Morgan E Nitta1, Jonathan Savitz1, Lindsay D Nelson1, T Kent Teague1, James B Hoelzle1, Michael A McCrea1, Timothy B Meier2. 1. From the Departments of Neurosurgery (M.E.N., L.D.N., M.A.M., T.B.M.), Neurology (L.D.N., M.A.M.), Cell Biology, Neurobiology and Anatomy (T.B.M.), and Biomedical Engineering (T.B.M.), Medical College of Wisconsin; Department of Psychology (M.E.N., J.B.H.), Marquette University, Milwaukee, WI; Laureate Institute for Brain Research (J.S.), Tulsa; Oxley College of Health Sciences (J.S.), The University of Tulsa; Departments of Surgery (T.K.T.) and Psychiatry (T.K.T.), University of Oklahoma School of Community Medicine; Department of Pharmaceutical Sciences (T.K.T.), University of Oklahoma College of Pharmacy; and Department of Biochemistry and Microbiology (T.K.T.), Oklahoma State University Center for Health Sciences, Tulsa. 2. From the Departments of Neurosurgery (M.E.N., L.D.N., M.A.M., T.B.M.), Neurology (L.D.N., M.A.M.), Cell Biology, Neurobiology and Anatomy (T.B.M.), and Biomedical Engineering (T.B.M.), Medical College of Wisconsin; Department of Psychology (M.E.N., J.B.H.), Marquette University, Milwaukee, WI; Laureate Institute for Brain Research (J.S.), Tulsa; Oxley College of Health Sciences (J.S.), The University of Tulsa; Departments of Surgery (T.K.T.) and Psychiatry (T.K.T.), University of Oklahoma School of Community Medicine; Department of Pharmaceutical Sciences (T.K.T.), University of Oklahoma College of Pharmacy; and Department of Biochemistry and Microbiology (T.K.T.), Oklahoma State University Center for Health Sciences, Tulsa. tmeier@mcw.edu.
Abstract
OBJECTIVE: To test the hypothesis that acute elevations in serum inflammatory markers predict symptom recovery after sport-related concussion (SRC). METHODS: High school and collegiate football players (n = 857) were prospectively enrolled. Forty-one athletes with concussion and 43 matched control athletes met inclusion criteria. Serum levels of interleukin (IL)-6, IL-1β, IL-10, tumor necrosis factor, C-reactive protein, interferon-γ, and IL-1 receptor antagonist and Sport Concussion Assessment Tool, 3rd edition (SCAT3) symptom severity scores were collected at a preinjury baseline, 6 and 24-48 hours postinjury, and approximately 8, 15, and 45 days following concussion. The number of days that athletes were symptomatic following SRC (i.e., duration of symptoms) was the primary outcome variable. RESULTS: IL-6 and IL-1RA were significantly elevated in athletes with concussion at 6 hours relative to preinjury and other postinjury visits, as well as compared to controls (ps ≤ 0.001). IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion (IL-6 area under receiver operating characteristic curve 0.79 [95% confidence interval (CI) 0.65-0.92], IL-1RA AUC 0.79 [95% CI 0.67-0.90]). Further, IL-6 levels at 6 hours postconcussion were significantly associated with the duration of symptoms (hazard ratio for symptom recovery = 0.61 [95% CI 0.38-0.96], p = 0.031). CONCLUSIONS: Results support the potential utility of IL-6 and IL-1RA as serum biomarkers of SRC and demonstrate the potential of these markers in identifying athletes at risk for prolonged recovery after SRC. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that serum levels of IL-6 and IL-1RA 6 hours postconcussion significantly discriminated concussed from control athletes.
OBJECTIVE: To test the hypothesis that acute elevations in serum inflammatory markers predict symptom recovery after sport-related concussion (SRC). METHODS: High school and collegiate football players (n = 857) were prospectively enrolled. Forty-one athletes with concussion and 43 matched control athletes met inclusion criteria. Serum levels of interleukin (IL)-6, IL-1β, IL-10, tumornecrosis factor, C-reactive protein, interferon-γ, and IL-1 receptor antagonist and Sport Concussion Assessment Tool, 3rd edition (SCAT3) symptom severity scores were collected at a preinjury baseline, 6 and 24-48 hours postinjury, and approximately 8, 15, and 45 days following concussion. The number of days that athletes were symptomatic following SRC (i.e., duration of symptoms) was the primary outcome variable. RESULTS:IL-6 and IL-1RA were significantly elevated in athletes with concussion at 6 hours relative to preinjury and other postinjury visits, as well as compared to controls (ps ≤ 0.001). IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion (IL-6 area under receiver operating characteristic curve 0.79 [95% confidence interval (CI) 0.65-0.92], IL-1RA AUC 0.79 [95% CI 0.67-0.90]). Further, IL-6 levels at 6 hours postconcussion were significantly associated with the duration of symptoms (hazard ratio for symptom recovery = 0.61 [95% CI 0.38-0.96], p = 0.031). CONCLUSIONS: Results support the potential utility of IL-6 and IL-1RA as serum biomarkers of SRC and demonstrate the potential of these markers in identifying athletes at risk for prolonged recovery after SRC. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that serum levels of IL-6 and IL-1RA 6 hours postconcussion significantly discriminated concussed from control athletes.
