Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
Monash-Epworth Rehabilitation Research Centre, School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
JAMA Netw Open. 2024 Jun 3;7(6):e2415983. doi: 10.1001/jamanetworkopen.2024.15983.
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.
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.
Sport-related concussion, defined as at least 1 observable sign and/or 2 or more symptoms.
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.
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]).
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.
运动相关性脑震荡（SRC）是一种轻度创伤性脑损伤，在碰撞运动中很常见。目前还没有建立良好的方法来跟踪 SRC 后的神经生物学恢复情况。
检测经历 SRC 的澳大利亚足球运动员的血清神经胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）水平。
设计、地点和参与者：一项队列研究于 2021 年 4 月 10 日至 2022 年 9 月 17 日通过澳大利亚墨尔本的维多利亚业余足球协会进行招募，参与者包括有或没有 SRC 的成年澳大利亚足球运动员。数据于 2023 年 5 月 26 日至 2024 年 3 月 27 日进行分析。
运动相关性脑震荡定义为至少有 1 个可观察到的体征和/或 2 个或更多症状。
主要结果是 24 小时、1 周、2 周、4 周、6 周、8 周、12 周和 26 周时的血清 GFAP 和 NfL 水平。次要结果是症状、认知表现和重返训练时间。
81 名 SRC 患者（中位数年龄，22.8[IQR，21.3-26.0]岁；89%为男性）和 56 名对照组参与者（中位数年龄，24.6[IQR，22.4-27.3]岁；96%为男性）共完成了 1057 次合格测试中的 945 次。与对照组参与者相比，SRC 患者在 24 小时（自然对数，pg/mL，0.66[95%CI，0.50-0.82]）和 4 周（MD，0.17[95%CI，0.02-0.32]）时的 GFAP 水平更高，并且在 1 到 12 周时的 NfL 水平更高（1 周 MD，0.31[95%CI，0.12-0.51]；2 周 MD，0.38[95%CI，0.19-0.58]；4 周 MD，0.31[95%CI，0.12-0.51]；6 周 MD，0.27[95%CI，0.07-0.47]；8 周 MD，0.36[95%CI，0.15-0.56]；12 周 MD，0.25[95%CI，0.04-0.46]）。增长混合模型确定了 2 个 GFAP 亚组：极度延长（16%）和中度短暂（84%）。对于 NfL，确定了 3 个亚组：极度延长（7%）、中度延长（15%）和最小或无变化（78%）。报告有脑震荡（LOC）的 SRC 患者（33%的 SRC 病例）在 24 小时（MD，1.01[95%CI，0.77-1.24]）、1 周（MD，0.27[95%CI，0.06-0.49]）、2 周（MD，0.21[95%CI，0.004-0.42]）和 4 周（MD，0.34[95%CI，0.13-0.55]）时的 GFAP 水平更高，并且在 1 到 12 周时的 NfL 水平更高（1 周 MD，0.73[95%CI，0.42-1.03]；2 周 MD，0.91[95%CI，0.61-1.21]；4 周 MD，0.90[95%CI，0.59-1.20]；6 周 MD，0.81[95%CI，0.50-1.13]；8 周 MD，0.73[95%CI，0.42-1.04]；12 周 MD，0.54[95%CI，0.22-0.85]）与 SRC 患者中没有 LOC 的参与者相比。GFAP 极端亚组与中度亚组（发病率比[IRR]，1.99[95%CI，1.69-2.34]）、NfL 极端（IRR，3.24[95%CI，2.63-3.97]）和中度（IRR，1.43[95%CI，1.18-1.72]）亚组相比，以及与没有 LOC 的个体相比，返回训练的时间更长，而对于有 LOC 的个体与没有 LOC 的个体相比（IRR，1.65[95%CI，1.41-1.93]）。
在这项队列研究中，一部分 SRC 病例，特别是那些有 LOC 的病例，表现出明显且持续至少 4 周的 GFAP 和 NfL 水平升高和延长。这些发现表明，连续的生物标志物测量可以识别出此类病例，从而根据神经生物学恢复情况指导重返赛场的决定。虽然还需要进一步的调查，但延长的生物标志物升高与 LOC 之间的关联可能支持对具有这种临床特征的运动员采用更保守的重返赛场时间表。
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