Standard Deep Brain Stimulation Research Articles

Prospective Connectomic-Based Deep Brain Stimulation Programming for Parkinson's Disease.

Efficacy of deep brain stimulation (DBS) relies on accurate lead placement as well as optimization of the stimulation parameters. Although clinical software tools are now available, programming still largely relies on a monopolar review, a tedious process for both patients and programmers. This study investigates the safety and feasibility of prospective automated connectomic DBS programming (automated connectomic programming [ACP]), focusing on the recruitment of specific white matter pathways. After DBS implantation, a detailed connectomic DBS model in patient-specific space was developed for each study participant. A driving-force model was used to quantify pathway recruitment across 2400 different DBS settings. Optimization algorithms maximized recruitment of therapeutic pathways while minimizing recruitment of side-effect pathways. Thirteen subjects were enrolled in two study phases that compared DBS settings derived from ACP to standard clinical DBS settings. Nine patients underwent reprogramming with ACP (5 globus pallidus interna [GPi], 4 subthalamic nucleus [STN]). Four patients underwent initial programming with ACP (3 GPi, 1 STN). All patients tolerated ACP without persistent side effects. In the reprogramming cohort, 3 patients preferred their ACP program, and 1 patient felt it was comparable to their clinical program. Unified Parkinson's Disease Rating Scale, Part III, scores for the initial ACP cohort (3 GPi, 1 STN) improved by an average of 43.5% (40.4-52.6 ± 5.6%). ACP appeared clinically safe and feasible. It provided reasonable motor improvement, which can be further optimized with subsequent clinical adjustment. Additional investigation is required to refine the optimization algorithm and to quantify the clinical benefit of ACP in a larger cohort. © 2024 International Parkinson and Movement Disorder Society.

A Technique of Deep Brain Stimulation of the Globus Pallidus Interna for Dystonia Under General Anesthesia With Sevoflurane.

Background Globus pallidus interna (GPi) deep brain stimulation (DBS) is an established surgical procedure that confers a benefit in medication refractory dystonia. Patients with generalized dystonia require general anesthesia (GA) for the surgery as their movements may hinder the surgical procedure. General anesthetics tend to dampen the microelectrode recordings (MERs) from the GPi. Methods We describe our experience with a series of consecutive patients with dystonia who underwent bilateral GPi DBS using standard DBS and MER under GA using sevoflurane as the maintenance general anesthetic drug. All patients had Medtronic 3,387 leads implanted and connected to an RC battery. Patients underwent sequential programming of the DBS after the surgery. Results The mean age of the 13 patients who underwent DBS of the GPi for dystonia was 46.5 years with a range from 29 to 71 years. Every patient in our case series received various doses of(1.37% to 2.11%) inhaled sevoflurane for anesthesia maintenance. Sevoflurane provided adequate anesthesia and allowed accurate MERs from the GPi.No adverse effects were encountered. On follow-up and sequential DBS programming, patients had significant improvements in dystoniaattesting to the accuracy of the electrode placements. Conclusions We report our experience using sevoflurane for maintenance of GA for bilateral GPi DBS for dystonia. The main benefits identified have been adequate anesthesia and reduction of dystonia-related movements to allow the performance of the DBS surgery. The MER signals from the GPi were not suppressed by sevoflurane. This allowed accurate mapping and placement of the DBS implants in the GPi.

Clinician vs. imaging-based subthalamic nucleus deep brain stimulation programming

