Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> When not corrected, geometrically distorted magnetic resonance images may be unsuitable for stereotactic intracranial neurosurgical procedures where accuracy of target localization is critical. On a GE Signa 1.5-tesla system, we implemented an imaging protocol designed to improve the accuracy of the determination of target coordinates by means of multiple scans utilizing reversal of the frequency-encoded readout gradient. Using a Cosman-Roberts-Wells (CRW) frame and a phantom, geometric shifts of important image features were found to occur. In patients undergoing functional neurosurgical procedures with the CRW system, localization of the posterior commissure by corrected MR images was compared to that obtained by intraoperative ventriculography. Unexpectedly, severe distortions in MR images were revealed by the studies, with shifts of some fiducial markers of 10 mm from their estimated true position. Most of this distortion was attributable to the magnetic properties of the stereotactic frame, and could be eliminated by appropriate design and manufacture of the frame system. Images obtained with an MRI-compatible Leksell stereotactic frame were found to be relatively free of major geometric distortion. This study points out that properties of frame systems used for stereotactic neurosurgery may greatly influence the accuracy of frame-based stereotactic neurosurgery, and that the accuracy of these frame systems is testable. <s> BIB001 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> A qualitative work-flow analysis of a neurosurgical procedwcud * 'hat the resolution of the image used to plan the intervention is the major source of inaccuracy. Quantitative experimental measurements confirm this observation. They fail, however, to explain the relationship between the accuracy of the frame components involved in a stereotactic procedure and the overall application accuracy. This investigation shows that the novel Gaussian approach is a flexible frame- work for the calculation of the application accuracy of frame systems. Therefore, the Gaussian approach provides a detailed understanding of the interplay between the various factors affecting accuracy. The basic ideas and limitations of the Gaussian approach are briefly explained. The effect of fiducial marker distribution and registration is investigated and shown to introduce a spatial dependence to the accuracy. The results of the Gaussian approach are compared with experimental data for three stereotactic frame devices: Leksell G, Cosman-Roberts-Wells, and Brown-Roberts- Wells. Although the Gaussian approach is an approximation, it reproduces the accuracy measured in the experiment within the statistical error of that experiment. Comp Aid Surg 4:77- 86 (1 999). 01999 Wiley-Liss, Inc. <s> BIB002 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Object. The actual distortion present in a given series of magnetic resonance (MR) images is difficult to establish. The purpose of this study was to validate an MR imaging‐based methodology for stereotactic targeting of the internal globus pallidus during electrode implantation in children in whom general anesthesia had been induced. Methods. Twelve children (mean follow up 1 year) suffering from generalized dystonia were treated with deep brain stimulation by using a head frame and MR imaging. To analyze the influence of distortions at every step of the procedure, the geometrical characteristics of the frame were first controlled using the localizer as a phantom. Then pre- and postoperative coordinates of fixed anatomical landmarks and electrode positions, both determined with the head frame in place, were statistically compared. No significant difference was observed between theoretical and measured dimensions of the localizer (Student’s t-test, |t| � 2.2 for 12 patients) in the x, y, and z directions. No significant differences were observed (Wilcoxon paired-sample test) between the following: 1) pre- and postoperative coordinates of the anterior commissure (AC) ( ∆ x = 0.3 � 0.29 mm and ∆ y = 0.34 � 0.32 mm) and posterior commissure (PC) (∆ x = 0.15 � 0.18 mm and ∆ y = 0.34 � 0.25 mm); 2) pre- and postoperative AC‐PC distance (∆ L = 0.33 � 0.22 mm); and 3) preoperative target and final electrode position coordinates ( ∆ x = 0.24 � 0.22 mm; ∆ y = 0.19 � 0.16 mm). Conclusions. In the authors’ center, MR imaging distortions did not induce detectable errors during stereotactic surgery in dystonic children. Target localization and electrode implantation could be achieved using MR imaging alone after induction of general anesthesia. The remarkable postoperative improvement in these patients confirmed the accuracy of the procedure (Burke‐Marsden‐Fahn Dystonia Rating Scale score ∆ = � 83.8%). <s> BIB003 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> BACKGROUND ::: For the treatment of medically refractory movement disorders such as Parkinson's disease, essential tremor and primary dystonia, deep brain stimulation (DBS) has become one of the main treatment options. The targets for implantation of the stimulation electrodes are various nuclei within the basal ganglia or the thalamic and subthalamic area. Accurate target localisation is of major importance for outcome and patient safety. The goal of this study was to evaluate the role of image fusion in the determination of target co-ordinates. ::: ::: ::: METHOD ::: We conducted a retrospective study on 10 patients in whom 17 DBS electrodes had been implanted. Coordinates of the anterior and posterior commissures and of the DBS targets were compared on pre- and postoperative computerised tomography (CT) and fused CT/magnetic resonance scans. The targets as defined on the images were further compared with the targets derived intra-operatively with microelectrode recordings (MER) and macrostimulation. ::: ::: ::: FINDINGS ::: The achievable