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MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety
Abstract
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology & Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording (MER). Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinson´s Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 (PDQ39) summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.
... Current clinical approaches to surgical planning for DBS rely on imaging interpretation and processing, including magnetic resonance imaging (MRI)-based direct targeting ( Holl et al., 2010;Foltynie et al., 2011;Aviles-Olmos et al., 2014) and image fusion techniques using co-registration with computed tomography (CT) and 1.5T and 3T MRI ( Neumann et al., 2015). Atlasbased coordinates can be used when visualization of targets is insufficient, or to improve accuracy ( Kochunov et al., 2002). ...
... We investigated DBS in the subthalamic nucleus (STN) and in the posterior subthalamic area, a closely related target ( Plaha et al., 2008;Blomstedt et al., 2009Blomstedt et al., , 2010). The STN is an important target for Parkinson's disease ( Bejjani et al., 2000;Foltynie et al., 2011;Aviles-Olmos et al., 2014) and the posterior subthalamic area is an effective target for essential tremor ( Plaha et al., 2008;Blomstedt et al., 2009Blomstedt et al., , 2010. ...
... For the STN target in Patient 2, the ratio between C and D was 20:2 and the ratio between C and E was 20:1. Thus, the posterior STN target (Blomstedt et al., 2009(Blomstedt et al., , 2010) is more posteriorly located than the STN target, which is closer to the red nuclei anterior margin line (Foltynie et al., 2011;Aviles-Olmos et al., 2014). ...
Background
The purpose of the present study was to evaluate deep learning-based image-guided surgical planning for deep brain stimulation (DBS). We developed deep learning semantic segmentation-based DBS targeting and prospectively applied the method clinically.
Methods
T2∗ fast gradient-echo images from 102 patients were used for training and validation. Manually drawn ground truth information was prepared for the subthalamic and red nuclei with an axial cut ∼4 mm below the anterior–posterior commissure line. A fully convolutional neural network (FCN-VGG-16) was used to ensure margin identification by semantic segmentation. Image contrast augmentation was performed nine times. Up to 102 original images and 918 augmented images were used for training and validation. The accuracy of semantic segmentation was measured in terms of mean accuracy and mean intersection over the union. Targets were calculated based on their relative distance from these segmented anatomical structures considering the Bejjani target.
Results
Mean accuracies and mean intersection over the union values were high: 0.904 and 0.813, respectively, for the 62 training images, and 0.911 and 0.821, respectively, for the 558 augmented training images when 360 augmented validation images were used. The Dice coefficient converted from the intersection over the union was 0.902 when 720 training and 198 validation images were used. Semantic segmentation was adaptive to high anatomical variations in size, shape, and asymmetry. For clinical application, two patients were assessed: one with essential tremor and another with bradykinesia and gait disturbance due to Parkinson’s disease. Both improved without complications after surgery, and microelectrode recordings showed subthalamic nuclei signals in the latter patient.
Conclusion
The accuracy of deep learning-based semantic segmentation may surpass that of previous methods. DBS targeting and its clinical application were made possible using accurate deep learning-based semantic segmentation, which is adaptive to anatomical variations.
... Despite significant advances in neuroimaging technology over the past decades, routinely acquired preoperative brain magnetic resonance imaging (MRI) sequences remain deficient at directly visualizing DBS targets for stereotactic planning purposes [7,8]. Some groups have developed dedicated MRI sequences that visualize some of the anatomical structures commonly targeted during DBS surgery on MRI at 1.5-T field strengths such as the STN [9][10][11][12] and the posteroventral GPi [13,14]. Nevertheless, some commonly used targets, such as the VIM, cannot be visualized on 1.5-T structural MRI, and many groups have continued to use indirect targeting methods when performing DBS-relying on identifiable surrogate anatomical landmarks and coupled with other techniques such as intraoperative microelectrode recordings (MER) and/or clinical evaluation in awake patients [15]. ...
Purpose of Review
Ablations and particularly deep brain stimulation (DBS) of a variety of CNS targets are established therapeutic tools for movement disorders. Accurate targeting of the intended structure is crucial for optimal clinical outcomes. However, most targets used in functional neurosurgery are sub-optimally visualized on routine MRI. This article reviews recent neuroimaging advancements for targeting in movement disorders.
Recent Findings
Dedicated MRI sequences can often visualize to some degree anatomical structures commonly targeted during DBS surgery, including at 1.5-T field strengths. Due to recent technological advancements, MR images using ultra-high magnetic field strengths and new acquisition parameters allow for markedly improved visualization of common movement disorder targets. In addition, novel neuroimaging techniques have enabled group-level analysis of DBS patients and delineation of areas associated with clinical benefits. These areas might diverge from the conventionally targeted nuclei and may instead correspond to white matter tracts or hubs of functional networks.
Summary
Neuroimaging advancements have enabled improved direct visualization-based targeting as well as optimization and adjustment of conventionally targeted structures.
... The stereotactic coordinates of the center of each active contact were identified on an intra-operative stereotactic MRI scan (T2 weighted) acquired immediately following lead implantations. The coordinates were then superimposed onto the pre-implantation stereotactic T2- weighted MRI scan (20). From these images, the electrode contact locations were allocated to five regions of the STN (superior, postero-lateral, central, inferior, and antero-medial). ...
Axial symptoms emerge in a significant proportion of patients with Parkinson's disease (PD) within 5 years of deep brain stimulation (STN-DBS). Lowering the stimulation frequency may reduce these symptoms. The objectives of the current study were to establish the relationship between gait performance and STN-DBS frequency in chronically stimulated patients with PD, and to identify factors underlying variability in this relationship. Twenty-four patients treated chronically with STN-DBS (>4 years) were studied off-medication. The effect of stimulation frequency (40–140 Hz, 20 Hz-steps, constant energy) on gait was assessed in 6 sessions spread over 1 day. Half of the trials/session involved walking through a narrow doorway. The influence of stimulation voltage was investigated separately in 10 patients. Gait was measured using 3D motion capture and axial symptoms severity was assessed clinically. A novel statistical method established the optimal frequency(ies) for each patient by operating on frequency-tuning curves for multiple gait parameters. Narrowly-tuned optimal frequencies (20 Hz bandwidth) were found in 79% of patients. Frequency change produced a larger effect on gait performance than voltage change. Optimal frequency varied between patients (between 60 and 140 Hz). Contact site in the right STN and severity of axial symptoms were independent predictors of optimal frequency (P = 0.009), with lower frequencies associated with more dorsal contacts and worse axial symptoms. We conclude that gait performance is sensitive to small changes in STN-DBS frequency. The optimal frequency varies considerably between patients and is associated with electrode contact site and severity of axial symptoms. Between-subject variability of optimal frequency may stem from variable pathology outside the basal ganglia.
... Electrode implantation is done under local or generalized anesthesia, with or without electrophysiological recordings, and with or without perioperative psychological and neurological tests ( Lefaucheur et al., 2008;Xie et al., 2010;Chen et al., 2011;Foltynie et al., 2011). DBS is a relatively safe method with a mortality rate below 0.3% ( Voges et al., 2006;McGovern et al., 2013). ...
Accumulating evidence suggests that non-invasive and invasive brain stimulation may reduce food craving and calorie consumption rendering these techniques potential treatment options for obesity. Non-invasive transcranial direct current stimulation (tDCS) or repetitive transcranial magnet stimulation (rTMS) are used to modulate activity in superficially located executive control regions, such as the dorsolateral prefrontal cortex (DLPFC). Modulation of the DLPFC’s activity may alter executive functioning and food reward processing in interconnected dopamine-rich regions such as the striatum or orbitofrontal cortex. Modulation of reward processing can also be achieved by invasive deep brain stimulation (DBS) targeting the nucleus accumbens. Another target for DBS is the lateral hypothalamic area potentially leading to improved energy expenditure. To date, available evidence is, however, restricted to few exceptional cases of morbid obesity. The vagal nerve plays a crucial role in signaling the homeostatic demand to the brain. Invasive or non-invasive vagal nerve stimulation (VNS) is thus assumed to reduce appetite, rendering VNS another possible treatment option for obesity. Based on currently available evidence, the U.S. Food and Drug Administration recently approved VNS for the treatment of obesity. This review summarizes scientific evidence regarding these techniques’ efficacy in modulating food craving and calorie intake. It is time for large controlled clinical trials that are necessary to translate currently available research discoveries into patient care.