IntroductionWe sought to explore whether electrode visualization tools (EVT) can accurately predict the selection of optimal Deep Brain Stimulation (DBS) electrode contacts. MethodsTwelve patients with Parkinson's disease (PD) undergoing STN-DBS at The Ohio State University were enrolled in a prospective analysis to evaluate the accuracy of EVT-based vs. standard DBS programming. EVTs were generated by the Surgical Information Sciences (SIS) system to develop a 3D model showing the implanted lead location relative to the STN. Then, imaging-based data were compared to the results of a standard monopolar review to evaluate concordance with clinical data and time spent selecting useable, non-useable, and borderline electrode contacts. ResultsA total of 18 DBS leads (n = 68 electrode contacts) were analyzed. The concordance between EVT and standard clinical programming expressed as the kappa coefficient was 0.65 (82.35% raw agreement) for non-useable, 0.52 for useable (64.71% raw agreement), and 0.52 for borderline (58.82% raw agreement). The average time spent determining whether an electrode contact was useable, non-useable, or borderline was 1.46 ± 0.76 min with EVT vs. 61.25 ± 17.47 with standard monopolar review. Eight different categories of side effects were identified, with facial pulling and speech difficulties being observed with the most frequency. The type of side effect observed was accurately predicted using EVT 90% of the time. ConclusionsThis study demonstrates that next-generation EVT-based programming can be implemented into STN-DBS programming workflows with a considerable saving of time and effort spent in testing combinations of stimulation settings, particularly for the identification of non-useable electrode contacts.

Sweet spots of standard and directional leads in patients with refractory essential tremor: white matter pathways associated with maximal tremor improvement.

In patients with essential tremor (ET) treated with standard deep brain stimulation (sDBS) whose ET had progressed and who no longer received optimal benefit from sDBS, directional deep brain stimulation (dDBS) may provide better tremor control. Current steering may provide better coverage of subcortical structures related to tremor control in patients with ET and significant progression without optimal response to sDBS. This study included 6 patients with ET initially treated with sDBS whose tremor later progressed and who then underwent reimplantation with dDBS to optimize their tremor control. To investigate the differences in the local effects of sDBS and dDBS, the authors generated the volume of tissue activation (VTA) to calculate the sweet spots associated with the best possible tremor control with no side effects. Then, to investigate the anatomical structures associated with maximal tremor control, the white matter pathways of the posterior subthalamic areas (PSAs) were generated and their involvement with the sDBS and dDBS sweet spots was calculated. Tremor improvement was significantly better with dDBS (68.4%) than with sDBS (48.7%) (p = 0.017). The sDBS sweet spot was located within the ventral intermediate nucleus, whereas the sweet spot of the dDBS was mainly located within the PSA. The sweet spots of both sDBS and dDBS involved a similar portion of the cerebellothalamic pathway. However, the dDBS had greater involvement of the pallidofugal pathways than the sDBS. In patients with ET treated with sDBS who later had ET progression, dDBS provided better tremor control, which was related to directionality and a more ventral position. The involvement of both the cerebellothalamic and pallidofugal pathways obtained with dDBS is associated with additional improvement over the sDBS.

Management of Lennox-Gastaut syndrome with deep brain stimulation: A systematic literature review.

To review the current literature regarding the efficacy and safety of deep brain stimulation (DBS) in Lennox-Gastaut syndrome (LGS). The authors conducted a systematic review of PubMed databases using keywords relevant to the objective of this research. Titles and abstracts were reviewed, after which studies that met the inclusion criteria were selected. Findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Thirteen studies were identified, and only 3 studies that reported 50 patients (age range from 3 to 65 years) met the inclusion criteria of DBS for LGS. Radiological imaging findings and neurophysiological findings were described in all studies. The thalamus nuclei, particularly the centromedian thalamic nucleus (CMN), were found to be highly active in LGS. By targeting this brain region, patients showed favorable outcomes. Overall, the mean seizure reduction was more than 50% in all patients (among whom 2 were seizure free) at a mean follow-up of 15 (12-18) months. According to this systemic review, DBS for LGS showed satisfactory outcomes, indicating that DBS should be considered a valid treatment option. However, more studies are needed to ensure the role of DBS in LGS by establishing accurate targeting of the CMN using proper lead positioning and radiological imaging, a standard DBS intervention, and long-term outcomes.

Temporally optimized patterned stimulation (TOPS®) as a therapy to personalize deep brain stimulation treatment of Parkinson's disease.