mean target accuracy was of the order of the diameter of the DBS electrode and of the accuracy of the image fusion algorithm, i.e. about 1 mm. However, the maximal differences were between 1.8 mm and 3.2 mm. ::: ::: ::: INTERPRETATION ::: Image fusion is a helpful tool for accurate determination of target point co-ordinates in DBS. In combination with intraoperative, electrophysiological recordings and stimulation which are still considered to be the most reliable localisation methods, image fusion may help to discern the anatomical and functional three-dimensionality of the target nuclei. Image fusion may reduce the number of trajectories needed for intraoperative electrophysiological determination of the optimal electrode localisation and thus lower the risk of complications. <s> BIB004 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Object. To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia. Methods. Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure—posterior commissure (AC—PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging—based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates... <s> BIB005 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> There is an ongoing controversy about whether it is necessary to use microelectrode recording (MER) techniques in stereotactic surgery for Parkinson’s disease and other movement disorders. This paper <s> BIB006 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Object. There is an active debate regarding whether pallidotomy should be performed using macroelectrode stimulation or the more sophisticated and expensive method of microelectrode recording. No prospective, randomized trial results have answered this question, although personnel at many centers claim one method is superior. In their metaanalysis the authors reviewed published reports of both methods to determine if there is a significant difference in clinical outcomes or complication rates associated with these methods. Methods. A metaanalysis was performed with data from reports on the use of unilateral pallidotomy in patients with Parkinson disease (PD) that were published between 1992 and 2000. A Medline search was conducted for the key word “pallidotomy” and additional studies were added following a review of the references. Only those studies dealing with unilateral procedures performed in patients with PD were included. Papers were excluded if they described a cohort smaller than 10 patients or a... <s> BIB007 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> High frequency electrical stimulation by means of electrodes implanted into the brain (deep brain stimulation; DBS) recently has become an accepted technique for the treatment of several movement disorders and in particular for Parkinson's disease. Because the effects produced by DBS are similar to those produced by making a lesion in the same region, it has been proposed that the overall effect of DBS is to inhibit the neural activity in the region stimulated. However, whether this is actually the case is presently not known, but various mechanisms have been proposed in an attempt to explain how DBS could mimic the effects of a lesion. We describe the various mechanisms that have been proposed to account for the inhibition or disruption of the pathologic outflow by high-frequency DBS, ranging from depolarisation block to stimulation-evoked release of γ-aminobutyric acid and describes preliminary findings that show that stimulation within these structures can result in inhibition. <s> BIB008 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been vaulted forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address the present knowledge of the effects of high frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS. Four general hypotheses have been developed to explain the mechanism(s) of DBS: depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathologic network activity. Using the results from microdialysis, neural recording, functional imaging, and neural modeling experiments, the authors address the main hypotheses and attempt to reconcile what have been considered conflicting results from different research modalities. <s> BIB009 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> The vast majority of centers use electrophysiological mapping techniques to finalize target selection during the im- plantation of deep brain stimulation (DBS) leads for the treat- ment of Parkinson's disease and tremor. This review discusses the techniques used for physiological mapping and addresses the questions of how various mapping strategies modify target selection and outcome following subthalamic nucleus (STN), globus pallidus internus (GPi), and ventralis intermedius (Vim) deep brain stimulation. Mapping strategies vary greatly across centers, but can be broadly categorized into those that use microelectrode or semimicroelectrode techniques to optimize position prior to implantation and macrostimulation through a macroelectrode or the DBS lead, and those that rely solely on macrostimulation and its threshold for clinical effects (benefits and side effects). Microelectrode criteria for implantation into the STN or GPi include length of the nucleus recorded, pres- ence of movement-responsive neurons, and/or distance from the borders with adjacent structures. However, the threshold for the production of clinical benefits relative to side effects is, in most centers, the final, and sometimes only, determinant of DBS electrode position. Macrostimulation techniques for map- ping, the utility of microelectrode mapping is reflected in its modification of electrode position in 17% to 87% of patients undergoing STN DBS, with average target adjustments of 1 to 4 mm. Nevertheless, with the absence of class I data, and in consideration of the large number of variables that impact clinical outcome, it is not possible to conclude that one tech- nique is