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Investigators at the Murdoch Children’s Research Institute (MCRI) say they have discovered a blood protein biomarker that could help detect which children will experience ongoing concussion symptoms more than two weeks after the initial injury. Reporting in the Journal of Neurotrauma, the MCRI teams demonstrate that levels of the protein alpha-1-antichymotrypsin (alpha-1-ACT) were significantly lower in children with longer recovery.

“Alpha-1-ACT has been investigated previously as a serum biomarker to grade the severity of (traumatic brain injury) TBI (n = 10 per group; mild, moderate, and severe TBI), and found to be increased across all strata of TBI compared with healthy controls,” the researchers wrote. “However, no study has investigated its plasma concentration or abundance in children with delayed recovery from concussion. The physiological function of alpha-1-ACT in the setting of concussion is largely unknown; however, this protein has been shown to play a role in upregulating the brain renin-angiotensin system (RAS).”

For this study, blood samples were collected from children aged five to 18 who presented at the emergency department at The Royal Children’s Hospital Melbourne, Australia, less than 48 hours after suffering a concussion. It is estimated that more than 25% of children who experience a concussion will have long-term symptoms, but half of them will not seek additional medical care. Concussion symptoms such as headaches, sensitivity to light and memory problems drag on for months and potential mental health conditions related to concussion can persist for many years.

“Delayed recovery from concussion spans emotional, behavioral, physical and cognitive symptoms, which can affect the well-being of the child, delaying their return to school and sport,” said lead author Ella Swaney, a PhD student at University of Melbourne and a researcher with MCRI. “Early detection of children at risk of delayed recovery is crucial to ensure effective treatment and targeted follow-up.”

The study, which involved 80 children, is the first to determine that alpha-1-ACT could be an important biomarker to determine children that will have delayed concussion recovery.

“If the finding holds up in larger studies, the discovery could contribute to acute clinical management by providing clinicians with an acute marker to guide more timely and targeted treatments to children most likely to experience long-term problems,” said Vicki Anderson, PhD, a professor at MCRI and director of psychology at The Royal Children’s Hospital.

The new research from MCRI builds upon the development of new consensus findings developed last year at the International Consensus Conference on Concussion in Sport. This deep dive into concussion management across 23 different research papers was published in the British Journal of Sports Medicine. New protocols developed from this effort aimed to change how concussion is viewed, to improve exercise and rehabilitation methods, and modernize return-to-school and return-to-sport protocols.

MCRI has taken a lead in Australia in concussion management. It runs the Concussion Essential Plus program for children with chronic and persistent concussion symptoms. The program incorporates weekly physiotherapy and psychology treatments over the course of the month while providing education on return to exercise, school, and sports.

Researchers at MCRI have also developed the HeadCheck app developed in collaboration with The Royal Children’s Hospital and the Australian Football League (AFL). HeadCheck aids in the early recognition of concussion to help manage recovery.

The hope is that this newly identified biomarker of persistent concussion symptoms can be integrated into clinical care to provide earlier, specialized treatment of this subset of patients.

“Pediatric concussion is now widely understood to be different to adult concussion in its symptomology and recovery. In addition, the pediatric proteome is vastly different from that of adults,” the researchers concluded. “Alpha-1-ACT has potential to transform acute clinical management by providing clinicians with a robust predictive marker with which to guide and target treatments to children most likely to experience delayed recovery.”

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