Abstract
Objective: Identification and validation of blood-based biomarkers for the diagnosis and prognosis of mild traumatic brain injury (mTBI) is of critical importance. There have been calls for more research on mTBI in older adults. We compared blood-based protein marker glial fibrillary acidic protein (GFAP) concentrations in serum and in plasma within the same cohort of older adults and assessed their ability to discriminate between individuals based on intracranial abnormalities and functional outcome following mTBI.Methods: A sample of 121 older adults [≥50 years old with head computed tomography (CT), n = 92] seeking medical care for a head injury [Glasgow Coma Scale scores of 14 (n = 6; 5.0%) or 15 (n = 115; 95.0%)] were enrolled from the emergency department (ED). The mean time between injury and blood sampling was 3.4 h (SD = 2.1; range = 0.5–11.7). Serum GFAP concentration was measured first using the Human Neurology 4-Plex Assay, while plasma GFAP concentration was later measured using the GFAP Discovery Kit, both on an HD-1 Single molecule array (Simoa) instrument. Glasgow Outcome Scale-Extended was assessed 1 week after injury.Results: Both serum and plasma GFAP levels were significantly higher in those with abnormal CT scans compared to those with normal head CT scans (plasma: U = 1,198, p < 0.001; serum: U = 1,253, p < 0.001). The ability to discriminate those with and without intracranial abnormalities was comparable between serum (AUC = 0.814) and plasma (AUC = 0.778). In the total sample, GFAP concentrations were considerably higher in plasma than in serum (Wilcoxon signed-rank test z = 0.42, p < 0.001, r = 0.42). Serum and plasma GFAP levels were highly correlated in the total sample and within all subgroups (Spearman's rho range: 0.826–0.907). Both serum and plasma GFAP levels were significantly higher in those with poor compared to good functional outcome (serum: U = 1,625, p = 0.002; plasma: U = 1,539, p = 0.013). Neither plasma (AUC = 0.653) nor serum (AUC = 0.690) GFAP were adequate predictors of functional outcome 1 week after injury.Conclusions: Despite differences in concentration, serum and plasma GFAP levels were highly correlated and had similar discriminability between those with and without intracranial abnormalities on head CT following an mTBI. Neither serum nor plasma GFAP had adequate discriminability to identify patients who would have poor functional outcome.
Highlights
Glial fibrillary acidic protein (GFAP) concentration is increased following a traumatic brain injury (TBI), in studies of patients with predominantly mild to moderate injuries [1,2,3,4,5,6]
The sample for the present study was limited to older adults in part because (i) most patients who presented to the emergency department (ED) who had abnormal head CT scans in the cohort were, coincidentally, older adults; (ii) GFAP has been shown to increase with age [32, 34]; and (iii) GFAP was recently approved to screen for intracranial abnormalities [24], making this a convenience study of older adults
In a cohort of older adults following mild TBIs (mTBI), GFAP levels were highly correlated in serum and plasma, and GFAP had similar ability to discriminate between individuals with and without intracranial abnormalities
Summary
Glial fibrillary acidic protein (GFAP) concentration is increased following a traumatic brain injury (TBI), in studies of patients with predominantly mild to moderate injuries [1,2,3,4,5,6]. Many studies have examined the utility of GFAP for identifying patients with intracranial abnormalities following TBI [20]. GFAP is considered useful for this purpose given that it is specific to brain injury [7, 21,22,23] and has a relatively long half-life compared to other biomarkers [19]. The Food and Drug Administration (FDA) recently approved GFAP and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) for use in the emergency department (ED) to screen for traumatic intracranial abnormalities and aid clinical decisions regarding acute head CT scanning [24]
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