MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study
TL;DR: MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor and potentially other disorders are treated.
Abstract: Summary Background Essential tremor is the most common movement disorder and is often refractory to medical treatment. Surgical therapies, using lesioning and deep brain stimulation in the thalamus, have been used to treat essential tremor that is disabling and resistant to medication. Although often effective, these treatments have risks associated with an open neurosurgical procedure. MR-guided focused ultrasound has been developed as a non-invasive means of generating precisely placed focal lesions. We examined its application to the management of essential tremor. Methods Our study was done in Toronto, Canada, between May, 2012, and January, 2013. Four patients with chronic and medication-resistant essential tremor were treated with MR-guided focused ultrasound to ablate tremor-mediating areas of the thalamus. Patients underwent tremor evaluation and neuroimaging at baseline and 1 month and 3 months after surgery. Outcome measures included tremor severity in the treated arm, as measured by the clinical rating scale for tremor, and treatment-related adverse events. Findings Patients showed immediate and sustained improvements in tremor in the dominant hand. Mean reduction in tremor score of the treated hand was 89·4% at 1 month and 81·3% at 3 months. This reduction was accompanied by functional benefits and improvements in writing and motor tasks. One patient had postoperative paraesthesias which persisted at 3 months. Another patient developed a deep vein thrombosis, potentially related to the length of the procedure. Interpretation MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor. If larger trials validate the safety and ascertain the efficacy and durability of this new approach, it might change the way that patients with essential tremor and potentially other disorders are treated. Funding Focused Ultrasound Foundation.
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TL;DR: The longitudinal experience with ablative procedures shows that there remains an important role for accurate, discrete lesions in disrupting affective circuitry in the treatment of TRD, and new modalities, such as MRgFUS, have the potential to further improve the accuracy of ablative Procedures, while enhancing safety by obviating the need for open brain surgery.
Abstract: Background: There is an urgent need to develop safe and effective treatments for patients with treatment-resistant depression (TRD). Several neurosurgical procedu
988 citations
TL;DR: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor and secondary outcome measures assessing disability and quality of life improved with active treatment as compared with the sham procedure.
Abstract: BackgroundUncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. MethodsWe enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label exte...
682 citations
CEU San Pablo University1, University of Marburg2, National and Kapodistrian University of Athens3, Rush University Medical Center4, Toronto Western Hospital5, University of Toronto6, University of Pennsylvania7, Newcastle University8, University of New South Wales9, University of Sydney10, Centre national de la recherche scientifique11, Peking Union Medical College12, Columbia University13, University of Paris14, Aarhus University15, UCL Institute of Neurology16, National Institutes of Health17, Emory University18, San Francisco VA Medical Center19, University of California, San Francisco20, Veterans Health Administration21, Erasmus University Medical Center22, Baylor College of Medicine23, University of Kiel24, Hebrew University of Jerusalem25, University of Barcelona26, Columbia University Medical Center27, McGill University28, University of Alabama at Birmingham29, Northwestern University30, Icahn School of Medicine at Mount Sinai31, University of Perugia32, University of British Columbia33, Vancouver Coastal Health34
TL;DR: This multiple‐author article provides a historical state‐of‐the‐art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease.
Abstract: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.
523 citations
TL;DR: Repeated scanning ultrasound treatments of the mouse brain to remove Aβ, without the need for any additional therapeutic agent such as anti-Aβ antibody, are used and suggest that repeated SUS may be a noninvasive method with potential for treating Alzheimer’s disease.
Abstract: Amyloid-β (Aβ) peptide has been implicated in the pathogenesis of Alzheimer's disease (AD). We present a nonpharmacological approach for removing Aβ and restoring memory function in a mouse model of AD in which Aβ is deposited in the brain. We used repeated scanning ultrasound (SUS) treatments of the mouse brain to remove Aβ, without the need for any additional therapeutic agent such as anti-Aβ antibody. Spinning disk confocal microscopy and high-resolution three-dimensional reconstruction revealed extensive internalization of Aβ into the lysosomes of activated microglia in mouse brains subjected to SUS, with no concomitant increase observed in the number of microglia. Plaque burden was reduced in SUS-treated AD mice compared to sham-treated animals, and cleared plaques were observed in 75% of SUS-treated mice. Treated AD mice also displayed improved performance on three memory tasks: the Y-maze, the novel object recognition test, and the active place avoidance task. Our findings suggest that repeated SUS is useful for removing Aβ in the mouse brain without causing overt damage, and should be explored further as a noninvasive method with therapeutic potential in AD.
