Directional sensory thalamus deep brain stimulation in poststroke refractory pain.

Thalamic deep brain stimulation (DBS) for chronic pain is performed in selected patients with a variable success rate. We report the use of recently developed directional DBS in a patient with hemibody central poststroke pain (CPSP) and its added value in the induction of pleasant, pain-distracting paresthesia's throughout the contralateral body side. A 68-year-old man suffered from multiple strokes in the left hemisphere 11 years before presentation, resulting in medically refractory right-sided hemibody CPSP. He was implanted with a directional DBS electrode in the left ventrocaudal nucleus of the thalamus. A directional single-segment contact configuration produced a better improvement throughout the contralateral body side than ring-mode and other directional configurations. Treatment led to a reduction of almost 50% in pain. This case demonstrates the value of directional DBS in the treatment of chronic pain, as steering increases selectivity and reduces side effects in a small target area surrounded by structures with high functional diversity.

Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia.

Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode's localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.

Using Preimplanted Deep Brain Stimulation Electrodes for Rescue Thalamotomy in a Case of Holmes Tremor: A Case Report and Review of the Literature.

BACKGROUND: Chronic stimulation of the thalamus is a surgical option in the management of intractable Holmes tremor. Patients with deep brain stimulation (DBS) can encounter infection as a postoperative complication, necessitating explantation of the hardware. Some studies have reported on the technique and the resulting efficacy of therapeutic lesioning through implanted DBS leads before their explantation. CASE DESCRIPTION: We report the case of a patient with Holmes tremor who had stable control of symptoms with DBS of the nucleus ventralis intermedius of the thalamus (VIM) but developed localized infection over the extension at the neck, followed by gradual loss of a therapeutic effect as the neurostimulator reached the end of its service life. Three courses of systemic antibiotic therapy failed to control the infection. After careful consideration, we decided to make a rescue lesion through the implanted lead in the right VIM before explanting the complete DBS hardware. The tremor was well controlled after the rescue lesion procedure, and the effect was sustained during a 2-year follow-up period. CONCLUSION: This case and the previously discussed ones from the literature demonstrate that making a rescue lesion through the DBS lead can be the last plausible option in cases where the DBS system has to be explanted because of an infection and reimplantation is a remote possibility.

Optical Measurements during Asleep Deep Brain Stimulation Surgery along Vim-Zi Trajectories.

BACKGROUND: Optics can be used for guidance in deep brain stimulation (DBS) surgery. The aim was to use laser Doppler flowmetry (LDF) to investigate the intraoperative optical trajectory along the ventral intermediate nucleus (VIM) and zona incerta (Zi) regions in patients with essential tremor during asleep DBS surgery, and whether the Zi region could be identified. METHODS: A forward-looking LDF guide was used for creation of the trajectory for the DBS lead, and the microcirculation and tissue greyness, i.e., total light intensity (TLI) was measured along 13 trajectories. TLI trajectories and the number of high-perfusion spots were investigated at 0.5-mm resolution in the last 25 mm from the targets. RESULTS: All implantations were done without complications and with significant improvement of tremor (p < 0.01). Out of 798 measurements, 12 tissue spots showed high blood flow. The blood flow was significantly higher in VIM than in Zi (p < 0.001). The normalized mean TLI curve showed a significant (p < 0.001) lower TLI in the VIM region than in the Zi region. CONCLUSION: Zi DBS performed asleep appears to be safe and effective. LDF monitoring provides direct in vivomeasurement of the microvascular blood flow in front of the probe, which can help reduce the risk of hemorrhage. LDF can differentiate between the grey substance in the thalamus and the transmission border entering the posterior subthalamic area where the tissue consists of more white matter tracts.

DBS dysfunction mimicking transient ischemic attacks-a case report.

