Different outcomes for dyskinesia and off-period dystonia after deep brain stimulation for Parkinson's disease-Review and a new hypothesis

In this review analyzed are the results of several clinical studies that addressed effects of deep brain stimulation (DBS) on motor complications of levodopa therapy, with emphasis on off-period dystonia. All studies found significant decrease in UPDRS IV scores (dyskinesia and motor fluctuations), regardless of target (STN or GPi), for up to 11 years after the surgery. Data from the studies show that the benefit of DBS for dyskinesia lasts longer than for off-period dystonia. Motor scores deteriorate to baseline after approximately 3 years of stimulation, while dyskinesia continue to benefit up to 11 years after surgery (longest follow-up). Interestingly, dyskinesia often resolve regardless of whether active stimulation is present, while off-dystonia always requires active stimulation. DBS works better for phasic (mobile) then tonic type of dystonia (such as off-dystonia). The effect of DBS on off-period dystonia is best within 1-2 years after the surgery and declines thereafter, tending to follow deterioration of motor scores. Only one study reported on effectiveness of GPi DBS for off-period dystonia, with resolution after one year and no further follow up. Further comparative studies are needed to provide evidence which target is better suited for patients with off-dystonia (and wearing-off) and whether targeting GPi provides a comparable benefit, or more. For this purpose, better and unified scaling system is needed for quantifying off-period dystonia in PD. Considerations in this paper lead to discussions presented in Appendix, where there is also presented a fundamental issue of obsolete D2 receptor activation during levodopa therapy and the need for metoclopramide in preventing wearing-off/off-dystonia.