Effects of deep brain stimulation on non motor fluctuations in Parkinson’s disease (assessed with the NMF severity scale)

Background: Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor fluctuations (MF) in Parkinson's disease (PD), but its impact on non-motor fluctuations (NMF) remains unclear. As NMFs are frequent, disabling, and affect quality of life, understanding their response to DBS is critical. Objectives: To assess the presence of NMF after STN-DBS, identify preoperative factors of improvement, and compare NMF responses to DBS and levodopa. Methods: This project is an ancillary study of the French multicenter PREDISTIM cohort. We used the validated Non-Motor Fluctuation Severity Scale (NMF2S) to evaluate NMFs one year after STN-DBS and before surgery when data were available. Evaluations were performed under standardized conditions (OFF-Dopa/OFF-Stim vs. OFF-Dopa/ON-Stim). Results: We included 284 PD patients assessed one year after STN-DBS using the NMF2S scale. Preoperative data were available for 153 patients. Evaluations were performed under standardized stimulation conditions (OFF-Dopa/OFF-Stim vs. OFF-Dopa/ON-Stim).STN-DBS led to a 41.1% reduction in NMF severity, with anxiety, concentration difficulties, and pain showing the most improvement. However, DBS effects were less pronounced than those of levodopa, especially for psychiatric symptoms. NMF improvement did not correlate with motor improvement. Among all preoperative variables, only the levodopa response in the cognitive domain was associated with post-DBS NMF benefit. Conclusions: STN-DBS significantly improves NMFs, although to a lesser extent than levodopa. The dissociation between motor and non-motor responses underscores the need for specific markers to predict NMF outcomes. These findings support the integration of NMF assessment into DBS indications and patient selection.