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October 09, 2018; 91 (15) Article

Glial fibrillary acidic protein elevations relate to neuroimaging abnormalities after mild TBI

Jessica Gill, Lawrence Latour, Ramon Diaz-Arrastia, Vida Motamedi, Christine Turtzo, Pashtun Shahim, Stefania Mondello, Christina DeVoto, Eliseo Veras, David Hanlon, Linan Song, Andreas Jeromin
First published September 12, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006321
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Abstract

Objectives To determine whether a panel of blood-based biomarkers can discriminate between patients with suspected mild traumatic brain injury (mTBI) with and without neuroimaging findings (CT and MRI).

Methods Study participants presented to the emergency department with suspected mTBI (n = 277) with a CT and MRI scan and healthy controls (n = 49). Plasma concentrations of tau, glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1, and neurofilament light chain (NFL) were measured using the single-molecule array technology.

Results Concentrations of GFAP, tau, and NFL were higher in patients with mTBI, compared with those of controls (p's < 0.01). GFAP yielded an area under the curve (AUC) of 0.93 (95% confidence interval [CI] 0.90–0.96), confirming its discriminatory power for distinguishing mTBI from controls. Levels of GFAP, tau, and NFL were higher in patients with trauma-related intracranial findings on CT compared with those with normal CT, with the only significant predictor being GFAP (AUC 0.77, 95% CI 0.70–0.84). Among patients with mTBI, tau, NFL, and GFAP differentiated subjects with and without MRI abnormalities with an AUC of 0.83, with GFAP being the strongest predictor. Combining tau, NFL, and GFAP showed a good discriminatory power (AUC 0.80, 95% CI 0.69–0.90) for detecting MRI abnormalities, even in patients with mTBI with a normal CT.

Conclusion Our study confirms GFAP as a promising marker of brain injury in patients with acute mTBI. A combination of various biomarkers linked to different pathophysiologic mechanisms increases diagnostic subgroup accuracy. This multimarker strategy may guide medical decision making, facilitate the use of MRI scanning, and prove valuable in the stratification of patients with brain injuries in future clinical trials.

Classification of evidence Class I evidence that blood concentrations of GFAP, tau, and NFL discriminate patients with mTBI with and without neuroimaging findings.

Glossary

AUC=
area under the curve;
CI=
confidence interval;
FLAIR=
fluid-attenuated inversion recovery;
GCS=
Glascow Coma Scale;
GFAP=
glial fibrillary acidic protein;
mTBI=
mild traumatic brain injury;
NFL=
neurofilament light chain;
ROC=
receiver operating curve;
TBI=
traumatic brain injury;
UCH-L1=
ubiquitin carboxyl-terminal hydrolase L1

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • CME Course: NPub.org/cmelist

  • Received January 19, 2018.
  • Accepted in final form June 29, 2018.
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