Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor

Abstract

Background: The ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS).Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long-term reduction of benefit seen with VIM-DBS. Objectives: To compare clinical outcomes and DBS programming in the long-term between VIM and cZI neurostimulation in ET-DBS patients. Materials and Methods: A retrospective review of 53 DBS leads from 47 patients was performed. Patients were classified into VIM or cZI groups according to the location of the activated DBS contact. Demographics, DBS settings, and Tremor Rating Scale scores were compared between groups at baseline and yearly follow-up to 4 years after DBS. Student t-tests and analysis of variance (ANOVA) were used to compare variables between groups. Results: Relative to baseline, an improvement in ON-DBS tremor scores was observed in both groups from 6 months to 4 years post-DBS (p < 0.05). Although improvement was still significant at 4 years, scores from month 6 to 2 years were comparable between groups but at 3 and 4 years post-DBS the outcome was better in the VIM group (p < 0.01). Stimulation settings were similar across groups, although we found a lower voltage in the VIM group at 3 years post-DBS. Conclusions: More ventral DBS contacts in the cZI region do improve tremor, however, VIM-DBS provided better long-term outcomes. Randomized controlled trials comparing cZI vs VIM targets should confirm these results.Essential Tremor (ET) is the most common adult-onset movement disorder, impairing approximately 10 million people in the United States.1,2 Current evidence-based guidelines recommend medical therapies as the first-line treatment option.3 However, nearly 50% of patients will have a suboptimal response to medical management or will experience medication side effects that may lead to discontinuation of therapy. 4 Thalamic ventralis intermedius nucleus (VIM) deep brain stimulation (DBS) received approval from the US Food and Drug Administration in 1997 and is well established as a safe and effective treatment for medically refractory tremor. 5-7Despite good patient selection and significant initial tremor suppression achieved with VIM-DBS, around 40-70% of patients will experience a worsening of tremor over time. 8,9

Unilateral Thalamic Deep Brain Stimulation for Voice Tremor

“…This is in contrast to stimulation-induced dysarthria which is caused by the electrodes placed more laterally and is more common following bilateral than unilateral stimulation [28, 49, 50]. Our results suggest that optimal voice outcomes following DBS are both target and side specific, in contrast to the improvement of limb tremor that can be achieved even with stimulation outside of the Vim nucleus [51-53]. …”

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

“…Targeting the VIM nucleus was regarded as a historical gold-standard since the beginnings of modern-day DBS (Benabid et al, 1991). Increasingly, the ventrally adjacent white matter has been proposed to lead to superior effects (Hamel et al, 2007;Sandvik et al, 2012;Eisinger et al, 2018).…”

Zona incerta as a therapeutic target in Parkinson’s disease

“…In an agreement with previous studies [47,49], DBS of this region induced a profound effect on tremor, had less influence on akinesia and was free of negative influence on speech [50]. Special involvement of the caudal ZI and prelemniscal radiation (located posteromedially to the posterodorsal STN) in tremor, in general, was proven also by findings that DBS of this region had strong effect on PD voice tremor, proximal, distal and axial essential tremor, postural and intention component of multiple sclerosis tremor, Holmes tremor (resting, postural and intention) and dystonic tremor [49,[51][52][53][54]. When therapeutic effectiveness of DBS in essential tremor was compared in relation to the location of stimulated fields, the best region seemed to incorporate the superior part of the cerebellothalamic fasciculus and caudal ZI [52].…”

“…However, according to general opinion of neurosurgeons, DBS of the caudal sector of the ZI was the most therapeutically effective, especially with respect to reduction of different forms of tremor, including parkinsonian tremor [46,47,[49][50][51][52][53]. The most probable explanation of this effect is that DBS affects the cerebellothalamic glutamatergic fibres arising from subcortical deep cerebellar nuclei [150] which traverse this region and form there collaterals and terminals [88,90,100].…”