Penn Medicine researchers find that elevated blood levels of a specific protein after traumatic brain injury are linked to white matter damage and lasting cognitive problems.
Researchers at the Perelman School of Medicine, University of Pennsylvania, working with colleagues at Baylor College of Medicine, report that a blood biomarker accurately identified which concussion patients later showed structural white matter damage and enduring cognitive dysfunction after a mild traumatic brain injury (mTBI). The biomarker, a calpain-cleaved fragment of αII-spectrin known as SNTF, was found at approximately twice the concentration in a subset of injured participants. If confirmed in larger cohorts, a single blood test measuring SNTF on the day of injury could help clinicians identify concussion patients at elevated risk of persistent cognitive deficits or progressive brain injury when considering a return to sports or military duty.
Concussion and mTBI affect more than 1.5 million children and adults annually in the United States, with hundreds of thousands more cases affecting military personnel worldwide. Current clinical tools and imaging methods cannot reliably determine the full extent of injury at the time of presentation, nor predict which individuals will develop the 15–30% rate of long-term cognitive impairments—difficulties that include slowed processing speed, impaired working memory, and reduced cognitive flexibility.
“Fast, simple, reliable tests are urgently needed to predict who is at risk for long-term problems after concussion, and to select patients for early treatment or clinical trials as therapeutic options develop,” said Robert Siman, PhD, research professor of Neurosurgery at Penn and lead author of the study. “Measuring SNTF levels in blood collected on the day of injury may help identify the subgroup of concussed patients who are most likely to develop persistent disability.”
The study, published in Frontiers in Neurology, analyzed blood samples and diffusion tensor imaging (DTI) data from a subset of 38 participants enrolled in a larger mTBI study. Participants were aged 15 to 25 years: 17 sustained head injuries from blunt trauma or acceleration/deceleration forces, 13 sustained orthopaedic injuries without reported head trauma, and 8 were uninjured, demographically matched controls.
All participants underwent repeated neuropsychological and cognitive testing over a three-month period. Results within the mTBI group showed substantial variation: some individuals performed on par with healthy controls throughout; others had transient impairments that recovered by three months; and a distinct group experienced cognitive impairments that persisted at the three-month follow-up. Importantly, nine participants exhibited abnormally high SNTF in blood samples drawn at presentation—seven from the mTBI group and two from the orthopaedic group—and these same individuals showed marked white matter abnormalities on DTI scans.
“Detecting SNTF in some orthopaedic injury patients suggests that certain injuries outside the head can still produce brain abnormalities that go unrecognized by standard testing,” said Douglas Smith, MD, director of the Penn Center for Brain Injury and Repair and professor of Neurosurgery. “SNTF is consistent with our earlier work showing calcium overload in neurons after trauma; this fragment serves as a marker of neurodegeneration triggered by calcium dysregulation.”
In this cohort, a blood test performed on the day of injury demonstrated 100% sensitivity for predicting which concussions would lead to persistent cognitive problems and 75% specificity for ruling out those without clinically meaningful concussion. While promising, these performance metrics require validation in larger, prospective studies. The Penn and Baylor teams plan follow-up studies to assess the robustness of SNTF as a prognostic marker, to optimize the timing of blood sampling after injury, and to determine whether SNTF measurement can detect when repeated concussions begin to cause cumulative brain damage and long-term disability.
Notes on the study and authorship
The research team includes Robert Siman, Nicholas Giovannone and Douglas H. Smith from the University of Pennsylvania, and Gerri Hanten, Elisabeth Wilde, Stephen R. McCauley, Jill V. Hunter, Xiaoqi Li and Harvey S. Levin from Baylor College of Medicine. This work was funded in part by the National Institute of Neurologic Disorders and Stroke (P01 NS056202).
Contact: Kim Menard – University of Pennsylvania Health System
Source: University of Pennsylvania Health System press release
Image source: The brain scan image is credited to NICHD/NIH and is in the public domain.
Original research: Full open access research for “Evidence that the blood biomarker SNTF predicts brain imaging changes and persistent cognitive dysfunction in mild TBI patients” by Robert Siman et al., Frontiers in Neurology. Published online November 18, 2013. doi:10.3389/fneur.2013.00190
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