Tremor Outcomes Research Articles

Frailty and outcomes after unilateral MRI-guided focused ultrasound thalamotomy for tremor.

Frailty is recognized as an important predictor of neurointerventional outcomes. MRI-guided focused ultrasound (MRgFUS) thalamotomy is a treatment option for patients with refractory essential tremor (ET) and tremor-dominant Parkinson's disease (TdPD). The aim of this study was to evaluate whether frailer MRgFUS thalamotomy patients had worse tremor outcomes or more complications. The authors performed a cohort analysis of patients treated with MRgFUS between 2020 and 2023. Inclusion criteria were unilateral MRgFUS thalamotomy for ET or TdPD with available follow-up data (minimum 3-month follow-up). Frailty was assessed using the 11-item modified frailty index (mFI-11), which includes 11 medical comorbidities. Tremor outcomes were assessed using the Clinical Rating Scale for Tremor Part B. Complications assessed included disturbances of sensation, speech and swallowing, balance and gait, and strength. In total, 169 eligible patients were identified, including 135 (79.9%) ET and 34 (20.1%) TdPD patients. Frailty did not result in significant differences in tremor outcomes in the combined (p = 0.833), ET (p = 0.902), or TdPD (p = 0.501) cohort, or in any adverse events at the last follow-up (all p > 0.05). The combined mean follow-up was 10.3 ± 5.8 months (range 3-24 months), with cohort-specific mean follow-ups of 10.8 ± 6.0 months for ET and 8.6 ± 4.6 months for TdPD. Between the ET and TdPD cohorts, no significant differences existed in age, sex, handedness, side treated, skull density ratio, number of sonications, peak and average temperatures, energy delivered, BMI, or American Society of Anesthesiologists classification. For medical comorbidities, only hypertension was significantly different (65.9% ET, 47.1% TdPD; p = 0.043). The ET patients were significantly frailer overall, with 20.7% ET and 35.3% TdPD patients considered robust (mFI-11 score of 0), 14.8% ET and 32.4% TdPD patients prefrail (mFI-11 score of 1), 25.9% ET and 8.8% TdPD patients frail (mFI-11 score of 2), and 38.5% ET and 23.5% TdPD patients severely frail (mFI-11 score ≥ 3) (p = 0.007). Increasing frailty is not associated with worse outcomes, suggesting that MRgFUS may be appropriate even for frailer patients. ET patients are frailer than TdPD patients selected for MRgFUS.

Motor and non-motor outcome in tremor dominant Parkinson’s disease after MR-guided focused ultrasound thalamotomy

Background and objectivesMagnetic Resonance-guided Focused Ultrasound (MRgFUS) is an emerging technique for the treatment of severe, medication-refractory tremor syndromes. We here report motor and non-motor outcomes 6 and 12 months after unilateral MRgFUS thalamotomy in tremor-dominant Parkinson’s disease (tdPD).Methods25 patients with tdPD underwent neuropsychological evaluation including standardized questionnaires of disability, quality of life (QoL), mood, anxiety, apathy, sleep disturbances, and cognition at baseline, 6 and 12 months after MRgFUS. Motor outcome was evaluated using the Clinical Rating Scale for Tremor (CRST) and Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). In addition, side effects and QoL of family caregivers were assessed.Results12 months after MRgFUS significant improvements were evident in the tremor subscores. Patients with concomitant rest and postural tremor showed better tremor outcomes compared to patients with predominant rest tremor. There were no differences in the non-motor assessments. No cognitive decline was observed. Side effects were mostly transient (54%) and classified as mild (62%). No changes in the caregivers' QoL could be observed.ConclusionWe found no changes in mood, anxiety, apathy, sleep, cognition or persistent worsening of gait disturbances after unilateral MRgFUS thalamotomy in tdPD. Concomitant postural tremors responded better to treatment than predominant rest tremors.

Enhancing outcomes in deep brain stimulation: a comparative study of direct targeting using 7T versus 3T MRI.

