Refractory Parkinson's Disease Research Articles

Deep brain stimulation for Parkinson's disease: experience, benefits and limitations in a center in Latin America

Parkinson's disease is poorly studied in Colombia. It is pharmacologically managed, but for refractory cases, surgery is a therapeutic option, positively impacting on quality of life. To determine the impact of deep brain stimulation as management in the control of progression in patients with Parkinson's disease attended our institution between the years 2014 to 2020. Descriptive retrospective study, with patients collected between 2014 and 2020 undergoing deep brain stimulation surgery. The MDS-UPDRS (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale) was applied in the pre- and postoperative period, and the results were compared. 21 patients were included and the UPDRS was applied, finding a decrease in scores in the postoperative period. One patient had an operative site infection. There was an improvement in the MDS-UPDRS score, with a low rate of complications. The procedure time was prolonged from the preoperative evaluation. Deep brain stimulation is the management of choice for refractory Parkinson's disease. The patients in this series showed improvement in their symptoms. Unfortunately, there are limitations to perform this procedure in Colombia, such as the delay in the authorization of the procedure.

Assessment of Superoxidized Solution Efficacy in Treating Pressure Ulcers: A Case Study of a 65-Year-Old Male with Refractory Parkinson's Disease

In the realm of pressure sore management, meticulous wound care is essential, serving not only to prevent infections but also as preparatory groundwork for potential surgical interventions. This study delves into the effectiveness of Superoxidized Solution in directly addressing pressure sores. Through a detailed case study of a 65-year-old male afflicted with refractory Parkinson's disease and presenting pressure sores in the greater trochanteric region, our findings indicate that the application of Superoxidized Solution fosters tissue regeneration while concurrently mitigating the risk of infection.

Subthalamic Deep Brain Stimulation in Parkinson's Disease: A Boon or Bane - A Single Centre Retrospective Observational Study from India.

Background Subthalamic deep brain stimulation (STN-DBS) for refractory Parkinson's disease (PD) is more of a modality of treatment that is empirical, for which a physiological explanation is being sought. This study was done to determine the outcome and complications of patients undergoing STN-DBS for PD. Methods This retrospective observational cohort study was conducted in an advanced neuromedicine facility in eastern India for 9 years (August 2013-August 2022), which included all patients undergoing STN-DBS. Results A total of 53 patients were operated on during the study period. The mean age group of the study population was 60.5 (standard deviation [SD]: 8.2) years with a male (33 [62.3%]) predominance. The most common presenting complaints included rigidity and hypokinesia (27), severe dyskinesia (21), and tremors (17). During the postoperative period, rigidity and hypokinesia (21), severe dyskinesia (16), and tremors (12) improved significantly in a subset of the patients. The majority (45 [84.9%]) of these cases received bilateral monopolar simulation, whereas three patients (5.7%) had bilateral bipolar stimulation. Unilateral bipolar stimulation was used in five (9.4%) patients. In the immediate postoperative period, they were initiated on limb, speech, and swallowing therapy as indicated. Surgery-related complications were seen in five (9.4%) cases. At 6 months of follow-up, a significant improvement in the Unified PD rating scale component (mainly motor examination and complication of PD therapy) was noted in the majority (36 [67.9%]) of patients. One patient developed neuroleptic malignant syndrome and succumbed to his illness on the fourth postoperative day. Conclusion Given these findings, STN-DBS appears to be a good, safe, and effective treatment for a subset of medically refractory PD with an overall improvement in two-thirds of the study cohort and less than 10% risk of complications.

Rubrospinal activation during asleep subthalamic nucleus deep brain stimulation: a false localizing sign. Illustrative case.

Deep brain stimulation (DBS) can be a life-changing intervention for patients with Parkinson's disease (PD), but its success is largely dependent on precise lead placement. The subthalamic nucleus (STN) is one of the most common surgical targets of DBS, but the close anatomical and physiological resemblance of the STN to the mediocaudal red nucleus renders these landmarks difficult to distinguish. We present an atypical case in which targeted localization of the STN resulted in symptoms pathognomonic of rubrospinal tract (RST) stimulation. A 79-year-old female with a 12-year history of right-hand resting tremor due to medically refractory PD presented for asleep bilateral STN-DBS surgery. Right STN intraoperative testing revealed left hand and elbow flexion contractures, initially suggestive of corticospinal tract activation, despite imaging studies demonstrating reasonable lead placement in the central dorsolateral STN. The lead was moved anteromedially near the medial border of the STN, but stimulation at this location revealed similar but more robust flexor hand and arm contractures, without any extraocular muscle involvement. Thus, activation of the RST was suspected. Isolated activation of the RST is possible during STN-DBS surgery. Its identification can help avoid false localization and suboptimal lead placement.

