Ventral Intermediate Nucleus Of Thalamus Research Articles

Staged deep brain stimulation of ventral intermediate nucleus of the thalamus for suppression of essential tremors

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is a powerful surgical option in the treatment of essential tremors (ETs). However, its therapeutic efficacy depends on the tremor distribution. DBS is highly efficient in the relief of distal appendicular tremor but not other types of tremor. We report a case of staged DBS of ventral intermediate nucleus (VIM) of thalamus for the suppression of ETs.

Gamma Knife Thalamotomy of Medication Refractory Tremor Disorders

To Investigate the effectiveness and safety of use of Gamma Knife radiosurgery for lesioning the Ventral Intermediate Thalamic Nucleus (VIM) for management of medication refractory tremor disorders. Patients with medication refractory tremor disorders were treated utilizing Gamma Knife radiosurgery. Patients received 130 Gy targeting the VIM nucleus utilizing a single 4 mm collimator shot. Plugs were customized to limit dose to the adjacent internal capsule. Patients were then followed for 2 years with serial standardized Fahn-Tolosa-Marin Tremor scale evaluation and any adverse events were recorded. Results from this testing were tabulated with numerical scores in four separate categories including postural, handwriting, drawing, and functioning. From 2/2013 through 8/2018, 18 patients were treated to 20 lesions. Median age was 69 (range 34-87). Sixteen treatments were directed at the left VIM nucleus to treat a right sided tremor. All of these 16 treatments were directed at the dominant hand. Two of the four patients treated to the non-dominant hand (right VIM nucleus) had also been treated previously to the contralateral side 1 year prior. Fahn-Tolosa-Marin testing was performed at 3-6 month intervals. Median follow up was 18 months (range 0-26) with one patient lost to follow up. 17/19 (89.5%)treatments demonstrated significant improvements on follow up. There were improvements in all assessed scores. Median postural scores improved from 6.0 to 3.0 (p <0.01), handwriting scores from 3.0 to 1.0 ( p<0.01), drawing scores from 9.0 to 3.0 (p<0.01), and functioning scores from 18 to 9.5 (p<0.01). Median time to improvement was 6 months (Range3-24 months). No acute or chronic adverse events were reported in any patient. Gamma Knife Thalamotomy is a safe and effective treatment for tremor disorders. With great care in the delineation of the internal capsule, no adverse events were noted. Treatments can safely be administered in a community setting. Patients who are deemed to be poor candidates for deep brain stimulation including the elderly, patients with pulmonary and cardiac comorbidities, and patients on anticoagulation should be considered for treatment.

Combination Targeting of Subthalamic Nucleus and Ventral Intermediate Thalamic Nucleus in Deep Brain Stimulation for Tremor-Dominant Parkinson's Disease: Experience and Outcomes

Abstract INTRODUCTION Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat the bradykinesia and rigidity of Parkinson's disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory to treat patients with tremor-dominant PD; yet, outcome data for this procedure remain sparse. METHODS We conducted a single-center retrospective review of all patients who underwent combined STN-VIM DBS. Demographic and outcome data, including Unified Parkinson Disease Rating Scale (UPDRS), changes in symptom severity, and levodopa equivalent daily dose (LEDD), were collected and analyzed. RESULTS Nineteen patients underwent combined STN-VIM trajectory DBS between January 2013 and April 2019. Patients were 90% male and 10% female, with an average age of 63.6 ± 12 yr. Average preoperative UPDRS was 24.2 and LEDD was 807.8. At an average follow-up of 23.9 mo, UPDRS and LEDD decreased by an average of 9.25 and 404.8, respectively. A total of 95% of our patients reported an improvement in tremor symptoms, and 58% were able to decrease the total medication burden. CONCLUSION Combined targeting of STN and VIM thalamus for tremor-dominant PD results in an excellent control of tremor symptoms, as well as a decrease in UPDRS and LEDD. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.

