title: Pathological response of cavernous malformations following radiosurgery.
abstract: OBJECTIVE
  Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients. The authors of the present study aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.
  
  
  METHODS
  During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors' institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.
  
  
  RESULTS
  Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.
  
  
  CONCLUSIONS
  Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role.
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Shin
authors.affiliation: Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Murdoch
authors.affiliation: Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Faraji
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kano
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Zwagerman
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gardner
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: L Dade
authors.initials: LD
authors.lastname: Lunsford
authors.affiliation: Departments of 1 Neurological Surgery and.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Friedlander
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000150:complications / Q000473:pathology* / Q000601:surgery*; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: AVM = arteriovenous malformation; CM = cavernous malformation; MMP-9 = matrix metallopeptidase 9; SRS = stereotactic radiosurgery; VEGF = vascular endothelial growth factor; bFGF = basic fibroblast growth factor; brain hemorrhage; cavernous malformation; stereotactic radiosurgery