... This study is the first to our knowledge that compares both the initial and long-term stimula- tion effects of DBS lead placement in the STN, between MER and iMRI approaches, in a contemporaneous cohort. Our findings are consistent with research that demonstrates similar accuracy and clinical outcome between MER-based strategies (4, 23) and non- MER direct targeting approaches (11,13,14,18,32,33). Thus, our results add further confirmation that anatomic validation of targeting is equivalent to traditional functional validation with MER. ...
In deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD), there is debate concerning the use of neuroimaging alone to confirm correct anatomic placement of the DBS lead into the STN, versus the use of microelectrode recording (MER) to confirm functional placement. We performed a retrospective study of a contemporaneous cohort of 45 consecutive patients who underwent either interventional-MRI (iMRI) or MER-guided DBS lead implantation. We compared radial lead error, motor and sensory side effect, and clinical benefit programming thresholds, and pre- and post-operative unified PD rating scale scores, and levodopa equivalent dosages. MER-guided surgery was associated with greater radial error compared to the intended target. In general, side effect thresholds during initial programming were slightly lower in the MER group, but clinical benefit thresholds were similar. No significant difference in the reduction of clinical symptoms or medication dosage was observed. In summary, iMRI lead implantation occurred with greater anatomic accuracy, in locations demonstrated to be the appropriate functional region of the STN, based on the observation of similar programming side effect and benefit thresholds obtained with MER. The production of equivalent clinical outcomes suggests that surgeon and patient preference can be used to guide the decision of whether to recommend iMRI or MER-guided DBS lead implantation to appropriate patients with PD.
BACKGROUND
Deep brain stimulation (DBS) is well-established, evidence-based therapy for Parkinson disease, essential tremor, and primary dystonia. Clinical outcome studies have recently shown that “asleep” DBS lead placement, performed using intraoperative imaging with stereotactic accuracy as the surgical endpoint, has motor outcomes comparable to traditional “awake” DBS using microelectrode recording (MER), but with shorter case times and improved speech fluency.
OBJECTIVE
To identify procedural variables in DBS surgery associated with improved surgical efficiency and stereotactic accuracy.
METHODS
Retrospective review of 323 cases with 546 leads placed (August 2011-October 2014). In 52% (n = 168) of cases, patients were asleep under general anesthesia without MER. Multivariate regression identified independent predictors of reduced surgery time and improved stereotactic accuracy.
RESULTS
MER was an independent contributor to increased procedure time (+44 min; P = .03). Stereotactic accuracy was better in asleep patients. Accuracy was improved with frame-based stereotaxy at head of bed 0° vs frameless stereotaxy at head of bed 30°. Improved accuracy was also associated with shorter procedures (r = 0.17; P = .049). Vector errors were evenly distributed around the planned target for the globus pallidus internus, but directionally skewed for the subthalamic (medial-posterior) and ventral intermediate nuclei (medial-anterior).
CONCLUSION
Distinct procedural variables in DBS surgery are associated with reduced case times and improved stereotactic accuracy.
BACKGROUND: A calibration technique that shifts the frame coordinates from the intended coordinates to correct a systematic stereotactic error has been reported for single-brain-pass deep brain stimulation.
OBJECTIVE: To analyze the intercenter reproducibility of this method for deep brain stimulation.
METHODS: A total of 310 leads from 166 patients undergoing surgery were analyzed, including 220 multitrack (primarily 3-track) subthalamic nucleus leads, 17 single-brain-pass subthalamic nucleus leads, and 73 single-brain-pass globus pallidus interna leads. We adopted the previously reported calibration factors. Calibration shifts the frame coordinates from the target coordinates to the left, anterior, and inferior directions by 0, 0.5, or 1 mm, respectively, according to the arc angles in each axis. We analyzed 9 subgroups of single-brain-pass, multitracks, operated sides, technical, and instrumental variations.
RESULTS: In total, the stereotactic error decreased from 1.5 ± 0.8 mm in the distance to the frame coordinates (error calculation before using the calibration technique) to 1.1 ± 0.6 mm in the distance to the intended target coordinates (error after using the calibration technique, 28% reduction, P < .000001). Frame-related errors were 0.1 to 0.3 mm when measured with the stereotactic simulator. The reduction of stereotactic errors by the calibration technique (median 0.4 mm, 0.1-0.7 mm, median 28%, 7%-45% in each subgroup) was significant in 8 of the 9 subgroups (P < .05).
CONCLUSION: Calibration is an effective and reproducible method for reducing systematic stereotactic errors both in single-brain-pass and multitrack deep brain stimulations, as well as in both sides using various instrumental and technical conditions.
BACKGROUND: Brain shift and pneumocephalus are major concerns regarding deep brain stimulation (DBS).
OBJECTIVE: To report the extent of brain shift in deep structures and pneumocephalus in intraoperative magnetic resonance imaging (MRI).
METHODS: Twenty patients underwent bilateral DBS implantation in an MRI suite. Volume of pneumocephalus, duration of procedure, and 6 anatomic landmarks (anterior commissure, posterior commissure, right fornix [RF], left fornix [LF], right putaminal point, and left putaminal point) were measured.
RESULTS: Pneumocephalus varied from 0 to 32 mL (median = 0.6 mL). Duration of the procedure was on average 195.5 min (118-268 min) and was not correlated with the amount of pneumocephalus. There was a significant posterior displacement of the anterior commissure (mean = −1.1 mm, P < .001), RF (mean = −0.6 mm, P < .001), LF (mean = −0.7 mm, P < .001), right putaminal point (mean = −0.9 mm, P = .001), and left putaminal point (mean = −1.0 mm, P = .001), but not of the posterior commissure (mean = 0.0 mm, P = .85). Both RF (mean = −.7 mm, P < .001) and LF (mean = −0.5 mm, P < .001) were posteriorly displaced after a right-sided burr hole. There was a correlation between anatomic landmarks displacement and pneumocephalus after 2 burr holes (rho = 0.61, P = .007), but not after 1 burr hole (rho = 0.16, P = .60).
CONCLUSION: Better understanding of how pneumocephalus displaces subcortical structures can significantly enhance our intraoperative decision making and overall targeting strategy.
Objectives:
Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.
Methods:
High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.
Results:
All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -13(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.
Interpretation:
These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.
Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures.
To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking.
Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift.
Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation.
The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.
CST, corticospinal tractDBS, deep brain stimulationDTI, diffusion tensor imagingfMRI, functional magnetic resonance imagingGPi, globus pallidus internusGRAPPA, generalized autocalibrating partially parallel acquisitionsMD, minimal distanceMEP, motor evoked potentialnTMS, navigated transcranial magnetic stimulationROI, regions of interestSTN, subthalamic nucleusVIM, ventral intermediate nucleus.
Microelectrode recording helps surgeons accurately localize boundaries of the subthalamic nucleus (STN) and surrounding structures in deep brain stimulation.
To describe a novel adaptation of the Ben's gun device to optimize efficient mapping.
Patients who underwent STN deep brain stimulation over a 3-year period were reviewed. For the final year, the Ben's gun was rotated 45 degrees and the target was offset 1.4 mm lateral and anterior in the plane orthogonal to the intended trajectory to allow for simultaneous parallel tracks at target, 2.8 mm anterior (localizing the front of STN), and 2.8 mm lateral (identifying the internal capsule). Prior to this step, the initial pass consisted of 1-2 tracks with the frame center targeted to STN. Primary outcome measure was the number of passes required for accurate localization of the nucleus and boundaries.
83 electrodes were implanted in 45 patients (mean age 62, range 37-78 years), of which 29 electrodes were placed using the new technique. One electrode (4%) required more than one pass using the new technique compared with 36 (67%) using the older technique (p < 0.01). Distance from original target to final electrode position increased from 0.67 +/- 0.13 mm to 1.06 +/- 0.15 mm (p < 0.05) with a greater tendency to move the final electrode position posteriorly. There was no statistically significant difference in benefit from neurostimulation.
