Thalamotomy For Essential Tremor Research Articles

Delayed clinical response to focused ultrasound thalamotomy in essential tremor in a patient with suboptimal skull density ratio – A case report

Delayed clinical response to focused ultrasound thalamotomy in essential tremor in a patient with suboptimal skull density ratio – A case report

Tremor Severity and Operative Parameters Predict Imbalance in Patients Undergoing Focused Ultrasound Thalamotomy.

Imbalance is the most commonly reported side effect following focused ultrasound (FUS) thalamotomy for essential tremor (ET). It remains unknown which patients are more likely to develop imbalance following FUS treatment. To identify preoperative and treatment-related sonication parameters that are predictive of imbalance following FUS treatment. We retrospectively collected demographic data, preoperative Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM) scores and FUS treatment parameters in patients undergoing FUS thalamotomy for treatment of ET. The presence of imbalance was evaluated at several discrete time-points with up to 4 years of follow-up. Multiple machine learning classifiers were built and evaluated, aiming to maximize accuracy while minimizing feature set. Of the 297 patients identified, the presence of imbalance peaked at 1 week following operation at 79%. This declined rapidly with 29% reporting imbalance at 3 months, and only 15% at 4 years. At 1 week, total preoperative FTM scores and Maximum Energy delivered in FUS could predict the presence of imbalance at 92.8% accuracy. At 3 months, the total preoperative FTM scores and maximum power delivered could predict the presence of imbalance with 90.6% accuracy. Post-operative lesion size and extent into thalamic nuclei, internal capsule, and subthalamic regions were identified as likely key underlying drivers of these predictors. A machine learning model based on preoperative tremor scores and maximum energy/power delivered predicted the development of short-term imbalance and long-term imbalance following FUS thalamotomy.

Quantitative Tractography-Based Evaluations in Essential Tremor Patients after MRgFUS Thalamotomy.

Magnetic resonance-guided focused ultrasound (MRgFUS) targeting the thalamic ventral intermediate nucleus (VIM) is an innovative treatment for drug-refractory essential tremor (ET). The relationship between lesion characteristics, dentate-rubro-thalamic-tract (DRTT) involvement and clinical benefit remains unclear. To investigate whether clinical outcome is related to lesion volume and/or its overlap with the DRTT. To compare the reliability of probabilistic versus deterministic tractography in reconstructing the DRTT and improving VIM targeting. Forty ET patients who underwent MRgFUS thalamotomy between 2019 and 2022 were retrospectively analyzed. Clinical outcomes and adverse effects were recorded at 1/6/12 months after the procedure. The DRTT was generated using deterministic and probabilistic tractography on preoperative diffusion-tensor 3 T-images and location and volume of the lesion were calculated. Probabilistic tractography identified both decussating (d-DRTT) and non-decussating (nd-DRTT) components of the DRTT, whereas the deterministic approach only identified one component overlapping with the nd-DRTT. Despite the lesions predominantly intersecting the medial portion of the d-DRTT, with a significantly greater overlap in responder patients, we observed only a non-significant correlation between tremor improvement and increased d-DRTT-lesion overlap (r = 0.22, P = 0.20). The lesion volume demonstrated a significant positive correlation with clinical improvement at 1-day MRI (r = 0.42, P < 0.01). Variability in the reconstructed DRTT position relative to the lesion center of mass, even among good responders, suggests that this fiber bundle is unlikely to be considered the sole target for a successful MRgFUS thalamotomy in ET. Indirect individualized targeting allows for more precise and reproducible identification of actual treatment coordinates than the direct method.

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.

Predicting tremor improvement after MRgFUS thalamotomy in essential tremor from preoperative spontaneous brain activity: A machine learning approach

