Vim Deep Brain Stimulation Research Articles

Case Series: Deep Brain Stimulation in Patients with FXTAS

Objective: We describe 3 carriers of the FMR1 premutation with the Fragile X-associated Tremor Ataxia Syndrome (FXTAS) whose tremor was significantly improved by bilateral Deep Brain Stimulation (DBS) to Ventral Intermediate nucleus (Vim) of the thalamus. Background: FXTAS is a recently described neurodegenerative disorder caused by CGG expansions of the FMR1 gene within the premutation range (55 to 200 CGG repeats). Individuals with FXTAS typically develop an intention tremor followed by gait ataxia within two years. Vim DBS has been shown to effectively treat tremor in a variety of disorders, including Parkinson’s disease and essential tremor. Design/Methods/Results: Three men ages 62, 59 and 70 with FXTAS were treated surgically with bilateral Vim DBS. All patients experienced a significantly beneficial effect on tremor. Ataxia improved in case 1 and temporarily in case 2, but worsened in case 3. All patients experienced mild worsening of dysarthria, although the patients and their families unanimously felt there was a worthwhile benefit overall. Conclusions: These cases provided first hand evidence that bilateral Vim DBS effectively manages tremor in selected patients with FXTAS. DBS may prove to be a viable therapeutic option for treating tremor and/or ataxia with or without other medical therapeutics in patients with FXTAS.

Direct stereotactic targeting of the ventrointermediate nucleus of the thalamus based on anatomic 1.5-T MRI mapping with a white matter attenuated inversion recovery (WAIR) sequence

BackgroundThe ventrointermediate nucleus (Vim) of the thalamus is still considered “invisible” on current magnetic resonance imaging (MRI), requiring indirect methods based on stereotactic atlases for estimation of its location. Direct visualization of Vim is desirable to improve targeting. ObjectiveTo evaluate the ability of Inversion-Recovery 1.5-T MR images to produce high-resolution, anatomical depiction of the thalamus suitable for direct Vim targeting. MethodsTwenty patients with essential tremor or tremor associated with Parkinson’s disease received Vim deep brain stimulation (DBS). Fahn-Tolosa-Marin and Unified Parkinson’s Disease Rating Scale (UPDRS) tremor scores were assessed pre- and postoperatively. Preoperative stereotactic 1.5-T MR images of the thalamus were acquired using a White Matter Attenuated Inversion Recovery (WAIR) sequence. Thalamic nuclei were manually contoured on the basis of spontaneous MRI contrasts; labeling relied on 3D identification from stereotactic books and in-house ex vivo 4.7-T microscopic MRI atlas. Vim was then directly probed for electrophysiological confirmation and determination of the optimal site for electrode placement. ResultsThe shape, spatial orientation, and signal contrast of Vim as depicted on our WAIR images were similar to those observed on the Schaltenbrand and Bailey atlas, as well as in our high-field MRI atlas. These images were successfully used for pure direct Vim targeting: at the last follow-up (median = 46.3 months), the average tremor score improved from 3.80 preoperatively to 0.50 postoperatively (on stimulation; P < 0.01). Conclusion1.5-T MRI with WAIR sequence provides high-quality images of Vim suitable in DBS surgery, for accurate preoperative planning, direct targeting and anatomic analysis.

Orthostatic Tremor Responds to Bilateral Thalamic Deep Brain Stimulation

<strong>Background:</strong> Orthostatic tremor (OT) is a disabling movement disorder manifested by postural and gait disturbance. Primarily a condition of elderly people, it can be progressive in up to 15% of patients. The primary treatments are medications that are often ineffective. <strong>Case Report:</strong> A 75-year-old male presented with a 10-year history of progressive and disabling OT. He had tried various medications without significant benefits. He underwent bilateral thalamic Vim deep brain stimulation (DBS). At 30-month follow-up, he has had continued significant improvement of his OT. <strong>Discussion:</strong> Bilateral thalamic DBS may be a viable option for medically refractory OT.

Orthostatic tremor responds to bilateral thalamic deep brain stimulation.

Orthostatic tremor (OT) is a disabling movement disorder manifested by postural and gait disturbance. Primarily a condition of elderly people, it can be progressive in up to 15% of patients. The primary treatments are medications that are often ineffective. A 75-year-old male presented with a 10-year history of progressive and disabling OT. He had tried various medications without significant benefits. He underwent bilateral thalamic Vim deep brain stimulation (DBS). At 30-month follow-up, he has had continued significant improvement of his OT. Bilateral thalamic DBS may be a viable option for medically refractory OT.

