Deep Brain Stimulation Electrode Placement Research Articles

An Optimized System for Interventional Magnetic Resonance Imaging-Guided Stereotactic Surgery

Deep brain stimulation electrode placement with interventional magnetic resonance imaging (MRI) has previously been reported using a commercially available skull-mounted aiming device (Medtronic Nexframe MR) and native MRI scanner software. This first-generation method has technical limitations that are inherent to the hardware and software used. A novel system (SurgiVision ClearPoint) consisting of an aiming device (SMARTFrame) and software has been developed specifically for interventional MRI, including deep brain stimulation. To report a series of phantom and cadaver tests performed to determine the capability, preliminary accuracy, and workflow of the system. Eighteen experiments using a water phantom were used to determine the predictive accuracy of the software. Sixteen experiments using a gelatin-filled skull phantom were used to determine targeting accuracy of the aiming device. Six procedures in 3 cadaver heads were performed to compare the workflow and accuracy of ClearPoint with Nexframe MR. Software prediction experiments showed an average error of 0.9 ± 0.5 mm in magnitude in pitch and roll (mean pitch error, -0.2 ± 0.7 mm; mean roll error, 0.2 ± 0.7 mm) and an average error of 0.7 ± 0.3 mm in X-Y translation with a slight anterior (0.5 ± 0.3 mm) and lateral (0.4 ± 0.3 mm) bias. Targeting accuracy experiments showed an average radial error of 0.5 ± 0.3 mm. Cadaver experiments showed a radial error of 0.2 ± 0.1 mm with the ClearPoint system (average procedure time, 88 ± 14 minutes) vs 0.6 ± 0.2 mm with the Nexframe MR (average procedure time, 92 ± 12 minutes). This novel system provides the submillimetric accuracy required for stereotactic interventions, including deep brain stimulation placement. It also overcomes technical limitations inherent in the first-generation interventional MRI system.

Subthalamic Nucleus Targeting Using Interpeduncular Cistern as an Internal Landmark

Internal landmarks for the subthalamic nucleus (STN) have been used in past. This study uses a yet-unused internal landmark to refine STN targeting. To determine the effect of the width of the interpeduncular cistern (IPC) on STN targeting during placement of deep brain stimulation (DBS) for Parkinson disease. Fifty consecutive patients with Parkinson disease underwent 90 STN DBS implantations. X, Y, and Z coordinates for the tip of the DBS electrodes and the active contact were recorded. Internal landmarks such as width of the third ventricle, width of IPC at a predefined point, and anterior commissure-posterior commissure length were measured. Statistical analysis was done using linear regression analysis and Pearson correlation coefficient. The average IPC diameter at the predefined point was 7.59 mm (range, 5- to 14 mm). Average X, Y, and Z coordinates for the location of the tip of lead were 11.5, -3.5, -5.4, and those of the location of active contact were 12.5, -1.9, -1.4 from the midcommissural point. The mediolateral location of the tip of the DBS as well as the location of the active contact for long-term stimulation were greatly dependent on IPC width (r = 0.83) (P = .0022). The width of the IPC is a strong predictor of laterality of STN DBS electrode placement in patients with Parkinson disease. It can be used as an additional internal landmark for refining STN targeting using the simple formula X coordinate for STN target = 0.6 × IPC width + 7 mm.

Design and analysis of a head-mounted parallel kinematic device for skull surgery

Precision skull surgery requires specialized instrumentation to satisfy demanding requirements in cochlear array implantation, deep brain stimulation electrode placement, and related applications. A miniaturized reconfigurable parallel kinematic mechanism which can be directly mounted on a patient's skull was designed, built, and tested for precision skull surgery. A Stewart-Gough platform is attached to a patient's skull so no optical tracking affecting the overall accuracy in keyhole surgery is required. Six bone anchors comprising the mechanism base joints are implanted at positions with sufficient skull thickness. Since no fixation frame is required, intervention planning flexibility is increased. The centers of the spherical shaped bone anchors can be localized accurately in the image space. An implicit registration to the physical space is performed by assembling the kinematics. Registration error is minimized compared to common optical tracker-based approaches. Due to the reconfigurable mechanism, an optimization of the hexapod's configuration is needed to maximize accuracy and mechanical stability during the incision. Mathematical simulation was conducted to estimate system performance. Simulation results revealed significant improvement in accuracy and stability when exploiting the redundant degrees of freedom and the implemented reconfigurability. Inaccurate localization of base points in the image data set was identified as the main source of error. A first prototype with passive prismatic actuators, i.e. micrometer calipers, was successfully built. A head-mounted parallel kinematic device for high precision skull surgery was developed that provides submillimetric accuracy in straight-line incisions. The system offers enhanced flexibility due to the absence of a rigid fixation frame.