Deep brain stimulation (DBS) is a well-established therapy for the motor symptoms of Parkinson’s disease (PD), but there remains an opportunity to improve symptom relief. The temporal pattern of stimulation is a new parameter to consider in DBS therapy, and we compared the effectiveness of Temporally Optimized Patterned Stimulation (TOPS) to standard DBS at reducing the motor symptoms of PD. Twenty-six subjects with DBS for PD received three different patterns of stimulation (two TOPS and standard) while on medication and using stimulation parameters optimized for standard DBS. Side effects and motor symptoms were assessed after 30 min of stimulation with each pattern. Subjects experienced similar types of side effects with TOPS and standard DBS, and TOPS were well-tolerated by a majority of the subjects. On average, the most effective TOPS was as effective as standard DBS at reducing the motor symptoms of PD. In some subjects a TOPS pattern was the most effective pattern. Finally, the TOPS pattern with low average frequency was found to be as effective or more effective in about half the subjects while substantially reducing estimated stimulation energy use. TOPS DBS may provide a new programing option to improve DBS therapy for PD by improving symptom reduction and/or increasing energy efficiency. Optimizing stimulation parameters specifically for TOPS DBS may demonstrate further clinical benefit of TOPS DBS in treating the motor symptoms of Parkinson’s disease.

Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System

ObjectivesPatients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. Materials and MethodsSix advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. ResultsThere was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. ConclusionsIn this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.

Connectivity Patterns of Deep Brain Stimulation Targets in Patients with Gilles de la Tourette Syndrome.

Since 1999, several targets for deep brain stimulation (DBS) in Gilles de la Tourette syndrome (GTS) have emerged showing similar success rates. Studies using different tractography techniques have identified connectivity profiles associated with a better outcome for individual targets. However, GTS patients might need individualized therapy. The objective of this study is to analyze the connectivity profile of different DBS targets for GTS. We identified standard target coordinates for the centromedian nucleus/nucleus ventro-oralis internus (CM/Voi), the CM/parafascicular (CM-Pf) complex, the anteromedial globus pallidus internus (amGPi), the posteroventral GPi (pvGPi), the ventral anterior/ventrolateral thalamus (VA/VL), and the nucleus accumbens/anterior limb of the internal capsule (Nacc/ALIC). Probabilistic tractography was performed from the targets to different limbic and motor areas based on patient-specific imaging and a normative connectome (HCP). Our analysis showed significant differences between the connectivity profiles of standard DBS targets (p < 0.05). Among all targets, the pvGPi showed the strongest connection to the sensorimotor cortex, while the amGPi showed the strongest connection to the prefrontal cortex in patient-specific imaging. Differences were observed between the connectivity profiles when using probabilistic tractography based on patient data and HCP. Our findings showed that the connectivity profiles of different DBS targets to major motor and limbic areas differ significantly. In the future, these differences may be considered when planning DBS for GTS patients employing an individualized approach. There were compelling differences in connectivity profiles when using different tractography techniques.

Efficacy of Deep Brain Stimulation on the Improvement of the Bladder Functions in Traumatic Brain Injured Rats

Objective: Traumatic brain injuries (TBIs) are a prime public health challenge with a high incidence of mortality, and also reflect severe economic impacts. One of their severe symptoms is bladder dysfunction. Conventional therapeutic methods are not effective in managing bladder dysfunction. Henceforth, a research endeavor was attempted to explore a new therapeutic approach for bladder dysfunction through deep brain stimulation (DBS) procedures in a TBI animal model. Methods: TBI in this animal model was induced by the weight-drop method. All rats with an induced TBI were housed for 4 weeks to allow severe bladder dysfunction to develop. Subsequently, an initial urodynamic measurement, the simultaneous recording of cystometric (CMG) and external urethral sphincter electromyography (EUS-EMG) activity was conducted to evaluate bladder function. Further, standard DBS procedures with varying electrical stimulation parameters were executed in the target area of the pedunculopontine tegmental nucleus (PPTg). Simultaneously, urodynamic measurements were re-established to compare the effects of DBS interventions on bladder functions. Results: From the variable combinations of electrical stimulation, DBS at 50 Hz and 2.0 V, significantly reverted the voiding efficiency from 39% to 69% in TBI rats. Furthermore, MRI studies revealed the precise localization of the DBS electrode in the target area. Conclusions: The results we obtained showed an insightful understanding of PPTg-DBS and its therapeutic applications in alleviating bladder dysfunction in rats with a TBI. Hence, the present study suggests that PPTg-DBS is an effective therapeutic strategy for treating bladder dysfunction.

