DBS Dystonia
(2006)Study Summary
• Bilateral pallidal (GPi) DBS significantly improved primary generalized/segmental dystonia: BFMDRS movement score improved 39.3% at 3 months vs 4.9% sham (P<0.001).
• 40 patients, sham-controlled.
• Published NEJM 2006 (Kupsch et al.).
• Effect sustained and improved further at 6 months (44.5% with active DBS).
• 40 patients, sham-controlled.
• Published NEJM 2006 (Kupsch et al.).
• Effect sustained and improved further at 6 months (44.5% with active DBS).
Intervention
Bilateral high-frequency stimulation of internal globus pallidus (pulse width 60–210 μs, frequency 130 Hz, amplitude up to 4.5 V) vs Electrodes implanted, stimulation amplitude set to 0 V (device on, no current delivered)
Study Design
Arms: Array
Outcome
Change in movement score on the Burke-Fahn-Marsden Dystonia Rating Scale at 3 months: −15.8 ± 11.6 (39%) vs −1.4 ± 4.1 (5%) (p=<0.001)
Bottom Line
Bilateral pallidal (GPi) DBS significantly improved primary generalized/segmental dystonia: BFMDRS movement score improved 39.3% at 3 months vs 4.9% sham (P<0.001). 40 patients, sham-controlled. Published NEJM 2006 (Kupsch et al.). Effect sustained and improved further at 6 months (44.5% with active DBS).
Major Points
- BFMDRS movement score: -39.3% (DBS) vs -4.9% (sham) at 3 months (P<0.001).
- BFMDRS disability score: -37.5% (DBS) vs -11.8% (sham) at 3 months (P=0.01).
- 40 patients with primary generalized/segmental dystonia. Double-blind, sham-controlled.
- Bilateral GPi stimulation. Sham: device implanted but not activated for 3 months.
- At 6 months (all active): 44.5% improvement in movement, 42.7% disability improvement.
- Mean age 15 years (range 8-75). DYT1-positive: ~45%. Duration of dystonia: mean ~10 years.
- AEs: 1 lead dislodgement, 1 wound infection, 4 stimulation-related (dysarthria, facial contractions).
- First sham-controlled RCT for DBS in dystonia. Published NEJM 2006 (Kupsch et al.).
- Established GPi-DBS as standard of care for medically refractory primary generalized dystonia.
- DYT1 carriers tended to respond better than non-carriers (post-hoc).
Study Design
- Study Type
- Randomized, double-blind, sham-controlled trial with open-label extension
- Randomization
- Yes
- Blinding
- Patients and clinical evaluators were blinded to stimulation; only programming physicians unblinded
- Sample Size
- 40
- Follow-up
- 3 months blinded, up to 6 months open-label
- Centers
- 10
- Countries
- Germany, Austria, Norway
Primary Outcome
Definition: Change in movement score on the Burke-Fahn-Marsden Dystonia Rating Scale at 3 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| −1.4 ± 4.1 (5%) | −15.8 ± 11.6 (39%) | - | <0.001 |
Limitations & Criticisms
- Small sample size (n=40) limits generalizability
- Short duration of blinded phase (3 months)
- Placebo effect not fully excluded despite blinding
- Surgical risks and device complications require long-term evaluation
Citation
N Engl J Med 2006;355:1978–1990. doi:10.1056/NEJMoa063618