Ultrahigh Frequency Deep Brain Stimulation at 10 000 Hz Improves Motor Function

Abstract INTRODUCTION Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250 Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultrahigh frequency (UHF) spinal cord stimulation at 10 kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. We evaluated the clinical effects and safety of UHF DBS in patients with subthalamic nucleus (STN) or ventral intermediate thalamic nucleus (VIM) DBS. METHODS We studied the effects of conventional (130 Hz) and UHF stimulation in 5 patients with Parkinson's disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. RESULTS Motor performance improved in all 6 patients with UHF DBS. About 10 kHz stimulation at amplitudes = 3.0 mA appeared to be as effective as 130 Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, P = .110, N = 90 trials). Interestingly, 10 kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130 Hz stimulation. CONCLUSION Our results indicate that DBS at 10 kHz produces clinical benefits in patients with movement disorders. Like 10 kHz spinal cord stimulation, 10 kHz DBS has the potential to produce clinical benefits while possibly reducing stimulation-induced adverse effects. Further studies will be required to optimize UHF DBS stimulation parameters and to determine its clinical utility.

Skull Density Ratio and Treatment Outcomes in Essential Tremor Patients Treated With Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy

Abstract INTRODUCTION Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) is an evolving treatment option for eligible patients with essential tremor (ET). Producing thermal lesions in the thalamic ventral intermediate nucleus results in a clinical improvement of tremor. Skull density ratio (SDR), the ratio of cortical to cancellous bone, is a limiting factor in successfully producing a thermal lesion. This study sought to delineate the relationship between SDR and treatment outcomes in these patients. METHODS Radiographic, treatment, and clinical outcome data of patients enrolled in our clinical trial (ET002) for the treatment of unilateral upper extremity ET with MRgFUS were reviewed. The relationships between SDR and time of procedure, maximal temperature recorded, and total Clinical Rating Scale for Tremor (CRST) score at 1 yr of follow-up were determined. RESULTS A total of 20 patients, 18 men and 2 women, were included in this study. The mean age was 72.4 yr (SE 1.1) and mean SDR was 0.60 (SE 0.03, range 0.41-0.82). The average treatment time was 106.3 min (SE 10.4, range 53.0-228.0) with a peak temperature achieved of 46.8°C to 66.4°C, and a mean of 60.2°C (SE 0.96). Total CRST score improved on average from 54.0 to 30.7 at 1 yr of follow-up (t-test, P &lt; .001). A higher SDR was associated with a shorter time of procedure (P = .020, R2 = 0.267). In addition, a higher SDR trended toward association with a higher peak temperature achieved (P = .109, R2 = 0.137). SDR was not associated with the percent improvement in total CRST score (P = .199, R2 = 0.090). CONCLUSION SDR continues to be a limiting factor in eligibility for the treatment of unilateral upper extremity ET with transcranial MRgFUS. In this small cohort of trial patients, a higher SDR portends a shorter procedure time; however, it is not associated with clinical outcome. Future studies could investigate lowering the threshold for treatment eligibility.

Targeting of the dentato-rubro-thalamic tract for MR-guided focused ultrasound treatment of essential tremor.

Magnetic resonance-guided focused ultrasound ablation of the thalamic ventral intermediate nucleus is a safe and effective treatment for medically refractory essential tremor. However, indirect targeting of the ventral intermediate nucleus using stereotactic coordinates from normal neuroanatomy can be inefficient. We therefore evaluated the feasibility of supplementing this method with direct targeting of the dentato-rubro-thalamic tract. We retrospectively identified four patients undergoing magnetic resonance-guided focused ultrasound ablation for essential tremor in which preoperative diffusion tractography imaging of the dentato-rubro-thalamic tract was fused with T2 weighted-imaging and utilized for intra-procedural targeting. The size and location of the dentato-rubro-thalamic tract and 24-hour lesion, as well as the center of the stereotactic coordinates, was evaluated. Finally, the amount of overlap between the dentato-rubro-thalamic tract and the lesion was calculated. The 24-hour lesion size was homogeneous in the cohort (mean 31.3 mm2, range 30-32 mm2), while there was substantial variation in the dentato-rubro-thalamic tract area (mean 14.3 mm2, range 3-24 mm2). The center of the stereotactic coordinates and dentato-rubro-thalamic tract diverged by more than 1 mm in mediolateral and anterposterior directions in all patients, while the dentato-rubro-thalamic tract and lesion centers were in close proximity (mean mediolateral separation 1 mm, range 0.1-2.2 mm; mean anteroposterior separation 0.75 mm, range 0.4-1.2 mm). There was greater than 50% coverage of the dentato-rubro-thalamic tract by the lesion in all patients (mean 82.9%, range 66.7-100%). All patients experienced durable tremor relief. Direct targeting of the dentato-rubro-thalamic tract using diffusion tractography imaging fused to T2 weighted-imaging may be a useful strategy for focused ultrasound treatment of essential tremor. Further investigation of the technique is warranted.

