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

John K. Yue, Esther L. Yuh, Frederick K. Korley, Ethan A. Winkler, Xiaoying Sun, Ross C. Puffer, Hansen Deng, Winward Choy, Ankush Chandra, Sabrina R. Taylor, Adam R. Ferguson, J. Russell Huie, Miri Rabinowitz, Ava M. Puccio, Pratik Mukherjee, Mary J. Vassar, Kevin K.W. Wang, Ramon Diaz-Arrastia, David O. Okonkwo, Sonia JainGeoffrey T. Manley, 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, 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, Paul M. Vespa, Ross Zafonte

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)953-961
Number of pages9
JournalThe Lancet Neurology
Volume18
Issue number10
DOIs
StatePublished - Oct 2019

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Glial Fibrillary Acidic Protein
Multicenter Studies
Blood Proteins
Prospective Studies
Wounds and Injuries
Point-of-Care Systems
Magnetic Resonance Imaging
ROC Curve
Orthopedics
Phlebotomy
Traumatic Brain Injury
Head
National Institute of Neurological Disorders and Stroke
Glasgow Coma Scale
Trauma Centers
Area Under Curve

ASJC Scopus subject areas

  • Clinical Neurology

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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. / Yue, John K.; Yuh, Esther L.; Korley, Frederick K.; Winkler, Ethan A.; Sun, Xiaoying; Puffer, Ross C.; Deng, Hansen; Choy, Winward; Chandra, Ankush; Taylor, Sabrina R.; Ferguson, Adam R.; Huie, J. Russell; Rabinowitz, Miri; Puccio, Ava M.; Mukherjee, Pratik; Vassar, Mary J.; Wang, Kevin K.W.; Diaz-Arrastia, Ramon; Okonkwo, David O.; Jain, Sonia; Manley, Geoffrey T.; Adeoye, Opeolu M.; Badjatia, Neeraj; Boase, Kim; Bodien, Yelena G.; Bullock, Malcom R.; Chesnut, Randall M.; Corrigan, John D.; Crawford, Karen; Dikmen, Sureyya S.; Duhaime, Ann Christine; Ellenbogen, Richard G.; Feeser, Venkata; Foreman, Brandon; Gardner, Raquel C.; Gaudette, Etienne; Giacino, Joseph T.; Goldman, Dana P.; Gonzalez, Luis; Gopinath, Shankar; Gullapalli, Rao; Hemphill, J. C.; Hotz, Gillian; Kramer, Joel H.; Kreitzer, Natalie P.; Levin, Harvey S.; Lindsell, Christopher J.; Machamer, Joan; Madden, Christopher J.; Martin, Alastair J.; McAllister, Thomas W.; McCrea, Michael; Merchant, Randall; Nelson, Lindsay D.; Noel, Florence; Palacios, Eva M.; Perl, Daniel P.; Robertson, Claudia S.; Rosand, Jonathan; Sander, Angelle M.; Satris, Gabriela G.; Schnyer, David M.; Seabury, Seth A.; Sherer, Mark; Stein, Murray B.; Temkin, Nancy R.; Toga, Arthur W.; Valadka, Alex B.; Vespa, Paul M.; Zafonte, Ross.

In: The Lancet Neurology, Vol. 18, No. 10, 10.2019, p. 953-961.

