EARLYSTIM
(2013)Objective
To determine whether subthalamic deep brain stimulation improves quality of life at an earlier stage of Parkinson's disease, before severe motor complications develop
Study Summary
• Younger patients (mean 52 years) with shorter disease duration (mean 7.5 years) than typical DBS candidates
• Quality of life improved 26% with DBS vs 1% worsening with medical therapy alone (P=0.002)
Intervention
Bilateral STN deep brain stimulation (Medtronic) plus optimized medical therapy vs medical therapy alone for 2 years
Inclusion Criteria
Age 18-60 years; PD duration ≥4 years; Hoehn & Yahr <3 on medication; ≥50% motor improvement with dopaminergic meds; fluctuations/dyskinesia ≤3 years
Study Design
Arms: Neurostimulation plus medical therapy, Medical therapy alone
Patients per Arm: Neurostimulation: 124, Medical therapy: 127
Outcome
• Secondary: UPDRS-III improved 53% with DBS; motor complications reduced 61%; medication reduced 39%
Bottom Line
In patients with PD and early motor complications (mean disease duration 7.5 years), bilateral STN-DBS plus medical therapy was superior to medical therapy alone in improving quality of life (8.0-point between-group difference on PDQ-39, P=0.002), motor disability, levodopa-induced complications, and time with good mobility at 2 years, though with higher rate of serious adverse events including suicides.
Major Points
- First randomized trial of DBS in early Parkinson's disease with motor complications (mean disease duration 7.5 years)
- Neurostimulation improved PDQ-39 quality of life score by 7.8 points vs worsening of 0.2 points with medical therapy (P=0.002)
- Off-medication UPDRS-III motor scores improved 16.4 points in DBS group vs favored neurostimulation (P<0.001)
- Activities of daily living (UPDRS-II), levodopa-induced complications (UPDRS-IV), time with good mobility all significantly improved (P<0.001)
- No significant differences in cognitive assessments (Mattis DRS) or emotional outcomes between groups
- Serious adverse events more frequent in neurostimulation group (54.8% vs 44.1%); 26 events related to surgery/device
- Two suicides in neurostimulation group vs one in medical therapy group
- Levodopa-equivalent daily dose reduced by 39% in DBS group but increased by 21% in medical therapy group
Study Design
- Study Type
- Randomized controlled trial
- Randomization
- Yes
- Blinding
- Blinded video assessments; expert raters unaware of study assignments except for rigidity assessment
- Sample Size
- 251
- Follow-up
- 24 months
- Centers
- 17
- Countries
- Germany, France
Primary Outcome
Definition: PDQ-39 summary index score (quality of life, 0-100, higher = worse)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Worsened by 0.2 points (-0.2±1.2) | Improved by 7.8 points (7.8±1.2) | - (8.0±1.6 (4.8 to 11.9) between-group difference) | 0.002 |
Limitations & Criticisms
- Higher rate of serious adverse events in neurostimulation group (54.8% vs 44.1%)
- Two suicides in neurostimulation group vs one in medical therapy group
- Blinding was incomplete - patients knew their treatment assignment
- Relatively young patient population (mean age 52 years) compared to typical advanced PD trials
- Disease duration relatively short (7.5 years) with motor complications present for mean of only 1.7 years
- Cannot exclude placebo effects or differences in medical management
- Surgery-related complications occurred in 17.7% of neurostimulation patients
Citation
N Engl J Med 2013;368:610-622