superior to the other in so far as motor Unified Parkinson's Disease Rating Scale outcome is concerned. More- over, mapping technique is only one out of many variables that determine the outcome. The increase in surgical risk of intra- cranial hemorrhage correlated to the number of microelectrode trajectories must be considered against the risk of suboptimal benefits related to omission of this technique. © 2006 Move- ment Disorder Society <s> BIB010 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Numerous factors need to be taken into account when implanting deep brain stimulation (DBS) systems into patients with Parkinson's disease. The surgical procedure itself can be divided into immediate preoperative, intraoperative, and immediate postoperative phases. Preoperative considerations include medication withdrawal issues, stereotactic equipment choices, imaging modalities, and targeting strategy. Intraoperative considerations focus on methods for physiological confirmation of a given target for DBS electrode deployment. Terms such as microelectrode recording, microstimulation, and macrostimulation will be defined to clarify inconsistencies in the literature. Advantages and disadvantages of each technique will be addressed. Furthermore, operative decisions such as staging, choice of electrode and implantable pulse generator, and methods of device fixation will be outlined. Postoperative issues include imaging considerations, including magnetic resonance safety, device–device interactions, and immediate surgical complications pertaining to the DBS procedure. This report outlines answers to a series of questions developed to address all aspects of the DBS surgical procedure and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society. It outlines answers to a series of questions developed to address all surgical aspects of deep brain stimulation. © 2006 Movement Disorder Society <s> BIB011 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Deep brain stimulation (DBS) is a widely accepted therapy for medically refractory Parkinson's disease (PD). Both globus pallidus internus (GPi) and subthalamic nucleus (STN) stimulation are safe and effective in improving the symptoms of PD and reducing dyskinesias. STN DBS is the most commonly performed surgery for PD as compared to GPi DBS. Ventral intermediate nucleus (Vim) DBS is infrequently used as an alternative for tremor predominant PD patients. Patient selection is critical in achieving good outcomes. Differential diagnosis should be emphasized as well as neurological and nonneurological comorbidities. Good response to a levodopa challenge is an important predictor of favorable long-term outcomes. The DBS surgery is typically performed in an awake patient and involves stereotactic frame application, CT/MRI imaging, anatomical targeting, physiological confirmation, and implantation of the DBS lead and pulse generator. Anatomical targeting consists of direct visualization of the target in MR images, formula-derived coordinates based on the anterior and posterior commissures, and reformatted anatomical stereotactic atlases. Physiological verification is achieved most commonly via microelectrode recording followed by implantation of the DBS lead and intraoperative test stimulation to assess benefits and side effects. The various aspects of DBS surgery will be presented. <s> BIB012 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Object Relationships between clinical effects, anatomy, and electrophysiology are not fully understood in DBS of the subthalamic region in Parkinson's disease. We proposed an anatomic study based on direct image-guided stereotactic surgery with a multiple source data analysis. ::: Materials and Methods A manual anatomic mapping was realized on coronal 1.5-Tesla MRI of 15 patients. Biological data were collected under local anesthesia: the spontaneous neu-ron activities and the clinical efficiency and the appearance of adverse effects. They were related to relevant current values (mA), the benefit threshold (bt, minimal current leading an clear efficiency), the adverse effect threshold (at, minimal current leading an adverse effect) and the stimulation margin (sm = at − bt); they were matched with anatomy. ::: Results We found consistent relationships between anatomy and biological data. The optimal stimulation parameters (low bt + high sm) were noted in the dorsolateral STN. The highest spontaneous neuron activity was found in the ventromedial STN. Dorsolateral (sensorimotor) STN seems the main DBS effector. The highest spontaneous neuron activity seems related to the anterior (rostral) ventromedial (limbic) STN. ::: Conclusion 1.5 Tesla images provide sufficiently detailed sub-thalamic anatomy for image-guided stereotactic surgery and may aid in understanding DBS mechanisms. <s> BIB013 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> A commonly adopted surgical target in deep brain stimulation (DBS) procedures, the subthalamic nucleus (STN) is located deep within the brain and is surrounded by delicate deep-brain structures. Symptoms of Parkinson's disease can be reduced by precisely implanting a multi-electrode stimulator at a specific location within the STN and delivering the appropriate signal to the target. A number of techniques have recently been proposed to facilitate STN DBS surgical targeting and thereby improve the surgical outcome. This paper presents a retrospective study evaluating the target localization accuracy and precision of six approaches in 55 STN DBS procedures. The targeting procedures were performed using a neurosurgical visualization and navigation system, which integrates normalized and standardized anatomical and functional information into the planning environment. In this study, we employed as the “gold standard” the actual surgical target locations determined by an experienced neurosurgeon using both pre... <s> BIB014 