Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson’s Disease: 10 Years and Beyond

Neurosurgery 91:726–733, 2022

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson’s disease (PD), but little is known about the long-term benefit.

OBJECTIVE: To investigate the survival rate and long-term outcome of DBS.

METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed.

RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson’s Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation.

CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Deep Brain Stimulations for Obsessive-Compulsive Disorder: Update of the 2014 Guidelines

 Neurosurgery 88:710–712, 2021

In 2020, the Guidelines Task Force conducted another systematic review of the relevant literature on deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) to update the original 2014 guidelines to ensure timeliness and accuracy for clinical practice.

OBJECTIVE: To conduct a systematic review of the literature and update the evidencebased guidelines on DBS for OCD.

METHODS: The Guidelines Task Force conducted another systematic review of the relevant literature, using the same search terms and strategies as used to search PubMed and Embase for relevant literature. The updated search included studies published between 1966 and December 2019. The same inclusion/exclusion criteria as the original guideline were also applied. Abstracts were reviewed and relevant full-text articles were retrieved and graded. Of 864 articles, 10 were retrieved for full-text review and analysis. Recommendations were updated according to new evidence yielded by this update.

RESULTS: Seven studies were included in the original guideline, reporting the use of bilateral DBS as more effective in improving OCD symptoms than sham treatment. An additional 10 studies were included in this update: 1 class II and 9 class III.

CONCLUSION: Based on the data published in the literature, the following recommendations can be made: (1) It is recommended that clinicians utilize bilateral subthalamic nucleus DBS over best medical management for the treatment of patients with medically refractory OCD (level I). (2) Cliniciansmay use bilateral nucleus accumbens or bed nucleus of stria terminalis DBS for the treatment of patientswithmedically refractory OCD (level II). There is insufficient evidence to make a recommendation for the identification of themost effective target. The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelinesdetail/ deep-brain-stimulation-obsessive-compulsive-disord.

Postmortem Dissections of Common Targets for Lesion and Deep Brain Stimulation Surgeries

Neurosurgery 86:860–872, 2020

The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many pathological conditions. Previous literature has focused on appropriate stimulation targets and their relationships with functional neuroanatomic pathways; however, comprehensive anatomic dissections illustrating these nuclei and their connections are lacking. This information will provide insight into the anatomic basis of stimulation-induced DBS benefits and side effects.

OBJECTIVE: To combine advanced cadaveric dissection techniques and ultrahigh field magnetic resonance imaging (MRI) to explore the anatomy of the STN, GPi, and PPN with their associated fiber pathways.

METHODS: A total of 10 cadaveric human brains and 2 hemispheres of a cadaveric head were examined using fiber dissection techniques. The anatomic dissections were compared with 11.1 Tesla (T) structural MRI and 4.7 T MRI fiber tractography.

RESULTS: The extensive connections of the STN (caudate nucleus, putamen, medial frontal cortex, substantia innominata, substantia nigra, PPN, globus pallidus externus (GPe), GPi, olfactory tubercle, hypothalamus, and mammillary body) were demonstrated. The connections of GPi to the thalamus, substantia nigra, STN, amygdala, putamen, PPN, and GPe were also illustrated. The PPN was shown to connect to the STN and GPi anteriorly, to the cerebellum inferiorly, and to the substantia nigra anteriorly and superiorly.

CONCLUSION: This study demonstrates connections using combined anatomic microdissections, ultrahigh field MRI, and MRI tractography. The anatomic findings are analyzed in relation to various stimulation-induced clinical effects. Precise knowledge of neuroanatomy, anatomic relationships, and fiber connections of the STN, GPi, PPN will likely enable more effective targeting and improved DBS outcomes.

Deep brain stimulation of the globus pallidus internus versus the subthalamic nucleus in isolated dystonia

J Neurosurg 132:721–732, 2020

Surgical procedures involving deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) are well-established treatments for isolated dystonia. However, selection of the best stimulation target remains a matter of debate. The authors’ objective was to compare the effectiveness of DBS of the GPi and the STN in patients with isolated dystonia.