Combined Deep Brain Stimulation of Subthalamic Nucleus and Ventral Intermediate Thalamic Nucleus in Tremor-Dominant Parkinson’s Disease Using a Parietal Approach

Despite its efficacy in tremor-suppression, the ventral intermediate thalamic (VIM) nucleus has largely been neglected in deep brain stimulation (DBS) for tremor-dominant Parkinson's disease (tdPD). The employment of a parietal approach, however, allows stimulation of VIM and subthalamic nucleus (STN) using one trajectory only and thus constitutes a promising alternative to existing strategies. In the present study, we investigate safety and efficacy of combined lead implantation and stimulation of STN and VIM using a parietal approach. Retrospective analysis of five patients with tdPD was performed who underwent DBS using a parietal approach. Changes in symptom severity, disease-specific health-related quality of life and l-dopa equivalent doses (LED) were evaluated over a total time course of 12 months. DBS within both targets yielded significant improvement of parkinsonian symptoms (median: 40.0%, p = 0.04) in the first 6 months of continuous stimulation and remained stable thereafter (median improvement at 12 months: 43.2%, p = 0.07). Sustained improvement of tremor (median at 6 months: 100.0%, p = 0.04; median at 12 months 83.3%, p = 0.04) and quality of life scores (median at 6 months: 29.8%, p = 0.04; median at 12 months: 32.6%, p = 0.04) was noted throughout the follow-up period. No significant change of LEDs was observed by the end of follow-up (median decrease: 2.2%, p = 0.89). Simultaneous DBS of VIM and STN using one trajectory is safe, yielding good control of parkinsonian tremors. Further studies, however, are necessary to determine whether a parietal trajectory affords better control over tremor symptoms than established strategies and hence justifies the potential risks associated with the alternative approach.

Network-level connectivity is a critical feature distinguishing dystonic tremor and essential tremor.

Dystonia is a movement disorder characterized by involuntary muscle co-contractions that give rise to disabling movements and postures. A recent expert consensus labelled the incidence of tremor as a core feature of dystonia that can affect body regions both symptomatic and asymptomatic to dystonic features. We are only beginning to understand the neural network-level signatures that relate to clinical features of dystonic tremor. At the same time, clinical features of dystonic tremor can resemble that of essential tremor and present a diagnostic confound for clinicians. Here, we examined network-level functional activation and connectivity in patients with dystonic tremor and essential tremor. The dystonic tremor group included primarily cervical dystonia patients with dystonic head tremor and the majority had additional upper-limb tremor. The experimental paradigm included a precision grip-force task wherein online visual feedback related to force was manipulated across high and low spatial feedback levels. Prior work using this paradigm in essential tremor patients produced exacerbation of grip-force tremor and associated changes in functional activation. As such, we directly compared the effect of visual feedback on grip-force tremor and associated functional network-level activation and connectivity between dystonic tremor and essential tremor patient cohorts to better understand disease-specific mechanisms. Increased visual feedback similarly exacerbated force tremor during the grip-force task in dystonic tremor and essential tremor cohorts. Patients with dystonic tremor and essential tremor were characterized by distinct functional activation abnormalities in cortical regions but not in the cerebellum. We examined seed-based functional connectivity from the sensorimotor cortex, globus pallidus internus, ventral intermediate thalamic nucleus, and dentate nucleus, and observed abnormal functional connectivity networks in dystonic tremor and essential tremor groups relative to controls. However, the effects were far more widespread in the dystonic tremor group as changes in functional connectivity were revealed across cortical, subcortical, and cerebellar regions independent of the seed location. A unique pattern for dystonic tremor included widespread reductions in functional connectivity compared to essential tremor within higher-level cortical, basal ganglia, and cerebellar regions. Importantly, a receiver operating characteristic determined that functional connectivity z-scores were able to classify dystonic tremor and essential tremor with 89% area under the curve, whereas combining functional connectivity with force tremor yielded 94%. These findings point to network-level connectivity as an important feature that differs substantially between dystonic tremor and essential tremor and should be further explored in implementing appropriate diagnostic and therapeutic strategies.

