Impact of skull density ratio on efficacy and safety of magnetic resonance–guided focused ultrasound treatment of essential tremor

2020 ◽  
Vol 132 (5) ◽  
pp. 1392-1397 ◽  
Author(s):  
Marissa D’Souza ◽  
Kevin S. Chen ◽  
Jarrett Rosenberg ◽  
W. Jeffrey Elias ◽  
Howard M. Eisenberg ◽  
...  

OBJECTIVESkull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.METHODSIn 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.RESULTSOf 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.CONCLUSIONSMRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohit Agrawal ◽  
Kanwaljeet Garg ◽  
Raghu Samala ◽  
Roopa Rajan ◽  
Vikas Naik ◽  
...  

Background: Magnetic resonance guided focused ultrasound (MRgFUS) is a relatively novel technique to treat essential tremor (ET). The objective of this review was to analyze the efficacy and the safety profile of MRgFUS for ET.Methods: A systematic literature review was done. The post procedure changes in the Clinical Rating Scale for Tremor (CRST) score, hand score, disability and quality of life scores were analyzed.Results: We found 29 studies evaluating 617 patients. DTI based targeting was utilized in six cohorts. A significant difference was observed in the pooled standard mean difference between the pre and postoperative total CRST score (p-value &lt; 0.001 and 0.0002), hand score (p-value 0.03 and 0.02); and the disability at 12 months (p-value 0.01). Head pain and dizziness were the most in procedure complications. The immediate pooled proportion of ataxia was 50%, while it was 20% for sensory complications, which, respectively, declined to 31 and 13% on long term follow up. A significant reduction (p = 0.03) in immediate ataxia related complications was seen with DTI targeting.Conclusion: MRgFUS for ET seems to be an effective procedure for relieving unilateral tremor. Use of DTI based targeting revealed a significant reduction in post procedure ataxia related complications as compared to traditional targeting techniques. Analysis of other complications further revealed a decreasing trend on follow up.


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.


2016 ◽  
Vol 124 (2) ◽  
pp. 411-416 ◽  
Author(s):  
Won Seok Chang ◽  
Hyun Ho Jung ◽  
Eyal Zadicario ◽  
Itay Rachmilevitch ◽  
Tal Tlusty ◽  
...  

OBJECT Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson’s disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS. METHODS The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive-compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined. RESULTS Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r2 = 0.206, y = 64.156 − 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r2 = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate. CONCLUSIONS Some skull-related factors correlated with the maximal target area temperature. Although the number of patients in the present study was relatively small, the results offer information that could guide the selection of MRgFUS candidates.


2021 ◽  
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.


2021 ◽  
pp. 1-9
Author(s):  
Myung Ji Kim ◽  
So Hee Park ◽  
Kyung Won Chang ◽  
Yuhee Kim ◽  
Jing Gao ◽  
...  

OBJECTIVE 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Sheng Wang ◽  
Lin-lin Zhao ◽  
Xin-jian Qiu ◽  
Dong-sheng Wang ◽  
Tao Tang ◽  
...  

Background. The traditional Chinese medicine formula Jiu Wei Zhen Xin Granula (JWZXG) is prescribed to treat generalized anxiety disorder (GAD) in China. This study was to assess the efficacy and safety of JWZXG in patients with GAD. Method. Data were pooled from 14 randomized controlled trials involving the assessment of mean changes of Hamilton Anxiety Rating Scale (HAMA) total scores, response rates, adverse event rates, quality, publication bias, and risk of bias. Results. Pooled analysis showed no significant difference in response rate (risk ratio 1.01, 95% CI [0.93–1.08]; Z test = 0.17, P=0.86) and no significant difference between JWZXG group and azapirones group (RR 0.69, 95% CI [0.45, 1.06]; Z test = 1.69, P=0.09) in rate of adverse events. Though no difference exists between JWZXG group and azapirones group in HAMA total score from baseline, JWZXG group was inferior to selective serotonin reuptake inhibitors (SSRIs) group (WMD −0.93, 95% CI [−1.64, −0.23]; Z test = 2.6, P=0.009) which had more adverse events than JWZXG group (RR 0.64, 95% CI [0.46, 0.89]; Z test = 2.63, P=0.009). Conclusions. This meta-analysis preliminarily suggests that JWZXG is as effective as azapirones, though having the same possibility of suffering AEs. JWZXG was inferior to SSRIs but causes fewer AEs in the treatment of GAD.


2021 ◽  
pp. jnnp-2020-325278
Author(s):  
Raúl Martínez-Fernández ◽  
Sujitha Mahendran ◽  
Jose Angel Pineda-Pardo ◽  
Lukas L Imbach ◽  
Jorge U Máñez-Miró ◽  
...  

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


Neurosurgery ◽  
2019 ◽  
Vol 87 (2) ◽  
pp. 256-265 ◽  
Author(s):  
José Angel Pineda-Pardo ◽  
Daniele Urso ◽  
Raul Martínez-Fernández ◽  
Rafael Rodríguez-Rojas ◽  
Marta del-Alamo ◽  
...  

Abstract BACKGROUND Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.


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