Objective: Neuropathological investigation of tissue changes in a case with pedunculopontine nucleus (PPN) DBS placed to address axial Parkinson’s disease symptoms and freezing of gait.

Background: Axial symptoms of Parkinson’s disease and freezing of gait may not respond well to typical DBS targets including STN and GPi. PPN has emerged in primates and in rodents as a potential target to treat axial symptoms and potentially improve freezing of gait (FOG). Results in humans have been mixed and challenges include patient selection, optimal contact of stimulation, anatomical targeting errors, optimal stimulation settings and co-stimulation of other targets (STN or GPi). Additionally, local tissue reaction to the DBS lead may affect outcome and there is scarce data on the pathological changes following PPN DBS. We report on a patient whose brain was deposited in the University of Florida DBS Brain Tissue Network Bank.

Methods: There is one PPN DBS case available for study in the University of Florida DBS Brain Tissue Network Bank. A 66 year old man with young onset Parkinson’s disease presented with initial symptoms of rest tremor and stiffness of the left hemibody. Records revealed he had PD with ON medication freezing of gait and right pallidotomy and left STN DBS. He had staged bilateral PPN DBS for his axial symptoms and his L PPN lead was repositioned. He reported only mild initial improvement of his FOG after PPN DBS. Routine neuropathological examination was performed for disease confirmation and for accuracy of lead placement. Immunohistochemistry using GFAP delineated the gliotic response to PPN lead.

Results: STN DBS (L) and pallidotomy improved bradykinesia and rigidity and relief of tremors. Therapeutic impedances for the left PPN DBS were normal. Significant was extensive fibrosis and significant pathological gliosis around the lead (~300um each), which was revealed upon neuropathological examination using Masson’s Trichrome staining and GFAP immunohistochemistry respectively.

Conclusions: It remains unclear what determines tissue reaction to DBS leads, and what consequence this reaction might have on clinical efficacy. Extensive gliosis around DBS leads may explain heterogeneity of results, particularly for FOG and axial symptoms. This case revealed extensive gliosis in the PPN target as compared to the STN. It is unknown if the gliosis is a characteristic of DBS in the brainstem region and whether this impacted clinical outcome. It will be important to collect more cases, as severe gliosis is not common in typical STN and GPi targets (~1/3 of cases with 100um gliosis).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/severe-gliosis-following-ppn-dbs/