Patients Undergoing Deep Brain Stimulation Surgery Research Articles

Neuronal tissue collection from intra-cranial instruments used in deep brain stimulation surgery for Parkinson’s disease with implications for study of alpha-synuclein

Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1–125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.

Analysis of alpha-synuclein harvested from intracranial instruments used in deep brain stimulation surgery for Parkinson's disease.

Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson's disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is purified from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is robustly detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 μg protein (n=15) is able to be purified, with immunoblot assays specific for αSyn reactive in all tested samples. Light microscopy revealed axons and capillaries as the primary components of purified tissue (n=3). Further analysis was conducted using western blot, demonstrating that truncated αSyn (1-125 αSyn) was significantly increased in PD (n=5) compared to ET (n=3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that pathologic αSyn can be reliably purified from living PD patients with this method.

Intraoperative transcutaneous electroacupoint stimulation on early postoperative fatigue in patients with Parkinson's disease undergoing deep brain stimulation surgery

BackgroundIn this clinical trial, we evaluated the effects of transcutaneous electroacupoint stimulation (TEAS) on postoperative fatigue (POF) in Parkinson disease (PD) patients undergoing deep brain stimulation (DBS) surgery. MethodsA total 60 PD patients undergoing DBS surgery were enrolled. They were randomized to receive either electrical stimulation [alternative frequency 2/10 Hz, dense and disperse, intensity adjusted to the maximum tolerated by the participants (6–15 mAmp)] via surface electrodes (TEAS group) or surface electrodes only without electrical stimulation (Con group) at bilateral Zusanli and Sanyinjiao acupuncture points. All participants received their assigned intervention (TEAS or Con) during the 1st stage of surgery [(except during microelectrode recording (MER)] and the entire 2nd stage of surgery. Intraoperative anesthetic requirements were adjusted based on bispectral index (BIS) monitor. POF was assessed by Christensen fatigue scales (ChrFS), along with Quality of Recovery-15 (QoR-15) and mini-mental state examination (MMSE) postoperatively over a 7-day-period. We recorded the usage of rescue analgesics and anti-emetics. ResultsFifty-nine patients’ datasets were included for final analyses. Fewer patients in TEAS experienced severe POF (defined as ChrFS ≥6) at T3 than those in the Con group (TEAS vs. Con: 7 vs. 22, p < 0.001). During the 1st stage of surgery, more patients in Con group required dexmedetomidine infusion (TEAS vs. Con: 2 vs. 6; P < 0.01). Total dosages of propofol and remifanil during the 2nd stage of surgery were TEAS vs. Con: 374.7 ± 61.2 vs 421.5 ± 81.9; p < 0.001 and 572.3 ± 82.0 vs. 662 ± 148.2; P < 0.001, respectively. Postoperative rescue analgesics (TEAS vs. Con: 2 vs. 6; P < 0.001) were used less in the TEAS group. TEAS patients reported better POF, MMSE and QoR15 scores than those in the Con group during most of the assessment period. ConclusionsIntraoperative TEAS decreased the severity of POF, reduced intraoperative anesthetic requirements and facilitated post-DBS recovery in this group of PD patients.

The guiding effect of local field potential during deep brain stimulation surgery for programming in Parkinson's disease patients.

Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery require subsequent programming, which is complex and cumbersome. The local field potential (LFP) in the deep brain is associated with motor symptom improvement. The current study aimed to identify LFP biomarkers correlated with improved motor symptoms in PD patients after DBS and verify their guiding role in postoperative programming. Initially, the study included 36 PD patients undergoing DBS surgery. Temporary external electrical stimulation was performed during electrode implantation, and LFP signals around the electrode contacts were collected before and after stimulation. The stimulating contact at 6 months of programming was regarded as the optimal and effective stimulating contact. The LFP signal of this contact during surgery was analyzed to identify potential LFP biomarkers. Next, we randomly assigned another 30 PD patients who had undergone DBS to physician empirical programming and LFP biomarker-guided programming groups and compared the outcomes. In the first part of the study, LFP signals of electrode contacts changed after electrical stimulation. Electrical stimulation reduced gamma energy and the beta/alpha oscillation ratio. The different programming method groups were compared, indicating the superiority of beta/alpha oscillations ratio-guided programming over physician experience programming for patients' improvement rate (IR) of UPDRS-III. There were no significant differences in the IR of UPDRS-III, post-LED, IR-PDQ39, number of programmings, and the contact change rate between the gamma oscillations-guided programming and empirical programming groups. Overall, the findings reveal that gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming in PD patients after DBS. Instead of relying solely on spike action potential signals from single neurons, LFP biomarkers can provide the appropriate depth for electrode placement.

