Meeting NewsPerspective

Saliva biomarkers may help predict concussion symptom duration in children

Analyzing saliva for changes in the micro-ribonucleic acid levels served as a prognostic indicator of symptom duration among children following a concussion, according to research presented at the 2017 Pediatric Academic Societies Meeting.

Researchers noted that this form of testing can more correctly assess potential lingering effects more successfully than the standard Sports Concussion Assessment Tool (SCAT-3).

Stephen D. Hicks
Steven Hicks

“Most clinicians feel comfortable making a clinical diagnosis of concussion, but our ability to predict how long concussion symptoms will last is limited by a lack of objective measures,” Steven Hicks, MD, PhD, FAAP, from the State University of New York (SUNY) Upstate Medical University in Syracuse, told Infectious Diseases in Children. “Our research group has identified a set of small molecules called microRNAs that are altered in both spinal fluid and saliva after a traumatic brain injury.”

To evaluate the efficacy of testing microRNA in saliva to predict possible symptoms in comparison to the SCAT-3, researchers documented the injury mechanism and demographic features of 50 children between 7 and 18 years who acquired a mild traumatic brain injury. Both children and their parents completed SCAT-3 surveys within 14 days of the injury and 4 weeks after sustaining the concussion.

During enrollment, children also provided expectorated saliva to be used for high-throughput RNA sequencing to examine microRNA content. Prolonged concussion symptoms were classified in children with scores of 5 or greater on the SCAT-3 at 4 weeks.

The researchers observed no difference in injury mechanisms between those within the acute and prolonged concussion groups. Those who had prolonged symptoms (29 children) reported higher scores related to headache and frequent fatigue measures in the SCAT-3, whereas their parents had concerns about their impaired concentration.

Eleven microRNAs were detected that demonstrated slight differences between both groups, and a logistic regression analysis that included six microRNAs established an area under the curve of 0.878 with 10-fold cross-validation (90% sensitivity; 87% specificity) in relation to the identification of those with prolonged symptoms. When the SCAT-3 was assessed using the same regression model, an area under the curve was noted at 0.662.

“This study shows we may be able to use salivary microRNA levels to predict how long it will take a patient to recover from a concussion,” Hicks said in an interview. “In this small pilot study, microRNA levels were more accurate at predicting concussion duration than standard survey measures.” by Katherine Bortz.

Reference:

Adesman A, et al. “Peripheral microRNA patterns predict prolonged concussion symptoms in pediatric patients.” Presented at: The Pediatric Academic Societies Meeting; May 6-9, 2017; San Francisco, CA.

Disclosure: This work is sponsored and funded in part by Motion Intelligence, Inc., a biotech company for whom Dr. Hicks serves as a consultant.

Analyzing saliva for changes in the micro-ribonucleic acid levels served as a prognostic indicator of symptom duration among children following a concussion, according to research presented at the 2017 Pediatric Academic Societies Meeting.

Researchers noted that this form of testing can more correctly assess potential lingering effects more successfully than the standard Sports Concussion Assessment Tool (SCAT-3).

Stephen D. Hicks
Steven Hicks

“Most clinicians feel comfortable making a clinical diagnosis of concussion, but our ability to predict how long concussion symptoms will last is limited by a lack of objective measures,” Steven Hicks, MD, PhD, FAAP, from the State University of New York (SUNY) Upstate Medical University in Syracuse, told Infectious Diseases in Children. “Our research group has identified a set of small molecules called microRNAs that are altered in both spinal fluid and saliva after a traumatic brain injury.”

To evaluate the efficacy of testing microRNA in saliva to predict possible symptoms in comparison to the SCAT-3, researchers documented the injury mechanism and demographic features of 50 children between 7 and 18 years who acquired a mild traumatic brain injury. Both children and their parents completed SCAT-3 surveys within 14 days of the injury and 4 weeks after sustaining the concussion.

During enrollment, children also provided expectorated saliva to be used for high-throughput RNA sequencing to examine microRNA content. Prolonged concussion symptoms were classified in children with scores of 5 or greater on the SCAT-3 at 4 weeks.

The researchers observed no difference in injury mechanisms between those within the acute and prolonged concussion groups. Those who had prolonged symptoms (29 children) reported higher scores related to headache and frequent fatigue measures in the SCAT-3, whereas their parents had concerns about their impaired concentration.

Eleven microRNAs were detected that demonstrated slight differences between both groups, and a logistic regression analysis that included six microRNAs established an area under the curve of 0.878 with 10-fold cross-validation (90% sensitivity; 87% specificity) in relation to the identification of those with prolonged symptoms. When the SCAT-3 was assessed using the same regression model, an area under the curve was noted at 0.662.

“This study shows we may be able to use salivary microRNA levels to predict how long it will take a patient to recover from a concussion,” Hicks said in an interview. “In this small pilot study, microRNA levels were more accurate at predicting concussion duration than standard survey measures.” by Katherine Bortz.

Reference:

Adesman A, et al. “Peripheral microRNA patterns predict prolonged concussion symptoms in pediatric patients.” Presented at: The Pediatric Academic Societies Meeting; May 6-9, 2017; San Francisco, CA.

Disclosure: This work is sponsored and funded in part by Motion Intelligence, Inc., a biotech company for whom Dr. Hicks serves as a consultant.

    Perspective

    Anthony P. Kontos

    In this study, the researchers reported that a micro RNA saliva test was more accurate than a commonly used acute assessment tool – 90% vs. 70% – in identifying pediatric patients aged 7-18 years with prolonged symptoms following a concussion.

    The investigators used the SCAT 3 tool, which is designed for acute (within 1-3 days of injury) assessment of concussion; however, they used the tool up to 14 days post-injury at the initial time point and again at a follow-up of 4 months post-injury. Given that this tool is not designed for use this far out from injury, and has limited validity at the time points it was used in the current study, the comparative utility of the saliva test in identifying patients with prolonged symptoms is likely inflated in the current study.

    The researchers also failed to consider other tools, including cognitive testing, vestibular and oculomotor assessments, in their approach to assessing concussion. In addition, the investigators did not appear to control for symptom burden at time of injury, which is one of the best predictors of poor outcome including prolonged symptoms following concussion, and may be better than the proposed saliva test.

    In short, we do not really know if the saliva test is better than an appropriate battery of currently used clinical tools, as the study was not designed appropriately to answer that question. The study was also quite small with only 50 patients from a wide age range and represented a very selective, more severely injured sample, as 29 of 50 (58%) patients had prolonged symptoms, when population estimates suggest about 1 in 3 or 1 in 4 typically have prolonged symptoms. Moreover, the prolonged symptoms group seemed to include patients reporting more headache, fatigue and difficulty concentrating- which is a very limited set of symptoms that may have influenced the over representation (58%) of patients with prolonged symptoms reported in the study.

    In spite of these limitations, it is important that researchers and clinicians continue to develop objective biomarkers for concussion that corroborate and extend current clinical tools. However, the premise that a single concussion test, whether saliva, blood or imaging, will identify all individuals with prolonged symptoms following this injury is counterintuitive to growing evidence that concussion is heterogeneous with different clinical profiles, symptoms and impairments.

    • Anthony P. Kontos, PhD
    • Research director, UPMC Sports Medicine Concussion Program
      Associate professor, Department of orthopaedic surgery
      University of Pittsburgh

    Disclosures: Kontos reported no relevant financial disclosures.

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