Reoperation of Deep Brain Stimulation in Patients with Essential Tremor

A s the number of patients with essential tremor (ET) who have been treated with deep brain stimulation (DBS) increases, the long-term consequences of therapy are eing realized. The classic target for ET during the last 2 decades as been the ventral intermediate nucleus (Vim) of the thalamus 4). In the present article, Blomstedt et al. describe five patients ith ET who had suboptimal responses to Vim DBS. In three atients who became refractory to long-term Vim DBS, these uthors describe the use of the caudal zona incerta (cZi) as an lternative target and show a modest benefit in tremor control. lomstedt et al. mention many important issues surrounding the fficacy of DBS in patients with ET, including the optimal target or DBS in ET, the short-term and long-term failure of DBS herapy, the natural history of the disease, and the effects of ong-term DBS on the brain. Most importantly, they also describe strategy to deal with the potential long-term failure of Vim DBS n patients with ET.

A case of tremor reduction and almost complete ageusia under bilateral thalamic (VIM) deep brain stimulation in essential tremor—a therapeutic dilemma

Essential tremor (ET) is a neurological disorder that can be treated effectively by means of bilateral thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS). We present a rare case of stimulation-dependent reversible ageusia that poses a therapeutic dilemma on the one hand and serves as an instructive example to elucidate the as yet incompletely defined gustatory pathways on the other. A 69-year-old patient with successful reduction of his disabling upper extremity ET experienced an almost complete but during stimulation cessation reversible ageusia under bilateral VIM DBS. An evaluation of diffusion tensor (DTI) neuroimaging studies was performed in order to detect effective electrode positions and volumes of activated tissue (VTA) in relation to the medial lemniscus (ML) and dentato-rubro-thalamic tract (DRT). Repeated subjective gustometry was conducted with differential manipulation of stimulation settings. This case report stresses the importance of fiber tracts for DBS surgery. Reconciled with previous findings in lesion cases, we assume the coexistence of decussating and non-decussating fibers in the gustatory tract combined with hemispheric dominance in the processing of gustatory information. A therapeutic option for this dilemma may be a patient-selectable stimulation program or bipolar stimulation establishing a smaller ovoid VTA.

Lateralized effects of unilateral thalamotomy and thalamic stimulation in patients with essential tremor.

Background and PurposeStereotactic thalamotomy has been an effective surgical procedure in the treatment of medically refractory essential tremor (ET), however, little is known about the bilateral effects of unilateral ventralis intermedius (Vim) thalamotomy and Vim deep brain stimulation (DBS). We studied the lateralized effects of unilateral Vim thalamotomy and Vim DBS in ET patients.MethodsVim thalamotomy was performed in 6 patients and Vim DBS in 6. Patients were evaluated preoperatively and at 3 and 6 months postoperatively using the Clinical Rating Scale for Tremor (CRST).ResultsThe contralateral Part A (tremor localization/severity rating) and Part B (specific motor tasks/function rating) subscores, and axial subscores of CRST significantly improved after unilateral Vim thalamotomy or Vim DBS. On the side ipsilateral to surgery, ET patients demonstrated no significant improvements in the Part A and Part B subscores of CRST. The Part C (functional disabilities resulting from tremor) subscores and total scores of CRST were significantly improved after surgery.ConclusionsVim thalamotomy and DBS may be equally effective for the management of contralateral and axial tremor in ET patients, but both interventions may not improve tremor on the side ipsilateral to surgery.

Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor

Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures.Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11–14 (hand tremor and hand function) were selected for analysis of tremor outcome.The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

Deep brain stimulation of the ventral intermediate nucleus in patients with essential tremor: Stimulation below intercommissural line is more efficient but equally effective as stimulation above

