Micro Ribonucleic Acid (miRNA) Markers of Hydrocephalus in Intraventricular Hemorrhage (IVH)
Micro Ribonucleic Acid (miRNA) Markers of Hydrocephalus in Intraventricular Hemorrhage (IVH)
A collection of biological samples (cerebrospinal fluid [CSF] and blood) from patients under
 6 years of age who are diagnosed with intraventricular hemorrhage or spina bifida.
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.