Phosphorylated TDP-43 and tau deposition around the tip of deep brain stimulation leads

Deep brain stimulation (DBS) is an established and effective surgical treatment for movement disorders, including Parkinson's disease (PD). However, postmortem studies of patients with PD have revealed the presence of gliosis and inflammatory responses around the tracts of DBS electrodes. The objective of this study was to investigate the deposition of abnormal proteins, including phosphorylated tau (p-tau) and transactivation response DNA-binding protein 43 kDa (p-TDP-43), around the tips of DBS electrodes. Neuropathological examination was performed in two Japanese patients with PD: Case 1 describes a patient who underwent DBS lead placement into the left ventral intermediate nucleus of the thalamus at 79 years of age, and died at 88 years of age; Case 2 describes a patient who underwent DBS lead placement into the bilateral subthalamic nuclei at 70 years of age, and died 14 years after surgery. Postmortem neuropathological examination revealed fibrous gliosis, mild infiltration of lymphocytes, and hemosiderin deposition around the DBS lead tip-associated defects. Moreover, p-TDP-43 and p-tau deposits were visible around the electrode termination sites in both cases. These findings suggest that p-TDP-43 and p-tau accumulated around the DBS lead tip in response to chronic DBS. This is the first study to report the deposition of p-TDP-43 around the tip of a DBS electrode.