Application of current steering with MICC directional lead in STN-DBS for Parkinson’s disease

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely performed for medically refractory Parkinson's disease (PD). Recent new technology of the multiple independent current control (MICC) with the directional lead provides both vertical and horizontal current steering on purposes. Consequently, MICC directional lead allows fine stimulation adjustment tailoring the condition of the individual patient. It is also expected to avoid stimulation induced adverse effects. MethodsWe retrospectively investigated the situation of current steering and the reason for doing so 3-month and 1-year after surgery in 80 patients who underwent bilateral STN-DBS for PD using MICC directional lead. ResultsIn 160 leads of 80 patients, current steering was used in 39 leads (24%) 3-month after surgery, but in 80 leads (50%) 1-year after surgery. As for the reason, vertical steering was used in 7 leads (4%) and horizontal steering was used in 28 leads (18%) to explore better stimulation effect for cardinal symptoms of PD. In addition, vertical steering was used for improving dyskinesia in 40 leads (25%) and alleviating tremor in 5 leads (3%). Horizontal steering was also used for avoiding adverse effects in 15 leads (9%), most of which were used to alleviate the symptoms of excessive stimulation of pyramidal tract. ConclusionsCurrent steering with the MICC directional lead was actually utilized in STN-DBS to explore more precise control of motor symptoms and also useful to avoid stimulation-induced adverse effect. Current steering is especially used in the later period after introduction of DBS.

Identifying the Sources of Racial Disparity in the Treatment of Parkinson's Disease With Deep Brain Stimulation.

Deep brain stimulation (DBS) is a highly efficacious treatment for appropriately selected patients with advanced, medically refractory Parkinson's disease (PD). It is severely underutilized in Black patients-constituting a major treatment gap. The source of this disparity is unknown, but its identification and correction are necessary to provide equitable care. To identify sources of racial disparity in DBS for PD. We predicted the demographics of potential DBS candidates by synthesizing published data on PD and race. We retrospectively examined the clinical course of a cohort including all patients with PD evaluated for DBS at our center from 2016 to 2020, testing whether the rate of DBS use and time from evaluation to surgery differed by race. We also tested whether the geographic distribution of patient catchment was biased relative to racial demographics. Far fewer Black patients were evaluated for DBS than would be expected, given regional demographics. There was no significant difference in the rate at which Black patients evaluated in our clinic were treated with DBS, compared with White patients. Fewer patients were recruited from portions of the surrounding area with larger Black populations. The known underuse of DBS in Black patients with PD was replicated in this sample from a center in a racially diverse metropolitan area, but was not attributable to the presurgical workup. Future work should examine the transition from medical management to surgical evaluation where drivers of disparity are potentially situated. Surgical practices should increase outreach to physicians managing PD in underserved areas.

Surgical Procedure for Subthalamic Nucleus Deep Brain Stimulation(STN-DBS)

Recently, deep brain stimulation(DBS)of the subthalamic nucleus(STN)has emerged as the most promising surgical treatment for medically refractory Parkinson disease, with the aim of achieving precise implantation of the DBS lead into the STN. DBS lead placement is performed using stereotactic surgery, with targeting based on MR imaging. Initial targeting is performed by a combination of indirect targeting based on the Schartenbrand and Wahren atlas and the direct visualization of anatomical structures on MRI. Surgical planning software is useful for target localization and simulation of the trajectory from the entry point to the target. A burr hole is placed under local anesthesia. Subsequently, the target region is physiologically explored by microelectrode recording, which is the gold standard to identify the STN. After lead placement, test stimulation is performed to assess symptom relief and to evaluate the threshold for adverse effects. Subsequently, the patient is placed under general anesthesia and the implantable pulse generator is placed in the infraclavicular subcutaneous pocket.

Levodopa affects spike and local field synchronisation in the pedunculopontine nucleus of a rat model of Parkinson's disease.

