Use Of Deep Brain Stimulation Research Articles

From Anatomy to Electrophysiology: Clinical Lasker Goes Deep

This year, the Lasker∼DeBakey Clinical Medical Research Award will be shared by Mahlon R.DeLong and Alim-Louis Benabid for elucidating the role of the subthalamic nucleus in mediating the motor dysfunction of Parkinson's disease and for pioneering the use of deep-brain stimulation to alleviate symptoms of the disease.

Deep brain stimulation in rats: Different targets induce similar antidepressant-like effects but influence different circuits

Recent studies in patients with treatment-resistant depression have shown similar results with the use of deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (Acb). As these brain regions are interconnected, one hypothesis is that by stimulating these targets one would just be influencing different relays in the same circuitry. We investigate behavioral, immediate early gene expression, and functional connectivity changes in rats given DBS in homologous regions, namely the ventromedial prefrontal cortex (vmPFC), white matter fibers of the frontal region (WMF) and nucleus accumbens. We found that DBS delivered to the vmPFC, Acb but not WMF induced significant antidepressant-like effects in the FST (31%, 44%, and 17% reduction in immobility compared to controls). Despite these findings, stimulation applied to these three targets induced distinct patterns of regional activity and functional connectivity. While animals given vmPFC DBS had increased cortical zif268 expression, changes after Acb stimulation were primarily observed in subcortical structures. In animals receiving WMF DBS, both cortical and subcortical structures at a distance from the target were influenced by stimulation. In regard to functional connectivity, DBS in all targets decreased intercorrelations among cortical areas. This is in contrast to the clear differences observed in subcortical connectivity, which was reduced after vmPFC DBS but increased in rats receiving Acb or WMF stimulation. In conclusion, results from our study suggest that, despite similar antidepressant-like effects, stimulation of the vmPFC, WMF and Acb induces distinct changes in regional brain activity and functional connectivity.

Deep brain stimulation for obsessive-compulsive disorder: systematic review and evidence-based guideline sponsored by the American Society for Stereotactic and Functional Neurosurgery and the Congress of Neurological Surgeons (CNS) and endorsed by the CNS and American Association of Neurological Surgeons.

It is estimated that 40% to 60% of patients with obsessive-compulsive disorder (OCD) continue to experience symptoms despite adequate medical management. For this population of treatment-refractory patients, promising results have been reported with the use of deep brain stimulation (DBS). To conduct a systematic review of the literature and develop evidence-based guidelines on DBS for OCD. A systematic literature search was undertaken using the PubMed database for articles published between 1966 and October 2012 combining the following words: "deep brain stimulation and obsessive-compulsive disorder" or "electrical stimulation and obsessive-compulsive disorder." Of 353 articles, 7 were retrieved for full-text review and analysis. The quality of the articles was assigned to each study and the strength of recommendation graded according to the guidelines development methodology of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Joint Guidelines Committee. Of the 7 studies, 1 class I and 2 class II double-blind, randomized, controlled trials reported that bilateral DBS is more effective in improving OCD symptoms than sham treatment. Based on the data published in the literature, the following recommendations can be made: (1) There is Level I evidence, based on a single class I study, for the use of bilateral subthalamic nucleus DBS for the treatment of medically refractory OCD. (2) There is Level II evidence, based on a single class II study, for the use of bilateral nucleus accumbens DBS for the treatment of medically refractory OCD. (3) There is insufficient evidence to make a recommendation for the use of unilateral DBS for the treatment of medically refractory OCD.

Neurohistopathological findings at the electrode-tissue interface in long-term deep brain stimulation: systematic literature review, case report, and assessment of stimulation threshold safety.

