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Promising Biomarker May ID Long-Term Concussion Damage

Shaw, Gina

doi: 10.1097/

    A new blood biomarker accurately predicted which concussion victims would have persistent cognitive dysfunction after a mild traumatic brain injury, according to researchers from the Perelman School of Medicine at the University of Pennsylvania and Baylor College of Medicine.

    If validated in larger studies, experts said it could help emergency physicians identify concussion patients at particular risk for long-term brain performance problems.

    Mild traumatic brain injury is the most common neurological injury, with estimates of its annual prevalence ranging from 1.5 to 3 million per year. “Most concussion sufferers will recover just fine, within hours or days, without developing any brain damage or persistent signs of brain functional problems,” said Robert Siman, PhD, a research professor of neurosurgery at the University of Pennsylvania and the lead investigator of the team researching the marker, a protein known as α II-spectrin N-terminal fragment (SNTF.)

    “The vast majority of concussions have a normal CT, but somewhere between 15 and 25 percent of those individuals go on to suffer brain damage and lasting cognitive problems from just a single concussion. But there is no traditional neuroradiological method that can detect any differences in these patients,” said Dr. Siman.

    Thirty-eight patients were treated in Houston emergency departments in the first of two SNTF studies, and elevations in SNTF levels in the blood found on the day of injury accurately identified those individuals who would have white-matter abnormalities in their brain tracts detected by diffusion tensor imaging. Those were also the patients who went on to have cognitive performance deficits measured in follow-up examinations months. (Front Neurol 2013;18[4]:190.) The test demonstrated 100 percent sensitivity in predicting concussions that would lead to persistent cognitive problems and 75 percent specificity in correctly ruling out those without functionally harmful concussions.

    The second study extended the findings to sports concussions; researchers enrolled all 255 players in the top Swedish professional ice hockey league. (J Neurotrauma 2014 Nov 24 [Epub ahead of print].) The 28 players who sustained in-game concussions during the first half of the season received serial blood draws from one hour post-concussion to six days later, and their findings were compared with players evaluated during the pre-season or after a training game without concussion.

    “In this study, the outcome measure was delay in return to play as a measure of the persistence of post-concussion effects. Eight of the players had their symptoms resolve relatively rapidly, and in those players, their SNTF blood levels remained unchanged from the preseason baseline.”

    Twenty players who had persistent symptoms and who were withheld from play for six days or longer, however, had SNTF levels statistically significantly higher at all-time points. “This is what the field has been looking for from a blood test: Something that can identify very early on which patients are at risk for long-term damage. If this can be proven to be a robust and validated prognostic test, it could easily be used in the ED setting,” said Dr. Siman.

    At this point, no drug treatments have been clinically proven to preserve brain structure and promote long-term brain function in concussion patients. “There isn't even a rehab protocol proven in controlled clinical research studies to help the afflicted the best way possible,” said Dr. Siman. “Part of the problem in testing such therapies is that there's no way of identifying when they might still be potentially treatable. If this biomarker is validated, patients in the ER could be identified as especially at risk and appropriate for enrollment in candidate drug treatment or rehab trials.”

    Jeffrey Bazarian, MD, MPH, a professor of emergency medicine and neurology and neurosurgery at the University of Rochester Medical Center, said the study was important and a “beautiful first look” at the SNTF protein's potential. “But that doesn't mean we can roll it out tomorrow,” he said. “Other proteins have undergone hundreds of studies and we know their strengths and weaknesses, but they haven't been rolled out clinically.”

    He pointed to the calcium-binding protein S100B, which is approved in Europe but not the United States to diagnose concussion. “The test is very accurate in Caucasians, but when it was studied in a more diverse population in North America, it didn't perform as well,” Dr. Bazarian said. “This protein seems like it could potentially be better, but based on one study, it's hard to know. We need to see how it performs in a large, diverse population — in children, in people of color, in victims of multiple trauma, in people who have something wrong with their brain that is not a concussion, such as epilepsy or a brain tumor. This study looks really good, and gives us the green light to dive deep and find out just exactly how good the protein is.”

    If the findings are replicated in broader populations, Dr. Bazarian said SNTF “could be a really big game changer,” reducing unnecessary CT scans and helping to identify many patients whose concussions are missed. “These guys did a great study, and I can't wait to see further results,” he said.

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