Timing of deep brain stimulation in Parkinson
Desouza R, Moro E, Lang A, Schapira A. Ann Neurol. Timing of deep brain stimulation in Parkinson , 2013 Mar 8. doi: 10.1002/ana.23890. [Epub ahead of print]
Intro: PD is a common and costly neurodegenerative disease that affects people worldwide. This disease affects both young/old, motor/nonmotor systems, quality of life for individuals/families, and truly is a “complex, chronic, multifaceted disease.”
Methods: The authors reviewed multiple articles available in the literature regarding “timing of DBS in PD” questioning whether the idea of utilizing DBS earlier in the disease course could have better motor as well as quality of life outcomes (QoL) for people with PD (PWP).
Medication is the most widely used treatment for PD; however, in the early 2000s DBS received FDA approval to treat PWP. Debate continues regarding the best stimulation site for DBS and it often is used later in the disease course after medications are no longer as effective, there are significant side effects, or the off-periods are quite long. The criteria for surgical candidacy often requires that the PWP is “medically and psychologically fit” enough to undergo the surgery, they do not have “cognitive dysfunction” (e.g. dementia, mild cognitive impairment, etc.), and their PD must have been responsive to dopamine medications. The criteria as written can be challenging for the PWP that has had the disease for decades, effectively robbed of their physical ability to complete such a surgery. Clinicians and researchers have recognized this limitation resulting in the suggestion of “individualized criteria” for each PWP to insure the optimal treatment outcomes. DBS continues to show promise in improving motor symptoms and some nonmotor symptoms, decreased medication levels, and improved QoL. However, there are also adverse outcomes with this treatment including hardware issues, “infection, bleeding, stroke, death, depression, apathy, weight gain, speech,” and cognitive changes. Notably, the article reported that adverse event rates are lower at facilities that complete the surgery more frequently. The authors also posited that there might be a difference in effects on QoL from DBS between younger and older PWP with younger PWP reporting more benefit.
Some small studies have looked at DBS in PWP completed earlier (defined in various lengths of times) in their disease course. These studies have shown that the PWP had similar rates of surgical complications as well as improvements in motor symptoms, QoL, and reduced need for medications as those PWP that received their DBS later in their disease. Critics of such studies note that the possible surgical complications and adverse events should make this a “last resort” therapy while proponents cite the possibility of multiple years of improved motor symptoms and general functionality.
Animal studies have also shown that DBS has neuroprotective factors regarding neuronal loss and dopamine levels, but often these findings are not reproducible in humans. Hypothetically, if such neuroprotection was there for humans as well, completing the surgery earlier on should have benefit, as there would be more neurons to protect. Unfortunately, the long-term studies to date have not shown such neuroprotection from DBS. These long-term studies have shown that there continues to be motor benefit from DBS, but the disease remains progressive.
Conclusion: Research on treatments for PD has flourished over the past decades and the authors suggest that clinicians and researchers alike challenge themselves to continue to look for new and inventive ways to combat this disease. They raise the possibility of earlier usage of DBS in PWP in order to improve motor symptoms and QoL based on some very promising small studies. The authors encourage studies looking at early DBS as compared to typical medicinal treatments to test that hypothesis.