This technique facilitates reliable localization of the STN with fewer passes, possibly decreasing risks associated with more passes and longer duration of surgery.
Image distortion limits direct 3T MR image application for stereotactic functional neurosurgery.
To test the application of a method to correct and curtail image distortion for 3T MR images.
We used a phantom head model mounted on a platform with the dimensions and features of a stereotactic frame. The phantom was scanned within the head coil of a Philips Achieva 3T X series ™. For each scan, 2 images were obtained-the normal and the reversed image (nMR and rMR, respectively). We applied the inverted gradient correction protocol to produce a corrected x, y and z coordinate. We applied the Cronbach test or coefficient of reliability to assess the internal consistency of the data.
For all analyzed data, the P value was above .05, indicating that the differences among the observers were not statistically significant. Moreover, the data rectification proved to be effective, as the average distortion after correction was 1.05 mm. The distortion varied between 0.7 mm and 3.7 mm, depending on the target location.
This study examined a rectifying technique for correcting geometric distortions encountered in the MR images related to static field inhomogeneities (resonance offsets), and the technique proved to be highly successful in producing consistently accurate stereotactic target registration. The technique is applicable to all routinely employed spin-echo MR images.
Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l-dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype-phenotype relationships.
Background:
The goal of our study was to investigate the influence of intraoperative microelectrode recordings and clinical testing on the location of the final stimulation site in deep brain stimulation in Parkinson's disease.
Methods:
In 22 patients with Parkinson's disease we compared magnetic resonance imaging (MRI)-based and atlas-based targets with the adjusted stimulation sites after intraoperative, multitrack microelectrode recording (MER) and intraoperative and postoperative clinical testing. The investigation included 176 target/stimulation sites in 44 subthalamic nuclei (STNs), which were related to a standardised three-dimensional, MRI-defined STN.
Results:
Atlas-based targets were positioned more superior and more medial than the MRI-based targets, which were located in the centre of the MRI-STN. The optimal stimulation sites, found intraoperatively after MER and clinical testing, were located more lateral and slightly more superior than both planned targets. In the majority of the cases the location of the active contact was the most superior and most lateral of all target sites. The differences in the distributions of those four targets reached statistical significance. However, final active contacts were distributed throughout the MRI-defined STN and its immediate surroundings.
Conclusions:
The adoption of microelectrode recordings and extensive clinical testing allows the adjustment of anatomical targeting even to unexpected stimulation sites in and around the MRI-defined STN.
Dear Sirs,Chorea-acanthocytosis (ChAc) belongs to the group ofneuroacanthocytosis (NA) syndromes and is predominantlymanifested by chorea and orofacial dyskinesias [1, 2].Deep brain stimulation (DBS) has been used as an exper-imental treatment in a limited number of refractory cases ofChAc, showing variable outcomes [3–9]. In this report wedescribe the effect of high-frequency DBS of globus pal-lidus internus (GPi) in two patients suffering from severeintractable ChAc.Patient 1 (54-year-old male) suffered from a movementdisorder, including orofacial dyskinesias and feeding dys-tonia, as well as violent trunk spasms. Patient 2 (43-year-old male) had developed a severe movement disorder withoromandibular dyskinesias, dysarthria, violent choreicmovements of upper and lower limbs, a lurching gait withoccasional axial spasms (head-drops) and poor balance. Inboth patients, investigations revealed acanthocytosis, andMRI scans showed atrophy predominantly in the caudatenuclei. Absence of chorein on western blot confirmed thediagnosis of ChAc. Conventional treatments, such as tet-rabenazine, atypical antipsychotic agents, and botulinumtoxin injections, were insufficient, and both patients wereseverely incapacitated by their involuntary movements.Hence, a trial of DBS was offered. Implantation of bilateralDBS electrodes (3389 Medtronic, Minneapolis, MN) intothe GPi was performed under general anaesthesia [10–12].Following introduction of stimulation there was sub-stantial attenuation of involuntary movements with com-plete resolution of uncontrolled mouth movements inpatient 1, allowing him to eat without involuntarily ejectingfood. Upper limb dexterity improved markedly, truncaldips almost disappeared, and he was able to walk unaidedfor a mile without difficulty, in marked contrast to hissituation before surgery (Table 1).In patient 2, high-frequency stimulation led to aremarkable reduction of choreic movements, accompaniedby a significant improvement in walking and truncal spasms(Table 1). Battery removal and intravenous antibiotictreatment was necessary 8 weeks following surgery due toIPG infection. Microbiological testing confirmed Staphy-lococcus aureus. Due to a marked rebound of patient’schorea, a new IPG was re-implanted on day 13, and thebeneficial effect in his chorea was rapidly regained.Removal of all implants was required due to developmentof an intra-cerebral pallidal abscess, 1 month later (Fig. 1c).Microbiological testing confirmed Staphylococcus aureusinfection and this was treated with linezolid for 2 weeksintravenously and for further 4 weeks orally, followed by
Object:
Reliable visualization of the subthalamic nucleus (STN) is indispensable for accurate placement of electrodes in deep brain stimulation (DBS) surgery for patients with Parkinson disease (PD). The aim of the study was to evaluate different promising new MRI methods at 3.0 T for preoperative visualization of the STN using a standard installation protocol.
Methods:
Magnetic resonance imaging studies (T2-FLAIR, T1-MPRAGE, T2*-FLASH2D, T2-SPACE, and susceptibility-weighted imaging sequences) obtained in 9 healthy volunteers and in 1 patient with PD were acquired. Two neuroradiologists independently analyzed image quality and visualization of the STN using a 6-point scale. Interrater reliability, contrast-to-noise ratios, and signal-to-noise ratios for the STN were calculated. For illustration of the anatomical accuracy, coronal T2*-FLASH2D images were fused with the corresponding coronal section schema of the Schaltenbrand and Wahren stereotactic atlas.
Results:
The STN was best and reliably visualized on T2*-FLASH2D imaging (in particular, the coronal view). No major artifacts in the STN were observed in any of the sequences. Susceptibility-weighted, T2-SPACE, and T2*-FLASH2D imaging provided significantly higher contrast-to-noise ratio values for the STN than standard T2-weighted imaging. Fusion of the coronal T2*-FLASH2D and the digitized coronal atlas view projected the STN clearly within the boundaries of the STN found in anatomical sections.
Conclusions:
For 3.0-T MRI, T2*-FLASH2D (particularly the coronal view) provides optimal delineation of the STN using a standard installation protocol.
Precision is the ultimate aim of stereotactic technique. Demands on stereotactic precision reach a pinnacle in stereotactic functional neurosurgery. Pitfalls are best avoided by possessing in-depth knowledge of the techniques employed and the equipment used. The engineering principles of arc-centered stereotactic frames maximize surgical precision at the target, irrespective of the surgical trajectory, and provide the greatest degree of surgical precision in current clinical practice. Stereotactic magnetic resonance imaging (MRI) provides a method of visualizing intracranial structures and fiducial markers on the same image without introducing significant errors during an image fusion process. Although image distortion may potentially limit the utility of stereotactic MRI, near-complete distortion correction can be reliably achieved with modern machines. Precision is dependent on minimizing errors at every step of the stereotactic procedure. These steps are considered in turn and include frame application, image acquisition, image manipulation, surgical planning of target and trajectory, patient positioning and the surgical procedure itself. Audit is essential to monitor and improve performance in clinical practice. The level of stereotactic precision is best analyzed by routine postoperative stereotactic MRI. This allows the stereotactic and anatomical location of the intervention to be compared with the anatomy and coordinates of the intended target, avoiding significant image fusion errors.
The authors analyze long-term outcome in a substantial number of patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) surgery under general anesthesia.
Eighty-two patients underwent bilateral placement of DBS electrodes under general anesthesia for advanced Parkinson disease; the STN was the target in all cases. All patients underwent intraoperative microelectrode recording of the STN. No intraoperative macrostimulation was performed. Unified Parkinson's Disease Rating Scale (UPDRS) data were recorded in 28 patients. Assessment of outcome was performed using the UPDRS (in 28 cases), the electrophysiological recordings (in all 82 cases), medication reduction (in 78 cases), and complications (in 82 cases).
