Hybrid deep brain stimulation system to manage stimulation-induced side effects in essential tremor patients

2019 ◽  
Vol 58 ◽  
pp. 85-86 ◽  
Author(s):  
Derrick Soh ◽  
Andres M. Lozano ◽  
Alfonso Fasano
Keyword(s):  
Deep Brain Stimulation ◽  
Side Effects ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Stimulation System ◽  
Deep Brain

scholarly journals Modeling mechanisms of tremor reduction for essential tremor using symmetric biphasic DBS

2019 ◽  
Author(s):  
Shane Lee ◽  
Wael F Asaad ◽  
Stephanie R Jones
Keyword(s):  
Deep Brain Stimulation ◽  
Side Effects ◽  
Movement Disorder ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Future Studies ◽  
Tremor Frequency ◽  
Ventral Intermediate Nucleus ◽  
Different Shapes ◽  
Deep Brain

AbstractEssential tremor (ET) is the most common movement disorder, in which the primary symptom is a prominent, involuntary 4–10 Hz movement. For severe, medication refractory cases, deep brain stimulation (DBS) targeting the ventral intermediate nucleus of the thalamus (VIM) can be an effective treatment for cessation of tremor and is thought to work in part by disrupting tremor frequency oscillations (TFOs) in VIM. However, DBS is not universally effective and may be further disrupting cerebellar-mediated activity in the VIM. Here, we applied biophysically detailed computational modeling to investigate whether the efficacy of DBS is affected by the mechanism of generation of TFOs or by the pattern of stimulation. We simulated the effects of DBS using standard, asymmetric pulses as well as biphasic, symmetric pulses to understand biophysical mechanisms of how DBS disrupts TFOs generated either extrinsically or intrinsically. The model results suggested that the efficacy of DBS in the VIM is affected by the mechanism of generation of TFOs. Symmetric biphasic DBS reduced TFOs more than standard DBS in both networks, and these effects were stronger in the intrinsic network. For intrinsic tremor frequency activity, symmetric biphasic DBS was more effective at reducing TFOs. Simulated non-tremor signals were also transmitted during symmetric biphasic DBS, suggesting that this type of DBS may help to reduce side effects caused by disruption of the cerebellothalamocortical pathway. Biophysical details in the model provided a mechanistic interpretation of the cellular and network dynamics contributing to these effects that can be empirically tested in future studies.Significance StatementEssential tremor (ET) is a common movement disorder, whose primary symptom is an involuntary rhythmic movement of the limbs or head. An area of the human tha-lamus demonstrates electrical activity that oscillates at the frequencies of tremor, and deep brain stimulation (DBS) in this area can reduce tremor. It is not fully understood how DBS affects tremor frequency activity in the thalamus, and studying different patterns of DBS stimulation may help to clarify these mechanisms. We created a computational model of different shapes of DBS and studied how they reduce different hypothesized generators of tremor frequency activity. A greater understanding of how DBS affects the thalamus may lead to improved treatments to reduce tremor and alleviate side effects in patients with ET.

scholarly journals Stimulation-Induced Side Effects of Deep Brain Stimulation in the Ventralis Intermedius and Posterior Subthalamic Area for Essential Tremor

2021 ◽  
Vol 12 ◽  
Author(s):  
Myung Ji Kim ◽  
Kyung Won Chang ◽  
So Hee Park ◽  
Won Seok Chang ◽  
Hyun Ho Jung ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Side Effects ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Gait Disturbance ◽  
Electrode Implantation ◽  
Electrode Contact ◽  
Deep Brain ◽  
Stimulation Of