Automatic extraction of upper-limb kinematic activity using deep learning-based markerless tracking during deep brain stimulation implantation for Parkinson's disease: A proof of concept study.

Optimal placement of deep brain stimulation (DBS) therapy for treating movement disorders routinely relies on intraoperative motor testing for target determination. However, in current practice, motor testing relies on subjective interpretation and correlation of motor and neural information. Recent advances in computer vision could improve assessment accuracy. We describe our application of deep learning-based computer vision to conduct markerless tracking for measuring motor behaviors of patients undergoing DBS surgery for the treatment of Parkinson’s disease. Video recordings were acquired during intraoperative kinematic testing (N = 5 patients), as part of standard of care for accurate implantation of the DBS electrode. Kinematic data were extracted from videos post-hoc using the Python-based computer vision suite DeepLabCut. Both manual and automated (80.00% accuracy) approaches were used to extract kinematic episodes from threshold derived kinematic fluctuations. Active motor epochs were compressed by modeling upper limb deflections with a parabolic fit. A semi-supervised classification model, support vector machine (SVM), trained on the parameters defined by the parabolic fit reliably predicted movement type. Across all cases, tracking was well calibrated (i.e., reprojection pixel errors 0.016–0.041; accuracies >95%). SVM predicted classification demonstrated high accuracy (85.70%) including for two common upper limb movements, arm chain pulls (92.30%) and hand clenches (76.20%), with accuracy validated using a leave-one-out process for each patient. These results demonstrate successful capture and categorization of motor behaviors critical for assessing the optimal brain target for DBS surgery. Conventional motor testing procedures have proven informative and contributory to targeting but have largely remained subjective and inaccessible to non-Western and rural DBS centers with limited resources. This approach could automate the process and improve accuracy for neuro-motor mapping, to improve surgical targeting, optimize DBS therapy, provide accessible avenues for neuro-motor mapping and DBS implantation, and advance our understanding of the function of different brain areas.

P 29 Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for PD. Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Excitatory and inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .007). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation, but not SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003). Interpretation: Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.

Use of Three-Dimensional Printed Brain Models During Deep Brain Stimulation Surgery Consultation for Patient Health Literacy: A Randomized Controlled Investigation

Advanced therapies in neurosurgery, such as deep brain stimulation (DBS), would benefit from improved patient education materials. Three-dimensional (3D) printed anatomical models represent a recent development for improving patient education for neurosurgical procedures. In this study, 40 patients undergoing DBS surgery consultation were randomly assigned to 1 of 2 groups: an experimental group, which received a demonstration of DBS therapeutic neuroanatomical targets in a 3D printed brain model plus standard patient education (PE), or a control group, which received standard PE alone. Patients in the DBS model plus PE group showed a significant increase in patient confidence and understanding of the brain structures targeted during a DBS procedure compared with patients in the PE-only group (P < 0.01). There was no difference in perceived risk, comfort, or anxiety related to the procedure. In the first randomized controlled study to our knowledge of 3D printed models for DBS consultation, our results demonstrate that patients had improved understanding of their therapy with the models. However, the models alone did not affect risk evaluation or comfort with surgery. A 3D printed brain model may help improve patient understanding of DBS surgery.

Use of Topical Vancomycin Powder to Reduce Surgical Site Infections after Deep Brain Stimulation Surgery: UCSF Experience and Meta-Analysis