There was improvement in UPDRS scores across all measures following surgery. The total UPDRS score, off medication, improved from 68.78 (geometrical mean, 95% CI 61.76-76.60) preoperatively to 45.89 (geometrical mean, 95% CI 34.86-60.41) at 1 year postoperatively (p = 0.003, data available in 26 patients). Improvements were obtained in UPDRS Part II (Activities of Daily Living) off medication (p = 0.001) and also UPDRS Part III (Motor Examination) off medication (p < 0.001). Results for the on-medication and on-stimulation states also showed a statistically significant improvement for UPDRS Part III (p = 0.047). Good microelectrode recording of the STN was obtained under general anesthesia; the median first-track length was 4.0 mm, and the median number of tracks passed per patient was 3.0. The median reduction in levodopa medication was 58.1% (interquartile range 42.9%-73.3%). One patient had an intracerebral hemorrhage in the track of 1 electrode but did not require surgical evacuation. One patient had generalized convulsive seizures 24 hours postoperatively and was intubated for seizure control. Unified Parkinson's Disease Rating Scale scores were obtained in 26 patients at 1 year, 28 patients at 3 years, 17 at 5 years, and 7 at 7 years postoperatively. Up to 7 years postoperatively, there was sustained improvement in the total UPDRS score. The results in these patients showed minimal deterioration in the motor section of the UPDRS over time, up to 7 years following the operation. The authors found no evidence that the UPDRS Part II scores changed significantly over the period of 1-7 years after surgery (p = 0.671, comparison of mean scores at 1 and 7 years using generalized estimating equations).
Long-term outcomes confirm that it is both safe and effective to perform STN DBS under general anesthesia. As part of patient choice, this option should be offered to all DBS candidates with advanced Parkinson disease to enable more of these patients to undergo this beneficial surgery.
Hemorrhagic complications carry by far the highest risk of devastating neurological outcome in functional neurosurgery. Literature published over the past 10 years suggests that hemorrhage, although relatively rare, remains a significant problem. Estimating the true incidence of and risk factors for hemorrhage in functional neurosurgery is a challenging issue.
The authors analyzed the hemorrhage rate in a consecutive series of 214 patients undergoing image-guided deep brain stimulation (DBS) lead placement without microelectrode recording (MER) and with routine postoperative MR imaging lead verification. They also conducted a systematic review of the literature on stereotactic ablative surgery and DBS over a 10-year period to determine the incidence and risk factors for hemorrhage as a complication of functional neurosurgery.
The total incidence of hemorrhage in our series of image-guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing permanent deficit in 0.0% of patients. Weighted means calculated from the literature review suggest that the overall incidence of hemorrhage in functional neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients, symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or death in 1.1%. Hypertension and age were the most important patient-related factors associated with an increased risk of hemorrhage. Risk factors related to surgical technique included use of MER, number of MER penetrations, as well as sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage in studies adopting an image-guided and image-verified approach without MER was significantly lower than that reported with other operative techniques (p < 0.001 for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004 for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent deficit; Fisher exact test).
Age and a history of hypertension are associated with an increased risk of hemorrhage in functional neurosurgery. Surgical factors that increase the risk of hemorrhage include the use of MER and sulcal or ventricular incursion. The meticulous use of neuroimaging-both in planning the trajectory and for target verification-can avoid all of these surgery-related risk factors and appears to carry a significantly lower risk of hemorrhage and associated permanent deficit.
Accurate placement of a probe to the deep regions of the brain is an important part of neurosurgery. In the modern era, magnetic resonance image (MRI)-based target planning with frame-based stereotaxis is the most common technique.
To quantify the inaccuracy in MRI-guided frame-based stereotaxis and to assess the relative contributions of frame movements and MRI distortion.
The MRI-directed implantable guide-tube technique was used to place carbothane stylettes before implantation of the deep brain stimulation electrodes. The coordinates of target, dural entry point, and other brain landmarks were compared between preoperative and intraoperative MRIs to determine the inaccuracy.
The mean 3-dimensional inaccuracy of the stylette at the target was 1.8 mm (95% confidence interval [CI], 1.5-2.1. In deep brain stimulation surgery, the accuracy in the x and y (axial) planes is important; the mean axial inaccuracy was 1.4 mm (95% CI, 1.1-1.8). The maximal mean deviation of the head frame compared with brain over 24.1 ± 1.8 hours was 0.9 mm (95% CI, 0.5-1.1). The mean 3-dimensional inaccuracy of the dural entry point of the stylette was 1.8 mm (95% CI, 1.5-2.1), which is identical to that of the target.
Stylette positions did deviate from the plan, albeit by 1.4 mm in the axial plane and 1.8 mm in 3-dimensional space. There was no difference between the accuracies at the dura and the target approximately 70 mm deep in the brain, suggesting potential feasibility for accurate planning along the whole trajectory.
Deep brain stimulation of the subthalamic nucleus is an accepted treatment for the motor complications of Parkinson's disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clinical neurophysiology suggests that the effects of subthalamic nucleus-deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Positron emission tomography/single-photon emission computed tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus-deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarifying whether clinically relevant effects from subthalamic nucleus-deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or antidromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus-deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation.
Deep brain stimulation of the subthalamic nucleus is the standard of care for treating medically intractable Parkinson's disease. Although the adjunct of microelectrode recording improves the targeting accuracy of subthalamic nucleus deep brain stimulation in comparison with image guidance alone, there has been no investigation of the financial cost of intraoperative microelectrode recording. This study was performed to address this issue. A comprehensive literature search of large subthalamic nucleus deep brain stimulation series (minimum, 75 patients) was performed, revealing a mean operating room time of 223.83 minutes for unilateral and 279.79 minutes for simultaneous bilateral implantation. The baseline operating room time was derived from the published operating room time for subthalamic nucleus deep brain stimulation without microelectrode recording. The total cost (operating room, anesthesia, neurosurgery) was then calculated based on hospitals geographically representative of the entire United States. The average cost for subthalamic nucleus deep brain stimulation implantation with microelectrode recording per patient is 33,481.43 for simultaneous bilateral, and 19,461.75, increasing the total cost by 267%. For simultaneous bilateral implantation, microelectrode recording costs 38,923.49, increasing the total cost by 267%. Microelectrode recording more than doubles the cost of subthalamic nucleus deep brain stimulation for Parkinson's disease and more than triples the cost for unilateral and staged bilateral procedures. The cost burden of microelectrode recording to subthalamic nucleus deep brain stimulation requires the clinical efficacy of microelectrode recording to be proven in a prospective evidence-based manner in order to curtail the potential for excessive financial burden to the health care system.
Deep brain stimulation remains an experimental treatment for patients with Gilles de la Tourette syndrome. Currently, a major controversial issue is the choice of brain target that leads to optimal patient outcomes within a presumed network of basal ganglia and cortical pathways involved in tic pathogenesis. This report describes our experience with patients with severe refractory Gilles de la Tourette syndrome treated with globus pallidus internus deep brain stimulation. Five patients were selected for surgery, 2 targeting the posteroventral globus pallidus internus and 2 targeting the anteromedial region. The remaining patient was first targeted on the posterolateral region, but after 18 months the electrodes were relocated in the anteromedial area. Tics were clinically assessed in all patients pre- and postoperatively using the Modified Rush Video protocol and the Yale Global Tic Severity Scale. Obsessive-compulsive behaviors were quantified with the Yale-Brown Obsessive Compulsive Scale. The Gilles de la Tourette Syndrome-Quality of Life Scale was also completed. All patients experienced improvements in tic severity but to variable extents. More convincing improvements were seen in patients with electrodes sited in the anteromedial region of the globus pallidus internus than in those with posterolateral implants. Mean reduction in the Modified Rush Video Rating scale for each group was 54% and 37%, respectively. Our open-label limited experience supports the use of the anteromedial globus pallidus internus as a promising target for future planned randomized double-blind trials of deep brain stimulation for patients with Gilles de la Tourette syndrome.
Laboratory evidence suggests that the pedunculopontine nucleus (PPN) plays a central role in the initiation and maintenance of gait. Translational research has led to reports on deep brain stimulation (DBS) of the rostral brainstem in parkinsonian patients. However, initial clinical results appear to be rather variable. Possible factors include patient selection and the wide variability in anatomical location of implanted electrodes. Clinical studies on PPN DBS efficacy would, therefore, benefit from an accurate and reproducible method of stereotactic localization of the nucleus. The present study evaluates the anatomical accuracy of a specific protocol for MRI-guided stereotactic targeting of the PPN in a human cadaver. Imaging at 1.5 and 9.4 T confirmed electrode location in the intended region as defined anatomically by the surrounding fiber tracts. The spatial relations of each electrode track to the nucleus were explored by subsequent histological examination. This confirmed that the neuropil surrounding each electrode track contained scattered large neurons morphologically consistent with those of the subnucleus dissipatus and compactus of the PPN. The results support the accuracy of the described specific MR imaging protocol.
Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients.
To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy.
Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (< 70 years vs > or = 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage > or = 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006.
Bilateral deep brain stimulation of the subthalamic nucleus (n = 60) or globus pallidus (n = 61). Patients receiving best medical therapy (n = 134) were actively managed by movement disorder neurologists.
The primary outcome was time spent in the "on" state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events.
Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P < .001). Motor function improved significantly (P < .001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (> or = 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores (P < .001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P < .001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage.
In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events.
clinicaltrials.gov Identifier: NCT00056563.
The application of nuclear magnetic resonance (NMR) imaging to a stereotactic method is described. The physical properties of NMR offer some important advantages such as good contrast between grey and white matter and the possibility to scan the brain in three planes and at any desired angle. Stereotactic localisation by NMR gives very satisfactory and precise visualisation of the target structures based on transaxial, coronal and sagittal scans. With the technique described stereotactic localisation is performed by the surgeon directly in the operating room.
to briefly outline the development and validation of the Parkinson's Disease Questionnaire (PDQ-39) and then to provide evidence for the use of the measure as either a profile of health status scores or a single index figure.
the PDQ-39 was administered in two surveys: a postal survey of patients registered with local branches of the Parkinson's Disease Society of Great Britain (n = 405) and a survey of patients attending neurology clinics for treatment for Parkinson's disease (n = 146). Data from the eight dimensions of the PDQ-39 were factor-analysed. This produced a single factor on the data from both surveys.
the eight dimensions of the PDQ-39 and the new single index score-the Parkinson's disease summary index (PDSI), together with clinical assessments (the Columbia rating scale and the Hoehn and Yahr staging score).
in the postal survey 227 patients returned questionnaires (58.2%). AH 146 patients approached in the clinic sample agreed to take part. Higher-order principal-components factor analysis was undertaken on the eight dimensions of the PDQ-39 and produced one factor on both datasets. Consequently it was decided that the scores of the eight domains could be summed to produce a single index figure. The psychometric properties of this index were explored using reliability tests and tests of construct validity. The newly derived single index was found to be both internally reliable and valid.
data from the PDQ-39 can be presented either in profile form or as a single index figure. The profile should be of value in studies aimed at determining the impact of treatment regimes upon particular aspects of functioning and well-being in patients with Parkinson's disease, while the PDSI will provide a summary score of the impact of the illness on functioning and well-being and will be of use in the evaluation of the overall effect of different treatments. Furthermore, the PDSI reduces the number of statistical comparisons and hence the role of chance when exploring data from the PDQ-39.
Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson's disease have been well documented, the long-term outcomes of the procedure are unknown.
We conducted a five-year prospective study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus. Patients were assessed at one, three, and five years with levodopa (on medication) and without levodopa (off medication), with use of the Unified Parkinson's Disease Rating Scale. Seven patients did not complete the study: three died, and four were lost to follow-up.
As compared with base line, the patients' scores at five years for motor function while off medication improved by 54 percent (P<0.001) and those for activities of daily living improved by 49 percent (P<0.001). Speech was the only motor function for which off-medication scores did not improve. The scores for motor function on medication did not improve one year after surgery, except for the dyskinesia scores. On-medication akinesia, speech, postural stability, and freezing of gait worsened between year 1 and year 5 (P<0.001 for all comparisons). At five years, the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced, as compared with base line (P<0.001 for each comparison). The average scores for cognitive performance remained unchanged, but dementia developed in three patients after three years. Mean depression scores remained unchanged. Severe adverse events included a large intracerebral hemorrhage in one patient. One patient committed suicide.
Patients with advanced Parkinson's disease who were treated with bilateral stimulation of the subthalamic nucleus had marked improvements over five years in motor function while off medication and in dyskinesia while on medication. There was no control group, but worsening of akinesia, speech, postural stability, freezing of gait, and cognitive function between the first and the fifth year is consistent with the natural history of Parkinson's disease.
Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI.
This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = -0.02).
In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.
We have previously performed detailed clinical and neuropsychological assessments in a community-based cohort of patients with newly diagnosed parkinsonism, and through analysis of a subcohort with idiopathic Parkinson's disease (PD), we have demonstrated that cognitive dysfunction occurs even at the time of PD diagnosis and is heterogeneous. Longitudinal follow-up of the cohort has now been performed to examine the evolution of cognitive dysfunction within the early years of the disease. One hundred and eighty (79%) eligible patients from the original cohort with parkinsonism were available for re-assessment at between 3 and 5 years from their initial baseline assessments. PD diagnoses were re-validated with repeated application of the UKPDS Brain Bank criteria in order to maximize sensitivity and specificity, following which a diagnosis of idiopathic PD was confirmed in 126 patients. Thirteen out of 126 (10%) had developed dementia at a mean (SD) of 3.5 (0.7) years from diagnosis, corresponding to an annual dementia incidence of 30.0 (16.4-52.9) per 1000 person-years. A further 57% of PD patients showed evidence of cognitive impairment, with frontostriatal deficits being most common amongst the non-demented group. However, the most important clinical predictors of global cognitive decline following correction for age were neuropsychological tasks with a more posterior cortical basis, including semantic fluency and ability to copy an intersecting pentagons figure, as well as a non-tremor dominant motor phenotype at the baseline assessment. This work clarifies the profile of cognitive dysfunction in early PD and demonstrates that the dementing process in this illness is heralded by both postural and gait dysfunction and cognitive deficits with a posterior cortical basis, reflecting probable non-dopaminergic cortical Lewy body pathology. Furthermore, given that these predictors of dementia are readily measurable within just a few minutes in a clinical setting, our work may ultimately have practical implications in terms of guiding prognosis in individual patients.
Background
Increased neuronal activity in the subthalamic nucleus and the pars interna of the globus pallidus is thought to account for motor dysfunction in patients with Parkinson's disease. Although creating lesions in these structures improves motor function in monkeys with induced parkinsonism and patients with Parkinson's disease, such lesions are associated with neurologic deficits, particularly when they are created bilaterally. Deep-brain stimulation simulates the effects of a lesion without destroying brain tissue.
Methods
We performed a prospective, double-blind, crossover study in patients with advanced Parkinson's disease, in whom electrodes were implanted in the subthalamic nucleus or pars interna of the globus pallidus and who then underwent bilateral high-frequency deep-brain stimulation. We compared scores on the motor portion of the Unified Parkinson's Disease Rating Scale when the stimulation was randomly assigned to be turned on or off. We performed unblinded evaluations of motor function preoperatively and one, three, and six months postoperatively.
Results
Electrodes were implanted bilaterally in 96 patients in the subthalamic-nucleus group and 38 patients in the globus-pallidus group. Three months after the procedures were performed, double-blind, crossover evaluations demonstrated that stimulation of the subthalamic nucleus was associated with a median improvement in the motor score (as compared with no stimulation) of 49 percent, and stimulation of the pars interna of the globus pallidus with a median improvement of 37 percent (P<0.001 for both comparisons). Between the preoperative and six-month visits, the percentage of time during the day that patients had good mobility without involuntary movements increased from 27 percent to 74 percent (P<0.001) with subthalamic stimulation and from 28 percent to 64 percent (P<0.001) with pallidal stimulation. Adverse events included intracranial hemorrhage in seven patients and infection necessitating removal of the leads in two.