Long-term efficacy of deep brain stimulation for essential tremor: An observer-blinded study.

Deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (Vim) is established for medically refractory severe essential tremor (ET), but long-term efficacy is controversial. Twenty patients with ET with DBS had standardized video-documented examinations at baseline, in the stimulation-on condition at short term (13.1 ± 1.9 months since surgery, mean ± SEM), and in the stimulator switched on and off (stim-ON/OFF) at long term; all assessments were done between 32 and 120 months (71.9 ± 6.9 months) after implantation. The primary outcome was the Tremor Rating Scale (TRS) blindly assessed by 2 trained movement disorder neurologists. Secondary outcomes were TRS subscores A, B, and C; Archimedes spiral score; and activities of daily living score. At long-term follow-up, tremor was additionally recorded with accelerometry. The rebound effect after switching the stimulator off was assessed for 1 hour in a subgroup. Tremor severity worsened considerably over time in both in the nonstimulated and stimulated conditions. Vim-DBS improved the TRS in the short term and long term significantly. The spiral score and functional measures showed similar improvements. All changes were highly significant. However, the stimulation effect was negatively correlated with time since surgery (ρ = -0.78, p < 0.001). This was also true for the secondary outcomes. Only one-third of the patients had a rebound effect terminated 60 minutes after the stimulator was switched off. Long-term worsening of the TRS was more profound during stim-ON than in the stim-OFF condition, indicating habituation to stimulation. Vim-DBS loses efficacy over the long term. Efforts are needed to improve the long-term efficacy of Vim-DBS. This study provides Class IV evidence that for patients with medically refractory severe ET, the efficacy of Vim-DBS severely decreases over 10 years.

Deep brain stimulation for dystonia-choreoathetosis in cerebral palsy: Pallidal versus thalamic stimulation

IntroductionDystonia-choreoathetosis is common in patients with cerebral palsy, and medical treatment is mostly unsatisfactory. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) has shown some effect, but there is still a need to optimize treatment strategies. We aimed to assess whether the thalamic ventral intermediate nucleus (Vim) might be an alternative DBS target in dystonia-choreoathetosis. MethodsThree patients with cerebral palsy and dystonia-choreoathetosis underwent implantation of DBS electrodes concurrently in the GPi and Vim. Final selection of stimulation site and switches during follow-up with corresponding clinical outcomes were assessed. ResultsOne patient with initial GPi stimulation was switched to Vim, but likewise did not improve significantly (BFM: pre-OP 142, GPi 140, Vim 134) and stimulation was discontinued. In one patient Vim was chosen as initial target for chronic DBS. Since clinical benefit was not yet satisfying, stimulation was switched to GPi resulting in further mild clinical improvement (BFM: pre-OP 99.5, Vim 82.5, GPi 82). In one patient GPi was selected and kept on follow-up due to some therapeutic effect (BFM: pre-OP 135, GPi DBS 121). ConclusionsThe GPi still represents the most convenient DBS target in patients with dystonia-choreoathetosis. Vim DBS did not show a relevant long-term advantage in everyday life in our patients. Further alternative DBS targets need to be considered in acquired dystonia.

