MR-Guided Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis

Inclusion Criteria:

• Male or Female aged 18-80 years

• Willing and able to give consent and attend all study visits

• A confirmed diagnosis of medication-refractory, MS-related hand tremor

• No clinical evidence of relapse over 12 months or more before enrollment

• No MRI activity over 3 months or more before enrollment

• Presence of disabling postural or kinetic tremor

• Unsatisfactory tremor response to adequate trials of at least two medications

• Able to communicate sensations during the treatment

• Stable doses of all medications for 30 days prior to and during study

Exclusion Criteria:

• Severe cerebellar dysfunction measured by Scale for the Assessment and Rating ofAtaxia (>35 out of 40)

• Severe weakness or sensory loss in arm contralateral to the side of the brainconsidered for MRgFUS

• Evidence of a superimposed or atypical movement disorder

• Unstable cardiac status such as angina pectoris, congestive heart failure, etc.

• Severe hypertension

• Patients with standard contraindications for MR imaging

• History of abnormal bleeding and/or coagulopathy

• Ischemic or hemorrhagic stroke 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

• Receiving anticoagulant or antiplatelet therapy within one week of focused ultrasoundprocedure or drugs known to increase risk or hemorrhage within one month of MRgFUSsurgery

• Not able or willing to tolerate the required prolonged stationary supine positionduring treatment

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

• Unable to communicate with the investigator and staff

• Presence of neurodegenerative disease or significant cognitive impairment

• Presence of significant cognitive impairment (≤24 on MMSE)

• Uncontrolled major psychiatric disorder or suicidal ideation

• Risk factors for intraoperative or postoperative bleeding or documented coagulopathy

• Presence of brain tumours

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

• Pregnancy or lactation

• Legal incapacity or limited legal capacity

• Deep Brain Stimulation or a prior stereotactic ablation of the basal ganglia

• A history of seizures within the past year