title: CSF protein profiling using Multiplex Immuno-assay: A potential new diagnostic tool for leptomeningeal metastases.
abstract: OBJECTIVE
  The diagnosis of leptomeningeal metastases (LM) is based on clinical symptoms, magnetic resonance imaging (MRI) of brain and spine and cytological analysis of cerebrospinal fluid (CSF). The clinical picture of LM is highly variable and both cytological CSF analysis and contrast-enhanced MRI are limited in sensitivity. More sensitive tools are needed to diagnose LM. We measured a profile of proteins involved in adhesion and inflammation in the CSF of LM and control patients and determined their potential diagnostic value for LM.
  
  
  METHODS
  Using Multiplex Immuno-Assay (MIA), the CSF concentrations of nine soluble adhesion molecules, cyto- and chemokines were measured in patients with cytologically proven LM (n = 57) and control patients with a systemic malignancy (n = 20), aseptic/viral meningitis (n = 11) or other (non-)neurological diseases (n = 19).
  
  
  RESULTS
  We found high CSF levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), soluble Intercellular Adhesion Molecule-1 (sICAM-1), Interleukin-8 (IL-8), Pulmonary and Activation Regulated Chemokine (PARC), Interleukin-18 (IL-18) and Interferon-gamma inducible protein (IP-10) in patients with LM. The CSF protein profile in LM patients differed significantly from the profile found in control patients. Multivariate logistic regression and ROC analysis showed that the MIA-measured CSF protein profile has an additive discriminating value for LM above standard CSF parameters. A combination of total protein, glucose, IL-8, PARC and IP-10 CSF levels proved to be most discriminative between LM and non-LM patients.
  
  
  CONCLUSIONS
  Our results warrant a prospective study to determine whether a CSF protein profile, including IL-8, PARC and IP-10 has diagnostic value compared with CSF cytology, the golden standard for LM.
authors.affiliation: Department of Neurology, G03.228, University Medical Center Utrecht, PO Box 85500, 3584 Utrecht, CX, The Netherlands. d.brandsma@umcutrecht.nl
authors.forename: Dieta
authors.initials: D
authors.lastname: Brandsma
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Hans
authors.initials: H
authors.lastname: Bonfrer
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.forename: Willem
authors.initials: W
authors.lastname: Boogerd
authors.forename: Tiny
authors.initials: T
authors.lastname: Korse
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.forename: Ger
authors.initials: G
authors.lastname: Rijkers
authors.forename: Martin J B
authors.initials: MJ
authors.lastname: Taphoorn
mesh_terms: D000328:Adult; D000368:Aged; D002556:Cerebrospinal Fluid Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D016015:Logistic Models; D008297:Male; D008577:Meningeal Neoplasms / Q000134:cerebrospinal fluid* / Q000556:secondary*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis*; D012372:ROC Curve
chemical_list: D002556:Cerebrospinal Fluid Proteins