METHODS In this matched retrospective cohort study, the authors searched an institutional database for data on all patients with isolated dystonia who had undergone bilateral implantation of DBS electrodes in either the GPi or STN in the period from January 30, 2014, to June 30, 2017. Standardized assessments of dystonia and health-related quality of life using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and SF-36 were conducted before and at 1, 6, and 12 months after surgery. No patients were lost to the 6-month follow-up; 5 patients were lost to the 12-month follow-up.

RESULTS Both GPi (14 patients) and STN (16 patients) stimulation produced significant improvement in dystonia and quality of life in all 30 patients found in the database search. At the 1-month follow-up, however, the percentage improvement in the BFMDRS total movement score was significantly (p = 0.01) larger after STN DBS (64%) than after GPi DBS (48%). At the 12-month follow-up, the percentage improvement in the axis subscore was significantly (p = 0.03) larger after GPi DBS (93%) than after STN DBS (83%). Also, the total amount of electrical energy delivered was significantly (p = 0.008) lower with STN DBS than with GPi DBS (124 ± 52 vs 192 ± 65 mJ, respectively).

CONCLUSIONS The GPi and STN are both effective targets in alleviating dystonia and improving quality of life. However, GPi stimulation may be better for patients with axial symptoms. Moreover, STN stimulation may produce a larger clinical response within 1 month after surgery and may have a potential economic advantage in terms of lower battery consumption.

Degradation of Neuronal Encoding of Speech in the Subthalamic Nucleus in Parkinson’s Disease

Neurosurgery 84:378–387, 2019

Most of the patients with Parkinson’s disease suffer from speech disorders characterized mainly by dysarthria and hypophonia.

OBJECTIVE: To understand the deterioration of speech in the course of Parkinson’s disease.

METHODS: We intraoperatively recorded single neuron activity in the subthalamic nucleus of 18 neurosurgical patients with Parkinson’s disease undergoing implantation of deep brain stimulator while patients articulated 5 vowel sounds.

RESULTS: Here, we report that single subthalamic neurons encode individual vowel phonemes and employ 1 of 2 encoding schemes: broad or sharp tuning. Broadly tuned units respond to all examined phonemes, each with a different firing rate, whereas sharply tuned ones are specific to 1 to 2 phonemes. We then show that in comparison with patients without speech deficits, the spiking activity in patients with speech disorders was lower during speech production, overt or imagined, but not during perception. However, patients with speech disorders employed a larger percentage of the neurons for the aforementioned tasks. Whereas the lower firing rates affect mainly sharply tuned units, the extra units used a broad tuning encoding scheme.

CONCLUSION: Our findings suggest mechanisms of neuronal degradation due to Parkinsonian speech disorders and their possible compensation. As impairment in sharply tuned units may be compensated by broadly tuned ones, the proposed compensation model appears to be suboptimal, lending support to the persistence of speech disorders in the course of the disease.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson’s Disease

Neurosurgery 82:753–756, 2018

QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson’s disease, as measured by improvements in Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III) scores?

RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson’s disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I)

QUESTION 2: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson’s disease?

RECOMMENDATION: When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson’s disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I)

QUESTION 3: Is bilateral STN DBSmore, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson’s disease?

RECOMMENDATION: There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of “on” medication dyskinesias, the GPi should be targeted. (Level I)

QUESTION 4: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson’s disease?

RECOMMENDATION:When considering improvements in quality of life in a patient undergoing DBS for Parkinson’s disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I) QUESTION 5: Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease?

RECOMMENDATION: If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I)

QUESTION 6: Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson’s disease?

RECOMMENDATION: If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I)

QUESTION 7: Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson’s disease?

RECOMMENDATION: There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events.

The full guideline can be found at: https://www.cns.org/guidelines/deep-brainstimulation- parkinsons-disease.


Deep brain stimulation for Parkinson’s disease: meta-analysis of results of randomized trials at varying lengths of follow-up

J Neurosurg 128:1199–1213, 2018

Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson’s disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up.

METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups.

RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99–4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar.

CONCLUSIONS The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.