Multichannel microelectrode recording influences final electrode placement in pallidal deep brain stimulation for Parkinson's disease: report of twenty consecutive cases.

Stereotactic placement of the permanent deep brain stimulating electrode can be based upon imaging guidance with or without microelectrode recordings (MER). We conducted a retrospective study of 20 PD patients who underwent bilateral pallidal DBS placement with MER. There were 14 males and 6 females. The mean age at implantation was 67 years (range 42 - 80 years). Paired t-tests were used to compare initial imaging target coordinates versus final electrode coordinates based on intraoperative MER. United Parkinson's Disease Rating Scale (UPDRS) scores pre-operatively (medication off) and at 6 months post-operatively (medication off, stimulation on) and daily levodopa equivalents preoperatively and 6 months post-operatively were analyzed. The mean difference between calculated imaging target and final electrophysiological target was 3 mm (SD + 1.53 mm; p < 0.0001) in the dorsal-ventral plane and 1.2 mm the axial plane, resulting in a calculated final electrophysiology-based target adjustment of 3.4 mm (SD = 1.4 mm). Patients' average daily levodopa equivalent dose dropped by 52% at six months post-operatively (SD=40.9; p = 0.002). UPDRS scores dropped 26.9 points six months postoperatively (SD=20.4; p = 0.0003). In our experience intraoperative microelectrode recordings can facilitate final electrode placement.

An Assessment of Current Brain Targets for Deep Brain Stimulation Surgery With Susceptibility-Weighted Imaging at 7 Tesla

Deep brain stimulation (DBS) surgery is used for treating movement disorders, including Parkinson disease, essential tremor, and dystonia. Successful DBS surgery is critically dependent on precise placement of DBS electrodes into target structures. Frequently, DBS surgery relies on normalized atlas-derived diagrams that are superimposed on patient brain magnetic resonance imaging (MRI) scans, followed by microelectrode recording and macrostimulation to refine the ultimate electrode position. Microelectrode recording carries a risk of hemorrhage and requires active patient participation during surgery. To enhance anatomic imaging for DBS surgery using high-field MRI with the ultimate goal of improving the accuracy of anatomic target selection. Using a 7-T MRI scanner combined with an array of acquisition schemes using multiple image contrasts, we obtained high-resolution images of human deep nuclei in healthy subjects. Superior image resolution and contrast obtained at 7 T in vivo using susceptibility-weighted imaging dramatically improved anatomic delineation of DBS targets and allowed the identification of internal architecture within these targets. A patient-specific, 3-dimensional model of each target area was generated on the basis of the acquired images. Technical developments in MRI at 7 T have yielded improved anatomic resolution of deep brain structures, thereby holding the promise of improving anatomic-based targeting for DBS surgery. Future study is needed to validate this technique in improving the accuracy of targeting in DBS surgery.

