Shahim, P;
Politis, A;
van der Merwe, A;
Moore, B;
Ekanayake, V;
Lippa, S;
Chou, Y-Y;
... Chan, L; + view all
(2020)
Time course and diagnostic utility of NfL, tau, GFAp, and UCH-L1 in subacute and chronic TBI.
Neurology
, 95
(6)
e623-e636.
10.1212/WNL.0000000000009985.
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Zetterberg_Time course and diagnostic utility of NfL, tau, GFAp, and UCH-L1 in subacute and chronic TBI_AAM.pdf - Accepted Version Download (1MB) | Preview |
Abstract
OBJECTIVE: To determine if 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 2009-2018. Of the 162 patients, 102 underwent repeated serum, functional outcome, brain MRI volumetry, and DTI assessments at 30, 90, and 180 days, and 1, 2, 3, 4, and 5 years after TBI. RESULTS: At enrolment, patients with TBI had increased serum NfL compared to controls (p<0.0001). Serum NfL decreased over the course of five years, but remained significantly elevated compared to controls. Serum NfL at 30 days distinguished patients with mild, moderate, and severe TBI from controls with Area Under the Receiver-Operating Characteristic Curve (AUROC) of 0.84, 0.92, and 0.92, respectively. At enrolment, serum GFAp was elevated in TBI patients compared to controls (p<0.001). GFAp showed a biphasic release in serum, with levels decreasing during the first six months of injury, whereafter increased over the subsequent study visits. The highest AUROC for GFAp was measured at 30 days distinguishing moderate and severe TBI patients from controls (both 0.89). Serum tau and UCH-L1 showed weak associations to 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.
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