Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

Abstract

SummaryBackgroundSurgical 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.MethodsThe 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. This trial is registered with , number ISRCTN34111222.Findings366 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 (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference 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 discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences between groups in all other domains of the PDQ-39 were not significant. 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.InterpretationAt 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 differences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefit might be warranted.FundingUK Medical Research Council, Parkinson's UK, and UK Department of Health.

Long-term outcome of subthalamic nucleus DBS in Parkinson's disease: From the advanced phase towards the late stage of the disease?

“…Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is very effective for the treatment of patients with advanced Parkinson's disease (PD), improving both motor PD symptoms and levodopainduced motor complications [1]. Some large randomized controlled clinical trials have shown that in the short-term follow-up STN-DBS is superior to best medical treatment alone in controlling motor symptoms and complications and thus improving self-reported quality of life [1], [2] and [3].…”

“…Some large randomized controlled clinical trials have shown that in the short-term follow-up STN-DBS is superior to best medical treatment alone in controlling motor symptoms and complications and thus improving self-reported quality of life [1], [2] and [3].…”

Neurostimulation for Parkinson's Disease with Early Motor Complications

“…After an initial honeymoon period, during which there is a sustained response to dopaminergic treatment, beneficial effects are hampered by levodopainduced motor complications, 1 progressively compromising quality of life. [2][3][4] Because levodopa-responsive parkinsonian symptoms are improved by high-frequency stimulation of the subthalamic nucleus, 5,6 neurostimulation has become an established treatment for advanced Parkinson's disease with medically intractable fluctuations and dyskinesia [7][8][9][10] and has shown long-term efficacy. [11][12][13] It is typically used after the disease has been present for 11 to 13 years, 7-10 when quality of life, social adjustment (psychosocial competence), 14 and professional activity are already severely impaired.…”

“…[11][12][13] It is typically used after the disease has been present for 11 to 13 years, 7-10 when quality of life, social adjustment (psychosocial competence), 14 and professional activity are already severely impaired. Neurostimulation improves quality of life, [7][8][9][10] in addition to motor symptoms. Moreover, later in the course of the disease, features unresponsive to dopaminergic treatment often predominate.…”

Safinamide for the treatment of Parkinson’s disease

“…Surgical treatment for PD, in the form of deep brain stimulation (DBS) of the subthalamic nucleus, globus pallidus interna or pedunclopontine nucleus, or lesioning has become an increasingly feasible option [9,10] and cost effective [11]. DBS has been proven in clinical trials to be superior to best medical therapy [12][13][14] and to be more effective in improving quality of life if used earlier in the course of the disease [15]. The effects of surgical therapy on non-motor features are under investigation and some may improve due to the DBS itself and others from a reduced drug burden [16].…”