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

BACKGROUND: Factors predicting clinical outcomes after MR-guided focused ultrasound (MRgFUS)-thalamotomy in patients with essential tremor (ET) are not well known. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Unilateral Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy Thalamotomy for Essential Tremor.

BACKGROUND: Essential tremor (ET) affects numerous adults, impacting quality of life (QOL) and often defying pharmacological treatment. Surgical interventions like deep brain stimulation (DBS) and lesional approaches, including radiofrequency, gamma-knife radiosurgery, and magnetic resonance imaging (MRI)-guided focused ultrasound, offer solutions but are not devoid of limitations. OBJECTIVES: This retrospective, single-center, single-blinded pilot study aimed to assess the safety and efficacy of unilateral MRI-guided laser interstitial thermal therapy (MRIg-LITT) thalamotomy for medically intractable ET. METHODS: Nine patients with ET, unresponsive to medications and unsuitable for DBS, underwent unilateral MRIg-LITT thalamotomy. We assessed tremor severity, QOL, cognitive function, and adverse events (AE) over a 12-month period. RESULTS: Tremor severity significantly improved, with a reduction of 83.37% at 12 months post-procedure. QOL scores improved by 74.60% at 12 months. Reported AEs predominantly included transient dysarthria, proprioceptive disturbances, and gait balance issues, which largely resolved within a month. At 3 months, 2 patients (22%) exhibited contralateral hemiparesis requiring physiotherapy, with 1 patient (11%) exhibiting persistent hemiparesis at 12 months. No significant cognitive impairment was detected post-procedure. CONCLUSIONS: Unilateral MRIg-LITT thalamotomy yielded substantial and enduring tremor alleviation and enhanced QOL in patients with ET that is resistant to medication. The AE profile was acceptable. Our findings support the need for additional research with expanded patient cohorts and extended follow-up to corroborate these outcomes and to refine the role of MRIg-LITT as a targeted and minimally invasive approach for ET management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor.

BACKGROUND: There remains high variability in clinical outcomes when the same magnetic resonance image-guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD). OBJECTIVE: Our goal is to refine the MRgFUS thalamotomy target for TDPD versus ET. METHODS: We retrospectively performed voxel-wise efficacy and structural connectivity mapping using 3-12-month post-procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24-hour T1-weighted post-MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients. RESULTS: The post-MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (ppermute < 0.05), with peak TDPD improvement (87%) at x = -13.5; y = -15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder-specific voxel-wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R2 = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R2 = 0.53; P = 0.025-voxel analysis). CONCLUSION: We demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Stepwise dual-target magnetic resonance-guided focused ultrasound in tremor-dominant Parkinson disease: One-year follow-up.

BACKGROUND AND PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) is a nonsurgical treatment for Parkinson disease (PD). Some selected anatomical structures can be targeted by MRgFUS in PD. However, there is no uniform target yet. We have reported that stepwise dual-target MRgFUS was successfully applied to treat refractory tremors with akinetic-rigid features in PD. It generated two precise thermal ablations in the ventral intermediate nucleus (VIM) and pallidothalamic tract (PTT). Here, we report more PD patients to verify the safety and efficacy of stepwise dual-target MRgFUS. METHODS: Ten tremor-dominant PD patients (mean age = 66.7 ± 3.2 years, eight men) received the stepwise dual-target MRgFUS treatment with a series of primary and secondary outcome measures. The VIM and PTT were navigated based on brain magnetic resonance images. Outcome measures were categorized into primary and secondary assessments. The primary outcome measures consisted of resting tremor, action/kinetic tremor, rigidity, and bradykinesia. Secondary outcome measures encompassed non-motor symptoms scale of PD. Data collected at follow-up time points, including 1 day, 3 months, 6 months, and 1 year posttreatment, were compared with baseline data. RESULTS: The severity of tremor and motor deficits represented by Clinical Rating Scale for Tremor parts A and B during off-medication status and Unified Parkinson's Disease Rating Scale III on the treated side were significantly improved (p < 0.05 by paired t-test) at 1-year follow-up. At the 1-year follow-up, significant improvement was observed in the non-motor symptoms scale. Additionally, no severe adverse effects were reported, except temporary treatment-related discomfort during the procedure. CONCLUSIONS: In conclusion, stepwise dual-target MRgFUS emerges as a safe and effective therapeutic modality for PD patients, particularly in addressing medication-refractory tremor and akinetic-rigid syndrome.

Radiosurgical thalamotomy for the management of tremors: a systematic review and meta-analysis.

