Imaging Study of Tremor Disorders

Study Overview
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Brief Summary
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To explore the pathogenesis underlying tremor in essential tremor (ET) and parkinson disease (PD) as well as the mechanisms of tremor suppression after Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy through multi-model MRI study, and to identify imaging biomarkers for triaging patients for the suitability of MRgFUS thalamotomy and predicting the treatment effectiveness. Essential tremor (ET) and Parkinson disease (PD) are the most prevalent tremor disorders. ET, considered as a pure tremor disease, is characterized by upper limb intention or postural tremor, while PD is characterized by a variety of motor and nonmotor symptoms, among them rest tremor. A number of studies have demonstrated that Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a minimally invasive and effective procedure suitable for medication-refractory tremor in patients with ET and patients with PD. However, the treatment effectiveness is variable among individuals. Therefore, it is important to clarify the pathogenesis of tremor in both ET and PD and the mechanisms of tremor arrest produced by MRgFUS thalamotomy to triage suitable candidates for MRgFUS thalamotomy and predict clinical outcomes. In addition, localization precision and individualized treatment remain to be improved.

Detailed Description
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Patients: Patients with medication-refractory ET and PD were included. Baseline materials, clinical rating scale for tremor (CRST) ,Unified Parkinson Disease Rating Scale (UPDRS), treatment parameters(energy, power, duration time, temperature, target location) , associated adverse effects were recorded. Imaging protocols: T2; T2 Flair; DWI; ESWAN; MRS; 3D ASL 2.0s; 3D-T1; DTI; rs-functional MRI Imaging evaluation: Lesion appearance and volume are measured by T2, T2 Flair, DWI, ESWAN, 3D-T1; ESWAN and MRS manifests the changes of iron deposition and metabolism，respectively; ASL shows regional cerebral blood flow associated with the procedure; DTI demonstrates the destruction of white matter integrity. Rs-functional MRI reflects alterations of resting-state brain activity. Treatment: MRgFUS thalamotomy Follow-up: Baseline (MRI+clinical evaluation); 1-day, 1-week, 1-month, 3-months, 6-months,1-year, 2-years,3-years,4-years, 5-years (MRI+clinical evaluation)

Official Title
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Multimodel Magnetic Resonance Imaging Study of Essential Tremor and Parkinson Disease

Conditions
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Movement Disorders

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age 22 years or older; A diagnosis of ET and PD as confirmed from clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder; Intolerance to side effects of medication or poor response to medication, severe and disabling tremor; Regarding PD patients, the ratio of mean Unified Parkinson Disease Rating Scale (UPDRS) tremor scores to the mean UPDRS postural instability/gait disorder scores equal or greater than 1.5; Able to communicate sensations during the ExAblate TcMRgFUS treatment; All MRI examination performed according to study protocol; Having complete medical history and clinical follow up; Imaging data can be processed. Exclusion Criteria: Subjects with unstable cardiac status; Severe hypertension (diastolic BP > 100 on medication); Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc; Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or Magnevist) including advanced kidney disease; Patient with severely impaired renal function; History of abnormal bleeding and/or coagulopathy; History of immunocompromise including those who are HIV positive; History of intracranial hemorrhage; Cerebrovascular disease (multiple CVA or CVA within 6 months); Subjects with uncontrolled symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema); Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment (can be up to 4 hrs of total table time); Significant claustrophobia that cannot be managed with mild medication; Presence of any other neurodegenerative disease such as Parkinson-plus syndromes suspected on neurological examination; Presence of significant cognitive impairment; Subjects with life-threatening systemic disease; Subjects with a history of seizures within the past year; Subjects with presence or history of psychosis. -

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the hand tremor score from baseline to 1 year after treatment | The change in the hand tremor score derived by summing eight items of the Clinical Rating Scale for Tremors (CRST) that evaluate hand tremor and ability to perform tasks will be evaluated for movement disorders subjects. Comparison will be performed from examinations at baseline and 1-year post-treatment. | 5 years | 
| Adverse Events assessed by Significant Clinical Complications | Adverse Events will be evaluated using Significant Clinical Complications for movement disorders subjects. Adverse Events will be reported and categorized by investigators as definitely, probably, possibly, or unrelated to the device or procedure and categorized by treatment group / treatment arm. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in total Clinical Rating Score for Tremor from baseline to 1 year after treatment | The change in total Clinical Rating Score for Tremor will be evaluated for movement disorders subjects. Comparison will be performed from examinations at baseline and 1-year post-treatment. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential tremor, Parkinson disease, MRgFUS, Multimodel MRI