Intermediate Nucleus Deep Brain Stimulation Research Articles

Neuropsychological assessment protocol in an ongoing randomized controlled trial on posterior subthalamic area vs. ventral intermediate nucleus deep brain stimulation for essential tremor.

Patients with essential tremor (ET) may experience cognitive-affective impairment. Deep brain stimulation (DBS) of different targets, such as the ventral intermediate nucleus (VIM) of the thalamus or the posterior subthalamic area (PSA), has been shown to be beneficial for refractory ET. However, there is little evidence regarding the possible neuropsychological effects of PSA-DBS on patients with ET, and there are few studies comparing it with VIM-DBS in this population.In this study, we aim to present the evaluation protocol and neuropsychological battery as used in an ongoing trial of DBS for ET comparing the already mentioned targets. As part of a randomized, double-blind, crossover clinical trial comparing the effectiveness and safety of PSA-DBS vs. VIM-DBS, 11 patients with refractory ET will undergo a multi-domain neuropsychological battery assessment. This will include a pre-/post-implantation assessment (3 months after the stimulation of each target and 6 months after an open stage of DBS on the most optimal target). Evidence on the neuropsychological effects of DBS in patients with refractory ET is very scarce, particularly in lesser-explored targets such as PSA. This study could contribute significantly in this field, particularly on pre-procedure safety analysis for tailored patient/technique selection, and to complete the safety analysis of the procedure. Moreover, if proven useful, this proposed neuropsychological assessment protocol could be extensible to other surgical therapies for ET.

Effect of Ventral Intermediate Nucleus Deep Brain Stimulation on Vocal Tremor in Essential Tremor.

There is a paucity of literature examining the effect of Ventral Intermediate Nucleus (VIM) deep brain stimulation (DBS) on voice in patients with vocal tremor (VT). Investigate the effect of unilateral and bilateral VIM DBS on voice in patients with Essential Tremor (ET) and VT. All patients receiving VIM DBS surgery underwent voice evaluation pre- and six-months post-operatively. We collected patient-reported quality-of-life outcome measures and acoustic voice measures of sustained phonation and connected speech. Acoustic measures specific to VT included amplitude tremor intensity index (ATRI), frequency tremor intensity index (FTRI), rate and extent of F0 modulation, and rate and extent of intensity modulation. Five patients, age 72.8 ± 2.6 years, 4 female, 1 male with mean disease duration of 29 ± 26.2 years met the inclusion criteria and were included. Two subjects had bilateral procedure and three had unilateral. We observed significant improvements in measures of vocal tremor including ATRI, FTRI, rate of F0 modulation, rate of intensity modulation, and extent of intensity modulation, as well as patient reported voice-related quality of life measured by VHI-10. Bilateral VIM DBS cases showed greater improvement in VT than unilateral cases. Both unilateral and bilateral VIM DBS resulted in significant improvement of VT, with more improvement demonstrated in patients having bilateral as compared to unilateral VIM DBS. In addition, patients also reported significant improvements in voice-related quality of life. If larger studies confirm our results, VIM DBS has the potential to become a treatment specifically for disabling VT.

Ventral intermediate nucleus deep brain stimulation for treatment-resistant focal aware motor seizures: illustrative case.

Resection of the seizure onset zone (SOZ) is considered the gold standard for treating refractory focal aware seizures (FASs). When resective surgery is unadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT; ANT-DBS) has been the procedure of choice. However, less than half of patients with FASs respond to ANT-DBS. The need for alternative targets to effectively treat FAS is thus evident. The authors report the case of a 39-year-old woman presenting with pharmaco-resistant focal aware motor seizures, with the SOZ located in the primary motor cortical area. She had previously undergone unsuccessful resection of the left temporoparietal operculum elsewhere. Considering the risk of new resective surgery, she was offered combined ventral intermediate nucleus (Vim)/ANT-DBS. Vim-DBS proved to be superior to ANT-DBS for seizure control (88% vs 32%), although the association of both provided the best results (97%). This is the first report on the use of the Vim as a target of DBS for the treatment of FAS. The excellent results were presumably obtained by modulation of the SOZ through Vim projections to the motor cortex. This opens a completely new avenue for treating FAS: chronic stimulation of specific thalamic nuclei.