Asleep Robot-Assisted Surgery for the Implantation of Subthalamic Electrodes Provides the Same Clinical Improvement and Therapeutic Window as Awake Surgery

OBJECTIVE: To study the impact of not performing awake clinical evaluation during the robot-assisted implantation of subthalamic nucleus deep brain stimulation (STN-DBS) electrodes on the stimulation parameters and clinical outcomes in patients with Parkinson disease (PD).

METHODS: A total of 23 patients with PD underwent robot-assisted surgery for the bilateral implantation of STN-DBS electrodes. Thirteen patients received general anesthesia (GA) and a limited intraoperative evaluation (side effects only), and the other 10 patients received local anesthesia (LA) and a full evaluation. The primary endpoint was the therapeutic window (TW), defined as the difference between the mean voltage threshold for motor improvement and the mean voltage threshold for side effects in the active contacts at 12 months after surgery. Motor scores were measured as well.

RESULTS: The TW was similar in the LA and GA groups, with mean  standard deviation values of 2.06  0.53 V and 2.28  0.99 V, respectively (P [ 0.32). In the short term, the Unified Parkinson Disease Rating Scale (UPDRS) III score in the “off-drug, on-stim” condition fell to a similar extent in the LA and GA groups (by 40.3% and 49%, respectively; P [ 0.336), as did the UPDRS III score in the “on-stim, ondrug” condition (by 57% and 70.7%, respectively; P [ 0.36).

CONCLUSIONS: Asleep, robot-assisted implantation of STN-DBS electrodes (with accurate identification of the STN and positioning of the DBS lead) produced the same motor results and TW as awake surgery.



Optimization of Microelectrode Recording in Deep Brain Stimulation Surgery Using Intraoperative Computed Tomography

WORLD NEUROSURGERY 103: 168-173, JULY 2017

Microelectrode recording (MER) is used to confirm targeting accuracy during deep brain stimulation (DBS) surgery. We describe a technique using intraoperative computed tomography (CT) extrapolation (iCTE) to predetermine and adjust the trajectory of the guide tube to improve microelectrode targeting accuracy. We hypothesized that this technique would decrease the number of MER tracks and operative time, while increasing the recorded length of the subthalamic nucleus (STN).

– METHODS: Thirty-nine patients with Parkinson’s disease who underwent STN DBS before the iCTE method were compared with 33 patients undergoing STN DBS using iCTE. Before dural opening, a guide tube was inserted and rested on dura. Intraoperative computed tomography (iCT) was performed, and a trajectory was created along the guide tube and extrapolated to the target using targeting software. If necessary, headstage adjustments were made to correct for error. The guide tube was inserted, and MER was performed. iCT was performed with the microelectrode tip at the target. Coordinates were compared with planned/ adjusted track coordinates. Radial error between the MER track and the planned/adjusted track was calculated. Cases before and after implementation of iCTE were compared to determine the impact of iCTE on operative time, number of MER tracks and recorded STN length.

– RESULTS: The use of iCTE reduced the average radial MER track error from 1.90  0.12 mm (n[54) to 0.84  0.09 mm (n[49) (P < 0.001) while reducing the operative time for bilateral lead placement from 272  9 minutes (n [ 30) to 233  10 minutes (n [ 24) (P < 0.001). The average MER tracks per hemisphere was reduced from 2.24  0.13 mm (n[66) to 1.75  0.09 mm (n[63) (P < 0.001), whereas the percentage of hemispheres requiring a single MER track for localization increased from 29% (n [ 66) to 43% (n [ 63). The average length of recorded STN increased from 4.01  0.3 mm (n [ 64) to 4.75  0.28 mm (n [ 56) (P < 0.05).

-CONCLUSION: iCTE improves microelectrode accuracy and increases the first-pass recorded length of STN, while reducing operative time. Further studies are needed to determine whether this technique leads to less morbidity and improved clinical outcomes.


Stimulation sites in the subthalamic nucleus and clinical improvement in Parkinson’s disease


J Neurosurg 125:1068–1079, 2016

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used in patients with Parkinson’s disease (PD). However, which target area of this region results in the highest antiparkinsonian efficacy is still a matter of debate. The aim of this study was to develop a more accurate methodology to locate the electrodes and the contacts used for chronic stimulation (active contacts) in the subthalamic region, and to determine the position at which stimulation conveys the greatest clinical benefit.

