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

Joshua W. Gatson, Jennifer Barillas, Linda S. Hynan, Ramon Diaz-Arrastia, Steven Wolf, Joseph P. Minei

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1232-1238
Number of pages7
JournalJournal of Neurosurgery
Volume121
Issue number5
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

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Brain Concussion
Intermediate Filaments
Wounds and Injuries
Serum
Glasgow Coma Scale
Area Under Curve
Skull Fractures
Contusions
ROC Curve
Rehabilitation
Biomarkers
Enzyme-Linked Immunosorbent Assay
Prospective Studies
Sensitivity and Specificity

Keywords

  • Mild traumatic brain injury
  • Neurofilament-H
  • Serum

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury. / Gatson, Joshua W.; Barillas, Jennifer; Hynan, Linda S.; Diaz-Arrastia, Ramon; Wolf, Steven; Minei, Joseph P.

In: Journal of Neurosurgery, Vol. 121, No. 5, 01.11.2014, p. 1232-1238.

Research output: Contribution to journalArticle

Gatson, Joshua W. ; Barillas, Jennifer ; Hynan, Linda S. ; Diaz-Arrastia, Ramon ; Wolf, Steven ; Minei, Joseph P. / Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury. In: Journal of Neurosurgery. 2014 ; Vol. 121, No. 5. pp. 1232-1238.
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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.",
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AU - Gatson, Joshua W.

AU - Barillas, Jennifer

AU - Hynan, Linda S.

AU - Diaz-Arrastia, Ramon

AU - Wolf, Steven

AU - Minei, Joseph P.

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N2 - 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.

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