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> The aim of the study was to investigate if laser Doppler perfusion monitoring (LDPM) can be used in order to differentiate between gray and white matter and to what extent microvascular perfusion can <s> BIB015 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Abstract Despite the clinical success of deep brain stimulation (DBS) for the treatment of movement disorders, many questions remain about its effects on the nervous system. This study presents a methodology to predict the volume of tissue activated (VTA) by DBS on a patient-specific basis. Our goals were to identify the intersection between the VTA and surrounding anatomical structures and to compare activation of these structures with clinical outcomes. The model system consisted of three fundamental components: (1) a 3D anatomical model of the subcortical nuclei and DBS electrode position in the brain, each derived from magnetic resonance imaging (MRI); (2) a finite element model of the DBS electrode and electric field transmitted to the brain, with tissue conductivity properties derived from diffusion tensor MRI; (3) VTA prediction derived from the response of myelinated axons to the applied electric field, which is a function of the stimulation parameters (contact, impedance, voltage, pulse width, frequency). We used this model system to analyze the effects of subthalamic nucleus (STN) DBS in a patient with Parkinson's disease. Quantitative measurements of bradykinesia, rigidity, and corticospinal tract (CST) motor thresholds were evaluated over a range of stimulation parameter settings. Our model predictions showed good agreement with CST thresholds. Additionally, stimulation through electrode contacts that improved bradykinesia and rigidity generated VTAs that overlapped the zona incerta/fields of Forel (ZI/H2). Application of DBS technology to various neurological disorders has preceded scientific characterization of the volume of tissue directly affected by the stimulation. Synergistic integration of clinical analysis, neuroimaging, neuroanatomy, and neurostimulation modeling provides an opportunity to address wide ranging questions on the factors linked with the therapeutic benefits and side effects of DBS. <s> BIB016 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> AIMS ::: To assess the variability of the subthalamic nucleus (STN) size, orientation and target coordinates from direct visualization on high-resolution magnetic resonance (MR) images in patients undergoing surgical intervention for Parkinson's disease. ::: ::: ::: METHODS ::: Sixty-six patients with Parkinson's disease were included in this study. The STN was visualized directly on high-resolution MR images, the size and orientation in both coronal and axial planes were recorded, as were the coordinates of the dorsolateral STN target in relation to the anterior-posterior commissural (AC-PC) line. The same STN target was defined in the Schaltenbrand atlas and atlas-based coordinates in proportion to the patient's AC-PC dimension were calculated. MR-imaging-based STN target coordinates were compared with the corresponding atlas-based coordinates. ::: ::: ::: RESULTS ::: Marked variation of STN size and orientation was observed. A significant difference was demonstrated on comparing left- and right-sided x and y coordinates. The comparison between MR-imaging-based and atlas-derived target coordinates demonstrated a significant difference in all directions except the left y coordinate. ::: ::: ::: CONCLUSIONS ::: This study demonstrates the substantial individual variability of STN size, orientation and target coordinates and a significant difference between target coordinates obtained by direct visual targeting on MR images and those obtained by indirect targeting based on atlases. <s> BIB017 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Background Over the last two decades, deep brain stimulation (DBS) has become a recognized and effective clinical therapy for numerous neurologic conditions. Since its inception, clinical DBS technology has progressed at a relatively slow rate; however, numerous advances in neural engineering research have the potential to improve DBS systems. One such advance is the concept of current steering, or the use of multiple stimulation sources to direct current flow through targeted regions of brain tissue. The goals of this study were to develop a theoretical understanding of the effects of current steering in the context of DBS, and use that information to evaluate the potential use of current steering during stimulation of the subthalamic nucleus. Methods We used finite element electric field models, coupled to multicompartment cable axon models, to predict the volume of tissue activated (VTA) by DBS as a function of the stimulation parameter settings. Results Balancing current flow through adjacent cathodes can increase the VTA magnitude, relative to monopolar stimulation, and current steering can be an effective technique to sculpt the shape of the VTA to fit a given anatomic target. Conclusions These results provide motivation for the integration of current steering technology into clinical DBS systems, thereby expanding opportunities to customize DBS to individual patients, and potentially enhancing therapeutic efficacy. <s> BIB018 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS. <s> BIB019 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in individuals with Parkinson’s disease (PD) has often been associated with reduced verbal fluency performance. This study aimed to directly assess semantic switching as a function of STN stimulation in PD participants with the Homophone Meaning Generation Test (HMGT). Seventeen participants with PD who had received STN DBS completed the HMGT in on and off stimulation conditions. Twenty-one non-neurologically impaired participants acted as controls. PD participants (in both on and