Neurohistopathological Findings of the Brain Parenchyma After Long-Term Deep Brain Stimulation: Case Series and Systematic Literature Review

Abstract

ABSTRACTIntroductionThe efficacy of deep brain stimulation (DBS) has been established to treat several movement and psychiatric disorders. However, several aspects, such as the mechanism of action and tissue changes after treatment are incompletely described. Hence, we aimed to describe the neurohistopathological findings of 9 patients who underwent DBS for movement disorders. Additionally, we performed a systematic literature review on postmortem studies after DBS implantation.MethodsWe performed a retrospective study of patients who underwent DBS for movement disorders between 2000-2023 and had postmortem autopsy. Demographics, clinical features, and outcomes were collected. Levodopa equivalent daily dose (LEDD) and total electrical energy delivered (TEED) were calculated. Neurohistopathological assessments were performed from autopsies. A systematic literature review was conducted to summarize the literature.ResultsPostmortem neurohistopathologic assessment of 9 patients who underwent DBS for movement disorders (8 Parkinson’s disease [multiple system atrophy was final diagnosis in 1], and 1 parkinsonism) was performed. Median age at DBS implantation was 65 years (range, 54-69), and most were male (8 patients, 89%). Most common DBS target was the subthalamic nucleus (8 patients, 89%). Median DBS duration was 65 months (range, 7-264 months). Post-DBS reduction in LEDD was found in 7/9 patients, and TEED was increased over time in 5/7 patients. No patients died due to DBS. Neurohistopathological assessment showed gliosis in 7 (78%) patients and activated microglial infiltration in 1 (11%). Additionally, postmortem findings (after DBS) of 59 patients (between 1977-2021) were identified in the literature: 26 (44%) for Parkinson’s disease, 20 (34%) for pain, and 13 (22%) for other conditions.ConclusionOur findings confirm the presence of a local tissue reaction, including gliosis and activated microglial infiltration around the implanted DBS electrodes. The effect of the local changes on the clinical efficacy of DBS is not established. Further DBS postmortem studies and standardization of tissue processing are needed.