Development and testing of implanted carbon electrodes for electromagnetic field mapping during neuromodulation.

Deep brain stimulation electrodes composed of carbon fibers were tested as a means of administering and imaging magnetic resonance electrical impedance tomography (MREIT) currents. Artifacts and heating properties of custom carbon-fiber deep brain stimulation (DBS) electrodes were compared with those produced with standard DBS electrodes. Electrodes were constructed from multiple strands of 7-μm carbon-fiber stock. The insulated carbon electrodes were matched to DBS electrode diameter and contact areas. Images of DBS and carbon electrodes were collected with and without current flow and were compared in terms of artifact and thermal effects in phantoms or tissue samples in 7T imaging conditions. Effects on magnetic flux density and current density distributions were also assessed. Carbon electrodes produced magnitude artifacts with smaller FWHM values compared to the magnitude artifacts around DBS electrodes in spin echo and gradient echo imaging protocols. DBS electrodes appeared 269% larger than actual size in gradient echo images, in sharp contrast to the negligible artifact observed in diameter-matched carbon electrodes. As expected, larger temperature changes were observed near DBS electrodes during extended RF excitations compared with carbon electrodes in the same phantom. Magnitudes and distribution of magnetic flux density and current density reconstructions were comparable for carbon and DBS electrodes. Carbon electrodes may offer a safer, MR-compatible method for administering neuromodulation currents. Use of carbon-fiber electrodes should allow imaging of structures close to electrodes, potentially allowing better targeting, electrode position revision, and the facilitation of functional imaging near electrodes during neuromodulation.

Randomized cortical stimulation could ameliorate locomotive inability in Parkinsonian rats: a pilot study

Objective: Parkinson’s disease (PD) is a neurodegenerative disease for which there is no known cure. Deep brain stimulation (DBS) is a surgical treatment effective in reducing motor symptoms for PD patients. Previous work implicates DBS may directly influence motor cortex through stochastic antidromic spikes originating from the site of stimulation. Here we tested the hypothesis that direct randomized cortical stimulation is therapeutically effective in PD animal models. Approach: As a proof-of-principle study, we utilized a multi-channel stimulating system to mimic the effects of stochastic antidromic activation on the motor cortex of rat, by delivering microcurrents randomized temporally and spatially, and assessed the efficacy in ameliorating motor symptoms in a rat PD model. Main results: We found that different combinations of frequency, amplitude and pulse width of randomized electrical currents delivered to the motor cortex exerted different effects on Parkinsonian rats. Among these, some stimulus patterns, defined by specific ranges of pulse width and stimulation frequencies, were able to produce transient beneficial effect on locomotive ability assessed by open-field locomotor activities. These results indicate that, in principle, cortical stimulation could achieve therapeutic outcome in PD. Significance: Direct cortical simulation based on a randomized protocol could be a less invasive approach than standard DBS in treating Parkinsonism. More refined mode of stimulation to achieve long-lasting and more robust effect should be explored.

Visualization of volume of tissue activated modeling in a clinical planning system for deep brain stimulation.

Pathway activating models try to describe stimulation spread in deep brain stimulation (DBS). Volume of tissue activated (VTA) models are simplified model variants allowing faster and easier computation. Our study aimed to investigate, how VTA visualization can be integrated into a clinical workflow applying directional electrodes using a standard clinical DBS planning system. Twelve patients underwent DBS, using directional electrodes for bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease. Preoperative 3T magnetic resonance imaging was used for automatic visualization of the STN outline, as well as for fiber tractography. Intraoperative computed tomography was used for automatic lead detection. The Guide XT software, closely integrated into the DBS planning software environment, was used for VTA calculation and visualization. VTA visualization was possible in all cases. The percentage of VTA covering the STN volume ranged from 25% to 100% (mean: 60±25%) on the left side and from 0% to 98% (51±30%) on the right side. The mean coordinate of all VTA centers was: 12.6±1.2 mm lateral, 2.1±1.2 mm posterior, and 2.3±1.4 mm inferior in relation to the midcommissural point. Stimulation effects can be compared to the VTA visualization in relation to surrounding structures, potentially facilitating programming, which might be especially beneficial in case of suboptimal lead placement. VTA visualization in a clinical planning system allows an intuitive adjustment of the stimulation parameters, supports programming, and enhances understanding of effects and side effects of DBS.

