Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury

Abstract

BackgroundThere is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting.MethodsAdult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011–2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13–15 was classified as mild (mTBI); GCS 9–12 as moderate (moTBI) and GCS 3–8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed.ResultsAmong 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls.ConclusionsS100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.

Trajectories of interleukin 10 and heart fatty acid-binding protein levels in traumatic brain injury patients with or without extracranial injuries

“…IL-10 and H-FABP may be promising in the acute diagnostics and outcome prediction of TBI ( 5 ). This study continues our previous line of research on these biomarkers ( 5 , 9 , 16 ). Before applying biomarkers for clinical use in TBI, factors that may influence their levels must be understood and controlled for in various clinical settings.…”

“…H-FABP is a cytoplasmic protein expressed in cardiac myocytes, making it a sensitive biomarker for myocardial infarction ( 8 ). H-FABP is also expressed in neurons and its blood levels increase after TBI ( 9 ). It is also a potential biomarker in the diagnostics of mTBI and in differentiating between CT-positive and CT-negative patients with mTBI ( 10 ).…”

Plasma Neurofilament Light Chain (NF-L) Is a Prognostic Biomarker for Cortical Damage Evolution but Not for Cognitive Impairment or Epileptogenesis Following Experimental TBI

“…Studies of patients with different types of TBI indicate an injury severity-dependent increase in serum levels of NF-L up to 100–200 pg/mL when sampled within 24 to 48 h post-admission [ 16 , 36 ]. Interestingly, the D2 serum NF-L levels were substantially lower in humans than in rats after severe TBI, approximately 200 pg/mL vs. 5000 pg/mL in rats [ 16 ].…”

Blood‐based biomarkers and traumatic brain injury—A clinical perspective

“…Most studies including all severities of TBI have shown that many biomarkers can distinguish mTBI from moderate to severe TBI––including the recent CENTER‐TBI study, which includes the largest biomarker study cohort to date 4 . Analogously with aforementioned concussion studies, it seems that distinguishing CT‐negative patients with mTBI acutely from patients with orthopaedic injuries using with clinically meaningful AU‐ROCs may not be possible 54,55 …”

“…4 Analogously with aforementioned concussion studies, it seems that distinguishing CTnegative patients with mTBI acutely from patients with orthopaedic injuries using with clinically meaningful AU-ROCs may not be possible. 54,55 Traumatic axonal damage, including diffuse axonal damage currently thought to be part of the pathophysiology of concussion, may explain the significantly elevated levels of biomarkers in imaging-negative TBI even days after injury.…”