ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) for Treatment of Tremor
ExAblate (Magnetic Resonance-guided Focused Ultrasound Surgery) for Treatment of Tremor
A feasibility Study to Evaluate Safety and Initial Effectiveness of ExAblate Transcranial MR
 Guided Focused Ultrasound for Unilateral Thalamotomy in the Treatment of Tremor
The non-invasive high-intensity focused ultrasound has been coupled with high resolution MRI
 to provide precise, consistent treatments that can be monitored in real-time. The development
 of phased array transducers allows for tightly focused treatment volumes and for the ability
 to compensate for distortions by tissue inhomogeneities. The landmark advance in MRgFUS for
 neurosurgeons occurred as the ability to sonicate through the intact cranium was achieved
 with phased array transducers and acoustic modeling using CT reconstructions of the skull. By
 coupling HIFU with MRI, detailed treatment plans can be generated and intra-procedure
 real-time monitoring is available. Standard MR sequences have been shown to reliably predict
 tissue damage during thermal lesioning with ultrasound. The precision of the technology has
 already been demonstrated in animal models and is currently being investigated in humans with
 brain tumors and neuropathic pain syndromes. Unlike stereotactic radiosurgery, the treatment
 can be monitored continuously in real time with MRI and MR-thermography. We anticipate that a
 MRgFUS non-invasive thermal lesioning is similarly as safe as DBS (or other current procedure
 and will provide several years of benefit through reduction of contralateral motor symptoms
 and potential medication side effects in ET, while still permitting subsequent treatment with
 DBS should that become clinically desirable.
Inclusion Criteria:

 1. Men and women, between 18 and 80 years, inclusive

 2. Patients who are able and willing to give consent and able to attend all study visits

 3. A diagnosis of ET as confirmed from clinical history and examination by a movement
 disorder neurologist

 4. Tremor refractory to adequate trials of at least two medications, one of which should
 be either propranolol or primidone. An adequate medication trial is defined as a
 therapeutic dose of each medication or the development of side effects as the
 medication dose is titrated.

 5. Vim nucleus of thalamus can be target by the ExAblate device. The Vim region of the
 thalamus must be apparent on MRI such that targeting can be performed with either
 direct visualization or by measurement from a line connecting the anterior and
 posterior commissures of the brain.

 6. Able to communicate sensations during the ExAblate MRgFUS treatment

 7. Postural or intention tremor severity score of greater than or equal to 2 in the
 dominant hand/arm as measured by the CRST rating scale.

 8. Stable doses of all medications for 30 days prior to study entry and for the duration
 of the study.

 9. May have bilateral appendicular tremor

 10. Significant disability due to essential tremor despite medical treatment (CRST score
 of 2 or above in any one of the items 16-23 from the Disability subsection of the
 CRST: [speaking, feeding other than liquids, bringing liquids to mouth, hygiene,
 dressing, writing, working, and social activities])

 11. Inclusion and exclusion criteria have been agreed upon by two members of the medical
 team.

 Exclusion Criteria:

 1. Patients with unstable cardiac status including:

 -  Unstable angina pectoris on medication

 -  Patients with documented myocardial infarction within six months of protocol
 entry

 -  Congestive heart failure requiring medication (other than diuretic)

 -  Patients on anti-arrhythmic drugs

 2. Alcohol or drug abuse within the past 6 months

 3. Severe hypertension (diastolic BP > 100 on medication)

 4. Patients with standard contraindications for MR imaging such as non-MRI compatible
 implanted metallic devices including cardiac pacemakers, size limitations, etc.

 5. Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or
 Magnevist) including advanced kidney disease

 6. Severely impaired renal function (estimated glomerular filtration rate < 30ml/min/1.73
 m2) or receiving dialysis

 7. History of abnormal bleeding and/or coagulopathy

 8. 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

 9. Active or suspected acute or chronic uncontrolled infection

 10. History of intracranial hemorrhage

 11. Cerebrovascular disease (multiple CVA or CVA within 6 months)

 12. 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.)

 13. Symptoms and signs of increased intracranial pressure (e.g. headache, nausea,
 vomiting, lethargy, and papilledema)

 14. Untreated, uncontrolled sleep apnea

 15. Are participating or have participated in another clinical trial in the last 30 days

 16. Patients unable to communicate with the investigator and staff.

 17. Presence of any other neurodegenerative disease like parkinson-plus syndromes
 suspected on neurological examination. These include: multisystem atrophy, progressive
 supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease. The presence
 of some mild parkinsonian features will be accepted since ET is recognized to be
 associated with overlap symptoms of PD. The mild PD symptoms that will be tolerated
 for inclusion into the trial include resting tremor, bradykinesia, and rigidity.

 18. Presence of significant cognitive impairment as determined with a score ≤ 24 on the
 Mini Mental Status Examination (MMSE)

 19. History of immunocompromise, including patient who is HIV positive

 20. Known life-threatening systemic disease

 21. Patients with a history of seizures within the past year

 22. Patients with psychiatric illness that are not well controlled. Any presence of
 psychosis will be excluded. Patients with mood disorders including depression will be
 excluded if they have exhibited symptoms within 6 months while on medication. Patients
 who have been treated with transcranial magnetic stimulation or ECT will be excluded.

 23. Patients with risk factors for intraoperative or postoperative bleeding (platelet
 count less than 100,000 per cubic millimeter, PT > 14, PTT > 36 or INR > 1.3) or a
 documented coagulopathy

 24. Patients with brain tumors

 25. Any illness that in the investigator's opinion preclude participation in this study.

 26. Pregnancy or lactation.

 27. Legal incapacity or limited legal capacity.

 28. Patients who have had deep brain stimulation or a prior stereotactic ablation of the
 basal ganglia