Methods The study group comprised 40 patients with PD in whom bilateral DBS electrodes had been implanted in the STN. Based on the Morel atlas, the authors created an adaptable 3D atlas that takes into account individual anatomical variability and divides the STN into functional territories. The locations of the electrodes and active contacts were obtained from an accurate volumetric assessment of the artifact using preoperative and postoperative MR images. Active contacts were positioned in the 3D atlas using stereotactic coordinates and a new volumetric method based on an ellipsoid representation created from all voxels that belong to a set of contacts. The antiparkinsonian benefit of the stimulation was evaluated by the reduction in the Unified Parkinson´s Disease Rating Scale Part III (UPDRS-III) score and in the levodopa equivalent daily dose (LEDD) at 6 months. A homogeneous group classification for contact position and the respective clinical improvement was applied using a hierarchical clustering method.

Results Subthalamic stimulation induced a significant reduction of 58.0% ± 16.5% in the UPDRS-III score (p < 0.001) and 64.9% ± 21.0% in the LEDD (p < 0.001). The greatest reductions in the total and contralateral UPDRS-III scores (64% and 76%, respectively) and in the LEDD (73%) were obtained when the active contacts were placed approximately 12 mm lateral to the midline, with no influence of the position being observed in the anteroposterior and dorsoventral axes. In contrast, contacts located about 10 mm from the midline only reduced the global and contralateral UPDRS-III scores by 47% and 41%, respectively, and the LEDD by 33%. Using the ellipsoid method of location, active contacts with the highest benefit were positioned in the rostral and most lateral portion of the STN and at the interface between this subthalamic region, the zona incerta, and the thalamic fasciculus. Contacts placed in the most medial regions of the motor STN area provided the lowest clinical efficacy.

Conclusions The authors report an accurate new methodology to assess the position of electrodes and contacts used for chronic subthalamic stimulation. Using this approach, the highest antiparkinsonian benefit is achieved when active contacts are located within the rostral and the most lateral parts of the motor region of the STN and at the interface of this region and adjacent areas (zona incerta and thalamic fasciculus).

Intraoperative MRI and DBS for Parkinson disease


J Neurosurg 124:62–69, 2016

The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes.

MethodsTwo hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes.

ResultsFifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients.

ConclusionsThe iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery.

Electrophysiological validation of STN-SNr boundary depicted by susceptibility-weighted MRI

Electrophysiological validation of STN-SNr boundary depicted by susceptibility-weighted MRI

Acta Neurochir (2015) 157:2129–2134

Direct targeting of subthalamic nucleus (STN) without secondary electrophysiological verification during deep brain stimulation (DBS) is replacing atlas-based indirect targeting techniques. Recent groups have reported increased contrast and better delineation of STN and substantia nigra (SNr) in susceptibility-weighted imaging protocols (SWI). We aim to validate the STN-SNr boundary seen in MRISWI by correlating with intraoperative microelectrode recordings (MER) as a part of developing a multi-contrast DBSMRI planning protocol.

Methods Prospective service evaluation involving electrophysiological verification by correlation of MER trajectory and STN-SNr boundary seen in SWI in seven consecutive patients undergoing DBS surgery were analyzed. The angle of inclination of the STN-SNr boundary and DBS trajectory in the coronal plane were calculated. Considering 4-mm dispersion of a coronal 3 MER array, we predicted, measured, and correlated the depths at which each electrode engaged the boundary.

Results All central microelectrodes identified the STN-SNr boundary within 1 mm of the predicted depth with 100 % accuracy. Ninety percent of the lateral MER identified the STN-SNr boundary as predicted from SWI and angle of the encounter of the MER front.

Conclusions The study demonstrates that STN morphology can be depicted using SWI MRI and coincides reliably with the electrophysiological MER boundary. Thus, this imaging modality can be used to refine STN direct targeting protocols in DBS surgery for PD.

