https://www.medpagetoday.com/pediatrics/generalpediatrics/69414?
Specific microRNAs linked to prolonged concussion symptoms
Changes in the composition of children's saliva, which have been found following traumatic brain injury (TBI), helped to identify patients with prolonged symptoms of concussion, a small study found.Specifically, concentrations of five specific microRNAs identified participants with prolonged concussion symptoms with more than 85% accuracy -- more accurate than using symptoms 4 weeks after injury or parent report, reported Jeremiah J. Johnson, of Pennsylvania State University in Hershey, and colleagues.
Notably, three of these microRNAs were linked with specific concussion symptoms -- memory difficulty, headaches, and fatigue, the authors wrote in JAMA Pediatrics.
They pointed out that more than 80% of concussions in children may result from mild traumatic brain injuries. One-third of these children experience prolonged concussion symptoms, but there is no objective tool to identify children at risk for these symptoms.
While clinical risk scores have a "modest ability" to determine risk of prolonged concussion symptoms, the authors cited feasibility problems in administering "multiple age-specific questionnaires" during a clinical encounter and suggested the potential use of biomarkers.
Johnson's group added that microRNAs were examined in prior studies of individuals with traumatic brain injury, but none of these studies focused solely on children.
An accompanying editorial by William P. Meehan III, MD, and Rebekah Mannix, MD, both of Boston Children's Hospital, characterized these findings as "novel" and "clinically relevant." They wrote that no single biomarker, or biomarker panel, has been an objective measure for either diagnosing or monitoring recovery from concussion, or determining who is at risk of prolonged recovery. They also noted that the ease and speed of collecting saliva samples is ideal for the pediatric patient population, as it can be used in diverse care settings.
"If validated in larger, multisite clinical trials, using this salivary microRNA panel to diagnose and manage concussions could be a major advancement to the field," Meehan and Mannix wrote. "Salivary microRNAs could also offer insights into the underlying biological mechanisms of injuries, potentially identifying specific targets to modify disease."
Johnson's group observed 52 patients, ages 7 to 21 years, who presented to evaluation of concussion within 2 weeks of initial head injury at a local medical center, based on prior research indicating that the symptoms and biomarkers return to baseline within 2 weeks of concussion, they explained.
Prolonged concussion symptoms were defined via a Sports Concussion Assessment Tool symptom score of ≥5, or a parent report 4 weeks after injury.
Participants had a mean age of 14 years, 42% were girls, and nearly all were white. There were 22 with acute concussion symptoms and 30 with prolonged concussion symptoms. Most participants were enrolled within 1 week of their concussion, the authors said, and about 40% had a concussion due to sports participation. Moreover, nearly half experienced a previous concussion. Also, nearly half of patients reported amnesia at the time of injury, while a quarter reported loss of consciousness.
Saliva was collected in patients in both groups and 437 microRNAs were identified in at least 22 of 30 samples. Fifteen of these microRNAs were associated with prolonged concussion symptoms. Of these, five identified patients with prolonged symptoms (area under the curve 0.856, 95% CI 0.822-0.890). The authors noted that "misclassified participants" had higher rates of sports participation and saliva collected sooner following injury, but "neither of these factors displayed statistical significance."
In fact, concentrations of five microRNAs exceeded the accuracy of symptom burden on child (AUC 0.649, 95% CI 0.388-0.887) and parent (AUC 0.562, 95% CI 0.219-0.734) for identifying patients with prolonged concussion symptoms.
The authors noted that validation of these microRNAs will need to be confirmed in an independent, larger cohort. They also said that while the study uses a validated tool to measure concussion symptoms, it does not provide functional measure, such as balance or processing speed.
The study was supported by the Children's Miracle Network group and Quadrant Biosciences.
Johnson disclosed no relevant relationships with industry. One co-author disclosed being a co-inventor of preliminary patents for microRNA biomarkers in disorders of the central nervous system, and a relevant relationship with Quadrant Biosciences.
Meehan and Mannix disclosed no relevant relationships with industry.
Johnson disclosed no relevant relationships with industry. One co-author disclosed being a co-inventor of preliminary patents for microRNA biomarkers in disorders of the central nervous system, and a relevant relationship with Quadrant Biosciences.
Meehan and Mannix disclosed no relevant relationships with industry.
Primary Source
JAMA Pedatrics
Source Reference: Johnson JJ, et al "Association of salivary microRNA changes with prolonged concussion symptoms" JAMA Pediatr 2017; DOI:10.1001/jamapediatrics.2017.3884.Secondary Source
JAMA Pediatrics
Source Reference: Meehan III WP and Mannix R "Promise of salivary microRNA for assessing concussion" JAMA Pediatr 2017; DOI:10.1001/jamapediatrics.2017.3924.
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