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) thalamotomy is an emerging technique for medication-refractory essential tremor (ET), but with variable outcomes. This study used pattern regression analysis to identify brain signatures predictive of tremor improvements. Fifty-four ET patients (mean age = 63.06 years, standard deviation (SD) = 10.55 years, 38 males) underwent unilateral MRgFUS thalamotomy and were scanned for resting-state functional magnetic resonance imaging (rs-fMRI). Seventy-four healthy controls (mean age = 58.09 years, SD = 10.30 years, 38 males) were recruited for comparison. Tremor responses at 12 months posttreatment were evaluated by the Clinical Rating Scale for Tremor. The fractional amplitude of low-frequency fluctuations (fALFF) was calculated from rs-fMRI data. Two-sample t-test was used to generate a disease-specific mask, within which Multivariate Kernel Ridge Regression analyses were conducted. Predicted and actual clinical scores were compared using Pearson’s correlation coefficient (r) and normalized mean squared error (Norm. MSE). Permutation test and leave-one-out strategy were applied for results validation. KRR identified fALFF patterns that significantly predicted the hand tremor improvement (r = 0.23, P = 0.025; Norm. MSE = 0.05, P = 0.026) and the postural tremor improvement (r = 0.28, P = 0.025; Norm. MSE = 0.06, P = 0.023), but not action tremor improvement. Lobule VI of right cerebellum (Cerebelum_6_R), right superior occipital gyrus (Occipital_Sup_R) and lobule X of vermis (Vermis_10) contributed most for hand tremor prediction (normalized weights (NW): 2.77%, 2.40%, 2.34%) while Vermis_10, left supplementary motor area (Supp_Motor_Area_L) and right hippocampus (Hippocampus_R) for postural tremor prediction (NW: 2.69%, 2.12%, 2.05%). The low contributing NW of the individual brain regions suggested that the fALFF pattern as a whole is an overall predicting feature. Preoperative fALFF pattern predicts tremor benefits induced by MRgFUS thalamotomy. ClinicalTrials.gov number: NCT04570046.

Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor

Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. ClinicalTrials.gov Identifier NCT04112381.

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS)-Thalamotomy for Essential Tremor: Lesion Location and Clinical Outcomes.

Factors predicting clinical outcomes after MR-guided focused ultrasound (MRgFUS)-thalamotomy in patients with essential tremor (ET) are not well known. To examine the clinical outcomes and their relationship with patients' baseline demographic and clinical features and lesion characteristics at 6-month follow-up in ET patients. A total of 127 patients were prospectively evaluated at 1 (n = 122), 3 (n = 102), and 6 months (n = 78) after MRgFUS-thalamotomy. Magnetic resonance imaging (MRI) was obtained at 6 months (n = 60). Primary outcomes included: (1) change in the Clinical Rating Scale of Tremor (CRST)-A+B score in the treated hand and (2) frequency and severity of adverse events (AEs) at 6 months. Secondary outcomes included changes in all subitems of the CRST scale in the treated hand, CRST-C, axial tremor (face, head, voice, tongue), AEs, and correlation of primary outcomes at 6 months with lesion characteristics. Statistical analysis included linear mixed, standard, and logistic regression models. Scores for CRST-A+B, CRST-A, CRST-B in the treated hand, CRST-C, and axial tremor were improved at each evaluation (P < 0.001). Five patients had severe AEs at 1 month that became mild throughout the follow-up. Mild AEs occurred in 71%, 45%, and 34% of patients at 1, 3, and 6 months, respectively. Lesion volume was associated with the reduction in the CRST-A (P = 0.003) and its overlapping with the ventralis intermedius nucleus (Vim) nucleus with the reduction in CRST-A+B (P = 0.02) and CRST-B (P = 0.008) at 6 months. MRgFUS-thalamotomy improves hand and axial tremor in ET patients. Transient and mild AEs are frequent. Lesion volume and location are associated with tremor reduction. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Real-world Experience of the Safety of Magnetic Resonance Imaging–guided Focused Ultrasound (MRgFUS)-thalamotomy for Essential Tremor (P3-3.008)

Real-world Experience of the Safety of Magnetic Resonance Imaging–guided Focused Ultrasound (MRgFUS)-thalamotomy for Essential Tremor (P3-3.008)

Long‐term outcome following magnetic resonance imaging‐guided focused ultrasound unilateral thalamotomy for medication‐refractory essential tremor

AbstractObjectiveTo investigate the long‐term outcome 5 years after transcranial magnetic resonance imaging‐guided focused ultrasound (MRgFUS) unilateral ventral intermediate nucleus (Vim) thalamotomy for essential tremor (ET), following our interim reports.MethodsThis was a prospective and open‐labeled study involving a single center. Ten medication‐refractory ET patients (8 men and 2 women, aged 67.1 ± 17.5 years, all right‐handed) underwent left MRgFUS Vim thalamotomy. They were assessed using the Clinical Rating Scale for Tremor (CRST) and the overall health and quality of life (QOL) scale of the Quality of Life in Essential Tremor Questionnaire (QUEST). Additionally, we assessed safety issues during the study period.ResultsRight‐hand tremor improved immediately after the procedure in all patients. The right‐hand CRST score remained significantly improved by 60.2% and 33.5% from baseline at both 1‐ and 5‐years post‐treatment, respectively (both p &lt; 0.05). On the other hand, the left‐hand CRST score and the overall QOL score of QUEST showed no improvement. Adverse events during and immediately after the procedure were mild and reversible. We observed no delayed adverse events.ConclusionMRgFUS unilateral Vim thalamotomy is adopted as one of the therapeutic options for intractable ET. Further investigation of the methodology for accurate targeting and sonication is important to improve long‐term outcomes involving a larger number of patients. In addition, not only unilateral but also bilateral Vim thalamotomy may be necessary to achieve a better quality of life.

