Pashtun Shahim1, Henrik Zetterberg2, Joel Simrén2, Nicholas J Ashton2, Gina Norato2, Michael Schöll2, Yelverton Tegner2, Ramon Diaz-Arrastia2, Kaj Blennow2. 1. From the Institute of Neuroscience and Physiology (P.S., H.Z., J.S., N.J.A., M.S., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., J.S., N.J.A., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Rehabilitation Medicine Department (P.S.), National Institutes of Health Clinical Center, Bethesda, MD; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, United Kingdom; UK Dementia Research Institute (H.Z.), London; Wallenberg Centre for Molecular and Translational Medicine (N.J.A., M.S.), University of Gothenburg, Sweden; King's College London (N.J.A.), Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), United Kingdom; Clinical Trials Unit (G.N.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Division of Health (Y.T.), Medicine and Rehabilitation, Department of Health Science, Luleå University of Technology, Sweden; and Department of Neurology (R.D.-A.), University of Pennsylvania Perelman School of Medicine, Philadelphia. Pashtun.shahim@gmail.com. 2. From the Institute of Neuroscience and Physiology (P.S., H.Z., J.S., N.J.A., M.S., K.B.), Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg; Clinical Neurochemistry Laboratory (P.S., H.Z., J.S., N.J.A., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Rehabilitation Medicine Department (P.S.), National Institutes of Health Clinical Center, Bethesda, MD; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square, United Kingdom; UK Dementia Research Institute (H.Z.), London; Wallenberg Centre for Molecular and Translational Medicine (N.J.A., M.S.), University of Gothenburg, Sweden; King's College London (N.J.A.), Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation (N.J.A.), United Kingdom; Clinical Trials Unit (G.N.), National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Division of Health (Y.T.), Medicine and Rehabilitation, Department of Health Science, Luleå University of Technology, Sweden; and Department of Neurology (R.D.-A.), University of Pennsylvania Perelman School of Medicine, Philadelphia.
Abstract
BACKGROUND AND OBJECTIVES: To examine whether the brain biomarkers total-tau (T-tau), glial fibrillary acidic protein (GFAP), and β-amyloid (Aβ) isomers 40 and 42 in plasma relate to the corresponding concentrations in CSF, blood-brain barrier integrity, and duration of postconcussion syndrome (PCS) due to repetitive head impacts (RHIs) in professional athletes. METHOD: In this cross-sectional study, professional athletes with persistent PCS due to RHI (median of 1.5 years after recent concussion) and uninjured controls were assessed with blood and CSF sampling. The diagnosis of PCS was based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The athletes were enrolled through information flyers about the study sent to the Swedish Hockey League (SHL) and the SHL Medicine Committee. The controls were enrolled through flyers at University of Gothenburg and Sahlgrenska University Hospital, Sweden. The participants underwent lumbar puncture and blood assessment at Sahlgrenska University Hospital. The main outcome measures were history of RHI and PCS severity (PCS >1 year vs PCS <1 year) in relation to plasma and CSF concentrations of T-tau, GFAP, Aβ40, and Aβ42. Plasma T-tau, GFAP, Aβ40, and Aβ42 were quantified using an ultrasensitive assay technology. RESULTS: A total of 47 participants (28 athletes [median age 28 years, range 18-52] with persistent PCS due to RHI and 19 controls [median age, 25 years, range 21-35]) underwent paired blood and CSF sampling. T-tau, Aβ40, and Aβ42 concentrations measured in plasma did not correlate with the corresponding CSF concentrations, while there was a correlation between plasma and CSF levels of GFAP (r = 0.45, p = 0.020). There were no significant relationships between plasma T-tau, GFAP, and blood-brain barrier integrity as measured by the CSF:serum albumin ratio. T-tau, GFAP, Aβ40, and Aβ42 measured in plasma did not relate to PCS severity. None of the markers measured in plasma correlated with number of concussions, except decreased Aβ42 in those with higher number of concussions (r = -0.40, p = 0.04). DISCUSSION: T-tau, GFAP, Aβ40, and Aβ42 measured in plasma do not correspond to CSF measures and may have limited utility for the evaluation of the late effects of RHI, compared with when measured in CSF. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in professional athletes with postconcussion symptoms, plasma concentrations of T-tau, GFAP, Aβ40, and Aβ42 are not informative in the diagnosis of late effects of repetitive head injuries.
BACKGROUND AND OBJECTIVES: To examine whether the brain biomarkers total-tau (T-tau), glial fibrillary acidic protein (GFAP), and β-amyloid (Aβ) isomers 40 and 42 in plasma relate to the corresponding concentrations in CSF, blood-brain barrier integrity, and duration of postconcussion syndrome (PCS) due to repetitive head impacts (RHIs) in professional athletes. METHOD: In this cross-sectional study, professional athletes with persistent PCS due to RHI (median of 1.5 years after recent concussion) and uninjured controls were assessed with blood and CSF sampling. The diagnosis of PCS was based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). The athletes were enrolled through information flyers about the study sent to the Swedish Hockey League (SHL) and the SHL Medicine Committee. The controls were enrolled through flyers at University of Gothenburg and Sahlgrenska University Hospital, Sweden. The participants underwent lumbar puncture and blood assessment at Sahlgrenska University Hospital. The main outcome measures were history of RHI and PCS severity (PCS >1 year vs PCS <1 year) in relation to plasma and CSF concentrations of T-tau, GFAP, Aβ40, and Aβ42. Plasma T-tau, GFAP, Aβ40, and Aβ42 were quantified using an ultrasensitive assay technology. RESULTS: A total of 47 participants (28 athletes [median age 28 years, range 18-52] with persistent PCS due to RHI and 19 controls [median age, 25 years, range 21-35]) underwent paired blood and CSF sampling. T-tau, Aβ40, and Aβ42 concentrations measured in plasma did not correlate with the corresponding CSF concentrations, while there was a correlation between plasma and CSF levels of GFAP (r = 0.45, p = 0.020). There were no significant relationships between plasma T-tau, GFAP, and blood-brain barrier integrity as measured by the CSF:serum albumin ratio. T-tau, GFAP, Aβ40, and Aβ42 measured in plasma did not relate to PCS severity. None of the markers measured in plasma correlated with number of concussions, except decreased Aβ42 in those with higher number of concussions (r = -0.40, p = 0.04). DISCUSSION: T-tau, GFAP, Aβ40, and Aβ42 measured in plasma do not correspond to CSF measures and may have limited utility for the evaluation of the late effects of RHI, compared with when measured in CSF. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in professional athletes with postconcussion symptoms, plasma concentrations of T-tau, GFAP, Aβ40, and Aβ42 are not informative in the diagnosis of late effects of repetitive head injuries.
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