title: Hypothalamic hamartomas: neuropathological features with and without prior gamma knife radiosurgery.
abstract: BACKGROUND
  The neuropathological consequences of Gamma Knife radiosurgery (GK) on hypothalamic hamartoma (HH) are unknown.
  
  
  OBJECTIVE
  In a cohort of patients undergoing surgery for treatment-resistant epilepsy, we compared surgically resected HH tissue from patients without (group I; n = 19) and with (group II; n = 10) a history of GK (median dose 16 Gy to the 50% isodose margin).
  
  
  METHODS
  Techniques included thick-section stereology for total nucleated and total neuron cell counts, and thin-section immunohistochemistry. Normal human hypothalamus derived from age-matched autopsy material was used as control tissue for CD68 immunohistochemistry. Qualitative scoring of tissue sections was performed by a neuropathologist who was blind to the GK treatment history.
  
  
  RESULTS
  GK is associated with decreased total cell density (p < 0.02). A dose-dependent association of GK with decreased total neuron density approached significance (p = 0.06). Group II HH tissue had significantly more (1) reactive gliosis, (2) thickened capillary endothelium and (3) microglial activation. Degenerative features, including karyorrhexis and pyknotic nuclei, were infrequent in group II and absent in group I HH tissue.
  
  
  CONCLUSIONS
  Nonnecrotizing doses of GK radiosurgery decrease cell density in human HH tissue. Cell loss resulting from GK may contribute to decreased excitation in the neuronal networks responsible for seizure onset in HH tissue.
authors.affiliation: Hypothalamic Hamartoma Program, Phoenix Children's Hospital, Phoenix, AZ 85013, USA. neuropub @ chw.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Kerrigan
authors.forename: Angela
authors.initials: A
authors.lastname: Parsons
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Rice
authors.forename: Kristina
authors.initials: K
authors.lastname: Simeone
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Shetter
authors.forename: Adib A
authors.initials: AA
authors.lastname: Abla
authors.forename: Erin
authors.initials: E
authors.lastname: Prenger
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Coons
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use; D002452:Cell Count; D016923:Cell Death; D002467:Cell Nucleus / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004730:Endothelium, Vascular / Q000473:pathology; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology / Q000601:surgery; D005260:Female; D005911:Gliosis / Q000209:etiology / Q000473:pathology; D006222:Hamartoma / Q000150:complications / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications / Q000473:pathology* / Q000601:surgery; D007223:Infant; D008297:Male; D017628:Microglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology; D016634:Radiosurgery; D012189:Retrospective Studies; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D000927:Anticonvulsants