NSTAPS 3-Year
(2016)Objective
To compare motor symptoms, cognition, mood, and behavior 3 years after deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) in advanced Parkinson disease (PD)
Study Summary
• Off-drug UPDRS-ME at 3 years was significantly better with STN DBS (median 28 vs 33, p=0.04)
• No difference in composite cognitive, mood, and behavioral adverse effects between groups
• STN DBS allowed significantly greater medication reduction (605 mg vs 1,060 mg, p<0.001)
• Significantly more GPi patients required reoperation to STN DBS due to lack of benefit (8 vs 1, p=0.03)
Intervention
Bilateral GPi DBS vs bilateral STN DBS. Surgery performed according to each center's standard protocol
Inclusion Criteria
Age ≥18 years, idiopathic PD, despite optimal pharmacologic treatment experienced at least one of: severe response fluctuations, bradykinesia, dyskinesias, or painful dystonias
Study Design
Arms: 2 arms: (1) GPi DBS - bilateral globus pallidus pars interna deep brain stimulation; (2) STN DBS - bilateral subthalamic nucleus deep brain stimulation
Patients per Arm: Total enrolled: 128 patients (GPi DBS n=65, STN DBS n=63). Completed 3-year follow-up: 90 patients (GPi n=47, STN n=43)
Outcome
Bottom Line
STN DBS provides significantly greater improvement in off-drug phase motor symptoms and functioning at 3 years compared to GPi DBS, with similar risk for cognitive, mood, and behavioral complications. STN DBS also allows greater reduction in dopaminergic medication but GPi DBS requires more reoperations due to waning effect.
Major Points
- Multicenter randomized controlled trial comparing bilateral GPi DBS vs bilateral STN DBS in 128 patients with advanced PD
- At 3-year follow-up, STN DBS showed significantly more improvement in off-drug UPDRS-ME scores (median GPi 33 vs STN 28, p=0.04)
- No between-group differences in composite score for cognitive, mood, behavioral effects, and inability to participate (GPi 83% vs STN 86%, p=0.69)
- STN DBS allowed significantly greater medication reduction (median LED: GPi 1,060 mg vs STN 605 mg, p<0.001)
- Eight patients in GPi group required reoperation to STN DBS due to waning effect vs only 1 in STN group (p=0.03)
- Off-drug functioning (ALDS) tended to be better with STN DBS (GPi 65.2±20.1 vs STN 72.6±18.0, p=0.05)
- Quality of life did not differ between groups despite motor differences
Study Design
- Study Type
- Multicenter randomized controlled trial
- Randomization
- Yes
- Blinding
- Single-blind (patients and assessors blinded, treating neurologist unblinded)
- Sample Size
- 128
- Follow-up
- 36 months
- Centers
- 5
- Countries
- Netherlands
Primary Outcome
Definition: UPDRS Motor Examination score in off-drug phase at 36 months
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| GPi DBS: 33 (IQR 23-41) | STN DBS: 28 (IQR 20-36) | - | 0.04 |
Limitations & Criticisms
- High dropout rate: only 70% of baseline cohort completed 3-year follow-up (90/128 patients)
- Primary outcome changed from time-weighted ALDS to UPDRS-ME 2 years before last patient assessment due to incomplete diary data
- Patients and assessors were blinded but treating neurologist was not blinded to treatment allocation
- Per-protocol analysis excludes 9 patients who underwent reoperation to different target, potentially introducing bias
- On-drug dyskinesia results are artifact of study design (same levodopa dose at baseline and follow-up despite medication reduction in STN group)
- Quality of life measured only in on-drug phase, may not capture off-drug motor benefits of STN DBS
Citation
Neurology 2016;86:755-761