We report on a patient with thalamic deep brain stimulation (DBS) for essential tremor who was admitted to a stroke unit with transient vertigo, dysarthria, and gait disturbance. Transient ischemic attacks were assumed but fluctuating neurological symptoms persisted until presentation to a DBS center. Here, unstable high monopolar impedances of the right-hemispheric electrode contacts were detected. Surgical revision revealed a fracture of the pocket adaptor connecting this electrode to the impulse generator. Replacement resulted in stable impedances and remitted the transient neurological symptoms. Emergency and stroke doctors should be aware of neurological symptoms induced by technical dysfunctions in DBS.

Deep Brain Stimulation for Pain in the Modern Era: A Systematic Review.

BACKGROUND: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative. OBJECTIVE: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy. METHODS: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected. RESULTS: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores. CONCLUSION: DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation.

Movement context modulates neuronal activity in motor and limbic-associative domains of the human parkinsonian subthalamic nucleus.

The subthalamic nucleus (STN), a preferred target for treating movement disorders, has a crucial role in inhibition and execution of movement. To better understand the mechanism of movement regulation in the STN of Parkinson's disease patients, we compared the same movement with different context, facilitation vs. inhibition context. We recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (off medications, n = 43 patients, 173 recording sites) performed increasingly complex oddball paradigms with frequent and deviant tones: first, passive listening to tone series with no movement ('None-Go' task, n = 7, 28 recording sites); second, pressing a button after every tone ('All-Go' task, n = 7, 26 recording sites); and third, pressing a button only for frequent tones, thus adding inhibition of movement following deviant tones ('Go-NoGo' task, n = 29, 119 recording sites). The STN responded mainly to movement-involving tasks. In the limbic-associative STN, evoked response to the deviant tone (inhibitory cue) was not significantly different between the Go-NoGo and the All-Go task. However, the evoked response to the frequent tone (go cue) in the Go-NoGo task was significantly reduced. The reduction was mainly prominent in the negative component of the evoked response amplitude aligned to the press. Successful movement inhibition was correlated with higher baseline activity. We suggest that the STN in Parkinson's disease patients adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the limbic- associative STN domains in movement planning and in global movement regulation.

Bayesian adaptive dual control of deep brain stimulation in a computational model of Parkinson's disease.

In this paper, we present a novel Bayesian adaptive dual controller (ADC) for autonomously programming deep brain stimulation devices. We evaluated the Bayesian ADC's performance in the context of reducing beta power in a computational model of Parkinson's disease, in which it was tasked with finding the set of stimulation parameters which optimally reduced beta power as fast as possible. Here, the Bayesian ADC has dual goals: (a) to minimize beta power by exploiting the best parameters found so far, and (b) to explore the space to find better parameters, thus allowing for better control in the future. The Bayesian ADC is composed of two parts: an inner parameterized feedback stimulator and an outer parameter adjustment loop. The inner loop operates on a short time scale, delivering stimulus based upon the phase and power of the beta oscillation. The outer loop operates on a long time scale, observing the effects of the stimulation parameters and using Bayesian optimization to intelligently select new parameters to minimize the beta power. We show that the Bayesian ADC can efficiently optimize stimulation parameters, and is superior to other optimization algorithms. The Bayesian ADC provides a robust and general framework for tuning stimulation parameters, can be adapted to use any feedback signal, and is applicable across diseases and stimulator designs.

Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.

OBJECTIVE: Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. METHODS: Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. RESULTS: Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). INTERPRETATION: Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.

Exploiting interfacial phenomena in organic bioelectronics: Conformable devices for bidirectional communication with living systems.

A novel fully organic bioelectronic device is presented and validated as electronic transducer and current stimulator for brain implants. The device integrates polymeric electrodes made of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) on paper thin foils, resulting in a high surface-to-volume ratio architecture that exhibits high sensitivity to interfacial ionic transport phenomena. The prototyping technique herein presented yields devices for the bidirectional communication with biological systems whose dimensionality can be controlled according to the desired application. Transduction of ultra-low local-field potentials and delivery of voltage pulse-trains alike those used in deep-brain stimulation are herein assessed, paving the way towards novel theranostic strategies for the treatment of Parkinson's Disease and other severe neurodegenerative and/or traumatic pathologies of the central nervous system.

Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more.

BACKGROUND: Directional Deep Brain Stimulation (D-DBS) allows axially asymmetric electrical field shaping, away from structures causing side-effects. However, concerns regarding the impact on device lifespan and complexity of the monopolar survey have contributed to sparing use of these features. OBJECTIVE: To investigate whether chronically implanted D-DBS systems can improve the therapeutic window, without a negative impact on device lifespan, in thalamic deep brain stimulation (DBS). METHODS: We evaluated stable outcomes of initial programming sessions (4-6 weeks post-implantation) retrospectively in 8 patients with drug-resistant disabling tremor syndromes. We assessed the impact of directional stimulation on the Therapeutic Window (TW), Therapeutic Current Strength (TCS), tremor scores, disability scores and total electrical energy delivered. Finally, we performed Volume of Tissue Activation (VTA) modelling, based on a range of parameters. RESULTS: We report significant gains in TW (91%) and reductions in TCS (31%) with stimulation in the best direction compared to best omnidirectional stimulation alternative. Tremor and ADL scores improvements remained unchanged at six months. There was no increase in averaged IPG power consumption (there is a 6% reduction over the omnidirectional-only alternative). Illustrative VTA modelling shows that D-DBS achieves 85% of the total activation volume at just 69% of the stimulation amplitude of non-directional configuration. CONCLUSIONS: D-DBS can improve the therapeutic window over non-directional DBS, leading to significant reduction in disability that may be sustained without additional reprogramming visits. When averaged across the cohort, power output and predicted device lifespan was not impacted by the use of directional stimulation in this study.

Sensory percepts induced by microwire array and DBS microstimulation in human sensory thalamus.

BACKGROUND: Microstimulation in human sensory thalamus (ventrocaudal, VC) results in focal sensory percepts in the hand and arm which may provide an alternative target site (to somatosensory cortex) for the input of prosthetic sensory information. Sensory feedback to facilitate motor function may require simultaneous or timed responses across separate digits to recreate perceptions of slip as well as encoding of intensity variations in pressure or touch. OBJECTIVES: To determine the feasibility of evoking sensory percepts on separate digits with variable intensity through either a microwire array or deep brain stimulation (DBS) electrode, recreating "natural" and scalable percepts relating to the arm and hand. METHODS: We compared microstimulation within ventrocaudal sensory thalamus through either a 16-channel microwire array (∼400 kΩ per channel) or a 4-channel DBS electrode (∼1.2 kΩ per contact) for percept location, size, intensity, and quality sensation, during thalamic DBS electrode placement in patients with essential tremor. RESULTS: Percepts in small hand or finger regions were evoked by microstimulation through individual microwires and in 5/6 patients sensation on different digits could be perceived from stimulation through separate microwires. Microstimulation through DBS electrode contacts evoked sensations over larger areas in 5/5 patients, and the apparent intensity of the perceived response could be modulated with stimulation amplitude. The perceived naturalness of the sensation depended both on the pattern of stimulation as well as intensity of the stimulation. CONCLUSIONS: Producing consistent evoked perceptions across separate digits within sensory thalamus is a feasible concept and a compact alternative to somatosensory cortex microstimulation for prosthetic sensory feedback. This approach will require a multi-element low impedance electrode with a sufficient stimulation range to evoke variable intensities of perception and a predictable spread of contacts to engage separate digits.

Ultrahigh-Magnitude Brain Magnetic Resonance Imaging Scan on Rhesus Monkeys With Implanted Deep Brain Stimulation Hardware.