Deep brain stimulation of the subthalamic nucleus: histological verification and 9.4-T MRI correlation

Deep brain stimulation of the subthalamic nucleus- histological verification and 9

Acta Neurochir (2015) 157:2143–2147

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using an MRI-guided and MRI-verified technique without microelectrode recording is an effective and safe surgical treatment for patients with Parkinson’s disease (PD).

Objectives To assess the anatomical accuracy of lead placement after MRI-guided, MRI-verified STN DBS using postmortem histology and high-field MRI at 9.4 T.

Methods We conducted post-mortem analysis of a patient’s brain who had had MRI-guided, MRI-verified STN DBS for PD, using 9.4-TMRI and histology. After death, the brain was retrieved and a block including the electrode tracks down to the mesencephalon was examined with high-field MRI at 9.4 T and histological analysis.

Results High-field MRI images and corresponding histological examination showed that each electrode track ended within the intended target area, and that DBS did not cause significant neuroparenchymal tissue damage.

Conclusions This study supports the anatomical accuracy of the MRI-guided and MRI-verified method of STN DBS.

Fully Automated Targeting Using Nonrigid Image Registration Matches Accuracy and Exceeds Precision of Best Manual Approaches to Subthalamic Deep Brain Stimulation Targeting in Parkinson Disease

DBS 2 leads metal head holder

Neurosurgery 76:756–765, 2015

Finding the optimal location for the implantation of the electrode in deep brain stimulation (DBS) surgery is crucial for maximizing the therapeutic benefit to the patient. Such targeting is challenging for several reasons, including anatomic variability between patients as well as the lack of consensus about the location of the optimal target.

OBJECTIVE: To compare the performance of popular manual targeting methods against a fully automatic nonrigid image registration-based approach.

METHODS: In 71 Parkinson disease subthalamic nucleus (STN)-DBS implantations, an experienced functional neurosurgeon selected the target manually using 3 different approaches: indirect targeting using standard stereotactic coordinates, direct targeting based on the patient magnetic resonance imaging, and indirect targeting relative to the red nucleus. Targets were also automatically predicted by using a leave-one-out approach to populate the CranialVault atlas with the use of nonrigid image registration. The different targeting methods were compared against the location of the final active contact, determined through iterative clinical programming in each individual patient.

RESULTS: Targeting by using standard stereotactic coordinates corresponding to the center of the motor territory of the STN had the largest targeting error (3.69 mm), followed by direct targeting (3.44 mm), average stereotactic coordinates of active contacts from this study (3.02 mm), red nucleus-based targeting (2.75 mm), and nonrigid image registration-based automatic predictions using the CranialVault atlas (2.70 mm). The CranialVault atlas method had statistically smaller variance than all manual approaches.

CONCLUSION: Fully automatic targeting based on nonrigid image registration with the use of the CranialVault atlas is as accurate and more precise than popular manual methods for STN-DBS.

Adverse Events Associated With Deep Brain Stimulation for Movement Disorders: Analysis of 510 Consecutive Cases

DBS 2 leads metal head holder

Operative Neurosurgery 11:190–199, 2015

Although numerous studies have focused on the efficacy of deep brain stimulation (DBS) for movement disorders, less is known about surgical adverse events, especially over longer time intervals.

OBJECTIVE: Here, we analyze adverse events in 510 consecutive cases from a tertiary movement disorders center at up to 10 years postoperatively.

METHODS: We conducted a retrospective review of adverse events from craniotomies between January 2003 and March 2013. The adverse events were categorized into 2 broad categories—immediate perioperative and time-dependent postoperative events.

RESULTS: Across all targets, perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware-related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation-related event was speech disturbance in 16 (3.1%) cases. There were no significant differences among surgical targets with respect to the incidence of these events. Time-dependent postoperative events leading to the revision of a given DBS electrode for any reason occurred in 4.7% 6 1.0%, 9.3% 6 1.4%, and 12.4% 6 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively. Staged bilateral DBS was associated with approximately twice the risk of repeat surgery for electrode replacement vs unilateral surgery (P = .020).

CONCLUSION: These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.

