Michael L. Schwartz, MD, MSc, FRCSC, Neurosurgeon,

Professor of Surgery, University of Toronto,

m.schwartz@utoronto.ca

MRI guided Focused Ultrasound(MRgFUS)

for essential tremor

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

The most common movement disorderPrevalence 0.4 – 5%

Essential tremor featuresPostural (with maintenance of a position) orKinetic (during voluntary movement)Often familialOften disabling: 15 – 25% retire early, 60% do not apply for

promotion

May respond to ethanol, primidone, propranololbut often progressive with medication failing and~1/3 abandoning medication

Surgery may be offered to patients with disabling, medication-resistant tremor

Essential Tremor Background

Prof. Ronald Tasker, University of Toronto

1960s

Prof. Lars LeksellKarolinska Institute

1960s

Leksell Stereotactic Arc and Frame1949

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 dataplotted exactly where obtained, fall over the expected location of Vim,5mm rostral to where they would have been expected from radiologicallocalization of the anterior and posterior commissures.”

RF thalamotomy circa 1974

Ann neurol 1997;42:292-299

Surgical Treatment with DBS

http://www.insightec.com/contentManagment/uploadedFiles/fileGallery/transcranial_mrgfus_white_paper.pdf

MRI guided Focused Ultrasound (MRgFUS)

MRI guided Focused Ultrasound (MRgFUS)

hemispheric array of 1024 transducers

rubber diaphragm

transducer arraycold water circulation

6 s 13 s 20 s 27 s

sonication cooling

Heating at the focal point: temporal progression

Perpendicular to

the axis of the

beam

Parallel to the

axis of the beam

Heat maps measured by MRI

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oC

MRI guided Focused Ultrasound (MRgFUS)

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 Inclusion 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 tumorsRecent seizures (<1yr)Unstable psychiatric disease or cognitive impairment (MMS < 25)

Pregnancy or lactationBleeding disorders

Previous DBS or thalamotomy

MRgFUS Exclusion criteria

• 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.

MRgFUS Study Methods

Patient 4October 2012

Nucleus ventralis intermedius (Vim)

Patient 4October 2012

Thermal imagingThermal feedback every 3 to 5 secondsShowing temperature at the focus of sonication

Magnetic Resonance Imaging Guidance

Patient 2July 2012

Day 1

Day 7

Day 30

Day 90

Post-treatment Imaging

Patient 2

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) onlyVertical lines are standard deviation around the mean

Total CRST = Total score on Clinical Rating Scale for TremorCRST A Dom = Tremor score for dominant (treated) hand onlyCRST B Dom = Objective disability score on gross and fine motor tasks using the dominant (treated) handCRST C = Subjective disability secondary to tremor

Vertical lines are standard deviation around the mean

Summary of ResultsFive patients followed to 3 months

All Male, average age 70 (4 Right hand dominant, 1 Left hand dominant)Average duration of illness 17 yearsAll patients trying and failing multiple medications and followedby movement disorder neurologist

At 1-month post-op: average 91.5% reduction in tremor score of dominant (treated) armAt 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