Plasma levels of thrombin-cleaved osteopontin as a surrogate biomarker of subsequent chronic shunt-dependent hydrocephalus development following aneurysmal subarachnoid hemorrhage

Chronic shunt-dependent hydrocephalus (SDHC) is a major contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH), reportedly with arachnoid fibrosis implicated in its pathophysiology. In the pathogenesis of fibrosis, N-terminal half of osteopontin (OPN N-half), generated via thrombin cleavage of full-length osteopontin (FL-OPN), is linked to a potent fibrinogenic factor. In this study, clinical data and plasma samples were prospectively collected from 141 consecutive aSAH patients treated with surgical clipping, and plasma FL-OPN and OPN N-half levels were measured. Plasma FL-OPN and OPN N-half levels at days 10-12 post-aSAH were intercorrelated and significantly higher in patients who subsequently developed SDHC. The areas under the receiver-operating characteristic curves (AUCs) for both levels were comparable. Multivariate analysis revealed that plasma OPN N-half levels ≥64.65 pmol/L was independently associated with SDHC development (adjusted odds ratio, 12.87; 95 % confidence interval, 3.69-44.90; p < 0.001) as well as ventricular drainage. In addition, the logistic regression model incorporating ventricular drainage and the optimal cut-off value of plasma OPN N-half levels demonstrated excellent discrimination (AUC, 0.847; 95 % confidence interval, 0.780-0.914) with satisfactory calibration. Based on these findings and prior evidence, OPN N-half appears to be associated with the pathophysiology of SDHC, and its elevation in plasma levels during the subacute phase may serve as a surrogate biomarker for predicting SDHC development in patients with aSAH treated with surgical clipping.