Improving Targeting in Image-Guided Frame-Based Deep Brain Stimulation

Deep brain stimulation (DBS) is commonly used in the treatment of movement disorders such as Parkinson disease (PD), dystonia, and other tremors. To examine systematic errors in image-guided DBS electrode placement and to explore a calibration strategy for stereotactic targeting. Pre- and postoperative stereotactic MR images were analyzed in 165 patients. The perpendicular error between planned target coordinates and electrode trajectory was calculated geometrically for all 312 DBS electrodes implanted. Improvement in motor unified PD rating scale III subscore was calculated for those patients with PD with at least 6 months of follow-up after bilateral subthalamic DBS. Mean (standard deviation) scalar error of all electrodes was 1.4(0.9) mm with a significant difference between left and right hemispheres. Targeting error was significantly higher for electrodes with coronal approach angle (ARC) ≥10° (P < .001). Mean vector error was X: -0.6, Y: -0.7, and Z: -0.4 mm (medial, posterior, and superior directions, respectively). Targeting error was significantly improved by using a systematic calibration strategy based on ARC and target hemisphere (mean: 0.6 mm, P < .001) for 47 electrodes implanted in 24 patients. Retrospective theoretical calibration for all 312 electrodes would have reduced the mean (standard deviation) scalar error from 1.4(0.9) mm to 0.9(0.5) mm (36% improvement). With calibration, 97% of all electrodes would be within 2 mm of the intended target as opposed to 81% before calibration. There was no significant correlation between the degree of error and clinical outcome from bilateral subthalamic nucleus DBS (R = 0.07). After calibration of a systematic targeting error an MR image-guided stereotactic approach would be expected to deliver 97% of all electrodes to within 2 mm of the intended target point with a single brain pass.

Minimizing Brain Shift in Stereotactic Functional Neurosurgery

Stereotactic functional neurosurgical interventions depend on precise anatomic targeting before lesioning or deep brain stimulation (DBS) electrode placement. To examine the degree of subcortical brain shift observed when adopting an image-guided approach to stereotactic functional neurosurgery. Coordinates for the anterior and posterior commissural points (AC and PC) were recorded on thin-slice stereotactic magnetic resonance imaging (MRI) scans performed before and immediately after DBS electrode implantation in 136 procedures. The changes in length of AC-PC and in stereotactic coordinates for AC and PC were calculated for each intervention. In patients with Parkinson disease undergoing bilateral subthalamic nucleus (STN) DBS with at least 6 months of follow-up, pre- and postoperative scores of the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS-III) were reviewed. Mean (SD) change in AC-PC length (DeltaAC-PC) was 0.6 (0.4) mm. There was no statistically significant difference in DeltaAC-PC between groups when examining anatomic target subgroups (P =.95), age subgroups (P = .63), sex (P = .59), and unilateral versus bilateral implantation (P =.15). The mean (SD) vector changes for the commissural points were: -0.1 (0.3) mm in X, -0.4 (0.6) mm in Y, and -0.1 (0.7) mm in Z for the AC; and -0.1 (0.3) mm in X, -0.2 (0.7) mm in Y, and 0.0 (0.7) mm in Z for the PC. There was a negligible correlation between the magnitude of brain shift and percentage improvement in UPDRS-III off-medication in patients undergoing STN DBS for PD (R <0.01). Brain shift has long been considered an issue in stereotactic targeting during DBS procedures. However, with the image-guided approach and surgical technique used in this study, subcortical brain shift was extremely limited and did not appear to adversely affect clinical outcome.

Parkinson’s Disease and Motor Fluctuations

Many important advances for the treatment of Parkinson's disease (PD) have been made over the past decade, and quality of life has improved for most patients. Nonetheless, motor fluctuations in the form of wearing off with the re-emergence of parkinsonian symptoms and hyperkinetic movements (dyskinesias) often arise as a complication of long-term dopaminergic therapy and can be disabling. Because treatment of motor fluctuations is difficult, clinicians should attempt to prevent them by using low doses of dopaminergic drugs in early PD, targeting functionally relevant symptoms. Instead of levodopa, dopamine agonists, amantadine, and rasagiline can be used with the aim of delaying the onset of motor fluctuations. Once motor fluctuations arise, off time can initially be addressed with more frequent dosing of levodopa. Later, adjunctive therapy with a dopamine agonist, COMT-inhibitor, or MAO-B inhibitor becomes necessary. For treatment of dyskinesias, reduction of the levodopa dose should be the first step. If this is not tolerated because of increased off time, then adjunctive therapy with levodopa-sparing agents should be attempted. The addition of amantadine (the only currently available antidyskinetic drug) is another useful strategy but is often only a temporary solution. Once medical attempts at treating motor fluctuations fail, deep brain stimulation (DBS) can be considered. Careful patient selection and skilled placement of DBS electrodes are important determinants of the surgical outcome.

