Morbidity Milestones Demonstrate Long Disability‐Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus

Abstract

Background Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. Objectives Objectives: To judge the long-term outcome of patients with STN-DBS. MethodsMethods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with raterbased scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. ResultsResults: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 AE 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 AE 0.8 years, which is comparable with patients with PD but without STN-DBS. Conclusions Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.Parkinson's disease (PD) is one of the most common neurodegenerative diseases. 1 Several efficient therapies for PD have been identified. The introduction of levodopa has improved overall survival in patients with PD. 2 Furthermore, deep brain stimulation (DBS) of the subthalamic nucleus (STN) and further targets can improve motor symptoms, 3 quality of life, 4 and the ability to perform activities of daily living. 5 DBS can also reduce motor fluctuations 6 and the amount of dopaminergic medicationwhich often lowers adverse effects. 7,8 Although many patients experience a significant amelioration of PD symptoms after DBS surgery, 9 the overall long-term benefit has not been demonstrated conclusively. 10

Serum neurofilament indicates accelerated neurodegeneration and predicts mortality in late-stage Parkinson’s disease

“…Specifically, the occurrence of morbidity milestones, which include visual hallucinations, recurrent falls, the onset of dementia, and admission to a nursing facility, have been associated with poor prognosis heralding the final five years of the disease 13 . Even in patients with long-term deep brain stimulation (DBS), the same rapid progression was found after the onset of morbidity milestones—in spite of more benign disease trajectories in DBS patients in early to mid-stage disease 14 . These findings indicate a pathophysiological process, which is inherent to the last phase of the disease or an age-modulated exponential progression culminating in comparable trajectories.…”

“…These findings indicate a pathophysiological process, which is inherent to the last phase of the disease or an age-modulated exponential progression culminating in comparable trajectories. Such an accelerated progression or “neurodegenerative storm” in the terminal stage can be illustrated in the form of a hockey-stick effect, which closes a steady linear deterioration with a steep upward curve at the end 13 , 14 . The underlying factors for these processes are unknown, however, both models could be caused by a failing stress compensation in already critically degenerated areas where only minor cellular loss acts as the straw breaking the camel’s back.…”

Serum Neurofilament Predicts Mortality and Indicates Accelerated Neurodegeneration in Late-Stage Parkinson’s Disease

“…Such an accelerated progression or "neurodegenerative storm" in the terminal stage can be illustrated in the form of a hockey-stick effect, which closes a steady linear deterioration with a steep upward curve at the end. 14,15 The underlying factors for these processes are unknown, however, both models could be caused by a failing stress compensation in already critically degenerated areas where only minor cellular loss acts as the straw breaking the camel's back. Another possible mechanism is the spread of alphasynuclein beyond the midbrain structures, including the cortex and the limbic system, which results in a pronounced increase in the size of affected gray matter.…”

Reply to: Disability Milestones and Death in Parkinson's Disease under Subthalamic Neurostimulation

“…We thank Mahlknecht and colleagues for their thoughtful comments on our recently published research in which we examined the occurrence of disability milestones (frequent falls, hallucinations, dementia, and nursing home placement) and their relationship to death in a cohort of 162 patients with Parkinson's disease (PD) and deep brain stimulation of the subthalamic nucleus (STN-DBS). 1 In response to our work, they reanalyzed data from one of their previous studies comparing patients with deep brain stimulation (DBS) to a matched control group. 2 Similar to our observations, they found that psychosis was the only milestone to occur less frequently in patients with STN-DBS, which could be a consequence of the lower daily dose of dopaminergic medication.…”

“…We thank Mahlknecht and colleagues for their thoughtful comments on our recently published research in which we examined the occurrence of disability milestones (frequent falls, hallucinations, dementia, and nursing home placement) and their relationship to death in a cohort of 162 patients with Parkinson's disease (PD) and deep brain stimulation of the subthalamic nucleus (STN‐DBS). 1 …”