Implementing novel trial methods to evaluate surgery for essential tremor

Area of Science:

• Neurology
• Neurosurgery
• Clinical Trials

Background:

• Essential tremor (ET) significantly impacts quality of life.
• Deep brain stimulation (DBS) is a promising treatment for ET.
• Lack of high-level evidence for DBS efficacy in ET.

Purpose of the Study:

• To provide Class I evidence for the efficacy of DBS in treating ET.
• To demonstrate the effectiveness of DBS for essential tremor relief.

Main Methods:

• Utilized traditional cohort analysis, N-of-1 single-patient randomized controlled trials, and signal-to-noise (S/N) analysis.
• 20 ET patients with DBS electrodes underwent randomized on/off stimulation periods.
• Tremor severity was objectively quantified, with patients blinded to stimulation status.

Main Results:

• Mean tremor severity was significantly lower with DBS on (0.84/10) versus off (6.62/10) (p < 0.0005).
• N-of-1 trials showed high patient perception accuracy (60% with 12 correct, p=0.001).
• S/N analysis revealed >80% tremor reduction in 87% of 'On' trials versus 3% of 'Off' trials.

Conclusions:

• The substantial effect of DBS on ET is too large to be explained by bias.
• N-of-1 trial design and S/N ratio analysis provide convincing evidence for DBS efficacy in ET.
• This study establishes Class I evidence for DBS in essential tremor treatment.