FUS ET
(2016)Objective
To evaluate the efficacy and safety of MRI-guided focused ultrasound thalamotomy for medication-refractory essential tremor.
Study Summary
• Benefits in tremor control and quality of life persisted at 12 months
• Common side effects included sensory disturbances and gait imbalance
Intervention
Randomized, double-blind, sham-controlled trial comparing unilateral MRI-guided focused ultrasound thalamotomy vs. sham procedure in 76 patients with essential tremor across 8 international centers; patients followed through 12 months
Inclusion Criteria
• Moderate-to-severe hand tremor (CRST ≥2)
• Disability score ≥2 on CRST Part C
• Failed ≥2 medications including one first-line (propranolol or primidone)
• Stable medications for ≥30 days
• MMSE ≥24 and PHQ-9 <20
• Skull density ratio ≥0.45
Study Design
Arms: Focused ultrasound thalamotomy, Sham procedure
Patients per Arm: 56 (active), 20 (sham)
Outcome
• Disability score improvement: −10.3 points (P<0.001)
• QUEST quality of life score improved by 46% vs. 3% in sham (P<0.001)
Bottom Line
MRI-guided focused ultrasound thalamotomy significantly reduced hand tremor by 47% at 3 months compared to sham procedure in patients with medication-refractory essential tremor, with sustained benefit at 12 months (40% improvement). The procedure also improved disability and quality of life but was associated with sensory disturbances (38%) and gait disturbances (36%), most of which resolved by 12 months.
Major Points
- First randomized, sham-controlled trial of MRI-guided focused ultrasound thalamotomy for essential tremor
- Hand tremor scores improved by 8.3 points more in thalamotomy group compared to sham at 3 months (P<0.001)
- Benefits sustained at 12 months with 40% improvement from baseline in hand tremor
- Significant improvements in disability (62% reduction) and quality of life (46% improvement) compared to sham
- Unilateral procedure targeting the VIM thalamus with real-time MRI guidance and thermometry
- Common adverse events: paresthesias/numbness (38%), gait disturbance (36%)
- At 12 months, persistent paresthesias in 14% and gait disturbance in 9%
- Non-invasive transcranial procedure requiring no incision or craniotomy
- Mean of 18.5 sonications delivered with peak temperatures of 55.6°C for ablation
Study Design
- Study Type
- Randomized, double-blind, sham-controlled trial
- Randomization
- Yes
- Blinding
- Double-blind (patients and assessors blinded; Tremor Research Group reviewed videotaped assessments)
- Sample Size
- 76
- Follow-up
- 12 months
- Centers
- 8
- Countries
- United States, Canada, South Korea, Japan
Primary Outcome
Definition: Change from baseline to 3 months in hand tremor score (CRST Parts A and B; 0-32 scale)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 16.0 at baseline to 15.8 at 3 months (0.1% change) | 18.1 at baseline to 9.6 at 3 months (47% improvement) | - (5.9 to 10.7 (between-group difference 8.3 points)) | <0.001 |
Limitations & Criticisms
- All procedures performed unilaterally - no reduction in ipsilateral tremor or axial tremors (head, neck, voice)
- Some patients may be unable to undergo MRI studies
- Transcranial delivery was difficult in 5 patients due to cranial characteristics
- No comparison group undergoing DBS
- Blinding partially compromised - 95% of active treatment and 80% of sham correctly guessed assignment
- Benefits and risks may differ from routine practice in diverse clinical settings
Citation
N Engl J Med 2016;375:730-9