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.

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 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

Comparative connectivity correlates of dystonic and essential tremor deep brain stimulation

Brain ◽  
2021 ◽  
Author(s):  
Takashi Tsuboi ◽  
Joshua K Wong ◽  
Robert S Eisinger ◽  
Lela Okromelidze ◽  
Mathew R Burns ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Structural Connectivity ◽  
Cortical Network ◽  
Dystonic Tremor ◽  
Intermediate Nucleus ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain

Abstract The pathophysiology of dystonic tremor and essential tremor remains partially understood. In patients with medication-refractory dystonic tremor or essential tremor, deep brain stimulation (DBS) targeting the thalamus or posterior subthalamic area has evolved into a promising treatment option. However, the optimal DBS targets for these disorders remains unknown. This retrospective study explored the optimal targets for DBS in essential tremor and dystonic tremor using a combination of volumes of tissue activated estimation and functional and structural connectivity analyses. We included 20 patients with dystonic tremor who underwent unilateral thalamic DBS, along with a matched cohort of 20 patients with essential tremor DBS. Tremor severity was assessed preoperatively and approximately 6 months after DBS implantation using the Fahn-Tolosa-Marin Tremor Rating Scale. The tremor-suppressing effects of DBS were estimated using the percentage improvement in the unilateral tremor-rating scale score contralateral to the side of implantation. The optimal stimulation region, based on the cluster centre of gravity for peak contralateral motor score improvement, for essential tremor was located in the ventral intermediate nucleus region and for dystonic tremor in the ventralis oralis posterior nucleus region along the ventral intermediate nucleus/ventralis oralis posterior nucleus border (4 mm anterior and 3 mm superior to that for essential tremor). Both disorders showed similar functional connectivity patterns: a positive correlation between tremor improvement and involvement of the primary sensorimotor, secondary motor and associative prefrontal regions. Tremor improvement, however, was tightly correlated with the primary sensorimotor regions in essential tremor, whereas in dystonic tremor, the correlation was tighter with the premotor and prefrontal regions. The dentato-rubro-thalamic tract, comprising the decussating and non-decussating fibres, significantly correlated with tremor improvement in both dystonic and essential tremor. In contrast, the pallidothalamic tracts, which primarily project to the ventralis oralis posterior nucleus region, significantly correlated with tremor improvement only in dystonic tremor. Our findings support the hypothesis that the pathophysiology underpinning dystonic tremor involves both the cerebello-thalamo-cortical network and the basal ganglia-thalamo-cortical network. Further our data suggest that the pathophysiology of essential tremor is primarily attributable to the abnormalities within the cerebello-thalamo-cortical network. We conclude that the ventral intermediate nucleus/ventralis oralis posterior nucleus border and ventral intermediate nucleus region may be a reasonable DBS target for patients with medication-refractory dystonic tremor and essential tremor, respectively. Uncovering the pathophysiology of these disorders may in the future aid in further improving DBS outcomes.

Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort

2021 ◽  
pp. 1-10
Author(s):  
Andre A. Wakim ◽  
Natasha A. Sioda ◽  
James J. Zhou ◽  
Margaret Lambert ◽  
Virgilio Gerald H. Evidente ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Anterior Commissure ◽  
Proton Density ◽  
Historical Cohort ◽  
Intermediate Nucleus ◽  
Ventral Intermediate Nucleus ◽  
Direct Targeting ◽  
Deep Brain

OBJECTIVE The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation (DBS) to control symptoms related to essential tremor. The VIM is typically targeted using indirect methods, although studies have reported visualization of the VIM on proton density–weighted MRI. This study compares the outcomes between patients who underwent VIM DBS with direct and indirect targeting. METHODS Between August 2013 and December 2019, 230 patients underwent VIM DBS at the senior author’s institution. Of these patients, 92 had direct targeting (direct visualization on proton density 3-T MRI). The remaining 138 patients had indirect targeting (relative to the third ventricle and anterior commissure–posterior commissure line). RESULTS Coordinates of electrodes placed with direct targeting were significantly more lateral (p < 0.001) and anterior (p < 0.001) than those placed with indirect targeting. The optimal stimulation amplitude for devices measured in voltage was lower for those who underwent direct targeting than for those who underwent indirect targeting (p < 0.001). Patients undergoing direct targeting had a greater improvement only in their Quality of Life in Essential Tremor Questionnaire hobby score versus those undergoing indirect targeting (p = 0.04). The direct targeting group had substantially more symptomatic hemorrhages than the indirect targeting group (p = 0.04). All patients who experienced a postoperative hemorrhage after DBS recovered without intervention. CONCLUSIONS Patients who underwent direct VIM targeting for DBS treatment of essential tremor had similar clinical outcomes to those who underwent indirect targeting. Direct VIM targeting is safe and effective.

scholarly journals Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

2019 ◽  
Author(s):  
Bassam Al-Fatly ◽  
Siobhan Ewert ◽  
Dorothee Kübler ◽  
Daniel Kroneberg ◽  
Andreas Horn ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Motor Cortex ◽  
Essential Tremor ◽  
Brain Stimulation ◽  
Brain Connectivity ◽  
Clinical Care ◽  
Hand Tremor ◽  
Intermediate Nucleus ◽  
Ventral Intermediate Nucleus ◽  
Deep Brain

AbstractEssential tremor is the most prevalent movement disorder and is often refractory to medical treatment. Deep brain stimulation offers a therapeutic approach that can efficiently control tremor symptoms. Several deep brain stimulation targets (ventral intermediate nucleus, zona incerta, posterior subthalamic area) have been discussed for tremor treatment. Effective deep brain stimulation therapy for tremor critically involves optimal targeting to modulate the tremor network. This could potentially become more robust and precise by using state-of-the-art brain connectivity measurements. In the current study, we utilized two normative brain connectomes (structural and functional) to show the pattern of effective deep brain stimulation electrode connectivity in 36 essential tremor patients. Our structural and functional connectivity models were significantly predictive of post-operative tremor improvement in out-of-sample data (p< 0.001 for both structural and functional leave-one-out cross-validation). Additionally, we segregated the somatotopic brain network based on head and hand tremor scores. These resulted in segregations that mapped onto the well-known somatotopic maps of both motor cortex and cerebellum. Crucially, this shows that slightly distinct networks need to be modulated to ameliorate head vs. hand tremor and that those networks could be identified based on somatotopic zones in motor cortex and cerebellum.Finally, we propose a multi-modal connectomic deep brain stimulation sweet spot that may serve as a reference to enhance clinical care, in the future. This spot resided in the posterior subthalamic area, encroaching on the inferior borders of ventral intermediate nucleus and sensory thalamus. Our results underscore the importance of integrating brain connectivity in optimizing deep brain stimulation targeting for essential tremor.

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