scholarly journals Two year data from a preliminary study of double lesion site MRgFUS treatment of Essential Tremor targeting the thalamus and the posterior subthalamic area

Author(s):  
Ayesha Jameel ◽  
Wladyslaw Gedroyc ◽  
Dipankar Nandi ◽  
Bryn Jones ◽  
Olga Kirmi ◽  
...  

AbstractBackgroundMR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined.ObjectiveTo assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET.Methods14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24 month data.Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores.ResultsThe mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p<0.001) whilst BFS-NTA worsened by 8.8% (p<0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p<0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p<0.001) reduction from post anterior-VIM/VOP to post-PSA ablation.Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p<0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p=0.001) and non-treated arm (UETTS-NTA) 30.5% (p=0.003). At 24 months residual adverse effects were slight unsteadiness (n=1) and mild hemi-chorea (n=1).ConclusionUnilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adverse event profile.

Neurology ◽  
2019 ◽  
Vol 93 (24) ◽  
pp. e2284-e2293 ◽  
Author(s):  
Casey H. Halpern ◽  
Veronica Santini ◽  
Nir Lipsman ◽  
Andres M. Lozano ◽  
Michael L. Schwartz ◽  
...  

ObjectiveTo 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.MethodsOutcomes 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.ResultsMeasured 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.ConclusionsResults 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.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.


2018 ◽  
Vol 128 (1) ◽  
pp. 202-210 ◽  
Author(s):  
Menashe Zaaroor ◽  
Alon Sinai ◽  
Dorith Goldsher ◽  
Ayelet Eran ◽  
Maria Nassar ◽  
...  

OBJECTIVEThalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation.METHODSPatients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39).RESULTSThirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46–87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2–30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6–24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14–45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13–24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850–23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°–60°C).CONCLUSIONSMRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse events profile of MRgFUS over other surgical approaches for treating tremor with similar efficacy. Large randomized studies are needed to assess prolonged efficacy and safety.


Author(s):  
Kenji Fukutome ◽  
Hidehiro Hirabayashi ◽  
Yosuke Osakada ◽  
Yoshihiro Kuga ◽  
Hideyuki Ohnishi

<b><i>Introduction:</i></b> Essential tremor is the most common movement disorder in adults. Bilateral symptoms are typical; however, bilateral thalamotomy for essential tremor is associated with a high probability of adverse events. We retrospectively investigated the efficacy and safety of staged bilateral ventral intermediate nucleus thalamotomy for refractory essential tremor using magnetic resonance imaging-guided focused ultrasound. <b><i>Methods:</i></b> We enrolled 5 consecutive patients with refractory essential tremor between September 2016 and March 2020. Patients underwent a second operation at least 1 year after the first operation. The second lesion was created asymmetrically to the first lesion. <b><i>Results:</i></b> Mean patient age was 57.6 years, and the mean interval between the 2 operations was 27.8 months. The second lesion center was superior to the first lesion in all patients. The mean baseline, second preoperative, and second postoperative Clinical Rating Scale for Tremor total scores were 63.6, 49.2, and 21.8, respectively. The mean baseline, second preoperative, and second postoperative Clinical Rating Scale for Tremor part C scores were 18.4, 8.2, and 2.6, respectively. One patient had permanent adverse events of slight dysarthria and discomfort in the tongue. No patient experienced dysphagia or cognitive dysfunction after the second operation. Four of the 5 patients were satisfied with the results of the bilateral treatment, including the patient who had permanent adverse events. <b><i>Conclusions:</i></b> Magnetic resonance imaging-guided focused ultrasound is an effective method for bilateral thalamotomy when adhering to the following considerations: (1) asymmetrical lesions are created and (2) sufficient interval (&#x3e;1 year) between operations.


2020 ◽  
Vol 133 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Alon Sinai ◽  
Maria Nassar ◽  
Ayelet Eran ◽  
Marius Constantinescu ◽  
Menashe Zaaroor ◽  
...  

OBJECTIVEThe authors report their experience in treating patients suffering from medication-resistant essential tremor (ET) with MR-guided focused ultrasound (MRgFUS) thalamotomy over a 5-year period.METHODSForty-four ET patients treated with unilateral MRgFUS ventral intermediate nucleus (VIM) thalamotomy were assessed using the Clinical Rating Scale for Tremor (CRST) score and the Quality of Life in Essential Tremor Questionnaire (QUEST) over a 5-year span.RESULTSTremor was significantly improved immediately following MRgFUS in all patients and ceased completely in 24 patients. CRST scores in the treated hand at baseline (median 19; range 7–32, 44 patients) improved by a median of 16 at 1 month (44 patients; p < 0.0001), 17 at 6 months (31 patients; p < 0.0001), 15 at 1 year (24 patients; p < 0.0001), 18 at 2 years (15 patients; p < 0.0001), 19 at 3 years, (10 patients; p < 0.0001), 21 at 4 years (6 patients; p < 0.01), and 23 at 5 years (2 patients, significance not tested). Return of tremor that impacted activities of daily living was reported in 5 patients (11%). QUEST scores showed significant improvement, with median change of 35 points (p < 0.0001; 44 patients) at 1 month, 33 (p < 0.0001; 31 patients) at 6 months, 27 (p < 0.0001; 24 patients) at 1 year, 26 (p < 0.001; 15 patients) at 2 years, 25 (p < 0.001; 10 patients) at 3 years, 33 (p < 0.001; 6 patients) at 4 years, and 28 (significance not tested, 2 patients) at 5 years. Adverse events after the procedure were reversible in all but 5 patients (11%).CONCLUSIONSMRgFUS thalamotomy for ET is an effective and safe procedure that provides long-term tremor relief and improvement in quality of life even in patients with medication-resistant disabling tremor. Additional studies with a larger group of patients is needed to substantiate these favorable results.


