Implantation accuracy of novel polyimide stereotactic electroencephalographic depth electrodes-a human cadaveric study.

Introduction: Stereoelectroencephalography (sEEG) is a minimally invasive procedure that uses depth electrodes stereotactically implanted into brain structures to map the origin and propagation of seizures in epileptic patients. Implantation accuracy of sEEG electrodes plays a critical role in the safety and efficacy of the procedure. This study used human cadaver heads, simulating clinical practice, to evaluate (1) neurosurgeon's ability to implant a new thin-film polyimide sEEG electrode according to the instructions for use (IFU), and (2) implantation accuracy. Methods: Four neurosurgeons (users) implanted 24 sEEG electrodes into two cadaver heads with the aid of the ROSA robotic system. Usability was evaluated using a questionnaire that assessed completion of all procedure steps per IFU and user errors. For implantation accuracy evaluation, planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative computer tomography (CT) images. Implantation accuracy was quantified using the Euclidean distance for entry point error (EPE) and target point error (TPE). Results: All sEEG electrodes were successfully placed following the IFU without user errors, and post-implant survey of users showed favorable handling characteristics. The EPE was 1.28 ± 0.86 mm and TPE was 1.61 ± 0.89 mm. Long trajectories (>50 mm) had significantly larger EPEs and TPEs than short trajectories (<50 mm), and no differences were found between orthogonal and oblique trajectories. Accuracies were similar or superior to those reported in the literature when using similar experimental conditions, and in the same range as those reported in patients. Discussion: The results demonstrate that newly developed polyimide sEEG electrodes can be implanted as accurately as similar devices in the marker without user errors when following the IFU in a simulated clinical environment. The human cadaver ex-vivo test system provided a realistic test system, owing to the size, anatomy and similarity of tissue composition to that of the live human brain.

Neural signal data collection and analysis of Percept™ PC BrainSense recordings for thalamic stimulation in epilepsy.

Deep brain stimulation (DBS) using Medtronic's Percept™ PC implantable pulse generator is FDA-approved for treating Parkinson's disease (PD), essential tremor, dystonia, obsessive compulsive disorder, and epilepsy. Percept™ PC enables simultaneous recording of neural signals from the same lead used for stimulation. Many Percept™ PC sensing features were built with PD patients in mind, but these features are potentially useful to refine therapies for many different disease processes. When starting our ongoing epilepsy research study, we found it difficult to find detailed descriptions about these features and have compiled information from multiple sources to understand it as a tool, particularly for use in patients other than those with PD. Here we provide a tutorial for scientists and physicians interested in using Percept™ PC's features and provide examples of how neural time series data is often represented and saved. We address characteristics of the recorded signals and discuss Percept™ PC hardware and software capabilities in data pre-processing, signal filtering, and DBS lead performance. We explain the power spectrum of the data and how it is shaped by the filter response of Percept™ PC as well as the aliasing of the stimulation due to digitally sampling the data. We present Percept™ PC's ability to extract biomarkers that may be used to optimize stimulation therapy. We show how differences in lead type affects noise characteristics of the implanted leads from seven epilepsy patients enrolled in our clinical trial. Percept™ PC has sufficient signal-to-noise ratio, sampling capabilities, and stimulus artifact rejection for neural activity recording. Limitations in sampling rate, potential artifacts during stimulation, and shortening of battery life when monitoring neural activity at home were observed. Despite these limitations, Percept™ PC demonstrates potential as a useful tool for recording neural activity in order to optimize stimulation therapies to personalize treatment.

Neurosurgery residency match for international medical graduates in the United States.

