Abstract
Objective: To investigate the longitudinal evolution of three blood biomarkers: neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and tau, in out-patients and hospitalized patients with mild traumatic brain injury (mTBI) compared to controls, along with their associations—in patients—with clinical injury characteristics and demographic variables, and ability to discriminate patients with mTBI from controls.Methods: A longitudinal observation study including 207 patients with mTBI, 84 age and sex-matched community controls (CCs) and 52 trauma controls (TCs). Blood samples were collected at 5 timepoints: acute (<24 h), 72 h (24–72 h post-injury), 2 weeks, 3 and 12 months. Injury-related, clinical and demographic variables were obtained at inclusion and brain MRI within 72 h.Results: Plasma GFAP and tau were most elevated acutely and NFL at 2 weeks and 3 months. The group of patients with mTBI and concurrent other somatic injuries (mTBI+) had the highest elevation in all biomarkers across time points, and were more likely to be victims of traffic accidents and violence. All biomarkers were positively associated with traumatic intracranial findings on MRI obtained within 72 h. Glial fibrillary acidic protein and NFL levels were associated with Glasgow Coma Scale (GCS) score and presence of other somatic injuries. Acute GFAP concentrations showed the highest discriminability between patients and controls with an Area Under the Curve (AUC) of 0.92. Acute tau and 2-week NFL concentrations showed moderate discriminability (AUC = 0.70 and AUC = 0.75, respectively). Tau showed high discriminability between mTBI+ and TCs (AUC = 0.80).Conclusions: The association of plasma NFL with traumatic intracranial MRI findings, together with its later peak, could reflect ongoing secondary injury or repair mechanisms, allowing for a protracted diagnostic time window. Patients experiencing both mTBI and other injuries appear to be a subgroup with greater neural injury, differing from both the mTBI without other injuries and from both control groups. Acute GFAP concentrations showed the highest discriminability between patients and controls, were highly associated with intracranial traumatic injury, and showed the largest elevations compared to controls at the acute timepoint, suggesting it to be the most clinically useful plasma biomarker of primary CNS injury in mTBI.
Highlights
Finding minimally invasive, cost-effective, CNS-specific, objective biomarkers capable of assessing mild traumatic brain injury pathology would greatly improve the clinical care of this group of patients that make up over 90% [1] of the 69 million annual TBI cases [2]
Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are approved by the FDA in the US to determine the presence of intracranial injury in mild traumatic brain injury (mTBI) during the acute phase [4, 5], and S100B is approved in Scandinavia for the triage of patients with mTBI to CT scanning during the first 24 h after injury [6]
We investigated the temporal evolution of three biomarkers in peripheral blood: glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and tau, from the acute phase across a period of 12 months in patients with mTBI, trauma controls (TCs) and community controls (CCs)
Summary
Cost-effective, CNS-specific, objective biomarkers capable of assessing mild traumatic brain injury (mTBI) pathology would greatly improve the clinical care of this group of patients that make up over 90% [1] of the 69 million annual TBI cases [2]. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are approved by the FDA in the US to determine the presence of intracranial injury in mTBI during the acute phase [4, 5], and S100B is approved in Scandinavia for the triage of patients with mTBI to CT scanning during the first 24 h after injury [6]. Blood biomarkers with such a short time window are suboptimal for mTBI as many patients present later to their general practitioner or the emergency room. A more granular investigation of the long-term evolution of biomarkers is relevant, as studies have shown significantly elevated concentrations of inflammatory markers in mTBI for up to 1 year following injury [8], and that collecting blood biomarkers prospectively increases sensitivity and specificity [3]
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