BackgroundThe posterior subthalamic area (PSA), ventral to the intercommissural line (ICL) and the ventral intermediate nucleus (VIM), has been suggested as a promising target for deep brain stimulation (DBS) in patients suffering from essential tremor (ET). In this study the clinical benefit of VIM and PSA DBS on postural tremor suppression was systematically evaluated in a two step approach with a 3D ultrasound kinematic analysis tool. MethodsWe defined the exact position of 40 VIM-DBS-electrodes from 21 ET patients. In a first experiment with a subgroup of electrodes we subsequently activated a thalamic and a contact below ICL (sub-ICL) with equal parameter settings for within subject comparison. In a second step, we divided all electrodes into two groups, i.e. one group with activated thalamic and the other group with activated contacts below ICL and performed a group comparison under patients' individual stimulation parameters. Here, the corrected amplitude required for tremor suppression was analyzed separately for both groups. ResultsWithin subject comparison with equal parameter settings revealed a significant improvement of sub-ICL compared to thalamic stimulation. In contrast, group comparison under patients' individual stimulation did not show any significant difference in tremor suppression between VIM and PSA DBS. Although higher corrected stimulation amplitude was needed in the thalamic group this difference was not significant. ConclusionThe data suggest that sub-ICL stimulation may be more efficient compared to thalamic stimulation but equally effective when patients' individual stimulation parameters are used.

Steady or not following thalamic deep brain stimulation for essential tremor

Deep brain stimulation (DBS) has become an important option for medication-refractory essential tremor (ET), but may contribute to worsened gait and falling. This study evaluates impaired gait in a cohort of patients treated with DBS with a retrospective review of ET patients before and after DBS implantation. Factors examined included: age, duration of symptoms, pre-morbid gait difficulties/falls, Fahn-Tolosa-Marin tremorrating scale (TRS) scores at baseline, 6 months post-unilateral DBS implantation, and 6 or 12 months post-bilateral implantation. All implantations targeted the nucleus ventralis intermediate (Vim). Thirty-eight patients (25 males, 13 females) were included. Twenty-five patients (65.8%) underwent unilateral DBS implantation and 13 (34.2%) bilateral. The mean age at surgery was 67.1 years ± 11.4 (range 34-81). The mean disease duration was 31 years ± 18.3 (range 6-67). Fifty-eight percent of patients had worsened gait post-operatively. Seventy percent of patients with unilateral Vim DBS experienced gait worsening while 55% of bilateral DBS patients experienced gait worsening. Patients with worsened gait post-DBS had higher baseline pre-operative TRS scores than those without worsened gait (43.1 points ± 8.4 vs. 33.1 points ± 10.1, p = 0.002) (odds ratio 2.5, p = 0.02). Gait/balance may worsen following DBS for medication refractory ET. Higher baseline TRS score may factor into these issues, although a larger prospective study will be required with a control population. The larger percentage of difficulties observed in unilateral versus bilateral cases likely reflected the bias not to proceed to second-sided surgery if gait/balance problems were encountered.

Parkinson's disease tremor-related metabolic network: Characterization, progression, and treatment effects

The circuit changes that mediate parkinsonian tremor, while likely differing from those underlying akinesia and rigidity, are not precisely known. In this study, to identify a specific metabolic brain network associated with this disease manifestation, we used FDG PET to scan nine tremor dominant Parkinson's disease (PD) patients at baseline and during ventral intermediate (Vim) thalamic nucleus deep brain stimulation (DBS). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject scan data to detect a significant spatial covariance pattern with consistent changes in subject expression during stimulation-mediated tremor suppression. The metabolic pattern was characterized by covarying increases in the activity of the cerebellum/dentate nucleus and primary motor cortex, and, to a less degree, the caudate/putamen. Vim stimulation resulted in consistent reductions in pattern expression (p<0.005, permutation test). In the absence of stimulation, pattern expression values (subject scores) correlated significantly (r=0.85, p<0.02) with concurrent accelerometric measurements of tremor amplitude.To validate this spatial covariance pattern as an objective network biomarker of PD tremor, we prospectively quantified its expression on an individual subject basis in independent PD populations. The resulting subject scores for this PD tremor-related pattern (PDTP) were found to exhibit: (1) excellent test–retest reproducibility (p<0.0001); (2) significant correlation with independent clinical ratings of tremor (r=0.54, p<0.001) but not akinesia-rigidity; and (3) significant elevations (p<0.02) in tremor dominant relative to atremulous PD patients.Following validation, we assessed the natural history of PDTP expression in early stage patients scanned longitudinally with FDG PET over a 4-year interval. Significant increases in PDTP expression (p<0.01) were evident in this cohort over time; rate of progression, however, was slower than for the PD-related akinesia/rigidity pattern (PDRP). We also determined whether PDTP expression is modulated by interventions specifically directed at parkinsonian tremor. While Vim DBS was associated with changes in PDTP (p<0.001) but not PDRP expression, subthalamic nucleus (STN) DBS reduced the activity of both networks (p<0.05). PDTP expression was suppressed more by Vim than by STN stimulation (p<0.05).These findings suggest that parkinsonian tremor is mediated by a distinct metabolic network involving primarily cerebello-thalamo-cortical pathways. Indeed, effective treatment of this symptom is associated with significant reduction in PDTP expression. Quantification of treatment-mediated changes in both PDTP and PDRP scores can provide an objective means of evaluating the differential effects of novel antiparkinsonian interventions on the different motor features of the disorder.

Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus for Tremor in Patients With Multiple Sclerosis

Tremor is an important cause of disability in patients with multiple sclerosis (MS). Deep brain stimulation (DBS) in the ventral intermediate nucleus (VIM) of the thalamus is said to be beneficial for MS tremor. To assess the long-term efficacy of VIM DBS for MS disabling tumor. We treated 10 patients (4 men and 6 women) with advanced MS-related medication-resistant tremor with DBS at the VIM thalamic nucleus. DBS was unilateral in 9 patients and bilateral in 1 patient in 2 stages. Contralateral arm tremor was assessed with the Fahn-Tolosa-Marin tremor rating scale. At 1 year, 5 of 10 patients (5 of 11 hemispheres) had a reduction in tremor scores with stimulation compared with baseline; in 3 patients, the reduction was > 50%. After 36 months, 3 patients continued benefiting from stimulation, 2 having > 50% improvement. Of the 6 symptomatic sides that did not benefit at 1 year, 3 failed to have even initial benefit, and 3 had a transient improvement lasting < 1 year. One patient stopped using stimulation because of a lack of improvement at 5 months after surgery and was lost to follow-up. Approximately one-half of the patients derived some benefit from VIM DBS 1 year after surgery, but this benefit reached a > 50% reduction in only 30% of the patients. This level of improvement may be related to the variability of the demyelinating lesions and the superimposition of ataxia in the MS patients. Developing better treatments for MS tremor continues to be a challenge.

Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor

The aim of this study was to evaluate the effects of unilateral and bilateral ventralis intermedius (Vim) deep brain stimulation (DBS) on mood and motor function. Thirty-one consecutive medication refractory patients with essential tremor who underwent unilateral or bilateral Vim DBS at University of Florida and returned for at least 6 -month follow-up completed the Visual Analog Mood (VAMS), the Beck Depression Inventory (BDI), and the Tremor Rating Scale (TRS) before and after surgery. We excluded all patients who were implanted at other institutions. The tense subscale of the VAMS improved significantly in both the unilateral and bilateral DBS groups (P < 0.001). On the VAMS afraid subscale, only the bilateral group trended toward improvement (P = 0.075). There were no significant changes for either group for the happy, confused, sad, angry, energetic or tired VAMS scores. TRS subscale scores all improved after unilateral and bilateral Vim DBS surgery (P < 0.001). Feelings of tenseness, tremor severity and ADLs improved following unilateral or bilateral Vim DBS for ET.

Long-term suppression of tremor by deep brain stimulation of the ventral intermediate nucleus of the thalamus combined with pallidotomy in hemiparkinsonian patients

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) is a powerful surgical option in the treatment of tremor-predominant Parkinson’s disease. However, its therapeutic efficacy depends on the tremor distribution. DBS is highly efficient in relief of distal appendicular tremor but not other types of tremor. Also, it is generally thought that DBS of the VIM has no significant beneficial effects on other motor symptoms of Parkinson’s disease. We report two hemiparkinsonian patients, in whom unilateral VIM DBS combined with posteroventral pallidotomy produced long-lasting suppression of not only hand tremor, but also leg or jaw tremor and other motor symptoms.

HIGHLY SELECTIVE LEPTOMENINGEAL AMYLOIDOSIS WITH TRANSTHYRETIN VARIANT ALA25THR

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%–90%), RS (range, 48%–63%) and FUS thalamotomy (range, 35%–75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%–78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET.

