Impact of target depth on safety and efficacy outcomes in MR-guided focused ultrasound thalamotomy for tremor patients.

OBJECTIVE: Target depth, defined by the z-coordinate in the dorsoventral axis relative to the anterior commissure-posterior commissure axial plane of the MR-guided focused ultrasound (MRgFUS) lesion, is considered to be critical for tremor improvement and the occurrence of side effects such as gait impairment. However, although different z-coordinates are used in the literature, there are no comparative studies available with information on optimal lesion placement. This study aimed to compare two different MRgFUS lesion targets (z = +2 mm vs z = 0 mm) regarding efficacy and safety outcomes. METHODS: The authors conducted a retrospective analysis of 52 patients with pharmacoresistant tremor disorders who received unilateral MRgFUS thalamotomy in the ventral intermediate nucleus for the first time between 2017 and 2022 by one neurosurgeon, with two different z-coordinates, either z = +2 mm (+2-mm group; n = 17) or z = 0 mm (0-mm group; n = 35), but otherwise identical parameters. Standardized video-recorded assessments of efficacy (including the Washington Heights-Inwood Genetic Study of Essential Tremor scale) and safety (using a standardized grading system) outcomes at baseline and at 6 months posttreatment were reviewed and compared. Moreover, overall patient satisfaction was extracted as documented by the examiner at 6 months. RESULTS: Based on a multiple logistic regression analysis, the authors found that a more dorsal target with a z-coordinate of +2 mm as compared with 0 mm was associated with a higher incidence of any persistent side effect at 6 months (p = 0.02). Most consistently, sensory disturbances, although mild and nondisturbing in most cases, occurred more frequently in the +2-mm group (35% vs 11%, p = 0.007), while no significant differences were found for gait impairment (29% vs 35%) and arm ataxia (24% vs 11%). On the other hand, average tremor suppression was similar (63.6% vs 60.2%) between the groups. Here, higher efficacy was associated with a higher side effect burden in the 0-mm group but not in the +2-mm group. Despite the occurrence of side effects, general patient satisfaction was high (87% would undergo MRgFUS again) as most patients valued tremor suppression more. CONCLUSIONS: A more ventral MRgFUS target of z = 0 mm seems to be associated with a more favorable safety and a comparable efficacy profile as compared with a more dorsal target of z = +2 mm, but prospective studies are warranted.

Bilateral Focused Ultrasound Pallidotomy for Parkinson-Related Facial Dyskinesia-A Case Report.

Background: For safety reasons, both magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) thalamotomy and pallidotomy are currently approved exclusively for unilateral treatment, but axial symptoms like levodopa-induced orofacial dyskinesia require a bilateral approach. Objectives: We report the first case of successful bilateral MRgHiFUS pallidotomy for peak-dose dyskinesia in a patient with Parkinson's disease (PD). Methods: The treatment decision was based on the patient's reluctance toward brain implants and pump therapies and the fact that he had limited access to a deep brain stimulation center in his home country. The treatment was planned as staged procedure with an interval of 18 months because of travel restrictions because of the coronavirus disease (COVID)-19 pandemic. Results: After the second treatment, levodopa-induced orofacial dyskinesia remitted and improved bradykinesia and rigidity with stable gait and good postural reflexes. Conclusions: This promising result suggests that in selected PD patients with dyskinesia, staged bilateral MRgHiFUS pallidotomy might be considered.

Differentiation of Parkinson's disease tremor and essential tremor based on a novel hand posture.

Background: Tremor is one of the most common movement disorders but the correct diagnosis of tremor disorders, especially the differentiation between Parkinson's disease tremor (PT) and essential tremor (ET) remains a challenge for clinicians. Method: We examined a novel hand position to distinguish PT from ET. We prospectively collected accelerometric tremor data in 14 ET patients and 14 PT patients with arms and hands fully stretched against arms stretched and hands relaxed, i. e. hanging down. The total acceleration from the three pairwise-perpendicular accelerometric axes during the 1-minute blocks of the two hand positions were computed and high-passed filtered at 2 Hz. The power spectral density during each hand position was calculated and summed up over the frequency domain. Results: Our results showed a significantly higher occurrence of tremor in the hands hanging down position in PT patients compared to ET patients (p = 0.0262). Moreover, in PT patients the tremor intensity significantly increased when transitioning from the stretched hand position to the hanging-down position (83 % of cohort) and vice versa in ET patients (75 % of cohort). Conclusion: In conclusion, the new hand posture can differentiate between PT and ET with high accuracy (sensitivity 83 %, specificity 75 % for PT) and may be a helpful tool in the clinical assessment of tremor.

Consensus Statement on High-Intensity Focused Ultrasound for Functional Neurosurgery in Switzerland.