A retrospective evaluation of thalamic targeting for tremor deep brain stimulation using high-resolution anatomical imaging with supplementary fiber tractography

ObjectivesDeep brain stimulation (DBS) of the ventral intermediate (Vim) thalamic nucleus is used to treat tremors. Here, we identified the Vim nucleus on fast gray matter acquisition T1 inversion recovery (FGATIR) images and delineated the dentate-rubrothalamic tract (DRT) to determine the DBS target. We evaluated whether this method could consistently identify the Vim nucleus by anatomical imaging and fiber tractography. MethodsWe retrospectively reviewed clinical data of patients who underwent unilateral thalamic DBS for severe tremor disorders. We evaluated outcomes at baseline, 6 months and 1 year following intervention, and annually thereafter. We reviewed preoperative planning to determine whether our tractography technique could consistently depict the DRT, and evaluated implanted electrode position by fusing postoperative CT scans to preoperative MR images. ResultsSeven patients (three men and four women) were included; preoperative diagnoses included essential tremor (n = 3), Parkinson's (n = 2), and Holmes tremor (n = 2). All patients responded to DBS therapy; motor scores improved at 6-month and last follow-up. The Vim nucleus was successfully identified, as the DRT was depicted in all cases. Of ten active DBS contacts in seven leads, four contacts were located outside of the depicted DRT, and these contacts tended to require higher stimulation intensity. ConclusionsThe Vim nucleus was successfully identified with FGATIR. Our methods may be useful to determine optimal DBS trajectory, and potentially improve outcomes.

Confined Thalamic Deep Brain Stimulation in Refractory Essential Tremor

Background: Thalamic ventral intermediate nucleus (VIM) deep brain stimulation (DBS) is an effective therapy for medication-refractory essential tremor (ET). However, 13–40% of patients with an initially robust tremor efficacy lose this benefit over time despite reprogramming attempts. At our institution, a cohort of ET patients with VIM DBS underwent implantation of a second anterior (ventralis oralis anterior; VOA) DBS lead to permit “confined stimulation.” We sought to assess whether confined stimulation conferred additional tremor capture compared to VIM or VOA stimulation alone. Methods: Seven patients participated in a protocol-based programming session during which a video-recorded Fahn-Tolosa-Marin Part A (FTM-A) tremor rating scale was used in the following 4 DBS states: off stimulation, VIM stimulation alone, VOA stimulation alone, and dual lead (confined) stimulation. Results: The average (SD) baseline FTM-A off score was 17.6 (4.0). VIM stimulation alone lowered the average FTM-A total score to 6.9 (4.0). Confined stimulation further attenuated the tremor, reducing the total score to 5.7 (2.8). Conclusions: Confined thalamic DBS can provide additional symptomatic benefits in patients with unsatisfactory tremor control from VIM or VOA stimulation alone.

Thalamic short pulse stimulation diminishes adverse effects in essential tremor patients.

To investigate the effect of directional current steering and short pulse stimulation in the ventral intermediate thalamic nucleus (VIM) on stimulation-induced side effects in patients with essential tremor. We recruited 8 patients with essential tremor in a stable postoperative condition (>3 months after electrode implantation of deep brain stimulation [DBS] electrodes) with segmented contacts implanted in the VIM. Tremor severity on acute stimulation was assessed by the Fahn-Tolosa-Marin Tremor Rating Scale. Cerebellar impairment was evaluated with the International Cooperative Ataxia Rating Scale. Patients rated paresthesia intensity with a visual analog scale. In all patients, tremor was reduced to the same extent by VIM stimulation regardless of pulse width using energy dose-equivalent amplitudes. Short pulse stimulation diminished stimulation-induced ataxia of the upper extremities and paresthesia compared with conventional parameters. Directional steering with monopolar stimulation of single segments successfully suppressed tremor but also induced ataxia. No differences in adverse effects were found between single-segment stimulation conditions. These proof-of-principle findings provide evidence that acute short pulse stimulation is superior to directional steering in the subthalamic area to decrease stimulation-induced side effects while preserving tremor suppression effects in patients with tremor. This study provides Class IV evidence that for patients with tremor with thalamic DBS, acute short pulse stimulation reduces adverse effects, while directional steering does not provide a generalizable benefit regarding adverse effects.

