Image: A recent study suggests clues taken from small molecules in saliva may be able to help diagnose and predict the duration of concussions in children (Photo courtesy of Penn State University College of Medicine).
A panel of microRNAs has been shown to be a potent biomarker for the detection of prolonged concussion symptoms in children.
MicroRNAs (miRNAs) are a family of noncoding 19- to 25-nucleotide RNAs that regulate gene expression by targeting messenger RNAs (mRNAs) in a sequence specific manner, inducing translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and their targets. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In fact, miRNAs have been shown to be involved in the regulation of gene expression during development, cell proliferation, apoptosis, glucose metabolism, stress resistance, and cancer. MiRNAs are transported through the extracellular space protected in exosomes and microvesicles, which allows them to be easily measured in biofluids, including serum, cerebrospinal fluid, and saliva. Because of their abundance, stability in fluctuating pH levels, resistance to enzymatic degradation, and essential role in transcriptional regulation, miRNAs make ideal biomarkers.
Approximately one-third of children who suffer a concussion develop prolonged concussion symptoms. These include headache, nausea, confusion, amnesia, or lack of consciousness. While most concussions disappear within two weeks, some patients will experience symptoms longer. There are currently no objective or easily administered tests for predicting prolonged concussion symptoms, and although several studies have identified alterations in miRNAs following traumatic brain injury, no studies have examined whether miRNA expression can detect prolonged concussion symptoms.
Investigators at Pennsylvania State University College of Medicine (Hershey, USA) recently published results of a study that was designed to fill this gap.
They conducted a prospective study comprising the observation of 52 patients aged seven to 21 years who had presented for evaluation of concussion within 14 days of initial head injury, with follow-up at four and eight weeks. Each participant was evaluated using the Sport Concussion Assessment Tool (SCAT-3), a common tool used to inventory concussion symptoms and severity. Salivary miRNA expression was measured at the time of initial clinical presentation in all patients.
Results revealed that levels of five miRNAs (miR-320c-1, miR-133a-5p, miR-769-5p, let-7a-3p, and miR-1307-3p) accurately identified patients with prolonged symptoms. Levels of three miRNAs were associated with specific symptoms four weeks after injury. MiR-320c-1 was associated with memory difficulty, miR-629 was associated with headaches, and let-7b-5p was associated with fatigue.
"The microRNAs were able to predict whether symptoms would last beyond four weeks with about 85% percent accuracy," said senior author Dr. Steven Hicks, assistant professor of pediatrics at Pennsylvania State University College of Medicine. "In comparison, using the SCAT-3 report of symptoms alone is about 64% accurate. If you just go off the parent's report of symptoms, it goes down to the mid-50s. In this pilot study, these molecular signatures are outperforming survey tools. The ultimate goal is to be able to objectively identify that a concussion has happened and then predict how long the symptoms will go on for. Then we can use that knowledge to improve the care that we provide for children who have concussions, either by starting medicine earlier or holding them out of activities for longer."
Pennsylvania State University College of Medicine