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.