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- Title
Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion.
- Authors
O'Brien, William T.; Spitz, Gershon; Xie, Becca; Major, Brendan P.; Mutimer, Steven; Giesler, Lauren P.; Bain, Jesse; Evans, Lauren J.; Duarte Martins, Beatriz; Piantella, Stefan; Alhassan, Afizu; Brady, Shelby; Cappellari, David; Somma, Vincenzo; McColl, Thomas; Symons, Georgia F.; Gore, Tenae; Sun, Matthew; Kuek, Timothy; Horan, Seamus
- Abstract
Key Points: Question: Do distinct trajectory subgroups exist in the serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) following sport-related concussion? Findings: In this cohort study of 81 individuals with sport-related concussion, in a subset of cases, increases in GFAP and NfL levels were substantial and persisted for at least 4 weeks. Individuals in these extreme biomarker subgroups were more likely to have experienced loss of consciousness (LOC) and longer to return to training times. Meaning: The findings of this study suggest the utility of serial measurements of GFAP and NfL to track neurobiologic recovery, with the association between LOC and extended biomarker elevations supporting the use of LOC for informing more conservative return-to-play timelines. Importance: Sport-related concussion (SRC), a form of mild traumatic brain injury, is a prevalent occurrence in collision sports. There are no well-established approaches for tracking neurobiologic recovery after SRC. Objective: To examine the levels of serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in Australian football athletes who experience SRC. Design, Setting, and Participants: A cohort study recruiting from April 10, 2021, to September 17, 2022, was conducted through the Victorian Amateur Football Association, Melbourne, Australia. Participants included adult Australian football players with or without SRC. Data analysis was performed from May 26, 2023, to March 27, 2024. Exposure: Sport-related concussion, defined as at least 1 observable sign and/or 2 or more symptoms. Main Outcomes and Measures: Primary outcomes were serum GFAP and NfL levels at 24 hours, and 1, 2, 4, 6, 8, 12, and 26 weeks. Secondary outcomes were symptoms, cognitive performance, and return to training times. Results: Eighty-one individuals with SRC (median age, 22.8 [IQR, 21.3-26.0] years; 89% male) and 56 control individuals (median age, 24.6 [IQR, 22.4-27.3] years; 96% male) completed a total of 945 of 1057 eligible testing sessions. Compared with control participants, those with SRC exhibited higher GFAP levels at 24 hours (mean difference [MD] in natural log, pg/mL, 0.66 [95% CI, 0.50-0.82]) and 4 weeks (MD, 0.17 [95% CI, 0.02-0.32]), and NfL from 1 to 12 weeks (1-week MD, 0.31 [95% CI, 0.12-0.51]; 2-week MD, 0.38 [95% CI, 0.19-0.58]; 4-week MD, 0.31 [95% CI, 0.12-0.51]; 6-week MD, 0.27 [95% CI, 0.07-0.47]; 8-week MD, 0.36 [95% CI, 0.15-0.56]; and 12-week MD, 0.25 [95% CI, 0.04-0.46]). Growth mixture modeling identified 2 GFAP subgroups: extreme prolonged (16%) and moderate transient (84%). For NfL, 3 subgroups were identified: extreme prolonged (7%), moderate prolonged (15%), and minimal or no change (78%). Individuals with SRC who reported loss of consciousness (LOC) (33% of SRC cases) had higher GFAP at 24 hours (MD, 1.01 [95% CI, 0.77-1.24]), 1 week (MD, 0.27 [95% CI, 0.06-0.49]), 2 weeks (MD, 0.21 [95% CI, 0.004-0.42]) and 4 weeks (MD, 0.34 [95% CI, 0.13-0.55]), and higher NfL from 1 week to 12 weeks (1-week MD, 0.73 [95% CI, 0.42-1.03]; 2-week MD, 0.91 [95% CI, 0.61-1.21]; 4-week MD, 0.90 [95% CI, 0.59-1.20]; 6-week MD, 0.81 [95% CI, 0.50-1.13]; 8-week MD, 0.73 [95% CI, 0.42-1.04]; and 12-week MD, 0.54 [95% CI, 0.22-0.85]) compared with SRC participants without LOC. Return to training times were longer in the GFAP extreme compared with moderate subgroup (incident rate ratio [IRR], 1.99 [95% CI, 1.69-2.34]; NfL extreme (IRR, 3.24 [95% CI, 2.63-3.97]) and moderate (IRR, 1.43 [95% CI, 1.18-1.72]) subgroups compared with the minimal subgroup, and for individuals with LOC compared with those without LOC (IRR, 1.65 [95% CI, 1.41-1.93]). Conclusions and Relevance: In this cohort study, a subset of SRC cases, particularly those with LOC, showed heightened and prolonged increases in GFAP and NfL levels, that persisted for at least 4 weeks. These findings suggest that serial biomarker measurement could identify such cases, guiding return to play decisions based on neurobiologic recovery. While further investigation is warranted, the association between prolonged biomarker elevations and LOC may support the use of more conservative return to play timelines for athletes with this clinical feature. This cohort study examines the levels of serum glial fibrillary acidic protein and neurofilament light in athletes in Australia who experience sport-related concussion.
- Subjects
VICTORIA; WOUNDS &; injuries; RESEARCH funding; LOSS of consciousness; SPORTS injuries; QUESTIONNAIRES; FISHER exact test; AUSTRALIAN football; CYTOSKELETAL proteins; DESCRIPTIVE statistics; PHYSICAL training &; conditioning; SEVERITY of illness index; MANN Whitney U Test; NEUROBIOLOGY; ATHLETES; NERVE tissue proteins; LONGITUDINAL method; SPORTS re-entry; CONVALESCENCE; DATA analysis software; EPIDEMIOLOGY; BIOMARKERS; BRAIN concussion; COGNITION
- Publication
JAMA Network Open, 2024, Vol 7, Issue 6, pe2415983
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.15983