2012 ◽  
Vol 117 (1) ◽  
pp. 156-161 ◽  
Author(s):  
Jules M. Nazzaro ◽  
Rajesh Pahwa ◽  
Kelly E. Lyons

Object The goal of this study was to evaluate short- and long-term benefits in quality of life (QOL) after unilateral deep brain stimulation (DBS) for essential tremor (ET). Methods Patients who received unilateral DBS of the ventral intermediate nucleus of the thalamus between 1997 and 2010 and who had at least 1 follow-up evaluation at least 1 year after surgery were included. Their QOL was assessed with the Parkinson Disease Questionnaire-39 (PDQ-39), and ET was measured with the Fahn-Tolosa-Marin tremor rating scale (TRS) prior to surgery and then postoperatively with the stimulation in the on mode. Results Ninety-one patients (78 at 1 year; 42 at 2–7 years [mean 4 years]; and 22 at > 7–12 years [mean 9 years]) were included in the analysis. The TRS total, targeted tremor, and activities of daily living (ADL) scores were significantly improved compared with presurgical scores up to 12 years. The PDQ-39 ADL, emotional well-being, stigma, and total scores were significantly improved up to 7 years after surgery compared with presurgical scores. At the longest follow-up, only the PDQ-39 stigma score was significantly improved, and the PDQ-39 mobility score was significantly worsened. Conclusions Unilateral thalamic stimulation significantly reduces ET and improves ADL scores for up to 12 years after surgery, as measured by the TRS. The PDQ-39 total score and the domains of ADL, emotional well-being, and stigma were significantly improved up to 7 years. Although scores were improved compared with presurgery, other than stigma, these benefits did not remain significant at the longest (up to 12 years) follow-up, probably related in part to changes due to aging and comorbidities.


2018 ◽  
Vol 44 (2) ◽  
pp. E8 ◽  
Author(s):  
Na Young Jung ◽  
Chang Kyu Park ◽  
Won Seok Chang ◽  
Hyun Ho Jung ◽  
Jin Woo Chang

OBJECTIVEAlthough neurosurgical procedures are effective treatments for controlling involuntary tremor in patients with essential tremor (ET), they can cause cognitive decline, which can affect quality of life (QOL). The purpose of this study is to assess the changes in the neuropsychological profile and QOL of patients following MR-guided focused ultrasound (MRgFUS) thalamotomy for ET.METHODSThe authors prospectively analyzed 20 patients with ET who underwent unilateral MRgFUS thalamotomy at their institute in the period from March 2012 to September 2014. Patients were regularly evaluated with the Clinical Rating Scale for Tremor (CRST), neuroimaging, and cognition and QOL measures. The Seoul Neuropsychological Screening Battery was used to assess cognitive function, and the Quality of Life in Essential Tremor Questionnaire (QUEST) was used to evaluate the postoperative change in QOL.RESULTSThe total CRST score improved by 67.3% (from 44.75 ± 9.57 to 14.65 ± 9.19, p < 0.001) at 1 year following MRgFUS thalamotomy. Mean tremor scores improved by 68% in the hand contralateral to the thalamotomy, but there was no significant improvement in the ipsilateral hand. Although minimal cognitive decline was observed without statistical significance, memory function was much improved (p = 0.031). The total QUEST score also showed the same trend of improving (64.16 ± 17.75 vs 27.38 ± 13.96, p < 0.001).CONCLUSIONSThe authors report that MRgFUS thalamotomy had beneficial effects in terms of not only tremor control but also safety for cognitive function and QOL. Acceptable postoperative changes in cognition and much-improved QOL positively support the clinical significance of MRgFUS thalamotomy as a new, favorable surgical treatment in patients with ET.


2021 ◽  
Vol 13 ◽  
Author(s):  
Peihan Wu ◽  
Wei Lin ◽  
Kun Hong Li ◽  
Hui-Chin Lai ◽  
Ming-Tsung Lee ◽  
...  

