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

Abstract

ObjectiveTo 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).MethodsMotor 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.ResultsMedian 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).ConclusionsWe 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 individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.

Neuronal Activity and Synaptic Plasticity in a Reimplanted STN-DBS Patient with Parkinson’s Disease: Recordings from Two Surgeries

“…However, a reduction in SNr plasticity was not observed. A recent clinical study [31] demonstrated a 22% worsening in akinetic symptoms and a 27% worsening in axial symptoms over the course of 0 to 2, 5, and 10 years after STN-DBS implantation surgery (with stimulation and medication ON). Assuming a linear progression of these symptoms (which was also demonstrated in the study), these values would deduce to 3.3% (1.32/40) and 4.05% (0.81/20), respectively, over the course of 1.5 years.…”

Effect of Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) on balance performance in Parkinson's disease

“…Exclusion criteria for DBS-group were: (1) balance dysfunction caused by secondary Parkinson's syndrome, hydrocephalus, intracranial tumors, and multiple cerebral infarctions. (2) patients with obvious cognitive dysfunction (Montreal Cognitive Assessment<26/30), serious anxiety, depression (Hamilton Anxiety Scale>21/56, Hamilton Depression Scale>24/68); (3) mental illness. All patients provided signed informed consent.…”

“…Falling can have a series of serious consequences, including hip fractures and brain injuries. Due to the fear of falling, the activities of patients with PD are restricted, which seriously affects their quality of life [2]. Until now, improvement of balance function by different treatments remains ambiguous.…”

Fading of Deep Brain Stimulation Efficacy Versus Disease Progression: Untangling a Gordian Knot

“…There are only a few uncontrolled longterm studies reporting frequencies of key disability milestones in DBS patients and a handful of controlled studies yielding conflicting findings. 3,[10][11][12][13][14][15][16] In this issue of Movement Disorders Clinical Practice, 2 elegant papers addressed whether STN DBS effects wear off and whether DBS patients acquire disability milestones earlier than non-DBS patients. Although driven by different objectives, these studies are complementary and challenged by the unavoidable confounder of evaluating the long-term outcome of a surgical technique adopted in a highly variable and progressive disorder.…”

“…These results contrast with a recent study suggesting that STN DBS patients with PD survive longer as long as axial symptoms are under control. 15 Despite the use of large cohorts and attempts to match groups properly, any long-term DBS study adopting a historical control cohort of non-DBS patients is heavily biased because of patient selection at baseline. For example, the development of dementia is paradoxically low in DBS cohorts perhaps as a result of strict cognitive screening to determine surgical eligibility.…”