Objective predictors of ‘early tolerance’ to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients

ObjectiveTo identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit ‘early tolerance’ to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS). MethodsIdentification of comparative characteristics of defined cases of ‘early tolerance’ versus patients with sustained satisfactory response treated with Vim DBS surgery for medically-refractory ET, based on retrospective chart review by a clinician blinded to the findings of computerized spiral analysis. ResultsStatistically significant differences in two spiral analysis indices, SWVI and DoS, were found in the dominant upper limbs of patients who developed ‘early tolerance’, whereas the clinical characteristics were not significantly different. ConclusionObjective measurements of upper limb kinematics using graphonomic tests like spiral analysis should be considered in the pre-operative evaluation for DBS, especially in the setting of moderate-severe predominantly action and proximal postural tremors. SignificanceOurs is the first investigation looking into the pre-operative clinical and objective physiologic characteristics of the patients who develop ‘early tolerance’ to Vim DBS for the treatment of essential tremor. The study has significant implications for pre-operative evaluation and potential surgical target selection for the treatment of tremors.

Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression.

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.

(P13) Treatment of the Ventral Intermediate Nucleus for Medically Refractory Tremor: A Cost-Analysis of Stereotactic Radiosurgery Versus Deep Brain Stimulation

The treatment of medically refractory tremor has evolved over the past half-century from intraoperative thalamotomy to deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM). VIM DBS has proven efficacious for patients with essential tremor (ET), tremor-dominant Parkinson’s disease (PD), and less common causes of tremor including multiple sclerosis and orthostatic tremor. Within the past 15 years, unilateral radiosurgical VIM thalamotomy has emerged as a comparably efficacious treatment modality, particularly for ET and tremor-dominant PD patients. Despite extensive investigation of these treatment modalities, there has been no cost-comparison of unilateral DBS versus radiosurgery of the VIM. An extensive literature search of VIM DBS series dating back to the seminal manuscript (Benabid et al., Lancet 1991) was performed to ascertain an estimated operative time for the procedure. The total cost of VIM DBS, comprised from the separate costs of the operating room, anesthesia, and neurosurgeon was then calculated from this operative time based on hospitals geographically representative of the entire United States using current procedural terminology (CPT) and work relative value unit (RVU) codes. The 2016 Medicare Ambulatory Payment Classification (APC) for stereotactic radiosurgery (SRS) was added to the work RVU to determine the total cost of VIM SRS for both Gamma Knife and linear accelerator SRS. Cost estimates assumed that VIM DBS was performed without intraoperative microelectrode recording. The mean operative time of unilateral VIM DBS was 146.4 minutes, yielding a mean operating room cost of $14,726.38, anesthesia cost of $2,420.25 and neurosurgeon cost of $785.78 for a total unilateral VIM DBS cost of $17,932.41 per patient. For SRS VIM, the APC was $8,827, and was added to the neurosurgeon cost of $613.90 for Gamma Knife ($528.53 for linear accelerator) and radiation oncology cost of $1370.87 to yield a total radiosurgery cost of $10,811.77 ($10,726.40 for linear accelerator). The Gamma Knife and linear accelerator costs were 40% less expensive than unilateral VIM DBS. Radiosurgery of the VIM is 40% less expensive than unilateral VIM DBS in treatment of medically refractory tremor, regardless of radiosurgical modality. This finding provides another important aspect to be considered for treatment modality decision-making, and argues for increased involvement of radiation oncologists in concert with movement disorder neurologists and functional neurosurgeons in the management of medically refractory tremor patients, particularly those who may not be able to medically or financially tolerate the stresses of operative intervention.

Stereotactic radiosurgery for tremor: systematic review.

The aim of this systematic review is to offer an objective summary of the published literature relating to stereotactic radiosurgery (SRS) for tremor and consensus guideline recommendations. This systematic review was performed up to December 2016. Article selection was performed by searching the MEDLINE (PubMed) and EMBASE electronic bibliographic databases. The following key words were used: "radiosurgery" and "tremor" or "Parkinson's disease" or "multiple sclerosis" or "essential tremor" or "thalamotomy" or "pallidotomy." The search strategy was not limited by study design but only included key words in the English language, so at least the abstract had to be in English. A total of 34 full-text articles were included in the analysis. Three studies were prospective studies, 1 was a retrospective comparative study, and the remaining 30 were retrospective studies. The one retrospective comparative study evaluating deep brain stimulation (DBS), radiofrequency thermocoagulation (RFT), and SRS reported similar tremor control rates, more permanent complications after DBS and RFT, more recurrence after RFT, and a longer latency period to clinical response with SRS. Similar tremor reduction rates in most of the reports were observed with SRS thalamotomy (mean 88%). Clinical complications were rare and usually not permanent (range 0%-100%, mean 17%, median 2%). Follow-up in general was too short to confirm long-term results. SRS to the unilateral thalamic ventral intermediate nucleus, with a dose of 130-150 Gy, is a well-tolerated and effective treatment for reducing medically refractory tremor, and one that is recommended by the International Stereotactic Radiosurgery Society.