Medical treatment for tremors may include beta-blockers, primidone, dopaminergic, and anticholinergic drugs but it frequently leads to pharmacoresistance. Therefore, surgical treatment gained relevance as an alternative for those patients.We aim to evaluate radiosurgical thalamotomy as an effective and safe alternative to manage tremors. Pubmed (MEDLINE), Embase, Web of Science, and the Cochrane Library databases were systematically searched for potential articles that evaluated radiosurgical thalamotomy for the management of tremor. Our analysis included 12 studies with 545 patients, 226 of whom were female. Of these, 64.6% of patients were diagnosed with essential tremor (ET), 34.6% with Parkinson's disease (PD), and 0.8% with both ET and PD. The FTM-TRS global score (MD -5.46; 95% CI [-10.44]-[-0.47]; I2 = 52%) and the drawing (MD -1.40; 95% CI [-2.03]-[-0.76]; I2 = 93%), drinking (MD -1.60; 95% CI [-1.82]-[-1.37]; I2 = 40%), and writing (MD -1.51; 95% CI [-1.89]-[-1.13]; I2 = 89%) grades showed significantly lower mean differences, favoring radiosurgical thalamotomy. A pooled proportion of 12% presented with tremor unchanged, while 38% presented with total elimination of tremor. Adverse events included: major paresis, minor paresis, dysarthria, and numbness. Thus, radiosurgical thalamotomy is a safe alternative for tremors resistant to medication, particularly in high-risk patients for RF or DBS procedures. The recommended dose of 130 to 150 Gy is effective and well-tolerated. However, randomized controlled trials (RCTs) are needed to understand the unpredictability of tissue response to radiation.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in Fahr's Disease: Case Report.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy effectively treats medication-resistant essential tremor (ET). Usually, intracranial calcifications are excluded as no-pass zones because of their low penetrability which may limit the effectiveness of treatment and lead to unintended side effects. This case report illustrates the efficacy of unilateral MRgFUS for tremor control in a patient with extensive basal ganglia calcifications due to Fahr's disease. CASE PRESENTATION: A 69-year-old right-handed male with debilitating Fahn-Tolosa-Marin grade 3-4 bilateral hand tremor underwent unilateral left MRgFUS thalamotomy. The treatment involved careful preoperative planning to accommodate his extensive basal ganglia calcifications, element path consideration, and skull density ratio to ensure accurate and effective lesioning. Posttreatment, the patient exhibited complete abolition of tremor on the treated side with minor transient dysarthria and imbalance. Follow-up at 12 weeks posttreatment showed sustained tremor relief and an absence of any adverse effects, validating the procedural adjustments made to accommodate the unique challenges posed by his intracranial calcifications. CONCLUSION: MRgFUS can be safely and effectively applied in certain patients with extensive basal ganglia calcifications - in this case, due to Fahr's disease. This case report suggests expanding the application of MRgFUS to patients with extensive intracranial calcifications who previously might not have been considered suitable candidates for MRgFUS.

Hand Dystonia after Focused Ultrasound Thalamotomy in Essential Tremor.

INTRODUCTION: Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im). CASE PRESENTATION: MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia. CONCLUSION: This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.

Magnetic resonance-guided focused ultrasound ventral intermediate thalamotomy for Tremor-Dominant Parkinson's disease: a systematic review and meta-analysis.

INTRODUCTION: Tremor-dominant Parkinson's Disease (TDPD) has a slower neurological decline compared to other phenotypes of the disease, but significantly impacts daily activities and is often less responsive to standard medications. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) lesioning of the Ventral Intermediate (VIM) nucleus of the thalamus may alleviate symptoms for these patients. METHODS: A systematic review and meta-analysis of English-language studies from PubMed, Cochrane, and Embase were conducted, assessing the efficacy and safety of MRgFUS VIM thalamotomy in TDPD patients. Tremor scores were evaluated using the Clinical Scale Rating for Tremor and the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRSIII). Neuropsychological outcomes were measured using the Parkinson Disease Questionnaire (PDQ) and the Montreal Cognitive Assessment. This analysis adhered to Cochrane and PRISMA guidelines. RESULTS: Thirteen studies with 211 patients were included. MDS-UPDRSIII scores showed significant improvement at 1, 6, and 12 months post-MRgFUS, respectively: (MD -8.92 points, 95% CI: -15.44 to -2.40, p < 0.01; MD -7.39 points, 95% CI: -11.47 to -3.30, p < 0.01; MD -10.66 points, 95% CI: -16.89 to -4.43, p < 0.01). PDQ scores at baseline compared to 6 months post-treatment also indicated a significant improvement (SMD - 0.86, 95% CI: -1.21 to -0.50, p < 0.01). Neurological adverse events were generally mild and transient, with gait instability and sensory deficits being the most common. CONCLUSION: This meta-analysis demonstrates significant improvements in tremor and neuropsychological outcomes following MRgFUS VIM thalamotomy in TDPD patients, with adverse events being typically mild and transient.

