Challenging the Traditional Paradigm: Clinical and Functional Outcomes of Early versus Very-Early Subthalamic Deep Brain Stimulation in Parkinson’s Disease
TL;DR
Very-early DBS was associated with greater postoperative medication reduction and more favorable early functional outcomes, while long-term motor outcomes remained comparable between groups, however, differences in baseline medication burden may have contributed to the observed LEDD reduction patterns.
Abstract
Abstract Introduction Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for advanced Parkinson’s disease (PD). While traditionally reserved for later stages, growing evidence suggests earlier intervention may offer benefits. This study compares outcomes of early versus very-early DBS in a single-center cohort. Methods This retrospective study included 65 PD patients undergoing STN-DBS (2015–2025), grouped as very-early (<5 years disease duration, n = 32) or early (≥5 years, n = 33). Groups were comparable in age, sex, and disease severity. Results included Hoehn and Yahr (H&Y), UPDRS-III, MMSE, and levodopa equivalent daily dose (LEDD) assessed preoperatively, early postoperatively, and at 3 years. Results Mean age was 62.45 ± 8.79 years; 69.2% were male. Both groups showed significant postoperative improvement in H&Y (p < 0.001), with partial decline at 3 years, though still better than baseline. No significant group-time interaction was observed for H&Y or UPDRS-III, indicating similar long-term motor outcomes. The group-by-time interaction for LEDD was significant (p = 0.002), reflecting different medication trajectories: both groups converged to similar postoperative LEDD levels despite the early DBS group starting from a substantially higher baseline (1,010 ± 514 vs 676 ± 394 mg/day; p = 0.005). Multivariable regression showed that baseline preoperative LEDD was the dominant predictor of postoperative medication reduction; after adjustment, surgical timing was no longer significantly associated with LEDD reduction (p = 0.622). Very-early DBS patients had lower early postoperative H&Y scores (p = 0.022). Six patients were reclassified as PD plus during follow-up; sensitivity analyses yielded consistent results. Conclusion Both very-early and early STN-DBS provide significant short-term motor benefits, though some decline occurs over time. Very-early DBS was associated with greater postoperative medication reduction and more favorable early functional outcomes, while long-term motor outcomes remained comparable between groups. However, differences in baseline medication burden may have contributed to the observed LEDD reduction patterns.