Depression Scores following Ventral Intermediate Nucleus Deep Brain Stimulation for Essential Tremor: A Meta-Analysis

Background: Essential tremor (ET) patients present with both motor and non-motor symptoms including depression. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is used to treat motor symptoms of ET, there is no consensus as to how VIM DBS influences non-motor symptoms, specifically depression. Objective: The objective of this study was to conduct a meta-analysis of available studies investigating change in pre- to postoperative depression scores as measured by Beck Depression Inventory (BDI) in ET patients receiving VIM DBS. Methods: Inclusion criteria were randomized control trials or observational studies of patients undergoing unilateral/bilateral VIM DBS. Non-ET patients, case reports, patients <18 years old, only non-VIM electrode placement, non-English articles, and abstracts were excluded. The primary outcome was change in BDI score from the preoperative time point to the last available follow-up. Pooled estimates of overall effect for BDI standardized mean difference were calculated using random effects models with the inverse variance method. Results: Seven studies divided into eight cohorts for a total of 281 ET patients met inclusion criteria. Pooled preoperative BDI score was 12.44 (95% CI [6.63–18.25]). A statistically significant decrease in depression scores was observed postoperatively (SMD = −0.29, 95% CI [−0.46 to −0.13], p = 0.0006). Pooled postoperative BDI score was 9.18 (95% CI [4.98–13.38]). A supplementary analysis which included an additional study with an estimated standard deviation at last follow-up was conducted. There was also a statistically significant decrease in depression postoperatively (9 cohorts, n = 352, SMD = −0.31, 95% CI [−0.46 to −0.16], p < 0.0001). Conclusions: Both quantitative and qualitative analyses of the existing literature suggest that VIM DBS improves depression postoperatively among ET patients. These results may guide surgical risk-benefit analysis and counseling for ET patients undergoing VIM DBS.

Additional Cover

CNS Neuroscience & TherapeuticsVolume 28, Issue 8 p. ii-ii ADDITIONAL COVEROpen Access Additional Cover First published: 04 July 2022 https://doi.org/10.1111/cns.13910AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract The Additional cover image is based on the Research Article Which one is the superior target? A comparison and pooled analysis between posterior subthalamic area and ventral intermediate nucleus deep brain stimulation for essential tremor by Yutong Bai et al., https://doi.org/10.1111/cns.13878. Volume28, Issue8August 2022Pages ii-ii RelatedInformation

Which one is the superior target? A comparison and pooled analysis between posterior subthalamic area and ventral intermediate nucleus deep brain stimulation for essential tremor.

Background/AimsThe efficacy and safety of posterior subthalamic area (PSA) and ventral intermediate nucleus (VIM) deep brain stimulation (DBS) in the treatment of essential tremor (ET) have not been compared in large‐scale studies. We conducted a secondary analysis to identify the superior target of ET‐DBS treatment.MethodsPubMed, Embase, Cochrane Library, and Google Scholar were searched for relevant studies before September 2021. The tremor‐suppression efficacy and rate of stimulation‐related complications (SRCR) after PSA‐DBS and VIM‐DBS treating ET were quantitatively compared. Secondary outcomes, including tremor subitem scores and quality of life results, were also analyzed. Subgroup analyses were further conducted to stratify by follow‐up (FU) periods and stimulation lateralities. This study was registered in Open Science Framework (DOI: 10.17605/OSF.IO/7VJQ8).ResultsA total of 23 studies including 122 PSA‐DBS patients and 326 VIM‐DBS patients were analyzed. The average follow‐up time was 12.81 and 14.66 months, respectively. For the percentage improvement of total tremor rating scale (TRS) scores, PSA‐DBS was significantly higher, when compared to VIM‐DBS in the sensitivity analysis (p = 0.030) and main analysis (p = 0.043). The SRCR after VIM‐DBS was higher than that of PSA‐DBS (p = 0.022), and bilateral PSA‐DBS was significantly superior to both bilateral and unilateral VIM‐DBS (p = 0.001).ConclusionsThis study provided level IIIa evidence that PSA‐DBS was more effective and safer for ET than VIM‐DBS in 12–24 months, although both PSA‐DBS and VIM‐DBS were effective in suppressing tremor in ET patients. Further prospective large‐scale randomized clinical trials are warranted in the future.