Deep brain stimulation (DBS) targeting the ventralis intermedius (VIM) nucleus of the thalamus and the posterior subthalamic area (PSA) has been shown to be an effective treatment for essential tremor (ET). The aim of this study was to compare the stimulation-induced side effects of DBS targeting the VIM and PSA using a single electrode. Patients with medication-refractory ET who underwent DBS electrode implantation between July 2011 and October 2020 using a surgical technique that simultaneously targets the VIM and PSA with a single electrode were enrolled in this study. A total of 93 patients with ET who had 115 implanted DBS electrodes (71 unilateral and 22 bilateral) were enrolled. The Clinical Rating Scale for Tremor (CRST) subscores improved from 20.0 preoperatively to 4.3 (78.5% reduction) at 6 months, 6.3 (68.5% reduction) at 1 year, and 6.5 (67.5% reduction) at 2 years postoperation. The best clinical effect was achieved in the PSA at significantly lower stimulation amplitudes. Gait disturbance and clumsiness in the leg was found in 13 patients (14.0%) upon stimulation of the PSA and in significantly few patients upon stimulation of the VIM (p = 0.0002). Fourteen patients (15.1%) experienced dysarthria when the VIM was stimulated; this number was significantly more than that with PSA stimulation (p = 0.0233). Transient paresthesia occurred in 13 patients (14.0%) after PSA stimulation and in six patients (6.5%) after VIM stimulation. Gait disturbance and dysarthria were significantly more prevalent in patients undergoing bilateral DBS than in those undergoing unilateral DBS (p = 0.00112 and p = 0.0011, respectively). Paresthesia resolved either after reducing the amplitude or switching to bipolar stimulation. However, to control gait disturbance and dysarthria, some loss of optimal tremor control was necessary at that particular electrode contact. In the present study, the most common stimulation-induced side effect associated with VIM DBS was dysarthria, while that associated with PSA DBS was gait disturbance. Significantly, more side effects were associated with bilateral DBS than with unilateral DBS. Therefore, changing active DBS contacts to simultaneous targeting of the VIM and PSA may be especially helpful for ameliorating stimulation-induced side effects.

scholarly journals Shorter pulse width reduces gait disturbances following deep brain stimulation for essential tremor

2019 ◽  
Vol 90 (9) ◽  
pp. 1046-1050 ◽  
Author(s):  
Daniel Kroneberg ◽  
Siobhan Ewert ◽  
Anne-Christiane Meyer ◽  
Andrea A Kühn
Keyword(s):  
Deep Brain Stimulation ◽  
Side Effects ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Pulse Width ◽  
Stride Length ◽  
Gait Parameters ◽  
Tremor Suppression ◽  
Gait Disturbances ◽  
Deep Brain

ObjectiveGait disturbances are frequent side effects occurring during chronic thalamic deep brain stimulation (DBS) in patients with essential tremor (ET). Adapting stimulation settings to shorter pulse widths has been shown to reduce side effects of subthalamic DBS. Here, we assess how a reduction of pulse width changes gait performance of affected patients.MethodsSensor-based gait assessment was performed to record spatiotemporal gait parameters in 10 healthy subjects (HS) and 7 patients with ET with gait disturbances following thalamic DBS. Patients were tested during standard DBS, after 72 hours of stimulation withdrawal and at least 30 days after adjusting DBS settings to a shorter pulse width of 40 µs (DBS40PW).ResultsPatients with ET on standard DBS showed significantly higher variability of several spatiotemporal gait parameters compared with HS. Variability of stride length and range of motion of the shanks significantly decreased OFF DBS as compared with standard DBS. This improvement was maintained over 30 days with DBS40PW while providing effective tremor suppression in six out of seven patients.ConclusionShorter pulse widths may reduce gait disturbances in patients with ET that are induced by DBS while preserving a level of tremor suppression equal to standard stimulation settings.

scholarly journals Closing the Loop With Cortical Sensing: The Development of Adaptive Deep Brain Stimulation for Essential Tremor Using the Activa PC+S

2021 ◽  
Vol 15 ◽  
Author(s):  
Tomasz M. Fra̧czek ◽  
Benjamin I. Ferleger ◽  
Timothy E. Brown ◽  
Margaret C. Thompson ◽  
Andrew J. Haddock ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Computational Models ◽  
Open Loop ◽  
Learning Approaches ◽  
Loop Design ◽  
Stimulation System ◽  
Neural Feedback ◽  
Deep Brain