Authors: Rashmi Singh; Jonathan Savitz; T Kent Teague; David W Polanski; Andrew R Mayer; Patrick S F Bellgowan; Timothy B Meier Journal: J Neurol Neurosurg Psychiatry Date: 2015-08-12 Impact factor: 10.154
Authors: Paul McCrory; Willem H Meeuwisse; Mark Aubry; Bob Cantu; Jirí Dvorák; Ruben J Echemendia; Lars Engebretsen; Karen Johnston; Jeffrey S Kutcher; Martin Raftery; Allen Sills; Brian W Benson; Gavin A Davis; Richard G Ellenbogen; Kevin Guskiewicz; Stanley A Herring; Grant L Iverson; Barry D Jordan; James Kissick; Michael McCrea; Andrew S McIntosh; David Maddocks; Michael Makdissi; Laura Purcell; Margot Putukian; Kathryn Schneider; Charles H Tator; Michael Turner Journal: Br J Sports Med Date: 2013-04 Impact factor: 13.800
Authors: Peter J Hutchinson; Mark T O'Connell; Nancy J Rothwell; Stephen J Hopkins; Jürgens Nortje; Keri L H Carpenter; Ivan Timofeev; Pippa G Al-Rawi; David K Menon; John D Pickard Journal: J Neurotrauma Date: 2007-10 Impact factor: 5.269
Authors: Alex P Di Battista; Shawn G Rhind; Michael G Hutchison; Syed Hassan; Maria Y Shiu; Kenji Inaba; Jane Topolovec-Vranic; Antonio Capone Neto; Sandro B Rizoli; Andrew J Baker Journal: J Neuroinflammation Date: 2016-02-16 Impact factor: 8.322
Authors: Benjamin L Brett; Jonathan Savitz; Morgan Nitta; Lezlie España; T Kent Teague; Lindsay D Nelson; Michael A McCrea; Timothy B Meier Journal: Brain Behav Immun Date: 2020-07-24 Impact factor: 7.217
Authors: Timothy B Meier; Vivian A Guedes; Ethan G Smith; Dilorom Sass; Sara Mithani; Rany Vorn; Jonathan Savitz; T Kent Teague; Michael A McCrea; Jessica M Gill Journal: Brain Behav Immun Date: 2021-11-27 Impact factor: 7.217
Authors: Veronica A Mullins; Sarah Graham; Danielle Cummings; Alva Wood; Vanessa Ovando; Ann C Skulas-Ray; Dennis Polian; Yiwei Wang; Gerson D Hernandez; Claudia M Lopez; Adam C Raikes; Roberta D Brinton; Floyd H Chilton Journal: Nutrients Date: 2022-05-20 Impact factor: 6.706
Authors: Timothy B Meier; Daniel L Huber; Luisa Bohorquez-Montoya; Morgan E Nitta; Jonathan Savitz; T Kent Teague; Jeffrey J Bazarian; Ronald L Hayes; Lindsay D Nelson; Michael A McCrea Journal: Ann Neurol Date: 2020-04-20 Impact factor: 10.422
Authors: Benjamin L Brett; Timothy B Meier; Jonathan Savitz; Kevin M Guskiewicz; Michael A McCrea Journal: J Head Trauma Rehabil Date: 2021 Jul-Aug 01 Impact factor: 2.710
Authors: Camilla Bjørnbak Holst; Ib Jarle Christensen; Jane Skjøth-Rasmussen; Petra Hamerlik; Hans Skovgaard Poulsen; Julia Sidenius Johansen Journal: Front Oncol Date: 2020-04-17 Impact factor: 6.244
Authors: Alex P Di Battista; Nathan Churchill; Shawn G Rhind; Doug Richards; Michael G Hutchison Journal: BMC Immunol Date: 2020-03-12 Impact factor: 3.615