The aim of this study was to compare outcomes of direct targeting in deep brain stimulation (DBS) for essential tremor using 7T MRI versus 3T MRI. The authors hypothesized that 7T MRI direct targeting would be noninferior to 3T MRI in early tremor outcomes. A retrospective study was conducted on patients undergoing unilateral thalamic DBS for essential tremor between 2021 and 2023. Two matched cohorts were assessed, one using 7T MRI and the other using 3T MRI for surgical planning. The primary endpoint was the percentage improvement in the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) scores. Additionally, the authors assessed optimized programming settings and variance in electrode position on postoperative imaging. Demographic and clinical data were compared using the nonparametric Mann-Whitney U-test. The squared Euclidean distance of each contact from the group mean centroid was calculated and averaged across the entire cohort to provide the variance (i.e., the mean squared distance) of electrode contact position. A total of 34 patients were analyzed, with 17 in each cohort. There were no significant differences in demographic information or mean surgical dates between the groups. There were no differences in intraoperative target repositioning or adverse events. The 7T group had a significantly greater TRS improvement than the 3T group (64.9% ± 11.4% vs 50.9% ± 16.4%, p = 0.004). Patients in the 7T cohort also had a lower mean stimulation current compared with those in the 3T cohort (2.0 ± 0.8 mA vs 2.7 ± 0.9 mA, p = 0.01). Image evaluation revealed that although the mean electrode position was comparable between 7T and 3T, the 7T electrode positioning was more clustered, indicating a lower variance in the final electrode location. The mean Euclidean distance between the individual electrode tips and the group centroid was significantly less at 7T than at 3T (1.82 ± 0.68 mm vs 2.75 ± 0.81 mm, p = 0.001). Despite concerns for increased artifacts and distortions at 7T, the authors show that these effects can be mitigated with an appropriate workflow, leading to improved surgical outcomes with direct targeting using 7T MRI. Their results suggest similar accuracy but greater precision in targeting with 7T MRI compared with 3T MRI, resulting in lower stimulation currents and improved tremor reduction. Future studies are needed to assess outcomes related to 7T MRI in targeting other subcortical structures.

Comparison of Dentatorubrothalamic Tractography Methods Based on the Anatomy of the Rubral Wing.

Precise localization of the dentatorubrothalamic (DRT) tract can facilitate anatomic targeting in MRI-guided high-intensity focused ultrasound (HIFU) thalamotomy and thalamic deep brain stimulation for tremor. The anatomic segment of DRT fibers adjacent to the ventral intermediate nucleus of the thalamus (VIM), referred to as the rubral wing (RW), may be directly visualized on the fast gray matter acquisition T1 inversion recovery. We compared reproducibility, lesion overlap, and clinical outcomes when reconstructing the DRT tract using a novel anatomically defined RW region of interest, DRT-RW, to an existing tractography method based on the posterior subthalamic area region of interest (DRT-PSA). We reviewed data of 23 patients with either essential tremor (n = 18) or tremor-predominant Parkinson's disease (n = 5) who underwent HIFU thalamotomy, targeting the VIM. DRT tractography, ipsilateral to the lesion, was created based on either DRT-PSA or DRT-RW. Volume sections of each tract were created and dice similarity coefficients were used to measure spatial overlap between the 2 tractographies. Post-HIFU lesion size and location (on postoperative T2 MRI) was correlated with tremor outcomes and side effects for both DRT tractography methods and the RW itself. DRT-PSA passed through the RW and DRT-RW intersected with the ROIs of the DRT-PSA in all 23 cases. A higher percentage of the RW was ablated in patients who achieved tremor control (18.9%, 95% CI 15.1, 22.7) vs those without tremor relief (6.7%, 95% CI% 0, 22.4, P = .017). In patients with tremor control 6 months postoperatively (n = 12), those with side effects (n = 6) had larger percentages of their tracts ablated in comparison with those without side effects in both DRT-PSA (44.8, 95% CI 31.8, 57.8 vs 24.2%, 95% CI 12.4, 36.1, P = .025) and DRT-RW (35.4%, 95% CI 21.5, 49.3 vs 21.7%, 95% CI 12.7, 30.8, P = .030). Tractography of the DRT could be reconstructed by direct anatomic visualization of the RW on fast gray matter acquisition T1 inversion recovery-MRI. Anatomic planning is expected to be quicker, more reproducible, and less operator-dependent.

Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation.

Magnetic-resonance-guided focused ultrasound (MRgFUS) thalamotomy uses multiple converging high-energy ultrasonic beams to produce thermal lesions in the thalamus. Early postoperative MR imaging demonstrates the location and extent of the lesion, but there is no consensus on the utility or frequency of postoperative imaging. We aimed to evaluate the evolution of MRgFUS lesions and describe the incidence, predictors, and clinical effects of lesion persistence in a large patient cohort. A total of 215 unilateral MRgFUS thalamotomy procedures for essential tremor (ET) by a single surgeon were retrospectively analyzed. All patients had MR imaging 1 day postoperatively; 106 had imaging at 3 months and 32 had imaging at 1 year. Thin cut (2 mm) axial and coronal T2-weighted MRIs at these timepoints were analyzed visually on a binary scale for lesion presence and when visible, lesion volumes were measured. SWI and DWI sequences were also analyzed when available. Clinical outcomes including tremor scores and side effects were recorded at these same time points. We analyzed if patient characteristics (age, skull density ratio), preoperative tremor score, and sonication parameters influenced lesion evolution and if imaging characteristics correlated with clinical outcomes. Visible lesions were present in all patients 1 day post- MRgFUS and measured 307.4 ± 128.7 mm3. At 3 months, residual lesions (excluding patients where lesions were not visible) were 83.6% smaller and detectable in only 54.7% of patients (n = 58). At 1 year, residual lesions were detected in 50.0% of patients (n = 16) and were 90.7% smaller than 24 h and 46.5% smaller than 3 months. Lesions were more frequently visible on SWI (100%, n = 17), DWI (n = 38, 97.4%) and ADC (n = 36, 92.3%). At 3 months, fewer treatment sonications, higher maximum power, and greater distance between individual sonications led to larger lesion volumes. Volume at 24 h did not predict if a lesion was visible later. Lesion visibility at 3 months predicted sensory side effects but was not correlated with tremor outcomes. Overall, lesions are visible on T2-weighted MRI in about half of patients at both 3 months and 1 year post-MRgFUS thalamotomy. Certain sonication parameters significantly predicted persistent volume, but residual lesions did not correlate with tremor outcomes.

Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort.

Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice. To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure. Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year. MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson's Disease.

Magnetic resonance-guided focused ultrasound (MRgFUS) has emerged as a precise, incisionless approach to cerebral lesioning and an alternative to neuromodulation in movement disorders. Despite rigorous clinical trials, long-term patient-centered outcome data after MRgFUS for tremor-predominant Parkinson's Disease (TPPD) are relatively lacking. To report long-term data on patient satisfaction and quality of life after MRgFUS thalamotomy for TPPD. In a retrospective study of patients who underwent MRgFUS thalamotomy for TPPD at our institution between 2015 and 2022, a patient survey was administered to collect self-reported measures of tremor improvement, recurrence, Patients' Global Impression of Change (PGIC), and side effects. Patient demographics, FUS parameters, and lesion characteristics were analyzed. A total of 29 patients were included with a median follow-up of 16 months. Immediate tremor improvement was achieved in 96% of patients. Sustained improvement was achieved in 63% of patients at last follow-up. Complete tremor recurrence to baseline occurred for 17% of patients. Life quality improvement denoted by a PGIC of 1 to 2 was reported by 69% of patients. Long-term side effects were reported by 38% of patients and were mostly mild. Performing a secondary anteromedial lesion to target the ventralis oralis anterior/posterior nucleus was associated with higher rates of speech-related side effects (56% vs 12%), without significant improvement in tremor outcomes. Patient satisfaction with FUS thalamotomy for tremor-predominant PD was very high, even at longer term. Extended lesioning to target the motor thalamus did not improve tremor control and may contribute to greater frequency of postoperative motor- and speech-related side effects.

Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy.

Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy. We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps. The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices. Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Immediate and Early Postoperative Tremor Fluctuation and 6 to 12-month Tremor Outcomes after Magnetic Resonance-guided Focused Ultrasound for Essential Tremor

Immediate and Early Postoperative Tremor Fluctuation and 6 to 12-month Tremor Outcomes after Magnetic Resonance-guided Focused Ultrasound for Essential Tremor

Response to Thalamic Ventralis Intermedius Nucleus Deep Brain Stimulation in Essential Tremor vs. Essential Tremor-Plus.

Introduction: Essential tremor (ET) is a tremor syndrome characterized by bilateral, upper limb action tremor. Essential tremor-plus (ET-plus) describes ET patients with additional neurologic signs. It is unknown whether there is a difference in response to treatment with ventralis intermedius nucleus deep brain stimulation (VIM DBS) in patients with ET and ET-plus. Due to potential variability in underlying etiology in ET-plus, there is a concern that ET-plus patients may have worse outcomes. The aim of this study was to identify whether patients with ET-plus have worse tremor outcomes after VIM DBS than patients with ET.Methods: This is a retrospective chart and video review evaluating VIM DBS outcomes by comparing changes from baseline in the Fahn-Tolosa-Marin Tremor Rating Scale Part B (FTM-B) for the treated limb between patients with ET and ET-plus at follow-up examinations. Patients were re-classified as having ET or ET-plus using pre-operative examination videos by two independent movement disorders neurologists blinded to patient characteristics. As a secondary outcome, we evaluated for correlations and potential predictors of treatment response.Results: Twenty-six patients were included: 13 with ET, 13 with ET-plus. There were no significant differences in the change in FTM-B scores between the ET and ET-plus patients at each follow-up examination. None of the included patients developed new symptoms compatible with dystonia, parkinsonism or gait disturbances.Conclusions: Patients with ET-plus had tremor improvement from VIM DBS, with no differences when compared to those with ET, without emergence of postoperative neurological issues. Patients with ET-plus should still be considered good candidates for VIM DBS for treatment of tremor.

Predictors of Outcomes After Focused Ultrasound Thalamotomy.

Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). To determine the predictors of outcomes after FUS-T. Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables. A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9%±24.9% vs 52.1%±24.9%, P=.009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7±2.5 vs 55.6±2.8°C, P=.004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F=7.9 [1,165], P=.005). We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications.

Optimal Parameters of Deep Brain Stimulation in Essential Tremor: A Meta-Analysis and Novel Programming Strategy.

The programming of deep brain stimulation (DBS) parameters for tremor is laborious and empirical. Despite extensive efforts, the end-result is often suboptimal. One reason for this is the poorly understood relationship between the stimulation parameters’ voltage, pulse width, and frequency. In this study, we aim to improve DBS programming for essential tremor (ET) by exploring a new strategy. At first, the role of the individual DBS parameters in tremor control was characterized using a meta-analysis documenting all the available parameters and tremor outcomes. In our novel programming strategy, we applied 10 random combinations of stimulation parameters in eight ET-DBS patients with suboptimal tremor control. Tremor severity was assessed using accelerometers and immediate and sustained patient-reported outcomes (PRO’s), including the occurrence of side-effects. The meta-analysis showed no substantial relationship between individual DBS parameters and tremor suppression. Nevertheless, with our novel programming strategy, a significantly improved (accelerometer p = 0.02, PRO p = 0.02) and sustained (p = 0.01) tremor suppression compared to baseline was achieved. Less side-effects were encountered compared to baseline. Our pilot data show that with this novel approach, tremor control can be improved in ET patients with suboptimal tremor control on DBS. In addition, this approach proved to have a beneficial effect on stimulation-related complications.