Comonitoring of adenosine and dopamine using the Wireless Instantaneous Neurotransmitter Concentration System: proof of principle

The authors of previous studies have demonstrated that local adenosine efflux may contribute to the therapeutic mechanism of action of thalamic deep brain stimulation (DBS) for essential tremor. Real-time monitoring of the neurochemical output of DBS-targeted regions may thus advance functional neurosurgical procedures by identifying candidate neurotransmitters and neuromodulators involved in the physiological effects of DBS. This would in turn permit the development of a method of chemically guided placement of DBS electrodes in vivo. Designed in compliance with FDA-recognized standards for medical electrical device safety, the authors report on the utility of the Wireless Instantaneous Neurotransmitter Concentration System (WINCS) for real-time comonitoring of electrical stimulation-evoked adenosine and dopamine efflux in vivo, utilizing fast-scan cyclic voltammetry (FSCV) at a polyacrylonitrile-based (T-650) carbon fiber microelectrode (CFM). The WINCS was used for FSCV, which consisted of a triangle wave scanned between -0.4 and +1.5 V at a rate of 400 V/second and applied at 10 Hz. All voltages applied to the CFM were with respect to an Ag/AgCl reference electrode. The CFM was constructed by aspirating a single T-650 carbon fiber (r = 2.5 microm) into a glass capillary and pulling to a microscopic tip using a pipette puller. The exposed carbon fiber (the sensing region) extended beyond the glass insulation by approximately 50 microm. Proof of principle tests included in vitro measurements of adenosine and dopamine, as well as in vivo measurements in urethane-anesthetized rats by monitoring adenosine and dopamine efflux in the dorsomedial caudate putamen evoked by high-frequency electrical stimulation of the ventral tegmental area and substantia nigra. The WINCS provided reliable, high-fidelity measurements of adenosine efflux. Peak oxidative currents appeared at +1.5 V and at +1.0 V for adenosine, separate from the peak oxidative current at +0.6 V for dopamine. The WINCS detected subsecond adenosine and dopamine efflux in the caudate putamen at an implanted CFM during high-frequency stimulation of the ventral tegmental area and substantia nigra. Both in vitro and in vivo testing demonstrated that WINCS can detect adenosine in the presence of other easily oxidizable neurochemicals such as dopamine comparable to the detection abilities of a conventional hardwired electrochemical system for FSCV. Altogether, these results demonstrate that WINCS is well suited for wireless monitoring of high-frequency stimulation-evoked changes in brain extracellular concentrations of adenosine. Clinical applications of selective adenosine measurements may prove important to the future development of DBS technology.

Subthalamic nucleus deep brain stimulator placement using high-field interventional magnetic resonance imaging and a skull-mounted aiming device: technique and application accuracy

The authors discuss their method for placement of deep brain stimulation (DBS) electrodes using interventional MR (iMR) imaging and report on the accuracy of the technique, its initial clinical efficacy, and associated complications in a consecutive series of subthalamic nucleus (STN) DBS implants to treat Parkinson disease (PD). A skull-mounted aiming device (Medtronic NexFrame) was used in conjunction with real-time MR imaging (Philips Intera 1.5T). Preoperative imaging, DBS implantation, and postimplantation MR imaging were integrated into a single procedure performed with the patient in a state of general anesthesia. Accuracy of implantation was assessed using 2 types of measurements: the "radial error," defined as the scalar distance between the location of the intended target and the actual location of the guidance sheath in the axial plane 4 mm inferior to the commissures, and the "tip error," defined as the vector distance between the expected anterior commissure-posterior commissure (AC-PC) coordinates of the permanent DBS lead tip and the actual AC-PC coordinates of the lead tip. Clinical outcome was assessed using the Unified Parkinson's Disease Rating Scale part III (UPDRS III), in the off-medication state. Twenty-nine patients with PD underwent iMR imaging-guided placement of 53 DBS electrodes into the STN. The mean (+/- SD) radial error was 1.2 +/- 0.65 mm, and the mean absolute tip error was 2.2 +/- 0.92 mm. The tip error was significantly smaller than for STN DBS electrodes implanted using traditional frame-based stereotaxy (3.1 +/- 1.41 mm). Eighty-seven percent of leads were placed with a single brain penetration. No hematomas were visible on MR images. Two device infections occurred early in the series. In bilaterally implanted patients, the mean improvement on the UPDRS III at 9 months postimplantation was 60%. The authors' technical approach to placement of DBS electrodes adapts the procedure to a standard configuration 1.5-T diagnostic MR imaging scanner in a radiology suite. This method simplifies DBS implantation by eliminating the use of the traditional stereotactic frame and the subsequent requirement for registration of the brain in stereotactic space and the need for physiological recording and patient cooperation. This method has improved accuracy compared with that of anatomical guidance using standard frame-based stereotaxy in conjunction with preoperative MR imaging.

