Predicting
clinical recovery of children with concussion is challenging. While concussion
symptoms typically resolve within one to three weeks, up to one-third of
children develop persistent post-concussive symptoms (PPCS), including
headache, nausea, dizziness, blurred vision and sensitivity to light and/or
sound. Compared with children without PPCS, children with PPCS are at increased
risk of experiencing disruption to their daily routines and functioning, such
as missed school days, depressed mood and loss of social activities, leading to
lower quality of life.
In a study
published in Frontiers in Public Health,
researchers with the Center for Injury Research and Policy, Division of Sports Medicine, and the Steve and Cindy Rasmussen Institute
for Genomic Medicine at Nationwide
Children’s Hospital have demonstrated a method by which increased risk of PPCS
in children with concussion can be identified. This could allow families and
their care teams to better assess recovery time of children with concussion.
“The diagnosis
of concussion is based on self-report, and it can be difficult for children,
especially those who are very young, to describe their symptoms following
injury,” explains senior author Jingzhen Ginger Yang, PhD, MPH, a principal investigator at the Center for
Injury Research and Policy of the Abigail Wexner Research Institute at
Nationwide Children’s Hospital. “Currently, there are no markers to objectively
predict who is going to recover sooner or later. If physicians could identify
children at risk for prolonged recovery, they may be able to intervene earlier,
providing personalized concussion care, to improve patient recovery.”
Previous
research suggests that salivary microRNAs – small molecules that can regulate
the amount of specific proteins a cell makes – may serve as potential markers
to identify children with concussion who are at increased risk of PPCS.
However, no studies have focused specifically on children, and it remains
unknown whether and how salivary microRNA expression levels differ over time
between children with or without PPCS.
In this study,
Dr. Yang and colleagues demonstrated that the expression levels of 13 salivary
microRNAs differ over time following concussion in children with versus without
PPCS. To identify microRNAs and evaluate their predictive value in children
with concussion, the researchers recruited 60 children between 11 and 17 years
of age who were diagnosed with a concussion by a physician at Nationwide
Children’s. They collected saliva at up to three timepoints (within one week of
injury, one to two weeks post-injury, and four weeks post-injury) and
participants’ daily post-concussion symptom ratings throughout their enrollment
using the Post-concussion Symptom Scale. PPCS was defined as symptoms that
persisted at 28 days post-concussion.
“The approach
we used for sample collection is very promising because it is noninvasive and
easy, for both the investigator and the patient, to collect the
sample. The lack of pain and convenience is appealing to families,”
explains co-first author James MacDonald, MD, MPH, a physician for Nationwide Children’s Division
of Sports Medicine and principal investigator of the study.
The researchers
measured expression levels of 827 salivary microRNAs in 135 collected saliva
samples. Of the 827 microRNAs analyzed, the team identified 91 that had
heightened expression levels, and of those 91 microRNAs, they identified 13
with significantly different expression levels across the three timepoints
post-concussion between children with and without PPCS. Among the 13 microRNAs
identified by the team, one was also found to have different expression levels
between children with and without PPCS in a prior study.
“This research
is an excellent example of the team science approach and what can be
accomplished with multidisciplinary collaborations,” adds co-first author Katherine Miller, PhD, a principal investigator in the Steve and
Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s. “The
value of our publication is that our findings come from multiple time points.
We need more studies like this to continue to track how these microRNAs change
over time and hone in on those that are most consistent across patient
populations.”
“It is critical
that we develop objective measures for diagnosis and prognosis of concussion,
as there is potential overlap between that diagnosis and so many others,” said
Dr. MacDonald. “Having this information can help us better assess the needs of
each patient and ensure that we are making the most informed recommendations
possible to prevent any long-term issues.”
The research
was supported by Nationwide Children’s Intramural Funding Program awarded to
Dr. MacDonald and Dr. Yang and by The Ohio State University’s Discovery Theme
Initiative in Chronic Brain Injury.
Reference:
Miller KE,
MacDonald JP, Sullivan L, Rao Venkata LR, Shi J, Yeates KO, Chen S, Alshaikh E,
Taylor HG, Hautmann A, Asa N, Cohen DM, Pommering TL, Mardis ER, Yang J, on
behalf of the NCH Concussion Research Group. Salivary miRNA expression in
children with persistent post-concussive symptoms. Frontiers in Public Health. 2022;10:890420.
About The Abigail Wexner Research Institute at
Nationwide Children's Hospital
Named to the Top 10 Honor Roll on U.S. News & World
Report’s 2022-23 list of “Best Children’s Hospitals,” Nationwide
Children’s Hospital is one of America’s largest not-for-profit free-standing
pediatric health care systems providing unique expertise in pediatric
population health, behavioral health, genomics and health equity as the next
frontiers in pediatric medicine, leading to best outcomes for the health of the
whole child. Integrated clinical and research programs are part of what allows
Nationwide Children’s to advance its unique model of care. As home to the
Department of Pediatrics of The Ohio State University College of Medicine,
Nationwide Children’s faculty train the next generation of pediatricians,
scientists and pediatric specialists. The Abigail Wexner Research Institute at
Nationwide Children’s Hospital is one of the Top 10 National Institutes of
Health-funded free-standing pediatric research facilities in the U.S.,
supporting basic, clinical, translational,
behavioral and population health research. The AWRI is comprised of
multidisciplinary Centers of Emphasis paired with advanced infrastructure
supporting capabilities such as technology commercialization for discoveries;
gene- and cell-based therapies; and genome sequencing and analysis. More
information is available at NationwideChildrens.org/Research.
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