Effect of Unilateral &amp; Bilateral Ventral Intermediate Nucleus Deep Brain Stimulation on Vocal Tremor and Voice in Patients with Essential Tremor and Vocal Tremor. A Case Series. (S32.004)

Effect of Unilateral &amp; Bilateral Ventral Intermediate Nucleus Deep Brain Stimulation on Vocal Tremor and Voice in Patients with Essential Tremor and Vocal Tremor. A Case Series. (S32.004)

Role of Directional Configuration in Deep Brain Stimulation for Essential Tremor: A Single Center Experience.

Background:Traditionally, the standard of care for medication refractory essential tremor has been to utilize omnidirectional deep brain stimulation of the ventral intermediate nucleus. The advent of directional stimulation allows for spatial restriction of the stimulation on selected targets without involving the neighboring structures, thereby limiting off-target side effects and improving clinical utility.Methods:We performed a retrospective review of patients between February 2017 and September 2019 who had received ventral intermediate nucleus deep brain stimulation that allowed for directional programming (specifically Abbott/St. Jude). Initial and final major programming sessions post-operatively (approximately 30- and 90-days post-surgery) were examined to determine frequency and reason for use of directional programming.Results:A total of 33 total patients were identified. A little over half were males (58%, N = 19), with an average age of 68 years old (SD 9.3) at the time of surgery, and a disease duration of almost 30 years (27.2, SD 19) with a wide range from 2–62 years. After initial programming, over 50% (17 of 33) of patients were using directional configurations. This increased to 85% (28 of 33) at the 90-day programming. Reasons for conversion to directional configuration included avoidance of side effects (specifically, muscle contractions (9/33), paresthesia (5/33), dysarthria (1/33) and gait ataxia (1/33)) or improved tremor control (12/33).Discussion:Our single-center experience suggests that in the large majority of cases, directional leads were utilized and offered advantages in tremor control or side effect avoidance.

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

To 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). We 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. Twenty-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. Overall, 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. This study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.

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

ObjectiveEssential tremor (ET) prominently affects the upper-limbs during voluntary movements, but can also affect the lower-limbs, head, and chin. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of thalamus improves both clinical ratings and quantitative measures of tremor, no study has quantified effects of DBS on tremor across multiple body parts. Our objective was to quantify therapeutic effects of DBS across multiple body parts in ET. MethodsWe performed quantitative assessment of tremor in ET patients who had DBS for at least one year. We assessed tremor on and off VIM-stimulation using triaxial accelerometers on the upper-limbs, lower-limbs, head and chin during seated and standing tasks. ResultsVIM-DBS significantly reduced tremor, but there was no statistical difference in degree of tremor reduction across the measured effectors. Compared to healthy controls, ET patients treated with DBS showed significantly greater tremor power (4–8 Hz) across all effectors during seated and standing tasks. ConclusionsVIM-DBS reduced tremor in ET patients. There was no significant difference in the degree of tremor reduction across the measured effectors. SignificanceThis study provides new quantitative evidence that VIM-DBS is effective at reducing tremor across multiple parts of the body.

