title: Neurohistopathological findings at the electrode-tissue interface in long-term deep brain stimulation: systematic literature review, case report, and assessment of stimulation threshold safety.
abstract: OBJECTIVE
  Despite the widespread use of deep brain stimulation (DBS) in the treatment of neurologic disorders for over a quarter of a century, there has not been a systematic review and analyses of cases in which long-term postmortem clinic-pathologic data have been collected demonstrating the effects of chronically implanted electrodes and electrical stimulation on human brain tissue. Our objective is to provide a comprehensive systematic review of the literature on clinicopathologic findings of DBS tissue-electrode interface (TEI) and to determine types and prevalences of neuropathological findings among electrode materials and stimulation parameters and to augment this with previously unpublished histopathological data, images, and analyses from a DBS case implanted for 12 years, providing the longest duration histopathological follow-up.
  
  
  METHODS
  A Medline literature review identified DBS cases upon which postmortem clinicopathologic follow-up was performed with adequate characterization of TEI. Direct follow-up with authors augmented this with unpublished data and neuropathological details.
  
  
  RESULTS
  We identified 40 cases, mean age 59.1 ± 13.0 (range: 21-88) years, involving 58 implanted DBS electrodes. The mean postmortem histopathological follow-up of the implanted DBS electrodes was 22.2 ± 29.2 (range: 0.067-146) months, including our case with a 12-year follow-up. The following histological changes were identified: fibrous sheaths (5-25 μm thickness) surrounding the electrode (94%), fibrillary gliosis (73%), reactive astrocytes (78%), multinucleated giant cells (75%), mononuclear leukocytes (92%), and macrophages (91%). Microglial activation (60%), axonal spheroids (64%), and neuronal loss (60%) were less common and absent at 12-year follow-up in the index case. This is seventh case reporting T cell presence at the TEI.
  
  
  CONCLUSIONS
  Neuropathological findings from published cases and our 12-year follow-up index case confirm the long-term safety of neuromodulation and stimulation thresholds and demonstrate persistence of T cells and occasional subclinical focal tissue injury.
authors.affiliation: Department of Neurosurgery, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DiLorenzo
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: Richard K
authors.initials: RK
authors.lastname: Simpson
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Takei
authors.forename: Suzanne Z
authors.initials: SZ
authors.lastname: Powell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D004567:Electrodes, Implanted / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000473:pathology* / Q000628:therapy*; D055815:Young Adult
keywords: Deep brain stimulation; electrodes; implanted electrodes; movement disorders; neuromodulation; pathology