OBJECTIVE: Training of international medical graduates (IMGs) offers opportunities for the US neurosurgery community to engage the global talent pool and impact national and international healthcare. Here, the authors analyzed the time trend of IMGs matching into US neurosurgery programs and identified potential opportunities for enhancing IMG engagement. METHODS: The authors analyzed the National Resident Matching Program (NRMP) match results, NRMP program director (PD) surveys, and applicant surveys from 2013 to 2022. Regression methods were used to analyze time trends. RESULTS: Between 2013 and 2022, the number of US neurosurgery residency positions increased by 17.6% (from 204 to 240). During this period, the percentage of IMGs matching into neurosurgery increased from 3.5% to 7%, translating into a 6.8% increase in the likelihood of a successful IMG match per year (95% CI 0.3%-13.8%, p = 0.042). The likelihoods of a successful match for US MDs and IMGs scoring > 260 on the USMLE Step 1 were > 90% and approximately 55%, respectively. In PD surveys, approximately 90% of PDs indicated that they seldom/never interview or rank IMGs. In terms of factors that influenced the PD decision for interviewing/ranking, IMGs are disadvantaged in several categories, including the ability to secure an audition elective/rotation, and proper letters of recommendation, as well as the influence of the culture on the preconceived perception of poor interpersonal skills. CONCLUSIONS: The number of IMGs matching successfully in neurosurgery has increased marginally during the past decade. The authors outline the challenges that IMGs encounter in this process and suggest strategies for considerations of IMG training in NRMP-associated institutions.

Paradoxical Modulation of STN ß-Band Activity with Medication Compared to Deep Brain Stimulation.

BACKGROUND: Excessive subthalamic nucleus (STN) ß-band (13-35 Hz) synchronized oscillations has garnered interest as a biomarker for characterizing disease state and developing adaptive stimulation systems for Parkinson's disease (PD). OBJECTIVES: To report on a patient with abnormal treatment-responsive modulation in the ß-band. METHODS: We examined STN local field potentials from an externalized deep brain stimulation (DBS) lead while assessing PD motor signs in four conditions (OFF, MEDS, DBS, and MEDS+DBS). RESULTS: The patient presented here exhibited a paradoxical increase in ß power following administration of levodopa and pramipexole (MEDS), but an attenuation in ß power during DBS and MEDS+DBS despite clinical improvement of 50% or greater under all three therapeutic conditions. CONCLUSIONS: This case highlights the need for further study on the role of ß oscillations in the pathophysiology of PD and the importance of personalized approaches to the development of ß or other biomarker-based DBS closed loop algorithms. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Low-frequency deep brain stimulation reveals resonant beta-band evoked oscillations in the pallidum of Parkinson's Disease patients.

Introduction: Evidence suggests that spontaneous beta band (11-35 Hz) oscillations in the basal ganglia thalamocortical (BGTC) circuit are linked to Parkinson's disease (PD) pathophysiology. Previous studies on neural responses in the motor cortex evoked by electrical stimulation in the subthalamic nucleus have suggested that circuit resonance may underlie the generation of spontaneous and stimulation-evoked beta oscillations in PD. Whether these stimulation-evoked, resonant oscillations are present across PD patients in the internal segment of the globus pallidus (GPi), a primary output nucleus in the BGTC circuit, is yet to be determined. Methods: We characterized spontaneous and stimulation-evoked local field potentials (LFPs) in the GPi of four PD patients (five hemispheres) using deep brain stimulation (DBS) leads externalized after DBS implantation surgery. Results: Our analyses show that low-frequency (2-4 Hz) stimulation in the GPi evoked long-latency (>50 ms) beta-band neural responses in the GPi in 4/5 hemispheres. We demonstrated that neural sources generating both stimulation-evoked and spontaneous beta oscillations were correlated in their frequency content and spatial localization. Discussion: Our results support the hypothesis that the same neuronal population and resonance phenomenon in the BGTC circuit generates both spontaneous and evoked pallidal beta oscillations. These data also support the development of closed-loop control systems that modulate the GPi spontaneous oscillations across PD patients using beta band stimulation-evoked responses.

Frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis.

INTRODUCTION: Deep Brain Stimulation (DBS) is an effective treatment for the motor symptoms of Parkinson's Disease. The targeted physiological structure for lead location is commonly the subthalamic nucleus (STN). The efficacy of DBS for improving motor symptoms is assessed via the Unified Parkinson's Disease Rating III Scale (UPDRS-III). In this study, we sought to compare the efficacy of frequency settings utilized for STN-DBS. METHODS: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include full-length randomized controlled trials evaluating STN-DBS. The frequency stimulation parameters and Unified Parkinson's Disease Rating Scale (UPDRS-III) outcomes were extracted in the search. High-frequency stimulation (HFS) was defined as ≥100 Hz and low-frequency stimulation (LFS) was defined as <100 Hz. A frequentist network meta-analysis was performed with odds ratios (OR) and pooling performed using the Mantel-Haenszel method. Statistics are presented as OR [95% CI]. RESULTS: 15 studies consisting of 298 patients were included for analysis. Bilateral HFS -0.68 [-0.89; -0.46] was associated with better UPDRS-III scores compared to bilateral LFS. On the other hand, bilateral LFS with medications (MEDS) was favored over HFS with MEDS (-0.28 [-0.63; 0.07]). Bilateral LFS and MEDS, HFS and MEDS, stimulation (STIM) OFF MEDS ON, HFS, LFS, STIM OFF MEDS OFF UPDRS outcomes were ranked from best to worst outcomes. DISCUSSION: The outcomes of this study suggest that bilateral HFS has better utility for those with no response to medication, while LFS has additive benefits to medication by improving unique symptoms via different neurophysiological mechanisms.

