjunct for subthalamic nucleus (STN) localization. We hypothesize that information in the nonspike background activity can help identify STN boundaries. We present results from a novel quantitative analysis that accomplishes this goal. Thirteen consecutive microelectrode recordings were retrospectively analyzed. Spikes were removed from the recordings with an automated algorithm. The remaining "despiked" signals were converted via root mean square amplitude and curve length calculations into "feature profile" time series. Subthalamic nucleus boundaries determined by inspection, based on sustained deviations from baseline for each feature profile, were compared against those determined intraoperatively by the clinical neurophysiologist. Feature profile activity within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity of STN entry was 60% and 90% for curve length and root mean square amplitude, respectively, when agreement within 0.5 mm of the neurophysiologist's prediction was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm, respectively. Reproducible activity patterns in deep brain stimulation microelectrode recordings can allow accurate identification of STN boundaries. Quantitative analyses of this type may provide useful adjunctive information for electrode placement in deep brain stimulation surgery.

The placement of deep brain stimulator leads requires a great deal of technology and equipment. We describe our 25-month experience with an integrated platform system, the StimPilot (Medtronic Inc., Minneapolis, MN), for the placement of deep brain stimulator leads. The platform consists of a neuronavigation station, microdrive control, and microelectrode recording display and control. This platform is run from a laptop-sized portable control unit. The unit was used in 147 patients for the placement of 262 leads. Leads were placed into the subthalamic nucleus, ventral intermediate nucleus, globus pallidus interna, and anterior thalamic nucleus. One patient required replacement of one lead during this time frame, with successful reimplantation. No system failures occurred.

Background: Brain shift may occur during deep brain stimulation (DBS) surgery, which may affect the position of subcortical structures, compromising target localization., Methods: We retrospectively evaluated pre- and postoperative magnetic resonance imaging in 50 Parkinson's disease patients who underwent bilateral subthalamic nucleus (STN) DBS. Patients were separated into two groups: group A - those with <2 mm cortical displacement (66 leads) and group B - those with >or=2 mm cortical displacement (34 leads). Pre and post-op coordinates of anterior (AC) and posterior commissures (PC), as well as the boundaries of red nucleus (RN) were compared., Results: AC-PC shortening due to posterior displacement of AC correlated with cortical displacement (p < 0.02) and was significantly greater in group B (0.41 +/- 0.68 mm) than A (0.04 +/- 0.76 mm; p < 0.005). Posterior shift of AC and RN's center positively correlated (p < 0.0001). Shift appeared to impact the number of microelectrode tracks made to optimize STN targeting. AC-PC shortening also correlated with age (p < 0.003) and duration of surgery (p < 0.04)., Conclusions: Subcortical structures shift during DBS surgery. This shift appears to be gravity-dependent since structures only shifted posteriorly, and patients were primarily in the supine position. Posterior shift of RN may indicate STN displacement. Such positional change may compromise target localization, requiring multiple microelectrode adjustments. This may provide indirect justification for the necessity of microelectrode recordings during DBS surgery., ((c) 2007 S. Karger AG, Basel.)

Many patients who suffer from medically refractory epilepsy are not candidates for resective brain surgery. Success of deep brain stimulation (DBS) in relieving a significant number of symptoms of various movement disorders paved the way for investigations into this modality for epilepsy. Open-label and small blinded trials have provided promising evidence for the use of DBS in refractory seizures, and the first randomized control trial of DBS of the anterior thalamic nucleus is currently underway. There are multiple potential targets, because many neural regions have been implicated in seizure propagation. Thus, it is difficult as yet to make any definitive judgments about the efficacy of DBS for seizure control. Future study is necessary to identify a patient population for whom this technique would be indicated, the most efficacious target, and optimal stimulation parameters.

Object: Medically refractory dystonia has recently been treated using deep brain stimulation (DBS) targeting the globus pallidus internus (GPI). Outcomes have varied depending on the features of the dystonia. There has been limited literature regarding outcomes for refractory dystonia following DBS of the subthalamic nucleus (STN)., Methods: Four patients with medically refractory, predominantly cervical dystonia underwent STN DBS. Intraoperative assessments with the patients in a state of general anesthesia were performed to determine the extent of fixed deformities that might predict outcome. Patients were rated using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) preoperatively and 3 and 12 months following surgery by a rater blinded to the study. Mean changes and standard errors of the mean in scores were calculated for each subscore of the two scales. Scores were also analyzed using analysis of variance and probability values were generated. Neuropsychological assessments and quality of life ratings using the 36-Item Short Form Health Survey (SF-36) were evaluated longitudinally., Results: Significant improvements were seen in motor (p = 0.04), disability (p = 0.02), and total TWSTRS scores (p = 0.03). Better outcomes were seen in those patients who did not have fixed deformities. There was marked improvement in the mental component score of the SF-36. Neuropsychological function was not definitively impacted as a result of the surgery., Conclusions: Deep brain stimulation of the STN is a novel target for dystonia and may be an alternative to GPI DBS. Further studies need to be performed to confirm these conclusions and to determine optimal candidates and stimulation parameters.