Despite the widespread use of deep brain stimulation (DBS) in the treatment of neurologic disorders for over a quarter of a century, there has not been a systematic review and analyses of cases in which long-term postmortem clinic-pathologic data have been collected demonstrating the effects of chronically implanted electrodes and electrical stimulation on human brain tissue. Our objective is to provide a comprehensive systematic review of the literature on clinicopathologic findings of DBS tissue-electrode interface (TEI) and to determine types and prevalences of neuropathological findings among electrode materials and stimulation parameters and to augment this with previously unpublished histopathological data, images, and analyses from a DBS case implanted for 12 years, providing the longest duration histopathological follow-up. A Medline literature review identified DBS cases upon which postmortem clinicopathologic follow-up was performed with adequate characterization of TEI. Direct follow-up with authors augmented this with unpublished data and neuropathological details. We identified 40 cases, mean age 59.1 ± 13.0 (range: 21-88) years, involving 58 implanted DBS electrodes. The mean postmortem histopathological follow-up of the implanted DBS electrodes was 22.2 ± 29.2 (range: 0.067-146) months, including our case with a 12-year follow-up. The following histological changes were identified: fibrous sheaths (5-25 μm thickness) surrounding the electrode (94%), fibrillary gliosis (73%), reactive astrocytes (78%), multinucleated giant cells (75%), mononuclear leukocytes (92%), and macrophages (91%). Microglial activation (60%), axonal spheroids (64%), and neuronal loss (60%) were less common and absent at 12-year follow-up in the index case. This is seventh case reporting T cell presence at the TEI. Neuropathological findings from published cases and our 12-year follow-up index case confirm the long-term safety of neuromodulation and stimulation thresholds and demonstrate persistence of T cells and occasional subclinical focal tissue injury.

Amygdalohippocampectomy for epilepsy in a patient with prior ipsilateral deep brain stimulator lead placement

In light of failed medical therapy for movement disorders, the use of deep brain stimulation (DBS) has increased the last two decades. Many complications may transpire; however, to our knowledge, the literature does not mention the phenomena of brain shift from a second unrelated neurosurgical procedure and its theoretical effect on lead displacement and lead function. We present a patient with a left sided DBS for essential tremor and subsequent left amygdalohippocampectomy for temporal lobe epilepsy with minimal radiographic distortion of the DBS lead and without clinical or functional complications. A 47-year-old woman presented with bitemporal epilepsy secondary to a brain injury acquired in childhood in addition to a comorbid bilateral essential tremor, both refractory to medical intervention. A successful left-sided DBS placement was performed with satisfactory resolution of her essential tremor. The patient subsequently developed deterioration of seizure control, becoming refractory to anti-epileptic medications, requiring surgical intervention. A left-sided selective amygdalohippocampectomy and techniques to minimize brain shift were performed without complications. Postoperative imaging suggested minimal distortion of the DBS lead. This did not correspond with reemergence of her essential tremor, implying that the lead maintained functional utility. Brain shift secondary to a craniotomy may cause DBS lead displacement. This phenomenon should be considered when planning operative approaches and can be limited by selective resections. With the growing propensity for placement of DBS leads and the risk of lead displacement, it is important to consider operative approaches to minimize brain shift.

Brain Stimulation for Epilepsy – Local and Remote Modulation of Network Excitability

The use of Deep Brain Stimulation (DBS) as a potential therapy for treatment resistant epilepsy remains an area of active clinical investigation. We recently reported the first chronic evaluation of an implantable, clinical-grade system that permits concurrent stimulation and recording, in a large animal (ovine) model developed to study DBS for epilepsy. In this study we extended this work to compare the effects of remote (anterior thalamic) and direct (hippocampal) stimulation on local field potential (LFP) activity and network excitability, and to assess closed-loop stimulation within this neural network. Following anesthesia and 1.5T MRI acquisition, unilateral anterior thalamic and hippocampal DBS leads were implanted in three subjects using a frameless stereotactic system. Chronic, awake recordings of evoked potentials (EPs) and LFPs in response to thalamic and hippocampal stimulation were collected with the implanted device and analyzed off-line. Consistent with earlier reports, thalamic DBS and direct stimulation of the hippocampus produced parameter-dependent effects on hippocampal activity. LFP suppression could be reliably induced with specific stimulation parameters, and was shown to reflect a state of reduced network excitability, as measured by effects on hippocampal EP amplitudes and after-discharge thresholds. Real-time modulation of network excitability via the implanted device was demonstrated using hippocampal theta-band power level as a control signal for closed-loop stimulation. The results presented provide evidence of network excitability changes induced by stimulation that could underlie the clinical effects that have been reported with both thalamic and direct cortical stimulation.