Objective: Surgical site infection (SSI) is the most common serious complication of deep brain stimulation (DBS) implantation surgery. Here, we report a single-surgeon experience on the efficacy of topical, intrawound vancomycin powder (VP) in reducing SSI for DBS surgery and present the first systematic review and meta-analysis examining the effect of topical vancomycin on SSI in patients after DBS surgery. Methods: For the retrospective review, all unique patients undergoing DBS surgery at UCSF for new hardware implantation or internal pulse generator (IPG) replacement by a single surgeon from September 2013 to March 2019, with at least 1 year of follow-up data, were included. For the meta-analysis, we included all primary studies that compared SSIs with and without application of topical vancomycin in DBS surgeries. Results: 368 unique patients met inclusion criteria; 195 patients received topical VP (VP group) and 173 did not (control). 99/195 patients in the VP group underwent new DBS implantation and 96/195 had IPG replacement. 71/173 patients in the control group had new DBS implantation and 102/173 had IPG replacement. There were 10 total cases of SSI: 4 patients from the VP group (3 new implants and 1 IPG replacement) and 6 patients from the control group (3 new implants and 3 IPG replacements), resulting in SSI rates of 2.1 and 3.5%, respectively (p value = 0.337). Including our retrospective analysis, 6 studies met inclusion criteria for the systematic review and meta-analysis. In the 4 studies that examined primary DBS implants, 479 total patients received topical VP and 436 did not; mean odds ratio for SSI with topical vancomycin was 0.802 (95% confidence interval [CI] 0.175–3.678). Across the 5 studies that examined IPG implantations or replacements, 606 total patients received topical VP while 1,173 patients did not; mean odds ratio for SSI with topical vancomycin was 0.492 (95% CI 0.164–1.475). In either case, topical VP application did not significantly decrease risk of SSI. Conclusion: Surgical infections after DBS surgery are uncommon events, with studies demonstrating mixed results on whether topical vancomycin reduces this risk. Our single-institution retrospective analysis and systematic review of prior studies both demonstrated no significant SSI rate reduction with topical VP. This is likely due to low baseline SSI rates, resulting in a small effect size for prevention. Given the cost-effectiveness, simplicity, and low risk, topical, intrawound VP remains a treatment option to further reduce risk of SSI, particularly in settings with higher baseline infection rates.

Perioperative complications of deep brain stimulation among patients with advanced age: a single-institution retrospective analysis.

Deep brain stimulation (DBS) is an elective procedure that can dramatically enhance quality of life. Because DBS is not considered lifesaving, it is important that providers produce consistently good outcomes, and one factor they usually consider is patient age. While older age may be a relative contraindication for some elective surgeries, the progressive nature of movement disorders treated with DBS may suggest that older patients stand to benefit substantially from surgery. To better understand the risks of treating patients of advanced age with DBS, this study compares perioperative complication rates in patients ≥ 75 to those < 75 years old. Patients undergoing DBS surgery for various indications by a single surgeon (May 2013-July 2019) were stratified into elderly (age ≥ 75 years) and younger (age < 75 years) cohorts. The risks of common perioperative complications and various outcome measures were compared between the two age groups using risk ratios (RRs) and 95% confidence intervals (CIs). A total of 861 patients were available for analysis: 179 (21%) were ≥ 75 years old and 682 (79%) were < 75 years old (p < 0.001). Patients ≥ 75 years old, compared with those < 75 years old, did not have significantly different RRs (95% CIs) of seizure (RR 0.4, 95% CI 0.1-3.3), cerebrovascular accident (RR 1.9, 95% CI 0.4-10.3), readmission within 90 days of discharge (RR 1.22, 95% CI 0.8-1.8), explantation due to infection (RR 2.5, 95% CI 0.4-15.1), or surgical revision (for lead, RR 2.5, 95% CI 0.4-15.1; for internal pulse generator, RR 3.8, 95% CI 0.2-61.7). Although the risk of postoperative intracranial bleeding was higher in the elderly group (6.1%) than in the younger group (3.1%), this difference was not statistically significant (p = 0.06). However, patients ≥ 75 years old did have significantly increased risk of altered mental status (RR 2.5, 95% CI 1.6-4.0), experiencing more than a 1-night stay (RR 1.7, 95% CI 1.4-2.0), and urinary retention (RR 2.3, 95% CI 1.2-4.2; p = 0.009). Although elderly patients had higher risks of certain outcome measures than younger patients, this study showed that elderly patients undergoing DBS for movement disorders did not have an increased risk of more serious complications, such as intracranial hemorrhage, infection, or readmission. Advanced age alone should not be considered a contraindication for DBS.

Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson\u2019s disease

Despite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130–180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

Frameless ROSA® Robot-Assisted Lead Implantation for Deep Brain Stimulation: Technique and Accuracy.

