Journal of Neurology

, Volume 253, Issue 9, pp 1177–1184 | Cite as

CSF protein profiling using Multiplex Immuno-assay

A potential new diagnostic tool for leptomeningeal metastases
  • Dieta Brandsma
  • Emile E. Voest
  • Wilco de Jager
  • Hans Bonfrer
  • Ale Algra
  • Willem Boogerd
  • Tiny Korse
  • Jaap C. Reijneveld
  • Marcel M. Verbeek
  • Ger Rijkers
  • Martin J.B. Taphoorn
ORIGINAL COMMUNICATION

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.

Patients and 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-γ 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.

Conclusion

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.

Keywords

leptomeningeal metastases cerebrospinal fluid multiplex immuno-assay soluble adhesion molecules cytokines 

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Copyright information

© Steinkopff Verlag Darmstadt 2006

Authors and Affiliations

  • Dieta Brandsma
    • 1
    • 2
  • Emile E. Voest
    • 2
  • Wilco de Jager
    • 3
  • Hans Bonfrer
    • 4
  • Ale Algra
    • 1
    • 5
  • Willem Boogerd
    • 6
  • Tiny Korse
    • 4
  • Jaap C. Reijneveld
    • 7
  • Marcel M. Verbeek
    • 8
  • Ger Rijkers
    • 3
  • Martin J.B. Taphoorn
    • 1
    • 9
  1. 1.Dept. of Neurology, G03.228University Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Laboratory of Medical Oncology, Dept. of Medical OncologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  3. 3.Dept. of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Center UtrechtIACOPO Institute for Translational MedicineUtrechtThe Netherlands
  4. 4.Dept. of Clinical ChemistryAntoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  5. 5.Dept. of Clinical EpidemiologyJulius Center for Health Sciences and Primary Care, University Medical Center UtrechtUtrechtThe Netherlands
  6. 6.Dept. of NeurologyAntoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  7. 7.Dept. of NeurologyVU University Medical CenterAmsterdamThe Netherlands
  8. 8.Dept. of NeurologyUniversity Medical CenterNijmegenThe Netherlands
  9. 9.Dept. of NeurologyMedical Center HaaglandenDen HaagThe Netherlands

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