Bilateral Deep Brain Stimulation of the Subthalamic Nucleus under Sedation with Propofol and Fentanyl.
ABSTRACT: Awakening during deep brain stimulation (DBS) surgery may be stressful to patients. The aim of the current study was to evaluate the effect on MER signals and their applicability to subthalmic nucleus (STN) DBS surgery for patients with Parkinson's disease (PD) under sedation with propofol and fentanyl. Sixteen consecutive patients with PD underwent STN-DBS surgery with propofol and fentanyl. Their MER signals were achieved during the surgery. To identify the microelectrodes positions, the preoperative MRI and postoperative CT were used. Clinical profiles were also collected at the baseline and at 6 months after surgery. All the signals were slightly attenuated and contained only bursting patterns, compared with our previous report. All electrodes were mostly located in the middle one third part of the STN on both sides of the brain in the fused images. Six months later, the patients were improved significantly in the medication-off state and they met with less dyskinesia and less off-duration. Our study revealed that the sedation with propofol and fentanyl was applicable to STN-DBS surgery. There were no significant problems in precise positioning of bilateral electrodes. The surgery also improved significantly clinical outcomes in 6-month follow-up.
Project description:Microelectrode recording (MER) is often used to identify electrode location which is critical for the success of deep brain stimulation (DBS) treatment of Parkinson's disease. The usage of anesthesia and its' impact on MER quality and electrode placement is controversial. We recorded neuronal activity at a single depth inside the Subthalamic Nucleus (STN) before, during, and after remifentanil infusion. The root mean square (RMS) of the 250-6000 Hz band-passed signal was used to evaluate the regional spiking activity, the power spectrum to evaluate the oscillatory activity and the coherence to evaluate synchrony between two microelectrodes. We compare those to new frequency domain (spectral) analysis of previously obtained data during propofol sedation. Results showed Remifentanil decreased the normalized RMS by 9% (P?<?0.001), a smaller decrease compared to propofol. Regarding the beta range oscillatory activity, remifentanil depressed oscillations (drop from 25 to 5% of oscillatory electrodes), while propofol did not (increase from 33.3 to 41.7% of oscillatory electrodes). In the cases of simultaneously recorded oscillatory electrodes, propofol did not change the synchronization while remifentanil depressed it. In conclusion, remifentanil interferes with the identification of the dorsolateral oscillatory region, whereas propofol interferes with RMS identification of the STN borders. Thus, both have undesired effect during the MER procedure.Trial registration: NCT00355927 and NCT00588926.
Project description:<h4>Background</h4>Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation electrodes is necessary for better clinical outcomes.<h4>Objective</h4>We applied deep learning techniques to microelectrode recording (MER) signals to better predict motor function improvement, represented by the UPDRS part III scores, after bilateral STN DBS in patients with advanced PD. If we find the optimal stimulation point with MER by deep learning, we can improve the clinical outcome of STN DBS even under restrictions such as general anesthesia or non-cooperation of the patients.<h4>Methods</h4>In total, 696 4-second left-side MER segments from 34 patients with advanced PD who underwent bilateral STN DBS surgery under general anesthesia were included. We transformed the original signal into three wavelets of 1-50 Hz, 50-500 Hz, and 500-5,000 Hz. The wavelet-transformed MER was used for input data of the deep learning. The patients were divided into two groups, good response and moderate response groups, according to DBS on to off ratio of UPDRS part III score for the off-medication state, 6 months postoperatively. The ratio were used for output data in deep learning. The Visual Geometry Group (VGG)-16 model with a multitask learning algorithm was used to estimate the bilateral effect of DBS. Different ratios of the loss function in the task-specific layer were applied considering that DBS affects both sides differently.<h4>Results</h4>When we divided the MER signals according to the frequency, the maximal accuracy was higher in the 50-500 Hz group than in the 1-50 Hz and 500-5,000 Hz groups. In addition, when the multitask learning method was applied, the stability of the model was improved in comparison with single task learning. The maximal accuracy (80.21%) occurred when the right-to-left loss ratio was 5:1 or 6:1. The area under the curve (AUC) was 0.88 in the receiver operating characteristic (ROC) curve.<h4>Conclusion</h4>Clinical improvements in PD patients who underwent bilateral STN DBS could be predicted based on a multitask deep learning-based MER analysis.