The incidence of seizures following Deep Brain Stimulating electrode implantation for movement disorders, pain and psychiatric conditions

Deep Brain Stimulation (DBS) for neuromodulation is now commonplace. However little is known about the incidence of either procedural related seizures or epilepsy following chronic DBS. This study aims to provide estimates of these complications for movement disorders, pain and psychiatric conditions. A literature review was performed. Because searches using the terms seizure, epilepsy, and deep brain stimulation revealed only papers dealing with experimental and clinical application of DBS to treat chronic seizures disorders, a search strategy trawling through papers that described clinical case series of DBS was used. Thirty-two papers were reviewed that described stereotactic placement of DBS electrodes for movement disorders, pain syndromes and psychiatric conditions with cohorts of n > 5. Sixteen of these papers describing at least 1418 DBS electrode placements in 1254 patients did not mention seizures as a complication (i.e., it was not possible to know whether seizures had or had not occurred). In 16 papers, describing at least 2101 electrode placements in 1555 patients, seizures were described in 42 patients (incidence 2.7%). The range of seizure incidence varied from 0% (three series encompassing 317 patients and 576 electrode placements) up to 10% (n = 130) and 13% (n = 15). The reasons for this variance were not obvious. At least 74% of seizures occurred around the time of electrode implantation and many of these patients also suffered intracranial hemorrhage. Follow up times were variable (range 6mths to 5 years). The analysis was complicated by multiple publications from some centres with duplication of some data. The quality of literature on seizures following DBS insertion for neuromodulation is highly variable. Analysis of the available data, after making corrections for publication of duplicate data, suggests strongly that the risk of seizures associated with DBS placement is probably lower than 2.4% (95% CI 1.7 to 3.3 %). The risk of postprocedural seizures associated with chronic deep brain stimulation is even lower with best estimates around 0.5% (95% CI .02 to 1.0%).

Outcome of Bilateral Subthalamic Nucleus Stimulation in the Treatment of Parkinson’s Disease: Correlation with Intra-Operative Multi-Unit Recordings but Not with the Type of Anaesthesia

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) gained general acceptance in the treatment of Parkinson’s disease (PD). Objective: To study the clinical outcome and the predicting factors of efficacy of chronic STN stimulation, while DBS electrodes were implanted under local or general anaesthesia with intra-operative electrophysiological guidance based on multi-unit recordings. Methods: We included a large single-centre cohort of 54 patients with advanced PD (mean age: 59 years; disease duration: 14 years). Clinical evaluation was performed by the Unified Parkinson’s Disease Rating Scale (UPDRS) before and 1 year after surgical placement of DBS electrodes. Results: In the on-stimulation and off-medication condition, the UPDRS part III score was reduced by 56% compared to the off-stimulation condition or pre-operative off-drug score. In the on-stimulation and on-medication condition, this score was reduced by 73%. The severity of motor fluctuations and dyskinesia (UPDRS part IV) and the activities of daily living (UPDRS part II) were reduced by 65 and 80%, respectively, in the on-stimulation/on-medication condition compared to the pre-operative baseline. The daily dose of antiparkinsonian treatment was diminished by 72%. Among the various pre- and intra-operative data, the most important predictive factor for clinical efficacy of STN stimulation was the length of hyperactivity along the best track observed in intra-operative multi-unit recordings. Other predictive factors included age, disease duration and pre-operative levodopa responsiveness or baseline off-drug values of the Hoehn and Yahr and UPDRS part III scores. In contrast, the type of anaesthesia (local vs. general) did not significantly influence the clinical outcome. Conclusion: The present results are in the average of previously published results, but they have been obtained from a large single-centre cohort of patients with important reductions in the daily dose of antiparkinsonian drugs. This study confirmed the efficacy of the STN-DBS technique and emphasized the value of an original intra-operative electrophysiological approach based on multi-unit and not single-unit quantified recordings. This method allows DBS electrode implantation to be safely performed under general anaesthesia without lessening the rate of efficacy of the procedure.

