title: Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Pashtun
authors.initials: P
authors.lastname: Shahim
authors.affiliation: Division of Medical Sciences, Department of Health Sciences, Luleå University of Technology, Luleå, Sweden.
authors.forename: Yelverton
authors.initials: Y
authors.lastname: Tegner
authors.affiliation: Capio Artro Clinic, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Gustafsson
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gren
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ärlig
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Olsson
authors.affiliation: Division of Medical Sciences, Department of Health Sciences, Luleå University of Technology, Luleå, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Lehto
authors.affiliation: Division of Medical Sciences, Department of Health Sciences, Luleå University of Technology, Luleå, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Engström
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kina
authors.initials: K
authors.lastname: Höglund
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden4Department of Molecular Neuroscience, University College London Institute of Neurology, London, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
mesh_terms: D000328:Adult; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D001265:Athletic Injuries / Q000134:cerebrospinal fluid*; D001924:Brain Concussion / Q000134:cerebrospinal fluid*; D001925:Brain Damage, Chronic / Q000134:cerebrospinal fluid*; D003430:Cross-Sectional Studies; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid; D006688:Hockey / Q000293:injuries*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D051579:Neurogranin / Q000134:cerebrospinal fluid; D038223:Post-Concussion Syndrome / Q000134:cerebrospinal fluid*; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins; D051579:Neurogranin