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Abstract
Objective To determine whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) measured in serum relate to traumatic brain injury (TBI) diagnosis, injury severity, brain volume, and diffusion tensor imaging (DTI) measures of traumatic axonal injury (TAI) in patients with TBI.
Methods Patients with TBI (n = 162) and controls (n = 68) were prospectively enrolled between 2011 and 2019. Patients with TBI also underwent serum, functional outcome, and imaging assessments at 30 (n = 30), 90 (n = 48), and 180 (n = 59) days, and 1 (n = 84), 2 (n = 57), 3 (n = 46), 4 (n = 38), and 5 (n = 29) years after injury.
Results At enrollment, patients with TBI had increased serum NfL compared to controls (p < 0.0001). Serum NfL decreased over the course of 5 years but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with an area under the receiver-operating characteristic curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrollment, serum GFAP was elevated in patients with TBI compared to controls (p < 0.001). GFAP showed a biphasic release in serum, with levels decreasing during the first 6 months of injury but increasing over the subsequent study visits. The highest AUROC for GFAP was measured at 30 days, distinguishing patients with moderate and severe TBI from controls (both 0.89). Serum tau and UCH-L1 showed weak associations with TBI severity and neuroimaging measures. Longitudinally, serum NfL was the only biomarker that was associated with the likely rate of MRI brain atrophy and DTI measures of progression of TAI.
Conclusions Serum NfL shows greater diagnostic and prognostic utility than GFAP, tau, and UCH-L1 for subacute and chronic TBI.
Classification of evidence This study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls.
Glossary
- AD=
- axial diffusivity;
- AUROC=
- area under the receiver operating characteristic curve;
- CC=
- corpus callosum;
- DoD=
- Department of Defense;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- GFAP=
- glial fibrillary acidic protein;
- GM=
- gray matter;
- GOS-E=
- Glasgow Outcome Scale–Extended;
- MD=
- mean diffusivity;
- mTBI=
- mild TBI;
- NfL=
- neurofilament light;
- RD=
- radial diffusivity;
- TAI=
- traumatic axonal injury;
- TBI=
- traumatic brain injury;
- UCH-L1=
- ubiquitin C-terminal hydrolase-L1;
- VA=
- Veterans Affairs;
- WM=
- white matter
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.
See the Highlighted Changes supplement, showing the changes made in this updated version: http://links.lww.com/WNL/B340.
Editorial, page 235
See page 241
Class of Evidence: NPub.org/coe
- Received August 28, 2019.
- Accepted in final form January 28, 2020.
- © 2020 American Academy of Neurology
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- Reader response: Time course and diagnostic utility of NfL, tau, GFAp, and UCH-L1 in subacute and chronic TBI
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