Deep Brain Stimulation (DBS) is an important tool in the treatment of pharmacologically resistant neurological movement disorders such as essential tremor (ET) and Parkinson's disease (PD). However, the open-loop design of current systems may be holding back the true potential of invasive neuromodulation. In the last decade we have seen an explosion of activity in the use of feedback to “close the loop” on neuromodulation in the form of adaptive DBS (aDBS) systems that can respond to the patient's therapeutic needs. In this paper we summarize the accomplishments of a 5-year study at the University of Washington in the use of neural feedback from an electrocorticography strip placed over the sensorimotor cortex. We document our progress from an initial proof of hardware all the way to a fully implanted adaptive stimulation system that leverages machine-learning approaches to simplify the programming process. In certain cases, our systems out-performed current open-loop approaches in both power consumption and symptom suppression. Throughout this effort, we collaborated with neuroethicists to capture patient experiences and take them into account whilst developing ethical aDBS approaches. Based on our results we identify several key areas for future work. “Graded” aDBS will allow the system to smoothly tune the stimulation level to symptom severity, and frequent automatic calibration of the algorithm will allow aDBS to adapt to the time-varying dynamics of the disease without additional input from a clinician. Additionally, robust computational models of the pathophysiology of ET will allow stimulation to be optimized to the nuances of an individual patient's symptoms. We also outline the unique advantages of using cortical electrodes for control and the remaining hardware limitations that need to be overcome to facilitate further development in this field. Over the course of this study we have verified the potential of fully-implanted, cortically driven aDBS as a feasibly translatable treatment for pharmacologically resistant ET.

scholarly journals Optimal Parameters of Deep Brain Stimulation in Essential Tremor: A Meta-Analysis and Novel Programming Strategy

2020 ◽  
Vol 9 (6) ◽  
pp. 1855
Author(s):  
I. Daria Bogdan ◽  
Teus van Laar ◽  
D.L. Marinus Oterdoom ◽  
Gea Drost ◽  
J. Marc C. van Dijk ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Side Effects ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Stimulation Parameters ◽  
Novel Approach ◽  
Patient Reported ◽  
Tremor Suppression ◽  
Deep Brain

The programming of deep brain stimulation (DBS) parameters for tremor is laborious and empirical. Despite extensive efforts, the end-result is often suboptimal. One reason for this is the poorly understood relationship between the stimulation parameters’ voltage, pulse width, and frequency. In this study, we aim to improve DBS programming for essential tremor (ET) by exploring a new strategy. At first, the role of the individual DBS parameters in tremor control was characterized using a meta-analysis documenting all the available parameters and tremor outcomes. In our novel programming strategy, we applied 10 random combinations of stimulation parameters in eight ET-DBS patients with suboptimal tremor control. Tremor severity was assessed using accelerometers and immediate and sustained patient-reported outcomes (PRO’s), including the occurrence of side-effects. The meta-analysis showed no substantial relationship between individual DBS parameters and tremor suppression. Nevertheless, with our novel programming strategy, a significantly improved (accelerometer p = 0.02, PRO p = 0.02) and sustained (p = 0.01) tremor suppression compared to baseline was achieved. Less side-effects were encountered compared to baseline. Our pilot data show that with this novel approach, tremor control can be improved in ET patients with suboptimal tremor control on DBS. In addition, this approach proved to have a beneficial effect on stimulation-related complications.

Concepts and Methods in Chronic Thalamic Stimulation for Treatment of Tremor: Technique and Application

Neurosurgery ◽  
2001 ◽  
Vol 48 (3) ◽  
pp. 535-543 ◽  
Author(s):  
Joachim K. Krauss ◽  
Richard K. Simpson ◽  
William G. Ondo ◽  
Thomas Pohle ◽  
Jean-Marc Burgunder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Side Effects ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Surgical Techniques ◽  
Symptomatic Improvement ◽  
Test Stimulation ◽  
Deep Brain