Benefits and risks of unilateral and bilateral ventral intermediate nucleus deep brain stimulation for axial essential tremor symptoms

IntroductionMany experts assume bilateral deep brain stimulation (DBS) is necessary to improve axial tremor in essential tremor (ET). In the largest clinical trial of DBS for ET to date evaluating a non-directional, constant current device, we studied the effects of unilateral and staged bilateral DBS on axial tremor. MethodsWe included all participants from the original trial with unilateral ventral intermediate nucleus (VIM) DBS and 90-day follow up at minimum. Primary outcomes were changes in pooled axial subscores in the Clinical Rating Scale for Tremor (CRST) at 90 and 180 days after activation of unilateral VIM DBS compared to pre-operative baseline (n=119). Additionally, we performed within-subject analyses for unilateral versus bilateral DBS at 180 days in the cohort who underwent staged surgery to bilateral DBS (n=39). ResultsUnilateral VIM DBS improved midline tremor by 58% at 90 days (median[IQR]) (3[3] to 1[2], p<0.001) and 65% at 180 days (3[3] to 1[2], p<0.001) versus pre-op baseline. In the staged to bilateral DBS cohort, midline tremor scores further improved after bilateral DBS at 180 days by 63% versus unilateral DBS (3[3] to 1[3], p=0.007). There were, however, 35 additional DBS and surgery-related adverse events, 14 related to incoordination, gait impairment, or speech impairment, versus 6 after unilateral DBS. ConclusionUnilateral VIM DBS for ET significantly improved associated axial tremor. Staged bilateral DBS was associated with additional axial tremor improvement but also additional adverse events. Unilateral VIM DBS may be sufficient to achieve a goal of contralateral limb and axial tremor attenuation.

Orthostatic Tremor: Pathophysiology Guiding Treatment.

Orthostatic tremor (OT) is a rare disorder characterized by tremor and a feeling of unsteadiness while standing that resolve upon walking or sitting. A pathognomonic 13-18Hz tremor is seen on surface EMG while standing. Though its clinical features have been better defined over time, much of its pathophysiology remains unknown and treatment options are limited. We review here recent developments in both of these areas. Several recent studies have furthered our understanding of the central oscillatory network involved in OT. fMRI and 18F-FDG-PET studies have identified a ponto-cerebello-thalamo-cortical network underlying OT, though the nature of its dysfunction remains unknown. Randomized trials of treatments for OT are few, so most data are from case reports or small case series. Clonazepam and gabapentin are likely the most effective medical therapies, while bilateral ventral intermediate nucleus deep brain stimulation shows promise for refractory cases. Though much about OT remains unknown, our understanding of its pathophysiology has improved through recent studies. Treatment benefit is overall modest and inconsistent, though better understanding of the disease could lead to new avenues for treatment.

Thalamic deep brain stimulation for orthostatic tremor: A multicenter international registry.

We report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor. Data from 17 patients were reviewed, comparing presurgical, short-term (0-48 months), and long-term (≥48 months) follow-up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment-related complications. There was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long-term follow-up (8 of 17). The latency of symptoms on standing significantly improved, both in the short-term (P = 0.001) and in the long-term (P = 0.018). Three patients obtained no/minimal benefit from the procedure. Deep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society.

Use of efficacy probability maps for the post-operative programming of deep brain stimulation in essential tremor.

Post-operative programming of deep brain stimulation for movement disorders can be both time consuming and difficult, which can delay the optimal symptom control for the patient. Probabilistic maps of stimulation response could improve programming efficiency and optimization. The clinically selected contacts of patients who had undergone ventral intermediate nucleus deep brain stimulation for the treatment of essential tremor at our institution were compared against contacts selected based on a probability map of symptom reduction built by populating data from a number of patients using non-rigid image registration. A subgroup of patients whose clinical contacts did not match the map-based selections prospectively underwent a tremor rating scale evaluation to compare the symptom relief achieved by the two options. Both the patient and video reviewer were blinded to the selection. 54% of the map-based and clinical contacts were an exact match retrospectively and were within one contact 83% of the time. In 5 of the 8 mismatched leads that were evaluated prospectively in a double blind fashion, the map-based contact showed equivalent or better tremor improvement than the clinically active contact. This study suggests that probability maps of stimulation responses can assist in selecting the clinically optimal contact and increase the efficiency of programming.