A method to estimate the spatial extent of activation in thalamic deep brain stimulation

Objective The goal of this study was to develop, evaluate, and apply a method to quantify the unknown spatial extent of activation in deep brain stimulation (DBS) of the ventral intermedius nucleus (Vim) of the thalamus. Methods The amplitude–distance relationship and the threshold amplitudes to elicit clinical responses were combined to estimate the unknown amplitude–distance constant and the distance between the electrode and the border between the Vim and the ventrocaudal nucleus (Vc) of the thalamus. We tested the sensitivity of the method to errors in the input parameters, and subsequently applied the method to estimate the amplitude–distance constant from clinically-measured threshold amplitudes. Results The method enabled estimation of the amplitude–distance constant with a median squared error of 0.07–0.23 V/mm 2 and provided an estimate of the distance between the electrode and the Vc/Vim border with a median squared error of 0.01–0.04 mm. Application of the method to clinically-measured threshold amplitudes to elicit paresthesias estimated the amplitude–distance constant to be 0.22 V/mm 2. Conclusions The method enabled robust quantification of the spatial extent of activation in thalamic DBS and predicted that stimulation amplitudes of 1–3.5 V would produce a mean effective radius of activation of 2.0–3.9 mm. Significance Knowing the spatial extent of activation may improve methods of electrode placement and stimulation parameter selection in DBS.

Failed DBS for palliation of visual problems in a case of oculopalatal tremor

Objective To report the results of attempted bilateral red nucleus (RN) deep brain stimulation (DBS) for the palliative treatment of visual problems associated with oculopalatal tremor (OPT). Background It is hypothesized that OPT results from a defect in the Guillain–Mollaret triangle, a circuit that includes connections with the dentate nucleus, the contralateral red nucleus, and the inferior olive. We present a high functioning patient (an accountant) who underwent a palliative trial of RN region DBS in an approach targeted through the subthalamic nucleus region. The aim was to reduce eye tremor and improve vision through interruption of the pathologically oscillating circuit in the Guillain–Mollaret triangle. Methods Following informed consent, a patient with OPT (and failure of multiple classes of medication and botulinum toxin therapy) underwent placement of bilateral DBS electrodes within the region of the RN. He underwent preoperative testing and testing after 12 months of continuous stimulation with the device in monopolar, bipolar, low frequency, and high frequency settings. Results The patient did not demonstrate significant changes in the neurological examination following the procedure and postoperative programming sessions. Eye tremor was monitored pre- and postoperatively by ocular EMG and did not change in frequency. Following the one-year trial, stimulation was discontinued as there were no improvements in vision. Conclusion DBS for OPT was not clinically effective. There were many potential reasons for failed efficacy including a failure to implant the electrodes deep and medial enough into the target region because of stimulation induced side effects. Other targets within the Guillain–Mollaret circuit (and outside of the circuit) may be more useful, though they may prove to be less safe and even more difficult to access. Better custom designed DBS leads may be needed for such small targets in critical brain regions.