BACKGROUND: Patients with implanted deep brain stimulation (DBS) hardware are prohibited from undergoing magnetic resonance imaging (MRI) scans at magnitudes greater than 1.5 T to avoid potential MRI-related heating injury. Whether DBS devices are compatible with higher field MRI scanning is unknown. This study aimed to investigate whether 7.0 T and 3.0 T MRI scans can be safely performed on rhesus monkeys with implanted DBS devices. METHODS: Eight male rhesus monkeys were included in this study and stereotactically implanted with DBS devices in the left anterior thalamus. Two weeks after DBS device implantation, 7.0 T and 3.0 T MRI scans were performed. The monkeys were observed for 72 hours. After explantation of the DBS system, 7.0 T MRI was repeated to determine potential lesions. Hematoxylin and eosin staining and transmission electron microscopy were conducted to assess pathological alterations. RESULTS: In both groups, the monkeys exhibited no behavioral changes related to neurological deficits. Post-explantation MRI showed no malacia foci surrounding the DBS tracks. Additionally, neither hematoxylin and eosin staining nor transmission electron microscopy showed clear injury near the DBS leads. CONCLUSION: These results indicate that no obvious heating injury was induced in the tissue surrounding the DBS leads by the 7.0 T and 3.0 T MRI scans. Although the results of this study may not be generalizable, these data suggest that patients with implanted DBS devices can undergo even 7.0 T MRI without risk of brain injury.

Neurostimulation Devices for the Treatment of Neurologic Disorders.

Rapid advancements in neurostimulation technologies are providing relief to an unprecedented number of patients affected by debilitating neurologic and psychiatric disorders. Neurostimulation therapies include invasive and noninvasive approaches that involve the application of electrical stimulation to drive neural function within a circuit. This review focuses on established invasive electrical stimulation systems used clinically to induce therapeutic neuromodulation of dysfunctional neural circuitry. These implantable neurostimulation systems target specific deep subcortical, cortical, spinal, cranial, and peripheral nerve structures to modulate neuronal activity, providing therapeutic effects for a myriad of neuropsychiatric disorders. Recent advances in neurotechnologies and neuroimaging, along with an increased understanding of neurocircuitry, are factors contributing to the rapid rise in the use of neurostimulation therapies to treat an increasingly wide range of neurologic and psychiatric disorders. Electrical stimulation technologies are evolving after remaining fairly stagnant for the past 30 years, moving toward potential closed-loop therapeutic control systems with the ability to deliver stimulation with higher spatial resolution to provide continuous customized neuromodulation for optimal clinical outcomes. Even so, there is still much to be learned about disease pathogenesis of these neurodegenerative and psychiatric disorders and the latent mechanisms of neurostimulation that provide therapeutic relief. This review provides an overview of the increasingly common stimulation systems, their clinical indications, and enabling technologies.

Advances in closed-loop deep brain stimulation devices.

BACKGROUND: Millions of patients around the world are affected by neurological and psychiatric disorders. Deep brain stimulation (DBS) is a device-based therapy that could have fewer side-effects and higher efficiencies in drug-resistant patients compared to other therapeutic options such as pharmacological approaches. Thus far, several efforts have been made to incorporate a feedback loop into DBS devices to make them operate in a closed-loop manner. METHODS: This paper presents a comprehensive investigation into the existing research-based and commercial closed-loop DBS devices. It describes a brief history of closed-loop DBS techniques, biomarkers and algorithms used for closing the feedback loop, components of the current research-based and commercial closed-loop DBS devices, and advancements and challenges in this field of research. This review also includes a comparison of the closed-loop DBS devices and provides the future directions of this area of research. RESULTS: Although we are in the early stages of the closed-loop DBS approach, there have been fruitful efforts in design and development of closed-loop DBS devices. To date, only one commercial closed-loop DBS device has been manufactured. However, this system does not have an intelligent and patient dependent control algorithm. A closed-loop DBS device requires a control algorithm to learn and optimize the stimulation parameters according to the brain clinical state. CONCLUSIONS: The promising clinical effects of open-loop DBS have been demonstrated, indicating DBS as a pioneer technology and treatment option to serve neurological patients. However, like other commercial devices, DBS needs to be automated and modernized.

Asleep Robot-Assisted Surgery for the Implantation of Subthalamic Electrodes Provides the Same Clinical Improvement and Therapeutic Window as Awake Surgery.

