Study – Biomarkers Could Help Identify CTE Risk in Athletes With History of Brain Injury

Mild traumatic brain injury is sometimes referred to as an ‘invisible injury’ as there is often no objective evidence to help diagnose the damage done. Instead a diagnosis is made based on a host of subjective complaints.  Repetitive concussive and sub-concussive blows are linked to CTE.  This disease also cannot be diagnosed with certainty in living individuals and objective criteria demonstrating risk of this disease are lacking.

An interesting study was published in JAMA Neurology this month, however, showing promise that certain biomarkers may be “an objective tool to assess the degree of central nervous system injury in individuals with PCS (post concussion syndrome)” and further that this tool may even be used to screen athletes that are at high risk of developing CTE.

In the study, titled “Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury” the authors reviewed 16 athletes with a history of Post Concussion Syndrome (approximately half of which recovered within a year and the others having persistent symptoms beyond a year) along with a control group.  Neurofilament light proteins were significantly increased in players with PCS for more than 1 year and players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals.

The authors concluded that these biomarkers could potentially be used to help screen athletes showing signs of too much damage which could, in turn, help athletes make a more informed retirement decision from combative and other contact sports.

Here is the study’s full abstract:

Importance  Evidence is accumulating that repeated mild traumatic brain injury (mTBI) incidents can lead to persistent, long-term debilitating symptoms and in some cases a progressive neurodegenerative condition referred to as chronic traumatic encephalopathy. However, to our knowledge, there are no objective tools to examine to which degree persistent symptoms after mTBI are caused by neuronal injury.

Objective  To determine whether persistent symptoms after mTBI are associated with brain injury as evaluated by cerebrospinal fluid biochemical markers for axonal damage and other aspects of central nervous system injury.

Design, Settings, and Participants  A multicenter cross-sectional study involving professional Swedish ice hockey players who have had repeated mTBI, had postconcussion symptoms for more than 3 months, and fulfilled the criteria for postconcussion syndrome (PCS) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) matched with neurologically healthy control individuals. The participants were enrolled between January 2014 and February 2016. The players were also assessed with Rivermead Post Concussion Symptoms Questionnaire and magnetic resonance imaging.

Main Outcomes and Measures  Neurofilament light protein, total tau, glial fibrillary acidic protein, amyloid β, phosphorylated tau, and neurogranin concentrations in cerebrospinal fluid.

Results  A total of 31 participants (16 men with PCS; median age, 31 years; range, 22-53 years; and 15 control individuals [11 men and 4 women]; median age, 25 years; range, 21-35 years) were assessed. Of 16 players with PCS, 9 had PCS symptoms for more than 1 year, while the remaining 7 returned to play within a year. Neurofilament light proteins were significantly increased in players with PCS for more than 1 year (median, 410 pg/mL; range, 230-1440 pg/mL) compared with players whose PCS resolved within 1 year (median, 210 pg/mL; range, 140-460 pg/mL) as well as control individuals (median 238 pg/mL, range 128-526 pg/mL; P = .04 and P = .02, respectively). Furthermore, neurofilament light protein concentrations correlated with Rivermead Post Concussion Symptoms Questionnaire scores and lifetime concussion events (ρ = 0.58, P = .02 and ρ = 0.52, P = .04, respectively). Overall, players with PCS had significantly lower cerebrospinal fluid amyloid-β levels compared with control individuals (median, 1094 pg/mL; range, 845-1305 pg/mL; P = .05).

Conclusions and Relevance  Increased cerebrospinal fluid neurofilament light proteins and reduced amyloid β were observed in patients with PCS, suggestive of axonal white matter injury and amyloid deposition. Measurement of these biomarkers may be an objective tool to assess the degree of central nervous system injury in individuals with PCS and to distinguish individuals who are at risk of developing chronic traumatic encephalopathy.

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