Evaluating DBS: Sooner is Not Always Better
An alliance of researchers in Germany and France recently published the results of a clinical trial that looked at the benefit of using Deep Brain Stimulation for younger people in earlier stages of PARKINSON’S DISEASE. These people have had relatively short term motor complication for less than three years. The subjects were not treated with standard pharmacological treatments, but instead, opted for the surgery earlier in the course of their disease. The study followed them for two years and reported significant improvements for the participants of the early DBS group over a control group receiving only best medical therapy..
The study caught the eye of several Canadian doctors with extensive experience in treating PARKINSON’S DISEASE, including Dr. Tony Lang, whose work with movement disorders and also with deep brain stimulation is very highly regarded in the medical field. He is affiliated with the Movement Disorders clinic at Toronto Western Hospital and also with University Health Network, Department of Neurology, University of Toronto, in Toronto, Canada. The Canadian researchers reviewed the results of the European trial and looked at it from many angles besides the actual clinical improvement of the patients.
The Canadian researchers acknowledged that the results of the surgery on younger subjects over all did result in better quality of life for the patient and reduction of tremor and rigidity.. But the European study also confirmed that DBS can also have serious adverse events, including risk of suicide, which has also been demonstrated in other clinical trials. In addition, the Canadian group feel that offering DBS to patients who have had motor symptoms for fewer than 5 years could include people with atypical parkinsonism that cannot benefit from the surgery. If symptoms are mild, the results from the surgery will also be mile, but the possibility of adverse events related to the surgery, such as infection, reaction to implanted materials or response to neuro-stimulation is the same as for patients with more advanced symptoms who would see greater benefit. Given that symptoms and severity of the symptoms vary for each individual with PARKINSON’S DISEASE, the decision over treatment must consider the seriousness of potential risks of DBS and whether there is an experienced team of practitioners who are able to respond quickly. DBS does not address all the problems of PD; bradykinesia is not helped, gait problems and freezing of gait may be worsened or even be induced by DBS.
The Canadian team pointed out that the European study was an open-label study, meaning that all participants received DBS and there was no control group receiving sham surgeries. Other Parkinson’s studies involving surgical procedures for cell transplantation have shown and extremely high, positive placebo response Expectation of benefit can be very powerful. Since all the participants in the European study willingly submitted to a serious invasive neurological procedure on their brain, it must be assumed that they had an extremely high expectation of benefit. This may have created an overly positive response to the surgery. Subjects that received only best available medical therapy may have also been negatively impacted, the lessebo effect, thinking they were not expected to show the same improvement as subjects receiving the DBS. This is supported by the fact that after the first, blinded part of the trial, most of the subjects in the medical therapy group elected to undergo the DBS. Caution must be used to interpret the results in light of these considerations.
The results from the European study do show some positive responses that are worth re-evaluating with further, better designed clinical trials. This trial was on a younger population, with a shorter duration of motor symptoms who were good candidates for surgery. At also only followed them for a relatively short time, two years. The results cannot necessarily be duplicated for old subjects with other motor or non-motor complications who might not be good candidates for surgery.
DBS can and has helped many people with Parkinson’s, it is not a question of its effectiveness. But it does bring into question the timing for the best applications of DBS for the best results for the individual undergoing the surgery. Many symptoms of Parkinson’s can be controlled for a long time with best medical therapies, without the risks involved with serious, invasive brain surgery. The decision to undergo this surgery, and the expected benefits or potential adverse events, has to be made by each individual. A multidisciplinary team experienced with Parkinson’s Disease as well ad DBS needs to be able to counsel the person and to be there to assist in the decision making as well as in follow up care.
Tiago A. Mestre, Alberto J. Espay, Connie Marras, Mark H. Eckman, Pierre Pollak and Anthony E. Lang
Article first published online: 16 SEP 2014 | DOI: 10.1002/mds.26024
Review by Marcia McCall