Background: Essential tremor (ET) is a common movement disorder among elderly individuals worldwide and is occasionally associated with a high risk for mild cognitive impairment and dementia. This retrospective study aimed to determine the clinical outcome of unilateral magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in Chinese patients with ET.Methods: In total, 31 male and 17 female patients with drug-refractory ET were enrolled in this research study from January 2017 to September 2019. The severity of tremor and disability were assessed using the Clinical Rating Scale for Tremor (CRST) within a 2-year follow-up period.Results: The mean age of the participants was 59.14 ± 13.5 years. The mean skull density ratio (SDR) was 0.5 ± 0.1. The mean highest temperature was 57.0 ± 2.4°C. The mean number of sonications was 10.0 ± 2.6. The average maximum energy was 19,710.5 ± 8,624.9 J. The total CRST scores and sub-scores after MRgFUS thalamotomy significantly reduced during each follow-up (p &lt; 0.001). All but four (8.3%) of the patients had reversible adverse events (AEs) after the procedure.Conclusions: MRgFUS had sustained clinical efficacy 2 years after treatment for intractable ET. Only few patients presented with thalamotomy-related AEs including numbness, weakness, and ataxia for an extended period. Most Chinese patients were treated safely and effectively despite their low SDR.


2019 ◽  
Vol 130 (6) ◽  
pp. 1853-1861 ◽  
Author(s):  
Na Young Jung ◽  
Chang Kyu Park ◽  
Minsoo Kim ◽  
Phil Hyu Lee ◽  
Young Ho Sohn ◽  
...  

OBJECTIVERecently, MR-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders, including essential tremor, Parkinson’s disease (PD), and some psychiatric disorders. Thus, clinical applications with this modality have been tried using various targets. The purpose of this study was to determine the feasibility, initial effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of parkinsonian dyskinesia.METHODSA prospective, nonrandomized, single-arm clinical trial was conducted between December 2013 and May 2016 at a single tertiary medical center. Ten patients with medication-refractory, dyskinesia-dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (InSightec) after providing written informed consent. Patients were serially evaluated for motor improvement, neuropsychological effects, and adverse events according to the 1-year follow-up protocol. Primary measures included the changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary measures consisted of neuropsychological batteries and quality of life questionnaire (SF-36). Technical failure and safety issues were also carefully assessed by monitoring all events during the study period.RESULTSUnilateral MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and patients were followed up for more than 6 months. Clinical outcomes showed significant improvements of 32.2% in the “medication-off” UPDRS part III score (p = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as 39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively. These results were accompanied by improvement in quality of life. Among 8 cases, 1 patient suffered an unusual side effect of sonication; however, no patient experienced persistent aftereffects.CONCLUSIONSIn the present study, which marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal lesioning using MRgFUS and certain limitations that are unavoidably associated with incomplete thermal lesioning due to technical issues. Further investigation and long-term follow-up are necessary to validate the use of MRgFUS in clinical practice.Clinical trial registration no.: NCT02003248 (clinicaltrials.gov)


2018 ◽  
Vol 44 (2) ◽  
pp. E4 ◽  
Author(s):  
Nasser Mohammed ◽  
Devi Patra ◽  
Anil Nanda

OBJECTIVEMagnetic resonance–guided focused ultrasound (MRgFUS) is a novel technique that uses high-intensity focused ultrasound to achieve target ablation. Like a lens focusing the sun’s rays, the ultrasound waves are focused to generate heat. This therapy combines the noninvasiveness of Gamma Knife thalamotomy and the real-time ablation of deep brain stimulation with acceptable complication rates. The aim of this study was to analyze the overall outcomes and complications of MRgFUS in the treatment of essential tremor (ET).METHODSA meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was made by searching PubMed, Cochrane library database, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Patients with the diagnosis of ET who were treated with MRgFUS were included in the study. The change in the Clinical Rating Scale for Tremor (CRST) score after treatment was analyzed. The improvement in disability was assessed with the Quality of Life in Essential Tremor Questionnaire (QUEST) score. The pooled data were analyzed by the DerSimonian-Laird random-effects model. Tests for bias and heterogeneity were performed.RESULTSNine studies with 160 patients who had ET were included in the meta-analysis. The ventral intermediate nucleus was the target in 8 of the studies. The cerebellothalamic tract was targeted in 1 study. There was 1 randomized controlled trial, 6 studies were retrospective, and 2 were prospective. The mean number of sonications given in various studies ranged from 11 ± 3.2 to 22.5 ± 7.5 (mean ± SD). The maximum delivered energy ranged from 10,320 ± 4537 to 14,497 ± 6695 Joules. The mean of peak temperature reached ranged from 53°C ± 2.3°C to 62.0°C ± 2.5°C. On meta-analysis with the random-effects model, the pooled percentage improvements in the CRST Total, CRST Part A, CRST Part C, and QUEST scores were 62.2%, 62.4%, 69.1%, and 46.5%, respectively. Dizziness was the most common in-procedure complication, occurring in 43.4%, followed by nausea and vomiting in 26.85% (pooled percentage). At 3 months, ataxia was the most common complication, occurring in 32.8%, followed by paresthesias in 25.1% of the patients. At 12 months posttreatment, the ataxia had significantly recovered and paresthesias became the most common persisting complication, at 15.3%.CONCLUSIONSThe MRgFUS therapy for ET significantly improves the CRST scores and improves the quality of life in patients with ET, with an acceptable complication rate. Therapy with MRgFUS is a promising frontier in functional neurosurgery.


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