Detection of meningeal fibrosis after subarachnoid haemorrhage by assaying procollagen propeptides in cerebrospinal fluid

Abstract

Objective: To study whether meningeal collagen synthesis under normal conditions is reflected in the CSF and whether a meningeal fibroproliferative reaction or fibrosis after subarachnoid haemorrhage can be detected by measuring markers of collagen synthesis in the CSF.

Methods: Serum samples and CSF were collected from 56 patients with various neurological symptoms and from nine patients with a recent subarachnoid haemorrhage. The concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were measured using radioimmunoassays.

Results: The mean(SD) concentration of PICP was 75.2 (SD 13.6) microgram/l and that of PIIINP 3.56 (SD 0.91) microgram/l in the CSF of the controls, and the CSF/serum ratios were 0.74 (SD 0.24) for PICP and 1.34 (SD 0.48) for PIIINP. A 1.4-fold increase in both the PICP (p=0.001) and the PIIINP (p=0.001) concentration was found in patients with a neurological disease and with an abnormal CSF leucocyte count or protein concentration. In eight patients with a recent subarachnoid haemorrhage the PICP was 5.9-fold higher (p<0.001) and the PIIINP concentration 7.7-fold higher (p<0.001) than that in the controls, whereas no difference was found in the serum values. Similar high concentrations were also found in a patient from whom the CSF sample was obtained before operation for aneurysm.

Conclusions: The intrathecal compartment is a site for active collagen synthesis under normal conditions. The synthesis rate is markedly increased in patients with a recent subarachnoid haemorrhage, suggesting a fibroproliferative reaction or fibrosis. Assays of procollagen propeptides may be useful in the clinical diagnosis of meningeal fibrosis and their use may enable the identification of diseases and symptoms aetiologically related to meningeal fibrosis.