Neurohistopathological findings of the brain parenchyma after long-term deep brain stimulation: Case series and systematic literature review

Introduction: Efficacy of deep brain stimulation (DBS) is established for several movement and psychiatric disorders. However, the mechanism of action and local tissue changes are incompletely described. We describe neurohistopathological findings of 9 patients who underwent DBS for parkinsonism and performed a systematic literature review on postmortem pathologic reports post-DBS.

Methods: We performed a retrospective study of patients who underwent DBS for Parkinsonism between 2000 and 2023 and had postmortem neurohistopathological assessments. Demographics and clinical features were collected. Levodopa equivalent daily dose (LEDD) and total electrical energy delivered (TEED) were calculated. A systematic literature review was conducted.

Results: Postmortem assessment of 9 DBS patients was performed (7 Parkinson's disease [PD], 1 Parkinsonism, 1 Multiple System Atrophy with pre-DBS clinical diagnosis of PD). Median age at DBS was 65 years (range, 54-69), 8 were male. Subthalamic nucleus was targeted in 8 patients, globus pallidus in 1. Median DBS duration was 65 months (range, 7-264). Post-DBS LEDD reduction was found in 7/9 patients and TEED increased over time in all cases. There were no DBS-related deaths. Neurohistopathological assessment showed gliosis in 7 patients and activated microglial infiltration in 1. In the literature (between 1977 and 2021), 59 patients with postmortem post-DBS findings were identified: 26 (44 %) PD, 20 (34 %) pain, and 13 (22 %) other conditions.

Conclusion: Findings confirm presence of a local tissue reaction (gliosis and activated microglia) around the implanted leads. The effect of local changes on the clinical efficacy of DBS is not established. Further DBS postmortem studies and standardization of tissue processing are needed.