# Feasibility Study on Inflammasome Proteins as Biomarkers in the Cerebrospinal Fluid of Pediatric Patients with Hydrocephalus Due to Intraventricular Hemorrhage

**Authors:** MaryLourdes Andreu, Alexandra Castellanos, Robert W. Keane, Juan Pablo de Rivero Vaccari, Jennifer C. Muñoz Pareja, Helen M. Bramlett, W. Dalton Dietrich, Nadine A. Kerr, Heather J. McCrea

PMC · DOI: 10.3390/biom16010035 · Biomolecules · 2025-12-25

## TL;DR

This study explores whether inflammasome proteins in cerebrospinal fluid can serve as reliable biomarkers for pediatric hydrocephalus caused by intraventricular hemorrhage.

## Contribution

The study identifies ASC, caspase-1, and interleukin-18 as potential biomarkers for pediatric hydrocephalus with high diagnostic accuracy.

## Key findings

- ASC, caspase-1, and interleukin-18 levels were significantly higher in hydrocephalic patients with IVH compared to controls.
- These proteins showed an area under the curve of 1.0, indicating perfect diagnostic accuracy with high sensitivity and specificity.
- The findings suggest these proteins are reliable indicators of the inflammatory response in pediatric hydrocephalus.

## Abstract

Pediatric hydrocephalus results from the overproduction, obstruction, or inability to resorb cerebrospinal fluid (CSF), which may lead to ventricular enlargement. Hydrocephalus may be secondary to other pathologies, including intraventricular hemorrhage (IVH). Surgical intervention may include a ventricular access device or a ventriculosubgaleal shunt in premature infants who are too small for permanent CSF diversion. Hydrocephalus, an inflammatory pathology, involves activation of the inflammasome. Elevation in pro-inflammatory proteins is often associated with worsening clinical outcomes in pediatric pathologies. Whether inflammasome proteins are reliable biomarkers for pediatric hydrocephalus has not been established. We analyzed CSF samples via an ELLA assay from pediatric hydrocephalic patients with IVH of prematurity vs. controls and compared changes in inflammasome protein concentrations post-reservoir surgery at different time points. The area under the curve was calculated using receiver operator characteristic curves. The levels of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-18 were significantly elevated in pediatric hydrocephalic patients with IVH vs. controls. Thus, these proteins are reliable biomarkers of the inflammatory response in pediatric hydrocephalus following ROC analysis, with an AUC of 1.0 and high sensitivity and specificity at the corresponding cut-off points. Ongoing work seeks to validate these findings in a larger cohort of pediatric hydrocephalic patients with varying etiologies.

## Linked entities

- **Proteins:** STS (steroid sulfatase), Caspase1 (caspase-1), IL18 (interleukin 18)
- **Diseases:** hydrocephalus (MONDO:0001150)

## Full-text entities

- **Genes:** PYCARD (PYD and CARD domain containing) [NCBI Gene 29108] {aka ASC, CARD5, TMS, TMS-1, TMS1}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}
- **Diseases:** ventricular enlargement (MESH:D006332), IVH (MESH:D000074042), Hydrocephalus (MESH:D006849), inflammatory (MESH:D007249)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12838929/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12838929/full.md

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Source: https://tomesphere.com/paper/PMC12838929