off stimulation conditions) generated significantly fewer meanings than control participants and consistent with the previous reports of verbal fluency impairment, PD participants produced fewer definitions in the on stimulation condition. PD participants (in both on and off stimulation conditions) also had greater difficulty generating definitions for nonhomographic homophones compared with homographic homographs. The results of this study indicate that STN stimulation exacerbates impairment in semantic switching. (JINS, 2008, 14, 890–894.) <s> BIB020 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> BACKGROUND ::: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in patients with Parkinson's disease (PD) and improves their quality of life; however, the effect of DBS on cognitive functions and its psychiatric side-effects are still controversial. To assess the neuropsychiatric consequences of DBS in patients with PD we did an ancillary protocol as part of a randomised study that compared DBS with the best medical treatment. ::: ::: ::: METHODS ::: 156 patients with advanced Parkinson's disease and motor fluctuations were randomly assigned to have DBS of the STN or the best medical treatment for PD according to the German Society of Neurology guidelines. 123 patients had neuropsychological and psychiatric examinations to assess the changes between baseline and after 6 months. The primary outcome was the comparison of the effect of DBS with the best medical treatment on overall cognitive functioning (Mattis dementia rating scale). Secondary outcomes were the effects on executive function, depression, anxiety, psychiatric status, manic symptoms, and quality of life. Analysis was per protocol. The study is registered at ClinicalTrials.gov, number NCT00196911. ::: ::: ::: FINDINGS ::: 60 patients were randomly assigned to receive STN-DBS and 63 patients to have best medical treatment. After 6 months, impairments were seen in executive function (difference of changes [DBS-best medical treatment] in verbal fluency [semantic] -4.50 points, 95% CI -8.07 to -0.93, Cohen's d=-;0.4; verbal fluency [phonemic] -3.06 points, -5.50 to -0.62, -0.5; Stroop 2 naming colour error rate -0.37 points, -0.73 to 0.00, -0.4; Stroop 3 word reading time -5.17 s, -8.82 to -1.52, -0.5; Stroop 4 colour naming time -13.00 s, -25.12 to -0.89, -0.4), irrespective of the improvement in quality of life (difference of changes in PDQ-39 10.16 points, 5.45 to 14.87, 0.6; SF-36 physical 16.55 points, 10.89 to 22.21, 0.9; SF-36 psychological 9.74 points, 2.18 to 17.29, 0.5). Anxiety was reduced in the DBS group compared with the medication group (difference of changes in Beck anxiety inventory 10.43 points, 6.08 to 14.78, 0.8). Ten patients in the DBS group and eight patients in the best medical treatment group had severe psychiatric adverse events. ::: ::: ::: INTERPRETATION ::: DBS of the STN does not reduce overall cognition or affectivity, although there is a selective decrease in frontal cognitive functions and an improvement in anxiety in patients after the treatment. These changes do not affect improvements in quality of life. DBS of the STN is safe with respect to neuropsychological and psychiatric effects in carefully selected patients during a 6-month follow-up period. ::: ::: ::: FUNDING ::: German Federal Ministry of Education and Research (01GI0201). <s> BIB021 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> High frequency deep brain stimulation (HFS) used to treat the symptoms of Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation in GPi might produce this directly by mechanisms such as depolarization block or activation of presynaptic inhibitory fibers, and the same mechanisms evoked by HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on GPi neurons. Although somatic recordings from neurons near the stimulation site may appear to support this potential mechanism, the action downstream from the site of stimulation often is not consistent with this interpretation. A more parsimonious explanation for the similar effects of HFS in STN or GPi and a lesion of either of these structures is that both HFS and pallidotomy interrupt an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that is responsible for the symptoms of PD. <s> BIB022 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Surgery combining stereotactically guided implantation of brain electrodes in subcortical key structures of the brain with the connection of these brain electrodes to subcutaneously implanted impulse generators is one precondition for the therapeutic application of deep brain stimulation (DBS). During the last 10-15 years minimal requirements concerning this surgery have been formulated, addressing in particular technical equipment and operational procedures and being also in parts supported quantitatively by systematic investigations. Only appropriate patient management, high technical standards and an adequate surgical technique can minimize the frequency of those complications, which are supposed to be directly caused by surgery. High-resolution imaging is the basis for target definition, determination of the surgical approach, documentation of final electrode position and postoperative exclusion of iatrogenic intracerebral haemorrhage. In addition, the quality of treatment planning depends largely on the image processing and viewing possibilities provided by specific planning software. Further issues, for which standards are defined, address electrophysiological and clinical examinations to be performed intraoperatively and general surgical measures, which should be considered during implantation of DBS systems. This review summarizes and evaluates requirements imposed on the aforementioned system components and working steps, taking into consideration data from the literature. <s> BIB023 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> OBJECTIVE ::: After