ExAblate Transcranial MRgFUS for the Management of Treatment-Refractory Movement Disorders

A Feasibility Clinical Trial of the Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for the Management of Treatment-Refractory Movement Disorders

The proposed study is to evaluate the effectiveness of ExAblate Transcranial MRgFUS as a tool for creating a unilateral lesion in the Vim thalamus or the globus pallidus (GPi) in patients with treatment-refractory symptoms of movement disorders.

The purpose of this study is to evaluate the safety and initial effectiveness of MRI-guided focused ultrasound thermal ablation of a designated area in the brain of patients suffering from movement disorder symptoms:

• FUS under MRI-guidance and MRI-based thermometry can be safely delivered to patients suffering from treatment-refractory movement disorders through an intact human skull with a low risk of transient adverse effects as evaluated during follow-up of up to 12-months.
• A pre-defined target volume inside the brain can be accurately ablated, as demonstrated on post-treatment MRI.
• Lesions generated with ExAblate Neuro will result in clinical effects that are similar to those seen with ablative procedures using other surgical techniques (e.g. RF procedure).

Inclusion Criteria:

• Men and women, between 18 and 85 years, inclusive.

• Subjects who are able and willing to give consent and able to attend all study visits.

• A movement disorder symptom that has been deemed treatment-refractory by a movement disorder neurologist, including:

  o akathisia, akinesia, athetosis, bradykinesia, chorea, dystonia, tremor, myoclonus, dyskinesia, spasms, tics

• Medication-refractoriness as determined by an adequate dose and duration of standard movement disorders treatment as determined by a specialist neurologist (e.g. a trial of primidone and propranolol for ET)

• Able to communicate sensations during the ExAblate Neuro treatment

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

Exclusion Criteria:

• 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

• Severe hypertension (diastolic BP > 100 on medication)

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

• History of abnormal bleeding and/or coagulopathy (including deep venous thrombosis)

• Cerebrovascular disease (multiple CVA or CVA within 6 months)

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

• Untreated, uncontrolled sleep apnea

• Active or suspected acute or chronic uncontrolled infection

• History of intracranial hemorrhage

• Individuals who are not able or willing to tolerate the required prolonged stationary supine position during treatment

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

• Patients unable to communicate with the investigator and staff.

• Presence of any other neurodegenerative disease like multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease.

• Patients with a history of seizures within the past year

• Patients with psychiatric illness that are not well controlled. Any presence of psychosis will be excluded.

• Patients with risk factors for intraoperative or postoperative bleeding (platelet count less than 100,000 per cubic millimeter) or a documented coagulopathy

• Patients with brain tumors

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

• Pregnancy or lactation.

• Patient is unable to provide his own consent for any reason.

• Legal incapacity or limited legal capacity.

• Patients who have DBS or a prior stereotactic ablation of the basal ganglia

• History of immunocompromise, including patient who is HIV positive

• Known life-threatening systemic disease