Time Course and Diagnostic Utility of Nfl, Tau, GFAP, and UCH-L1 in Subacute and Chronic TBI
| Autor: | Kaj Blennow, John A. Butman, Jessica M. Gill, Sara M. Lippa, Leighton Chan, David L. Brody, Brian Moore, Henrik Zetterberg, Yi-Yu Chou, Andre van der Merwe, Adam Politis, Ramon Diaz-Arrastia, Dzung L. Pham, Vindhya Ekanayake, Pashtun Shahim |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Oncology Diffuse Axonal Injury 0302 clinical medicine Neurofilament Proteins Brain Injuries Traumatic Prospective Studies 030212 general & internal medicine Prospective cohort study Glial fibrillary acidic protein biology Brain Organ Size Middle Aged Diffusion Tensor Imaging Correction and Replacement Area Under Curve Brain size Female Psychology Ubiquitin Thiolesterase Adult medicine.medical_specialty Traumatic brain injury Neurofilament light tau Proteins Article 03 medical and health sciences Atrophy Internal medicine Glial Fibrillary Acidic Protein medicine Humans Psychiatry business.industry Recovery of Function medicine.disease United States 030104 developmental biology ROC Curve nervous system Chronic Disease Time course biology.protein Neurology (clinical) business Biomarkers 030217 neurology & neurosurgery Diffusion MRI |
| Zdroj: | Neurology |
| ISSN: | 1526-632X |
| Popis: | ObjectiveTo 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.MethodsPatients 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.ResultsAt 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.ConclusionsSerum NfL shows greater diagnostic and prognostic utility than GFAP, tau, and UCH-L1 for subacute and chronic TBI.Classification of evidenceThis study provides Class III evidence that serum NfL distinguishes patients with mild TBI from healthy controls. |
| Databáze: | OpenAIRE |
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