Introduction: In 2015, directional leads have been released in Europe for deep brain stimulation (DBS) and have been particularly used for subthalamic nucleus (STN) DBS for Parkinson’s disease (PD). In this study, we aimed to compare an omnidirectional and directional leads cohort of PD patients when it comes to clinical effectiveness and to assess the correlation with volume of tissue activated-target overlap (VTA-target). Methods: A total of 60 consecutive patients were retrospectively included. Twenty-seven patients with bilateral directional leads were compared to 33 patients with bilateral omnidirectional leads. MDS-UPDRS part III scores, levodopa equivalent daily dose (LEDD), and VTA overlaps using both motor STN region and motor improvement sweet spot volume were compared at 12 months after surgery. Results: There is a significantly higher LEDD reduction in the directional leads group (51.3% reduction vs. 42.7% reduction, p = 0.042) when compared to the omnidirectional group, with similar MDS-UPDRS III motor scores at 12 months. Omnidirectional leads patients had a significantly superior VTA-motor STN overlap volume than directional leads patients (32.01 mm3 vs. 20.38 mm3, p = 0.0226). In directional leads patients, LEDD reduction was correlated to VTA overlap with the overall motor improvement mean map sweet spot (R = 0.36, p = 0.036), which was not the case for omnidirectional leads patients (R = 0.11, p = 0.276). Forty-one percent of patients implanted with directional leads had a directional stimulation setting at 12 months, compared to 33% at 3 months follow-up. In directional leads patient’s subgroup analysis, there was no significant difference in MDS UPDRS III scores, LEDD reduction, VTA overlaps with motor STN, or overall motor improvement mean map sweet spot between patients stimulated omnidirectionally and directionally at 12 months. Conclusion: At 12 months, when compared to omnidirectional leads, directional leads manage with smaller VTA-target overlaps to obtain comparable MDS-UPDRS III scores with greater LEDD reduction in STN DBS for PD patients.

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