Unsupervised clustering reveals spatially varying single neuronal firing patterns in the subthalamic nucleus of patients with Parkinson's disease

IntroductionSubthalamic nucleus (STN) is an effective target for deep brain stimulation (DBS) to reduce the motor symptoms of Parkinson's disease (PD). It is important to identify firing patterns within the structure for a better understanding of the electro-pathophysiology of the disease. Using recently established metrics, our study aims to autonomously identify the discharge patterns of individual cells and examine their spatial distribution within the STN. MethodsWe recorded single unit activity (SUA) from 12 awake PD patients undergoing a standard clinical DBS surgery. Three extracted features from raw SUA (local variation, bursting index and prominence of peak) were used with k-means clustering to achieve the aforementioned unsupervised grouping of firing patterns. Results279 neurons were isolated and four distinct firing patterns were identified across patients: tonic (11%), irregular (55%), periodic (9%) and non-periodic bursts (25%). The mean firing rates for irregular discharges were significantly lower (p < 0.05) than the rest. Tonic firings were significantly ventral (p < 0.05) while periodic (p < 0.05) and non-periodic (p < 0.01) bursts were dorsal. The percentage of periodically bursting neurons in dorsal region and entire STN were significantly correlated with off state UPDRS tremor scores (r = 0.51, p = 0.04) and improvement in bradykinesia and rigidity (r = 0.57, p = 0.02) respectively. ConclusionStrengthening the application of unsupervised clustering for firing patterns of individual cells, this study shows a unique spatial affinity of tonic activity towards the ventral and bursting activity towards the dorsal region of STN in PD patients. This spatial preference, together with the correlation of clinical scores, can provide a clue towards understanding Parkinsonian symptom generation.

Implementation of Intraoperative Computed Tomography for Deep Brain Stimulation: Pitfalls and Optimization of Workflow, Accuracy, and Radiation Exposure

Deep brain stimulation (DBS) is an effective treatment for movement disorders. Stereotactic electrode placement can be guided by intraoperative imaging, which also allows for immediate intraoperative quality control. This article is about implementation and refining a workflow applying intraoperative computed tomography (iCT) for DBS. Eighteen patients underwent DBS with bilateral implantation of directional electrodes applying a 32-slice movable computed tomography scanner in combination with microelectrode recording. iCT led to a significant decrease in overall procedural time, despite performing multiple scans. In 3 of the initial 5 cases, iCT caused an adjustment of the final electrodes demonstrating the learning curve and the necessity to integrate road mapping for the exchange of microelectrode to final electrode. Implementation of low-dose computed tomography protocols added microelectrode iCT to the refined workflow, resulting in an intraoperative adjustment of a trajectory in 1 patient. Low-dose protocols lowered the total effective dose to 1.15 mSv, that is, a reduction by a factor of 3.5 compared to a standard non-iCT DBS procedure, despite repeated iCTs. Intraoperative lead detection based on final iCT revealed a radial error of 1.04 ± 0.58 mm and a vector error of 2.28 ± 0.97 mm compared to the preoperative planning, adjusted by the findings of microelectrode recording. iCT can be easily integrated into the surgical workflow resulting in an overall efficient time-saving procedure. Repeated intraoperative scanning ensures reliable electrode placement, although low-dose scanning protocols prevent extensive radiation exposure. iCT of microelectrodes is feasible and led to the adjustment of 1 electrode.

Noise-Induced Improvement of the Parkinsonian State: A Computational Study.

