Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study - 13/09/19

Doi : 10.1016/S1474-4422(19)30282-0

John K Yue, MD ^a,^c,^{*
Contributed equally}, Esther L Yuh, MD ^b,^c,^{*
Contributed equally}, Frederick K Korley, MD ^d,^{*
Contributed equally}, Ethan A Winkler, MD ^a,^c, Xiaoying Sun, MS ^e, Ross C Puffer, MD ^f,^g, Hansen Deng, MD ^g, Winward Choy, MD ^a,^c, Ankush Chandra, MS ^a,^c, Sabrina R Taylor, PhD ^a,^c, Adam R Ferguson, PhD ^a,^c, J Russell Huie, PhD ^a,^c, Miri Rabinowitz, PhD ^g, Ava M Puccio, PhD ^g, Pratik Mukherjee, ProfMD ^b,^c, Mary J Vassar, MS ^a,^c, Kevin K W Wang, PhD ^h, Ramon Diaz-Arrastia, ProfMD ⁱ, David O Okonkwo, ProfMD ^g, Sonia Jain, ProfPhD ^e, Geoffrey T Manley, ProfMD ^a,^c,⁎
and the
TRACK-TBI Investigators^{^†}
TRACK-TBI Investigators are listed at the end of the paper

Opeolu M Adeoye, Neeraj Badjatia, Kim Boase, Yelena G Bodien, Malcom R Bullock, Randall M Chesnut, John D Corrigan, Karen Crawford, Sureyya S Dikmen, Ann-Christine Duhaime, Richard G Ellenbogen, Venkata Feeser, Brandon Foreman, Raquel C Gardner, Etienne Gaudette, Joseph T Giacino, Dana P Goldman, Luis Gonzalez, Shankar Gopinath, Rao Gullapalli, J C Hemphill, Gillian Hotz, Joel H Kramer, Natalie P Kreitzer, Harvey S Levin, Christopher J Lindsell, Joan Machamer, Christopher J Madden, Alastair J Martin, Thomas W McAllister, Michael McCrea, Randall Merchant, Lindsay D Nelson, Florence Noel, Eva M Palacios, Daniel P Perl, Ava M Puccio, Miri Rabinowitz, Claudia S Robertson, Jonathan Rosand, Angelle M Sander, Gabriela G Satris, David M Schnyer, Seth A Seabury, Mark Sherer, Murray B Stein, Nancy R Temkin, Arthur W Toga, Alex B Valadka, Mary J Vassar, Paul M Vespa, Esther L Yuh, Ross Zafonte

^a Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA

^b Department of Radiology, University of California San Francisco, San Francisco, CA, USA

^c Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, CA, USA

^d Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA

^e Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA, USA

^f Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA

^g Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

^h Department of Psychiatry and Neurosciences, McKnight Brain Institute, University of Florida, Gainesville, FL, USA

ⁱ Department of Neurology, Center for Neurodegeneration and Repair, University of Pennsylvania, Philadelphia, PA, USA

^* Correspondence to: Prof Geoffrey T Manley, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94110, USA Department of Neurological Surgery University of California San Francisco San Francisco CA 94110 USA

Summary

Background

After traumatic brain injury (TBI), plasma concentration of glial fibrillary acidic protein (GFAP) correlates with intracranial injury visible on CT scan. Some patients with suspected TBI with normal CT findings show pathology on MRI. We assessed the discriminative ability of GFAP to identify MRI abnormalities in patients with normal CT findings.

Methods

TRACK-TBI is a prospective cohort study that enrolled patients with TBI who had a clinically indicated head CT scan within 24 h of injury at 18 level 1 trauma centres in the USA. For this analysis, we included patients with normal CT findings (Glasgow Coma Scale score 13–15) who consented to venepuncture within 24 h post injury and who had an MRI scan 7–18 days post injury. We compared MRI findings in these patients with those of orthopaedic trauma controls and healthy controls recruited from the study sites. Plasma GFAP concentrations (pg/mL) were measured using a prototype assay on a point-of-care platform. We used receiver operating characteristic (ROC) analysis to evaluate the discriminative ability of GFAP for positive MRI scans in patients with negative CT scans over 24 h (time between injury and venepuncture). The primary outcome was the area under the ROC curve (AUC) for GFAP in patients with CT-negative and MRI-positive findings versus patients with CT-negative and MRI-negative findings within 24 h of injury. The Dunn Kruskal–Wallis test was used to compare GFAP concentrations between MRI lesion types with Benjamini–Hochberg correction for multiple comparisons. This study is registered with ClinicalTrials.gov, number NCT02119182.

Findings

Between Feb 26, 2014, and June 15, 2018, we recruited 450 patients with normal head CT scans (of whom 330 had negative MRI scans and 120 had positive MRI scans), 122 orthopaedic trauma controls, and 209 healthy controls. AUC for GFAP in patients with CT-negative and MRI-positive findings versus patients with CT-negative and MRI-negative findings was 0·777 (95% CI 0·726–0·829) over 24 h. Median plasma GFAP concentration was highest in patients with CT-negative and MRI-positive findings (414·4 pg/mL, 25–75th percentile 139·3–813·4), followed by patients with CT-negative and MRI-negative findings (74·0 pg/mL, 17·5–214·4), orthopaedic trauma controls (13·1 pg/mL, 6·9–20·0), and healthy controls (8·0 pg/mL, 3·0–14·0; all comparisons between patients with CT-negative MRI-positive findings and other groups p<0·0001).

Interpretation

Analysis of blood GFAP concentrations using prototype assays on a point-of-care platform within 24 h of injury might improve detection of TBI and identify patients who might need subsequent MRI and follow-up.

Funding

National Institute of Neurological Disorders and Stroke and US Department of Defense.

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Plan

Introduction

Methods

Study population

Sample collection and biomarker analysis

CT imaging evaluation and analysis

MRI methods and analysis

Statistical analysis

Role of the funding source

Results

Discussion

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Vol 18 - N° 10

P. 953-961 - octobre 2019 Retour au numéro

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Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study - 13/09/19

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