Research output: Contribution to journalArticle

Yue, JK, Yuh, EL, Korley, FK, Winkler, EA, Sun, X, Puffer, RC, Deng, H, Choy, W, Chandra, A, Taylor, SR, Ferguson, AR, Huie, JR, Rabinowitz, M, Puccio, AM, Mukherjee, P, Vassar, MJ, Wang, KKW, Diaz-Arrastia, R, Okonkwo, DO, Jain, S, Manley, GT, Adeoye, OM, Badjatia, N, Boase, K, Bodien, YG, Bullock, MR, Chesnut, RM, Corrigan, JD, Crawford, K, Dikmen, SS, Duhaime, AC, Ellenbogen, RG, Feeser, V, Foreman, B, Gardner, RC, Gaudette, E, Giacino, JT, Goldman, DP, Gonzalez, L, Gopinath, S, Gullapalli, R, Hemphill, JC, Hotz, G, Kramer, JH, Kreitzer, NP, Levin, HS, Lindsell, CJ, Machamer, J, Madden, CJ, Martin, AJ, McAllister, TW, McCrea, M, Merchant, R, Nelson, LD, Noel, F, Palacios, EM, Perl, DP, Robertson, CS, Rosand, J, Sander, AM, Satris, GG, Schnyer, DM, Seabury, SA, Sherer, M, Stein, MB, Temkin, NR, Toga, AW, Valadka, AB, Vespa, PM & Zafonte, R 2019, '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', The Lancet Neurology, vol. 18, no. 10, pp. 953-961. https://doi.org/10.1016/S1474-4422(19)30282-0
Yue, John K. ; Yuh, Esther L. ; Korley, Frederick K. ; Winkler, Ethan A. ; Sun, Xiaoying ; Puffer, Ross C. ; Deng, Hansen ; Choy, Winward ; Chandra, Ankush ; Taylor, Sabrina R. ; Ferguson, Adam R. ; Huie, J. Russell ; Rabinowitz, Miri ; Puccio, Ava M. ; Mukherjee, Pratik ; Vassar, Mary J. ; Wang, Kevin K.W. ; Diaz-Arrastia, Ramon ; Okonkwo, David O. ; Jain, Sonia ; Manley, Geoffrey T. ; Adeoye, Opeolu M. ; Badjatia, Neeraj ; Boase, Kim ; Bodien, Yelena G. ; Bullock, Malcom R. ; Chesnut, Randall M. ; Corrigan, John D. ; Crawford, Karen ; Dikmen, Sureyya S. ; Duhaime, Ann Christine ; Ellenbogen, Richard G. ; Feeser, Venkata ; Foreman, Brandon ; Gardner, Raquel C. ; Gaudette, Etienne ; Giacino, Joseph T. ; Goldman, Dana P. ; Gonzalez, Luis ; Gopinath, Shankar ; Gullapalli, Rao ; Hemphill, J. C. ; Hotz, Gillian ; Kramer, Joel H. ; Kreitzer, Natalie P. ; Levin, Harvey S. ; Lindsell, Christopher J. ; Machamer, Joan ; Madden, Christopher J. ; Martin, Alastair J. ; McAllister, Thomas W. ; McCrea, Michael ; Merchant, Randall ; Nelson, Lindsay D. ; Noel, Florence ; Palacios, Eva M. ; Perl, Daniel P. ; Robertson, Claudia S. ; Rosand, Jonathan ; Sander, Angelle M. ; Satris, Gabriela G. ; Schnyer, David M. ; Seabury, Seth A. ; Sherer, Mark ; Stein, Murray B. ; Temkin, Nancy R. ; Toga, Arthur W. ; Valadka, Alex B. ; Vespa, Paul M. ; Zafonte, Ross. / 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. In: The Lancet Neurology. 2019 ; Vol. 18, No. 10. pp. 953-961.
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title = "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",
abstract = "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.",
author = "Yue, {John K.} and Yuh, {Esther L.} and Korley, {Frederick K.} and Winkler, {Ethan A.} and Xiaoying Sun and Puffer, {Ross C.} and Hansen Deng and Winward Choy and Ankush Chandra and Taylor, {Sabrina R.} and Ferguson, {Adam R.} and Huie, {J. Russell} and Miri Rabinowitz and Puccio, {Ava M.} and Pratik Mukherjee and Vassar, {Mary J.} and Wang, {Kevin K.W.} and Ramon Diaz-Arrastia and Okonkwo, {David O.} and Sonia Jain and Manley, {Geoffrey T.} and Adeoye, {Opeolu M.} and Neeraj Badjatia and Kim Boase and Bodien, {Yelena G.} and Bullock, {Malcom R.} and Chesnut, {Randall M.} and Corrigan, {John D.} and Karen Crawford and Dikmen, {Sureyya S.} and Duhaime, {Ann Christine} and Ellenbogen, {Richard G.} and Venkata Feeser and Brandon Foreman and Gardner, {Raquel C.} and Etienne Gaudette and Giacino, {Joseph T.} and Goldman, {Dana P.} and Luis Gonzalez and Shankar Gopinath and Rao Gullapalli and Hemphill, {J. C.} and Gillian Hotz and Kramer, {Joel H.} and Kreitzer, {Natalie P.} and Levin, {Harvey S.} and Lindsell, {Christopher J.} and Joan Machamer and Madden, {Christopher J.} and Martin, {Alastair J.} and McAllister, {Thomas W.} and Michael McCrea and Randall Merchant and Nelson, {Lindsay D.} and Florence Noel and Palacios, {Eva M.} and Perl, {Daniel P.} and Robertson, {Claudia S.} and Jonathan Rosand and Sander, {Angelle M.} and Satris, {Gabriela G.} and Schnyer, {David M.} and Seabury, {Seth A.} and Mark Sherer and Stein, {Murray B.} and Temkin, {Nancy R.} and Toga, {Arthur W.} and Valadka, {Alex B.} and Vespa, {Paul M.} and Ross Zafonte",
year = "2019",
month = "10",
doi = "10.1016/S1474-4422(19)30282-0",
language = "English (US)",
volume = "18",
pages = "953--961",
journal = "The Lancet Neurology",
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TY - JOUR

