Independent elevation of plasma fibulin-5 proceeding chronic hydrocephalus development after aneurysmal subarachnoid hemorrhage

Background

Aneurysmal subarachnoid hemorrhage (aSAH) causes chronic hydrocephalus (CH) due to disturbance in the reabsorption of cerebrospinal fluid following subarachnoidal fibrosis via inflammatory reactions or blood clotting products. Fibulin-5 (FBLN5) is one of matricellular proteins associated with fibrosis processes.

Objective

The aim of this study was to assess whether FBLN5 elevation is related to CH after aSAH.

Methods

This study prospectively enrolled consecutive aSAH patients at 9 institutions in Japan from 2013 to 2016. Plasma FBLN5 levels at days 1–3, 4–6, 7–9, and 10–12 were measured. Relationships between plasma FBLN5 levels and incidence of CH were analyzed. Multivariate logistic regression analyses were performed on clinical variables with a p value of < 0.05 on univariate analyses and plasma FBLN5 levels with the highest area under the receiver-operating characteristic (ROC) curve.

Results

A total of 229 aSAH patients were analyzed, and CH occurred in 67 patients. FBLN5 levels at days 4–6 from aSAH onset elevated in patients resulting in subsequent CH occurrence. The ROC curve analyses revealed that the area under the curve (AUC) at days 4–6 post-aSAH was the highest (AUC, 0.592; 95 % confidence interval, 0.514–0.671) among the four time points. Multivariate logistic regression analyses using clinical variables related to CH on univariate analyses and plasma FBLN5 levels at days 4–6 post-aSAH revealed that FBLN5 levels at days 4–6 post-aSAH ≥ 366.4 ng/mL (adjusted odds ratio, 3.14) were an independent determinant of subsequent CH development.

Conclusion

The elevation of plasma FBLN5 levels in a subacute phase of aSAH may contribute to the development of CH. FBLN5 may be a molecular target to develop a new therapy against post-aSAH CH.