WITHDRAWN: Laterality and frequency settings of subthalamic nucleus DBS for Parkinson's disease: A systematic review and network meta-analysis.

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Clinical Benefit of Vagus Nerve Stimulation for Epilepsy: Assessment of Randomized Controlled Trials and Prospective Non-Randomized Studies.

We examined the efficacy of vagal nerve stimulation (VNS) for patients suffering from medically intractable epilepsy. Four randomized controlled trials (RCTs - 3 adult RCTs and 1 pediatric RCT) were identified in our comprehensive literature search. Across the 4 studies, high frequency VNS stimulation (frequency >20 Hz) consistently achieved a greater seizure frequency reduction (23.4-33.1%) relative to low frequency VNS stimulation (1 Hz, .6-15.2%). We identified 2 RCTs examining whether the parameters of stimulation influenced seizure control. These studies reported that VNS achieved seizure control comparable to those reported by the first 4 RCTs (22-43% seizure frequency reduction), irrespective of the parameters utilized for VNS stimulation. In terms of VNS associated morbidity, these morbidities were consistently higher in adults who underwent high frequency VNS stimulation (eg dysphonia 37-66%, dyspnea 6-25.3%). However, no such differences were observed in the pediatric population. Moreover, <2% of patients withdrew from the RCTs/prospective studies due to intolerable symptoms. To provide an assessment of how the risks and benefits of VNS impact the patient experience, 1 study assessed the well-being of enrolled patients (as a secondary end point) and found VNS was associated with an overall improvement in well-being. Consistent with this observation, we identified a prospective, non-randomized study that demonstrated improved quality of life for epilepsy patients managed with VNS and best medical practice relative to best medical practice alone. In aggregate, these RCT studies support the efficacy and benefit of VNS as a neuro-modulatory platform in the management of a subset of medically refractory epilepsy patients.

Reliability of visual review of intracranial electroencephalogram in identifying the seizure onset zone: A systematic review and implications for the accuracy of automated methods.

Visual review of intracranial electroencephalography (iEEG) is often an essential component for defining the zone of resection for epilepsy surgery. Unsupervised approaches using machine and deep learning are being employed to identify seizure onset zones (SOZs). This prompts a more comprehensive understanding of the reliability of visual review as a reference standard. We sought to summarize existing evidence on the reliability of visual review of iEEG in defining the SOZ for patients undergoing surgical workup and understand its implications for algorithm accuracy for SOZ prediction. We performed a systematic literature review on the reliability of determining the SOZ by visual inspection of iEEG in accordance with best practices. Searches included MEDLINE, Embase, Cochrane Library, and Web of Science on May 8, 2022. We included studies with a quantitative reliability assessment within or between observers. Risk of bias assessment was performed with QUADAS-2. A model was developed to estimate the effect of Cohen kappa on the maximum possible accuracy for any algorithm detecting the SOZ. Two thousand three hundred thirty-eight articles were identified and evaluated, of which one met inclusion criteria. This study assessed reliability between two reviewers for 10 patients with temporal lobe epilepsy and found a kappa of .80. These limited data were used to model the maximum accuracy of automated methods. For a hypothetical algorithm that is 100% accurate to the ground truth, the maximum accuracy modeled with a Cohen kappa of .8 ranged from .60 to .85 (F-2). The reliability of reviewing iEEG to localize the SOZ has been evaluated only in a small sample of patients with methodologic limitations. The ability of any algorithm to estimate the SOZ is notably limited by the reliability of iEEG interpretation. We acknowledge practical limitations of rigorous reliability analysis, and we propose design characteristics and study questions to further investigate reliability.