The benefit of noise in improving the basal ganglia (BG) dysfunctions, especially Parkinsonian state, is explored in this paper. High frequency (≥ 100 Hz) deep brain stimulation (DBS), as a clinical effective stimulation method, has compelling and fantastic results in alleviating the motor symptoms of Parkinson's disease (PD). However, the mechanism of DBS is still unclear. And the selection of the DBS waveform parameters faces great challenges to further optimize the stimulation effects and to reduce its energy expenditure. Considering that the desynchronization of the BG neuronal activities is benefited from the forced high frequency regular spikes driven by standard high frequency DBS, we expect to explore a novel stimulation method that has capability of restoring the BG physiological firing patterns without introducing artificial high-frequency fires. In this paper, a colored noise stimulation is used as a neuromodulation method to disrupt the firing patterns of the pathological neuronal activities. A computational model of the BG that exhibits the intrinsic properties of the BG neurons and their interactions with the thalamic (Th) cells is employed. Based on the model, we investigate the effects of noise stimulation and explore the impacts of the noise stimulation parameters on both relay reliability of the Th neurons and energy expenditure of the stimulation. By comparison, it can be found that noise stimulation does not entrain the network to an artificial high-frequency firing state, but induces the pathological increased synchronous activities back to a normal physiological level. Moreover, besides the capability of restoring the neuronal state, the benefits of the noise also include its balanced waveform to avert potential tissue or electrode damage and its ability to reduce the energy expenditure to 50% less than that of the standard DBS, when the noise stimulation has low frequency (≤ 100 Hz) and appropriate intensity. Thus, the exploration of the optimal noise-induced improvement of the BG dysfunction is of great significance in treating symptoms of neurological disorders such as PD.

EP 62. Motor evoked potentials mapping improves detection of capsular side effects during deep brain stimulation

Introduction One of the main reasons to perform deep brain stimulation (DBS) on awake patient is detection of activation of descending capsular motor pathways as they represent therapy-limiting side effect. Current technique of capsular activation detection is based on visual detection of muscular contraction during stimulation with standard “tonic” DBS stimulation parameters. Intraoperative mapping of subcortical motor evoked potentials (MEP) during DBS surgery, as already shown in the literature, is feasible and time-efficient, also in patients under general anesthesia. We investigate value of motor evoked potentials mapping in basal ganglia as alternative measurement of safe therapeutic window in stimulation parameters. Methods This study includes recording data of 7 Patients, undergoing awake DBS surgery in subthalamic nucleus or in thalamus and of 1 DBS patient under general anesthesia. Recording data of 16 trajectories and 32 stimulation sites was available. Anodal stimulation was applied in stereotactic target on the macroelectrode tip (microTargeting electrodes, FHC, USA) using train-of-five technique in 1 mA steps 0–5 mA. Recordings were obtained using skin surface electrodes on projection of m. mentalis, m. abductor pollicis brevis, m. flexor digitorum, m. tibialis anterior on contralateral to stimulation side. Visual detection of motor contraction under 130 Hz 60 μs stimulation in 1 mA steps (0–5 mA) was used as standard control parameter. Results MEP recordings were successful in all stimulation sites. MEP threshold current correlated with current values of 130 Hz stimulation, which caused visually detectable muscle contractions and with postoperative DBS side effect thresholds. Detection of muscle response activation was very sensitive and muscle-specific and remained stable under repeated stimulation. Patients described very little or no discomfort during MEP mapping, significantly lower comparing to classical 130 Hz stimulation on motor-threshold. MEP threshold detection was easily obtainable under propofol-remifentanyl general anesthesia and had same current values as “tonic” stimulation postoperatively. Conclusions MEP mapping in basal ganglia is safe and feasible alternative to standard motor side-effect detection, which can improve safety and comfort of DBS procedure. MEP motor threshold correlates well to capsular activation with standard DBS parameters and can be obtained under general anesthesia.

DBS in Tourette syndrome: where are we standing now?

Deep brain stimulation (DBS) has emerged as an established effective and safe treatment option for a small subset of patients with severe Tourette syndrome (TS) refractory to psychological and pharmacological treatments. Several targets have been implicated in the study of the effects of DBS on TS symptomatology. The targets applied for DBS in TS include the thalamus, the globus pallidus internus, the internal capsule/nucleus accumbens, the globus pallidus externus and the subthalamic nucleus. In the majority of studies there has been a significant clinical benefit on tics. Nevertheless, the best target has not been defined yet. Up until now, only five double blind randomized controlled trials have been carried out worldwide for a total of 32 patients. Thus, the new recommendations for DBS in TS emphasize the importance of standardized recordings of all pre-, intra-, and postoperative data to optimize the registration of patients so that results can be compared. Recent reports have shown that standard continuous DBS for TS patients may not be the most optimal paradigms to pursue. Adaptive stimulation and the use of human-computer interfaces might in the future optimize the results of DBS in TS because of the paroxysmal nature of the disease.

