GFAP-BDP as an Acute Diagnostic Marker in Traumatic Brain Injury: Results from the Prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

Self Cite

371

308

Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r = 0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. (ClinicalTrials.gov Identifier NCT01565551)

Section: Uchl-1 and Gfap Distinguish Between Tbi And Healthy Controlsmentioning

confidence: 99%

Acute Biomarkers of Traumatic Brain Injury: Relationship between Plasma Levels of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein

Diaz‐Arrastia

Wang

Papa

et al. 2014

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371

308

“…We have recently demonstrated the diagnostic accuracy of elevated levels of plasma GFAP in TBI, and candidate-gene allelic association analyses are currently underway. 33 …”

Section: Biospecimensmentioning

confidence: 99%

Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot: Multicenter Implementation of the Common Data Elements for Traumatic Brain Injury

Yue

Vassar

Lingsma

et al. 2013

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306

267

Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide, with enormous negative social and economic impacts. The heterogeneity of TBI combined with the lack of precise outcome measures have been central to the discouraging results from clinical trials. Current approaches to the characterization of disease severity and outcome have not changed in more than three decades. This prospective multicenter observational pilot study aimed to validate the feasibility of implementing the TBI Common Data Elements (TBI-CDEs). A total of 650 subjects who underwent computed tomography (CT) scans in the emergency department within 24 h of injury were enrolled at three level I trauma centers and one rehabilitation center. The TBI-CDE components collected included: 1) demographic, social and clinical data; 2) biospecimens from blood drawn for genetic and proteomic biomarker analyses; 3) neuroimaging studies at 2 weeks using 3T magnetic resonance imaging (MRI); and 4) outcome assessments at 3 and 6 months. We describe how the infrastructure was established for building data repositories for clinical data, plasma biomarkers, genetics, neuroimaging, and multidimensional outcome measures to create a high quality and accessible information commons for TBI research. Risk factors for poor follow-up, TBI-CDE limitations, and implementation strategies are described. Having demonstrated the feasibility of implementing the TBI-CDEs through successful recruitment and multidimensional data collection, we aim to expand to additional study sites. Furthermore, interested researchers will be provided early access to the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data set for collaborative opportunities to more precisely characterize TBI and improve the design of future clinical treatment trials. (ClinicalTrials.gov Identifier NCT01565551.)

“…Some of the protein biomarkers that have been used are S100b, NSE, glial fibrillary acidic protein (and its breakdown products), ubiquitin carboxyl-terminal esterase L1, and C-tau. 18,[74][75][76][77][78][79][80][81][82] However, there are issues in the use of these proteins for assessing TBI, which includes sensitivity and specificity, use in adult versus pediatric patients, lack of correlation between the values in blood and CSF, and lack of correlation with the different levels of TBI severity.…”

Section: Rubenstein Et Almentioning

confidence: 99%

A Novel, Ultrasensitive Assay for Tau: Potential for Assessing Traumatic Brain Injury in Tissues and Biofluids

Rubenstein

Chang

Davies

et al. 2015

103

Traumatic brain injury (TBI) is a cause of death and disability and can lead to tauopathy-related dementia at an early age. Pathologically, TBI results in axonal injury that is coupled to tau hyperphosphorylation, leading to microtubule instability and tau-mediated neurodegeneration. This suggests that the forms of this protein might serve as neuroinjury-related biomarkers for diagnosis of injury severity and prognosis of the neurological damage prior to clinical expression. We initially determined whether we could detect tau in body fluids using a highly sensitive assay. We used a novel immunoassay, enhanced immunoassay using multi-arrayed fiberoptics (EIMAF) either alone or in combination with rolling circle amplification (a-EIMAF) for the detection of total (T) and phosphorylated (P) tau proteins from brains and biofluids (blood, CSF) of rodents following controlled cortical impact (CCI) and human patients post severe TBI (sTBI). This assay technology for tau is the most sensitive to date with a detection limit of approximately 100 ag/mL for either T-tau and Ptau. In the rodent models, T-tau and P-tau levels in brain and blood increased following CCI during the acute phase and remained high during the chronic phase (30 d). In human CSF samples, T-tau and P-tau increased during the sampling period (5-6 d). T-tau and P-tau in human serum rose during the acute phase and decreased during the chronic stage but was still detectable beyond six months post sTBI. Thus, EIMAF has the potential for assessing both the severity of the proximal injury and the prognosis using easily accessible samples.