Chronic Adaptive versus Conventional Deep Brain Stimulation in Patients with Parkinson’s Disease: A Randomized Crossover Trial with Exploratory Analysis of Baseline-Dependent Response Patterns
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Adaptive deep brain stimulation (aDBS) modulates stimulation based on real-time biomarkers, potentially offering advantages over conventional DBS (cDBS). Clinical evidence under chronic stimulation remains inconclusive.
Objective
To compare aDBS versus cDBS efficacy in Parkinson’s disease under chronic stimulation and explore baseline-dependent patterns of comparative treatment response across outcomes.
Methods
This was a double-blind, randomized crossover trial in nine Parkinson’s disease patients with bilateral subthalamic nucleus DBS. Patients underwent consecutive one-month periods of cDBS and aDBS after a four-month postoperative interval, administered in randomized order. aDBS was delivered using the dual-threshold algorithm that adjusted amplitude in response to subthalamic beta-band LFP power. Primary outcomes were daily ON/OFF durations and dyskinesia duration under optimized medication. A mixed-effects analysis of covariance estimated treatment effects with false discovery rate adjustments. Exploratory analyses examined treatmentby-baseline interactions to characterize patterns of effect modification across outcomes.
Results
No statistically significant differences emerged between the aDBS and cDBS results. However, heterogeneous directional effects were observed: ON duration measures favored cDBS (1.91 h/day shorter in aDBS), while duration of troublesome dyskinesias (0.10 h/day shorter in aDBS) and total UPDRS scores (5.93 points lower in aDBS) favored aDBS. There was substantial between-patient heterogeneity. Exploratory analyses suggested an overall pattern that higher baseline disease burden enhanced cDBS advantages for motor fluctuations and aDBS advantages for motor severity, though the direction and magnitude of modification effects varied across outcome–baseline combinations.
Conclusions
aDBS and cDBS showed no significant differences across clinical outcomes under chronic stimulation with optimized medication. The baseline clinical characteristics of patients may shape the results of aDBS. These findings support comparable efficacy between treatments, warranting larger trials to identify patient subgroups who may benefit from each stimulation approach.
