Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury

Abstract

Object In previous studies of traumatic brain injury (TBI), neural biomarkers of injury correlate with injury severity and predict neurological outcome. The object of this paper was to characterize neurofilament-H (NFL-H) as a predictor of injury severity in patients who have suffered mild TBI (mTBI). Thus, the authors hypothesized that phosphorylated NFL-H (pNFL-H) levels are higher in mTBI patients than in healthy controls and identify which subjects experienced a more severe injury such as skull fractures, intracranial hemorrhaging, and/or contusions as detected by CT scans. Methods In this prospective clinical study, blood (8 ml) was collected from subjects (n = 34) suffering from mTBI (as defined by the American Congress of Rehabilitation and Glasgow Coma Scale scores between 13 and 15) at Parkland Hospital, Dallas, Texas, on Days 1 and 3 after injury). Additional clinical findings from the CT scans were also used to categorize the TBI patients into those with and those without clinical findings on the scans (CT+ and CTgroups, respectively). The serum levels of pNFL-H were measured using the enzyme-linked immunosorbent assay. Results Compared with healthy controls, the mTBI patients exhibited a significant increase in the serum levels of pNFL-H on Days 1 (p = 0.00001) and 3 (p = 0.0001) after TBI. An inverse correlation was observed between pNFL-H serum levels and Glasgow Coma Scale scores, which was significant. Additionally, using receiver operating characteristic curve analysis to compare the mTBI cases with controls to determine sensitivity and specificity, an area under the curve of 100% was achieved for both (p = 0.0001 for both). pNFL-H serum levels were only significantly higher on Day 1 in mTBI patients in the CT+ group (p < 0.008) compared with the CT− group. The area under the curve (82.5%) for the CT+ group versus the CT− group was significant (p = 0.021) with a sensitivity of 87.5% and a specificity of 70%, using a cutoff of 1071 pg/ml of pNFL-H in serum. Conclusions This study describes the serum profile of pNFL-H in patients suffering from mTBI with and without CT findings on Days 1 and 3 after injury. These results suggest that detection of pNFL-H may be useful in determining which individuals require CT imaging to assess the severity of their injury.