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Abstract BACKGROUND Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET). OBJECTIVE To determine the predictors of outcomes after FUS-T. METHODS 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. RESULTS 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). CONCLUSION 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.

Abstract BACKGROUND Several feasibility studies and a randomized, controlled, multicenter trial have demonstrated the safety and efficacy of unilateral transcranial magnetic resonance-guided focused ultrasound (FUS) lesioning of the ventral intermediate thalamic nucleus in treating essential tremor. OBJECTIVE To evaluate the safety and efficacy of FUS thalamotomy in a Japanese patient cohort through a prospective, multicenter, single-arm confirmatory trial. METHODS A total of 35 patients with disabling refractory essential tremor underwent unilateral FUS thalamotomy and were followed up for 12 post-treatment months. Safety was measured as the incidence and severity of treatment-related adverse events. Efficacy was measured as the tremor severity and quality of life improvements using the Clinical Rating Scale for Tremor and Questionnaire for Essential Tremor. RESULTS The mean skull density ratio (SDR) was 0.47. There was a significant decrease in the mean postural tremor score of the treated hand from baseline to 12 mo by 56.4% (95% CI: 46.7%-66.1%; P < .001), which was maintained at last follow-up. Quality of life improved by 46.3% (mean overall Questionnaire for Essential Tremor score of 17.4 [95% CI: 12.1-22.7]) and there were no severe adverse events. The most frequent adverse event was gait disturbance and all events resolved. CONCLUSION Unilateral FUS thalamotomy allowed significant and sustained tremor relief and improved the quality of life with an outstanding safety profile. The observed safety and efficacy of FUS thalamotomy were comparable to those reported in a previous multicenter study with a low SDR, and inclusion of the low SDR group did not affect effectiveness. Graphical Abstract Graphical Abstract

Stereotactic radiosurgery (SRS) is one of the surgical alternatives for drug-resistant essential tremor (ET). Here, we aimed at evaluating whether biologically effective dose (BED Gy2.47 ) is relevant for tremor improvement after stereotactic radiosurgical thalamotomy in a population of patients treated with one (unplugged) isocenter and a uniform dose of 130 Gy. This is a retrospective longitudinal single center study. Seventy-eight consecutive patients were clinically analyzed. Mean age was 69.1 years (median 71, range 36–88). Mean follow-up period was 14 months (median 12, 3–36). Tremor improvement was assessed at 12 months after SRS using the ET rating assessment scale (TETRAS, continuous outcome) and binary (binary outcome). BED was defined for an alpha/beta of 2.47, based upon previous studies considering such a value for the normal brain. Mean BED was 4573.1 Gy 2.47 (median 4612, 4022.1–4944.7). Mean beam-on time was 64.7 min (median 61.4; 46.8–98.5). There was a statically significant correlation between delta (follow-up minus baseline) in TETRAS (total) with BED ( p  = 0.04; beta coefficient − 0.029) and beam-on time ( p  = 0.03; beta coefficient 0.57) but also between TETRAS (ADL) with BED ( p  = 0.02; beta coefficient 0.038) and beam-on time ( p  = 0.01; beta coefficient 0.71). Fractional polynomial multivariate regression suggested that a BED > 4600 Gy 2.47 and a beam-on time > 70 min did not further increase clinical efficacy (binary outcome). Adverse radiation events (ARE) were defined as larger MR signature on 1-year follow-up MRI and were present in 7 out of 78 (8.9%) cases, receiving a mean BED of 4650 Gy 2.47 (median 4650, range 4466–4894). They were clinically relevant with transient hemiparesis in 5 (6.4%) patients, all with BED values higher than 4500 Gy 2.47 . Tremor improvement was correlated with BED Gy 2.47 after SRS for drug-resistant ET. An optimal BED value for tremor improvement was 4300–4500 Gy 2.47 . ARE appeared for a BED of more than 4500 Gy 2.47 . Such finding should be validated in larger cohorts.

Background MRgFUS Vim ablation is increasingly used for the treatment of tremor in ET e PD patients but there is little published research on the importance of operator experience in this procedure. This study aims to evaluate the learning curve and the influence of the operator experience on the procedural and clinical outcomes. Methods We retrospectively evaluated 90 patients (38 ET, 52 PD) submitted to MRgFUS unilateral thalamotomy in the period between February 2018 and July 2020. Clinical endpoints, procedural times, and technical parameters were recorded in all procedures. Based on the time of treatment, patients were divided into three groups of 30 units each, comparing all variables between each time period group. Results In Group A, the average patient preparation time was 120.6 min, the treatment time was 105.2 min, the number of was sonications 14.1, and the mean target shifts 3.1. In Group B, the mean preparation time was 105.5 min, the treatment time was 89.5 min, the number of sonications was 13.2, and the target shifts 3.0. Group C showed inferior values of preparation time (101.9 min), treatment time (71.7 min), numbers of sonications (10.6), and shifts (1.7). Thalamotomy-related complications occurred in 9 patients of Group A, 2 of Group B, and 5 of Group C. Tremor relapse occurred in 7 patients of Group A, 3 of Group B, and 2 of Group C. The days of hospitalization were comparable in the three groups. Conclusions The operators experience is associated with the improvement of clinical and procedural outcome in MRgFUS thalatomy for the treatment of ET and PD tremor.