Objective: Microelectrode recording during deep brain stimulation surgery improves the likelihood of successful target localization and enables the electrophysiological characterization of human neural structures. Many clinical recording systems do not support the ability to capture research-quality recordings. Established clinical centers already using such equipment may be prevented from acquiring human intracranial data because of the need to completely change recording systems to obtain research-quality recordings. This technical note describes the novel design and implementation of a recording system that significantly improves research capabilities without disrupting the existing clinical setup., Methods: This design introduces a second recording system (including pre-amplifier, differential amplifier, analog-to-digital converter, and computer with analysis software) that divides the microelectrode signal into two independent streams., Results: This design preserves the existing intraoperative recording setup, but significantly improves research-level recording, data storage, and analysis capabilities., Conclusion: We provide the first description of such a system using components that are all commercially available and relatively inexpensive. This approach presents an appealing alternative to the purchase of an entirely new system for surgical teams that already perform intraoperative recordings to assist in stereotactic target localization, yet wish to expand their neurophysiological recording capabilities.

Background: An understanding of the relationships between the anterior commissure-posterior commissure line (AC-PC), the subthalamic nucleus (STN), and red nucleus (RN) is imperative if these structures are to be used for targeting in deep brain stimulation. Currently, these relationships are incompletely understood and difficult to assess using conventional MRI. We examined the location and relationships of the STN and the RN to the AC-PC line and to each other in order to provide a greater understanding of their utility when targeting the STN, and the consistency of these anatomic relationships when examined using conventional MRI., Methods: A total of 52 STN and RN in 26 patients with Parkinson's disease were evaluated on T2-weighted MR images. The anterior and posterior commissures and the border coordinates of the STN and RN were derived using frame coordinates. The distances from the midcommissural point (mcp) to the centers of the STN and RN, the diameters for each nucleus, and the distances between the nuclei were calculated in the x-, y-, and z-axes., Results: The mean AC-PC length was 26.1 +/- 1.3 mm. The distance from the mcp to the center of the STN was 10 +/- 0.7 mm in the x-axis, 0.2 +/- 0.7 mm in the y-axis, and 3.3 +/- 0.9 mm in the z-axis. The distance from the mcp to the center of the RN was 4.7 +/- 0.6 mm in the x-axis, -5.9 +/- 1.0 mm in the y-axis, and 6.1 +/- 1.3 mm in the z-axis. The distance between the STN and RN was 2.3 +/- 0.7 mm in the x-axis, 2.1 +/- 1.0 mm in the y-axis, and -0.2 +/- 1.3 mm in the z-axis., Conclusions: Although recent studies imply that the RN can be used as a relatively consistent marker for the position of the STN, the present data suggest otherwise. These data indicate that a single targeting method may be inadequate given the resolution of conventional MRI, and that it is imperative to use multiple anatomical measurements when targeting the STN for deep brain stimulation in Parkinson's disease., (2006 S. Karger AG, Basel)

Background: In patients with advanced Parkinson's disease (PD), deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to improve motor function and decrease medication requirements in the short term. However, the long-term benefits of DBS are not yet established., Objective: It was the aim of this study to evaluate long-term outcomes of patients with PD treated with bilateral DBS of the STN., Design and Methods: Thirty-three subjects who had bilateral STN DBS were followed prospectively after surgery. We evaluated subjects, using the Unified Parkinson's Disease Rating Scale (UPDRS), preoperatively, 12 months after surgery and at a long-term follow-up visit. Ratings were performed on and off dopaminergic medications. We compared postoperative UPDRS scores, dyskinesia ratings and medication dosages with preoperative values., Results: Twenty-seven subjects had evaluations beyond 18 months (median 33.7 months). Total UPDRS scores in the 'medication-off' state were improved by 37% (p < 0.001) at 12 months and 17.7% (p = 0.0051) at the long-term evaluation. Medication-off state UPDRS part III scores were significantly improved at both 1 year and at the last evaluation (37.6 and 29.3%; p < 0.001). Dopaminergic medication requirements were decreased by 35.3% (p < 0.001) during the first postoperative year and remained below preoperative levels at the long-term evaluation. Average duration of 'off' time remained decreased by about 40% at both 1 year and at the time of last evaluation. Subjects had a sustained reduction in dyskinesia severity (88.6% at 1 year and 68.8% at last evaluation)., Conclusions: In this cohort of subjects with advanced PD, bilateral STN stimulation improved 'off' medication motor function, reduced time spent in the medication-off state and reduced medication requirements for up to 4 years after surgery. We conclude that STN DBS is an effective long-term therapy for selected patients with advanced PD., (Copyright 2006 S. Karger AG, Basel.)

