title: Brain alterations with deep brain stimulation: New insight from a neuropathological case series.
abstract: BACKGROUND
  Previous studies on human brain tissue alterations caused by deep brain stimulation described glial and reactive inflammatory changes. In the current pathoanatomical study, we extended the analysis to signs of axonal changes and the influence of concomitant disease.
  
  
  METHODS
  Brains of 10 patients with Parkinson's disease or essential tremor and a total of 18 electrodes were systematically examined up to 7.5 y after surgery.
  
  
  RESULTS
  In general, tissue that had long-term contact with the electrode material exhibited astrogliosis in all, T-lymphocytes in 93%, and multinucleated giant cells in 68% of patients. Immunohistochemistry showed an increase in amyloid precursor protein immunoreactive axonal swellings in the brain at the electrically active parts of the electrodes. Patients who died of septicemia showed a more severe astrogliosis and giant cell reaction than patients who died of cardiovascular events. Parkinson's disease or essential tremor did not differentially produce histopathological changes around the electrodes.
  
  
  CONCLUSIONS
  Long-term electrical stimulation by deep brain stimulation causes minor axonal changes. The cause of death, but not the underlying neurological disease, affects the histopathological changes around the electrode. The findings need to be reproduced by examining larger patient subgroups.
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.|Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kronenbuerger
authors.affiliation: Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Kay Wilhelm
authors.initials: KW
authors.lastname: Nolte
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: Volker Arnd
authors.initials: VA
authors.lastname: Coenen
authors.affiliation: Department of Neurology, University of Berne, Inselspital, Berne, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Burgunder
authors.affiliation: Department of Neurosurgery, Medical School Hannover (MHH), Hannover, Germany.
authors.forename: Joachim K
authors.initials: JK
authors.lastname: Krauss
authors.affiliation: Institute of Neuropathology, RWTH Aachen University Hospital, Aachen, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology*; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D004567:Electrodes, Implanted / Q000009:adverse effects*; D020329:Essential Tremor / Q000473:pathology / Q000628:therapy*; D005260:Female; D005549:Foreign-Body Reaction / Q000209:etiology*; D005911:Gliosis / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000473:pathology / Q000628:therapy*; D016037:Single-Blind Method
keywords: axonal lesions; deep brain stimulation; gliosis; inflammation; post-mortem analysis