Summary

Most neurosurgery for Parkinson’s disease has been done on the thalamus, globus pallidus pars interna, or subthalamic nucleus, using either lesioning or high frequency deep brain stimulation. In recent years, advances in imaging have increased the precision of surgical interventions; this and advances in the understanding of basal ganglia physiology3–5 have meant that deep brain stimulation of the subthalamic nucleus has been preferred.In the late 1990s, there was little reliable evidence from randomised trials on the efficacy and safety of surgery. Thus, we started the PD SURG trial with the aim of comparing the effect of surgery with best medical therapy
in patients with advanced Parkinson’s disease. This report presents the results at 1 year’s follow-up.

Background

Surgical intervention for advanced Parkinson’s disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson’s disease.

Methods

The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson’s disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone.

Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson’s disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests.

Findings

366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (diff erence –4·7, 95% CI –7·6 to –1·8; p=0·001); the diff erence in mean change in PDQ-39
score in the mobility domain between the surgery group and the best medical therapy group was –8·9 (95% CI –13·8 to –4·0; p=0·0004), in the activities of daily living domain was –12·4 (–17·3 to –7·5; p<0·0001), and in the bodily is comfort domain was –7·5 (–12·6 to –2·4; p=0·004). Diff erences between groups in all other domains of the PDQ-39 were not signifi cant. 36 (19%) patients had serious surgery-related adverse events; there were no suicides but there was one procedure-related death. 20 patients in the surgery group and 13 in the best medical therapy group had serious adverse events related to Parkinson’s disease and drug treatment.

Interpretation At 1 year, surgery and best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson’s disease. These diff erences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefi t might be warranted.

The full paper is available here

Funding UK Medical Research Council, Parkinson’s UK, and UK Department of Health.