implantation of the first electrode in bilateral deep brain stimulation (DBS) lead implantation, brain shift effects in the target region and along the implantation trajectory of the second electrode are quantified with intraoperative magnetic resonance imaging (MRI). We investigated intraoperative X-ray imaging for its feasibility in indirect detection of brain shift. ::: ::: ::: METHODS ::: In 25 patients who underwent bilateral DBS lead implantation, X-ray and MRI were performed before and after implantation of the first electrode. Two parameters of brain shift were assessed with nonrigid free-form deformation field analysis of the MRI data: global brain shift along the anterior and posterior commissure (AC-PC) line and specific brain shift along the implantation trajectory of the second electrode. Pre- and intraoperative X-ray images were geometrically and intensity corrected for detection of significant signal changes through intracranial air accumulation during implantation of the first electrode. ::: ::: ::: RESULTS ::: After implantation of the first electrode, brain shift greater than 1 mm (maximum 1.3 mm) was observed at the AC and brain shift greater than 2 mm (maximum 2.5 mm) was observed along the planned implantation trajectory of the second electrode. In 1 patient, the implantation trajectory of the second electrode went through a sulcus after cortical brain shift. In 9 patients, intracranial air volume between 0.1 and 38.5 ml was observed with MRI after implantation of the first electrode. Significant X-ray absorption changes were induced by an intracranial air volume of greater than 8 ml. ::: ::: ::: CONCLUSION ::: In bilateral DBS implantation, brain shift effects can cause misallocation of the second electrode with the risk of adverse or no stimulation effects as well as unnecessary cortical damage. A lack of X-ray signal changes caused by intracranial air invasion during DBS lead implantation indicates a lack of clinically relevant brain shift. <s> BIB024 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> AIM ::: The aim of this study is to assess reflected light intensity combined with impedance as a navigation aid during stereotactic neurosurgery. ::: ::: ::: METHODS ::: During creation of 21 trajectories for stereotactic implantation of deep brain stimulation electrodes in the globus pallidus internus or subthalamus (zona incerta or subthalamic nucleus), impedance at 512 kHz and reflected light intensity at 780 nm were measured continuously and simultaneously with a radio frequency electrode containing optical fibres. The signals were compared with the anatomy, determined from pre- and post-operative MRI and CT. The measurements were performed within minutes, and signal analysis was done post-operatively. ::: ::: ::: RESULTS ::: Reflected light intensity was low from the cortex, lateral ventricle, caudate nucleus and putamen; intermediate from the globus pallidus and thalamus; while it was high from the subcortical white matter, internal capsule and subthalamus. The electrical impedance was less consistent, but generally low in the cortex, intermediate in the subcortical white matter, putamen, globus pallidus and thalamus, and high in the internal capsule and subthalamus. ::: ::: ::: CONCLUSION ::: Reflected light intensity and electrical impedance give complementary information about passed tissue, and the combination seems promising as a navigation aid during stereotactic neurosurgery. <s> BIB025 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease and related movement disorders. The success of DBS is highly dependent on electrode location, electrical parameter settings and the surgical procedure. In this paper an overview of the current status of optical measurements for intracerebral guidance performed during DBS implantation is presented. Laser Doppler perfusion monitoring and/or reflection spectroscopy measurements have been done in relation to more than 70 DBS lead implantations to wards targets in the deep brain structures. The techniques have also been compared with impedance monitoring, and simulation of the measurement depth has been done with Monte Carlo technique. These studies show that grey-white matter boundaries can be determined with a resolution higher than for both impedance measurements and magnetic resonance imaging. <s> BIB026 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Objective: Despite the clinical success of deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD), little is known about the electrical spread of the stimulation. The primary goal of this study was to integrate neuroimaging, neurophysiology and neurostimulation data sets from 10 patients with PD, unilaterally implanted with subthalamic nucleus (STN) DBS electrodes, to identify the theoretical volume of tissue activated (VTA) by clinically defined therapeutic stimulation parameters. Methods: Each patient specific model was created with a series of five steps: (1) definition of the neurosurgical stereotactic coordinate system within the context of preoperative imaging data; (2) entry of intraoperative microelectrode recording locations from neurophysiologically defined thalamic, subthalamic and substantia nigra neurons into the context of the imaging data; (3) fitting a three dimensional brain atlas to the neuroanatomy and neurophysiology of the patient; (4) positioning the DBS electrode in the documented stereotactic location, verified by postoperative imaging data; and (5) calculation of the VTA using a diffusion tensor based finite element neurostimulation model. Results: The patient specific models show that therapeutic benefit was achieved with direct stimulation of a wide range of anatomical structures in the subthalamic region. Interestingly, of the five patients exhibiting a greater than 40% improvement in their Unified PD Rating Scale (UPDRS), all but one had the majority of their VTA outside the atlas