The use of deep brain stimulation in Tourette's syndrome

Tourette's syndrome (TS) is a childhood neuropsychiatric disorder characterized by multiple involuntary motor and vocal tics. It is commonly associated with other behavioral disorders including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, depression, and self-injurious behaviors. Tourette's syndrome can be effectively managed with psychobehavioral and pharmacological treatments, and many patients experience an improvement in tics in adulthood. However, symptoms may persist and cause severe impairment in a small subset of patients despite available therapies. In recent years, deep brain stimulation (DBS) has been shown to be a promising treatment option for such patients. Since the advent of its use in 1999, multiple targets have been identified in DBS for TS, including the medial thalamus, globus pallidus internus, globus pallidus externus, anterior limb of the internal capsule/nucleus accumbens, and subthalamic nucleus. While the medial thalamus is the most commonly reported trajectory, the optimal surgical target for TS is still a topic of much debate. This paper provides a review of the available literature regarding the use of DBS for TS.

Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain—At the Tipping Point?

The term “neuropathic pain” (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.

First U.S. Test of Brain Stimulation in Alzheimer's

Investigational use of deep brain stimulation for Alzheimer's disease has arrived in the United States. As a part of a new multicenter trial, the ADvance Study, funded by the National Institute on Aging and Functional Neuromodulation, Johns Hopkins University neurosurgeons recently implanted the first device into a patient with mild Alzheimer's disease. Via two implanted ultra-thin wires, the device delivers 4-8 V electrical charges directly to the fornix on both sides of the brain. One of the first to be destroyed by Alzheimer's, the brain region relays signals between the hippocampus and hypothalamus. About 40 patients are expected to receive the deep brain stimulation implant over the next year or so at Johns Hopkins, Toronto Western Hospital, the University of Pennsylvania, Philadelphia, the University of Florida, Gainesville, and Banner Alzheimer's Institute in Phoenix. Half of the patients in the study will have the devices activated 2 weeks after surgery, while the others will have the device turned on after 1 year. All study participants will be regularly assessed for at least 18 months to measure their rate of Alzheimer's progression. As part of a preliminary safety study in 2010, the devices were implanted in six Alzheimer's disease patients at the University of Toronto. Researchers found that patients with mild forms of the disorder showed sustained increases in glucose metabolism, an indicator of neuronal activity, over a 13-month period (Ann. Neurol. 2010;68:521-34). Most Alzheimer's disease patients show decreases in glucose metabolism during such a timespan.

Using acceleration sensors to quantify symptoms during deep brain stimulation surgery

The use of Deep Brain Stimulation (DBS) surgery is increasing as a treatment for movement related disorders. One of the important areas of improvement is the target selection procedure. To do so, we measured the acceleration of tremor by sensors in 6 patients during their DBS surgeries to evaluate the changes quantitatively. The post-operative data analysis revealed that acceleration measurements are very sensitive to the changes in tremor and that they can be used to identify clinically effective stimulation amplitudes. With the aim to increase objectivity in symptom evaluation, we intend to introduce real-time analysis so as to provide more information to the neurosurgeon to aid him in his target selection during the surgery.

