Nucleus basalis of Meynert neuronal activity in Parkinson’s disease

J Neurosurg 132:574–582, 2020

Neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer’s disease and Parkinson’s disease (PD). In nonhuman primates, the nbM firing pattern (5–40 Hz) has also been correlated with working memory and sustained attention. In this study, authors performed microelectrode recordings of the globus pallidus pars interna (GPi) and the nbM immediately prior to the implantation of bilateral deep brain stimulation (DBS) electrodes in PD patients to treat motor symptoms and cognitive impairment, respectively. Here, the authors evaluate the electrophysiological properties of the nbM in patients with PD.

METHODS Five patients (4 male, mean age 66 ± 4 years) with PD and mild cognitive impairment underwent bilateral GPi and nbM DBS lead implantation. Microelectrode recordings were performed through the GPi and nbM along a single trajectory. Firing rates and burst indices were characterized for each neuronal population with the patient at rest and performing a sustained-attention auditory oddball task. Action potential (AP) depolarization and repolarization widths were measured for each neuronal population at rest.

RESULTS In PD patients off medication, the authors identified neuronal discharge rates that were specific to each area populated by GPi cells (92.6 ± 46.1 Hz), border cells (34 ± 21 Hz), and nbM cells (13 ± 10 Hz). During the oddball task, firing rates of nbM cells decreased (2.9 ± 0.9 to 2.0 ± 1.1 Hz, p < 0.05). During baseline recordings, the burst index for nbM cells (1.7 ± 0.6) was significantly greater than those for GPi cells (1.2 ± 0.2, p < 0.05) and border cells (1.1 ± 0.1, p < 0.05). There was no significant difference in the nbM burst index during the oddball task relative to baseline (3.4 ± 1.7, p = 0.20). With the patient at rest, the width of the depolarization phase of APs did not differ among the GPi cells, border cells, and nbM cells (p = 0.60); however, during the repolarization phase, the nbM spikes were significantly longer than those for GPi high-frequency discharge cells (p < 0.05) but not the border cells (p = 0.20).

CONCLUSIONS Neurons along the trajectory through the GPi and nbM have distinct firing patterns. The profile of nbM activity is similar to that observed in nonhuman primates and is altered during a cognitive task associated with cholinergic activation. These findings will serve to identify these targets intraoperatively and form the basis for further research to characterize the role of the nbM in cognition.

Subthalamic deep brain stimulation under general anesthesia and neurophysiological guidance while on dopaminergic medication

Acta Neurochirurgica (2018) 160:823–829

The authors have previously reported on the technical feasibility of subthalamic nucleus deep brain stimulation (STN DBS) under general anesthesia (GA) with microelectrode recording (MER) guidance in Parkinsonian patients who continued dopaminergic therapy until surgery. This paper presents the results of a prospective cohort analysis to verify the outcome of the initial study, and report on wider aspects of clinical outcome and postoperative recovery. Methods All patients in the study group continued dopaminergic therapy until GA was administered. Baseline characteristics, intraoperative neurophysiological markers, and perioperative complications were recorded. Long-term outcome was assessed using selective aspects of the unified Parkinson’s disease rating scale motor score. Immediate postoperative recovery from GA was assessed using the Btime needed for extubation^ and Btotal time of recovery.^ Data for the Bstudy group^ was collected prospectively. Examined variables were compared between the Bstudy group^ and Bhistorical control group^ who stopped dopaminergic therapy preoperatively. Results The study group, n = 30 (May 2014–Jan 2016), were slightly younger than the Bcontrol group,^ 60 (51–64) vs. 64 (56– 69) years respectively, p = 0.043. Both groups were comparable for the recorded intraoperative neurophysiological parameters;number of MER tracks: 60% of the study group had single track vs. 58% in the control group, p = 1.0. Length of STN MER detected was 9 vs. 7 mm (median) respectively, p = 0.037. A trend towards better recovery from GA in the study group was noted, with shorter total recovery time: 60 (50–84) vs. 89 (62–120) min, p = 0.09. Long-term improvement in motor scores and reduction in L-dopa daily equivalent dose were equally comparable between both groups. No cases of dopamine withdrawal or problems with immediate postop dyskinesia were recorded in the on medications group. The observed rate of dopamine withdrawal side effects in the off-medications group was 15%.