Individualized Anatomy-Based Targeting for VIM-cZI DBS in Essential Tremor

Deep brain stimulation of the ventral intermediate nucleus (VIM) or caudal zona incerta (cZI) is effective for refractory essential tremor (ET). To refine stereotactic planning for lead placement, we developed a unique individualized anatomy-based planning protocol that targets both the VIM and the cZI in patients with ET. 33 patients with ET underwent VIM-cZI lead implantation with targeting based on our protocol. Indirect targeting was adjusted based on anatomic landmarks as reference lines bisecting the red nuclei and ipsilateral subthalamus. Outcomes were evaluated through the follow-up of 31.1 ± 18.4 months. Active contact coordinates were obtained from reconstructed electrodes in the Montreal Neurological Institute space using the MATLAB Lead-DBS toolbox. Mean tremor improvement was 79.7% ±22.4% and remained stable throughout the follow-up period. Active contacts at last postoperative visit had mean Montreal Neurological Institute coordinates of 15.5 ± 1.6 mm lateral to the intercommissural line, 15.3± 1.8 mm posterior to the anterior commissure, and 1.4 ± 2.9 mm below the intercommissural plane. No hemorrhagic complications were observed in the analyzed group. Individualized anatomy-based VIM-cZI targeting is feasible and safe and is associated with favorable tremor outcomes.

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

To assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET). We retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2-3 years, 4-5 years, and ≥6 years after surgery. Twenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4-5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2-3 years follow-up. Overall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features. This study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.

MR-Guided Focused Ultrasound Versus Radiofrequency Capsulotomy for Treatment-Refractory Obsessive-Compulsive Disorder: A Cost-Effectiveness Threshold Analysis.

Meta-analytic techniques support neuroablation as a promising therapy for treatment-refractory obsessive-compulsive disorder (OCD). This technique appears to offer a more favorable complication rate and higher utility than deep brain stimulation. Moreover, these pooled findings suggest that bilateral radiofrequency (RF) capsulotomy has marginally greater efficacy than stereotactic radiosurgery or cingulotomy. MR-guided focused ultrasound (MRgFUS) capsulotomy is an emerging approach with a potentially more favorable profile than RF ablation and radiosurgery, with preliminary data suggesting safety and efficacy. As a clinical trial is being developed, our study examined the cost and clinical parameters necessary for MRgFUS capsulotomy to be a more cost-effective alternative to RF capsulotomy. A decision analytical model of MRgFUS with RF capsulotomy for OCD was performed using outcome parameters of percent surgical improvement in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score, complications, and side effects. The analysis compared measured societal costs, derived from Medicare reimbursement rates, and effectiveness, based on published RF data. Effectiveness was defined as the degree to which MRgFUS lowered Y-BOCS score. Given that MRgFUS is a new therapy for OCD with scant published data, theoretical risks of MRgFUS capsulotomy were derived from published essential tremor outcomes. Sensitivity analysis yielded cost, effectiveness, and complication rates as critical MRgFUS parameters defining the cost-effectiveness threshold. Literature search identified eight publications (162 subjects). The average reduction of preoperative Y-BOCS score was 56.6% after RF capsulotomy with a 22.6% improvement in utility, a measure of quality of life. Complications occurred in 16.2% of RF cases. In 1.42% of cases, complications were considered acute-perioperative and incurred additional hospitalization cost. The adverse events, including neurological and neurobehavioral changes, in the other 14.8% of cases did not incur further costs, although they impacted utility. Rollback analysis of RF capsulotomy yielded an expected effectiveness of 0.212 quality-adjusted life years/year at an average cost of $24,099. Compared to RF capsulotomy, MRgFUS was more cost-effective under a range of possible cost and complication rates. While further study will be required, MRgFUS lacks many of the inherent risks associated with more invasive modalities and has potential as a safe and cost-effective treatment for OCD.

Prospective Tractography-Based Targeting for Improved Safety of Focused Ultrasound Thalamotomy.

Focused ultrasound thalamotomy (FUS-T) was recently approved for the treatment of refractory essential tremor (ET). Despite its noninvasive approach, FUS-T reinitiated concerns about the adverse effects and long-term efficacy after lesioning. To prospectively assess the outcomes of FUS-T in 10 ET patients using tractography-based targeting of the ventral intermediate nucleus (VIM). VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo, were assessed independently by the Tremor Research Group. We analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilisitic tractography. Quantitative diffusion-weighted imaging changes were also studied in fiber tracts of interest. The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3 mo (tremor score: 18.3 ± 6.9 vs 8.1 ± 4.4, P = .001). No motor weakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex. This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes.