Abstract OBJECTIVE To rationalize the technique and reduce the costs associated with chronic deep brain stimulation of the thalamus for treatment of refractory tremor. METHODS The efficacy and safety of a modification in surgical techniques was prospectively assessed in 94 patients with tremor. Bilateral electrodes were implanted in 29 patients, and 65 patients received unilateral implants. Forty-five patients had Parkinson's disease tremor, 42 patients had essential tremor, and 7 patients had kinetic tremors of different causes. In all instances, intraoperative stimulations to analyze the thresholds of intrinsic and extrinsic responses were performed directly with the implanted leads. The electrodes were repositioned until satisfactory results were achieved. The pulse generators were implanted directly after the first step in the same operative session. Patients were not subjected to interoperative test stimulation trials. RESULTS Postoperative improvement of tremor at a mean follow-up of 11.9 months was rated as excellent in 47 patients (50%), marked in 37 patients (39%), moderate in 8 patients (9%), and minor in 2 patients (2%). There was no persistent morbidity related to surgery. In patients with Parkinson's disease, the symptomatic improvement of tremor was rated as excellent in 51% of patients, marked in 36%, moderate in 11%, and minor in 2%. In patients with essential tremor, symptomatic outcome was classified as excellent in 57% of patients, marked in 36%, moderate in 5%, and minor in 2%. Six of the seven patients with kinetic tremor achieved marked symptomatic improvement, and one patient experienced moderate improvement. Forty patients experienced stimulation-related side effects. Side effects were mild in general, and they were reversible with a change in electrical parameters. They occurred more frequently in patients who had bilateral stimulation. CONCLUSION Excellent to marked improvement of tremor is achieved in the majority of patients with physiological target determination via implanted leads in thalamic deep brain stimulation. Interoperative test stimulation trials are unnecessary. Modifications in technique may help to reduce the costs of the related hospital stay.

Reducing Ataxic Side Effects from Ventral Intermediate Nucleus of the Thalamus Deep Brain Stimulation Implantation in Essential Tremor: Potential Advantages of Directional Stimulation

2021 ◽  
pp. 1-9
Author(s):  
Daniel Alberto Roque ◽  
Eldad Hadar ◽  
Ying Zhang ◽  
Fei Zou ◽  
Richard Murrow
Keyword(s):  
Deep Brain Stimulation ◽  
Side Effects ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Tertiary Care ◽  
Retrospective Chart Review ◽  
Intermediate Nucleus ◽  
Academic Center ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain

<b><i>Objective:</i></b> The aim of the study was to retrospectively evaluate the effect of directional deep brain stimulation (DBS) on ataxia in an essential tremor patient population. <b><i>Materials and Methods:</i></b> A retrospective chart review of documented Scale for Assessment and Rating of Ataxia (SARA) scores were analyzed using a case-control design. All subjects we evaluated were treated at a single, tertiary care academic center. We reviewed 14 patients who underwent bilateral ventral intermediate nucleus of the thalamus (VIM) implantation with microelectrode recording, with electrodeposition and segmented contact orientation confirmed via postoperative computed tomography. The main outcome was to determine change in ataxia scores between directional versus monopolar circumferential stimulation. <b><i>Results:</i></b> Fourteen patients (9 males, median age at implantation 69 [range 63–82]) underwent surgery between October 2017 and July 2020 at the UNC Movement Disorders Center. SARA scores between directional stimulation and monopolar circumferential stimulation demonstrated a significant reduction in total scores with best possible segmented stimulation (<i>n</i> = 13, <i>p</i> &#x3c; 0.0001, 95% confidence interval [CI] −3.496 to −6.789). This difference remained statistically significant even after removing the SARA tremor subscore (<i>n</i> = 13, <i>p</i> &#x3c; 0.0001, 95% CI −3.155 to −6.274). In line with prior reports, SARA score changes from the preoperative state were generally worsened when applying monopolar circumferential stimulation bilaterally (<i>n</i> = 13, <i>p</i> = 0.655; 95% CI −2.836 to 4.359), but improved with directional stimulation (<i>n</i> = 13, <i>p</i> = 0.010; 95% CI −1.216 to −7.547). <b><i>Conclusion:</i></b> This retrospective analysis appears to show evidence for improved outcomes through directional stimulation in bilateral VIM DBS implantation with reduction of ataxic side effects that have traditionally plagued postoperative results, all while providing optimized tremor reduction via stimulation.

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