A Clinical Trial for the Safety and Effect of MRGuided FUS Subthalamotomy for Medication Refractory Parkinson's Disease

Exclusion Criteria

• •1. Hoehn and Yahr stage in the ON medication state of 2.5 or greater
• •2. Presence of severe dyskinesia as noted by a score of 3 or 4 on questions 4.1 and 4.2 of the MDS-UPDRS
• •3. Presence of other central neurodegenerative disease suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimer's disease.
• •4. Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications
• •5. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia
• •6. Presence of significant cognitive impairment defined as score ≤ 21 on the Montreal Cognitive Assessment (MoCA)
• •7. Unstable psychiatric disease, defined as active uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation. Subjects with stable, chronic anxiety or depressive disorders may be included provided their medications have been stable for at least 60 days prior to study entry and if deemed appropriately managed
• •8. Subjects with significant depression as determined following a comprehensive assessment. Significant depression is being defined quantitatively as a score of greater than 19 on the Beck Depression Inventory.
• •9. Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the following occurring within the preceding 12-month period:
• •* Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household).
• •* Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use)
• •* Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)
• •* Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).
• •10. Subjects with unstable cardiac status including:
• •* Unstable angina pectoris on medication
• •* Subjects with documented myocardial infarction within six months of protocol entry
• •* Significant congestive heart failure defined with ejection fraction \< 40
• •* Subjects with unstable ventricular arrhythmias
• •* Subjects with atrial arrhythmias that are not rate-controlled
• •11. Severe hypertension (diastolic BP \> 100 on medication)
• •12. History of or current medical condition resulting in abnormal bleeding and/or coagulopathy
• •13. Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure. For anticoagulants with washout period shorter than one week the minimum period of time between stopping this medication and ExAblate procedure will be in accordance with washout time as per official effective medication labeling.
• •14. Subjects with risk factors for intraoperative or postoperative bleeding as indicated by: platelet count less than 100,000 per cubic millimeter, a documented clinical coagulopathy, or INR coagulation studies exceeding the institution's laboratory standard
• •15. Patient with severely impaired renal function with estimated glomerular filtration rate \<30mL/min/1.73m2 (or per local standards should that be more restrictive) and/or who is on dialysis;
• •16. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
• •17. Significant claustrophobia that cannot be managed with mild medication.
• •18. Subject who weigh more than the upper weight limit of the MR table and who cannot fit into the MR scanner
• •19. Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment.
• •20. History of intracranial hemorrhage
• •21. History of multiple strokes, or a stroke within past 6 months
• •22. Subjects with a history of seizures within the past year
• •23. Subjects with malignant brain tumors
• •24. Subjects with lower limbarterial blood flow disorder
• •25. Subjects with intracranial aneurysms requiring treatment or arterial venous malformations (AVMs) requiring treatment.
• •26. Any illness that in the investigator's opinion preclude participation in this study.
• •27. Subjects unable to communicate with the investigator and staff.
• •28. Subject is pregnant or lactating
• •29. Subjects who is enrolled or will be enrolled in clinical study or clinical research
• •30. Subjects who have an Overall Skull Density Ratio of 0.30 or less as calculated from the screening CT