Ventralis Intermedius Deep Brain Stimulation Research Articles

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor

BackgroundSymmetric biphasic pulses have been shown to acutely increase the therapeutic window of ventralis intermedius deep brain stimulation (Vim-DBS) for essential tremor (ET) compared to cathodic pulses. Acute supratherapeutic stimulation can induce ataxic side effects in Vim-DBS. ObjectiveTo investigate the effect on tremor, ataxia and dysarthria of 3 h of biphasic stimulation in patients with DBS for ET. MethodsA randomized, doubled-blind, cross-over design was used to compare standard cathodic pulses with symmetric biphasic pulses (anode-first) during a 3-h period per pulse shape. During each 3-h period, all stimulation parameters were identical, except for the pulse shape. Tremor (Fahn-Tolosa-Marin Tremor Rating Scale), ataxia (International Cooperative Ataxia Rating Scale) and speech (acoustic and perceptual measures) were assessed hourly during the 3-h periods. ResultsTwelve ET patients were included. During the 3-h stimulation period, tremor control was equivalent between the two pulse shapes. Biphasic pulses elicited significantly less ataxia than cathodic pulses (p = 0.006). Diadochokinesis rate of speech was better for the biphasic pulse (p = 0.048), but other measures for dysarthria were not significantly different between the pulses. ConclusionSymmetric biphasic pulses induce less ataxia than conventional pulses after 3 h of stimulation DBS in ET patients.

Suppression of Axial Tremor by Deep Brain Stimulation in Patients with Essential Tremor: Effects on Gait and Balance Measures.

Background:Deep brain stimulation (DBS) of the ventralis intermedius (VIM) nucleus of the thalamus has been successful in mitigating upper limb tremor, but the effect on gait and balance performance is unclear. Here, we aim to examine the effectiveness of VIM DBS on stride length variability, sway path length, and task-relevant tremor of various body segments in essential tremor (ET).Methods:Seventeen ET individuals treated with DBS (ET DBS) and 17 age-and sex-matched healthy controls (HC) performed a postural balance and overground walking task. In separate and consecutive visits, ET DBS performed gait and balance tasks with DBS ON or OFF. The main outcome measures were sway path length, stride length variability, and tremor quantified from upper limb, lower limb, upper and lower trunk (axial) during the gait and balance tasks.Results:With DBS OFF, ET DBS exhibited significantly greater stride length variability, sway path length, and tremor during gait and balance task relative to HC. Relative to DBS OFF, DBS ON reduced stride length variability and sway path length in ET DBS. The DBS-induced reduction in stride length variability was associated with the reduction in both upper trunk tremor and upper limb tremor. The DBS-induced reduction in sway path length was associated with the reduction in upper trunk tremor.Discussion:The findings of this study revealed that VIM DBS was effective in improving gait and balance in ET DBS and that improvements in gait and postural balance were associated with a reduction of axial tremor during the tasks.Highlights:ET patients exhibit tremor in various body locations during gait and balance.DBS reduced stride length variability and sway path length.DBS-induced improvements in gait and balance were associated with reduction in axial tremor.

Connectomic analysis of unilateral dual-lead thalamic deep brain stimulation for treatment of multiple sclerosis tremor.

Tremor is a common symptom in multiple sclerosis and can present as a severe postural and action tremor, leading to significant disability. Owing to the diffuse and progressive nature of the disease, it has been challenging to characterize the pathophysiology underlying multiple sclerosis tremor. Deep brain stimulation of the ventralis intermedius and the ventralis oralis posterior thalamic nuclei has been used to treat medically refractory multiple sclerosis tremors with variable results. The aim of this study was to characterize multiple sclerosis tremor at the network level by applying modern connectomic techniques to data from a previously completed single-centre, randomized, single-blind prospective trial of 12 subjects who were treated with unilateral dual-lead (ventralis intermedius + ventralis oralis posterior) thalamic deep brain stimulation. Preoperative T1-weighted MRI and postoperative head CTs were used, along with applied programming settings, to estimate the volume of tissue activated for each patient. The volumes of tissue activated were then used to make voxel-wise and structural connectivity correlations with clinically observed tremor suppression. The volume of the tissue-activated analyses identified the optimal region of stimulation at the ventralis oralis posterior ventralis intermedius border intersecting with the dentato-rubro-thalamic tract. A regression model showed strong connectivity to the supplemental motor area was positively associated with tremor suppression (r = 0.66) in this cohort, whereas connectivity to the primary motor cortex was negatively associated with tremor suppression (r = −0.69), a finding opposite to that seen in ventralis intermedius deep brain stimulation for essential tremor. Comparing the structural connectivity to that of an essential tremor cohort revealed a distinct network that lies anterior to the essential tremor network. Overall, the volumes of tissue activated and connectivity observations converge to suggest that optimal suppression of multiple sclerosis tremor will likely be achieved by directing stimulation more anteriorly toward the ventralis oralis posterior and that a wide field of stimulation synergistically modulating the ventralis oralis posterior and ventralis intermedius nuclei may be more effective than traditional ventralis intermedius deep brain stimulation at suppressing the severe tremors commonly seen in complex tremor syndromes such as multiple sclerosis tremor.