defined borders of the STN. Furthermore, of the five patients with less than 40% UPDRS improvement, all but one had the majority of their VTA inside the STN. Conclusions: Our results are consistent with previous studies suggesting that therapeutic benefit is associated with electrode contacts near the dorsal border of the STN, and provide quantitative estimates of the electrical spread of the stimulation in a clinically relevant context. <s> BIB027 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Deep-brain stimulation (DBS) surgery involves placing electrodes within specific deep-brain target nuclei. Surgeons employ MR imaging for preoperative selection of targets and computed tomography (CT) imaging for designing stereotactic frames used for intraoperative placement of electrodes at the targets. MR distortion may contribute to target-selection error in the MR scan and also to MR-CT registration error, each of which contributes to error in electrode placement. In this paper, we analyze the error contributed by the MR distortion to the total DBS targeting error. Distortion in conventional MR scans, both T1 and T2 weighted, were analyzed for six bilateral DBS patients in the typical areas of brain using typical scans on a 3-T clinical scanner. Mean targeting error due to MR distortion in T2 was found to be 0.07 ± 0.025 mm with a maximum of 0.13 mm over 12 targets; error in the T1 images was smaller by 4%. <s> BIB028 </s> Stereotactic implantation of deep brain stimulation electrodes: a review of technical systems, methods and emerging tools <s> Discussion and conclusion <s> Background/Aims: Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson’s disease. The aim of this study was to investigate the anat <s> BIB029
A review of the state-of-the art of technical aids for the stereotactic implantation procedure of deep brain stimulation electrodes has been presented. The preoperative planning, surgical intervention and postoperative follow-up of DBS electrodes include many steps and use a range of information-related technologies. A procedure is normally a full day surgery, and this makes it both time-and resourceconsuming. As the number of clinical indications and target areas are expected to increase and thus the number of implantation procedures, it is of outmost importance to Simulations MRI based planning Fig. 5 From ''mental imagination'' to ''intuitive visualisation'': the objective in the long term should be to replace the mental interpretation of the high quantity of intraoperatively obtained data by a software-guided data presentation BIB010 BIB013 make the different steps as effective as possible, but without increasing the surgical risks and jeopardise the final clinical outcome. For any stereotactic procedure, safe, accurate and precise targeting of the brain structure to be treated is essential for an optimal clinical outcome with minimal side disorders. In order to judge the implantation accuracy, it is important to be aware of limits and risks of the whole surgical procedure from the planning to the postoperative follow-up. In general, it is possible to distinguish between accuracy of the target identification on the anatomical images and the surgical precision. The former one includes the stereotactic image acquisition and the use of the images. While stereotactic CT acquisitions do not show any geometrical distortion due to the presence of the stereotactic frame, distortions of MR-images and the fiducials cannot be excluded. They have shown to be insignificant for specific MR sequences BIB028 BIB001 BIB003 . To avoid distortion, many centres coregister non-stereotactic MR to stereotactic CT images for the preoperative planning. The accuracy of the coregistration seems to remain in acceptable limits BIB011 BIB023 , around 1.3 mm for example when applying the mutual information algorithm BIB004 . Groups using anatomical atlases during the targeting procedure have to be aware of the uncertainties introduced by the non-rigid MRI/atlas fusion BIB014 BIB005 due to the interindividual anatomical variations. It has been shown that, especially in case of GPi and STN targeting, the direct method has obvious benefits over indirect atlas-based targeting BIB012 BIB017 BIB023 . Another factor influencing the planning accuracy is the identification of the stereotactic reference system which is the basis for the target calculation. Depending on how many image slices are used for the calculation of the transformation parameters and how the fiducial points are identified, automatically or semi-automatically, target coordinates can slightly differ. In addition to all these factors influencing the planning accuracy, especially two aspects have to be considered concerning the surgical accuracy. First, there is the application accuracy of the frame systems themselves, i.e. the targeting precision, which has been estimated for the different probe positions and stereotactic frames by Zylka et al. BIB002 . They studied imaging accuracy and mechanical errors and came to the result that frame systems equipped with a phantom base allow compensating for mechanical inaccuracies and errors. The second phenomenon introducing an inaccuracy, but difficult to predict, is the ''brain shift''. The only way to reduce the causing liquid loss is to keep the burr hole as small as possible and to perform the surgery as fast as possible BIB024 . Intracerebral measurements can help the surgeon to compensate for the ''brain shift''. The paper has also reviewed a number of emerging tools, several of them being research prototypes today but with great potential to become available in the health care system in the near future. Among these, further development of established brain stimulation electrodes and new stimulation devices developed for specific treatments are expected to push the use of DBS. Miniaturised cranial implantable pulse generators are suggested in order to