Frameless robotic-assisted surgery is an innovative technique for deep brain stimulation (DBS) that has not been assessed in a large cohort of patients. To evaluate accuracy of DBS lead placement using the ROSA® robot (Zimmer Biomet) and a frameless registration. All patients undergoing DBS surgery in our institution between 2012 and 2016 were prospectively included in an open label single-center study. Accuracy was evaluated by measuring the radial error (RE) of the first stylet implanted on each side and the RE of the final lead position at the target level. RE was measured on intraoperative telemetric X-rays (group 1), on intraoperative O-Arm® (Medtronic) computed tomography (CT) scans (group 2), and on postoperative CT scans or magnetic resonance imaging (MRI) in both groups. Of 144 consecutive patients, 119 were eligible for final analysis (123 DBS; 186 stylets; 192 leads). In group 1 (76 patients), the mean RE of the stylet was 0.57±0.02 mm, 0.72±0.03 mm for DBS lead measured intraoperatively, and 0.88±0.04 mm for DBS lead measured postoperatively on CT scans. In group 2 (43 patients), the mean RE of the stylet was 0.68±0.05 mm, 0.75±0.04 mm for DBS lead measured intraoperatively; 0.86±0.05 mm and 1.10±0.08 mm for lead measured postoperatively on CT scans and on MRI, respectively No statistical difference regarding the RE of the final lead position was found between the different intraoperative imaging modalities and postoperative CT scans in both groups. Frameless ROSA® robot-assisted technique for DBS reached submillimeter accuracy. Intraoperative CT scans appeared to be reliable and sufficient to evaluate the final lead position.

Investigating Risk Factors and Predicting Complications in Deep Brain Stimulation Surgery with Machine Learning Algorithms

Deep brain stimulation (DBS) surgery is an option for patients experiencing medically resistant neurologic symptoms. DBS complications are rare; finding significant predictors requires a large number of surgeries. Machine learning algorithms may be used to effectively predict these outcomes. The aims of this study were to 1) investigate preoperative clinical risk factors and 2) build machine learning models to predict adverse outcomes. This multicenter registry collected clinical and demographic characteristics of patients undergoing DBS surgery (n= 501) and tabulated occurrence of complications. Logistic regression was used to evaluate risk factors. Supervised learning algorithms were trained and validated on 70% and 30%, respectively, of both oversampled and original registry data. Performance was evaluated using area under the receiver operating characteristics curve (AUC), sensitivity, specificity, and accuracy. Logistic regression showed that the risk of complication was related to the operating institution in which the surgery was performed (odds ratio [OR]= 0.44, confidence interval [CI]= 0.25-0.78), body mass index (OR= 0.94, CI= 0.89-0.99), and diabetes (OR= 2.33, CI= 1.18-4.60). Patients with diabetes were almost 3×more likely to return to the operating room (OR= 2.78, CI= 1.31-5.88). Patients with a history of smoking were 4× more likely to experience postoperative infection (OR= 4.20, CI= 1.21-14.61). Supervised learning algorithms demonstrated high discrimination performance when predicting any complication (AUC= 0.86), a complication within 12 months (AUC= 0.91), return to the operating room (AUC= 0.88), and infection (AUC= 0.97). Age, body mass index, procedure side, gender, and a diagnosis of Parkinson disease were influential features. Multiple significant complication risk factors were identified, and supervised learning algorithms effectively predicted adverse outcomes in DBS surgery.

Procedural outcomes of deep brain stimulation (DBS) surgery in rural and urban patient population settings

Presently, disparities exist between race, sex, socioeconomic status, hospitals, income, comorbidities, and insurance profiles of patients undergoing DBS surgery. Here, we aim to highlight several variables and their predictive powers of DBS surgery outcomes as measured by dischargelocation, length of hospital stays, and total hospital charges. A retrospective cohort study using discharge data from NIS and HCUP for analyses and regression model statistics is performed. Comparative analyses demonstrate urban patients were more often non-routinely discharged, possessed private insurance, and accrued greater hospital costs compared to rural patients. Moreover, regression analyses predicts urban patients have 70% lower odds of routine discharge while those with a major loss of function prior to surgery also have 81% lower odds of routine discharge compared to those with minor loss of function. Ultimately, our study found urban patients or patients with major illnesses have higher hospital charges, longer hospitalization, and more often non-routinely discharged.