Multitract Orthogonal Microelectrode Localization of the Subthalamic Nucleus

Multitract Orthogonal Microelectrode Localization of the Subthalamic Nucleus

Operative Neurosurgery 10:240–245, 2014

Microelectrode recording helps surgeons accurately localize boundaries of the subthalamic nucleus (STN) and surrounding structures in deep brain stimulation.

OBJECTIVE: To describe a novel adaptation of the Ben gun device to optimize efficient mapping.

METHODS: Patients who underwent STN deep brain stimulation over a 3-year period were reviewed. For the final year, the Ben gun was rotated 45 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). Before this step, the initial pass consisted of 1 to 2 tracks with the frame center targeted to STN. The primary outcome measure was the number of passes required for accurate localization of the nucleus and boundaries.

RESULTS: Eighty-three electrodes were implanted in 45 patients (mean age, 62; range, 37-78 years), of which 29 electrodes were placed by the use of the new technique. One electrode (4%) required more than 1 pass using the new technique compared with 36 (67%) using the older technique (P , .01). The distance from original target to final electrode position increased from 0.67 6 0.13 mm to 1.06 6 0.15 mm (P , .05) with a greater tendency to move the final electrode position posteriorly. There was no statistically significant difference in benefit from neurostimulation.

CONCLUSION: This technique facilitates reliable localization of the STN with fewer passes, possibly decreasing the risks associated with more passes and longer duration of surgery.

An Optimized 3-T Magnetic Resonance Imaging Sequence for Targeting the Subthalamic Nucleus

High-Resolution 3-Dimensional T2*-Weighted Angiography (HR 3-D SWAN)- An Optimized 3-T Magnetic Resonance Imaging Sequence for Targeting the Subthalamic Nucleus

Neurosurgery 74:615–627, 2014

Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for Parkinson’s disease.

OBJECTIVE: To characterize an optimized magnetic resonance imaging (MRI) sequence (high-resolution 3-dimensional T2*-weighted angiography [HR 3-D SWAN]) for direct STN targeting.

METHODS: Sequence distortions were measured using the Leksell stereotactic phantom. Eight consecutive candidates for STN-DBS underwent HR 3-D SWAN MRI for direct identification of the 16 STN. Two senior neurosurgeons independently determined the boundaries of STN on a semiquantitative scale (ranging from 1 [identification very easy] to 4 [identification very difficult]) and the anatomic target within the nucleus. The anatomic data were compared with electrophysiological recordings (48 microrecordings). We examined the anatomic location of the active contacts on MRI.

RESULTS: The mean distortion error over the phantom was 0.16 mm. For the 16 STNs, identification of the upper, internal, anterior, and external edges was considered to be easy (scores of 1 or 2). The distinction between the substantia nigra and the STN was rated 1 or 2 for all but 6 nuclei. In the mediolateral axis, electrophysiological recordings covered perfectly anatomic data. In the craniocaudal axis, the mean differences between the electrophysiological data and the anatomic data were 0.8 mm and 0.19 mm for the “entry” and “exit” of the STN, respectively. All active contacts were located within the STN on MRI.

CONCLUSION: HR 3-D SWAN allows easy visualization of the STN. Adapted to stereotactic requirement, the sequence simplifies direct targeting in STN-DBS surgery.

Stimulation sites in the subthalamic nucleus projected onto a mean 3-D atlas of the thalamus and basal ganglia


Acta Neurochir (2013) 155:1655–1660

In patients with severe forms of Parkinson’s disease (PD), deep brain stimulation (DBS) commonly targets the subthalamic nucleus (STN). Recently, the mean 3-D Morel-Atlas of the basal ganglia and the thalamus was introduced. It combines information contained in histological data from ten post-mortem brains. We were interested whether the Morel-Atlas is applicable for the visualization of stimulation sites.
In a consecutive PD patient series, we documented preoperative MRI planning, intraoperative target adjustment based on electrophysiological and neurological testing, and perioperative CT target reconstruction. The localization of the DBS electrodes and the optimal stimulation sites were projected onto the Morel-Atlas.
We included 20 patients (median age 62 years). The active contact had mean coordinates Xlat = ±12.1 mm, Yap = −1.8 mm, Zvert = −3.2 mm. There was a significant difference between the initially planned site and the coordinates of the postoperative active contact site (median 2.2 mm). The stimulation site was, on average, more anterior and more dorsal. The electrode contact used for optimal stimulation was found within the STN of the atlas in 38/40 (95 %) of implantations.
The cluster of stimulation sites in individual patients—as deduced from preoperative MR, intraoperative electrophysiology and neurological testing—showed a high degree of congruence with the atlas. The mean 3D Morel Atlas is thus a useful tool for postoperative target visualization. This represents the first clinical evaluation of the recently created atlas.