Pedunculopontine nucleus microelectrode recordings in movement disorder patients

The pedunculopontine nucleus (PPN) lies within the brainstem reticular formation and is involved in the motor control of gait and posture. Interest has focused recently on the PPN as a target for implantation of chronic deep brain stimulation (DBS) electrodes for Parkinson's disease (PD) and progressive supranuclear palsy (PSP) therapy. The aim of this study was to examine the neurophysiology of the human PPN region and to identify neurophysiological landmarks that may aid the proper placement of DBS electrodes in the nucleus for the treatment of PD and PSP. Neuronal firing and local field potentials were recorded simultaneously from two independently driven microelectrodes during stereotactic neurosurgery for implantation of a unilateral DBS electrode in the PPN in five PD patients and two PSP patients. Within the PPN region, the majority (57%) of the neurons fired randomly while about 21% of the neurons exhibited 'bursty' firing. In addition, 21% of the neurons had a long action potential duration and significantly lower firing rate suggesting they were cholinergic neurons. A change in firing rate produced by passive and/or active contralateral limb movement was observed in 38% of the neurons that were tested in the PPN region. Interestingly, oscillatory local field potential activity in the beta frequency range ( approximately 25 Hz) was also observed in the PPN region. These electrophysiological characteristics of the PPN region provide further support for the proposed role of this region in motor control. It remains to be seen to what extent the physiological characteristics of the neurons and the stimulation-evoked effects will permit reliable identification of PPN and determination of the optimal target for DBS therapy.

Neuromodulation of the cingulum for neuropathic pain after spinal cord injury

The authors present a case in which high-frequency electrical stimulation of the cingulum using standard deep brain stimulation (DBS) technology resulted in pain relief similar to that achieved with cingulotomy and superior to that achieved with periventricular gray matter (PVG) stimulation. This patient had a complete spinal cord injury at the C-4 level and suffered from medically refractory neuropathic pain. He underwent placement of bilateral cingulum and unilateral PVG DBS electrodes and a 1-week blinded stimulation trial prior to permanent implantation of a pulse generator. During the stimulation trial, the patient's pain level was assessed using a visual analog scale, and pain medication usage was recorded. During this period the patient was blinded to stimulation parameters. Stimulation of the cingulum provided better pain control than PVG stimulation or medication alone. The authors believe that cingulum stimulation can benefit patients with severe neuropathic pain that is refractory to other treatments. Advantages over cingulotomy include reversibility and the ability to adjust stimulation parameters for optimum efficacy.

Stimulation of the Posterior Hypothalamus for Medically Intractable Impulsive and Violent Behavior

Objective: To describe the therapeutic effect of deep brain stimulation for the treatment of patients with below-average IQs who are affected by aggressive and disruptive behavior and who are resistant to any drug and/or conservative treatment (including occupational therapy). Patients and Methods: Two consecutive patients suffering from mental retardation with aggressive and disruptive behavior and resistant to any pharmacological treatment underwent deep brain stimulation electrode placement in the posteromedial hypothalamus for continuous chronic high-frequency stimulation (HFS). The stereotactic coordinates of the target were chosen according to the study by Sano et al., which involved hypothalamic stereotactic lesions. Results: HFS of the posteromedial hypothalamus demonstrated consistent improvement of disruptive behavior in both patients at the follow-up evaluation 1 year later. Conclusions: HFS of the posteromedial hypothalamus showed similar results to those obtained by Sano et al. in the 1960s with radiofrequency lesions of the same target volume. The reversibility of neurostimulation allows HFS to control disruptive behavior when conservative treatments are ineffective, and drug therapy is uneventful or causes severe side effects. In conclusion, this neuromodulation procedure improved the quality of life and the range of social relationships for both of the treated patients.

