Aug 1, 2018 | Digital Pathology, Instruments & Equipment, Laboratory Instruments & Laboratory Equipment, Laboratory Management and Operations, Laboratory News, Laboratory Operations, Laboratory Pathology, Laboratory Testing, Management & Operations
Identifying patients who will likely develop prolonged concussion symptoms could lead to new clinical laboratory tests and personalized medicine treatments
Researchers are homing in on a new diagnostic assay for concussion that could potentially generate significant numbers of test referrals to the nation’s clinical laboratories. This innovative work is targeting how concussions are diagnosed and treated.
Each year, thousands of children receive sports-related injuries, including concussions. There are ways for anatomic pathologists and hospital medical laboratories to diagnose concussions; however, testing can be invasive and doesn’t always reveal a complete picture of the injury state.
Additionally, about one third of children with concussions develop prolonged symptoms. However, when prescribing treatment plans, physicians have been unable to predict which patients are likely to recover quickly versus those who will have a longer recovery.
Now, researchers at Penn State College of Medicine (Penn State) believe they have discovered five microRNAs in saliva that could be used to identify patients who will likely experience prolonged concussion symptoms even one month after the initial injury.
The study also found that certain materials in saliva can help diagnose the severity of concussions and could hold the key to more effective clinical laboratory tests and personalized medicine treatments.
The Penn State researchers published their study results in JAMA Pediatrics, a publication of the Journal of the American Medical Association (JAMA).
Concussion Leading Sports-related Brain Injury
There are approximately 3.8 million sports and recreation-related traumatic brain injuries in the United States each year and the majority of those cases are concussions, according to The Concussion Place. Most concussions treated in emergency rooms are due to falls, motor-vehicle related injuries, being struck by an object, assaults, or playing sports.
Also known as mild traumatic brain injuries (mTBI), concussions are caused by blows or jolts to the head or body that cause the brain to move with excessive force inside the skull. The sudden impact damages brain cells and causes chemical changes within the brain that alter normal functioning. Though usually not life threatening, the damage can be serious and linger for months.
Symptoms of concussion include: headaches, fatigue, nausea, vomiting, dizziness, balance problems, confusion, memory problems, sleep disturbances, and double or blurry vision. Symptoms usually occur immediately, but could take days or even weeks to appear.
Identifying Severity/Predicting Prolonged Symptoms of Traumatic Brain Injuries
After a concussion occurs, brain cells release small fragments of genetic material known as microRNAs while they attempt to repair themselves. A portion of these microRNAs appear in the injured person’s blood and saliva.
In order to determine whether these microRNAs could be used to determine the severity of a traumatic brain injury and predict whether prolonged symptoms would occur, the prospective cohort study researchers gathered saliva samples from 52 concussion patients between the ages of seven and 21:
- The average age of the subjects was 14;
- Twenty-two of the participants were female;
- They were all athletes; and,
- The majority of the samples were collected one to two weeks after the initial injury.
The researchers examined distinct microRNAs in the samples and identified some that enabled them to predict how long a patient’s concussion symptoms might last. In addition, they found one microRNA in children and young adults that accurately predicted which subjects would experience memory and problem-solving difficulties as part of their symptomatology.
The researchers also evaluated the concussion patients using the Sport Concussion Assessment Tool (SCAT-3), Third Edition. Physicians use this questionnaire to assess the symptoms and severity of concussions. The researchers also asked the parents of the concussed patients for observations about their children’s symptoms.
During follow up visits, which occurred at four- and eight-week increments following the original assessment, the Penn State researchers collected additional saliva samples and re-evaluated the patients using SCAT-3.
New Biomarkers Based on MicroRNAs Instead of Protein
“There’s been a big push recently to find more objective markers that a concussion has occurred, instead of relying simply on patient surveys,” Steven Hicks, MD, PhD, Assistant Professor of Pediatrics, Penn State College of Medicine, Hershey, Pa., one of the study researchers, told Penn State News.
“Previous research has focused on proteins, but this approach is limited because proteins have a hard time crossing the blood-brain barrier. What’s novel about this study is we looked at microRNAs instead of proteins, and we decided to look in saliva rather than blood,” he noted.