Temperature control at DBS electrodes using a heat sink: experimentally validated FEM model of DBS lead architecture

There is a growing interest in the use of deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or coupling with an external source (e.g. magnetic resonance imaging) remains poorly understood and methods to mitigate temperature increases are being actively investigated. We developed a heat transfer finite element method (FEM) simulation of DBS incorporating the realistic architecture of Medtronic 3389 leads. The temperature changes were analyzed considering different electrode configurations, stimulation protocols and tissue properties. The heat-transfer model results were then validated using micro-thermocouple measurements during DBS lead stimulation in a saline bath. FEM results indicate that lead design (materials and geometry) may have a central role in controlling temperature rise by conducting heat. We show how modifying lead design can effectively control temperature increases. The robustness of this heat-sink approach over complimentary heat-mitigation technologies follows from several features: (1) it is insensitive to the mechanisms of heating (e.g. nature of magnetic coupling); (2) it does not interfere with device efficacy; and (3) can be practically implemented in a broad range of implanted devices without modifying the normal device operations or the implant procedure.

Alleviation of Developmental Stuttering Following Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus

Back to table of contents Previous article Next article Communications and UpdatesFull AccessAlleviation of Developmental Stuttering Following Deep Brain Stimulation of the Ventral Intermediate Nucleus of the ThalamusGerald A. Maguire, M.D., Jerry Ngo, M.D., P.K. Fonsworth III, Jimmy Doan, M.D., Jennifer A. Birch, R.N., M.S.N., and Igor Fineman, M.D.Gerald A. MaguireIrvine, Calif.Search for more papers by this author, M.D., Jerry NgoIrvine, Calif.Search for more papers by this author, M.D., P.K. Fonsworth IIIIrvine, Calif.Search for more papers by this author, Jimmy DoanIrvine, Calif.Search for more papers by this author, M.D., Jennifer A. BirchPasadena, Calif.Search for more papers by this author, R.N., M.S.N., and Igor FinemanPasadena, Calif.Search for more papers by this author, M.D.Published Online:1 Jul 2012https://doi.org/10.1176/appi.ajp.2012.12010016AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Stuttering is a disorder of speech fluency characterized by prolongations, repetitions, and blocks. Developmental stuttering has an early onset, and acquired stuttering typically occurs later in life and is often secondary to neurological injury. While the full etiological nature of stuttering is still unclear, a growing body of evidence suggests that the basal ganglia provide internal timing cues to signal the next motor pattern in a sequence and are thus implicated in the dysfunction in stuttering. Further evidence stems from the clinical observation that extrapyramidal movement disorders, such as Parkinson's disease, can exacerbate developmental stuttering or cause acquired stuttering (1). Previous reports describe the use of deep brain stimulation (DBS) to improve acquired stuttering (2). To our knowledge, this is the first report of alleviation of developmental stuttering using DBS.A 64-year-old woman developed an essential tremor in her right upper extremity at the age of 18 that gradually worsened over decades and was refractory to medical treatment. The patient also had a history of severe developmental stuttering since she was 5 years old that was characterized by significant blocks and prolongations. The combination of developmental stuttering and essential tremor was severe enough to cause impairment of daily functioning, avoidant behavior, and anxiety. The patient received extensive speech therapy in her youth with no improvement of dysfluency. At age 62, a deep brain stimulator was implanted in the left ventral intermediate nucleus of the thalamus to treat her essential tremor. The stereotactic coordinates of the deepest midpoint contact were 11.4 mm left, 4.2 mm posterior, and 0 mm inferior to the anterior commissure-posterior commissure midpoint. The patient experienced complete resolution of her tremor and decreased frequency and duration of her stuttering immediately after DBS. Subsequent adjustment of the stimulation parameters to achieve optimal tremor control maintained this improvement in fluency. The final settings of the device were case positive, lead 2 negative, 2.40 mA, pulse width set at 104 μs, and frequency at 184 Hz.This direct manipulation lends support to previous reports of the importance of the basal ganglia and other subcortical structures in the mechanism of stuttering. While the ventral intermediate nucleus of the thalamus is not formally part of the basal ganglia, the thalamus receives input from pathways of the basal ganglia for subsequent cortical modulation. Thus, stimulation of the ventral intermediate nucleus of the thalamus may shift the balance of the pathways to alleviate the aberrant timing responsible for developmental stuttering. Because of the limited data regarding DBS on developmental stuttering, further research is necessary to elucidate its potential role as a treatment strategy. Since coexisting essential tremor in stuttering is unique, generalizability to other patients may be limited.Irvine, Calif.Pasadena, Calif.Dr. Maguire has served on the speakers bureau for Eli Lilly, Lund-beck, Merck, Novartis, and Sunovian; received research grants from Eli Lilly, Endo, Merck, and Otsuka; and is a consultant for Eli Lilly, Endo, and Merck. Drs. Ngo, Doan, and Fineman and Mr. Fonsworth and Ms. Birch report no financial relationships with commercial interests.Accepted for publication in March 2012.

