Clinical and Blood Biomarker Trajectories after Concussion: New Insights from a Longitudinal Pilot Study of Professional Flat-Track Jockeys

McDonald, Stuart J.; Piantella, Stefan; O’Brien, William T.; Hale, Matthew W.; O’Halloran, Paul; Kinsella, Glynda; Horan, Ben; O’Brien, Terence J.; Maruff, Paul; Shultz, Sandy R.; Wright, Bradley J.

doi:10.1089/neu.2022.0169

Cited by 15 publications

(14 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like other recent studies in SRC, 16,17 we found elevated plasma NfL and good classification accuracy in our ED mTBI cohort at 7 days. Notably, this subacute NfL classification accuracy (AUC 0.81) was comparable with acute GFAP (AUC 0.85), the best-performing acute biomarker with high brain specificity.…”

Section: Discussionsupporting

confidence: 89%

“…There was an observable trend toward a higher proportion of participants with mTBI reporting a history of mTBI compared with controls. While studies have demonstrated that our exclusion period for previous mTBI (i.e., 12 months) is generally sufficient for resolution of GFAP, NfL, tau, and UCH-L1 levels to control values in most participants, 17,48 cytokine profiles are less well understood, and possibly, ongoing neurobiological changes resulting from a prior mTBI could potentially affect biomarker levels and thereby affect classification accuracy. The lack of a trauma control group prohibited insights on the influence of extracranial trauma on IL-6 levels.…”

Section: Discussionmentioning

confidence: 98%

“…Therefore, the window for NfL to assist mTBI diagnosis is likely to be greater than 7 days. Considering recent evidence that blood NfL levels may indicate vulnerability to repeated mTBI 47 and that NfL trajectories can differ between cases with mTBI, 16,17 it seems likely that subacute NfL measures might assist retrospectively grading the significance of an mTBI and for helping with return to play/work decisions.…”

Section: Discussionmentioning

confidence: 99%

“…7,11 Thus, findings from studies that collect blood at various time points postinjury may not reflect classification performance in an ED setting where presentations primarily occur within 5 hours. 6,15 In addition, although biomarkers with an extended elevation may be more likely to assist with delayed presentations, 16,17 it is unknown whether these have comparable classification accuracy with acute biomarkers. Third, while loss of consciousness (LOC; ≤30 minutes) and post-traumatic amnesia (PTA; <24 hours) are strong indicators of mTBI, their association with biomarkers is poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury

Reyes,

Spitz,

Major

et al. 2023

Neurology

Self Cite

View full text Add to dashboard Cite

Objectives: Blood biomarkers GFAP and UCH-L1 have recently been FDA approved as predictors of intracranial lesions on CT after mild traumatic brain injury (mTBI). However, the vast majority of mTBI cases are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. Here we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults aged under 50 presenting to an ED within 6h of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post traumatic amnesia (LOC/PTA), and delayed presentation, affected classification performance.Methods: Blood samples, symptom questionnaires and cognitive tests were conducted prospectively for mTBI participants recruited from The Alfred Hospital Level 1 Emergency & Trauma Centre and uninjured controls. Follow-up testing was conducted at 7 days. Simoa® quantified plasma GFAP, UCH-L1, Tau, NfL, IL-6 and IL-1β. AUC analysis assessed classification accuracy for diagnosed mTBI and logistic regression models identified optimal biomarker combinations.Results: Plasma IL-6 (AUC=0.91, 95%CI=0.86-0.96), GFAP (AUC=0.85, 95%CI=0.78-0.93) and UCH-L1 (AUC=0.79, 95%CI=0.70-0.88) best differentiated mTBI (n=74) from controls (n=44) acutely (<6h), with NfL (AUC=0.81, 95%CI=0.72-0.90) the only marker to have such utility sub-acutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP AUC=0.71, 95%CI=0.55-0.88; IL-6 AUC=0.71, 95%CI=0.55-0.87) and those with LOC/PTA (GFAP AUC=0.73, 95%CI=0.59-0.86; IL-6 AUC=0.71, 95%CI=0.57-0.84). Acute IL-6 (R2=0.50, 95%CI=0.34-0.64) outperformed GFAP and UCH-L1 combined (R2=0.35, 95%CI=0.17-0.50), with the best acute model featuring GFAP and IL-6 (R2=0.54, 95%CI=0.34-0.68).Discussion:These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults under 50. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best performing acute markers, sub-acute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury

Reyes,

Spitz,

Major

et al. 2023

Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the current issue of Journal of Neurotrauma, McDonald et al undertook a longitudinal prospective study of professional flat-track jockeys with and without incident concussion to examine how the recently developed blood biomarkers for neuroaxonal injury (neurofilament light [NfL] and tau) and astrocytic activation/injury (glial fibrillary acidic protein [GFAP]) can be used together with computerized cognitive testing to diagnose the condition and characterize its time course. 5 Among 64 professional flat-track jockeys who donated baseline (non-concussed) blood samples and underwent cognitive testing using a computerized test (CogSport), 15 medically diagnosed concussions occurred during the training and competition season. The concussed jockeys were followed with repeated blood sampling and cognitive testing during a year at time points of high relevance to concussion dynamics (2-and 7-days, and 1-and 12-months post-concussion).…”

mentioning

confidence: 99%

Combinatorial Diagnostics of Sports-Related Concussion

Zetterberg

Brody

2023

Journal of Neurotrauma

View full text Add to dashboard Cite

Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion

O’Brien,

Spitz,

Xie

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceSport-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.ObjectiveTo examine the levels of serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in Australian football athletes who experience SRC.Design, Setting, and ParticipantsA 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.ExposureSport-related concussion, defined as at least 1 observable sign and/or 2 or more symptoms.Main Outcomes and MeasuresPrimary 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.ResultsEighty-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 RelevanceIn 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.

show abstract

Clinical and Blood Biomarker Trajectories after Concussion: New Insights from a Longitudinal Pilot Study of Professional Flat-Track Jockeys

Cited by 15 publications

References 29 publications

Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury

Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury

Combinatorial Diagnostics of Sports-Related Concussion

Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion

Contact Info

Product

Resources

About