Conclusions
Bilateral stimulation of the subthalamic nucleus or pars interna of the globus pallidus is associated with significant improvement in motor function in patients with Parkinson's disease whose condition cannot be further improved with medical therapy.
We sought to define the influence of ageing in clinical, cognitive, and quality-of-life outcomes after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We performed motor assessment (UPDRS), mood tests, cognitive, and quality of life evaluation (PDQ-39) on PD patients before surgery, and 12 and 24 months after, and we recorded adverse events. The variations of these parameters after surgery were correlated with age using regression statistical tests. Cerebral bleeding risk was evaluated by a nonparametric test. We enrolled 45 patients (mean age 60 ± 9 years, range 40–73). No significant correlation was found between age and motor scores and PDQ-39 improvements at 12 months. At 24 months, there was a significant negative correlation between age and the improvement of three dimensions of PDQ 39 (mobility, activities of daily life, and cognition). Cognitive impairment showed no correlation, but apathy and depression were positively correlated with age. Significant statistical difference was observed between cerebral bleeding and age. STN-DBS is an effective treatment for elderly patients with advanced PD. A longer follow-up duration and a larger population seem necessary to better assess the quality of life perception in elderly patients and to determinate the real risk of hemorrage. © 2007 Movement Disorder Society
Hemorrhage is an infrequent but potentially devastating complication of deep brain stimulation (DBS) surgery. We examined the factors associated with hemorrhage after DBS surgery and evaluated a modified microelectrode design that may improve the safety of this procedure.
All microelectrode-guided DBS procedures performed at our institution between January 2000 and March 2008 were included in this study. A new microelectrode design with decreased diameter was introduced in May 2004, and data from the 2 types of electrodes were compared.
We examined 246 microelectrode-guided lead implantations in 130 patients. Postoperative imaging revealed 7 hemorrhages (2.8%). Five of the 7 (2.0%) resulted in focal neurological deficits, all of which resolved within 1 month with the exception of 1 patient lost to follow-up. The new microelectrode design significantly decreased the number of hemorrhages (P = 0.04). A surgical trajectory traversing the ventricle also contributed significantly to the overall hemorrhage rate (P = 0.02) and specifically to the intraventricular hemorrhage rate (P = 0.01). In addition, the new microelectrode design significantly decreased the rate of intraventricular hemorrhage, given a ventricular penetration (P = 0.01). The mean age of patients with hemorrhage was significantly higher than that of patients without hemorrhage (P = 0.02). Hypertension, sex, and number of microelectrodes passed did not significantly contribute to hemorrhage rates in our population.
The rate of complications after DBS surgery is not uniformly distributed across all cases. In particular, the rates of hemorrhage were increased in older patients. Importantly, transventricular electrode trajectories appeared to increase the risk of hemorrhage. A new microelectrode design minimizing the volume of brain parenchyma penetrated during microelectrode recording leads to decreased rates of hemorrhage, particularly if the ventricles are breached.
The authors examined the accuracy of anatomical targeting during electrode implantation for deep brain stimulation in functional neurosurgical procedures. Special attention was focused on the impact that ventricular involvement of the electrode trajectory had on targeting accuracy.
The targeting error during electrode placement was assessed in 162 electrodes implanted in 109 patients at 2 centers. The targeting error was calculated as the shortest distance from the intended stereotactic coordinates to the final electrode trajectory as defined on postoperative stereotactic imaging. The trajectory of these electrodes in relation to the lateral ventricles was also analyzed on postoperative images.
The trajectory of 68 electrodes involved the ventricle. The targeting error for all electrodes was calculated: the mean +/- SD and the 95% CI of the mean was 1.5 +/- 1.0 and 0.1 mm, respectively. The same calculations for targeting error for electrode trajectories that did not involve the ventricle were 1.2 +/- 0.7 and 0.1 mm. A significantly larger targeting error was seen in trajectories that involved the ventricle (1.9 +/- 1.1 and 0.3 mm; p < 0.001). Thirty electrodes (19%) required multiple passes before final electrode implantation on the basis of physiological and/or clinical observations. There was a significant association between an increased requirement for multiple brain passes and ventricular involvement in the trajectory (p < 0.01).
Planning an electrode trajectory that avoids the ventricles is a simple precaution that significantly improves the accuracy of anatomical targeting during electrode placement for deep brain stimulation. Avoidance of the ventricles appears to reduce the need for multiple passes through the brain to reach the desired target as defined by clinical and physiological observations.
The authors analyzed deep brain stimulation electrode trajectories on MR images to identify risks of cerebrovascular complications associated with the number of electrode insertions, traversal of a sulcus, and penetration of the ventricle.
Pre- and postoperative MR volumes were fused to determine the proximity of electrodes to a sulcus or ventricle and whether there were cortical, subcortical, or intraventricular complications. Complications were further classified as hemorrhagic or nonhemorrhagic and symptomatic or asymptomatic. The authors examined 258 electrode implantation for deep brain stimulation. There were 4 symptomatic events (1.6% incidence): 3 hemorrhagic and 1 nonhemorrhagic, all within the cortex. Asymptomatic events included cortical hemorrhage in 1 patient, nonhemorrhagic cortical changes in 6, pallidal hemorrhage in 1, thalamic infarction in 1, and intraventricular hemorrhage (IVH) in 5 patients.
Proximity to a sulcus was a significant risk factor for hemorrhagic and nonhemorrhagic cortical complications (p = 0.001). There was a complication rate of 10.1% within the trajectories penetrating or adjacent to a sulcus, and a 0.7% rate with trajectories clearly positioned within the gyrus. Asymptomatic IVH was observed in 5% of ventricular penetrations. A history of hypertension was a risk factor for cortical hemorrhage (p = 0.019), but not for cortical ischemic/edematous events (p = 0.605). The number of electrode penetrations did not differ between patients with and without complications (p = 0.868), and the sequence of electrode insertions was not a risk factor in bilateral surgeries.
Symptomatic cortical complications occur when electrodes traverse close to a sulcus. Asymptomatic IVH occurs infrequently with ventricular penetration. Despite intraoperative efforts to avoid cortical sulci, a higher than expected incidence of electrode proximity to the sulci was identified on careful postoperative trajectory analysis. This finding emphasizes the importance of assiduously planning trajectories and reviewing cases with thorough MR analysis.
Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.
An articulatory inventory was administered to 19 dysarthric adults and scored using two judging formats--phoneme identification and traditional testing. Results indicated that samples judged using the traditional testing format, in which the judge knew the target phoneme, were consistently scored more accurately than those that had been judged using a phoneme identification format, in which the target was not known. Although overall both judging formats were characterized by high inter-rater reliability, the traditional testing format was less reliable than phoneme identification with samples obtained from severely involved speakers. Potential uses of articulatory inventories for dysarthric adults are described.
In monkeys rendered parkinsonian, lesions and electrical stimulation of the subthalamic nucleus reduce all major motor disturbances. The effect of electrical stimulation of the subthalamic nucleus was assessed in three patients with disabling akinetic-rigid Parkinson's disease and severe motor fluctuations. Quadripolar electrodes connected to a pulse generator were implanted in the subthalamic nuclei on both sides. Patients were evaluated with the unified Parkinson's disease rating scale and timed motor tests. 3 months after surgery, activities of daily living scores had improved by 58-88% and motor scores by 42-84%. This improvement was maintained for up to 8 months in the first patient operated upon. One patient was confused for 2 weeks after surgery, and another developed neuropsychological impairment related to a thalamic infarction which improved over 3 months. In one patient, stimulation could induce ballism that was stopped by reduction of stimulation. This is the first demonstration in human beings of the part played by the subthalamic nuclei in the pathophysiology of Parkinson's disease.