Competency-Based Curricula in DBS and ITB Therapies for Movement Disorders (P06.022)

Objective: To improve clinician education in the use of deep brain stimulation and intrathecal baclofen device therapy for movement disorders through the systematic development of competency-based curricula as part of an overarching competency-based neuromodulation curriculum. Background Although competency-based curricula are effective in developing continuing competence in clinical practice, the process of identifying competencies is often cumbersome. To streamline the process, a short-term, modified Nominal Group Technique (NGT) was tested as a means of more efficiently validating and stratifying clinical competencies. Design/Methods: Educational planners used evidence-based methodologies to review existing course content and derive competencies for FDA-approved uses of DBS and ITB device implantation. The content covered DBS for Parkinson9s disease, tremor, and dystonia, and ITB for spasticity in disorders such as cerebral palsy, multiple sclerosis, deep brain injury, and stroke. In three rounds of NGT, therapy-specific physician and midlevel provider panels reviewed the competencies to validate their accuracy, reliability, and relevance; to identify whether they are core or therapy specific; to assess their appropriate learner level (novice, intermediate-to-advanced, or master); and to specify their sequence within clinical practice (preoperative, operative, postoperative, and postoperative with complications). Educational planners revised the competencies based on the panelists9 feedback and assisted panelists in coming to consensus. Results: Panelists validated and delineated relevance, type, learner level, and sequencing for 220 ITB-specific competencies for physicians/fellows and 232 for midlevel providers; and 121 DBS-specific competencies for physicians/fellows and 98 for midlevels. The process took ten weeks. The validated competencies were then used in developing a competency-based curriculum to train clinicians in patient identification, stimulation and implantation, programming, pharmacological action and safety profile, and postoperative management. Conclusions: The NGT method was successful in streamlining the process of identifying competencies, learner levels, and prerequisites for use in developing comprehensive, competency-based curricula for training in DBS and ITB therapies. Supported by: Medtronic, Inc. Disclosure: Dr. Bellande has nothing to disclose. Dr. Winicur has nothing to disclose. Dr. Gallo has received personal compensation for activities with Medtronic, St Jude Medical, Teva Neuroscience, Boeringher Ingelheim Pharmaceuticals and Novartis as a consultant. Dr. Gallo has received research support from St. Jude Medical. Dr. Turner has received personal compensation for activities with Medtronic as consultant, speaker and a participant on an advisory board. Dr. Turner has received research support from Medtoronic. Dr. Saulino has received personal compensation for activities with Einstein Physician Practice Incorporated and Albert Einstein Healthcare Network. Dr. Saulino has received research support from Albert Einstein Healthcare Network. Dr. Heath has received personal compensation for activities with Medtronic as a speaker. Dr. Bennett has nothing to disclose. Dr. Nelson has received personal compensation for activities with Medtronic, Inc. Ms. Reese has received personal compensation for activities with Medtronic as an employee. Ms. Larson has received personal compensation for activities with Medtronic, Inc. as an employee. Ms. Dawidowicz has received personal compensation for activities with Medtronic as an employee. Dr. Boche has received personal compensation for activities with Medtronic, Inc as an employee. Dr. Cox has nothing to disclose.

