ABSTRACT
OBJECTIVE: To investigate the diagnostic value of transforming growth factor beta(1) (TGFbeta(1)), 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.
Subject(s)
Breast Neoplasms/cerebrospinal fluid , Meningeal Neoplasms/cerebrospinal fluid , Plasminogen Activators/cerebrospinal fluid , Vascular Endothelial Growth Factor A/cerebrospinal fluid , Adult , Aged , Biomarkers , Breast Neoplasms/pathology , Breast Neoplasms/secondary , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Magnetic Resonance Imaging/methods , Male , Meningeal Neoplasms/pathology , Meningeal Neoplasms/secondary , Middle Aged , Neoplasm Metastasis/pathology , Plasminogen Activators/blood , Vascular Endothelial Growth Factor A/bloodABSTRACT
OBJECT: Hydrocephalus is characterised by elevated intracranial pressure (ICP) and gives rise to brain damage. The aim of this study was to investigate the significance of brain specific proteins as markers in the evaluation of brain damage in hydrocephalus. Therefore we determined the levels of four brain specific proteins in cerebrospinal fluid (CSF) and serum of symptomatic hydrocephalic patients. METHODS: During 41 CSF shunt-operations (both primarily placed shunts and shunt-revisions) CSF and blood samples were obtained and analysed for neuron-specific enolase (NSE), S-100b, glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). The results were compared with an age-matched control group. Patients with varying clinical symptoms, denoting different levels of increased intracranial pressure prior to surgery, were included in this study. RESULTS: We observed significantly increased CSF-levels of S-100b and GFAP in the hydrocephalic patients, whereas NSE and MBP were markedly increased only in patients with very severe symptoms. Serum levels of all proteins were only minimally increased and did not correlate with CSF-levels. The slightly elevated levels of CSF-NSE in most of the patients suggest only subtle neuronal damage, which is not related to permanent neurological symptoms. The elevated levels of S-100b and GFAP are indicative of a reactive astrogliosis, which has also been demonstrated in histopathological studies. No demyelination seems to occur, according to the normal levels of MBP observed in this study. CONCLUSIONS: Although CSF levels of brain specific proteins are elevated in hydrocephalic patients, indicating brain damage due to hydrocephalus, neither CSF- nor serum-concentrations of brain specific proteins seem to be valuable tools in the clinical evaluation of the severity of hydrocephalus.
