Congratulations to Drs. Stiep, Rameriz-Zamora and Okun on the publication of “Apathy Following Bilateral Subthalamic Deep Brain Stimulation for Parkinson’s Disease: The INTREPID Randomized Controlled Trial (P8-11.001),” in the May issue of Neurology.

Abstract

Objective: To determine frequency and predictors of both improvement and worsening of apathy in participants receiving bilateral subthalamic deep brain stimulation (STN-DBS) for treatment of Parkinson’s Disease (PD) as part of the INTREPID randomized controlled trial.

Background: Many studies have suggested that apathy can be associated with dopaminergic denervation and can possibly be unmasked by drug withdrawal and by aggressive drug tapering following STN-DBS surgery. Additionally, it has been suspected that stimulation of the limbic-associative sub-regions of the STN might serve as a catalyst, an independent cause or act synergistically with dopaminergic medication reduction.

Design/Methods: INTREPID (ClinicalTrials.gov: NCT01839396) is a multi-center, prospective, double-blinded, randomized controlled trial. Participants with advanced PD received bilateral STN-DBS and completed a neuropsychological battery at screening (prior to DBS) and at follow up (12-months). Apathy was assessed using the Starkstein Apathy Scale (SAS). Demographic and clinical data including age, gender, disease duration, disease severity, levodopa-equivalent daily dose (LEDD), and imaging correlates of DBS (including location and volume of stimulated tissue) were analyzed.

Results: There were a total of 160 subjects evaluated at 1-year following STN-DBS, 44 (27.5%) reported an improvement in apathy scores of at least 5-points, and 7 (4.4%) an improvement >10 points. Eighteen (11.3%) participants had worsening apathy scores > 5 points, and 8 (5%) reported worsening > 10 points. Aggregation of stimulation field models (SFM) across the cohorts, indicated that worsening of apathy was associated with activation of limbic and associative areas of STN.

Conclusions: Bilateral STN-DBS in a large and prospective dataset revealed both improvement and worsening of apathy at 1-year follow-up visits. Further analysis of LEDD, dopamine agonist use, and volume of tissue activation may help us to understand the clinical factors underpinning apathy following DBS. Appropriate counseling preoperatively coupled with post-operative monitoring will be important for setting expectations and for employing appropriate treatment when necessary.



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