Dynamic functional changes upon thalamotomy in essential tremor depend on baseline brain morphometry

Patients with drug-resistant essential tremor (ET) may undergo Gamma Knife stereotactic radiosurgical thalamotomy (SRS-T), where the ventro-intermediate nucleus of the thalamus (Vim) is lesioned by focused beams of gamma radiations to induce clinical improvement. Here, we studied SRS-T impacts on left Vim dynamic functional connectivity (dFC, n = 23 ET patients scanned before and 1 year after intervention), and on surface-based morphometric brain features (n = 34 patients, including those from dFC analysis). In matched healthy controls (HCs), three dFC states were extracted from resting-state functional MRI data. In ET patients, state 1 spatial stability increased upon SRS-T (F1,22 = 19.13, p = 0.004). More frequent expression of state 3 over state 1 before SRS-T correlated with greater clinical recovery in a way that depended on the MR signature volume (t6 = 4.6, p = 0.004). Lower pre-intervention spatial variability in state 3 expression also did (t6 = − 4.24, p = 0.005) and interacted with the presence of familial ET so that these patients improved less (t6 = 4.14, p = 0.006). ET morphometric profiles showed significantly lower similarity to HCs in 13 regions upon SRS-T (z ≤ − 3.66, p ≤ 0.022), and a joint analysis revealed that before thalamotomy, morphometric similarity and states 2/3 mean spatial similarity to HCs were anticorrelated, a relationship that disappeared upon SRS-T (z ≥ 4.39, p < 0.001). Our results show that left Vim functional dynamics directly relates to upper limb tremor lowering upon intervention, while morphometry instead has a supporting role in reshaping such dynamics.

Bilateral Radiofrequency Ventral Intermediate Thalamotomy for Essential Tremor

Introduction: With the advent of MR-guided focused ultrasound, the importance of the efficacy and safety of bilateral ventral intermediate (Vim) thalamotomy for essential tremor (ET) has increased. However, reports on bilateral Vim thalamotomy for ET remain scarce. Methods: To review the results and complications of bilateral Vim thalamotomy for the treatment of ET in the upper extremities, we retrospectively analyzed the patients with ET who underwent bilateral Vim thalamotomy with radiofrequency (RF) thermal coagulation. As bilateral simultaneous thalamotomy can cause surgical complications, thalamotomy was performed in stages. The interval between the first and second thalamotomies was 21.3 ± 14.7 months. We evaluated the efficacy using the Clinical Rating Scale for Tremor (CRST) before and after the first and second treatments, respectively. We also evaluated the complications before and after the first and second treatments, respectively. Moreover, we assessed the adverse events. Results: Seventeen patients were included in the study. The mean follow-up period following the second thalamotomy was 29.3 ± 15.0 months. The CRST part A + B scores were 34.9 ± 9.7, 20.8 ± 7.0, and 7.4 ± 6.8 before, following the first (40.4% improvement, p < 0.0001) and second thalamotomies (78.6% improvement, p < 0.0001), respectively. Nine patients presented with prolonged adverse events, including dysarthria, dysgeusia, dysphagia, tongue numbness, unsteady gait, and postural instability at the last available evaluation. All adverse events were mild and did not interfere with the patient’s daily activities. Discussion/Conclusions: Bilateral Vim thalamotomy with RF thermal coagulation was an effective treatment for ET in both upper extremities. Despite most possible complications being mild, additional studies with a larger sample size are required to ensure patient safety.

MRI-guided focused-ultrasound thalamotomy in essential tremor: Immediate and delayed changes in cortico-muscular coherence and cortico-cortical out-strength

