Comparing deep brain stimulation in the ventral intermediate nucleus versus the posterior subthalamic area in essential tremor patients

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.

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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

Journal of Neurosurgery ◽

10.3171/2021.2.jns203815 ◽

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.

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Objective predictors of ‘early tolerance’ to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients

Clinical Neurophysiology ◽

10.1016/j.clinph.2018.05.012 ◽

2018 ◽

Vol 129 (8) ◽

pp. 1628-1633 ◽

Cited By ~ 7

Author(s):

Shabbir Hussain Merchant ◽

Sheng-Han Kuo ◽

Yu Qiping ◽

Linda Winfield ◽

Guy McKhann ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Brain Stimulation ◽

Intermediate Nucleus ◽

Ventral Intermediate Nucleus ◽

Deep Brain

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Thalamic organization in essential tremor patients with neuropathy: implication for functional neurosurgery

10.1101/2021.02.21.21251847 ◽

2021 ◽

Author(s):

Francesco Sammartino ◽

Vinayak Narayan ◽

Barbara Changizi ◽

Aristide Merola ◽

Vibhor Krishna

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Clinical Outcomes ◽

Brain Stimulation ◽

Element Model ◽

Target Coverage ◽

Thalamic Nuclei ◽

Intermediate Nucleus ◽

Ventral Intermediate Nucleus ◽

Deep Brain

AbstractBackgroundMechanisms underlying the suboptimal effect of ventral intermediate nucleus deep brain stimulation in patients with essential tremor and co-morbid peripheral neuropathy remain unclear.ObjectivesWe compared disease-related (location and extension of the ventral intermediate nucleus) and surgery-related (targeting, intraoperative testing) factors in essential tremor patients with and without peripheral polyneuropathy treated with deep brain stimulation of the ventral intermediate nucleus, testing whether the overlap between volume of tissue activated and ventral intermediate nucleus (target coverage) was associated with clinical outcomes.MethodsPreoperative diffusion magnetic resonance imaging was used for thalamic segmentation, based on preferential cortical connectivity. The target coverage was estimated using a finite element model. Tremor severity was scored at rest, posture, action, and handwriting at baseline, 6, and 12 months. Tremor improvement <50% at 12 months was deemed suboptimal. Vertex-wise shape analysis and edge analysis were performed to compare the ventral intermediate nucleus location and extension.Results9.7% (18/185) of essential tremor patients treated with deep brain stimulation had co-morbid polyneuropathy. These patients showed a more medial (p=0.03) and anterior (p=0.04) location of the ventral intermediate nucleus, lower target coverage (p=0.049), and worse clinical outcomes (p=0.006) compared to those without polyneuropathy. No differences were observed in the volume of tissue activated between the two groups. Optimal clinical outcomes were associated with greater target coverage (optimal coverage >48%).ConclusionsIn essential tremor, co-morbid polyneuropathy may result in suboptimal deep brain stimulation outcomes and lower target coverage, likely related to a reorganization of the ventral thalamic nuclei.

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

10.1101/575209 ◽

2019 ◽

Cited By ~ 4

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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