The pedunculopontine nucleus (PPN) undergoes significant anatomic and electrophysiological alterations in Parkinson’s disease (PD), severely impacting locomotion. However, the effect of 6-hydroxydopamine (6-OHDA) lesion and levodopa (L-DOPA) therapy on the relationships between spike activities and local field potential (LFP) within the PPN is not well-understood. Synchronisation between the spike activity of individual neurones and LFP of neuronal ensembles is a crucial problem in the pathogenesis of PD. In this study, LFP signals and spikes in the PPN of rats in control, lesioned, and L-DOPA groups were recorded synchronously with a multi-unit electrical signal acquisition system and analysed for their coherence value, spike-field coherence, and phase-lock relationship. The spike-LFP relationship in the PPN was markedly increased in specific frequency bands because of the 6-OHDA lesion but differed depending on the animal locomotion state and neuronal type. L-DOPA had a limited therapeutic effect on the 6-OHDA-induced increase in the coherence value. Our study demonstrates that the PPN spike-LFP relationship is involved in the pathogenesis of PD and is critical for the effects of L-DOPA, providing a basis for the clinical treatment of refractory PD symptoms.

Long-Lasting Desynchronization of Plastic Neural Networks by Random Reset Stimulation.

Excessive neuronal synchrony is a hallmark of neurological disorders such as epilepsy and Parkinson's disease. An established treatment for medically refractory Parkinson's disease is high-frequency (HF) deep brain stimulation (DBS). However, symptoms return shortly after cessation of HF-DBS. Recently developed decoupling stimulation approaches, such as Random Reset (RR) stimulation, specifically target pathological connections to achieve long-lasting desynchronization. During RR stimulation, a temporally and spatially randomized stimulus pattern is administered. However, spatial randomization, as presented so far, may be difficult to realize in a DBS-like setup due to insufficient spatial resolution. Motivated by recently developed segmented DBS electrodes with multiple stimulation sites, we present a RR stimulation protocol that copes with the limited spatial resolution of currently available depth electrodes for DBS. Specifically, spatial randomization is realized by delivering stimuli simultaneously to L randomly selected stimulation sites out of a total of M stimulation sites, which will be called L/M-RR stimulation. We study decoupling by L/M-RR stimulation in networks of excitatory integrate-and-fire neurons with spike-timing dependent plasticity by means of theoretical and computational analysis. We find that L/M-RR stimulation yields parameter-robust decoupling and long-lasting desynchronization. Furthermore, our theory reveals that strong high-frequency stimulation is not suitable for inducing long-lasting desynchronization effects. As a consequence, low and high frequency L/M-RR stimulation affect synaptic weights in qualitatively different ways. Our simulations confirm these predictions and show that qualitative differences between low and high frequency L/M-RR stimulation are present across a wide range of stimulation parameters, rendering stimulation with intermediate frequencies most efficient. Remarkably, we find that L/M-RR stimulation does not rely on a high spatial resolution, characterized by the density of stimulation sites in a target area, corresponding to a large M. In fact, L/M-RR stimulation with low resolution performs even better at low stimulation amplitudes. Our results provide computational evidence that L/M-RR stimulation may present a way to exploit modern segmented lead electrodes for long-lasting therapeutic effects.

Impact of number of stimulation sites on long-lasting desynchronization effects of coordinated reset stimulation.

Excessive neuronal synchrony is a hallmark of several neurological disorders, e.g., Parkinson's disease. An established treatment for medically refractory Parkinson's disease is high-frequency deep brain stimulation. However, it provides only acute relief, and symptoms return shortly after cessation of stimulation. A theory-based approach called coordinated reset (CR) has shown great promise in achieving long-lasting effects. During CR stimulation, phase-shifted stimuli are delivered to multiple stimulation sites to counteract neuronal synchrony. Computational studies in plastic neuronal networks reported that synaptic weights reduce during stimulation, which may cause sustained structural changes leading to stabilized desynchronized activity even after stimulation ceases. Corresponding long-lasting effects were found in recent preclinical and clinical studies. We study long-lasting desynchronization by CR stimulation in excitatory recurrent neuronal networks of integrate-and-fire neurons with spike-timing-dependent plasticity (STDP). We focus on the impact of the stimulation frequency and the number of stimulation sites on long-lasting effects. We compare theoretical predictions to simulations of plastic neuronal networks. Our results are important regarding CR calibration for two reasons. We reveal that long-lasting effects become most pronounced when stimulation parameters are adjusted to the characteristics of STDP-rather than to neuronal frequency characteristics. This is in contrast to previous studies where the CR frequency was adjusted to the dominant neuronal rhythm. In addition, we reveal a nonlinear dependence of long-lasting effects on the number of stimulation sites and the CR frequency. Intriguingly, optimal long-lasting desynchronization does not require larger numbers of stimulation sites.

