Dataset Information

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.

ABSTRACT:

Background/aims

The 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.

Methods

PubMed, 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).

Results

A 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).

Conclusions

This 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.

SUBMITTER: Fan H

PROVIDER: S-EPMC9344089 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

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.

Fan Houyou H Bai Yutong Y Yin Zixiao Z An Qi Q Xu Yichen Y Gao Yuan Y Meng Fangang F Zhang Jianguo J

CNS neuroscience & therapeutics 20220610 9

<h4>Background/aims</h4>The 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.<h4>Methods</h4>PubMed, Embase, Cochrane Library, and Google Scholar were searched for relevant studies before September 2021. The tremor-suppression efficacy and rate of st ...[more]

PMID: 35687507

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Project description:Ventral intermediate thalamic deep brain stimulation is a standard therapy for the treatment of medically refractory essential tremor and tremor-dominant Parkinson's disease. Despite the therapeutic benefits, the mechanisms of action are varied and complex, and the pathophysiology and genesis of tremor remain unsubstantiated. This intraoperative study investigated the effects of high frequency microstimulation on both neuronal firing and tremor suppression simultaneously. In each of nine essential tremor and two Parkinson's disease patients who underwent stereotactic neurosurgery, two closely spaced (600 µm) microelectrodes were advanced into the ventral intermediate nucleus. One microelectrode recorded action potential firing while the adjacent electrode delivered stimulation trains at 100 Hz and 200 Hz (2-5 s, 100 µA, 150 µs). A triaxial accelerometer was used to measure postural tremor of the contralateral hand. At 200 Hz, stimulation led to 68 ± 8% (P < 0.001) inhibition of neuronal firing and a 53 ± 5% (P < 0.001) reduction in tremor, while 100 Hz reduced firing by 26 ± 12% (not significant) with a 17 ± 6% (P < 0.05) tremor reduction. The degree of cell inhibition and tremor suppression were significantly correlated (P < 0.001). We also found that the most ventroposterior stimulation sites, closest to the border of the ventral caudal nucleus, had the best effect on tremor. Finally, prior to the inhibition of neuronal firing, microstimulation caused a transient driving of neuronal activity at stimulus onset (61% of sites), which gave rise to a tremor phase reset (73% of these sites). This was likely due to activation of the excitatory glutamatergic cortical and cerebellar afferents to the ventral intermediate nucleus. Temporal characteristics of the driving responses (duration, number of spikes, and onset latency) significantly differed between 100 Hz and 200 Hz stimulation trains. The subsequent inhibition of neuronal activity was likely due to synaptic fatigue. Thalamic neuronal inhibition seems necessary for tremor reduction and may function in effect as a thalamic filter to uncouple thalamo-cortical from cortico-spinal reflex loops. Additionally, our findings shed light on the gating properties of the ventral intermediate nucleus within the cerebello-thalamo-cortical tremor network, provide insight for the optimization of deep brain stimulation technologies, and may inform controlled clinical studies for assessing optimal target locations for the treatment of tremor.

Project description:Deep Brain Stimulation of the posterior subthalamic area is an emergent target for the treatment of Essential Tremor. Due to the heterogeneous and complex anatomy of the posterior subthalamic area, it remains unclear which specific structures mediate tremor suppression and different side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate the different clinical effects observed during directional deep brain stimulation of that area. We analysed a consecutive series of 12 essential tremor patients. Imaging analysis and systematic clinical testing performed 4-6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual activation volumes and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects. Stimulation of the dentato-rubro-thalamic tract and the zona incerta was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus. Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts. The best directional contacts did not provide significantly larger therapeutic windows than omnidirectional stimulation at the same level. Deep brain stimulation of the posterior subthalamic area effectively suppresses all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the dentato-rubro-thalamic tract and the zona incerta. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated modelling of activation volumes taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.

Project description:ObjectiveThis study was aimed at identifying the potential outcome predictors, comparing the efficacy in patients with different tremor characteristics, and summarizing the adverse effect rates (AERs) of deep brain stimulation on the ventral intermediate nucleus (VIM-DBS) for essential tremor (ET).MethodsAn extensive search of articles published to date in 2019 was conducted, and two main aspects were analyzed. Improvement was calculated as a percentage of change in any objective tremor rating scale (TRS) and analyzed by subgroup analyses of patients' tremor characteristics, laterality, and stimulation parameters. Furthermore, the AERs were analyzed as follows: the adverse effects (AEs) were classified as stimulation-related, surgical-related, or device-related effects. A simple regression analysis was used to identify the potential prognostic factors, and a two-sample mean-comparison test was used to verify the statistical significance of the subgroup analyses.ResultsForty-six articles involving 1714 patients were included in the meta-analysis. The pooled improvement in any objective TRS score was 61.3% (95% CI: 0.564-0.660) at the mean follow-up visit (20.0 ± 17.3 months). The midline and extremity symptoms showed consistent improvement (P = 0.440), and the results of the comparison of postural and kinetic tremor were the same (P = 0.219). In addition, the improvement in rest tremor was similar to that in action tremor (OR = 2.759, P = 0.120). In the simple regression analysis, the preoperative Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores and follow-up time were negatively correlated with the percentage change in any objective TRS score (P < 0.05). The most common adverse event was dysarthria (10.5%), which is a stimulation-related AE (23.6%), while the rates of the surgical-related and device-related AEs were 6.4% and 11.5%, respectively.ConclusionVIM-DBS is an efficient and safe surgical method in ET, and the efficacy was not affected by the body distribution of tremor, age at surgery, and disease duration. Lower preoperative FTM-TRS scores likely indicate greater improvement, and the effect of VIM-DBS declines over time.

Project description:Holmes tremor is a symptomatic tremor that develops secondary to central nervous system disorders. Stereotactic neuromodulation is considered when the tremors are intractable. Targeting the ventral intermediate nucleus (Vim) is common; however, the outcome is often unsatisfactory, and the posterior subthalamic area (PSA) is expected as alternative target. In this study, we report the case of a patient with intractable Holmes tremor who underwent dual-lead deep brain stimulation (DBS) to stimulate multiple locations in the PSA and thalamus. The patient was a 77-year-old female who complained of severe tremor in her left upper extremity that developed one year after her right thalamic infarction. Vim-thalamotomy using focused ultrasound therapy (FUS) was initially performed but failed to control tremor. Subsequently, we performed DBS using two leads to stimulate four different structures. Accordingly, one lead was implanted with the aim of targeting the ventral oralis nucleus (Vo)/zona incerta (Zi), and the other with the aim of targeting the Vim/prelemniscal radiation (Raprl). Electrode stimulation revealed that Raprl and Zi had obvious effects. Postoperatively, the patient achieved good tremor control without any side effects, which was maintained for two years. Considering that she demonstrated resting, postural, and intention/action tremor, and Vim-thalamotomy by FUS was insufficient for tremor control, complicated pathogenesis was presumed in her symptoms including both the cerebellothalamic and the pallidothalamic pathways. Using the dual-lead DBS technique, we have more choices to adjust the stimulation at multiple sites, where different functional networks are connected. Intractable tremors, such as Holmes tremor, may have complicated pathology, therefore, modulating multiple pathological networks is necessary. We suggest that the dual-lead DBS (Vo/Raprl and Vim/Zi) presented here is safe, technically feasible, and possibly effective for the control of Holmes tremor.

Dataset Information

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/aims

Methods

Results

Conclusions

Publications

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.

Similar Datasets

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