Closed-loop DBS in the non-human primate model of Parkinsonism

High-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson’s disease (PD) management. However, the mechanisms by which DBS exerts its alleviating effect remain to be described. Furthermore, due to its non-adaptive nature, standard DBS is not ideally suited for the treatment of this highly dynamic and progressive disorder. We have devised several closed-loop stimulation strategies for PD and tested them in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD. These included stimulation of the internal pallidal segment (GPi) according to a predefined trigger in the ongoing neuronal activity. Application of pallido-pallidal closed-loop stimulation leads to dissociation between changes in basal ganglia (BG) discharge rates and patterns, providing insights into PD pathophysiology. Notably, cortico-pallidal closed-loop stimulation has a significantly greater effect on akinesia and on cortical and pallidal discharge patterns than standard open-loop DBS and matched control stimulation paradigms. These results demonstrate that closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD. Such strategies have the potential to be effective in additional brain disorders in which a pathological neuronal discharge pattern can be recognized.

A suggested minimum standard deep brain stimulation evaluation for essential tremor

BackgroundA comprehensive, multidisciplinary screening process for deep brain stimulation (DBS) candidates is recommended, but is often time-consuming. ObjectiveTo determine the number of essential tremor (ET) referrals excluded from surgery and why, in order to develop recommendations for a minimum standard DBS evaluation process. MethodsWe reviewed the referrals of 100 consecutive potential DBS candidates with presumed ET at our center, identified reasons for excluding patients from DBS, and the point at which they dropped out of our evaluation process. ResultsOf the 100 tremor patients referred for DBS, 36 patients were approved for surgery. Patients were mainly excluded because of the movement disorders neurologist and neuropsychologist evaluations. Reasons included an inadequate medication trial (n=20), incorrect diagnosis (n=3), dementia (n=3), and antagonistic interactions with the team (n=1). 37 patients did not present, were uninterested or lost to follow-up. Neither neurosurgical evaluation nor brain imaging excluded candidates in this study, but are needed to proceed with DBS. ConclusionsOur suggested minimum standard DBS screening process begins with a movement disorders neurologist and neuropsychologist evaluation in order to determine eligibility. Neurosurgical evaluation and brain imaging can then be performed if candidates are deemed eligible.

Targeting the affective component of chronic pain: a case series of deep brain stimulation of the anterior cingulate cortex.

Deep brain stimulation (DBS) has shown considerable promise for relieving nociceptive and neuropathic symptoms of refractory chronic pain. Nevertheless, for some patients, standard DBS for pain remains poorly efficacious. Pain is a multidimensional experience with an affective component: the unpleasantness. The anterior cingulate cortex (ACC) is a structure involved in this affective component, and targeting it may relieve patients' pain. To describe the first case series of ACC DBS to relieve the affective component of chronic neuropathic pain. Sixteen patients (13 male and 3 female patients) with neuropathic pain underwent bilateral ACC DBS. The mean age at surgery was 48.7 years (range, 33-63 years). Patient-reported outcome measures were collected before and after surgery using a Visual Analog Scale, SF-36 quality of life survey, McGill Pain Questionnaire, and EQ-5D (EQ-5D and EQ-5D Health State) questionnaires. Fifteen patients (93.3%) transitioned from externalized to fully internalized systems. Eleven patients had data to be analyzed with a mean follow-up of 13.2 months. Post-surgery, the Visual Analog Scale score dropped below 4 for 5 of the patients, with 1 patient free of pain. Highly significant improvement on the EQ-5D was observed (mean, +20.3%; range, +0%-+83%; P = .008). Moreover, statistically significant improvements were observed for the physical functioning and bodily pain domains of the SF-36 quality-of-life survey: mean, +64.7% (range, -8.9%-+276%; P = .015) and mean +39.0% (range, -33.8%-+159%; P = .050), respectively. Affective ACC DBS can relieve chronic neuropathic pain refractory to pharmacotherapy and restore quality of life.