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Objective: Deep brain stimulation (DBS) is an effective therapy for different neurological diseases, despite the lack of comprehension of its mechanism of action. The use of nonhuman primates (NHPs) has been historically important in advancing this field and presents a unique opportunity to uncover the therapeutic mechanisms of DBS, opening the way for optimization of current applications and the development of new ones. To be informative, research using NHPs should make use of appropriate electrode implantation tools. In the present work, the authors report on the feasibility and accuracy of targeting different deep brain regions in NHPs using a commercially available frameless stereotactic system (microTargeting platform)., Methods: Seven NHPs were implanted with DBS electrodes, either in the subthalamic nucleus or in the cerebellar dentate nucleus. A microTargeting platform was designed for each animal and used to guide implantation of the electrode. Imaging studies were acquired preoperatively for each animal, and were subsequently analyzed by two independent evaluators to estimate the electrode placement error (EPE). The interobserver variability was assessed as well., Results: The radial and vector components of the EPE were estimated separately. The magnitude of the vector of EPE was 1.29 ± 0.41 mm and the mean radial EPE was 0.96 ± 0.63 mm. The interobserver variability was considered negligible., Conclusions: These results reveal the suitability of this commercial system to enhance the surgical insertion of DBS leads in the primate brain, in comparison to rigid traditional frames. Furthermore, our results open up the possibility of performing frameless stereotaxy in primates without the necessity of relying on expensive methods based on intraoperative imaging.

Objective: Parkinson's disease (PD) is a progressive neurological movement disorder that is commonly treated with deep brain stimulation (DBS) surgery in advanced stages. The purpose of this study was to investigate factors that affect time to placement of a second-sided DBS lead for PD when a unilateral lead is initially placed for asymmetrical presentation. The decision whether to initially perform unilateral or bilateral DBS is largely based on physician and/or patient preference., Methods: This study was a retrospective cohort analysis of patients with PD undergoing initial unilateral DBS for asymmetrical disease between January 1999 and December 2017 at the authors' institution. Patients treated with DBS for essential tremor or other conditions were excluded. Variables collected included demographics at surgery, time since diagnosis, Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III), patient-reported quality-of-life outcomes, side of operation, DBS target, intraoperative complications, and date of follow-up. Paired t-tests were used to assess mean changes in UPDRS-III. Cox proportional hazards analysis and the Kaplan-Meier method were used to determine factors associated with time to second lead insertion over 5 years., Results: The final cohort included 105 patients who underwent initial unilateral DBS for asymmetrical PD; 59% of patients had a second-sided lead placed within 5 years with a median time of 34 months. Factors found to be significantly associated with early second-sided DBS included patient age 65 years or younger, globus pallidus internus (GPi) target, and greater off-medication reduction in UPDRS-III score following initial surgery. Older age was also found to be associated with a smaller preoperative UPDRS-III levodopa responsiveness score and with a smaller preoperative to postoperative medication-off UPDRS-III change., Conclusions: Younger patients, those undergoing GPi-targeted unilateral DBS, and patients who responded better to the initial DBS were more likely to undergo early second-sided lead placement. Therefore, these patients, and patients who are more responsive to medication preoperatively (as a proxy for DBS responsiveness), may benefit from consideration of initial bilateral DBS.

OBJECTIVEThe authors' aim in this study was to evaluate placement accuracy and clinical outcomes in patients who underwent implantation of deep brain stimulation devices with the aid of frame-based stereotaxy and intraoperative MRI after induction of general anesthesia.METHODSThirty-three patients with movement disorders (27 with Parkinson's disease) underwent implantation of unilateral or bilateral deep brain stimulation systems (64 leads total). All patients underwent the implantation procedure with standard frame-based techniques under general anesthesia and without microelectrode recording. MR images were acquired immediately after the procedure and fused to the preoperative plan to verify accuracy. To evaluate clinical outcome, different scales were used to assess quality of life (EQ-5D), activities of daily living (Unified Parkinson's Disease Rating Scale [UPDRS] part II), and motor function (UPDRS part III during off- and on-medication and off- and on-stimulation states). Accuracy was assessed by comparing the coordinates (x, y, and z) from the preoperative plan and coordinates from the tip of the lead on intraoperative MRI and postoperative CT scans.RESULTSThe EQ-5D score improved or remained stable in 71% of the patients. When in the off-medication/on-stimulation state, all patients reported significant improvement in UPDRS III score at the last follow-up (p < 0.001), with a reduction of 25.2 points (46.3%) (SD 14.7 points and 23.5%, respectively). There was improvement or stability in the UPDRS II scores for 68% of the Parkinson's patients. For 2 patients, the stereotactic error was deemed significant based on intraoperative MRI findings. In these patients, the lead was removed and replaced after correcting for the error during the same procedure. Postoperative lead revision was not necessary in any of the patients. Based on findings from the last intraoperative MRI study, the mean difference between the tip of the electrode and the planned target was 0.82 mm (SD 0.5 mm, p = 0.006) for the x-axis, 0.67 mm (SD 0.5 mm, p < 0.001) for the y-axis, and 0.78 mm (SD 0.7 mm, p = 0.008) for the z-axis. On average, the euclidian distance was 1.52 mm (SD 0.6 mm). In patients who underwent bilateral implantation, accuracy was further evaluated comparing the first implanted side and the second implanted side. There was a significant mediolateral (x-axis) difference (p = 0.02) in lead accuracy between the first (mean 1.02 mm, SD 0.57 mm) and the second (mean 0.66 mm, SD 0.50 mm) sides. However, no significant difference was found for the y- and z-axes (p = 0.10 and p = 0.89, respectively).CONCLUSIONSFrame-based DBS implantation under general anesthesia with intraoperative MRI verification of lead location is safe, accurate, precise, and effective compared with standard implantation performed using awake intraoperative physiology. More clinical trials are necessary to directly compare outcomes of each technique.

Objective: The number of patients who benefit from deep brain stimulation (DBS) for Parkinson's disease (PD) has increased significantly since the therapy was first approved by the FDA. Suboptimal outcomes, infection, or device failure are risks of the procedure and may require lead removal or repositioning. The authors present here the results of their series of revision and reimplantation surgeries., Methods: The data were reviewed from all DBS intracranial lead removals, revisions, or reimplantations among patients with PD over a 6-year period at the authors' institution. The indications for these procedures were categorized as infection, suboptimal outcome, and device failure. Motor outcomes as well as lead location were analyzed before removal and after reimplant or revision., Results: The final sample included 25 patients who underwent 34 lead removals. Thirteen patients had 18 leads reimplanted after removal. There was significant improvement in the motor scores after revision surgery among the patients who had the lead revised for a suboptimal outcome (p = 0.025). The mean vector distance of the new lead location compared to the previous location was 2.16 mm (SD 1.17), measured on an axial plane 3.5 mm below the anterior commissure-posterior commissure line. When these leads were analyzed by subgroup, the mean distance was 1.67 mm (SD 0.83 mm) among patients treated for infection and 2.73 mm (SD 1.31 mm) for those with suboptimal outcomes., Conclusions: Patients with PD who undergo reimplantation surgery due to suboptimal outcome may experience significant benefits. Reimplantation after surgical infection seems feasible and overall safe.