title: Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis.
abstract: OBJECTIVE
  To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM).
  
  
  METHODS
  The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM.
  
  
  RESULTS
  High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges.
  
  
  CONCLUSIONS
  In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.
authors.affiliation: Departments of Neurology, University of Innsbruck, Innsbruck, Austria. Guenther.Stockhammer@uibk.ac.at
authors.forename: G
authors.initials: G
authors.lastname: Stockhammer
authors.forename: W
authors.initials: W
authors.lastname: Poewe
authors.forename: S
authors.initials: S
authors.lastname: Burgstaller
authors.forename: F
authors.initials: F
authors.lastname: Deisenhammer
authors.forename: A
authors.initials: A
authors.lastname: Muigg
authors.forename: S
authors.initials: S
authors.lastname: Kiechl
authors.forename: E
authors.initials: E
authors.lastname: Schmutzhard
authors.forename: H
authors.initials: H
authors.lastname: Maier
authors.forename: S
authors.initials: S
authors.lastname: Felber
authors.forename: P
authors.initials: P
authors.lastname: Schumacher
authors.forename: E
authors.initials: E
authors.lastname: Gunsilius
authors.forename: G
authors.initials: G
authors.lastname: Gastl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002277:Carcinoma / Q000150:complications* / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D003937:Diagnosis, Differential; D016228:Endothelial Growth Factors / Q000097:blood / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008577:Meningeal Neoplasms / Q000150:complications* / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D008581:Meningitis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000134:cerebrospinal fluid; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D015415:Biomarkers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012709:Serum Albumin; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors