Heterogeneity in Blood Biomarker Trajectories After Mild TBI Revealed by Unsupervised Learning

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

“…This underlines how critical it is to take into account the biomechanical forces and the primary injury mechanism and the heterogeneity of TBI and also suggests that additional factors control serum NFL levels 110 . In further support of the heterogeneity in biomarker trajectories in TBI patients, the CARE study demonstrated clustering of individuals with or without significant blood NFL increase post‐TBI 122 . NFL is not specific for TBI and elevated plasma or serum levels have been reported in other central or peripheral neurological conditions with neuroaxonal injury, which highlight the importance of considering same‐subject baselines and trajectories of plasma biomarker levels after TBI but also support the value of using panels of biomarkers to improve predictive value and interpretation 110,123 …”

“…110 In further support of the heterogeneity in biomarker trajectories in TBI patients, the CARE study demonstrated clustering of individuals with or without significant blood NFL increase post-TBI. 122 NFL is not specific for TBI and elevated plasma or serum levels have been reported in other central or peripheral neurological conditions with neuroaxonal injury, which highlight the importance of considering same-subject baselines and trajectories of plasma biomarker levels after TBI but also support the value of using panels of biomarkers to improve predictive value and interpretation. 110,123 We also identified candidate biomarkers predicting neuromotor functional recovery at 7d after LFPI, which included markers of inflammatory response [(7d-2d)-HMGB1, 2d-HMGB1, and 2d-TNF] or of astroglial injury and blood brain barrier permeability [(7d-2d)-GFAP, 2d-S100B] (prognostic biomarkers).…”

COVID-19 and Traumatic Brain Injury (TBI); What We Can Learn From the Viral Pandemic to Better Understand the Biology of TBI, Improve Diagnostics and Develop Evidence-Based Treatments

“…Elevated body temperature can indicate that an individual has COVID-19 but they could also be suffering from dozens of other infectious diseases. With respect to TBI, we are currently only “checking body temperatures.” Injury markers such as ubiquitin carboxy-terminal hydroxylase 1 (UCH-L1), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NF-L) are excellent and sensitive indicators of neuron and glia injury ( 7 ) but single post-injury time point data greatly limit their full diagnostic potential ( 8 ). They however do not provide information about the underlying pathobiological changes and cannot be used to identify disease phenotype(s).…”