Project description:OBJECTIVE:Intraoperative microelectrode recording (MER) and test-stimulation are regarded as the gold standard for proper placement of subthalamic (STN) deep brain stimulation (DBS) electrodes in Parkinson's disease (PD), requiring the patient to be awake during the procedure. In accordance with good clinical practice, most attending neurologists will request the clinically most efficacious trajectory for definite lead placement. However, the necessity of microelectrode-test-stimulation is disputed, as it may limit the access to DBS therapy, excluding those not willing or incapable of undergoing awake surgery. METHODS:We retrospectively analyzed the MERs and microelectrode-test-stimulation results with regard to the decision on definite lead placement and clinical outcome in a cohort of 67 PD-patients with STN-DBS. All patients received bilateral quadripolar ring electrodes. To ascertain overall procedural efficacy, we calculated the surgical index (SI) by comparing preoperative motor improvement induced by levodopa to that induced by stimulation 7 to 18 months after surgery, measured as the relative difference between ON and OFF-states on the Unified Parkinson's Disease Rating Scale motor part (UPDRS-3). Additionally, a side-specific surgical index (SSSI) was calculated using the unilateral assessable items of the UPDRS-3. The SSSI where microelectrode-test-stimulation overruled MER were compared to those where the result of microelectrode-test-stimulation was congruent to MER results. RESULTS:A total of 134 electrodes were analyzed. For final lead placement, the central trajectory was chosen in 54% of patient hemispheres. The mean SI was 0.99 (± 0.24). SSSI averaged 1.04 (± 0.45). In 37 lead placements, microelectrode-test-stimulation overruled MER in the final trajectory selection, in 27 of these lead placements adverse effects during microelectrode-test-stimulation were decisive. Neither the number of test electrodes used nor the STN-signal length had an impact on the SSSI. The SSSI did not differ between lead placements with MER/microelectrode-test-stimulation congruency and those where the results of microelectrode-test-stimulation initiated lead placement in a trajectory with shorter STN signal. CONCLUSION:Intraoperative testing is mandatory to ensure an optimal motor outcome of STN DBS in PD-patients when using quadripolar ring electrodes. However, we also demonstrated that neither the length of the STN-signal on MER nor the number of test electrodes influenced the motor outcome.
Project description:Deep brain stimulation (DBS) surgery of the subthalamic nucleus (STN) under general anesthesia (GA) had been used in Parkinson's disease (PD) patients who are unable tolerate awake surgery. The effect of anesthetics on intraoperative microelectrode recording (MER) remains unclear. Understanding the effect of anesthetics on MER is important in performing STN DBS surgery with general anesthesia. In this study, we retrospectively performed qualitive and quantitative analysis of STN MER in PD patients received STN DBS with controlled desflurane anesthesia or LA and compared their clinical outcome. From January 2005 to March 2006, 19 consecutive PD patients received bilateral STN DBS surgery in Hualien Tzu-Chi hospital under either desflurane GA (n = 10) or LA (n = 9). We used spike analysis (frequency and modified burst index [MBI]) and the Hilbert transform to obtain signal power measurements for background and spikes, and compared the characterizations of intraoperative microelectrode signals between the two groups. Additionally, STN firing pattern characteristics were determined using a combined approach based on the autocorrelogram and power spectral analysis, which was employed to investigate differences in the oscillatory activities between the groups. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) before and after surgery. The results revealed burst firing was observed in both groups. The firing frequencies were greater in the LA group and MBI was comparable in both groups. Both the background and spikes were of significantly greater power in the LA group. The power spectra of the autocorrelograms were significantly higher in the GA group between 4 and 8 Hz. Clinical outcomes based on the UPDRS were comparable in both groups before and after DBS surgery. Under controlled light desflurane GA, burst features of the neuronal firing patterns are preserved in the STN, but power is reduced. Enhanced low-frequency (4-8 Hz) oscillations in the MERs for the GA group could be a characteristic signature of desflurane's effect on neurons in the STN.
Project description:BACKGROUND:Microelectrode recordings (MER) are used to optimize lead placement during subthalamic nucleus deep brain stimulation (STN-DBS). To obtain reliable MER, surgery is usually performed while patients are awake. Procedural sedation and analgesia (PSA) is often desirable to improve patient comfort, anxiolysis and pain relief. The effect of these agents on MER are largely unknown. The objective of this study was to determine the effects of commonly used PSA agents, dexmedetomidine, clonidine and remifentanil and patient characteristics on MER during DBS surgery. METHODS:Data from 78 patients with Parkinson's disease (PD) who underwent STN-DBS surgery were retrospectively reviewed. The procedures were performed under local anesthesia or under PSA with dexmedetomidine, clonidine or remifentanil. In total, 4082 sites with multi-unit activity (MUA) and 588 with single units were acquired. Single unit firing rates and coefficient of variation (CV), and MUA total power were compared between patient groups. RESULTS:We observed a significant reduction in MUA, an increase of the CV and a trend for reduced firing rate by dexmedetomidine. The effect of dexmedetomidine was dose-dependent for all measures. Remifentanil had no effect on the firing rate but was associated with a significant increase in CV and a decrease in MUA. Clonidine showed no significant effect on firing rate, CV or MUA. In addition to anesthetic effects, MUA and CV were also influenced by patient-dependent variables. CONCLUSION:Our results showed that PSA influenced neuronal properties in the STN and the dexmedetomidine (DEX) effect was dose-dependent. In addition, patient-dependent characteristics also influenced MER.