ObjectiveDrug-resistant essential tremor (ET) can be treated by Magnetic-Resonance-guided Focused-Ultrasound (MRgFUS) targeted to thalamic ventralis-intermediate nucleus (ViM). We are presenting the results obtained in ET patients by evaluating the cortico-muscular coherence (CMC) and the out-strength among cortical areas. MethodsWe recorded MEG-EMG signals in 16 patients with predominant tremor on the right upper limb. The examination was performed the day before MRgFUS (T0) treatment, 24 hours (T1), and 3-months (T2) after lesioning the left ViM. Normalized CMC (nCMC) and cortico-cortical out-strength among cortical areas were assessed during isometric extension of the right hand. ResultsAccording to the Essential Tremor Rating Assessment Scale, 13 of 16 patients were considered responders. At T1, in the beta-band, nCMC increased in the left hemisphere, namely in the areas directly involved in motor functions. At T2, the nCMC in non-motor areas decreased and the out-strength from other examined cortical areas toward the left motor-area decreased. ConclusionsIn patients positively responding to MRgFUS, the CMC increased in the motor-area of the treated hemisphere immediately after the treatment, while the reorganization of CMC and cortico-cortical out-strength toward the cortical motor area occurred with a delay. SignificanceThe effective treatment with MRgFUS corresponds with a readjustment of the CMC and of the communication between cortical areas.

3D-printed gradient-index phononic crystal lens for transcranial focused ultrasound

Transcranial focused ultrasound (tFUS) shows great promise as a noninvasive tool to treat neurological conditions such as essential tremor. The existing clinical phased array systems are mostly intended for ultrasound delivery to the center of the brain (as in thalamotomy for essential tremor), in addition to being complex and expensive. To seek an alternative focusing approach especially for the brain periphery, we explore a 3D-printed gradient-index (GRIN) lens as a simple and an orders of magnitude more cost-effective approach. The lens is constructed using a phononic crystal (PC) architecture with varying lattice geometry and hence refractive index distribution. Specifically, the lens uses an axisymmetric hyperbolic secant refractive index profile to focus ultrasonic waves generated by a 1 MHz single-element ultrasonic transducer. Finite element simulations are performed to design and analyze the GRIN-PC lens, and to explore the effects of various parameters such as the distance from the skull and the incidence angle. The numerical results are validated experimentally for a 3D-printed lens by scanning the 3D pressure field generated through a temporal bone. This cost-effective approach to tFUS can open new possibilities to 3D print lenses based on patient computed tomography scans for various applications from tissue ablation to neurostimulation.

Treatment-Specific Network Modulation of MRI-Guided Focused Ultrasound Thalamotomy in Essential Tremor

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.

Patient-Reported Outcomes and Predictive Factors following Focused Ultrasound Thalamotomy for Essential Tremor

Introduction: The objectives of this study were to determine long-term patient-reported outcomes with magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET) and to identify risk factors for a poor clinical outcome. Methods: We administered a telephone or mail-in survey to patients who consecutively underwent unilateral MRgFUS thalamotomy for ET at our institution over an 8-year period. Patients were asked to self-report measures of hand tremor improvement, degree of overall postprocedure improvement, activities of daily life, side effects, and willingness to undergo the procedure again. Specific patient characteristics, ultrasound treatment parameters, and postoperative radiological findings from magnetic resonance imaging performed 1 day after the procedure were analyzed, and multivariable linear regression was used to determine if these factors could serve as predictors of clinical outcome. Results: A total of 85 patients were included in this study with a mean follow-up time of 3.0 years (range 2 months to 1 8.4 years). The mean patient-reported improvement in hand tremor at last follow-up was 66%, and 73% of patients reported meaningful change in their overall condition after the procedure. The percentages of patients reporting normal or only minimal limitations with feeding, drinking, and writing ability at last follow-up were 60%, 71%, and 48%, respectively. In the position of their former selves, 89% of patients would again choose to undergo the procedure. Larger lesions were correlated with a higher risk of adverse events. Discussion/Conclusion: While subjective hand tremor improvement declines with time, willingness to undergo the procedure again following MRgFUS thalamotomy for ET remains very high even several years after the procedure.

Technical and operative factors affecting magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: experience from 250 treatments.

