Surgical Modification of Motor Circuitry

Deep brain stimulation of the subthalamic nucleus can, in some patients and in some conditions, induce or worsen cognitive deficits, including impulsivity, executive dysfunction, and psychiatric symptoms. These side effects could be potentially minimized with appropriate care and reprogramming, although  research is needed to determine whether this is the case. Physicians should be aware of potential cognitive complications which can pose a significant burden to quality of life.

In this months issue of the Lancet Neurology, the PD SURG trial which was conducted by a multicenter team of collaborative investigators from around Britain report their one year findings.  The trial was randomized and it compared DBS to best medical therapy.  The primary outcome variable was quality of life, and interestingly, patients in the best medical therapy arm had access to apomorphine pumps.  Though sites were allowed to use the subthalamic nucleus, the globus pallidus interna, and even lesion therapy, 174/178 patients in the surgery group underwent subthalamic nucleus DBS.  There was a five point improvement in quality of life scores in the surgical compared to medical group, and although compared to other studies the quality of life improvement was less robust, this may have reflected a longer study duration, or potentially disease progression.  There were unmistakable improvements in dyskinesias, and on time in the surgical group, although diaries were not utilized.

Though, not a perfect trial, its large size and use of a medical control group along with unique access to apomorphine made it unique among available publications.  The results underscored the powerful influence that DBS may have on motor fluctuations.  Additionally, these SURGE investigators plan a long term (9 year) follow-up and this will surely enlighten the field as to disease progression, and other issues potentially important to DBS cohorts.

One unique and hidden aspect of this trial was the report of the “reasons why patients sought DBS surgery.”  Severe off periods, dyskinesia and tremor were far and away the most common indications cited for DBS therapy.  As DBS moves into a tailoring phase (the right target and approach for a particular symptom or symptom cluster)  this type of information will be very useful to clinicians.

People may criticize the lower total motor change scores reported in PD SURGE when comparing pre- and post-operative operative outcomes, however they must remember that as the blinded DBS trial results emerge internationally (VA PADRECC study, Cleveland Clinic/Emory Study, UF COMPARE trial), that the open label improvements previously documented will almost certainly be less robust.  The results of the PD SURGE trial may also offer a look at what DBS outcomes may realistically look like as the therapy migrates to centers with less expertise.

It is fascinating to see that 174/178 implants were chosen to be placed in the subthalamic nucleus.  Though this target has many strengths, it also has relative weaknesses.  Emerging data is now strongly suggestive that the motor outcomes in pallidum and subthalamic nucleus are actually similar and that targets in the future should be tailored for individual patients and individual symptoms.

In conclusion can we say the PD SURGE trial was a surge forward for the PD community? The answer is certainly yes, as the publication of more carefully controlled DBS trials will be important in guiding DBS therapy into the future.

*Dr. Okun also writes a column for What’s Hot in Parkinson’s disease on the NPF website and this piece will appear in the May edition of that series.