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Background: Closed-loop neurostimulation is a novel alternative therapy for medically intractable focal epilepsy for patients who are not candidates for surgical resection of a seizure focus. Electrodes for this system can be implanted either within the brain parenchyma or in the subdural space. The electrodes then serve the dual role of detecting seizures and delivering an electrical signal aimed at aborting seizure activity. The Responsive Neurostimulation (RNS®) system (Neuropace, Mountain View, CA, USA) is an FDA-approved implantable device designed for this purpose. Objective: One of the challenges of the brain machine interface devices is the potential for implanted neurostimulator devices to induce progressive gliosis, apart from that associated with the minimal trauma at implantation. Gliosis has the potential to alter impedances over time, thereby affecting the clinical efficacy of these devices, and also poses a challenge to the prospects of in vivo repositioning of depth electrodes. We present a clinical case with 3-year follow-up and pathology. Methods: Single-case, retrospective review within a randomized trial with specific minimum follow-up and impedance measurements. Results: Impedance changes in the surface electrode over time were observed. Surgical pathological findings revealed significant gliosis in the leptomeninges of the cortices. Conclusion: We report, for the first time, long-term impedance recordings from a surface electrode associated with pathologic findings of gliosis at the Neuropace device-tissue interface in a patient who was enrolled in the multicenter RNS System Pivotal Clinical Investigation. Further study is required to elucidate the temporal relationship of pathological findings over time. Impedance changes were more complex than can be explained by a progressive or transient pathological mechanism. Further effort is required to elucidate the relationship between impedance change and seizure event capture. [ABSTRACT FROM AUTHOR]