Reduced long-term cost and increased patient satisfaction with rechargeable implantable pulse generators for deep brain stimulation.

Deep brain stimulation (DBS) has revolutionized the treatment of neurological disease, but its therapeutic efficacy is limited by the lifetime of the implantable pulse generator (IPG) batteries. At the end of the battery life, IPG replacement surgery is required. New IPGs with rechargeable batteries (RC-IPGs) have recently been introduced and allow for decreased reoperation rates for IPG replacements. The authors aimed to examine the merits and limitations of these devices. The authors reviewed the medical records of patients who underwent DBS implantation at their institution. RC-IPGs were placed either during initial DBS implantation or during an IPG change. A cost analysis was performed that compared RC-IPGs with standard IPGs, and telephone patient surveys were conducted to assess patient satisfaction. The authors identified 206 consecutive patients from 2011 to 2016 who underwent RC-IPG placement (mean age 61 years; 67 women, 33%). Parkinson's disease was the most common indication for DBS (n = 144, 70%), followed by essential tremor (n = 41, 20%), dystonia (n = 13, 6%), depression (n = 5, 2%), multiple sclerosis tremor (n = 2, 1%), and epilepsy (n = 1, 0.5%). DBS leads were typically placed bilaterally (n = 192, 93%) and targeted the subthalamic nucleus (n = 136, 66%), ventral intermediate nucleus of the thalamus (n = 43, 21%), internal globus pallidus (n = 21, 10%), ventral striatum (n = 5, 2%), or anterior nucleus of the thalamus (n = 1, 0.5%). RC-IPGs were inserted at initial DBS implantation in 123 patients (60%), while 83 patients (40%) were converted to RC-IPGs during an IPG replacement surgery. The authors found that RC-IPG implantation resulted in $60,900 of cost savings over the course of 9 years. Furthermore, patient satisfaction was high with RC-IPG implantation. Overall, 87.3% of patients who responded to the survey were satisfied with their device, and only 6.7% found the rechargeable component difficult to use. In patients who were switched from a standard IPG to RC-IPG, the majority who responded (70.3%) preferred the rechargeable IPG. RC-IPGs can provide DBS patients with long-term therapeutic benefit while minimizing the need for battery replacement surgery. The authors have implanted rechargeable stimulators in 206 patients undergoing DBS surgery, and here they demonstrate the cost-effectiveness and high patient satisfaction associated with this procedure.

Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson's disease patients

Both phase-amplitude coupling (PAC) and beta-bursts in the subthalamic nucleus have been significantly linked to symptom severity in Parkinson's disease (PD) in humans and emerged independently as competing biomarkers for closed-loop deep brain stimulation (DBS). However, the underlying nature of subthalamic PAC is poorly understood and its relationship with transient beta burst-events has not been investigated. To address this, we studied macro- and micro electrode recordings of local field potentials (LFPs) and single unit activity from 15 hemispheres in 10 PD patients undergoing DBS surgery. PAC between beta phase and high frequency oscillation (HFO) amplitude was compared to single unit firing rates, spike triggered averages, power spectral densities, inter spike intervals and phase-spike locking, and was studied in periods of beta-bursting. We found a significant synchronisation of spiking to HFOs and correlation of mean firing rates with HFO-amplitude when the latter was coupled to beta phase (i.e. in the presence of PAC). In the presence of PAC, single unit power spectra displayed peaks in the beta and HFO frequency range and the HFO frequency was correlated with that in the LFP. Furthermore, inter spike interval frequencies peaked in the same frequencies for which PAC was observed. Finally, PAC significantly increased with beta burst-duration. Our findings offer new insight in the pathology of Parkinson's disease by providing evidence that subthalamic PAC reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with beta-burst duration. These findings suggest that beta-bursts capture periods of increased subthalamic input/output synchronisation in the beta frequency range and have important implications for therapeutic closed-loop DBS. Significance statementIdentifying biomarkers for closed-loop deep brain stimulation (DBS) has become an increasingly important issue in Parkinson's Disease (PD) research. Two such biomarkers, phase-amplitude coupling (PAC) and beta-bursts, recorded from the implanted electrodes in subthalamic nucleus in PD patients, correlate with motor impairment. However, the physiological basis of PAC, and it relationship to beta bursts, is unclear. We provide multiple lines of evidence that PAC in the human STN reflects the locking of spiking activity to network beta oscillations and that this coupling progressively increases with the duration of beta-bursts. This suggests that beta-bursts capture increased subthalamic input/output synchronisation and provides new insights in PD pathology with direct implications for closed-loop DBS therapy strategies.