According to Steven Hicks, MD, PhD (above), who worked on the Penn State College of Medicine study, microRNAs could be more accurate than the traditional questionnaire when diagnosing and forecasting the effects of concussions. “The microRNAs were able to predict whether symptoms would last beyond four weeks with about 85% accuracy,” he told Penn State News. “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.” (Photo copyright: MD Magazine.)
The goal of this research was to develop a way to definitively ascertain that a concussion had occurred, predict the length and type of symptoms, and then use that data to improve and personalize care for children and young adults who have had a concussion.
“With that knowledge physicians could make more informed decisions about how long to hold a child out of sports, whether starting more aggressive medication regimens might be warranted, or whether involving a concussion specialist might be appropriate,” Hicks told MD Magazine. “Anytime we can use accurate, objective measures to guide medical care, I think that represents an opportunity to improve concussion treatment.”
Further research and clinical trials will be needed to solidify the effectiveness and accuracy of these new biomarkers. However, a rapid, non-invasive saliva test that can determine the severity of a concussion, and predicted whether prolonged symptoms will likely occur, would be widely used and could be an important assay for clinical laboratories. Particularly those associated with hospital medical laboratories and emergency rooms.
—JP Schlingman
Related Information:
Association of Salivary MicroRNA Changes with Prolonged Concussion Symptoms
Saliva Test May Detect Biomarker for Prolonged Concussion
Molecules in Spit May be Able to Diagnose and Predict Length of Concussions
Prolonged Concussion Symptoms Identifiable by Salivary MicroRNA
Spit Test May Help Reveal Concussion Severity
Saliva Test May Lead to Improved Concussion Care for Youths
Feb 5, 2018 | Digital Pathology, Instruments & Equipment, Laboratory News, Laboratory Pathology, Laboratory Testing, Management & Operations
Research published in JAMA Pediatrics reports that non-invasive salivary microRNA testing identifies prolonged concussion symptoms with 85% accuracy
Sports-related concussions are always tragic, but doubly so when they involve child athletes. Quick diagnoses and treatments are critical to prevent permanent brain injury. But doctors are often hampered by the pace at which traditional medical imaging modalities and clinical laboratory diagnostic technologies provide crucial feedback.
Now, researchers at Penn State Health Children’s Hospital have determined that microRNA in saliva could be used as biomarkers in point-of-care concussion testing during sports events, according to a Penn State Health news release. Such sideline saliva analyses could provide quick feedback to field doctors on whether a head injury is serious enough to put injured athletes out of play, and how long the effects of such injuries might last. But is it accurate?
Jeremiah J. Johnson, MA, BS, Department of Pediatrics, at Penn State College of Medicine in Hershey, Pa., et al, recently published a study in the Journal of the American Medical Association (JAMA) Pediatrics that evaluated the ability of salivary microRNA to identify concussion in children. The salivary test of microRNA levels, Johnson and colleagues argued, does accurately identify the “duration and character of concussion symptoms.” According to the researchers, the test demonstrated high prognostic potential as a “toolset for facilitating concussion management” and may provide an additional biomarker source for use in clinical laboratory testing.
MicroRNA Offers New Biomarkers for Concussion Diagnosis
The study tested the saliva of 52 adolescents with a clinical diagnosis of mild traumatic brain injury in the form of concussion for specific microRNA expressions. Researchers identified five microRNA molecules which “accurately identify” patients with concussion symptoms. Three of those molecules served to diagnose specific symptoms of headache, fatigue, and memory difficulties up to one month after injury with low false detection rates. Because these microRNA molecules are not specific to children, could the test maintain diagnostic accuracy for patients of all ages?
William P. Meehan III, MD, with the Micheli Center for Sports Injury Prevention at Boston General Hospital, and Rebekah Mannix, MD, MPH, with the Brain Injury Center at Boston Children’s Hospital wrote an editorial responding to the original research article stating that “the use of salivary microRNA in this study is both novel and clinically relevant.” Adding that “using this salivary microRNA panel to diagnose and manage concussions could be a major advancement to the field.”
