Thursday April 29 2010
The invasive implant surgery is not suitable for everyone
A brain “pacemaker” can fight Parkinson's disease, according to The Independent. The newspaper said that combining deep brain stimulation (DBS) implant surgery with standard drug treatment has been found to give greater improvement in motor function and to reduce symptoms more than drug treatment alone.
The research behind this news was a trial involving 366 people with advanced Parkinson’s disease that was not being adequately controlled with medication. It found that after a year, those who had a DBS implant had greater improvements in quality of life than those receiving medical treatment alone. This was particularly due to improvements in mobility, bodily discomfort and the ability to carry out the activities of daily living. However, DBS surgery was not without risks, and about 19% of patients had serious adverse effects, mainly infections.
This trial suggests that combining DBS with medication has some benefits beyond drug therapy alone. Importantly, though, DBS treatment is invasive and will not be appropriate for everyone with Parkinson’s. This means that the potential benefits of DBS would need to be balanced against its risks for each patient.
Where did the story come from?
This research was carried out by Professor Adrian Williams and colleagues from the Queen Elizabeth Hospital in Birmingham and other hospitals and research centres in the UK. The study was funded by the UK Medical Research Council, Parkinson’s UK and the Department of Health. It was published in the peer-reviewed medical journal The Lancet.
The BBC News website, Daily Mail and The Independent covered this story in an accurate and balanced way. The Daily Mail and BBC News reported that this was a decade-long trial, although the trial recruited participants between 2000 and 2006, so a number of the patients will not yet have been followed for a full ten years. The current results are also only based on follow-up in the year after surgery, with longer-term results awaited. The Independent reported that 5% of people receiving DBS had severe complications, such as infections. However, 19% were reported to have serious surgery-related adverse events in the research paper.
What kind of research was this?
This was a randomised controlled trial (RCT) called PD-SURG, which looked at the effect of deep brain stimulation (DBS) on quality of life in people with advanced Parkinson’s disease. Treatment with DBS involves implanting wire electrodes into the brain. These electrodes are attached to a “pacemaker” device, which regularly sends electrical impulses through the electrodes and into the brain. In most cases, the pacemakers in this trial were implanted into an area of the brain known as the subthalamic nucleus, although other DBS procedures may use alternative sites.
An RCT is the most appropriate way to compare the effects of different treatments. This RCT compared the best medical treatment alone with the same type of medical treatment combined with a DBS implant. This study design would be the best way to tell whether DBS provided any additional benefits over and above standard treatment.
What did the research involve?
The researchers recruited 366 people with Parkinson’s disease that was not adequately controlled with medical treatment for Parkinson's disease alone. They were randomised to continue to receive best medical treatment alone (drugs such as dopamine agonists, MAO type B inhibitors, COMT inhibitors and apomorphine) or to receive DBS surgery in addition to the best medical treatment. The researchers followed the participants up for one year and measured their quality of life to see whether DBS had any effect on this outcome.
The participants in this trial were enrolled at 13 neurosurgery centres in the UK between 2000 and 2006. They had to have Parkinson’s disease diagnosed according to standard criteria, and to be fit enough to undergo surgery. Before being randomised, the participants filled out a standard Parkinson’s disease questionnaire (PDQ-39), which assessed their quality of life. One year after being randomised and receiving their assigned treatment, the participants filled in this questionnaire again.
The researchers then compared changes in quality of life in the group that received DBS and the group that did not. A change of 10 points on the questionnaire score (based on a 39-point scale) was considered to be large enough to be meaningful to patients. A secondary outcome assessed by researchers was clinical assessment of the participants’ functioning using UPDRS scores, a standard scale for measuring Parkinson’s symptoms.
As one group had surgery and the other did not, it was not possible to blind participants to which treatment they received. The researchers also knew what treatments the participants had received as the study did not have sufficient resources to use independent blinded assessors for clinical assessments. People in the standard treatment group (the non-surgery group) could have surgery after one year if their treatment was still not adequately effective.
What were the basic results?
One year after surgery, people who received DBS in addition to best medical treatment showed greater improvement in their quality of life than those who received best medical treatment alone. The DBS group improved by 5 points on the PDQ-39 scale and the medical group by only 0.3 points.
The quality of life questionnaire assessed different areas of life and showed that people who received DBS had greater improvements in mobility, activities of daily living and bodily discomfort. The difference between the groups was 8.9 points for mobility, 12.4 points for activities of daily living, and 7.5 points for bodily discomfort. Participants who received DBS also showed greater improvements in clinically assessed overall functioning at one year than participants receiving medication alone. Participants who received DBS had reduced their drug dose by about 34% compared with the medical treatment group.
Just under one in five people who received DBS had serious adverse effects associated with their surgery (19%), and one patient died from bleeding during surgery. Similar proportions of patients had side effects of their medical treatment in both groups (11% with DBS plus medical treatment, and 7% with medical treatment alone).
How did the researchers interpret the results?
The researchers concluded that one year after the study began, treatment that combined 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”.
They also say that the improvements seen were clinically meaningful, but that the risks associated with DBS surgery may warrant only offering the surgery to those people most likely to benefit from it.
This study used a robust design to assess the effects of deep brain stimulation (DBS) on quality of life in people with Parkinson’s disease that had not responded adequately to medical treatment. Points to note include:
- Blinding participants and researchers to the treatment received was not possible, so participants’ ratings of their quality of life may have been affected if they had pre-existing expectations of DBS or if they were disappointed not to have received DBS.
- The trial has so far collected and reported one year’s worth of data. The researchers are continuing to collect information on the patients’ outcomes so that the longer-term effects of DBS can be studied.
- The researchers suggest that the group of patients treated were representative of those who would be offered surgery at neuroscience centres in the UK.
- A questionnaire was given to participants in the DBS group about surgery-related adverse effects six months after surgery, but a similar questionnaire was not given to the medical treatment only group. Therefore, adverse effects in the latter group could have been missed. The researchers also note that they did not record adverse effects that were not serious enough to cause a patient to be admitted to hospital or to extend their stay in hospital.
- People who received DBS continued to receive medical therapy, although the drug dose could be reduced in many cases. Therefore, news reports that “brain surgery is more effective than medication” or “implants have given us our life back” should not be misinterpreted to mean that DBS is a complete cure or that a person will no longer need any form of drug treatment. People should also be aware that all surgical procedures are associated with some degree of risk and this treatment would not be suitable for everyone. Advances and developments in the DBS technique are likely to continue.
Overall, the results suggest that combining DBS with the best medical therapy can improve quality of life more than medical treatment alone in people with Parkinson’s disease that has not responded adequately to medical treatment.