Basal ganglia engagement during REM sleep movements in Parkinson's disease.

To elucidate the role of the basal ganglia during REM sleep movements in Parkinson's disease (PD) we recorded pallidal neural activity from four PD patients. Unlike desynchronization commonly observed during wakeful movements, beta oscillations (13-35 Hz) synchronized during REM sleep movements; furthermore, high-frequency oscillations (150-350 Hz) synchronized during movement irrespective of sleep-wake states. Our results demonstrate differential engagement of the basal ganglia during REM sleep and awake movements.

Controlling pallidal oscillations in real-time in Parkinson's disease using evoked interference deep brain stimulation (eiDBS): Proof of concept in the human.

Approaches to control basal ganglia neural activity in real-time are needed to clarify the causal role of 13-35 Hz ("beta band") oscillatory dynamics in the manifestation of Parkinson's disease (PD) motor signs. Here, we show that resonant beta oscillations evoked by electrical pulses with precise amplitude and timing can be used to predictably suppress or amplify spontaneous beta band activity in the internal segment of the globus pallidus (GPi) in the human. Using this approach, referred to as closed-loop evoked interference deep brain stimulation (eiDBS), we could suppress or amplify frequency-specific (16-22 Hz) neural activity in a PD patient. Our results highlight the utility of eiDBS to characterize the role of oscillatory dynamics in PD and other brain conditions, and to develop personalized neuromodulation systems.

Mapping spreading depolarisations after traumatic brain injury: a pilot clinical study protocol.

INTRODUCTION: Cortical spreading depolarisation (CSD) is characterised by a near-complete loss of the ionic membrane potential of cortical neurons and glia propagating across the cerebral cortex, which generates a transient suppression of spontaneous neuronal activity. CSDs have become a recognised phenomenon that imparts ongoing secondary insults after brain injury. Studies delineating CSD generation and propagation in humans after traumatic brain injury (TBI) are lacking. Therefore, this study aims to determine the feasibility of using a multistrip electrode array to identify CSDs and characterise their propagation in space and time after TBI. METHODS AND ANALYSIS: This pilot, prospective observational study will enrol patients with TBI requiring therapeutic craniotomy or craniectomy. Subdural electrodes will be placed for continuous electrocorticography monitoring for seizures and CSDs as a research procedure, with surrogate informed consent obtained preoperatively. The propagation of CSDs relative to structural brain pathology will be mapped using reconstructed CT and electrophysiological cross-correlations. The novel use of multiple subdural strip electrodes in conjunction with brain morphometric segmentation is hypothesised to provide sufficient spatial information to characterise CSD propagation across the cerebral cortex and identify cortical foci giving rise to CSDs. ETHICS AND DISSEMINATION: Ethical approval for the study was obtained from the Hennepin Healthcare Research Institute's ethics committee, HSR 17-4400, 25 October 2017 to present. Study findings will be submitted for publication in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT03321370.

Modulation of Beta Oscillations in the Pallidum During Externally Cued Gait.

Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson's disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase. In the STN, beta-band oscillations are modulated by external cues, but it is unknown if this relationship holds in the globus pallidus (GP). Here we report LFP data recorded from the left GP, using a Medtronic PC + S device, in a 68-year-old man with PD and FOG during treadmill walking. A "stepping stone" task was used during which stepping was cued using visual targets of constant color or targets that unpredictably changed color, requiring a step length adjustment. Gait performance was quantified using measures of treadmill ground reaction forces and center of pressure and body kinematics from video monitoring. Beta-band power (12-30 Hz) and number of freezing episodes were measured. Cues which unpredictably changed color improved FOG more than conventional cues and were associated with greater modulation of beta-band power in phase with gait. This preliminary finding suggests that cueing-induced improvement of FOG may relate to beta-band modulation.

Learning Curve Associated with ClearPoint Neuronavigation System: A Case Series.