Background: Magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) has evolved into a viable ablative treatment option for functional neurosurgery. However, it is not clear yet, how this new technology should be integrated into current and established clinical practice and a consensus should be found about recommended indications, stereotactic targets, patient selection, and outcome measurements. Objective: To sum up and unify current knowledge and clinical experience of Swiss neurological and neurosurgical communities regarding MRgHiFUS interventions for brain disorders to be published as a national consensus paper. Methods: Eighteen experienced neurosurgeons and neurologists practicing in Switzerland in the field of movement disorders and one health physicist representing 15 departments of 12 Swiss clinical centers and 5 medical societies participated in the workshop and contributed to the consensus paper. All experts have experience with current treatment modalities or with MRgHiFUS. They were invited to participate in two workshops and consensus meetings and one online meeting. As part of workshop preparations, a thorough literature review was undertaken and distributed among participants together with a list of relevant discussion topics. Special emphasis was put on current experience and practice, and areas of controversy regarding clinical application of MRgHiFUS for functional neurosurgery. Results: The recommendations addressed lesioning for treatment of brain disorders in general, and with respect to MRgHiFUS indications, stereotactic targets, treatment alternatives, patient selection and management, standardization of reporting and follow-up, and initialization of a national registry for interventional therapies of movement disorders. Good clinical evidence is presently only available for unilateral thalamic lesioning in treating essential tremor or tremor-dominant Parkinson's disease and, to a minor extent, for unilateral subthalamotomy for Parkinson's disease motor features. However, the workgroup unequivocally recommends further exploration and adaptation of MRgHiFUS-based functional lesioning interventions and confirms the need for outcome-based evaluation of these approaches based on a unified registry. MRgHiFUS and DBS should be evaluated by experts familiar with both methods, as they are mutually complementing therapy options to be appreciated for their distinct advantages and potential. Conclusion: This multidisciplinary consensus paper is a representative current recommendation for safe implementation and standardized practice of MRgHiFUS treatments for functional neurosurgery in Switzerland.

Bilateral staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of essential tremor: a case series study.

BACKGROUND: Unilateral magnetic resonance-guided focused ultrasound (FUS) thalamotomy is efficacious for the treatment of medically refractory essential tremor (ET). Viability of bilateral FUS ablation is unexplored. METHODS: Patients diagnosed with medically refractory ET and previously treated with unilateral FUS thalamotomy at least 5 months before underwent bilateral treatment. The timepoints were baseline (before first thalamotomy) and FUS1 and FUS2 (4 weeks before and 6 months after second thalamotomy, respectively). The primary endpoint was safety. Efficacy was assessed through the Clinical Rating Scale for Tremor (CRST), which includes subscales for tremor examination (part A), task performance (part B) and tremor-related disability (part C). RESULTS: Nine patients were treated. No permanent adverse events were registered. Six patients presented mild gait instability and one dysarthria, all resolving within the first few weeks. Three patients reported perioral hypoesthesia, resolving in one case. Total CRST score improved by 71% from baseline to FUS2 (from 52.3±12 to 15.5±9.4, p<0.001), conveying a 67% reduction in bilateral upper limb A+B (from 32.3±7.8 to 10.8±7.3, p=0.001). Part C decreased by 81% (from 16.4±3.6 to 3.1±2.9, p<0.001). Reduction in head and voice tremor was 66% (from 1.2±0.44 to 0.4±0.54, p=0.01) and 45% (from 1.8±1.1 to 1±0.8, p=0.02), respectively. CONCLUSION: Bilateral staged FUS thalamotomy for ET is feasible and might be safe and effective. Voice and head tremor might also improve. A controlled study is warranted.

Tremor analysis with wearable sensors correlates with outcome after thalamic deep brain stimulation.

INTRODUCTION: Thalamic deep brain stimulation (DBS) provides excellent tremor control in most patients with essential tremor (ET). However, not all tremor patients show clinically significant improvement after DBS surgery. Currently, there is no reliable clinical or instrument-based measure to predict how patients respond to DBS. Therefore, we set out to provide a method for tremor outcome prediction prior to surgery. METHODS: We retrospectively analysed quantitative tremor data collected with inertial measurement units (IMU) in 13 patients who underwent DBS surgery in the ventral intermediate nucleus of the thalamus (VIM). All patients were diagnosed with either ET or ET-plus according to current diagnostic criteria of the movement disorder society. We used linear and logistic regression models to evaluate the influence of different tremor characteristics on tremor outcome. RESULTS: We found that the ratio between the amplitude of the first overtone and the amplitude of the fundamental frequency, denoted as the Harmonic Index, has a significant influence on tremor reduction after DBS surgery. This measure shows a strong correlation with the post-operative improvement of tremor outcome based on the Whiget Tremor Rating Scale. CONCLUSION: Based on these findings, we propose a novel approach to predict tremor outcome after DBS surgery. Quantitative tremor assessment adds to the preoperative prediction of DBS response and might therefore have a relevant clinical impact in the management of patients suffering from pharmacoresistant tremor.