Objective: To examine neuropathological changes surrounding deep brain stimulation (DBS) electrode in pedunculopontine nucleus (PPN) region.

Background: Freezing of gait (FOG) in Parkinson’s disease (PD) is characterized by episodes of temporary halting of gait and can have severe impact on quality of life. Pathogenesis of FOG is not understood, but responds poorly to medication. Subthalamic nucleus (STN) or globus pallidus internus (GPi) DBS can be effective in 30-40% of cases, and PPN has emerged as a potential target. DBS of the STN, GPi or of the PPN alone, or in combination has been shown in a few cases to improve symptoms of FOG. Challenges of PPN region DBS include optimal patient selection, targeting errors, and determination of optimal stimulation settings. Tissue reaction immediately surrounding the DBS lead could affect therapeutic outcomes. Studies of pathological changes around DBS leads are very few, and do not exist for PPN DBS. Here we present a patient with PD with FOG, with right pallidotomy, left STN DBS and bilateral PPN DBS. We report a slight improvement of FOG, with a pronounced gliotic tissue reaction associated with DBS leads.

Method: Over 80 cases from the UF DBS Brain Tissue Bank were examined to assess tissue responses associated with DBS electrodes. A routine neuropathological examination was performed to confirm clinical diagnosis, to confirm DBS lead placements, and tissue response to electrode determined using immunohistochemical techniques. One case in a 66-year-old man, with young onset PD and initial symptoms of rest tremor and stiffness of the left side revealed a very significant gliotic capsule surrounding the PPN lead.

Results: The left STN DBS had good clinical benefit whereby bradykinesia and rigidity were improved, alongwith tremor suppression. The left PPN DBS had not delivered clinical benefit, and neuropathologic examination showed extensive peri-lead gliosis. The therapeutic impedances measured from the left STN DBS and left PPN DBS were within normal range, despite capsule formation.

Conclusion: We still do not fully comprehend why some patients have an extensive tissue reaction to DBS leads, and whether this can result in a lowered clinical efficacy. This case highlights the importance of DBS brain tissue repositories to facilitate detailed neuropathologic evaluation and translational research efforts.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuropathological-changes-following-ppn-region-dbs/