Reliability of Intraoperative Testing During Deep Brain Stimulation Surgery

Deep brain stimulation (DBS) is an effective treatment for medically refractory Parkinson's disease (PD). During DBS surgery, intraoperative testing is performed to confirm optimal lead placement by determining the stimulation thresholds for symptom improvement and side effects. However, the reliability of intraoperative testing in predicting distant postoperative thresholds is unknown. In this study, we hypothesized that intraoperative testing reliably estimates postoperative thresholds for both symptom improvement and side effects. We retrospectively analyzed a prospective database with intraoperative and postoperative thresholds for symptom improvement and side effects from a cohort of 66 PD patients who underwent STN DBS. We recorded the stimulation locations relative to the mid-commissural point. Within-patient stimulation pairs were generated by clustering the intraoperative stimulation locations closest to the DBS contacts. We computed the distance between stimulation locations and atlas-based pyramidal tract (PT) and medial lemniscus (ML) masks. A leave-one-out cross-validation analysis was performed to determine the reliability of intraoperative testing in predicting postoperative thresholds while controlling for the distance from the relevant tracks. Intraoperative testing reliably predicted (area under ROC >0.8) postoperative thresholds for tremor and rigidity improvements, as well as stimulation-induced motor contractions and paresthesias. The reliability was poor for improvement in bradykinesia. Intraoperative testing reliably predicts postoperative thresholds. These results are relevant during the informed consent process and patient counseling for DBS surgery. These will also guide the development of future methods for intraoperative feedback, especially during asleep DBS.

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

IntroductionCognitive symptoms from Parkinson’s disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology.MethodsWe enrolled seven participants with medically refractory Parkinson’s disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS).ResultsDominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3–8 Hz) and/or beta (10–30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample.ConclusionAcute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

Techniques for pneumocephalus and brain shift reduction in DBS surgery: a review of the literature.

Deep brain stimulation has become an established therapeutic choice to manage the symptoms of medically refractory Parkinson's disease. Its efficacy is highly dependent on the accuracy of electrodes' positioning in the correct anatomical target. During DBS procedure, the opening of the dura mater induces the displacement of neural structures. This effect mainly depends on the loss of the physiological negative intracranial pressure, air inflow, and loss of cerebrospinal fluid. Several studies concentrated on correcting surgical techniques for DBS electrodes' positioning in order to reduce pneumocephalus which may result in therapeutic failure. The authors focused in particular on reducing the brain air window and maintaining the pressure gradient between intra- and extracranial compartments. A significant reduction of pneumocephalus and brain shift was obtained by excluding the opening of the subarachnoid space, by covering the dura mater opening with tissue sealant and by reducing the intracranial pressure in general anesthesia. Smaller burr hole diameters were not statistically relevant for reducing air inflow and displacement of anatomical targets. The review of the literature showed that conserving a physiological intra-extracranial pressure gradient plays a fundamental role in avoiding pneumocephalus and consequent displacement of brain structures, which improves surgical accuracy and DBS long-term results.

Deep Brain Stimulation for Parkinson's Disease

There is a long history of surgical treatment for Parkinson's disease (PD). Formerly, ablative stereotactic procedures such as thalamotomy or pallidotomy were performed. Currently, deep brain stimulation (DBS) is the most promising surgical treatment option for patients with medically refractory PD. DBS modulates neurological function of the target region using implanted medical devices to deliver electrical stimulation to the brain. Currently, the most common target of DBS for PD is the subthalamic nucleus (STN). The appropriate surgical candidate for STN-DBS suffers from motor complications from levodopa such as fluctuations and dyskinesia. STN-DBS significantly improves motor function in the medication-off state, motor fluctuations and dyskinesia with reduction of dopaminergic medication. Long-term outcomes are favorable for cardinal motor symptoms such as tremor, rigidity, and bradykinesia. However, refractory axial symptoms concerning speech, swallowing, gait and postural stability gradually deteriorated with progression of disease. New strategy to treat these axial symptoms is the future subject.