We report a patient with advanced Parkinson's disease (PD) who developed a recurrence of major depression with psychotic features after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Electroconvulsive therapy (ECT) dramatically improved the depression without shifting electrode position or damaging the DBS hardware. This case suggests that ECT can be a safe and effective option for severe depression in PD patients treated with STN DBS.

The role of subthalamic nucleus (STN) deep brain stimulation (DBS) is well established in Parkinson's disease, but experience with STN DBS in other movement disorders is limited. We report on a patient with medically refractory cervical dystonia and essential tremor resulting in dystonic head tremor and action tremor of the hands who obtained complete tremor suppression and near resolution of her cervical dystonia with bilateral STN stimulation. The results in this case demonstrate that STN DBS can dramatically improve dystonia and tremor in nonparkinsonian movement disorders.

Two months after bilateral DBS surgery in a patient with PD, the stimulator had to be removed temporarily due to an infection. After successful antibiotic treatment, a new stimulator and extension wire were reimplanted 2 months later. Intraoperative testing of the replacement device yielded unusually high electrode impedances and low currents on one lead across all four contacts. Since the results did not change on repeated measurements, a lead fracture was suspected. Visual inspection of the exposed hardware, however, did not reveal any obvious defects. It was then decided to activate the lead for a prolonged time with significant currents. Subsequent impedance measurements yielded normal values and after the patient awoke from anesthesia, good symptom control was again achieved. It is advisable if a lead fracture is suspected under similar circumstances to 'condition' the electrode with high currents. Failure to do so could lead to a false conclusion of a lead fracture and unnecessary stereotactic surgery to replace it., (2005 S. Karger AG, Basel.)

Stereotactic deep brain stimulation (DBS) is the surgical treatment of choice for medication-refractory patients with Parkinson's disease and essential tremor. The subthalamic nucleus and ventral intermediate nucleus of the thalamus appear to be effective targets for electrode placement. Because these targets are small and encased in fiber tracts, their localization can be exceedingly difficult. However, the precision of electrode placement is crucial for obtaining successful results. Currently, surgeons rely on preoperative MRI or CT images to derive stereotactic coordinates for targeting sites such as the subthalamic nucleus and ventral intermediate nucleus of the thalamus coupled with microelectrode recordings during surgery for proper electrode placement. However, it has been argued that the stereotactic head frame produces detrimental artifacts during MRI. We examined MRI images taken from 11 patients undergoing repeat DBS surgery, and determined the coordinates of the previously placed electrode. We then set the Leksell G stereotactic frame to these coordinates and obtained fluoroscope-localizing images. Using MATLAB image analysis tools, we were able to quantify the 3-dimensional error in target localization by measuring the distance from the electrode tip to the targeted coordinate. The mean errors were 0.09 +/- 0.34 mm perpendicular, lateral to medial, 0.01 +/- 0.32 perpendicular, posterior to anterior, and -0.08 +/- 0.33 mm parallel to the electrode, superior to inferior. According to statistical analysis, the error was random and did not seem to move in any predictable fashion. Therefore, we conclude that preoperative MRI images can be safely used in DBS surgery, and they do not negatively affect its accuracy.

We describe 2 patients with advanced Parkinson's disease (PD) treated with bilateral deep brain stimulation of the subthalamic nucleus in whom unilateral stimulator battery depletion resulted in the rapid appearance of disabling PD symptoms (severe rigidity, bradykinesia and gait difficulty). Both patients did not respond to high doses of dopaminergic medications and were restored to their previous level of function only with battery replacement. One patient developed a deep vein thrombosis and pulmonary emboli as a result of prolonged immobility. Although extreme worsening of PD secondary to battery depletion may be rare, such patients should have their stimulators replaced promptly., (2004 S. Karger AG, Basel.)