Stimulation-Induced Side Effects of Deep Brain Stimulation in the Ventralis Intermedius and Posterior Subthalamic Area for Essential Tremor.

Deep brain stimulation (DBS) targeting the ventralis intermedius (VIM) nucleus of the thalamus and the posterior subthalamic area (PSA) has been shown to be an effective treatment for essential tremor (ET). The aim of this study was to compare the stimulation-induced side effects of DBS targeting the VIM and PSA using a single electrode. Patients with medication-refractory ET who underwent DBS electrode implantation between July 2011 and October 2020 using a surgical technique that simultaneously targets the VIM and PSA with a single electrode were enrolled in this study. A total of 93 patients with ET who had 115 implanted DBS electrodes (71 unilateral and 22 bilateral) were enrolled. The Clinical Rating Scale for Tremor (CRST) subscores improved from 20.0 preoperatively to 4.3 (78.5% reduction) at 6 months, 6.3 (68.5% reduction) at 1 year, and 6.5 (67.5% reduction) at 2 years postoperation. The best clinical effect was achieved in the PSA at significantly lower stimulation amplitudes. Gait disturbance and clumsiness in the leg was found in 13 patients (14.0%) upon stimulation of the PSA and in significantly few patients upon stimulation of the VIM (p = 0.0002). Fourteen patients (15.1%) experienced dysarthria when the VIM was stimulated; this number was significantly more than that with PSA stimulation (p = 0.0233). Transient paresthesia occurred in 13 patients (14.0%) after PSA stimulation and in six patients (6.5%) after VIM stimulation. Gait disturbance and dysarthria were significantly more prevalent in patients undergoing bilateral DBS than in those undergoing unilateral DBS (p = 0.00112 and p = 0.0011, respectively). Paresthesia resolved either after reducing the amplitude or switching to bipolar stimulation. However, to control gait disturbance and dysarthria, some loss of optimal tremor control was necessary at that particular electrode contact. In the present study, the most common stimulation-induced side effect associated with VIM DBS was dysarthria, while that associated with PSA DBS was gait disturbance. Significantly, more side effects were associated with bilateral DBS than with unilateral DBS. Therefore, changing active DBS contacts to simultaneous targeting of the VIM and PSA may be especially helpful for ameliorating stimulation-induced side effects.

Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads.

Clinical VignetteA 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation.Clinical DilemmaDo elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction?Clinical SolutionLead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings.Gaps in KnowledgeThere are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an “inching” evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear.Expert CommentaryThis case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.

Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads

<strong>Clinical Vignette:</strong> A 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation. <strong>Clinical Dilemma:</strong> Do elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction? <strong>Clinical Solution:</strong> Lead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings. <strong>Gaps in Knowledge:</strong> There are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an ‘‘inching’’ evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear. <strong>Expert Commentary:</strong> This case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.

Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor

Ventralis intermedius deep brain stimulation is an established intervention for medication-refractory essential tremor. Newer constant current stimulation technology offers theoretical advantage over the traditional constant voltage systems in terms of delivering a more biologically stable therapy. There are no previous reports on the outcomes of constant current deep brain stimulation in the treatment of essential tremor. This study aimed to evaluate the long-term efficacy of ventralis intermedius constant current deep brain stimulation in patients diagnosed with essential tremor. Essential tremor patients implanted with constant current deep brain stimulation for a minimum of three years were evaluated. Clinical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. The quality of life in the patients was assessed using the Quality of Life in Essential Tremor questionnaire. Ten patients were evaluated with a median age at evaluation of 74 years (range 66-79) and a mean follow up time of 49.7 (range 36-78) months since starting stimulation. Constant current ventralis intermedius deep brain stimulation was well tolerated and effective in all patients with a mean score improvement from 50.7 ± 5.9 to 17.4 ± 5.7 (p = 0.0020) in the total Fahn-Tolosa-Marin rating scale score (65.6%). Furthermore, the total combined mean Quality of Life in Essential Tremor score was improved from 56.2 ± 4.9 to 16.8 ± 3.5 (p value = 0.0059) (70.1%). This report shows that long-term constant current ventralis intermedius deep brain stimulation is a safe and effective intervention for essential tremor patients.

Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial

IntroductionThis study of thalamic deep brain stimulation (DBS) investigated whether a novel constant-current device improves tremor and activities of daily living (ADL) in patients with essential tremor (ET). MethodsA prospective, controlled, multicenter study was conducted at 12 academic centers. We investigated the safety and efficacy of unilateral and bilateral constant-current DBS of the ventralis intermedius (VIM) nucleus of the thalamus in patients with essential tremor whose tremor was inadequately controlled by medications. The primary outcome measure was a rater-blinded assessment of the change in the target limb tremor score in the stimulation-on versus stimulation-off state six months following surgery. Multiple secondary outcomes were assessed at one-year follow-up, including motor, mood, and quality-of-life measures. Results127 patients were implanted with VIM DBS. The blinded, primary outcome variable (n = 76) revealed a mean improvement of 1.25 ± 1.26 points in the target limb tremor rating scale (TRS) score in the arm contralateral to DBS (p < 0.001). Secondary outcome variables at one year revealed significant improvements (p ≤ 0.001) in quality of life, depression symptoms, and ADL scores. Forty-seven patients had a second contralateral VIM-DBS, and this group demonstrated reduction in second-sided tremor at 180 days (p < 0.001). Serious adverse events related to the surgery included infection (n = 3), intracranial hemorrhage (n = 3), and device explantation (n = 3). ConclusionUnilateral and bilateral constant-current VIM DBS significantly improves upper extremity tremor, ADL, quality of life, and depression in patients with severe ET.

Unilateral Thalamic Deep Brain Stimulation for Disabling Kinetic Tremor in Multiple Sclerosis

Surgical options of multiple sclerosis (MS) tremor treatment are limited and narrowed to thalamotomy or deep brain stimulation of the thalamic nucleus ventralis intermedius. Lack of qualification protocol frequently results in poor outcome. To determine prospectively the efficacy and safety of unilateral ventralis intermedius deep brain stimulation as a tool to control disabling kinetic arm tremor related to MS. Neurological and neuropsychological evaluations were performed 1 month and 1 day before surgery and 1, 3, and 6 months after surgery. The evaluation included measurement of tremor and dexterity, Extended Disability Status Scale, Mini Mental State Examination, and quality-of-life assessment. Nine consecutive patients were enrolled in the group. Mean age at the time of surgery was 38.9 ± 9 years; median Extended Disability Status Scale at baseline was 7.1. Mean MS duration was 11.7 years, and mean tremor duration was 6.11 years. Mean postural and kinetic scores and hand capacity were measured. One month after surgery, median scores off and on stimulation were 12 and 6 for postural tremor, 12 and 10.5 for kinetic tremor score, 12 and 7.5 for manual capacity, and 22 and 20 for functional handicap, respectively. Similar results were 10 and 4, respectively, at the 3-month follow-up. Six months after surgery, median scores off and on stimulation were 10.4 and 4 for postural tremor and 12 and 7.8 for kinetic tremor, respectively. This prospective study confirms the value and safety of ventralis intermedius deep brain stimulation for treatment of kinetic tremor related to MS. Accurate and precise presurgical qualification plays a key role in successful treatment.

Changes in cortical excitability with thalamic deep brain stimulation

Deep brain stimulation (DBS) is an effective treatment for several movement disorders. However, its mechanism of action is largely unknown. Both lesioning and DBS of the ventralis intermedius (VIM) nucleus of thalamus improve essential tremor. Although DBS was initially thought to inhibit the target neurons, recent studies suggest that DBS activates neurons. To test the hypothesis that thalamic DBS activates the target area in patients with essential tremor. Cortical excitability was assessed in seven unmedicated patients with essential tremor using unilateral stimulators implanted in the VIM of the dominant hemisphere and in 11 healthy controls using transcranial magnetic stimulation (TMS). Patients were studied during optimal DBS (ON condition), half the optimal frequency (HALF), and with DBS off (OFF) in random order. Tremor was assessed after a change in DBS setting. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex using single and paired pulses to elicit motor evoked potentials (MEPs). MEP recruitment was determined using stimulus intensities from 100% to 150% of motor threshold. Tremor scores were significantly improved with DBS ON. Analysis of variance showed a significant interaction between condition (ON, HALF, OFF, Normal) and stimulus intensity on MEP amplitude. During DBS ON MEP amplitudes were significantly higher compared with controls at high but not at low TMS intensities. Because the ventralis intermedius (VIM) projects directly to the motor cortex, the high motor evoked potential amplitude with deep brain stimulation ON suggests that VIM DBS activates rather than inhibits the target area.