Brain targeting for focused ultrasound essential tremor ablation: proceedings from the 2023 Focused Ultrasound Foundation workshop.

Essential tremor (ET) is the most common movement disorder globally and has negative impacts on quality of life. While medical treatments exist, approximately 50% of patients have tremor that is refractory to medication or experience intolerable medication side effects. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an option for these patients and while incisionless, it is still invasive, although less so than other surgical treatments such as deep brain stimulation and radiofrequency thalamotomy. Despite MRgFUS being FDA-approved since 2016, there is still no current consensus on the best approaches for targeting, imaging, and outcome measurement. A 2-day workshop held by the Focused Ultrasound Foundation in September of 2023 convened experts and critical stakeholders in the field to share their knowledge and experiences. The goals of the workshop were to determine the optimal target location within the thalamus and compare best practices for localizing the target and tracking patient outcomes. This paper summarizes the current landscape, important questions, and discussions that will help direct future treatments to improve patient care and outcomes.

Stereotactic robot-assisted MRI-guided laser interstitial thermal therapy thalamotomy for medically intractable Holmes tremor: a pilot study and literature review.

OBJECTIVE: Holmes tremor (HT) is a complex syndrome characterized by resting, postural, and kinetic tremors. HT significantly impacts patients' quality of life (QOL) and daily activities. Conventional pharmacological treatments for HT often yield inconsistent results. Emerging surgical treatments such as deep brain stimulation and various thalamotomy techniques show promise but come with challenges, including adverse events (AEs) and potential tremor recurrence. This study aimed to evaluate the clinical outcomes of unilateral MRI-guided laser interstitial thermal therapy (MRIgLITT) thalamotomy in patients with medically intractable HT, focusing on tremor reduction, QOL, and AE incidence, and provide a comprehensive review of the literature on thalamotomy techniques for HT. METHODS: Five patients with medically intractable HT underwent unilateral MRIgLITT thalamotomy between June 2020 and January 2023. Tremor severity was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) at baseline and at 3 and 12 months postoperatively. QOL was measured using the Quality of Life in Essential Tremor (QUEST) questionnaire and 39-item Parkinson's Disease Questionnaire (PDQ-39). Subjective patient-rated improvement was evaluated using the Patient Global Impression of Clinical Status (PGI-C) scale at 12 months. Cognitive performance was assessed using the Mini-Mental State Examination (MMSE) before the procedure and at 12 months postoperatively. AEs were monitored throughout the follow-up period. RESULTS: The mean patient age was 50.2 ± 22.37 years, with a mean tremor duration of 5.8 ± 4.55 years. Significant tremor reduction was observed in the treated hand, with mean TRS scores decreasing from 19.00 ± 4.36 at baseline to 11.20 ± 4.44 (p = 0.043) at 3 months and 13.40 ± 5.94 (p = 0.042) at 12 months, indicating a relative reduction of 41.05% and 29.47%, respectively. A significant effect was observed on the QUEST scale at 3 months (p = 0.043), but this effect was no longer present at 12 months. No significant effect was found on the PDQ-39 QOL scale. The PGI-C scale showed a high mean subjective improvement of 88.60% ± 8.36% at 12 months. One patient experienced severe AEs, including dysarthria, hemiparesis, and swallowing difficulties, which required prolonged hospitalization and multidisciplinary rehabilitation, but regressed within 3 months. Cognitive performance, as measured by the MMSE, remained stable (p = 0.785). CONCLUSIONS: Unilateral MRIgLITT thalamotomy showed promise as a treatment for medically intractable HT, providing significant tremor reduction with a favorable safety profile. However, the potential for tremor recurrence and minimal functional improvement in fine motor skills highlight the need for long-term follow-up and further research. Larger, multicenter studies are necessary to validate these findings.

