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

Abstract

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: To judge the long-term outcome of patients with STN-DBS.

Methods: 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 rater-based 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.

Results: 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 ± 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 ± 0.8 years, which is comparable with patients with PD but without STN-DBS.

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.

Keywords: Parkinson's disease; deep brain stimulation; long‐term outcome; milestones; morbidity..

FIG. 1

Flowchart of patients. DBS, deep brain stimulation.

FIG. 2

Parkinson's disease burden is reduced after DBS of the subthalamic nucleus. Trajectory of clinical characteristics after DBS surgery in patients with DBS of the subthalamic nucleus derived from the cross‐sectional analysis of the READ‐PD cohort as described in Figure 1. (A) UPDRS Part IV, (B) Hoehn and Yahr stage in the ON state, (C) UPDRS Part III in the ON state, (D) LEDD in mg, (E) UPDRS Part II in percentage of baseline value, and (F) cognition as measured by either Montreal Cognitive Assessment (READ‐PD) or Mini Mental Satus Test (others) in percentage of baseline value. The values from this study (READ‐PD, boxes and dotted lines) are superimposed with the following published cohorts for comparison: Lilleeng et al, Krack et al, Ostergaard et al, Piboolnurak et al, Gervais‐Bernard et al, Simonin et al, Fasano et al, Moro et al, Castrioto et al, Merola et al, Zibetti et al, and Hacker et al. DBS, deep brain stimulation; LEDD, levodopa equivalent daily dose; READ‐PD, Register of Patients with Advanced Parkinson's Disease; UPDRS, Unified Parkinson's Disease Rating Scale.

FIG. 3

Morbidity milestones occur late in patients with STN‐DBS. (A) Overall incidence (in percent of the entire cohort, on the y‐axis) and time of occurrence (in years after diagnosis, on the x‐axis) of the morbidity milestones hallucinations, dementia, nursing home placement, and falls. Red markers are mean values for this study (PD patients with STN‐DBS, READ‐PD, n = 162); blue markers are mean values of the cohort described by Kempster et al (PD patients on medical treatment). (B) Time until death after occurrence of the morbidity milestones hallucinations, nursing home, dementia, and falls in the READ‐PD cohort (n = 39) and the cohort described by Kempster et al. No estimates of precision are displayed for clarity. READ‐PD, Register of Patients with Advanced Parkinson's Disease; STN‐DBS, deep brain stimulation of the subthalamic nucleus

FIG. 4

Health‐related quality of life and functional measures deteriorate with occurrence of the first morbidity milestone. Comparison of functional scales and health‐related quality of life with respect to milestone development at the first post–deep brain stimulation study visit. Scores of patients without a milestone (“−,”n = 35) are displayed to the left, and scores of patients after the first milestone (“+,” n = 80) are displayed to the right: (A) UPDRS III (motor score), (B) UPDRS IV (dyskinesia score), (C) Tinetti, (D) SPPB, (E) MoCA (cognition), and (F) PDQ‐39 (health‐related quality of life). Bold lines in violins indicate median, and dotted lines indicate quartiles. Groups were compared by Mann–Whitney U test. P values are indicated above violin plots. The y‐axis covers the entire range of each scale. MoCA, Montreal Cognitive Assessment; ns, not significant; PDQ‐39, Parkinson's Disease Questionnaire 39; SPPB, Short Physical Performance Battery; Tinetti, Tinetti Mobility Test; UPDRS III, Unified Parkinson's Disease Rating Scale Part III; UPDRS IV, Unified Parkinson's Disease Rating Scale Part IV.

FIG. 5

Schematic visualization of the concept of compressed morbidity with respect to milestone development. (A) Comparison of disease burden with proposed linear symptom progression (blue) versus compressed morbidity (red). (B) Milestone manifestation defines the turning point toward a higher disease burden, and milestone manifestation is delayed in DBS of the subthalamic nucleus (red) versus MT (blue). (C) Milestones only become visible when data are organized according to milestone manifestation; individual increased disease burden due to milestone manifestation is lost in the mean (dotted red line) due to different disease durations. DBS, deep brain stimulation; MT, medical treatment.