Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial

Summary

Background

Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS.

Methods

We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074.

Findings

Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups.

Interpretation

Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease.

Funding

Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Introduction

Patients with advanced Parkinson's disease (PD) often show rapid, seemingly unpredictable swings between mobility (the on phase), usually with dyskinesias, and immobility (the off phase). Many of these patients respond unsatisfactorily to adjustments in pharmacological treatment.¹ Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) for advanced PD was first used in the 1990s.2, 3 The results of subsequent studies by different groups suggested that bilateral STN DBS reduces both PD motor symptoms and dyskinesias by about 50%.4, 5, 6 The effectiveness of bilateral DBS of the globus pallidus pars interna (GPi) was also explored.7, 8 The results of non-randomised comparative studies suggested that bilateral GPi DBS was slightly less effective than STN DBS for the treatment of PD motor symptoms and was equally effective for the treatment of dyskinesias.4, 9 However, the STN was already thought by many to be the better target for DBS in patients with PD, which might have caused a major bias in these series.10, 11 The results of two randomised controlled trials that compared bilateral STN with GPi DBS suggested that the procedures were equally effective for PD motor symptoms and dyskinesias.12, 13 DBS-associated problems in cognitive, mood, and behavioural features seemed to occur more often in the STN groups.10, 12, 14

The Netherlands SubThalamic and Pallidal Stimulation (NSTAPS) study was initiated in 2007 to test the hypothesis that bilateral GPi DBS would produce greater improvement in disability than would bilateral STN DBS, assuming a lower rate of cognitive, mood, and behavioural complications, with similar improvement of motor symptoms.

By contrast with previous studies that investigated the effectiveness of DBS, we chose a generic disability scale as a primary outcome measure. This was because GPi DBS and STN DBS might have different effects on the various motor symptoms and because both procedures might be accompanied by cognitive and psychiatric adverse effects.14, 15 Cognitive status and mood might have an effect on self-reported quality of life, which could lead to interpretation issues with these scales.