Minimum and early high-energy sonication protocol of MR-guided focused ultrasound thalamotomy for low-skull density ratio patients with essential tremor and Parkinson's disease.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless neurosurgical treatment for patients with medically refractory essential tremor and tremor-dominant Parkinson's disease. A low skull density ratio (SDR) < 0.40 is a known risk factor for treatment failure. The aim of this study was to identify useful sonication strategies for patients with a low SDR < 0.40 by modifying the standard sonication protocol using maximum high-energy sonication while minimizing the number of sonications. METHODS: The authors retrospectively analyzed the effects of modified MRgFUS sonication on low-SDR tremor patients. All patients underwent head CT scans to calculate their SDR. The SDR threshold for MRgFUS thalamotomy was 0.35. The patients in the early series underwent the standard sonication protocol targeting the ventral intermediate nucleus contralateral to the treated hand side. The patients with a low SDR < 0.40 in the late series underwent a modified sonication protocol, in which the number of alignment sonications was minimized and high-energy treatment sonication (> 36,000 J) was used. The authors evaluated the lesion volume the following day and tremor improvement and adverse events 3 and 12 months after the procedure. The sonication patterns between low-SDR patients treated using different sonication protocols were examined using Fisher's exact test. ANOVA was used to examine the lesion volume and tremor improvement in high- and low-SDR patients treated using different sonication protocols. RESULTS: Among 41 patients with an SDR < 0.40, 14 underwent standard sonication and 27 underwent modified sonication. Fewer alignment sonications and high-energy treatment sonications were used in the modified sonication group compared with the standard group (p < 0.001). The duration of modified sonication was significantly shorter than that of standard sonication (p < 0.001). The lesion volume and tremor improvement significantly differed among the high- and low-SDR groups with different sonication protocols (p < 0.001). Low-SDR patients treated using modified sonication protocols had comparable lesion volume and tremor improvement to the high-SDR group. The modified sonication protocol did not significantly increase adverse intraprocedural and postprocedural events. CONCLUSIONS: Minimizing alignment sonications and applying high-energy sonication in early treatment help to create an optimal lesion volume and control tremor in low-SDR patients.

3-T MR-guided focused ultrasound thalamotomy for tremor in patients with a cardiac pacemaker: case series and review of the literature.

MR-guided focused ultrasound (MRgFUS) has proven its efficacy and safety for the treatment of essential tremor (ET) and/or Parkinson's disease (PD). However, having a cardiac pacemaker has been considered an exclusion criterion for the use of MRgFUS. Only 2 patients with a cardiac pacemaker treated with MRgFUS have been previously reported, both treated using 1.5-T MRI. In this paper, the authors present their experience performing 3-T MRgFUS thalamotomy in 4 patients with an implanted cardiac pacemaker. Treatments were uneventful regarding complications or severe side effects. MRgFUS using 3-T MRI was found to be an efficient and safe treatment for ET and/or PD in patients with an MRI-compatible pacemaker.

Unilateral gamma knife thalamotomy for tremor safety and efficacy in multimodal assessment: a prospective case-control study with two-year follow-up.

INTRODUCTION: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND: 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. OBJECTIVES: To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. METHODS: 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. RESULTS: 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. CONCLUSIONS: MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.

Limb Preference Changes after Focused-Ultrasound Thalamotomy for Tremor.

BACKGROUND: Magnetic resonance-guided focused-ultrasound (MRgFUS) thalamotomy is an effective treatment for essential and other tremors. It targets the ventrointermedius (Vim) nucleus, which is the thalamic relay in a proprioceptive pathway, and contains kinesthetic cells. Although MRgFUS thalamotomy reduces some risks associated with more invasive surgeries, it still has side effects, such as balance and gait disturbances; these may be caused by the lesion impacting proprioception. OBJECTIVES: Our aim was to quantitatively measure the effects of MRgFUS on proprioception and limb use in essential tremor patients. We hypothesized that this thalamotomy alters proprioception, because the sensorimotor Vim thalamus is lesioned. METHODS: Proprioception was measured using the Kinarm exoskeleton robot in 18 patients. Data were collected pre-operatively, and then 1 day, 3 months, and 1 year after surgery. Patients completed four tasks, assessing motor coordination and postural control, goal-directed movement and bimanual planning, position sense, and kinesthesia. RESULTS: Immediately after surgery there were changes in posture speed (indicating tremor improvement), and in bimanual hand use, with the untreated limb being preferred. However, these measures returned to pre-operative baseline over time. There were no changes in parameters related to proprioception. None of these measures correlated with lesion size or lesion-overlap with the dentato-rubro-thalamic tract. CONCLUSIONS: This is the first quantitative assessment of proprioception and limb preference following MRgFUS thalamotomy. Our results suggest that focused-ultrasound lesioning of the Vim thalamus does not degrade proprioception but alters limb preference. This change may indicate a required "relearning" in the treated limb, because the effect is transient. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A phase 1 open-label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy.

OBJECTIVE: Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open-label, single-center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment-refractory epilepsy. METHODS: Two adult subjects with treatment-refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy. RESULTS: The patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure-free at 12 months, and in the second patient, the frequency reduced from 90-100 seizures per month to 3-6 seizures per month. SIGNIFICANCE: This is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment-refractory focal onset epilepsy.

