HCRN Update: Biomarkers in Post Hemorrhagic Hydrocephalus

This Research blog series is dedicated to highlighting the current studies of the Hydrocephalus Clinical Research Network (HCRN). The HCRN is a collaborative research network of nine pediatric children’s hospitals conducting important research on hydrocephalus. We hope you enjoy reading about the important work of the HCRN.

Our blog series continues with a discussion with St. Louis Children’s Hospital HCRN principal investigator, David Limbrick, MD, PhD. Dr. Limbrick is an Assistant Professor of neurological surgery and pediatrics at Washington University in St. Louis. He is the principal investigator for the HCRN study, Biomarkers in Post Hemorrhagic Hydrocephalus, which collects cerebrospinal fluid (CSF) and analyzes it for potential biomarkers.
His project is closely connected to another HCRN study, Shunt Outcomes in Post Hemorrhagic Hydrocephalus (SOPHH), previously highlighted in this blog series. The CSF collected in the biomarker study is from patients with post hemorrhagic hydrocephalus that are enrolled in the SOPHH study.

HA: How did you become involved with HCRN?

DR. LIMBRICK: Originally, the HCRN had five member centers. In 2010, the HCRN was seeking to add more centers so they announced a request for applications from institutes interested in participating. HCRN is a model for high-level clinical research with an emphasis on patient outcomes and is doing important research in the field of hydrocephalus. Washington University was interested. We submitted an application and were accepted to join the network. We were interested in building the CSF repository and contributing to the many other projects that the HCRN were doing.

HA: Can you describe your research? What do you believe to be the significance of your research for the hydrocephalus research community in furthering the knowledge base?

DR. LIMBRICK: My main research focus pertains to post hemorrhagic hydrocephalus (PHH) in premature babies. This is a common problem in very premature infants, and it creates a life-long set of circumstances and challenges for each infant that is affected. In general, about a quarter of very premature births develop intraventricular hemorrhage (IVH), or bleeding into the brain ventricles, and about a quarter to half of those go on to develop PHH and require surgical treatment. These infants are at a high risk of developing cerebral palsy or a cognitive delay.

PHH results in a number of problems. First, there is hydrocephalus and the need for a shunt. Second is the injury from the initial hemorrhage, and then there is a need for multiple shunt revisions and other downstream effects from the hydrocephalus. All of these factors combine to contribute to the complex, multifactorial clinical condition that we see.

With that as background, our research is directed at establishing better methods of determining how to treat patients who are likely to develop PHH. Currently, we only really have one tool: imaging (such as a CT scan, ultrasound, or an MRI). However, imaging has many limitations in this particular population and using ventricle size as a single metric to identify hydrocephalus and to determine the time to treat is not ideal. What we are trying to do with this research is to develop a complementary tool to supplement the information from imaging in order to determine the best time to treat these infants. This is to ensure that the treatment we are administering is efficient and effective. To do this, we have been looking at cerebrospinal fluid samples from infants who were treated for PHH, and we have found a number of proteins that are promising candidate biomarkers for hydrocephalus and developmental disabilities.

At Washington University in St. Louis, we have established a CSF Repository, with each HCRN center contributing CSF samples through the SOPHH study. On a quarterly basis, each of the HCRN centers sends us their CSF samples. This allows us to bank the CSF in a central location under standardized conditions and then analyze them in a uniform way.

We are just now starting to get samples in from the other centers, and it is a very exciting time! The CSF Repository will increase our research findings exponentially.

HA: What do you see as the challenges to your specific field of interest within hydrocephalus research?

DR. LIMBRICK: Perhaps the most significant challenge is the enormous variability in the way that surgeons and neonatologist think about and treat PPH. There really are no evidence-based guidelines to know if, when, or how to treat these infants. This is the basis of both the SOPHH study and the CSF Biomarkers study. We want to develop common protocols—based on research data—that can be used across institutions and will bring better outcomes to infants affected by this condition.