title: A blood-based biomarker panel to risk-stratify mild traumatic brain injury.
abstract: Mild traumatic brain injury (TBI) accounts for the vast majority of the nearly two million brain injuries suffered in the United States each year. Mild TBI is commonly classified as complicated (radiographic evidence of intracranial injury) or uncomplicated (radiographically negative). Such a distinction is important because it helps to determine the need for further neuroimaging, potential admission, or neurosurgical intervention. Unfortunately, imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are costly and not without some risk. The purpose of this study was to screen 87 serum biomarkers to identify a select panel of biomarkers that would predict the presence of intracranial injury as determined by initial brain CT. Serum was collected from 110 patients who sustained a mild TBI within 24 hours of blood draw. Two models were created. In the broad inclusive model, 72kDa type IV collagenase (MMP-2), C-reactive protein (CRP), creatine kinase B type (CKBB), fatty acid binding protein-heart (hFABP), granulocyte-macrophage colony-stimulating factor (GM-CSF) and malondialdehyde modified low density lipoprotein (MDA-LDL) significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.975 and a negative predictive value (NPV) of 98.6. In the parsimonious model, MMP-2, CRP, and CKBB type significantly predicted injury visualized on CT, yielding an overall c-statistic of 0.964 and a negative predictive value (NPV) of 97.2. These results suggest that a serum based biomarker panel can accurately differentiate patients with complicated mild TBI from those with uncomplicated mild TBI. Such a panel could be useful to guide early triage decisions, including the need for further evaluation or admission, especially in those environments in which resources are limited.
authors.affiliation: School of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Richa
authors.initials: R
authors.lastname: Sharma
authors.affiliation: School of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rosenberg
authors.affiliation: Department of Neurology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Ellen R
authors.initials: ER
authors.lastname: Bennett
authors.affiliation: School of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.|Department of Neurology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.affiliation: Durham VA Medical Center, Durham, North Carolina, United States of America.|Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Shawn K
authors.initials: SK
authors.lastname: Acheson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001924:Brain Concussion / Q000097:blood* / Q000000981:diagnostic imaging* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D052276:Creatine Kinase, BB Form / Q000097:blood; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D015600:Glasgow Coma Scale; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000031:analogs & derivatives / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D059906:Neuroimaging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D008077:Lipoproteins, LDL; C569869:malondialdehyde-low density lipoprotein, human; D008315:Malondialdehyde; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002097:C-Reactive Protein; D052276:Creatine Kinase, BB Form; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2