BACKGROUND: The ClearPoint neuronavigation system affords real-time magnetic resonance imaging (MRI) guidance during stereotactic procedures. While such information confers potential clinical benefits, additional operative time may be needed. METHODS: We conducted a retrospective analysis of procedural time associated with ClearPoint Stereotaxis, with hypothesis that this procedural time is comparable with that associated with frame-based biopsy. RESULTS: Of the 52 patients evaluated, the total procedural time for ClearPoint stereotactic biopsy averaged 150.0 (±40.4) minutes, of which 111.5 (±16.5) minutes were dedicated to real-time MRI acquisition and trajectory adjustment. This procedural time is within the range of those reported for frame-based needle biopsies. Approximately 5 minutes of the procedural time is related to the mounting of the MRI-compatible stereotactic frame. Based on the procedural time, we estimate that four cases are required in the learning curve to achieve this efficiency. Efficient algorithms for distortion corrections and isocenter localization are keys to ClearPoint stereotaxis. Routine quality assurance/control after each MRI software update and institutional information technology maintenance also contribute to efficiency. Real-time MRI is essential for definitive diagnosis in select cases. CONCLUSIONS: ClearPoint stereotactic needle biopsy can be achieved in time frames comparable to frame-based stereotaxis. However, procedural efficiency requires 4 "learning curve" cases as well as vigilance in terms of MR distortion correction and information technology maintenance.

High-Frequency Oscillations in the Pallidum: A Pathophysiological Biomarker in Parkinson's Disease?

BACKGROUND: Abnormal oscillatory neural activity in the beta-frequency band (13-35 Hz) is thought to play a role in Parkinson's disease (PD); however, increasing evidence points to alterations in high-frequency ranges (>100 Hz) also having pathophysiological relevance. OBJECTIVES: Studies have found that power in subthalamic nucleus (STN) high-frequency oscillations is increased with dopaminergic medication and during voluntary movements, implicating these brain rhythms in normal basal ganglia function. The objective of this study was to investigate whether similar signaling occurs in the internal globus pallidus (GPi), a nucleus increasingly used as a target for deep brain stimulation (DBS) for PD. METHODS: Spontaneous and movement-related GPi field potentials were recorded from DBS leads in 5 externalized PD patients on and off dopaminergic medication, as well as from 3 rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. RESULTS: In the parkinsonian condition, we identified a prominent oscillatory peak centered at 200-300 Hz that increased during movement. In patients the magnitude of high-frequency oscillation modulation was negatively correlated with bradykinesia. In monkeys, high-frequency oscillations were mostly absent in the naive condition but emerged after the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In patients, spontaneous high-frequency oscillations were significantly attenuated on-medication. CONCLUSIONS: Our findings provide evidence in support of the hypothesis that exaggerated, movement-modulated high-frequency oscillations in the GPi are pathophysiological features of PD. These findings suggest that the functional role(s) of high-frequency oscillations may differ between the STN and GPi and motivate additional investigations into their relationship to motor control in normal and diseased states.

Deep-learning based fully automatic segmentation of the globus pallidus interna and externa using ultra-high 7 Tesla MRI.

Deep brain stimulation (DBS) surgery has been shown to dramatically improve the quality of life for patients with various motor dysfunctions, such as those afflicted with Parkinson's disease (PD), dystonia, and essential tremor (ET), by relieving motor symptoms associated with such pathologies. The success of DBS procedures is directly related to the proper placement of the electrodes, which requires the ability to accurately detect and identify relevant target structures within the subcortical basal ganglia region. In particular, accurate and reliable segmentation of the globus pallidus (GP) interna is of great interest for DBS surgery for PD and dystonia. In this study, we present a deep-learning based neural network, which we term GP-net, for the automatic segmentation of both the external and internal segments of the globus pallidus. High resolution 7 Tesla images from 101 subjects were used in this study; GP-net is trained on a cohort of 58 subjects, containing patients with movement disorders as well as healthy control subjects. GP-net performs 3D inference in a patient-specific manner, alleviating the need for atlas-based segmentation. GP-net was extensively validated, both quantitatively and qualitatively over 43 test subjects including patients with movement disorders and healthy control and is shown to consistently produce improved segmentation results compared with state-of-the-art atlas-based segmentations. We also demonstrate a postoperative lead location assessment with respect to a segmented globus pallidus obtained by GP-net.

Personalizing Dual-Target Cortical Stimulation with Bayesian Parameter Optimization Successfully Treats Central Post-Stroke Pain: A Case Report.

