title: Serum SNTF Increases in Concussed Professional Ice Hockey Players and Relates to the Severity of Postconcussion Symptoms.
abstract: Biomarkers for diffuse axonal injury could have utilities for the acute diagnosis and clinical care of concussion, including those related to sports. The calpain-derived αII-spectrin N-terminal fragment (SNTF) accumulates in axons after traumatic injury and increases in human blood after mild traumatic brain injury (mTBI) in relation to white matter abnormalities and persistent cognitive dysfunction. However, SNTF has never been evaluated as a biomarker for sports-related concussion. Here, we conducted longitudinal analysis of serum SNTF in professional ice hockey players, 28 of whom had a concussion, along with 45 players evaluated during the preseason, 17 of whom were also tested after a concussion-free training game. Compared with preseason levels, serum SNTF increased at 1 h after concussion and remained significantly elevated from 12 h to 6 days, before declining to preseason baseline. In contrast, serum SNTF levels were unchanged after training. In 8 players, postconcussion symptoms resolved within a few days, and in these cases serum SNTF levels were at baseline. On the other hand, for the 20 players withheld from play for 6 days or longer, serum SNTF levels rose from 1 h to 6 days postconcussion, and at 12-36 h differed significantly from the less-severe concussions (p=0.004). Serum SNTF exhibited diagnostic accuracy for concussion, especially so with delayed return to play (area under the curve=0.87). Multi-variate analyses of serum SNTF and tau improved the diagnostic accuracy, the relationship with the delay in return to play, and the temporal window beyond tau alone. These results provide evidence that blood SNTF, a biomarker for axonal injury after mTBI, may be useful for diagnosis and prognosis of sports-related concussion, as well as for guiding neurobiologically informed decisions on return to play.
authors.affiliation: 1 Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Robert
authors.initials: R
authors.lastname: Siman
authors.affiliation: 2 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital , Molndal, Sweden .
authors.forename: Pashtun
authors.initials: P
authors.lastname: Shahim
authors.affiliation: 3 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: 2 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital , Molndal, Sweden .
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: 2 Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Sahgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital , Molndal, Sweden .|4 University College London, Institute of Neurology , London, United Kingdom .
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: 1 Department of Neurosurgery, Center for Brain Injury and Repair, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
mesh_terms: D000328:Adult; D001265:Athletic Injuries / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001924:Brain Concussion / Q000097:blood* / Q000503:physiopathology; D020833:Diffuse Axonal Injury / Q000097:blood; D006688:Hockey; D006801:Humans; D008297:Male; D009784:Occupational Diseases / Q000097:blood* / Q000503:physiopathology; D038223:Post-Concussion Syndrome / Q000097:blood / Q000503:physiopathology; D012720:Severity of Illness Index; D013049:Spectrin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D013049:Spectrin
keywords: calpain; diffuse axonal injury; mild traumatic brain injury; sports concussion; tau