Several methods are used for stereotactically guided implantation of electrodes into the subthalamic nucleus (STN) for continuous high-frequency stimulation in the treatment of Parkinson's disease (PD). The authors present a stereotactic magnetic resonance (MR) method relying on three-dimensional (3D) T1-weighted images for surgical planning and multiplanar T2-weighted images for direct visualization of the STN, coupled with electrophysiological recording and stimulation guidance.
Twelve patients with advanced PD were enrolled in this study of bilateral STN implantation. Both STNs were visible as 3D ovoid biconvex hypointense structures located in the upper mesencephalon. The coordinates of the centers of the STNs were determined with reference to the patient's anterior commissure-posterior commissure line by using a new landmark, the anterior border of the red nucleus. Electrophysiological monitoring through five parallel tracks was performed simultaneously to define the functional target accurately. Microelectrode recording identified high-frequency, spontaneous, movement-related activity and tremor-related cells within the STNs. Acute STN macrostimulation improved contralateral rigidity and akinesia, suppressed tremor when present, and could induce dyskinesias. The central track, which was directed at the predetermined target by using MR imaging, was selected for implantation of 19 of 24 electrodes. No surgical complications were noted.
At evaluation 6 months after surgery, continuous STN stimulation was shown to have improved parkinsonian motor disability by 64% and 78% in the "off' and "on" medication states, respectively. Antiparkinsonian drug treatment was reduced by 70% in 10 patients and withdrawn in two patients. The severity of levodopa-induced dyskinesias was reduced by 83% and motor fluctuations by 88%. Continuous high-frequency stimulation of the STN applied through electrodes implanted with the aid of 3D MR imaging and electrophysiological guidance is a safe and effective therapy for patients suffering from severe, advanced levodopa-responsive PD.
Several recent publications have stated that the use of microelectrode recording (MER) during pallidotomy or deep brain stimulation (DBS) contributes to decreasing risks and side effects of surgery, and that such a technique is a prerequisite for minimizing lesion size and for accurate placement of the stereotactic lesion or the DBS electrode. To evaluate the consistency of these statements, we reviewed hundreds of papers and congress reports on MER- and non-MER-guided procedures published since 1992. This review showed that MER groups published more often than non-MER groups. While side effects of surgery were not uncommon in both groups, the rate of severe complications, such as hematoma, and mortality appeared to be higher when microelectrodes were used, both in ablative surgery and in DBS procedures. Besides, the nonaccurate placement of lesions or DBS electrodes, as assessed on published MRI figures, was not uncommon in MER publications. Lesion volume was, when reported, not different in both techniques. The electrical parameters of stimulation of implanted electrodes in the thalamic ventral intermediate (Vim) nucleus for treatment of tremor were higher in MER-guided surgery. The available literature suggests that MER techniques may increase the risks of surgery without enhancing its accuracy, compared to MRI-based macrostimulation techniques. To date, there is no randomized trial by one and the same group on the use of micro- versus macroelectrodes in surgery for movement disorders. A prerequisite for such a trial in the future must imply that the investigators have an equal nonprejudiced attitude towards, and equal confidence and experience in, either technique. Since such a prerequisite does not exist so far in the functional stereotactic community, a critical and comparative study of the available literature remains the only way to evaluate the pros and cons of either technique, in terms of targeting accuracy and surgical complications.
The authors conducted an evidence-based review of contemporary published articles on pallidotomy to obtain an appraisal of this procedure in the treatment of Parkinson disease (PD).
A search of the Pubmed database performed using the key word "pallidotomy" yielded 263 articles cited between January 1, 1992, and July 1, 1999. Articles that included original, nonduplicated descriptions of patients with PD treated with radiofrequency pallidotomy were selected. In 85 articles identified for critical review, 1959 patients with PD underwent pallidotomies at 40 centers in 12 countries. There were 1735 unilateral (88.6%) and 224 bilateral procedures (11.4%). The mean age of the patients was 61.4+/-3.6 years and the mean duration of PD symptoms in these patients was 12.3+/-1.9 years. Microelectrode recordings were used in 46.2% of cases. Outcomes were objectively documented using the Unified Parkinson Disease Rating Scale (UPDRS) in 501 (25.6%) of the cases at 6 months and in 218 (11.1%) of the cases at 1 year. There was a consensus on the benefits of pallidotomy for off period motor function and on period, drug-induced dyskinesias, with variations in the extent of symptomatic benefit across studies. At the 1-year assessment, the mean improvement in the UPDRS motor score during off periods was 45.3% and the mean improvement in contralateral dyskinesias during on periods was 86.4%. The overall mortality rate was 0.4% and the rate of persistent adverse effects was estimated at 14%. Major adverse events, including intracerebral hemorrhages, contralateral weakness, and visual field defects, occurred in 5.3% of patients reported.
Unilateral pallidotomy is effective and relatively safe in the treatment of PD; however, limited data are available on the long-term outcome of this procedure.
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 consists of a critical review of the published literature in order to analyze the value of MER in providing safe, efficient and accurate functional stereotactic surgery. Review of the literature revealed that MER techniques do not necessarily improve targeting accuracy or clinical results, compared to techniques using impedance monitoring and macrostimulation. In terms of safety for the patients, however, MER techniques are relatively safe, but non-Mer techniques, based on macrostimulation-guided surgery, are at least five times safer.
For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.
Although hemorrhage is a well-known complication of microelectrode-guided deep brain stimulation (DBS) surgery, risk factors for the development of hemorrhage have not been well defined. We analyzed the risk factors for symptomatic and asymptomatic hemorrhage in a large series of DBS implantations into the subthalamic nucleus, ventrolateral thalamus, and internal globus pallidus.
All DBS procedures performed by a single surgeon at our institution between June 1998 and May 2004 were included in this study. All patients had postoperative imaging (magnetic resonance imaging or computed tomography) 4 to 24 hours after surgery. Hematomas were noted and scored as symptomatic or asymptomatic. Statistical correlation of factors affecting risk of hematoma formation was performed by use of logistic regression analysis.
The total number of lead implantations was 481. There were 6 symptomatic hematomas and 10 asymptomatic hematomas. Three of the symptomatic hematomas resulted in permanent new neurological deficit. The risk of hematoma (of any type) per lead implantation was 3.3%, whereas the risk of permanent deficit from hematoma was 0.6%. Patients who developed hematomas had a slightly greater number of microelectrode recording penetrations than patients who did not have hematomas, but this difference did not reach statistical significance. There was not a statistically significant relationship between risk of hematoma and patient age or diagnosis. There was a significant effect of brain target (P = 0.001), with only 1 hemorrhage detected after thalamic DBS.
DBS is generally safe, with only 0.6% of implantations associated with permanent neurological deficit. The incremental risk of successive serial microelectrode penetrations is small.
To evaluate the benefits and adverse effects of bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease (PD) by systematically reviewing the published literature.
A search of the PubMed database using the key words subthalamic, nucleus, and stimulation yielded 624 articles published between 1966 and December 2003. Only articles that included original, nonduplicated descriptions of patients with PD treated with bilateral subthalamic nucleus stimulation were selected for further analysis.
A total of 38 studies from 34 neurosurgical centers in 13 countries were identified for critical review. The outcomes for 471 patients with PD treated with bilateral subthalamic nucleus stimulation were assessed according to the Unified Parkinson's Disease Rating Scale in both on-medication and off-medication conditions. With stimulation, Unified Parkinson's Disease Rating Scale motor scores in the off-medication condition improved by 50% after 6 months, 56% after 12 months, 51% after 2 years, and 49% after 5 years compared with preoperative off-medication scores. At 12 months of subthalamic nucleus stimulation, the mean improvement in tremor was 81%, in rigidity was 63%, in bradykinesia was 52%, in gait was 64%, and in postural instability was 69% when compared with preoperative off-medication subscores. On-medication dyskinesias were reduced by 94%, as assessed 12 months after stimulation using the Unified Parkinson's Disease Rating Scale IV complications of therapy score. There was an overall 52% reduction in the l-dopa-equivalent dose intake after 12 months of stimulation. Most adverse effects were mild to moderate. There was a 1 to 2% incidence of severe adverse effects (death or permanent neurological deficits related to intracerebral hemorrhages). Nineteen percent of the patients had adverse effects related to stimulation that could be reversed by changing stimulation parameters. There was a 9% incidence of adverse effects related to the hardware (infections, lead and pulse generator problems).