Central pain disorders, such as central post-stroke pain, remain clinically challenging to treat, despite many decades of pharmacological advances and the evolution of neuromodulation. For treatment refractory cases, previous studies have highlighted some benefits of cortical stimulation. Recent advances in new targets for pain and the optimization of neuromodulation encouraged our group to develop a dual cortical target approach paired with Bayesian optimization to provide a personalized treatment. Here, we present a case report of a woman who developed left-sided facial pain after multiple thalamic strokes. All previous pharmacologic and interventional treatments failed to mitigate the pain, leaving her incapacitated due to pain and medication side effects. She subsequently underwent a single burr hole for placement of motor cortex (M1) and dorsolateral prefrontal cortex (dlPFC) paddles for stimulation with externalization. By using Bayesian optimization to find optimal stimulation parameters and stimulation sites, we were able to reduce pain from an 8.5/10 to a 0/10 during a 5-day inpatient stay, with pain staying at or below a 2/10 one-month post-procedure. We found optimal treatment to be simultaneous stimulation of M1 and dlPFC without any evidence of seizure induction. In addition, we found no worsening in cognitive performance during a working memory task with dlPFC stimulation. This personalized approach using Bayesian optimization may provide a new foundation for treating central pain and other functional disorders through systematic evaluation of stimulation parameters.

Resective epilepsy surgery: assessment of randomized controlled trials.

Epilepsy is the most common form of chronic neurologic disease. Here, we review the available randomized controlled trials (RCTs) that examined the efficacy of resective epilepsy surgery in select patients suffering from medically intractable epilepsy (defined as persistent epilepsy despite two or more antiepileptic drugs [AEDs]). Three RCTs (two adult RCTs and one pediatric RCT) consistently supported the efficacy of resective surgery as treatment for epilepsy with semiology localized to the mesial temporal lobe. In these studies, 58-100% of the patients who underwent resective surgery achieved seizure freedom, in comparison to 0-13% of medically treated patients. In another RCT, the likelihood of seizure freedom after resective surgery was independent of the surgical approach (transSylvian [64%] versus subtemporal [62%]). Two other RCTs demonstrated that hippocampal resection is essential to optimize seizure control. But, no significant gain in seizure control was achieved beyond removing 2.5 cm of the hippocampus. Across RCTs, minor complications (deficit lasting < 3 months) and major complications (deficit > 3 months) ranged 2-5% and 5-11% respectively. However, nonincapacitating superior subquadrantic visual-field defects (not typically considered a minor or major complication) were noted in up to 55% of the surgical cohort. The available RCTs provide compelling support for resective surgery as a treatment for mesial temporal lobe epilepsy and offer insights toward optimal surgical strategy.

Factors Influencing Electrode Position and Bending of the Proximal Lead in Deep Brain Stimulation for Movement Disorders.

BACKGROUND: The introduction of intracranial air (ICA) during deep brain stimulation (DBS) surgery is thought to have a negative influence on targeting and clinical outcomes. OBJECTIVE: To investigate ICA volumes following surgery and other patient-specific factors as potential variables influencing translocation of the DBS electrode and proximal lead bowing. METHODS: High-resolution postoperative computed tomography scans (≤1.0 mm resolution in all directions) within 24 h following DBS surgery and 4-6 weeks of follow-up were acquired. A total of 50 DBS leads in 33 patients were available for analysis. DBS leads included Abbott/St. Jude Medical InfinityTM, Boston Scientific VerciseTM, and Medtronic 3389TM. RESULTS: Both ICA volume and anatomical target were significantly associated with measures of DBS electrode translocation. ICA volume and DBS lead model were found to be significant predictors of proximal lead bowing. Measures of proximal lead bowing and translocation along the electrode trajectory for the Medtronic 3389TM DBS lead were significantly larger than measures for the Abbott/St. Jude Medical InfinityTM and Boston Scientific VerciseTM DBS leads. CONCLUSION: The association between ICA volume and translocation of the DBS electrode is small in magnitude and not clinically relevant for DBS cases within a normal range of postoperative subdural air volumes. Differences in proximal lead bowing observed between DBS leads may reflect hardware engineering subtleties in the construction of DBS lead models.

Subthalamic nucleus deep brain stimulation with a multiple independent constant current-controlled device in Parkinson's disease (INTREPID): a multicentre, double-blind, randomised, sham-controlled study.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease. METHODS: This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396. FINDINGS: Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation. INTERPRETATION: This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes. FUNDING: Boston Scientific.