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NEUROLOGY 2006;67:114-119
© 2006 American Academy of Neurology

CSF levels of growth factors and plasminogen activators in leptomeningeal metastases

B. van de Langerijt, MD, J. M. Gijtenbeek, MD, H.P.M. de Reus, F. C.G.J. Sweep, PhD, A. Geurts-Moespot, J. C.M. Hendriks, PhD, A. C. Kappelle, PhD and M. M. Verbeek, PhD

From the Department of Neurology (B.v.d.L., J.M.G., A.C.K., M.M.V.), Laboratory of Pediatrics and Neurology (B.v.d.L., H.P.M.d.R., M.M.V.), and Departments of Chemical Endocrinology (F.C.G.J.S., A.G.-M.) and Epidemiology and Biostatistics (J.C.M.H.), Radboud University Nijmegen Medical Centre, the Netherlands.

Address correspondence and reprint requests to Dr Verbeek, Department of Neurology, Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, 830 LKN, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands; e-mail: m.verbeek{at}cukz.umcn.nl

Objective: To investigate the diagnostic value of transforming growth factor ß1 (TGFß1), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) in CSF for leptomeningeal metastasis (LM).

Methods: The authors measured concentrations of biomarkers by ELISA in matched samples of CSF and serum, collected from 132 patients with a solid malignancy with LM (n = 19) and without LM (n = 54) and patients with viral (n = 16) and bacterial (n = 16) meningitis and a variety of nonmalignant, noninfectious neurologic disorders (n = 27). Indexes of the biomarkers (CSF/serum value relative to CSF/serum albumin ratios) were calculated to correct for the serum contribution to the CSF marker concentration.

Results: CSF VEGF concentration was significantly higher in LM than in all other groups. VEGF indexes were also higher, although not significant. In contrast, the tPA index was significantly decreased in LM compared with all other groups. The combination of the VEGF and tPA indexes resulted in a sensitivity of 100% for LM and a specificity of 73% for the patient group with a primary tumor but without LM.

Conclusion: Patients with leptomeningeal metastasis have high vascular endothelial growth factor (VEGF) indexes and low tissue-type plasminogen activator (tPA) indexes. As cytologic examination of CSF lacks 100% sensitivity for the diagnosis of leptomeningeal metastasis (LM), the combination VEGF and tPA index analysis may be of additional value in the diagnostic workup of patients suspected of having LM.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the July 11 issue to find the title link for this article.

Disclosure: The authors report no conflicts of interest.

Received September 21, 2005. Accepted in final form Mach 20, 2006.






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