Background An increasing number of studies utilize intracranial electrophysiology in human subjects to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects' motivations for participation. Yet a thorough empirical examination of these issues in a participant population has been lacking. The present study therefore aimed to empirically investigate ethical concerns regarding informed consent and voluntariness in Parkinson's disease patients undergoing deep brain stimulator (DBS) placement who participated in an intraoperative neuroscience study. Methods Two semi-structured 30-minute interviews were conducted preoperatively and postoperatively via telephone. Interviews assessed participants' motivations for participation in the parent intraoperative study, recall of information presented during the informed consent process, and participants' postoperative reflections on the research study. Results Twenty-two participants (mean age = 60.9) completed preoperative interviews at a mean of 7.8 days following informed consent and a mean of 5.2 days prior to DBS surgery. Twenty participants completed postoperative interviews at a mean of 5 weeks following surgery. All participants cited altruism or advancing medical science as "very important" or "important" in their decision to participate in the study. Only 22.7% (n = 5) correctly recalled one of the two risks of the study. Correct recall of other aspects of the informed consent was poor (36.4% for study purpose; 50.0% for study protocol; 36.4% for study benefits). All correctly understood that the study would not confer a direct therapeutic benefit to them. Conclusion Even though research coordinators were properly trained and the informed consent was administered according to protocol, participants demonstrated poor retention of study information. While intraoperative studies that aim to advance neuroscience knowledge represent a unique opportunity to gain fundamental scientific knowledge, improved standards for the informed consent process can help facilitate their ethical implementation. [ABSTRACT FROM AUTHOR]

Neuronal firing in the substantia nigra (SN) immediately following reward is thought to play a crucial role in human reinforcement learning. As in Ramayya et al. (2014a) we applied microstimulation in the SN of patients undergoing deep brain stimulation (DBS) for the treatment of Parkinson's disease as they engaged in a two-alternative reinforcement learning task. We obtained microelectrode recordings to assess the proximity of the electrode tip to putative dopaminergic and GABAergic SN neurons and applied stimulation to assess the functional importance of these neuronal populations for learning. We found that the proximity of SN microstimulation to putative GABAergic neurons predicted the degree of stimulation-related changes in learning. These results extend previous work by supporting a specific role for SN GABA firing in reinforcement learning. Stimulation near these neurons appears to dampen the reinforcing effect of rewarding stimuli. [ABSTRACT FROM AUTHOR]

The success of deep brain stimulation (DBS) for movement disorders and the improved understanding of the neurobiologic and neuroanatomic bases of psychiatric diseases have led to proposals to expand current DBS applications. Recent preclinical and clinical work with Alzheimer's disease and obsessive-compulsive disorder, for example, supports the safety of stimulating regions in the hypothalamus and nucleus accumbens in humans. These regions are known to be involved in addiction and overeating associated with obesity. However, the use of DBS targeting these areas as a treatment modality raises common ethical considerations, which include informed consent, coercion, enhancement, threat to personhood, and manipulation of the reward center. Pilot studies for both of these conditions are currently investigational. If these studies show promise, then there is a need to address the ethical concerns related to the initiation of clinical trials including the reliability of preclinical evidence, patient selection, study design, compensation for participation and injury, cost-effectiveness, and the need for long-term follow-up. Multidisciplinary teams are necessary for the ethical execution of such studies. In addition to establishing safety and efficacy, the consideration of these ethical issues is vital to the adoption of DBS as a treatment for these conditions. We offer suggestions about the pursuit of future clinical trials of DBS for the treatment of addiction and overeating associated with obesity and provide a framework for addressing ethical concerns related to treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A response by Casey H. Halpern and colleagues to a letter to the editor about their article "Deep brain stimulation compared with methadone maintenance for the treatment of heroin dependence: a threshold and cost-effectiveness analysis," in the March 2012 issue, is presented.

We report a case of thalamic deep brain stimulation (DBS) for treatment of posttraumatic tremor. An 18-year-old right-handed man developed a disabling and medically refractory action tremor in the right upper extremity 9 months after sustaining diffuse axonal injury in a motor vehicle collision. DBS of the left ventral intermediate nucleus of the thalamus (Vim) suppressed the tremor without complication and should be considered as an option for the management of intractable posttraumatic tremor. [Copyright &y& Elsevier]

Background: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus.Methods: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474.Findings: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups.Interpretation: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation.Funding: St Jude Medical Neuromodulation Division. [ABSTRACT FROM AUTHOR]