Clinical trial: ExAblate Transcranial MR Guided Focused Ultrasound in the Treatment of Essential Tremor (NCT02037217)

Eligibility criteria:
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:

             1.1 Unstable angina pectoris on medication 1.2 Patients with documented myocardial
             infarction within six months of protocol entry 1.3 Congestive heart failure requiring
             medication (other than diuretic) 1.4 Patients on anti-arrhythmic drugs

          2. Patients 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 a 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).

          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 < 45ml/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 pressue (e.g. headache, nausea, vomiting,
             lethargy, and papilledema)

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

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

         16. 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.

         17. Anyone suspected to have the diagnosis of idiopathic Parkinson"s disease. This
             includes excluding anyone with the presence of parkinsonian features including
             bradykinesia rigidity, or postural instability. Subjects who exhibit only mild resting
             tremor but no other symptoms or signs of PD may be included.

         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 current or a prior history of any psychiatric illness will be excluded.
             Any presence or history of psychosis will be excluded. Patients with mood disorders
             including depression will be excluded. For the purpose of this study, we consider a
             significant mood disorder to include any patient who has:

               -  been under the care of a psychiatrist for over 3 months

               -  taken antidepressant medications for greater than 6 months

               -  has participated in cognitive-behavioral therapy

               -  been hospitalized for the treatment of a psychiatric illness

               -  received transcranial magnetic stimulation

               -  received electroconvulsive therapy

         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
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 80 Years

Patient description (medical language): A 60-year-old man comes to the clinic complaining of hand tremor that started few months ago.  It is most bothering when he wants to drink from a glass or pour from a bottle. He does not smoke, but drinks occasionally. He recently started consuming more alcohol as his tremor subsides somewhat when he drinks small amounts of alcohol.  Family history is significant for similar problems in his mother.  Vital signs are normal and the patient has no other medical conditions.  Neurologic examination shows bilateral tremor in the upper extremities. The diagnosis of essential tremor is confirmed.

Patient description (patient's own words): I'm only a 60 years old man but I already suffer from shaky hands. It started a few months ago, and it really bothers me when I want to pour myself a glass or even while drinking. I don't smoke, but I drink alcohol from time to time. To be honest, I've been drinking a little more lately since it helps me with the shaking. My mom had the same issue when she was my age. The doctor took my vitals, and they were normal. I don't have any other medical issues. I underwent neurological exams and it showed that I’m shaky from both sides. The doctor diagnosed me with essential tremor.

Does the patient match the trial criteria? Entailment