Bilateral subthalamic nucleus stimulation is effective in the treatment of PD. Further refinements in patient selection and surgical technique may lessen the incidence of complications associated with this procedure.
Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients.
From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1-2 weeks before outpatient pulse generator implantation.
Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days.
Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.
Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta-analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery were generated using random-effects models. Sources of heterogeneity were explored with meta-regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty-seven cohorts were included in the review. Twenty-two studies with estimates of standard errors were included in the meta-analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%), respectively. Average reduction in L-dopa equivalents following surgery was 55.9% (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/- 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L-dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow-up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.
Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management.
In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III).
Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08).
In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).
This paper describes the construction of an atlas of the human basal ganglia. The successive steps of the construction were as follows. First a postmortem specimen was subjected to a MRI acquisition prior to extraction of the brain from the skull. The brain was then cryosectioned (70 microm thickness). One section out of ten (80 sections) was Nissl-stained with cresyl violet, another series of 80 sections was immunostained for the calcium binding protein calbindin. Contours of basal ganglia nuclei including their calbindin-stained functional subdivisions, fiber bundles and ventricles (n=80 structures) were traced from histological sections and digitized. A novelty of this atlas is the MRI acquisition, which represents the core data element of the study. MRI was used for the coregistration of the atlas data and permitted, through multimodal (Nissl, calbindin, images of cryosectioning, T1 and T2 MRI) and 3D optimization, the production of anatomically and geometrically consistent 3D surfaces, which can be sliced through any desired orientation. The atlas MRI is also used for its deformation to provide accurate conformation to the MRI of living patients, thus adding information at the histological level to the patient's MRI volume. This latter aspect will be presented in a forthcoming paper.
Because of concerns about direct visualization of the subthalamic nucleus (STN) on magnetic resonance imaging (MRI), many functional neurosurgeons continue to rely on atlas-based coordinates to reach this target. T2-weighted MRI does allow direct visualisation of the STN. In order to compare the coordinates of the target point within the visualised STN with those obtained from standard brain atlases, the preoperative stereotactic T2-weighted MRI used to implant 55 deep brain stimulation electrodes in the visualised STN of 29 consecutive patients with Parkinson's disease treated in two European centres were studied. The coordinates of the directly visualised STN were significantly different from those of the atlas target. Variability of the position of the STN may render direct visualisation a more accurate means of targeting this nucleus.
Intracranial hemorrhage (ICH) is the most significant complication associated with the placement of stereotactic intracerebral electrodes. Previous reports have suggested that hypertension and the use of microelectrode recording (MER) are risk factors for cerebral hemorrhage. The authors evaluated the incidence of symptomatic ICH in a large cohort of patients with various diseases treated with stereotactic electrode placement. They examined the effect of comorbidities on the risk of ICH and independently assessed the risks associated with age, sex, use of MER, diagnosis, target location, hypertension, and previous use of anticoagulant medications. The authors also evaluated the effect of hemorrhage on length of hospital stay and discharge disposition.
Between 1991 and 2005, 567 electrodes were placed by two neurosurgeons during 337 procedures in 259 patients. Deep brain stimulation (DBS) was performed in 167 procedures, radiofrequency lesioning (RFL) of subcortical structures in 74, and depth electrodes were used in 96 procedures in patients with epilepsy. Electrodes were grouped according to target, patient diagnosis, use of MER, patient history of hypertension, and patient prior use of anticoagulant medication (stopped 10 days before surgery). The Charlson Comorbidity Index (CCI) was used to evaluate the effect of comorbidities. The CCI score, patient age, length of hospital stay, and discharge status were continuous variables. Symptomatic hemorrhages were grouped as transient or leading to permanent neurological deficits.
The risk of hemorrhage leading to permanent neurological deficits in this study was 0.7%, and the risk of symptomatic hemorrhage was 1.2%. A patient history of hypertension was the most significant factor associated with hemorrhage (p = 0.007). Older age, male sex, and a diagnosis of Parkinson disease (PD) were also significantly associated with hemorrhage (p = 0.01, 0.04, 0.007, respectively). High CCI scores, specific target locations, and prior use of anticoagulant therapy were not associated with an increased risk of hemorrhage. The use of MER was not found to be correlated with an increased hemorrhage rate (p = 0.34); however, the number of hemorrhages in the patients who underwent DBS was insufficient to draw definitive conclusions. The mean length of stay for the DBS, RFL, and depth electrode patient groups was 2.9, 2.6, and 11.0 days, respectively. For patients who received DBS and RFL, the mean duration of hospitalization in cases of symptomatic hemorrhage was 8.2 days compared with 2.7 days in those without hemorrhaging (p < 0.0001). Three of the seven patients with symptomatic hemorrhages were discharged home.
The placement of stereotactic electrodes is generally safe, with a symptomatic hemorrhage rate of 1.2%, and a 0.7% rate of permanent neurological deficit. Consistent with prior reports, this study confirms that hypertension is a significant risk factor for hemorrhage. Age, male sex, and diagnosis of PD were also significant risk factors. Patients with symptomatic hemorrhage had longer hospital stays and were less likely to be discharged home.
Ongoing adverse events (AEs) at 4-years postsurgery in 69 patients with advanced Parkinson's disease (PD) who received deep brain stimulation (DBS) of the subthalamic nucleus (STN) (n = 49) or the internal globus pallidus (GPi) (n = 20), in the framework of a subset of eight centers of a multicenter study, were analyzed by an independent ad hoc committee. At baseline, the patients' age, sex, disease duration, and clinical condition were virtually identical, as was the duration of follow-up. There were 64 AEs reported in 53% of STN DBS patients and eight AEs reported in 35% of GPi DBS patients. Most of the AEs were not deemed severe and were reported to be present "both with and without stimulation." The majority of the AEs affected patients' cognitive, psychiatric and behavioral status, as well as speech, gait, and balance, and most of these AEs occurred in STN DBS patients. When comparing patients who exhibited AEs with those who did not, it was found that in the STN DBS group, the patients with AEs had a longer disease duration, as well as more gait disorders and psychiatric disturbances at baseline.
We present a magnetic resonance imaging-directed stereotactic system using implantable guide tubes for targeting deep brain nuclei in functional neurosurgery.
Our method relies on visualization of the deep brain nuclei on high-resolution magnetic resonance images that delineate the target boundaries and enable direct targeting of specific regions of the nucleus. The delivery system comprises a modified stereoguide capable of delivering an implantable guide tube to the vicinity of the desired target. The guide tube (in-house investigational device) has a hub at its proximal end that is fixed within a burr hole and accommodates a radioopaque stylette that is inserted such that its distal end is at the desired target. After perioperative radiological confirmation of the stylette's relationship to the desired brain target, it is withdrawn from the guide tube, which may then act as a port for the implantation of an electrode for deep brain stimulation (DBS) or radiofrequency lesioning. Alternatively, the guide tube can be used to insert a catheter for drug delivery, cell transplantation, or viral-vector delivery. Implantation and verification are guided by magnetic resonance imaging or computed tomography, which enable the entire procedure to be performed under general anesthesia. The technique of implantation helps ensure optimal accuracy, and we have successfully used this device for implanting electrodes for DBS in the treatment of Parkinson's disease, essential tremor, and dystonia, and for implanting catheters for continuous delivery of glial-derived neurotrophic factor in the treatment of Parkinson's disease. The device also aids in securely fixing the DBS electrode or catheter to the cranium with ease, limiting hardware problems.
A total of 205 guide tubes have been implanted in 101 patients. Major complications in these cases were limited to 4% of patients. At the initial implantations, 96.3% of the guide tubes were within 1.5 mm of the target. Ten guide tubes required reimplantation secondary to target errors. With corrections, the DBS electrode was delivered to within 1.5 mm from the planned target in all cases.
This system provides a safe and accurate magnetic resonance imaging-directed system for targeting deep brain nuclei in functional neurosurgery under general anesthesia and avoids the need for electrophysiological monitoring.