The Anatomical and Electrophysiological Subthalamic Nucleus Visualized by 3-T Magnetic Resonance Imaging

The Anatomical and Electrophysiological Subthalamic Nucleus Visualized by 3-T Magnetic Resonance Imaging

Neurosurgery 71:1089–1095, 2012

Accurate localization of the subthalamic nucleus (STN) is critical to the success of deep brain stimulation surgery for Parkinson disease. Recent developments in high-field-strength magnetic resonance imaging (MRI) have made it possible to visualize the STN in greater detail. However, the relationship of the MR-visualized STN to the anatomic, electrophysiological, or atlas-predicted STN remains controversial.

OBJECTIVE: To evaluate the size of the STN visualized on 3-T MRI compared with anatomic measurements in cadaver studies and to compare the predictions of 3-T MRI and those of the Schaltenbrand-Wahren (SW) atlas for intraoperative STN microelectrode recordings.

METHODS: We evaluated the STN by 3-T MRI and intraoperative microelectrode recordings in 20 Parkinson disease patients undergoing deep brain stimulation surgery. We compared our findings with anatomic cadaver studies and with the individually scaled SW atlas-based predictions for each patient.

RESULTS: The dimensions of the 3-T MR-visualized STN were very similar to those of the largest anatomic study (MRI length, width, and height: 9.8 6 1.6, 11.5 6 1.6, and 3.7 6 0.7 mm, respectively; n = 40; cadaver length, width, and height: 9.3 6 0.7, 10.6 6 0.9, and 3.1 6 0.5 mm, respectively; n = 100). The amount of STN traversed during intraoperative microelectrode recordings was better correlated to the 3-T MR-visualized STN than the SW atlas-predicted STN (R = 0.38 vs R = 20.17).

CONCLUSION: The STN as visualized on 3-T MRI corresponds well with cadaveric anatomic studies and intraoperative electrophysiology. STN visualization with 3-T MRI may be an improvement over SW atlas-based localization for STN deep brain stimulation surgery in Parkinson disease.

Long-term Recordings of Local Field Potentials From Implanted Deep Brain Stimulation Electrodes

Neurosurgery 71:804–814, 2012 

Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for Parkinson disease. However, DBS is not responsive to an individual’s disease state, and programming parameters, once established, do not change to reflect disease state. Local field potentials (LFPs) recorded from DBS electrodes are being investigated as potential biomarkers for the Parkinson disease state. However, no patient data exist about what happens to LFPs over the lifetime of the implant.

OBJECTIVE: We investigated whether LFP amplitude and response to limb movement differed between patients implanted acutely with subthalamic nucleus DBS electrodes and patients implanted 2 to 7 years previously.

METHODS: We recorded LFPs at DBS surgery time (9 subjects), 3 weeks after initial placement (9 subjects), and 2 to 7 years (median: 3.5) later during implanted programmable generator replacement (11 sides). LFP power-frequency spectra for each of 3 bipolar electrode derivations of adjacent contacts were calculated over 5-minute resting and 30-second movement epochs. Monopolar impedance data were used to evaluate trends over time.

RESULTS: There was no significant difference in b-band LFP amplitude between initial electrode implantation (OR) and 3-week post-OR times (P = .94). However, b-band amplitude was lower at implanted programmable generator replacement times than in OR (P = .008) and post-OR recordings (P = .039). Impedance measurements declined over time (P < .001).

CONCLUSION: Postoperative LFP activity can be recorded years after DBS implantation and demonstrates a similar profile in response to movement as during acute recordings, although amplitude may decrease. These results support the feasibility of constructing a closed-loop, patient-responsive DBS device based on LFP activity.

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