make the entire surgical procedure as one incision  and steering of the electric field for tailoring the treatment and reduce potential side disorders  BIB018 . However, even with such improvements, the implantation procedure of DBS electrodes will still require stereotactic surgery and support from technical aids. Furthermore, imaging quality related to MRI and DTI is expected to improve and may in the future make ''invisible'' structures possible to visualise. Transcranial sonography may become as well an interesting and promising complementary monitoring technique if the highly echogenic imaging artefacts of the metal parts of the electrode can be reduced. It may allow further intraoperative refinement of the electrode position as well as simultaneous prevention of haemorrhages. Despite this, the ''brain shift'' will still be an obstacle to overcome, and intraoperative measurements will therefore still be required. To date, microelectrode recording is the most commonly used technique for intracerebal identification of the DBS target areas. Being well established, MER is however sometimes questioned, and some researchers point out that the thin needles used may increase the risk of bleeding and does not guarantee proper targeting BIB006 BIB007 . Furthermore, MER can be relatively time-consuming; as the signals are in general studied in the time domain, they may be difficult to interpret in real time. Optical measurements  BIB025 BIB015 are a highly interesting alternative to MER. It has the advantage of real time presentation of grey-white boundaries passed during probe insertion. A recording is done within minutes. In addition to grey-white boundary determination, vessels in the vicinity to, and along the trajectory, may be detected by means of simultaneous microvascular recordings with laser Doppler technique BIB026 . By using a multipurpose probe, the optical measurements can be combined with impedance recordings BIB025 . The optical alternative to MER could be especially beneficial for newer target areas, where well-defined grey-white matter boundaries are passed as the tissue is ''seen'' before it is reached. An additional promising tool for exploring new target areas is the use of patient-specific models and simulations of the electric field BIB019 BIB016 . These can also be used to advance and optimise the treatment of an individual patient, and act as a tool for training and for simulation of electric field in target areas before the actual surgical procedure is done. Such simulations can allow for 3D visualisations of the electric field influenced by the stimulation and match it to the patient's clinical outcome BIB029 BIB027 . As DBS has become more commonly used, there have been increasing reports of postoperative neuropsychiatric complications, including depression, behaviour problems, aggression and language disturbances BIB020  BIB021 . Even though several hypothesis of the fundamental mechanisms exist underlying both the therapeutic effects and the adverse side effects of DBS, the mechanism remains largely unknown BIB008  BIB022 BIB009 . In a broader context, simulations can, together with, e.g. neuroimaging, biochemical monitoring and neuronal mapping, be one additional corner stone for increased knowledge of the DBS mechanisms. Another important and selfevident basis of the analysis of the mechanism of action of DBS is the obtained clinical result. Here appears the problem of the comparability of the evaluations performed by different medical doctors and in different medical centres. For Parkinson patients, for example, it is crucial to assess the severity of the cardinal Parkinson disease symptoms (tremor, bradykinesia, rigidity and postural instability) and dyskinesia to document the clinical changes quantitatively. Current methods such as the Unified Parkinson's Disease Rating Scale (UPDRS)  are mainly semi-quantitative and not fully objective: these clinical scales rely on ordinal ratings based on descriptive terms such as ''mild'', ''moderate'' and ''severe''. The literature review has shown that many groups have worked on quantitative movement pattern analysis, but that there is no gold standard and no complete pre-and postoperative evaluation of all Parkinson's disease symptoms. This is valid as well for the intraoperative evaluation process. Only few groups have tried to introduce quantitative measurement methods in the operating theatre which could further increase the precision of the target choice. For other disorders treated with DBS, such as psychiatric illness, techniques in parallel to movement pattern monitoring should be developed in order to optimise the objectivity of the clinical evaluation. Another key point which could improve the surgical decision-making process would be to introduce data and information technologies in the DBS procedure, i.e. by means of ''intuitive visualisation'' of parameters and images recorded in relation to the intervention. As already mentioned, existing homemade and commercialised software provides in general an integration of microelectrode recordings with the patients MR images and sometimes as well with the test stimulation results. An extended system for visualisation of additional parameters could include presentation of the patient MR batch of images together with the DBS electric field simulation or physiological information such as tissue impedance, neural activity recorded by MER, grey-white boundaries, microvascular perfusion related to small vessel structures or tissue chromophores measured by optics. Furthermore, depending on clinical symptoms for the implantation procedure, movement pattern could be included. In consequence, there still seems to be a high potential to optimise the surgery and its precision by means of objectification and improved data management for patients suffering from various movement disorders or other diseases treated by deep brain stimulation.