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.

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.

Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

2021 ◽  
Author(s):  
Maarten Bot ◽  
Anne-Fleur van Rootselaari ◽  
Vincent Odekerken ◽  
Joke Dijk ◽  
Rob M A de Bie ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Red Nucleus ◽  
Brain Regions ◽  
Superior Cerebellar Peduncle ◽  
Beneficial Effects ◽  
Ventral Intermediate Nucleus ◽  
Cerebellar Peduncle ◽  
Deep Brain

Abstract BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.

scholarly journals Deep-Brain Stimulation for Essential Tremor and Other Tremor Syndromes: A Narrative Review of Current Targets and Clinical Outcomes

2020 ◽  
Vol 10 (12) ◽  
pp. 925
Author(s):  
Christian Iorio-Morin ◽  
Anton Fomenko ◽  
Suneil K. Kalia
Keyword(s):  
Multiple Sclerosis ◽  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Zona Incerta ◽  
Future Directions ◽  
Ventral Intermediate Nucleus ◽  
Prevalent Symptom ◽  
Multiple Conditions ◽  
Deep Brain

Tremor is a prevalent symptom associated with multiple conditions, including essential tremor (ET), Parkinson’s disease (PD), multiple sclerosis (MS), stroke and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (ventral intermediate nucleus of the thalamus (Vim), prelemniscal radiations (Raprl), caudal zona incerta (Zi), thalamus (Vo) and subthalamic nucleus (STN)) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.

scholarly journals Longitudinal follow-up with VIM thalamic deep brain stimulation for dystonic or essential tremor

Neurology ◽  
2020 ◽  
Vol 94 (10) ◽  
pp. e1073-e1084 ◽  
Author(s):  
Takashi Tsuboi ◽  
Zakia Jabarkheel ◽  
Pamela R. Zeilman ◽  
Matthew J. Barabas ◽  
Kelly D. Foote ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Statistical Significance ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain

ObjectiveTo assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET).MethodsWe retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2–3 years, 4–5 years, and ≥6 years after surgery.ResultsTwenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4–5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2–3 years follow-up.ConclusionOverall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features.Classification of evidenceThis study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.

scholarly journals Effects of ventral intermediate nucleus deep brain stimulation across multiple effectors in essential tremor

2020 ◽  
Vol 131 (1) ◽  
pp. 167-176 ◽  
Author(s):  
B.J. Wilkes ◽  
A. Wagle Shukla ◽  
A. Casamento-Moran ◽  
C.W. Hess ◽  
E.A. Christou ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Intermediate Nucleus ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain
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