Stereotactic Staged Asymmetric Bilateral Radiofrequency Lesioning for Parkinson's Disease.

INTRODUCTION: Parkinson's disease (PD) is one of the most common neurodegenerative progressive disorders. Despite the dominance of neurostimulation technology, stereotactic lesioning operations play a significant role in the treatment of PD. The aim of the study was to evaluate the effectiveness and safety of staged bilateral asymmetric radiofrequency (RF) stereotactic lesioning in a highly selected group of PD patients. MATERIAL AND METHODS: A retrospective review of 418 consecutive patients undergoing stereotactic ablation for advanced PD at our institution revealed 28 patients who underwent staged asymmetric bilateral ablation. In this subset, after initial RF thalamotomy, contralateral pallidotomy was performed in 16 (57.1%) patients (group Vim-GPi), and contralateral lesion of the subthalamic nucleus (STN) was performed in 12 (32.9%) patients (group Vim-STN). The mean duration of disease before the first surgery was 9.9 ± 0.8 years. The mean interval between the two operations was 3.5 ± 0.4 years (range, 1-10 years); in the Vim-GPi group, it was 3.1 ± 0.4 years; and in the Vim-STN group, it was 4.3 ± 0.1 years. After the second operation, the long-term follow-up lasted from 1 to 8 years (mean 4.8 ± 0.5 years). All patients were evaluated 1 year after the second operation. RESULTS: One year after staged bilateral lesioning, the mean tremor score improved from baseline, prior to the first operation, from 19.8 to 3.8 (improvement of 81%), the overall mean rigidity score improved from 11.0 to 3.7 (improvement of 66%), and hypokinesia improved from 14.8 to 8.9 (improvement of 40%). One year after staged bilateral lesioning, the total UPDRS score improved in the Vim-GPi group by 47% in the OFF and 45.9% in the ON states. In the Vim-STN group, the total UPDRS score improved from baseline, prior to the first operation, by 44.8% in the OFF and 51.6% in the ON states. Overall, levodopa dose was reduced by 43.4%. Neurological complications were observed in 4 (14.3%) cases; among them, 1 (3.6%) patient had permanent events related to local ischemia after pallidotomy. CONCLUSION: Staged asymmetric bilateral stereotactic RF lesioning can be a safe and effective method in highly selected patients with advanced PD, particularly where deep brain stimulation is not available or desirable. Careful identification and selection of patients for ablative surgery allow achieving optimal results in the treatment of PD with bilateral symptoms.

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.

Hemorrhagic Safety of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor without Interruption of Antiplatelet or Anticoagulant Therapy.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies. METHODS: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. RESULTS: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. CONCLUSION: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.

Gait Function after High-Intensity Focused Ultrasound Thalamotomy for Essential Tremor: Searching for Technique Optimization.

INTRODUCTION: Essential tremor (ET) is one of the most prevalent movement disorders in adults and may be highly disabling for some. Magnetic resonance image-guided high-intensity focused ultrasound (MRIgFUS) has been shown to control tremor efficaciously and with acceptable risk. To date, paresthesia and ataxia are the most common adverse effects (AE). Nevertheless, the impact of MRIgFUS thalamotomy on balance is not well established. METHODS: Thirty-two patients underwent MRIgFUS for ET and completed 6 months of follow-up. Tremor severity and functional disability were assessed using the Essential Tremor Rating Scale and the Quality of Life in Essential Tremor Questionnaire. The Berg Balance Scale (BBS) was applied to objectively measure balance status. RESULTS: All treatments were successful. The sonication target was 1-2 mm above the depth of the intercommissural line. Procedures lasted less the 2 h, with an average of 8 sonications per patient. Twenty-four patients were included in the tremor analysis. The hand tremor score was improved by 76% after 6 months of follow-up and 87% of patients self-reported marked improvement (≥75%). Disability scores showed marked improvement (78%), leading to a significant improvement in quality of life. At the final follow-up, 48% of the patients reported no side effects. When present, AE were generally transient and were considered mild in 96% of affected patients. Paresthesia and subjective feeling of unsteadiness were the most common persistent complaints (23% and 20%, respectively). Regarding objective ataxia, BBS scores remained stable throughout follow-up for most patients. Only 2 patients suffered a mild worsening of balance although no patients experienced moderate or severe ataxia. CONCLUSIONS: Subjective feeling of unsteadiness is one of the most frequent AE after MRIgFUS, although objective ataxia is infrequent and mild. Selecting the most appropriate lesion location and procedural parameters should increase treatment benefits while reducing side effects.