MRI guided Focused Ultrasound (MRgFUS) for essential tremor Michael L. Schwartz, MD, MSc, FRCSC, Neurosurgeon, Professor of Surgery, University of Toronto, m.schwartz@utoronto.ca

The development of MRgFUS has been motivated by the desire to develop less invasive functional neurosurgery

Essential Tremor Background The most common movement disorder Prevalence 0.4 – 5% Essential tremor features Postural (with maintenance of a position) or Kinetic (during voluntary movement) Often familial Often disabling: 15 – 25% retire early, 60% do not apply for promotion May respond to ethanol, primidone, propranolol but often progressive with medication failing and ~1/3 abandoning medication Surgery may be offered to patients with disabling, medication-resistant tremor

Leksell Stereotactic Arc and Frame Movement disorder surgery started to become very common around the world…thanks to the standardization of the procedure The huge advantage is the uniformity of it, and how it standardized the procedure, so surgeons around the world can do the same procedure in the same way. Leksell in action, and it was transported around the world, including to Toronto. Indeed, even today, surgeons in Toronto, ad surgeons in New York, and surgeons in Shanghai perform DBS in more or less a similar fashion. Prof. Lars Leksell Karolinska Institute 1960s Prof. Ronald Tasker, University of Toronto 1960s Leksell Stereotactic Arc and Frame 1949

RF thalamotomy circa 1974 No cross-sectional imaging! Air and iodinated contrast in the ventricles to measure the AC-PC line and see the top of the thalamus. Computer generated “operative template” customizing the S&B atlas. Stimulation mapping to correct for distortions. “…somatosensory data plotted exactly where obtained, fall over the expected location of Vim, 5mm rostral to where they would have been expected from radiological localization of the anterior and posterior commissures.”

Surgical Treatment with DBS Ann neurol 1997;42:292-299

MRI guided Focused Ultrasound (MRgFUS) http://www.insightec.com/contentManagment/uploadedFiles/fileGallery/transcranial_mrgfus_white_paper.pdf

MRI guided Focused Ultrasound (MRgFUS) hemispheric array of 1024 transducers rubber diaphragm cold water circulation transducer array

MRI guided Focused Ultrasound (MRgFUS) Heat maps measured by MRI Heating at the focal point: temporal progression oC Heat maps measured by MRI Parallel to the axis of the beam Perpendicular to the axis of the beam 6 s 13 s 20 s 27 s sonication cooling

MRgFUS Inclusion criteria Age between 18-80 years and able to consent Diagnosis of essential tremor by movement disorder neurologist Tremor refractory to medication: adequate dose or side effects (propranolol, primidone) Stable doses of medication for 30 days prior to treatment Able to communicate during the procedure Clinical Rating Sale for Tremor (CRST) postural or intention tremor = or > 2 (tremor amplitude in cm) disability subsection score = or > 2 (unable to bring food to mouth with one hand = 3)

MRgFUS Exclusion criteria Standard MRI contraindications (pacemaker, size limitations) Allergy to MRI contrast material Inability to lie still or communicate during the procedure Cardiovascular instability (angina, recent infarct, heart failure, hypertension) Cerebrovascular disease (recent stroke) Presence of other neurodegenerative diseases (Parkinson’s +, PSP etc.) Brain tumors Recent seizures (<1yr) Unstable psychiatric disease or cognitive impairment (MMS < 25) Pregnancy or lactation Bleeding disorders Previous DBS or thalamotomy

MRgFUS Study Methods All patients were awake during the procedure and were examined after each sonication. Average of 22.5 sonications across the 4 patients. Nucleus ventralis intermedius was the target One patient reported tingling and numbness at the corner of the mouth and in the index finger at temperatures below 50oC.

Nucleus ventralis intermedius (Vim) Patient 4 October 2012

Patient 4 October 2012

Magnetic Resonance Imaging Guidance Thermal imaging Thermal feedback every 3 to 5 seconds Showing temperature at the focus of sonication

Patient 2 July 2012

Post-treatment Imaging Day 30 Day 1 Day 90 Patient 2 Day 7

CRST (B) pre post

Clinical Rating Scale for Tremor (CRST) Vertical lines are standard deviation around the mean

Mean tremor scores for the dominant (treated arm) only Vertical lines are standard deviation around the mean

Total CRST = Total score on Clinical Rating Scale for Tremor CRST A Dom = Tremor score for dominant (treated) hand only CRST B Dom = Objective disability score on gross and fine motor tasks using the dominant (treated) hand CRST C = Subjective disability secondary to tremor Vertical lines are standard deviation around the mean

Significant improvements in subjective and objective disability. Summary of Results Five patients followed to 3 months All Male, average age 70 (4 Right hand dominant, 1 Left hand dominant) Average duration of illness 17 years All patients trying and failing multiple medications and followed by movement disorder neurologist At 1-month post-op: average 91.5% reduction in tremor score of dominant (treated) arm At 3-months post-op: average 85% reduction Adverse events: numbness in thumb/finger of treated arm (resolved in one and persistent in another patient), gait unsteadiness (resolved) Pre-treatment: all patients unable to write, feed themselves, or dress themselves Significant improvements in subjective and objective disability. All patients able to write, drink from a cup and eat unassisted at 3-months follow-up

Conclusion MRgFUS may offer a non-invasive alternative to standard neurosurgical techniques. The sample is very small but we have treated six patients safely and effectively. From a radiographic perspective, the lesions are indistinguishable from those made by the standard RF method. The treatment has produced a lasting reduction in the tremor of six patients.  

A patient’s story