Project description:<h4>Objective</h4>Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change.<h4>Methods</h4>Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year.<h4>Results</h4>Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2%±20.15% off-medication and 16.9%±21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6%±5.5% and 4.5%±8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year.<h4>Conclusion</h4>The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients.<h4>Classification of evidence</h4>This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy.
Project description:Refinement of the subthalamic nucleus (STN) coordinates using intraoperative microelectrode recordings (MER) is routinely performed during deep brain stimulation (DBS) surgeries in Parkinson disease (PD). The commonly used criteria for electrophysiological localization of the STN are qualitative. The goal of this study was to validate quantitative STN detection algorithm (QD) derived from the multi-unit activity in a prospective setting.Ten PD patients underwent STN DBS surgery. The MUA was obtained by removing large spikes close to microelectrode using wavelet method and integrating the 500-2000Hz band in the power spectral density. The qualitative intraoperative mapping of the STN using MER (IOM) versus QD was compared using Bland-Altman and Pearson's correlation analysis.The clinical efficacy was confirmed in all subjects. The mean difference between IOM and QD of the dorsal/ventral border was 0.31±0.84/0.44±0.47mm. Using Bland-Altman statistic, only 2/36 (5.6%) differences (one for the dorsal border and one for the ventral border) were out of ±2 sd line of measurement differences. Correlation between dorsal border/ventral border positions obtained by IOM and QD was 0.79, p<0.0001/0.91, p<0.0001.Both methods are in reasonable agreement and are strongly correlated. The QD gives objective coordinates of the STN borders at high precision and may be more accurate than IOM. Prospective blinded comparative studies where the DBS leads will be placed using either QD or IOM are warranted.
Project description:BACKGROUND:Implantation of deep brain stimulation (DBS) electrodes for the treatment of involuntary movement disorders, such as Parkinson's disease, routinely relies on the use of intraoperative electrophysiological confirmation to identify the optimal therapeutic target in the brain. However, only a few options exist to visualize the relative anatomic localization of intraoperative electrophysiological recordings with respect to post-operative imaging. We have developed a novel processing pipeline to visualize intraoperative electrophysiological signals registered to post-operative neuroanatomical imaging. NEW METHOD:We developed a processing pipeline built on the use of ITK-SNAP and custom MATLAB scripts to visualize the anatomical localization of intraoperative electrophysiological recordings mapped onto the post-operative MRI following implantation of DBS electrodes. This method combines the user-defined relevant electrophysiological parameters measured during the surgery with a manual segmentation of the DBS electrode from post-operative MRI; mapping the microelectrode recording (MER) depths along the DBS lead track. RESULTS:We demonstrate the use of our processing pipeline on data from Parkinson's disease patients undergoing DBS implantation targeted to the subthalamic nucleus (STN). The primary processing components of the pipeline are: extrapolation of the lead wire and alignment of intraoperative electrophysiology. CONCLUSION:We describe the use of a processing pipeline to aid clinicians and researchers engaged in deep brain stimulation work to correlate and visualize the intraoperative recording data with the post-operative DBS trajectory.
Project description:Single cell neuronal activity (SUA) and local field potentials (LFP) in the subthalamic nucleus (STN) of unmedicated Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery have been well-characterized during microelectrode recordings (MER). However, there is limited knowledge about the changes in the firing patterns and oscillations above and within the territories of STN after the intake of dopaminergic medication. Here, for the first time, we report the STN single cell and oscillatory neural dynamics in a medicated patient with idiopathic PD using intraoperative MER. We recorded LFP and SUA with microelectrodes at various depths during bilateral STN-DBS electrode implantation. We isolated 26 neurons in total and observed that tonic and irregular firing patterns of individual neurons predominated throughout the territories of STN. While burst-type firings have been well-characterized in the dorsal territories of STN in unmedicated patients, interestingly, this activity was not observed in our medicated subject. LFP recordings lacked the excessive beta (8-30 Hz) activity, characteristic of the unmedicated state and signal energy was mainly dominated by slow oscillations below 8 Hz. We observed sharp gamma oscillations between 70 and 90 Hz within and above the STN. Despite the presence of a broadband high frequency activity in 200-400 Hz range, no cross-frequency interaction in the form of phase-amplitude coupling was noted between low and high frequency oscillations of LFPs. While our results are in agreement with the previously reported LFP recordings from the DBS lead in medicated PD patients, the sharp gamma peak present throughout the depth recordings and the lack of bursting firings after levodopa intake have not been reported before. The lack of bursting in SUA, the lack of excessive beta activity and cross frequency coupling between HFOs and lower rhythms further validate the link between bursting firing regime of neurons and pathological oscillatory neural activity in PD-STN. Overall, these observations not only validate the existing literature on the PD electrophysiology in healthy/medicated animal models but also provide insights regarding the underlying electro-pathophysiology of levodopa-induced dyskinesias in PD patients through demonstration of multiscale relationships between single cell firings and field potentials.
Project description:To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease (PD).We retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson's Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups.At 12 months, the mean changes in the UPDRS total and part I-IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697).The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.