Irvine: Researchers from the University of California, Irvine, Georgetown University and the University of Rochester have found that specific small molecules in blood plasma may be useful in determining whether someone has sustained a mild traumatic brain injury (mTBI), commonly known as a concussion. The article, “Plasma metabolomic biomarkers accurately classify acute mild traumatic brain injury from controls,” is now online at the PLOS One journal. Six specific small molecules from blood plasma were discovered in a group of college athletes who had been diagnosed with concussions. When these molecules were assessed, their combined presence accurately predicted whether teammates had sustained a mTBI or not. This suggests that these small molecules, and possibly others, might be clinically relevant biomarkers of mTBI. The same six biomarkers were then tested in a separate group of individuals, without and with mTBI, and the results replicated the athlete findings.
Although the results are encouraging, the authors report
limitations to their study and recommend additional investigations
related to these and other mTBI biomarkers in blood that will further
clarify their utility in clinical management.
“Such blood tests are important in determining not only whether
someone has sustained a concussion, which is not currently an easy
task, but may eventually prove useful in defining when injured
individuals may be eligible to safely return to regular activities,”
said Massimo S. Fiandaca, MD, the paper’s first author, a retired
neurosurgeon and co-director of the Georgetown and UCI research groups
led by the paper’s senior author, Howard J. Federoff, MD, PhD.
An objective biomarker of mTBI is not yet available to
healthcare providers, coaches and trainers, and military commanders and
combat medics. Such a diagnostic test might revolutionize the management
of civilian and military concussions, including strategies to avoid
post-concussive complications and more severe consequences, such as
chronic traumatic encephalopathy (CTE). Researchers at UCI are helping
advance technologies and therapeutic approaches that may benefit all
societies, but are directly relevant to their local populations.
The estimated 40 million individuals worldwide diagnosed with
mTBI likely represent a gross underestimation of those actually
sustaining such injuries. Clinical practitioners require a relevant and
reliable, minimally invasive, objective diagnostic test to determine
high versus low probability of mTBI in a timely manner.
Fiandaca said there is a clear need to improve diagnostic
capabilities, which could reduce underreporting of mTBI and allow more
appropriate care to be delivered to concussed individuals. Falls
represent the most common cause associated with mTBI among civilians in
the United States and around the world. In the U.S., sport-related mTBI
produces up to 3.8 million documented injuries per year. Changes in
warfare practices in the last two decades have elevated blast (i.e.,
explosive) injuries to the primary cause for mTBI in the US active duty
military. Between 2000-2016 approximately 82% of all military TBI fell
into this category.
Although current technologies for defining the discovered small
molecules in today’s publication lack the rapid, point-of-care
platforms being developed for other measures, the study authors
anticipate a growing technological momentum to develop such novel
platforms resulting from this and similar investigations.
This research was supported through a grant from the U.S.
Department of Defense to Federoff, initiated while he was at Georgetown
in collaboration with investigators from Rochester, and completed at UCI
in 2017. In addition to Federoff and Fiandaca, collaborators included
Mark Mapstone, PhD, Amin Mahmoodi, Thomas Gross and Fabio Macciardi, MD,
PhD, from UCI; Amrita K. Cheema from Georgetown University; and Jeffrey
Bazarian, MD, MPH, and Kian Merchant-Borna, MPH, from University of
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