Challenging the Traditional Paradigm: Clinical and Functional Outcomes of Early Versus Very-Early Subthalamic Deep Brain Stimulation in Parkinson's Disease.

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 very-early versus 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 & Yahr (H&Y), Unified Parkinson's Disease Rating Scale pt III (UPDRS-III), Mini Mental State Examination (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 (1010±514 vs 676±394mg/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.