•Early series of thalamotomy for tremor led to a high incidence of dysarthria and ataxia after bilateral lesions.•DBS has largely supplanted bilateral lesions for tremor control.•Limited recent studies support the safety of bilateral thalamotomy for patients with essential tremor (ET).•Study of less invasive lesioning methods, such as MRgFUS, are justified for bilateral thalamotomy in patients with ET. MRI guided focused ultrasound surgery (MRgFUS) has been FDA approved for unilateral treatment of essential tremor (ET). Before this non-incisional lesioning method can be applied to the treatment of both hemispheres the previous experience with bilateral thalamic ablation must be addressed. In particular, the high incidence of worsening of speech and balance associated with bilateral surgical thalamotomy, a rationale for the development of deep brain stimulation. The highest incidence of these complication occurred in the early years of surgery for movement disorders, when neither MRI nor current stereotactic methods were available. The vast majority of these initial patients suffering these complications had Parkinson’s disease where approximately 30% developed worsening dysarthria and ataxia after bilateral thalamotomy. Patients suffering these complications commonly had baseline abnormalities in speech and balance or worsening symptoms after a first unilateral procedure. The more contemporary experience with bilateral thalamotomy in the ET population is both much more limited in patient numbers (includes patients after Gamma Knife radiosurgery), and shows a much lower rate of these complications (approximately 5%). This more recent experience suggests that bilateral thalamotomy using closed incisionless methods such as MRgFUS has the potential to safely improve ET patients with axial or bilateral limb involvement, if done in a staged manner excluding patients with baseline dysarthria or ataxia or transient worsening of these symptoms following a unilateral procedure.

Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT. Patients were assessed with psychological tests and acoustic voice analysis. Tremor assessment was performed with a digitising table using the Fahn-Tolosa-Marin rating scale (FTMRS). The Unified Parkinson's Disease rating scale part III (UPDRS-III) was also used in the PD group. Gait and balance was assessed using clinical tests, stabilometric platform, and treadmill. No side effects were observed in a two-year follow-up. There was no notable deterioration observed in the patients' psychological evaluation, speech, or assessment of gait and balance. The scores were significantly lower (p = 0.01) in parts A and B of FTMRS one year after GKT. In post hoc analysis, the scores did not differ significantly between V0 and V24. In FTMRS part C (activities of daily living), no significant change was observed. There was no significant difference in total UPDRS part III score or in score of UPDRS part III domains 3 and 4 ('tremor at rest' and 'action and postural tremor of hands') between measurements. UGKT may be a safe treatment modality if performed in an experienced centre. Tremor reduction may diminish over time, and UGKT did not lead to cognitive, gait or speech deterioration in a long-term observation.

Tremor can be an incapacitating symptom that leads to functional impairment. In patients with Parkinson's disease and in those with essential tremor, pharmacologic treatment often does not adequately control tremor. In patients with multiple sclerosis, intention tremor can add considerably to their disability. Neurosurgical thalamotomy is effective in 73 to 93 percent of patients with incapacitating tremor that is refractory to drug therapy. 1 – 6 However, this procedure is accompanied by permanent complications in 9 to 23 percent of patients with Parkinson's disease or essential tremor 1 , 2 , 5 – 8 and in 16 to 41 percent of patients with multiple sclerosis. 7 , . . .

This letter to the editor critiques a recent study evaluating the role of biologically effective dose (BED) in stereotactic radiosurgical thalamotomy for essential tremor (ET). The study, conducted retrospectively on 78 ET patients, demonstrates a significant correlation between BED and tremor improvement post-SRS. Moreover, the study suggests adjusting the prescribed dose rather than changing cobalt-60 sources to maintain treatment efficacy while minimizing toxicity. This suggestion aligns with previous research indicating an annual decrease in BED due to cobalt-60 decay. The letter emphasizes the importance of considering BED and cobalt-60 decay in optimizing treatment outcomes for ET patients undergoing stereotactic radiosurgery. Further research is recommended to explore innovative techniques for dose modulation in response to cobalt-60 decay and validate findings in larger cohorts.

Purpose of ReviewLesioning therapies have been some of the earliest, most effective surgical treatments in movement disorders. This review summarizes recent studies, emerging modalities, and trends in lesioning procedures for movement disorders.Recent FindingsMagnetic resonance–guided high-intensity focused ultrasound (MRgFUS) is the newest incisionless technology for lesioning procedures in movement disorders. It has recent FDA approval for thalamotomy in essential tremor and tremor-dominant Parkinson disease. There are current studies exploring subthalamotomy and pallidotomy in PD. Gamma knife is another incisionless modality that has been studied for decades and remains an effective treatment, albeit with less recent studies and more risks for adverse events, in movement disorders. Radiofrequency lesioning remains an efficacious treatment, particularly for unilateral pallidotomy in PD, but has fallen out of favor compared with other modalities, particularly MRgFUS.SummaryLesioning therapies in movement disorders have shown efficacy in treating a variety of movement disorders. Enthusiasm for their use has waned with the advent of deep brain stimulation. The recent development of MRgFUS has recentered attention on lesioning therapy and its potential. Patient preference and access to care will remain determinants in the use of lesioning therapy as more data are being collected on the long-term benefit and safety.