Conclusions The continuation of dopaminergic treatment for patients with PD does not affect the feasibility/outcome of the STN DBS surgery. This strategy appears to reduce the risk of dopamine-withdrawal adverse effects and may improve the recovery in the immediate postoperative period, which would help enhance patients’ perioperative experience.

 

Simultaneous bilateral stereotactic procedure for deep brain stimulation implants

Simultaneous bilateral stereotactic procedure for deep brain stimulation implants

J Neurosurg 125:85–89, 2016

Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads.

Methods Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson’s disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared.

Results Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time.

Conclusions A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional stereotactic procedures.

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.

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.

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.

Discrepancies between the MRI and the electrophysiologically defined subthalamic nucleus

Acta Neurochir (2011) 153:2307–2318. DOI 10.1007/s00701-011-1081-7

The aim of our study was to evaluate discrepancies between the electrophysiologically and MRI-defined subthalamic nucleus (STN) in order to contribute to the ongoing debate of whether or not microelectrode recording (MER) provides additional information to imageguided targeting in deep brain stimulation.

Methods: Forty-four STNs in 22 patients with Parkinson’s disease were investigated. The three-dimensional MRI-defined STN was derived from segmentations of axial and coronal T2-weighted images. The electrophysiological STNs were generated from intraoperative MERs in 1,487 locations. The stereotactical coordinates of positive and negative STN recordings were re-imported to the planning software, where a three-dimensional reconstruction of the electrophysiological STN was performed and fused to the MRI data set. The estimated borders of the MRI- and MERSTN were compared. For statistical analysis Student’s t, Mann-Whitney rank sum and Fisher’s exact tests were used.

Results: MER-STN volumes, which were found outside the MRI-STN, ranged from 0 mm3 to 87 mm3 (mean: 45 mm3). A mean of 44% of the MER-STN volumes exceeded the MRI-STN (maximum: 85.1%; minimum: 15.1 %); 53.4% (n=793) of the microelectrode recordings were concordant and 46.6% (n=694) discordant with the MRI-defined anatomical STN. Regarding the dorsal borders, we found discrepancies between the MER- and MRI-STN of 0.27 mm (= mean; SD: 0.51 mm) on the first operated side and 1.51 mm (SD: 1.5 mm) on the second (p=0.010, t-test).

Conclusions: MER provides additional information to highresolution anatomical MR images and may help to detect the amount and direction of brain shift.

Bilateral subthalamic deep brain stimulation using single track microelectrode recording

Acta Neurochir (2011) 153:1087–1095 DOI 10.1007/s00701-011-0953-1

Microelectrode recording (MER) is widely used during deep brain stimulation (DBS) procedures because MER can identify structural borders and eloquent structures, localize somatotopic arrangements, and provide an outline of the three-dimensional shapes of target nuclei. However, MER may cause intracranial hemorrhage. We performed single track MER during DBS procedures, analyzed the accuracy of electrode positioning with MRI, and compared the amount of air and the potential risk of intracranial hemorrhage.

Method A total of 46 electrodes were placed in 23 patients who suffered from advanced Parkinson’s disease and who underwent bilateral subthalamic nucleus DBS using single track MER. Each patient’s Unified Parkinson’s Disease Rating Scale (UPDRS) score and levo-dopa equivalent dosage (LED) were estimated pre- and postoperatively. The accuracy of electrode positioning and fontal air thickness was measured by a pre- or postoperative magnetic resonance imaging (MRI) merging technique.

Findings The mean electrode positioning error was 0.92 mm (0.3–2.94 mm). The mean frontal air thickness on postoperative MRI was 3.85 mm (0–10.3 mm), which did not affect the electrode accuracy statistically (p=0.730). A total of nine electrodes required repositioning after single-track MER because they affected microstimulation or because an abnormally short STN length was observed during MER. In this series, one patient suffered from an intracranial hemorrhage after surgery that appeared to be due to venous infarction rather than related to MER.

Conclusions Although MER can facilitate accurate positioning of electrodes, multi-track MER may increase the risk of intracranial hemorrhage. The accuracy of electrode positioning appears to be acceptable under single track MER during STN DBS with careful electrophysiological and neurological monitoring. The risk of intracranial hemorrhage appears to be minimal, especially in elderly patients with atrophic brains.