399 citations
TL;DR: Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the blood-brain barrier at discrete targets and would offer a flexible means to target therapeutics to desired points or volumes in the brain.
310 citations
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TL;DR: In this paper, the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis were examined.
Abstract: Background Deep-brain stimulation through an electrode implanted in the thalamus was developed as an alternative to thalamotomy for the treatment of drug-resistant tremor. Stimulation is thought to be as effective as thalamotomy but to have fewer complications. We examined the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis. Methods Sixty-eight patients (45 with Parkinson's disease, 13 with essential tremor, and 10 with multiple sclerosis) were randomly assigned to undergo thalamotomy or thalamic stimulation. The primary outcome measure was the change in functional abilities six months after surgery, as measured by the Frenchay Activities Index. Scores for this index can range from 0 to 60, with higher scores indicating better function. Secondary outcome measures were the severity of tremor, the number of adverse effects, and patients' assessment of the outcome. Results Functional status ...
963 citations
University of California, Los Angeles1, Icahn School of Medicine at Mount Sinai2, University of Toronto3, University of Kiel4, University of Rome Tor Vergata5, Oregon Health & Science University6, University of Florida7, Joseph Fourier University8, University of Kansas9, Stanford University10, University College London11, Rush University Medical Center12, Cleveland Clinic13, University of California, San Francisco14, United States Department of Veterans Affairs15, Emory University16
TL;DR: Recommendations are provided to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD) to be considered in a select group of appropriate patients.
Abstract: Objective: To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). Data Sources and Study Selection: An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. Data Extraction and Synthesis: A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. Conclusions: (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients. Arch Neurol. 2011; 68(2):165-171. Published online October 11, 2010. doi:10.1001/archneurol.2010.260
820 citations
TL;DR: Chronic high‐frequency stimulation of the ventral intermedius nucleus of the thalamus is safe and highly effective in ameliorating essential and parkinsonian tremor and measures of function were significantly improved in patients with essential tremor.
Abstract: Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.
488 citations
TL;DR: In this paper, the clinical feasibility of transcranial MRI-guided focused ultrasound surgery (TcMRgFUS) was evaluated and evaluated using a clinical feasibility study, and the results showed that the feasibility of the TcMR gFUS was high.
Abstract: Objective
This work evaluated the clinical feasibility of transcranial MRI-guided focused ultrasound surgery (TcMRgFUS).
488 citations
TL;DR: The purpose is to provide an overview of existing studies, to examine methodologic issues that may account for this tremendous variability in results, and to provide a more precise estimate of the prevalence of ET.
Abstract: Essential tremor (ET) is the most common adult movement disorder, as much as 20 times more prevalent than Parkinson's disease. Estimates of the crude prevalence of ET range widely from 0.08 to 220 cases per 1000 persons, a 2750-fold difference. There has been no formal attempt to synthesize these disparate results. Our purpose is to provide an overview of existing studies, to examine methodologic issues that may account for this tremendous variability in results, and to provide a more precise estimate of the prevalence of ET. Nineteen studies of the prevalence of ET were reviewed. Factors that contribute to the broad range of prevalence estimates include (a) differences in study design that influence validity and (b) differences in characteristics of study populations that influence comparability of studies. If we limit our examination to studies that (a) provided diagnostic criteria for ET, (b) defined ET as an action tremor, and (c) used community-based rather than service-based designs, then five studies remain, and the prevalence of ET is 4.1 to 39.2 cases per 1000, a 9.6-fold difference. Four of these five provided age-stratified data. Among these four, the prevalence of ET in those over the age of 60 years was 13.0 to 50.5 cases per 1000, a 3.9-fold difference.
421 citations