Axial symptoms predict mortality in patients with Parkinson disease and subthalamic stimulation

Objective To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS). Methods Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms off and on levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality. Results Median observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1-10 after surgery (on dopamine/on STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score). Conclusions We quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts risk of death after surgery, which may be useful for planning therapeutic strategies in PD.