Micro Ribonucleic Acid (miRNA) Markers of Hydrocephalus in Intraventricular Hemorrhage (IVH)

IVH is an important cause of brain injury in newborns and more so in those born prematurely.
Depending on the severity of the hemorrhage and the care provided the newborn, the impact of
IVH can range from a temporary issue with no permanent consequences to a life-threatening
condition with severe neurodevelopmental sequelae. The outcomes of patients with IVH are not
only dictated by the direct effects of the hemorrhage, but to associated processes such as
hydrocephalus, periventricular infarction and leukomalacia. Despite the availability of
better diagnostic and therapeutic tools, the incidence of IVH has remained constant over the
past 50 years, and is mostly due to the increased survival rates of very low weight
premature infants. Recent statistics demonstrate that close to 12,000 premature infants
develop IVH in the United 'states every year and more than 50% of them develop some degree
of posthemorrhagic hydrocephalus (PHH). It is believed that PHH originates as a result or
arachnoiditis, gliosis, and subsequent fibrosis impairing the flow and reabsorption of
cerebrospinal fluid (CSF). Despite the lack of clarity about the pathogenesis of PHH, it is
well accepted that its presence exacerbates the damage caused by the hemorrhage to the
periventricular white matter. Multiple efforts have been made to identify the mechanisms and
mediators of the development of PHH and white matter damage. Molecules such as transforming
growth factor-beta (TGF-beta) have been demonstrated to enhance the expression of genes
encoding for fibronectin, collagen and other extracellular matrix components. Unfortunately,
not enough evidence has been generated to be able to envision a potential solution for the
problem. The current management of PHH is focused on controlling the damage that pressure,
distortion, and/or ischemia may cause to the immature brain. Direct evacuation of
ventricular contents with CSF diversion mechanisms remains, such as sequential lumber
punctures, external ventricular draining, and reservoir placement. Intraventricular
fibrinolytic therapy or permanent shunting represent most effective tools by mechanically
evacuating bleeding products and preventing the accumulation of CSF. However, they are all
highly invasive techniques that carry major risks and complications. The use of diuretics
has been presented as a non-invasive alternative, but the results prove them inefficient.
Extracellular miRNA sequences have been found to be major modulators of protein coding genes
involved in differentiation, proliferation, and apoptosis. Several studies have reported the
presence of significant amounts of miRNA in extracellular fluids such as plasma, urine,
saliva, and semen. The researchers believe that extracellular miRNAs are present in CSF and
that sequential evaluation of their expression can provide a unique biomarker signature,
time sensitive enough to reflect the evolution of pathological events underlying the
development of PHH. The identification of a miRNA biomarker for PHH development and/or
hemorrhagic related injury would also be a means to quickly evaluate treatment response.

Inclusion Criteria:

- Age between 0 and 6 years.

- Diagnosis of IVH or spina bifida

- Granted access to CSF and blood via surgery, CSF diversion device, venous access,
and/or arterial access.

Exclusion Criteria:

- Older than 6 years.

- Diagnosis of infection or other acute inflammatory process involving the central
nervous system.