Gait and balance in essential tremor: Variable effects of bilateral thalamic stimulation

Essential tremor (ET) is a multi-faceted condition best known for postural and action tremor but also may include disordered gait and postural instability. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus provides substantial tremor reduction yet some patients with bilateral VIM DBS have gait and balance impairment. This study examines gait and balance performance in 13 participants with ET who have bilateral VIM DBS compared with a matched control group. Participants with ET were tested with their stimulators off (DBS OFF) and on (DBS ON). For both standard and tandem walking, participants with ET walked significantly more slowly than controls, with significantly lower cadence, spending a lower percentage of the gait cycle in single limb support and a higher percentage in double support compared with controls. Participants with ET also had significantly lower tandem and one leg stance times, Berg balance scores, balance confidence, and required significantly greater time to perform the Timed Up-and-Go relative to controls. There were no significant differences in any gait or balance measures in the DBS OFF versus DBS ON conditions, but the effects of DBS on gait and balance were highly variable among individuals. Future studies are needed to determine why some individuals experience gait and balance difficulties after bilateral thalamic DBS and others do not. A better understanding of the mechanisms underlying gait and balance impairments in those with bilateral DBS is critical to reduce falls and fractures in this group.

Deep brain stimulation of the ventral intermediate nucleus of the thalamus in medically refractory orthostatic tremor: Preliminary observations

Orthostatic tremor (OT) is a disabling movement disorder associated with postural and gait impairment in the elderly. Medical therapy often yields insufficient benefit. We report the clinical and electrophysiological data on two patients with medication-refractory OT treated with deep brain stimulation of the ventral intermediate thalamic nucleus (Vim DBS). Patient 1 underwent bilateral deep brain stimulation (DBS) and Patient 2 unilateral Vim DBS following 28 and 30 years of disease duration, respectively. Both patients showed increased latency to symptom onset after rising from a seated position, improved tolerance for prolonged standing, and slower crescendo of tremor severity when remaining upright. Postoperative evaluation demonstrated decreased amplitude of electromyographic activity with persistence of well-defined oscillatory behavior showing strong coherence at 15 Hz between all muscles tested in the upper and lower limbs. Postural sway was unchanged. Clinical benefits have been sustained for over 18 months in Patient 1, and receded after 3 months in Patient 2. These findings support the consideration of bilateral Vim DBS implantation as a therapeutic option in patients with medically refractory OT. Further efficacy studies on chronic stimulation to disrupt the abnormal oscillatory activity in this disorder are warranted.

Bilateral effects of unilateral thalamic deep brain stimulation: A case report

A recent study has proved that unilateral deep brain stimulation (DBS) of the subthalamic nucleus has bilateral effects. However, it is still unclear whether unilateral ventral intermediate thalamic nucleus (Vim) DBS exerts exclusively contralateral or bilateral effects on tremor. Previous studies demonstrated a clinically irrelevant improvement on the nontarget side after thalamic stimulator implantation, which was considered to be solely the result of mechanical effects. We report here the case of a 55-year-old woman in whom unilateral thalamic DBS can stop the disabling postural-kinetic tremor in both hands. Simultaneous surface electromyography (sEMG), accelerometry, and video recordings were obtained to evaluate the underlying mechanism. After the right Vim DBS was turned off, moderate rest tremor appeared in both hands accompanied by bilateral bursts on sEMG. Because right hand tremor cannot simply reflect the mechanical overflow of the left side, the bilateral improvement caused by right Vim DBS is probably due to an active tremor reduction in this particular case.

Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up

Aim:To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson’s disease (PD) at 6 years post surgery.Methods:This was a prolonged follow-up...

Effects of thalamic stimulation frequency on intention and postural tremor

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus improves essential tremor. Suppression of the amplitude of the postural tremor component with VIM DBS depends on stimulation frequency. The purpose of this study was to determine the effect of DBS frequency on the intention tremor component, that is, tremor that is enhanced by target-directed movement, and to compare it to the effect of DBS frequency on postural tremor in people with essential tremor. We measured tremor frequency and amplitude during trials of postural holding and voluntary reaching between two targets at 10 different stimulation frequency settings between 0 and 185 Hz. Tremor frequency did not change with changes in stimulation frequency. Amplitude suppression of both intention and postural tremor depended on stimulation frequency. Maximal tremor reduction occurred at approximately 130 Hz for both forms of tremor. However, at optimal frequencies, the percent reduction in tremor amplitude relative to the DBS OFF condition was greater for postural than for intention tremor. These results suggest that VIM DBS stimulation frequencies near 130 Hz may provide maximal control of intention and postural tremor. Identification of optimal stimulation settings should consider assessment of intention tremor, not just postural tremor, as intention tremor may not be as well controlled as postural tremor but may be a better gauge for functional benefit.