Deep brain stimulation in early-stage Parkinson disease: Five-year outcomes

Abstract

Objective: To report 5-year outcomes from the subthalamic nucleus (STN) deep brain stimulation (DBS) in early-stage Parkinson disease (PD) pilot clinical trial.

Methods: The pilot was a prospective, single-blind clinical trial that randomized patients with early-stage PD (Hoehn & Yahr II off medications) to receive bilateral STN DBS plus optimal drug therapy (ODT) vs ODT alone (IDEG050016, NCT0282152, IRB040797). Participants who completed the 2-year trial participated in this observational follow-up study, which included annual outpatient visits through 5 years. This analysis includes 28 patients who were taking PD medications for 6 months to 4 years at enrollment. Outcomes were analyzed using both proportional odds logistic regression and linear mixed effects models.

Results: Early STN DBS + ODT participants required lower levodopa equivalent daily doses (p = 0.04, β = -240 mg, 95% confidence interval [CI] -471 to -8) and had 0.06 times the odds of requiring polypharmacy at 5 years compared to early ODT participants (p = 0.01, odds ratio [OR] 0.06, 95% CI 0.00 to 0.65). The odds of having worse rest tremor for early STN DBS + ODT participants were 0.21 times those of early ODT participants (p < 0.001, OR 0.21, 95% CI 0.09 to 0.45). The safety profile was similar between groups.

Conclusions: These results suggest that early DBS reduces the need for and complexity of PD medications while providing long-term motor benefit over standard medical therapy. Further investigation is warranted, and the Food and Drug Administration has approved the conduct of a prospective, multicenter, pivotal clinical trial of DBS in early-stage PD (IDEG050016).

Classification of evidence: This study provides Class II evidence that DBS implanted in early-stage PD decreases the risk of disease progression and polypharmacy compared to optimal medical therapy alone.

Trial registration: ClinicalTrials.gov NCT00282152.

Figure 1. Motor symptoms

(A) Single-blind motor examination (Unified Parkinson's Disease Rating Scale, part III [UPDRS-III]) scores, baseline through 5 years (p = 0.12, β = −3.70, 95% confidence interval [CI] −8.42 to 1.01). (B) Single-blind rest tremor (UPDRS-III item 20) scores, baseline through 5 years (p = 0.005, β = −2.0, 95% CI −3.4 to −0.7). DBS = deep brain stimulation; ODT = optimal drug therapy.

Figure 2. Parkinson disease medications

(A) Levodopa equivalent daily dose (LEDD) (mg), baseline through 5 years (p = 0.04, β = −240 mg, 95% confidence interval −471 to −8). (B) Proportion of participants requiring polypharmacy at each annual study visit. DBS = deep brain stimulation; ODT = optimal drug therapy.

Figure 3. Presence and severity of dyskinesia

Baseline through 5 years (Unified Parkinson's Disease Rating Scale, part IV items 32–35). DBS = deep brain stimulation; ODT = optimal drug therapy.