Implantation of bilateral deep brain stimulators in patients with Parkinson disease and preexisting cardiac pacemakers

Deep brain stimulation (DBS) has become an important modality in the treatment of refractory Parkinson disease (PD). In patients with comorbid arrhythmias requiring cardiac pacemakers, DBS therapy is complicated by concerns over a possible electrical interaction between the devices (or with device programming) and the inability to use magnetic resonance imaging guidance for implantation. The authors report two cases of PD in which patients with preexisting cardiac pacemakers underwent successful implantation of bilateral DBS electrodes in the subthalamic nucleus (STN). Each patient underwent computerized tomography-guided stereotactic frame-based placement of DBS electrodes with microelectrode recording. Both extension wires were passed from the right side of the head and neck (contralateral to the pacemaker) to place the cranial pulse generators subcutaneously in the left and right abdomen. The cranial pulse generators were placed farther than 6 in from the cardiac pacemaker and from each other to decrease the chance of interference between the devices during telemetry reprogramming. Postoperative management involved brain stimulator programming sessions with simultaneous cardiological monitoring of pacemaker function and cardiac rhythm. No interference was noted at any time, and proper pacemaker function was maintained throughout the follow-up period. With bilateral STN stimulation, both patients experienced a dramatic improvement in their PD symptoms, including elimination of dyskinesias, reduction of "off" severity, and increase of "on" duration. With some modifications of implantation strategy, two patients with cardiac pacemakers were successfully treated with bilateral DBS STN therapy for refractory PD. To our knowledge, this is the first report on patients with cardiac pacemakers undergoing brain stimulator implantation.

P.2.115 The schizophrenia quality of life scale (SOL)42-item short form (SOL-42): Conceptual framework and item selection

The use of deep brain stimulation (DBS) in treatment resistant patients with schizophrenia is of considerable current interest, but where to site the electrodes is challenging. This article reviews rationales for electrode placement in schizophrenia based on evidence for localized brain abnormality in the disorder and the targets that have been proposed and employed to date. The nucleus accumbens and the subgenual anterior cingulate cortex are of interest on the grounds that they are sites of potential pathologically increased brain activity in schizophrenia and so susceptible to the local inhibitory effects of DBS; both sites have been employed in trials of DBS in schizophrenia. Based on other lines of reasoning, the ventral tegmental area, the substantia nigra pars reticulata and the habenula have also been proposed and in some cases employed. The dorsolateral prefrontal cortex has not been suggested, probably reflecting evidence that it is underactive rather than overactive in schizophrenia. The hippocampus is also of theoretical interest but there is no clear functional imaging evidence that it shows overactivity in schizophrenia. On current evidence, the nucleus accumbens may represent the strongest candidate for DBS electrode placement in schizophrenia, with the substantia nigra pars reticulata also showing promise in a single case report; the ventral tegmental area is also of potential interest, though it remains untried.

Microelectrode recording revealing a somatotopic body map in the subthalamic nucleus in humans with Parkinson disease.

The subthalamic nucleus (STN) is a key structure for motor control through the basal ganglia. The aim of this study was to show that the STN in patients with Parkinson disease (PD) has a somatotopic organization similar to that in nonhuman primates. A functional map of the STN was obtained using electrophysiological microrecording during placement of deep brain stimulation (DBS) electrodes in patients with PD. Magnetic resonance imaging was combined with ventriculography and intraoperative x-ray film to assess the position of the electrodes and the STN units, which were activated by limb movements to map the sensorimotor region of the STN. Each activated cell was located relative to the anterior commissure-posterior commissure line. Three-dimensional coordinates of the cells were analyzed statistically to determine whether those cells activated by movements of the arm and leg were segregated spatially. Three hundred seventy-nine microelectrode tracks were created during placement of 71 DBS electrodes in 44 consecutive patients. Somatosensory driving was found in 288 tracks. The authors identified and localized 1213 movement-related cells and recorded responses from 29 orofacial cells, 480 arm-related cells, 558 leg-related cells, and 146 cells responsive to both arm and leg movements. Leg-related cells were localized in medial (p < 0.0001) and ventral (p < 0.0004) positions and tended to be situated anteriorly (p = 0.063) relative to arm-related cells. Evidence of somatotopic organization in the STN in patients with PD supports the current theory of highly segregated loops integrating cortex-basal ganglia connections. These loops are preserved in chronic degenerative diseases such as PD, but may subserve a distorted body map. This finding also supports the relevance of microelectrode mapping in the optimal placement of DBS electrodes along the subthalamic homunculus.