Peri-lead edema after deep brain stimulation surgery for Parkinson's disease: a prospective magnetic resonance imaging study.

The aim of this study was to define the prevalence and characteristics of peri-electrode edema in a prospective cohort of patients undergoing deep brain stimulation (DBS) surgery and to correlate it with clinical findings. We performed brain magnetic resonance imaging (MRI) between 7 and 20days after surgery in 19 consecutive patients undergoing DBS surgery for Parkinson's disease. The T2-weighted hyperintensity surrounding DBS leads was characterized and quantified. Any evidence of bleeding around the leads was also evaluated. Clinical and follow-up data were recorded. In a subgroup of patients, a follow-up MRI was performed 3-6weeks after surgery. We also retrospectively reviewed the post-operative computed tomography scans of patients who underwent DBS at our center since 2013. Magnetic resonance imaging showed a peri-lead edematous reaction in all (100%) patients, which was unilateral in three patients (15.8%). In six patients (31.6%), we detected minor peri-lead hemorrhage. Edema completely resolved in eight out of 11 patients with a follow-up MRI and was markedly reduced in the others. Most patients were asymptomatic but six (31.6%) manifested various degrees of confusional state without motor symptoms. We found no significant correlation between edema volume, distribution and any clinical feature, including new post-operative neurological symptoms. The retrospective computed tomography analysis showed that peri-electrode hypodensity consistent with edema is absent at early post-operative imaging but is common at scans performed >3days after surgery. Peri-electrode edema is a common, transient reaction to DBS lead placement and a convincing relation between edema and post-operative clinical status is lacking.

Improved accuracy using a modified registration method of ROSA in deep brain stimulation surgery

OBJECTIVE The aim of this study was to determine whether a modified registration method could reduce registration error and postoperative electrode vector error and to analyze the method's clinical significance in deep brain stimulation (DBS) surgery. METHODS The first part of the study involved a skull model, in which three registration methods were tested using the ROSA (robotic stereotactic assistance) system. In the second part, four registration methods were clinically tested in patients undergoing DBS surgery using the ROSA system. Thirty-three patients (65 sides, group I) underwent the conventional registration method 2E, and registration errors were recorded. Thirty-eight patients (75 sides, group II) underwent four types of modified registration methods including 2A, 2B, 2C, and 2D. Registration and electrode vector errors, intraoperative electrophysiological signal length (IESL), and DBS power-on voltage were recorded. The primary measure of efficacy was the change in the Unified Parkinson's Disease Rating Scale (UPDRS) and UPDRS Part III scores from baseline to 10 weeks after surgery. RESULTS In the skull model, the registration error (mean ± SD) was 0.56 ± 0.11 mm for method 1A, 0.35 ± 0.11 mm for method 1B (vs. 1A, p < 0.001), and 0.90 ± 0.15 mm for method 1C (vs. 1A, p < 0.001). In the clinical study, method 2C was selected for DBS surgery in group II since it had the smallest registration error among the four methods tested. The registration error was 0.62 ± 0.22 mm (mean ± SD) for group I and 0.27 ± 0.07 mm for group II (p < 0.001). Postoperative electrode vector error was 0.97 ± 0.31 mm for group I and 0.65 ± 0.23 mm for group II (p < 0.001). There was a positive correlation between registration error and electrode vector error in both groups (group I: r = 0.69, p < 0.001; group II: r = 0.71, p < 0.001). The mean IESL was 5.0 ± 0.9 mm in group I and 5.8 ± 0.7 mm in group II (p < 0.001). The mean DBS power-on voltage was 1.63 ± 0.44 V in group I and 1.48 ± 0.38 V in group II (p = 0.027). In the UPDRS score, group I showed 50% ± 16% improvement and group II showed 52% ± 18% improvement (p = 0.724); there was no statistically significant difference in improvement on the UPDRS. CONCLUSIONS In DBS surgery assisted by the ROSA system, registration error and electrode vector error showed a positive correlation. The modified registration method could reduce the registration error and electrode vector error, but the long-term effects need to be further observed and evaluated.