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) provides real-time monitoring of patients to assess tremor control and document any adverse effects. MRgFUS of the ventral intermediate nucleus (VIM) of the thalamus has become an effective treatment option for medically intractable essential tremor (ET). The aim of this study was to analyze the correlations of clinical and technical parameters with 12-month outcomes after unilateral MRgFUS thalamotomy for ET to help guide future clinical treatments. From October 2013 to January 2019, data on unilateral MRgFUS thalamotomy from the original pivotal study and continued-access studies from three different geographic regions were collected. Authors of the present study retrospectively reviewed those data and evaluated the efficacy of the procedure on the basis of improvement in the Clinical Rating Scale for Tremor (CRST) subscore at 1 year posttreatment. Safety was based on the rates of moderate and severe thalamotomy-related adverse events. Treatment outcomes in relation to various patient- and sonication-related parameters were analyzed in a large cohort of patients with ET. In total, 250 patients were included in the present analysis. Improvement was sustained throughout the 12-month follow-up period, and 184 (73.6%) of 250 patients had minimal or no disability due to tremor (CRST subscore < 10) at the 12-month follow-up. Younger age and higher focal temperature (Tmax) correlated with tremor improvement in the multivariate analysis (OR 0.948, p = 0.013; OR 1.188, p = 0.025; respectively). However, no single statistically significant factor correlated with Tmax in the multivariate analysis. The cutoff value of Tmax in predicting a CRST subscore < 10 was 55.8°C. Skull density ratio (SDR) was positively correlated with heating efficiency (β = 0.005, p < 0.001), but no significant relationship with tremor improvement was observed. In the low-temperature group, 1-3 repetitions to the right target with 52°C ≤ Tmax ≤ 54°C was sufficient to generate sustained tremor suppression within the investigated follow-up period. The high-temperature group had a higher rate of balance disturbances than the low-temperature group (p = 0.04). The authors analyzed the data of 250 patients with the aim of improving practices for patient screening and determining treatment endpoints. These results may improve the safety, efficacy, and efficiency of MRgFUS thalamotomy for ET.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

The Role of Focused Ultrasound in the Management of Movement Disorders: Insights after 5 Years of Experience.

Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in Essential Tremor: A Comprehensive Lesion Characterization.

Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients. To provide a comprehensive characterization of the radiological, topographical, and volumetric aspects of the tcMRgFUS thalamic lesion, and to quantify how they relate to the clinical outcomes. In this study, clinical and radiological data from forty patients with medically-refractory essential tremor treated with unilateral tcMRgFUS thalamotomy were retrospectively analyzed. Treatment efficacy was assessed with Clinical Rating Scale for Tremor (CRST). Lesions were manually segmented on T1, T2, and susceptibility-weighted images, and 3-dimensional topographical analysis was then carried out. Statistical comparisons were performed using nonparametric statistics. The greatest clinical improvement was correlated with a more inferior and posterior lesion, a bigger lesion volume, and percentage of the ventral intermediate nucleus covered by the lesion; whereas, the largest lesions accounted for the occurrence of gait imbalance. Furthermore, the volume of the lesion was significantly predicted by the number of sonications surpassing 52°C. Here we provide a comprehensive characterization of the thalamic tcMRgFUS lesion including radiological and topographical analysis. Our results indicate that the location and volume of the lesion were significantly associated with the clinical outcome and that mid-temperatures may be responsible for the lesion size. This could serve ultimately to improve targeting and judgment and to optimize clinical outcome of tcMRgFUS thalamotomy.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. NCT01827904. This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Neuroanatomical Correlates of Response to Focused Ultrasound Thalamotomy in Essential Tremor

Abstract INTRODUCTION Essential tremor (ET) is the most common movement disorder. While for the majority of patients medical management has shown to decrease tremor by more than 60%, disabling tremor persists in a significant subset of this population. Recently, MR-guided focused ultrasound (MRgFUS), a non-invasive means to ablate biological tissue, has proven to be a minimally invasive, effective treatment option to achieve thalamotomy. METHODS Sixty-eight patients (mean age 72.6 yr, 72% male) diagnosed with ET undergoing MRgFUS thalamotomy between 2012 and 2018 were included for analysis. Baseline ipsilateral hand and axial tremor scores were compared to 3-mo post-treatment scores. Clinically weighted probabilistic maps were generated to localize areas associated with improvement and decline in ipsilateral hand as well as axial symptoms. White matter tracts and functional connectivity related to these areas were interrogated. RESULTS The probability maps corresponding to the axial or ipsilateral hand tremor improvement phenotypes were similar, occupying a space near the posterior border of the VIM nucleus, at the boundary of the VIM and VC nuclei. The probability map corresponding to worsening of ipsilateral hand tremor was also infringed the posterior border of the VIM nucleus, although relatively medial compared to the improvement-associated maps. The probability map corresponding to axial decline was located more posteriorly relative to the other 3 maps, sharing no overlap with VIM. Compared to our previously published optimal zone for contralateral hand tremor improvement, areas associated with axial or ipsilateral hand tremor abatement demonstrated 53% and 10% overlap with this zone, respectively. In terms of functional connectivity, activity in the dentate nucleus was more closely associated with ipsilateral hand and axial improvement than with decline phenotypes. The decline phenotypes showed greater association with the motor cortex. CONCLUSION These findings can be used to improve ipsilateral hand and axial tremor symptomatology in ET by honing neuromodulatory and neuroablative treatment strategies.