OBJECTIVE: To study the impact of not performing awake clinical evaluation during the robot-assisted implantation of subthalamic nucleus deep brain stimulation (STN-DBS) electrodes on the stimulation parameters and clinical outcomes in patients with Parkinson disease (PD). METHODS: A total of 23 patients with PD underwent robot-assisted surgery for the bilateral implantation of STN-DBS electrodes. Thirteen patients received general anesthesia (GA) and a limited intraoperative evaluation (side effects only), and the other 10 patients received local anesthesia (LA) and a full evaluation. The primary endpoint was the therapeutic window (TW), defined as the difference between the mean voltage threshold for motor improvement and the mean voltage threshold for side effects in the active contacts at 12 months after surgery. Motor scores were measured as well. RESULTS: The TW was similar in the LA and GA groups, with mean ± standard deviation values of 2.06 ± 0.53 V and 2.28 ± 0.99 V, respectively (P = 0.32). In the short term, the Unified Parkinson Disease Rating Scale (UPDRS) III score in the "off-drug, on-stim" condition fell to a similar extent in the LA and GA groups (by 40.3% and 49%, respectively; P = 0.336), as did the UPDRS III score in the "on-stim, on-drug" condition (by 57% and 70.7%, respectively; P = 0.36). CONCLUSIONS: Asleep, robot-assisted implantation of STN-DBS electrodes (with accurate identification of the STN and positioning of the DBS lead) produced the same motor results and TW as awake surgery.

Efficacy of Fiber Tractography in the Stereotactic Surgery of the Thalamus for Patients with Essential Tremor.

Several targets and targeting methods are utilized in stereotactic surgery to achieve tremor suppression for patients with intractable tremor. Recent developments in magnetic resonance imaging, including diffusion tensor imaging, have enabled the setting of appropriate targets in stereotactic surgery. In this retrospective study, the optimal target to suppress tremors in stereotactic surgery was explored using diffusion tensor image-based fiber tractography. Four tracts were focused on in this study, namely: the cerebello-thalamo-premotor cortical fiber tract, cerebello-thalamo-primary motor cortical fiber tract, spino-thalamo-somatosensory cortical fiber tract, and pyramidal tract. In 10 patients with essential tremor, we evaluated the thalamotomy lesions and active contacts of the lead in thalamic stimulation by diffusion tensor image-based fiber tractography to reveal which part of the cerebral cortex is most affected by stereotactic surgery. Tremor suppression and adverse events were also evaluated in the patients involved in this study. Consequently, the good tremor suppression was achieved in all patients. There had been no permanent adverse events 3 months after surgery. Twelve lesions in thalamotomy patients or active contacts of the lead in thalamic stimulation patients were on the cerebello-thalamo-premotor cortical fiber tract (12/14 lesions or active contacts: 86%). In conclusion, the cerebello-thalamo-premotor cortical fiber tract may be an optimal target for tremor suppression. Diffusion tensor image-based fiber tractography may enable us to both determine the optimal target to achieve strong tremor suppression and to reduce the number of adverse events by keeping lesions or electrodes away from important fiber tracts, such as the pyramidal tract and spinothalamic fibers.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial.

INTRODUCTION: This study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET). METHODS: A prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications. The primary outcome measure was a rater-blinded assessment of the change in the target limb tremor score in the stimulation-on versus stimulation-off state six months following surgery. Multiple secondary outcomes were assessed at one-year follow-up, including motor, mood, and quality-of-life measures. RESULTS: 127 patients were implanted with VIM DBS. The blinded, primary outcome variable (n = 76) revealed a mean improvement of 1.25 ± 1.26 points in the target limb tremor rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary outcome variables at one year revealed significant improvements (p ≤ 0.001) in quality of life, depression symptoms, and ADL scores. Forty-seven patients had a second contralateral VIM-DBS, and this group demonstrated reduction in second-sided tremor at 180 days (p < 0.001). Serious adverse events related to the surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device explantation (n = 3). CONCLUSION: Unilateral and bilateral constant-current VIM DBS significantly improves upper extremity tremor, ADL, quality of life, and depression in patients with severe ET.