Meehan and Mannix also remarked on the speed and relative ease of obtaining saliva samples, stating that “salivary microRNAs could also offer insights into the underlying biological mechanisms of injuries, potentially identifying specific targets to modify disease.”
More Accurate than Current Concussion Diagnosis Tools
There has been a marked interest in microRNA analysis and testing in recent years. MicroRNA analysis and testing has found use in cancer prognosis and personalized medicine that help predict responses to specific treatments for individual patients with a variety of chronic diseases. The news that microRNA can be used to predict concussion and duration of symptoms further solidifies the role microRNA may play in medical laboratory testing in the near future.
In an interview with CNN, Steve Hicks, MD, PhD, senior author of the JAMA Pediatrics research article and Assistant Professor of Pediatrics at Penn State College of Medicine, reported that the salivary microRNA test predicted concussion with 85% accuracy in comparison to current clinical survey measures, which are “approximately 65% accurate.” Hicks added that “the technology required to measure saliva RNA is already employed in medicine” as a common means of testing for upper respiratory viruses and that “modifying this approach for patients with concussions could potentially provide a rapid, objective tool for managing brain injury.”
Currently the Standard Concussion Assessment Tool, Third Edition (SCAT 3), which includes a series of cognitive and physical tests, is used on sports sidelines to detect concussion symptoms. Hicks notes that one problem with SCAT 3 is that “an athlete may have a concussion even if [his or her] score is ‘normal.’” Therefore, the microRNA saliva test could provide objective evidence of concussion in patients SCAT 3 fails to accurately diagnose.
Steven D. Hicks, MD, PhD (above), led the research team that studied the use of microRNA in saliva, rather than in blood, as a biomarker to identify concussions symptoms in children, and determine how long effects of the injury might last. (Photo copyright: Penn State Health.)
Too Early to Know How Helpful the Test May Be?
In the same CNN interview, Neurologist Jeffery Kutcher, MD, head of the Sports Neurology Clinic at The Core Institute in Brighton, Mich., stated that the Penn State study’s findings were “promising” and that “work like this is important because it does provide potential for tests that can be helpful in the clinical setting.” Kutcher cautioned however, that it was “too early to know what this type of tool can do for us.”
In an NPR article, Manish Bhomia, M.Eng., PhD, a brain injury researcher with the Uniformed Services University of the Health Sciences commented that “a saliva test could greatly improve care for young people who don’t have obvious symptoms of a concussion.” Bhomia stated that “micro-RNAs offer a promising way to assess concussions in adults as well as children,” but he is wary to laud saliva tests as the best method of measuring relevant microRNA molecules. Bhomia states that blood samples “which tend to contain greater numbers of the genetic fragments” are perhaps a better option.
Hicks disagrees. In an article from Penn State News, Hicks stated that the novel aspect of this study was that it focused on microRNA levels “in saliva rather than blood.” Thus, a test based on saliva, rather than a phlebotomy stick or more invasive blood testing, requires no need for venous blood.
“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,” Hicks noted in the Penn State News article. “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.”
Quadrant Biosciences, a biotech company in Syracuse, N.Y., that helped fund the study, is hoping to “bring a saliva test for concussion to market in the next 12 to 24 months,” according to Hicks in his CNN interview. If development proceeds as planned, the saliva test could prove a “game changer” for sports medicine diagnostics and possibly open new avenues for related microRNA in clinical laboratory testing.
—Amanda Warren
Related Information:
Prolonged Concussion Symptoms Identifiable by Salivary MicroRNA
Association of Salivary MicroRNA Changes with Prolonged Concussion Symptoms
Promise of Salivary MicroRNA for Assessing Concussion
Spit Test May Diagnose, Predict Duration of Concussion in Kids
Molecules in Spit May Be Able to Diagnose and Predict Length of Concussions
Spit Test May Help Reveal Concussion Severity
Meet the Clinical Pathology Laboratory on the Palm of a Hand: Japanese Researchers Announce A Point-Of-Care Testing Device That Detects MicroRNA in 20 Minutes
With Launch of RNAcentral Database, Pathologists Now Have Unprecedented Access to RNA Data