A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

Distinct cortical responses evoked by electrical stimulation of the thalamic ventral intermediate nucleus and of the subthalamic nucleus.

ObjectiveTo investigate the spatial and temporal pattern of cortical responses evoked by deep brain stimulation (DBS) of the subthalamic nucleus (STN) and ventral intermediate nucleus of the thalamus (VIM).MethodsWe investigated 7 patients suffering from Essential tremor (ET) and 7 patients with Parkinson's Disease (PD) following the implantation of DBS electrodes (VIM for ET patients, STN for PD patients). Magnetoencephalography (MEG) was used to record cortical responses evoked by electric stimuli that were applied via the DBS electrode in trains of 5 Hz. Dipole fitting was applied to reconstruct the origin of evoked responses.ResultsBoth VIM and STN DBS led to short latency cortical responses at about 1 ms. The pattern of medium and long latency cortical responses following VIM DBS consisted of peaks at 13, 40, 77, and 116 ms. The associated equivalent dipoles were localized within the central sulcus, 3 patients showed an additional response in the cerebellum at 56 ms. STN DBS evoked cortical responses peaking at 4 ms, 11 ms, and 27 ms, respectively. While most dipoles were localized in the pre- or postcentral gyrus, the distribution was less homogenous compared to VIM stimulation and partially included prefrontal brain areas.ConclusionMEG enables localization of cortical responses evoked by DBS of the VIM and the STN, especially in the sensorimotor cortex. Short latency responses of 1 ms suggest cortical modulation which bypasses synaptic transmission, i.e. antidromic activation of corticofugal fiber pathways.

Clinical improvement associated with targeted interruption of the cerebellothalamic tract following MR-guided focused ultrasound for essential tremor.

OBJECTIVE The objective of this study was to evaluate the utility of diffusion tensor imaging (DTI) tractography-based targeting of the dentatorubrothalamic tract (DRT) for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in patients with essential tremor (ET) and correlate postprocedural tract disruption with clinical outcomes. METHODS Four patients received preprocedural and immediate postprocedural DTI in addition to traditional anatomical MRI sequences for MRgFUS thalamotomy. Optimal ablation sites were selected based on the patient-specific location of the DRT as demonstrated by DTI (direct targeting) and correlated with traditional atlas-based measurements for thalamic ventral intermediate nucleus (Vim) lesioning (indirect targeting). Fiber tracts were displayed three-dimensionally during the procedure and used in conjunction with clinical signs of tremor control for fine correction of the ablation site. Immediately following the conclusion of the procedure, the MRgFUS head frame was removed and patients were placed in a 32-channel MRI head coil for follow-up DTI and anatomical MRI sequences. RESULTS All patients had excellent postoperative tremor control and successful pre- and postprocedural DTI fiber tracking of the corticospinal tract, medial lemniscus, and DRT. Immediate postprocedure DTI failed to track the DRT ipsilateral to the lesion site with a preserved contralateral DRT, coincident with substantial resolution of contralateral tremor. CONCLUSIONS DTI can reliably identify the optimal ablation target and demonstrates tract disruption on immediate postprocedural imaging. A clinical improvement of ET was observed immediately following the procedure, correlating with DRT disruption and suggesting that interruption of the DRT is a consequence of clinically successful MRgFUS thalamotomy. These findings may have utility for both MRgFUS procedure planning in surgically naive patients and retreatment of patients who have previously undergone unsuccessful thalamic Vim lesioning.