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Original Investigation
November 2016

Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury

Author Affiliations
  • 1Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden
  • 2Division of Medical Sciences, Department of Health Sciences, Luleå University of Technology, Luleå, Sweden
  • 3Capio Artro Clinic, Stockholm, Sweden
  • 4Department of Molecular Neuroscience, University College London Institute of Neurology, London, United Kingdom
JAMA Neurol. 2016;73(11):1308-1315. doi:10.1001/jamaneurol.2016.2038
Key Points

Question  Is repeated mild traumatic brain injury associated with cerebrospinal fluid biomarkers of amyloid pathology, tau pathology, and synaptic loss?

Findings  In a cross-sectional study, among 16 professional ice hockey players who have had repeated mild traumatic brain injury and fulfilled the criteria for postconcussion syndrome compared with 15 neurologically healthy control individuals, we observed increased cerebrospinal fluid neurofilament light protein and reduced amyloid β levels. Our findings provide neurochemical evidence of white matter injury and amyloid deposition.

Meaning  Measurement of these biomarkers may be an objective tool to assess the degree of brain injury in individuals with postconcussion syndrome and to distinguish individuals who are at risk of developing progressive neurodegeneration.

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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