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CSF protein profiling using Multiplex Immuno-assay

A potential new diagnostic tool for leptomeningeal metastases

Journal of Neurology volume 253, pages 1177–1184 (2006)Cite this article

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.

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Author information

Affiliations

  1. Dept. of Neurology, G03.228, University Medical Center Utrecht, PO Box 85500, 3584, Utrecht, CX, The Netherlands

    Dieta Brandsma, Ale Algra & Martin J.B. Taphoorn

  2. Laboratory of Medical Oncology, Dept. of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

    Dieta Brandsma & Emile E. Voest

  3. Dept. of Pediatric Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, IACOPO Institute for Translational Medicine, Utrecht, The Netherlands

    Wilco de Jager & Ger Rijkers

  4. Dept. of Clinical Chemistry, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Hans Bonfrer & Tiny Korse

  5. Dept. of Clinical Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    Ale Algra

  6. Dept. of Neurology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

    Willem Boogerd

  7. Dept. of Neurology, VU University Medical Center, Amsterdam, The Netherlands

    Jaap C. Reijneveld

  8. Dept. of Neurology, University Medical Center, Nijmegen, The Netherlands

    Marcel M. Verbeek

  9. Dept. of Neurology, Medical Center Haaglanden, Den Haag, The Netherlands

    Martin J.B. Taphoorn

Authors
  1. Dieta Brandsma
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  2. Emile E. Voest
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  3. Wilco de Jager
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  4. Hans Bonfrer
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  5. Ale Algra
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  6. Willem Boogerd
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  7. Tiny Korse
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  8. Jaap C. Reijneveld
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  9. Marcel M. Verbeek
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  10. Ger Rijkers
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  11. Martin J.B. Taphoorn
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Corresponding author

Correspondence to Dieta Brandsma.

Additional information

Received in revised form: 2 November 2005

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Brandsma, D., Voest, E.E., de Jager, W. et al. CSF protein profiling using Multiplex Immuno-assay. J Neurol 253, 1177–1184 (2006). https://doi.org/10.1007/s00415-006-0187-y

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  • DOI: https://doi.org/10.1007/s00415-006-0187-y

Keywords

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