T1 - Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort

T2 - a prospective multicentre study

AU - Yue, John K.

AU - Yuh, Esther L.

AU - Korley, Frederick K.

AU - Winkler, Ethan A.

AU - Sun, Xiaoying

AU - Puffer, Ross C.

AU - Deng, Hansen

AU - Choy, Winward

AU - Chandra, Ankush

AU - Taylor, Sabrina R.

AU - Ferguson, Adam R.

AU - Huie, J. Russell

AU - Rabinowitz, Miri

AU - Puccio, Ava M.

AU - Mukherjee, Pratik

AU - Vassar, Mary J.

AU - Wang, Kevin K.W.

AU - Diaz-Arrastia, Ramon

AU - Okonkwo, David O.

AU - Jain, Sonia

AU - Manley, Geoffrey T.

AU - Adeoye, Opeolu M.

AU - Badjatia, Neeraj

AU - Boase, Kim

AU - Bodien, Yelena G.

AU - Bullock, Malcom R.

AU - Chesnut, Randall M.

AU - Corrigan, John D.

AU - Crawford, Karen

AU - Dikmen, Sureyya S.

AU - Duhaime, Ann Christine

AU - Ellenbogen, Richard G.

AU - Feeser, Venkata

AU - Foreman, Brandon

AU - Gardner, Raquel C.

AU - Gaudette, Etienne

AU - Giacino, Joseph T.

AU - Goldman, Dana P.

AU - Gonzalez, Luis

AU - Gopinath, Shankar

AU - Gullapalli, Rao

AU - Hemphill, J. C.

AU - Hotz, Gillian

AU - Kramer, Joel H.

AU - Kreitzer, Natalie P.

AU - Levin, Harvey S.

AU - Lindsell, Christopher J.

AU - Machamer, Joan

AU - Madden, Christopher J.

AU - Martin, Alastair J.

AU - McAllister, Thomas W.

AU - McCrea, Michael

AU - Merchant, Randall

AU - Nelson, Lindsay D.

AU - Noel, Florence

AU - Palacios, Eva M.

AU - Perl, Daniel P.

AU - Robertson, Claudia S.

AU - Rosand, Jonathan

AU - Sander, Angelle M.

AU - Satris, Gabriela G.

AU - Schnyer, David M.

AU - Seabury, Seth A.

AU - Sherer, Mark

AU - Stein, Murray B.

AU - Temkin, Nancy R.

AU - Toga, Arthur W.

AU - Valadka, Alex B.

AU - Vespa, Paul M.

AU - Zafonte, Ross

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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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U2 - 10.1016/S1474-4422(19)30282-0

DO - 10.1016/S1474-4422(19)30282-0

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EP - 961

JO - The Lancet Neurology

JF - The Lancet Neurology

SN - 1474-4422

IS - 10

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