Parvocellular Red Nucleus - A Neuromodulation Target for Medically Refractory Meige Syndrome? (P01.239)

Objective: To study the behavioral and motor responses following chemical modulation of parvocellular red nucleus in primates. Background Craniocervical dystonias are the most common forms of adult-onset focal dystonia. Blepharospasm, oromandibular, lingual, laryngeal and cervical dystonia are the various form of craniocervical dystonia. Meige syndrome is characterized by blepharospasm, cervical dystonia, and facial oromandibular dystonia. There is a growing interest in the use of deep brain stimulation (DBS) in medically refractory forms of dystonia but the optimal target for Meige syndrome remains unclear. Design/Methods: Experiments were performed using Cynomaglous monkey (Macaca Fascicularis). Monkey was trained to perform a self initiated behavioral task of reaching out and grabbing presented food reward for 6 weeks. After behavioral training implant surgery was performed. Neural activity within parvocellular red nucleus was identified and mapped using tungsten microelectrodes (10-30 m tip exposure length). Micropipettes ( 10μ m tip opening diameter) were used to record neural activity and to perform activation of parvocellular red nucleus by injecting Bicuculline(100nl), Kainic Acid(200nl,0.25 Mmol) and Gabazine (250 nl,0.2 Mmol). To avoid any residual effects injections were made at weekly intervals. Ten minutes after the injection, micropipette was removed and monkey was observed for any behavioral change. Results: Following Bicuculline injection dystonic tremors were noticed in the contralateral distal hindlimb. Contralateral focal dystonia of the neck and oro-facial dystonia including jaw deviation was noted with Gabazine injection. Kainic acid stimulation caused hypervigilence and contralateral focal dystonia of neck along with circling motion to side contralateral to injection. These motor responses were short lasting and reversible. Topography of stimulation site was correlated with histology after completion of experiments. Conclusions: Chemical neuromodulation of parvocellular red nucleus causes cervical and oromandibular dystonia. Further studies are needed to verify these changes and evaluate the target as potential site for neuromodulation of medically refractory Meige syndrome. Disclosure: Dr. Deep has nothing to disclose. Dr. Pati has nothing to disclose. Dr. Dhall has received personal compensation for activities with Teva Pharmacuticals as a speaker. Dr. Lieberman has nothing to disclose. Dr. Horn has nothing to disclose. Dr. Horn has nothing to disclose.

Deep Brain Stimulation

Dr. Riley is a Neurological Surgery Resident, Emory University School of Medicine, Mr. Lamanna is an MD/PhD student, Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, and Dr. Boulis is Assistant Professor, Department of Neurosurgery, Emory University School of Medicine, 1365B Clifton Rd NE, Ste B6200, Atlanta, GA 30322; E-mail: [email protected]. All faculty and staff in a position to control the content of this CME activity and their spouses/life partners, if any, have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity. The authors have disclosed that the use of deep brain stimulation for treatment of affective disorders as discussed in this article has not been approved by the U.S. Food and Drug Administration. Category: Functional Lippincott Continuing Medical Education Institute, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc. designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed form, answering at least 70% of the quiz questions correctly. This activity expires on March 29, 2013.

Postmortem observation of collagenous lead tip region fibrosis as a rare complication of DBS

Despite the widespread effective use of deep brain stimulation (DBS) for various movement and psychiatric disorders, little is known about its safety and tissue responses. The University of Florida Deep Brain Stimulation Brain Tissue Network (DBS-BTN) conducted postmortem brain examinations on 26 cases to identify and characterize (using histological techniques) pathologic tissue changes associated with the placement of DBS devices. We report the unusual finding of prominent collagenous fibrosis around the lead tip in a 74-year-old man with idiopathic Parkinson's disease who had bilateral STN-DBS. Histological study confirmed the diagnosis of idiopathic Parkinson's disease, and there was striking, dense collagenous fibrosis at the distal end of the right DBS lead associated with focal hemosiderin deposition, chronic inflammation, and mild gliosis. We have in our brain bank 25 other DBS cases that on examination showed only mild to moderate gliosis and no dramatic tissue response to DBS lead placement. We are not aware of any prior reports of such a dramatic reaction to DBS placement to date.