Voice Tremor Outcomes of Subthalamic Nucleus and Zona Incerta Deep Brain Stimulation in Patients With Parkinson Disease

We aimed to study the effect of deep brain stimulation (DBS) in the subthalamic nucleus (STN) and caudal zona incerta (cZi) on level of perceived voice tremor in patients with Parkinson disease (PD). This is a prospective nonrandomized design with consecutive patients. Perceived voice tremor was assessed in patients with PD having received either STN-DBS (8 patients, 5 bilateral and 3 unilateral, aged 43.1-73.6 years; median = 61.2 years) or cZi-DBS (14 bilateral patients, aged 39.0-71.9 years; median = 56.6 years) 12 months before the assessment. Sustained vowels that were produced OFF and ON stimulation (with simultaneous l-DOPA medication) were assessed perceptually in terms of voice tremor by two raters on a four-point rating scale. The assessments were repeated five times per sample and rated in a blinded and randomized procedure. Three out of the 22 patients (13%) were concluded to have voice tremor OFF stimulation. Patients with PD with STN-DBS showed mild levels of perceived voice tremor OFF stimulation and a group level improvement. Patients with moderate/severe perceived voice tremor and cZi-DBS showed marked improvements, but there was no overall group effect. Six patients with cZi-DBS showed small increases in perceived voice tremor severity. STN-DBS decreased perceived voice tremor on a group level. cZi-DBS decreased perceived voice tremor in patients with PD with moderate to severe preoperative levels of the symptom.

Voice Tremor in Patients With Essential Tremor: Effects of Deep Brain Stimulation of Caudal Zona Incerta

The present study aimed at evaluating the effect of deep brain stimulation (DBS) of the caudal zona incerta (cZi) on voice tremor in patients with essential tremor (ET). This is a prospective nonrandomized design with consecutive patients. Twenty-six patients operated with cZi DBS were evaluated under two conditions: without stimulation (Stim OFF) and with stimulation (Stim ON). Voice tremor was assessed on the basis of recordings of sustained vowel productions using a four-point rating scale in a blinded and randomized procedure. Averaged values of multiple assessments for each stimulus were used in statistical testing. The group of patients with voice tremor in Stim OFF was analyzed separately from the group of patients without voice tremor. Voice tremor was significantly reduced on stimulation compared with off for the subgroup with initial voice tremor. Voice tremor prevalence was found to be 50% (13 patients). Individual differences in voice tremor outcome were noticeable. Six of the patients with voice tremor at baseline improved substantially by cZi DBS treatment. On the group level, voice tremor in patients with ET was found to reduce when stimulating the cZi. Bilateral stimulation was indicated to be more effective in reducing voice tremor than unilateral stimulation. However, individual voice tremor outcomes suggest that not all patients benefit from cZi DBS. Severity of voice tremor at baseline may not be a good predictor of voice tremor outcome after cZi DBS. Patients should be informed before surgery regarding individual differences in response to DBS treatment.

Quantitatively measured tremor in hand-arm vibration-exposed workers.

Objectives The aim of the present study was to investigate the possible increase in hand tremor in relation to hand-arm vibration (HAV) exposure in a cohort of exposed and unexposed workers.MethodsParticipants were 178 male workers with or without exposure to HAV. The study is cross-sectional regarding the outcome of tremor and has a longitudinal design with respect to exposure. The dose of HAV exposure was collected via questionnaires and measurements at several follow-ups. The CATSYS Tremor Pen® was used for measuring postural tremor. Multiple linear regression methods were used to analyze associations between different tremor variables and HAV exposure, along with predictor variables with biological relevance.ResultsThere were no statistically significant associations between the different tremor variables and cumulative HAV or current exposure. Age was a statistically significant predictor of variation in tremor outcomes for three of the four tremor variables, whereas nicotine use was a statistically significant predictor of either left or right hand or both hands for all four tremor variables.ConclusionsIn the present study, there was no evidence of an exposure–response association between HAV exposure and measured postural tremor. Increase in age and nicotine use appeared to be the strongest predictors of tremor.