Safety of Noncontrast Imaging–Guided Deep Brain Stimulation Electrode Placement in Parkinson Disease

Deep brain stimulation (DBS) is considered standard of care for the treatment of medically refractory Parkinson disease (PD). The placement of brain electrodes is performed using contrast imaging to enhance blood vessel identification during stereotactic planning. We present our experience with a series of patients implanted using noncontrast imaging. All cases of DBS surgery for PD performed between 2012 and 2018 with noncontrast imaging were retrospectively reviewed. Clinical features, postoperative imaging, and complications were analyzed. A total of 287 deep-seated electrodes were implanted in 152 patients. Leads were placed at the subthalamic nucleus and globus pallidus internus in 258 and 29 hemispheres, respectively. We identified 2 cases of intracranial hemorrhage (0.7%). DBS lead placement can be performed without the use of intravenous contrast with a postoperative intracranial hemorrhage rate comparable with other reported series.

Propofol Reduces Microelectrode-Recording Artefacts caused by Parkinsonian Tremor during Deep Brain Stimulation

AbstractA 51-year-old male with medically refractory Parkinson's disease was scheduled for bilateral deep brain stimulation (DBS). During microelectrode recordings (MERs) of right side DBS, the patient developed severe sustained whole-body tremors causing severe artefacts in MER. The right side DBS electrode was inserted with suboptimal MER. For the creation of left burr hole, propofol infusion at a rate of 20 μg/kg/min, was used and soon after, all tremor activity ceased. Propofol infusion was continued during left side MER. With the absence of tremors, left subthalamic nucleus spike activity was better identified and neurological testing could take place. At 6 months after DBS, the patient’s symptoms had improved significantly without the need for levodopa.

Stereotactic Radiosurgery for Intractable Tremor-Dominant Parkinson Disease: A Retrospective Analysis

Objective: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory Parkinson disease (PD) tremor. Methods: We retrospectively studied the outcomes of 33 patients who were treated with gamma knife thalamotomy (GKT) over a 19-year period. Twelve patients were ≥80 years. A median dose of 140 Gy (range, 130-150 Gy) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to the last follow-up was 23 months (range, 9-144 months). Results: After GKT, 31 patients (93.9%) experienced improvement in tremor. Twenty-three patients (70.0%) had complete or nearly complete tremor arrest. Nine patients (27.2%) noted tremor arrest and resolution of impairment in writing, drawing, and ability to drink fluids. One patient (3%) improved in bradykinesia, 3 patients (9%) improved in rigidity, and 3 patients (9%) decreased their dosage of dopa after GKT. Tremor relief was fully maintained in the last follow-up for 96.8% of responding patients. Two patients (6%) experienced temporary adverse radiation effects. Conclusions: GKT is a safe and effective treatment for medically refractory PD tremor, especially for the elderly or those not suitable for deep brain stimulation or thermal thalamotomy.

Is That the Same Person? Case Studies in Neurosurgery

Do neurosurgical procedures ever result in the patient prior to the procedure not being identical with the individual who wakes up postsurgery in the hospital bed? We address this question by offering an analysis of the persistence of persons that emphasizes narrative, rather than numerical, identity. We argue that a narrative analysis carries the advantage of highlighting what matters to patients in their ordinary lives, explaining the varying degrees of persistence of personal identity, and enhancing our understanding of patients' experiences. We illustrate these points in cases involving temporal lobectomy for treatment of refractory epilepsy and deep brain stimulation for refractory Parkinson's disease.

Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression.

Clinical VignetteA 67-year-old female with advanced Parkinson’s disease (PD), medically refractory tremor, and a history of significant depression presented for evaluation of deep brain stimulation (DBS) candidacy.Clinical DilemmaTraditionally, the subthalamic nucleus (STN) has been preferred over the globus pallidus interna (GPi) as a DBS target for PD patients with levodopa-responsive fluctuations in rigidity and akinesia, for whom tremor is also a significant source of impairment. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.Clinical SolutionBilateral DBS of the GPi led to significant short-term improvement in PD motor symptoms, including significant tremor reduction.Gap in KnowledgeThere is insufficient evidence to support or refute clinicians’ traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson’s Disease

Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p < 0.0001), 0.206 (p = 0.00219), 0.168 (p = 0.0119), and 0.159 (p = 0.0136), respectively. Third ventricular width, gender, AC-PC distance, and age each account for 44.06% (21.38-65.69%, 95% CI), 20.82% (10.51-35.88%), 21.46% (8.28-37.05%), and 13.66% (2.62-28.64%) of the R2 value, respectively. Effect size calculation was significant for a change in the GPi laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization.