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  • 1.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Gustafsson, Bengt
    Capio Artro Clinic, Stockholm.
    Gren, Magnus
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Ärlig, Johan
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Olsson, Martin
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Lehto, Niklas
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Engström, Åsa
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Höglund, Kina
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Portelius, Erik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospita.
    Neurochemical Aftermath of Repetitive Mild Traumatic Brain Injury2016In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 73, no 11, p. 1308-1315Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Wilson, David H.
    Quanterix Corp, Lexington, MA.
    Randall, Jeffrey
    Quanterix Corp, Lexington, MA.
    Skillbäck, Tobias
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Pazooki, David
    Department of Surgery, Sahlgrenska University Hospital.
    Kallberg, Birgitta
    Clinical Chemistry Laboratory, Sahlgrenska University Hospital.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Blood biomarkers for brain injury in concussed professional ice hockey players2014In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 71, no 6, p. 684-692Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Lack of objective biomarkers for brain damage hampers acute diagnosis and clinical decision making about return to play after sports-related concussion. OBJECTIVES To determine whether sports-related concussion is associated with elevated levels of blood biochemical markers of injury to the central nervous system and to assess whether plasma levels of these biomarkers predict return to play in professional ice hockey players with sports-related concussion. DESIGN, SETTING, AND PARTICIPANTS Multicenter prospective cohort study involving all 12teams of the top professional ice hockey league in Sweden, the Swedish Hockey League. Two hundred eighty-eight professional ice hockey players from 12 teams contesting during the 2012-2013 season consented to participate. All players underwent clinical preseason baseline testing regarding concussion assessment measures. Forty-seven players from 2 of the 12 ice hockey teams underwent blood sampling prior to the start of the season. Thirty-five players had a concussion from September 13, 2012, to January 31, 2013; of these players, 28 underwent repeated blood sampling at 1, 12, 36, and 144 hours and when the players returned to play. MAIN OUTCOMES AND MEASURES Total tau, S-100 calcium-binding protein B, and neuron-specific enolase concentrations in plasma and serum were measured.

  • 3.
    Shahim, Pashtun
    et al.
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Tegner, Yelverton
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Wilson, David H.
    Quanterix Corp, Lexington, MA.
    Randall, Jeffrey
    Quanterix Corp, Lexington, MA.
    Skillbäck, Tobias
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Pazooki, David
    Department of Surgery, Sahlgrenska University Hospital.
    Kallberg, Birgitta
    Clinical Chemistry Laboratory, Sahlgrenska University Hospital.
    Blennow, Kaj
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Zetterberg, Henrik
    Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg.
    Blood biomarkers for brain injury in concussed professional ice hockey players: correction2014In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 73, no 9, p. 1160-Article in journal (Refereed)
    Abstract [en]

    Reports an error in 'Blood biomarkers for brain injury in concussed professional ice hockey players' by Pashtun Shahim, Yelverton Tegner, David H. Wilson, Jeffrey Randall, Tobias Skillbäck, David Pazooki, Birgitta Kallberg, Kaj Blennow and Henrik Zetterberg (JAMA Neurology, 2014[Jun], Vol 71[6], 684-692). In the original article, there were errors in Table 1 and Figure 2A. The corrections are present in the erratum. (The following abstract of the original article appeared in record 2014-24656-005). Importance: Lack of objective biomarkers for brain damage hampers acute diagnosis and clinical decision making about return to play after sports-related concussion. Objectives: To determine whether sports-related concussion is associated with elevated levels of blood biochemical markers of injury to the central nervous system and to assess whether plasma levels of these biomarkers predict return to play in professional ice hockey players with sports-related concussion. Design, Setting, and Participants: Multicenter prospective cohort study involving all 12 teams of the top professional ice hockey league in Sweden, the Swedish Hockey League. Two hundred eighty-eight professional ice hockey players from 12 teams contesting during the 2012-2013 season consented to participate. All players underwent clinical preseason baseline testing regarding concussion assessment measures. Forty-seven players from 2 of the 12 ice hockey teams underwent blood sampling prior to the start of the season. Thirty-five players had a concussion from September 13, 2012, to January 31, 2013; of these players, 28 underwent repeated blood sampling at 1, 12, 36, and 144 hours and when the players returned to play. Main Outcomes and Measures: Total tau, S-100 calcium-binding protein B, and neuron-specific enolase concentrations in plasma and serum were measured. Results: Concussed players had increased levels of the axonal injury biomarker total tau(median, 10.0 pg/mL; range, 2.0-102 pg/mL) compared with preseason values (median, 4.5pg/mL; range, 0.06-22.7 pg/mL) (P < .001). The levels of the astroglial injury biomarker S-100 calcium-binding protein B were also increased in players with sports-related concussion(median, 0.075 μg/L; range, 0.037-0.24 μg/L) compared with preseason values (median,0.045 μg/L; range, 0.005-0.45 μg/L) (P < .001). The highest biomarker concentrations of total tau and S-100 calcium-binding protein B were measured immediately after a concussion, and they decreased during rehabilitation. No significant changes were detected in the levels of neuron-specific enolase from preseason values (median, 6.5 μg/L; range,3.45-18.0 μg/L) to postconcussion values (median, 6.1 μg/L; range, 3.6-12.8 μg/L) (P = .10). Conclusions and Relevance: Sports-related concussion in professional ice hockey players is associated with acute axonal and astroglial injury. This can be monitored using blood biomarkers, which may be developed into clinical tools to guide sport physicians in the medical counseling of athletes in return-to-play decisions

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