Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Obsessive-compulsive disorder is a worldwide psychiatric disorder with a lifetime prevalence of 2% and mainly characterized by obsessional ideas and compulsive behaviors and rituals. Many patients show improvement under cognitive behavioral and/or pharmacological treatment. A minority of patients is refractory to all available therapy and may benefit from capsulotomy. This study aims to investigate deep brain stimulation (DBS) as a last resort treatment alternative to capsulotomy in treatment refractory obsessive-compulsive disorder. Eight patients have been implanted bilaterally in the anterior limbs of the internal capsules with a quadripolar electrode. This paper presents the results of the first 4 operated patients. Acute deep brain stimulation displays an immediate improvement of the speech, mood, eye contact and motor function. Chronic deep brain stimulation improves significantly the obsessional and compulsive symptomatology in three out of the four patients. This study definitely needs replication, but the results are promising. Reversible deep brain stimulation may improve the symptomatology of treatment refractory OCD patients, without significant side effects. <s> BIB001 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Neurostimulation is an emerging treatment for neurological diseases. Different types of neurostimulation exist mainly depending of the part of the nervous system that is being affected and the way this stimulation is being administered. Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with medically or surgically refractory epilepsy. Over 30,000 patients have been treated with VNS. No clear predictive factors for responders have been identified. To date, the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond better to VNS and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. Deep brain stimulation (DBS) has been used extensively as a treatment for movement disorders. Several new indications such as obsessive compulsive behaviour and cluster headache are being investigated with promising results. The vast progress in biotechnology along with the experience in other neurological diseases in the past ten years has led to a renewed interest in intracerebral stimulation for epilepsy. Epilepsy centers around the world have recently reinitiated trials with deep brain stimulation in different intracerebral structures such as the thalamus, the hippocampus and the subthalamic nucleus. <s> BIB002 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical s... <s> BIB003 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself. <s> BIB004 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Schizophrenia is a chronic and disabling psychiatric illness that is often refractory to treatment. Psychotic symptoms (e.g. hallucinations and delusions) in schizophrenia are reliably correlated with excess dopamine levels in the striatum, and have more recently been related to excess metabolic activity in the hippocampus. Multiple lines of evidence suggest that aberrantly high hippocampal activity may, via hippocampal connections with the limbic basal ganglia, drive excessive dopamine release into the striatum. In the present paper, we hypothesize that inhibition or stabilization of neural activity with high-frequency electrical stimulation of the hippocampus or nucleus accumbens, through different mechanisms, would treat the positive symptoms of schizophrenia. Thus, we suggest a direction for further experimentation aimed at developing neurosurgical therapeutic approaches for this devastating disease. <s> BIB005 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Abstract Deep brain stimulation (DBS) has proven a powerful treatment for medication refractory movement disorders. Success in this group of patients has allowed preliminary studies of DBS to proceed in severe and medication resistant cases of depression, obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Pathophysiological and imaging studies along with attempts at lesioning the basal ganglia, have offered clues as to nodes in the circuitry that may be amenable to neuromodulation. DBS in neuropsychiatric illness has offered hope, but at this time rigorous screening by interdisciplinary and ethical teams should be employed when establishing treatment candidacy. A cautious approach to these disorders utilizing institutional review board approved research protocols will hopefully shed light onto patient selection and brain target(s) for each disorder. We need to keep an open mind as we move forward and especially that rational therapy may need to be patient and symptom specific. This review will summarize each disorder (depression, OCD and TS), review pathophysiology (both known and speculated), and update the current observations on DBS in each neuropsychiatric condition. <s> BIB006 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Target areas and clinical symptoms in deep brain stimulation <s> Tourette's Syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics, often associated with behavioral disorders. Symptoms often disappear before or during adulthood. The pathophysiology of TS is still a matter of considerable debate. Current knowledge of cortico-basal ganglia-thalamocortical circuits provide explanations for the beneficial effects of deep brain stimulation (DBS) on tics. When conservative treatment fails in patients with severe TS, DBS may be a therapeutic option. In 1999, thalamic DBS was introduced for intractable TS. Since then, multiple targets have been used in a small number of patients, including the globus pallidus pars interna and the nucleus accumbens. Inclusion and exclusion criteria have been formulated to identify good candidates for DBS. <s> BIB007
As the target area, often located in the basal ganglia or thalamus, is usually only slightly larger than the DBSelectrode itself (diameter 1.27 mm Medtronic Model 3389, while the target diameter ranges from a few mm to about 1 cm), the positioning of the electrode is of utmost importance if an optimal clinical outcome, with minimal sideeffects, is to be achieved. The structures deep within the brain that are commonly used as targets for the reduction of motor Parkinsonian manifestations are, for tremor and rigidity, the subthalamic nucleus (STN); for tremor alone, the nucleus ventrointermedius of the thalamus (Vim); and for rigidity, for L-DOPA-induced dyskinesia or for dystonia (characterised by involuntary muscle contractions), the globus pallidus internus (GPi). Depending on the particular motor manifestations that are to be treated, other structures can be targeted as well, such as the zona incerta (Zi) or a thalamic subnucleus. Additional targets for deep brain stimulation are currently the subject of intensive research, and it can thus be expected that further types of neurological disturbances will become treatable with DBS. Examples of newer target areas include the pedunculopontine nucleus (PPN, for Parkinsonian manifestations such as impaired gait and balance)  , the internal capsule (for obsessivecompulsive disorder) BIB001 BIB006 and Brodmann area 25 (for depression) BIB003 BIB006 . Other disorders that are under trial for DBS are epilepsy BIB002 , Tourette syndrome BIB007 BIB006 , cluster headache BIB004 and schizophrenia BIB005 . Thus, the future clinical applications of DBS are expected to include stimulation not just in the already identified targets, but also in a wide range of brain structures and nuclei, each target corresponding to a particular clinical manifestation or set of manifestations to be treated or reduced. The concept of DBS is thus expected to go towards a more general concept of ''BS''-brain stimulation.