Functional anatomy of headache: hypothalamus

There is now compelling evidence that the hypothalamus exerts a major role in the mechanism of headache triggering. Pain and concomitant changes in the hormonal secretory pattern occur during an attack of headache when hypothalamic structures are involved. During spontaneous migraine or cluster headache attacks activation of the hypothalamus is shown by positron emission tomography. Over the past 10 years a number of patients with refractory chronic cluster headache have received neurostimulation of the posteroinferior hypothalamus as a form of treatment. The clinical use of deep brain stimulation (DBS) is based on the theory of posterior hypothalamic nucleus dysfunction as the cause of cluster headache attacks. In this article the authors review the functional anatomy of the hypothalamic region and its neighborhood, using silicone-injected cadaveric head and MRI. In conclusion, a better understanding of the functional anatomy of the hypothalamus and its neighborhood is imperative for understanding the pathophysiology of several of the primary headaches, particularly migraine and the trigemino-autonomic headaches. Direct stimulation of the posterior hypothalamic region using DBS devices is now the "state of the art" form of treatment indicated for refractory chronic cluster headache. The exact mechanism and the actual region where the DBS may act are still unknown, and studies on the functional anatomy of the hypothalamus are crucial to the progress in this marvelous field of functional neurosurgery.

Overcoming Artifacts and Fears: Electrophysiology Study and Radiofrequency Ablation in a Parkinsonian Patient with Supraventricular Tachycardia and a Brain Neurostimulator

With the ageing of the population and expanding use of deep brain stimulation in the treatment of various neurological and neuropsychiatric conditions, there will be an increasing number of patients with these devices who present with cardiac conditions necessitating electrophysiology studies (EPS). However, neurostimulator devices have been shown to cause significant artifacts on electrocardiography recordings. We present the case of a 53-year-old Parkinsonian woman with a brain neurostimulator device who underwent a successful EPS with radiofrequency ablation.

Severe agitation following deep brain stimulation for parkinsonism

The use of deep brain stimulation has become increasingly common for the treatment of movement disorders, including Parkinson disease. Although deep brain stimulation is generally very successful in alleviating the extrapyramidal symptoms of Parkinson disease, side effects can occur. This case report describes a patient presenting to the emergency department in a state of extreme aggression 3 days after a change in the parameters of his bilateral subthalamic nucleus stimulator. We review the complications of deep brain stimulation relevant to the emergency physician and provide some practical information on stimulator adjustment in an emergency.

ETHICAL CONCERNS REGARDING COMMERCIALIZATION OF DEEP BRAIN STIMULATION FOR OBSESSIVE COMPULSIVE DISORDER

The United States Food and Drug Administration's recent approval of the commercial use of Deep Brain Stimulation (DBS) as a treatment for Obsessive Compulsive Disorder (OCD) will be discussed within the context of the existing USA regulatory framework. The purpose will be to illustrate the current lack of regulation and oversight of the DBS market, which has resulted in the violation of basic ethical norms. The discussion will focus on: 1) the lack of available evidence on procedural safety and efficacy, 2) the numerous conflicts of interest held by research investigators, and 3) the ambiguity of both aforementioned categories due to an inherent lack of transparency in the research. It is argued that in order to address these issues, ethical analyses of DBS for psychiatric disorders must include the role of the industry forces that have become the primary impetus for this research. As such, DBS for OCD serves as an important case example in studies of neurotechnology and innovative surgery.