Analysis of adverse effects of stimulation during DBS surgery by patient-specific FEM simulations.

Deep brain stimulation (DBS) represents today a well-established treatment for movement disorders. Nevertheless the exact mechanism of action of DBS remains incompletely known. During surgery, numerous stimulation tests are frequently performed in order to evaluate therapeutic and adverse effects before choosing the optimal implantation site for the DBS lead. Anatomical structures responsible for the induced adverse effects have been investigated previously, but only based on stimulation data obtained with the implanted DBS lead. The present study introduces a methodology to identify these anatomical structures during intraoperative stimulation tests based on patient-specific electric field simulations and visualization on the patient specific anatomy. The application to 4 patients undergoing DBS surgery and presenting dysarthria, paresthesia or pyramidal effects shows the different anatomical structures, which might be responsible for the adverse effects. Several of the identified structures have been previously described in the literature. To draw any statistically significant conclusions, the methodology has to be applied to further patients. Together with the visualization of the therapeutic effects, this new approach could assist the neurosurgeons in the future in choosing the optimal implant position.

P 72 Influence of anesthesia on the outcome in patients with Parkinson’s disease undergoing deep brain stimulation of the subthalamic nucleus

Background Currently, implantation of electrodes for Deep Brain Stimulation (DBS) as a treatment for patients with Parkinson’s Disease (PD) is usually performed under local anaesthesia (LA) to allow intraoperative testing of effects and side effects. Recently, several studies have indicated that surgery under general anaesthesia (GA) may lead to comparable outcomes. However, most of these studies did not compare the types of anesthesia directly. Objective This study aims to investigate whether the type of anesthesia (LA vs. GA) affects the outcome of motor and cognitive symptoms and reduction of levodopa-equivalent daily dose (LEDD) after subthalamic nucleus (STN)-DBS over a period of one year in a large single center population. Methods 48 patients underwent DBS in GA between 2008 and 2015 at the center of movement disorders in Dusseldorf. From the other 140 patients operated by the standard procedure in LA in the same period of time, 48 patients were matched to the GA group. These groups were compared regarding improvement in motor function measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) III, decrease of LEDD, setting of stimulation parameters, cognitive function measured with neuropsychological tests and occurrence of stimulation induced side effect. Results Motor function measured by the UPDRS III score in the medication off, stimulation on state was significantly better in the LA group compared to the GA group. Subscore analysis revealed that axial symptoms “freezing” and “speech” were significantly worse in the GA group at three months and one year, respectively. Postoperative LEDD-reduction was significant in both groups and did not differ between the groups over the whole period of one year. There were no significant differences of stimulation amplitude and cognition between the groups. Stimulation induced side effects tended to be less frequent in the LA group but did not reach statistical significance. Conclusions In our study, motor function of patients undergoing DBS surgery in LA improved significantly more over the period of one year postoperatively compared to those operated in GA. Furthermore postoperative stimulation induced side effects tended to be less frequent in the LA group. We therefore conclude that surgery in LA with intraoperative testing is still significantly advantageous for PD patients undergoing STN-DBS and should be first choice if there are no other specific limitations that make GA unavoidable.

Hemodynamic Perturbations in Deep Brain Stimulation Surgery: First Detailed Description.

Background: Hemodynamic perturbations can be anticipated in deep brain stimulation (DBS) surgery and may be attributed to multiple factors. Acute changes in hemodynamics may produce rare but severe complications such as intracranial bleeding, transient ischemic stroke and myocardium infarction. Therefore, this retrospective study attempts to determine the incidence of hemodynamic perturbances (rate) and related risk factors in patients undergoing DBS surgery.Materials and Methods: After institutional approval, all patients undergoing DBS surgery for the past 10 years were recruited for this study. Demographic characteristics, procedural characteristics and intraoperative hemodynamic changes were noted. Event rate was calculated and the effect of all the variables on hemodynamic perturbations was analyzed by regression model.Results: Total hemodynamic adverse events during DBS surgery was 10.8 (0–42) and treated in 57% of cases.Conclusion: Among all the perioperative variables, the baseline blood pressure including systolic, diastolic, and mean arterial pressure was found to have highly significant effect on these intraoperative hemodynamic perturbations.