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 ; 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.
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.