Absence of STN Neuronal Activity during MER in DBS Surgery: Diagnostic and Clinical Implications.

INTRODUCTION: Intraoperative microelectrode recording (MER) is a widely employed technique for the physiological identification of the subthalamic nucleus (STN) during deep brain stimulation (DBS) surgery targeting the STN. However, failure to detect typical STN activity may raise concerns about diagnostic accuracy and treatment efficacy. Objective of this study were to retrospectively evaluate the clinical characteristics and long-term outcomes of patients with advanced Parkinson's disease (PD) in whom STN neuronal activity was not detected during intraoperative MER and to explore the implications of this finding for differential diagnosis and DBS candidacy. METHODS: Among 624 STN-DBS procedures performed at Juntendo University Hospital between 2012 and 2024, we identified 3 patients (0.5%) in whom intraoperative MER failed to detect typical STN neuronal activity. Clinical records were reviewed retrospectively, including demographic data, levodopa responsiveness, preoperative images, intraoperative MER findings, surgical decision-making processes, and postoperative clinical courses. RESULTS: All 3 patients were male, in their 60s at the time of surgery, with disease durations ranging from 5 to 7 years. Cognitive function was preserved in all cases. Gait disturbance was a prominent early symptom, and all patients experienced relatively early wearing-off phenomena. None exhibited dyskinesia, yet all showed good responsiveness to levodopa, confirmed by preoperative levodopa challenge tests. Despite multiple MER trajectories, no characteristic STN neuronal firing patterns were observed. DBS electrodes were implanted according to the initial surgical plan in 2 cases; in the other case, implantation was aborted. Following surgery, all patients demonstrated progressive axial motor deterioration. Based on their clinical course and imaging findings, all were ultimately diagnosed with or strongly suspected to have progressive supranuclear palsy-parkinsonism (PSP-P). CONCLUSIONS: The absence of detectable STN activity during intraoperative MER may reflect underlying neurodegenerative pathology distinct from idiopathic PD, such as PSP-P. These findings suggest that MER, beyond its role in anatomical targeting, may serve as a valuable intraoperative biological indicator for diagnostic refinement. Even within a multidisciplinary setting led by movement disorder specialists, distinguishing PD from PSP-P prior to surgery remains a significant challenge. Improved diagnostic accuracy is critical to optimize patient selection for DBS and to prevent ineffective or potentially deleterious interventions.