The microlesion effect is associated with global cognitive impairment and predicts motor outcomes after subthalamic deep brain stimulation in Parkinson's disease

J Neurol. 2025 Oct 18;272(11):708. doi: 10.1007/s00415-025-13443-z.

Abstract

Objective: A postoperative microlesion effect (MLE) is regarded as a reliable predictor of the subsequent efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS) treatment. However, the predictive ability of MLE for postoperative motor improvement after DBS surgery in PD patients with global cognitive impairment (GCI) has not been fully explored.

Methods: This was a prospective, open-label, single-center study with a 6-month follow-up. Patients were divided into three groups based on the MLE response. After separately stratifying by MLE and by global cognitive impairment, we compared postoperative motor symptoms, as assessed by the MDS-UDPRS III, across these strata. To further investigate the impact of global cognitive impairment on long-term postoperative motor outcomes, a mediation analysis was conducted.

Results: There were 18 patients (40%) classified as the Low MLE group, 19 patients (42.2%) as the Medium MLE group, and 8 patients (17.8%) as the High MLE group. Overall, the interaction effects of Group and Time (P = 0.008) were observed for changes in the MDS-UPDRS III score from baseline. The NC group exhibited a greater improvement compared to the GCI group. Global cognitive impairment was strongly associated with long-term postoperative motor outcomes (P = 0.002), with MLE serving as a mediator (indirect effect = - 0.10, P = 0.042).

Interpretation: In summary, our study demonstrated that postoperative MLE is common and has strong predictive value for the efficacy of motor symptoms six months after STN-DBS. Additionally, MLE may partially mediate the detrimental effects on motor outcomes caused by global cognitive impairment.

Trial registry: CLINICALTRIALS.

Gov identifier: NCT06685510.

Keywords: Deep brain stimulation; Global Cognitive Impairments; Microlesion effect; Parkinson’s Disease; Subthalamic nucleus.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Deep Brain Stimulation* / adverse effects
  • Deep Brain Stimulation* / methods
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease* / complications
  • Parkinson Disease* / physiopathology
  • Parkinson Disease* / therapy
  • Prospective Studies
  • Subthalamic Nucleus* / surgery
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT06685510