EBioMedicine (Sep 2024)

Association of early blood-based biomarkers and six-month functional outcomes in conventional severity categories of traumatic brain injury: capturing the continuous spectrum of injuryResearch in context

  • Lindsay Wilson,
  • Virginia F.J. Newcombe,
  • Daniel P. Whitehouse,
  • Stefania Mondello,
  • Andrew I.R. Maas,
  • David K. Menon,
  • Cecilia Ackerlund,
  • Krisztina Amrein,
  • Nada Andelic,
  • Lasse Andreassen,
  • Audny Anke,
  • Anna Antoni,
  • Gérard Audibert,
  • Philippe Azouvi,
  • Maria Luisa Azzolini,
  • Ronald Bartels,
  • Pál Barzó,
  • Romuald Beauvais,
  • Ronny Beer,
  • Bo-Michael Bellander,
  • Antonio Belli,
  • Habib Benali,
  • Maurizio Berardino,
  • Luigi Beretta,
  • Morten Blaabjerg,
  • Peter Bragge,
  • Alexandra Brazinova,
  • Vibeke Brinck,
  • Joanne Brooker,
  • Camilla Brorsson,
  • Andras Buki,
  • Monika Bullinger,
  • Manuel Cabeleira,
  • Alessio Caccioppola,
  • Emiliana Calappi,
  • Maria Rosa Calvi,
  • Peter Cameron,
  • Guillermo Carbayo Lozano,
  • Marco Carbonara,
  • Ana M. Castaño-León,
  • Simona Cavallo,
  • Giorgio Chevallard,
  • Arturo Chieregato,
  • Giuseppe Citerio,
  • Hans Clusmann,
  • Mark Steven Coburn,
  • Jonathan Coles,
  • Jamie D. Cooper,
  • Marta Correia,
  • Amra Čović,
  • Nicola Curry,
  • Endre Czeiter,
  • Marek Czosnyka,
  • Claire Dahyot-Fizelier,
  • Paul Dark,
  • Helen Dawes,
  • Véronique De Keyser,
  • Vincent Degos,
  • Francesco Della Corte,
  • Hugo den Boogert,
  • Bart Depreitere,
  • Đula Đilvesi,
  • Abhishek Dixit,
  • Emma Donoghue,
  • Jens Dreier,
  • Guy-Loup Dulière,
  • Ari Ercole,
  • Patrick Esser,
  • Erzsébet Ezer,
  • Martin Fabricius,
  • Valery L. Feigin,
  • Kelly Foks,
  • Shirin Frisvold,
  • Alex Furmanov,
  • Pablo Gagliardo,
  • Damien Galanaud,
  • Dashiell Gantner,
  • Guoyi Gao,
  • Pradeep George,
  • Alexandre Ghuysen,
  • Lelde Giga,
  • Ben Glocker,
  • Jagoš Golubović,
  • Pedro A. Gomez,
  • Johannes Gratz,
  • Benjamin Gravesteijn,
  • Francesca Grossi,
  • Russell L. Gruen,
  • Deepak Gupta,
  • Juanita A. Haagsma,
  • Iain Haitsma,
  • Raimund Helbok,
  • Eirik Helseth,
  • Lindsay Horton,
  • Jilske Huijben,
  • Peter J. Hutchinson,
  • Bram Jacobs,
  • Stefan Jankowski,
  • Mike Jarrett,
  • Ji-yao Jiang,
  • Faye Johnson,
  • Kelly Jones,
  • Mladen Karan,
  • Angelos G. Kolias,
  • Erwin Kompanje,
  • Daniel Kondziella,
  • Evgenios Kornaropoulos,
  • Lars-Owe Koskinen,
  • Noémi Kovács,
  • Ana Kowark,
  • Alfonso Lagares,
  • Linda Lanyon,
  • Steven Laureys,
  • Fiona Lecky,
  • Didier Ledoux,
  • Rolf Lefering,
  • Valerie Legrand,
  • Aurelie Lejeune,
  • Leon Levi,
  • Roger Lightfoot,
  • Hester Lingsma,
  • Marc Maegele,
  • Marek Majdan,
  • Alex Manara,
  • Geoffrey Manley,
  • Hugues Maréchal,
  • Costanza Martino,
  • Julia Mattern,
  • Catherine McMahon,
  • Béla Melegh,
  • Tomas Menovsky,
  • Ana Mikolic,
  • Benoit Misset,
  • Visakh Muraleedharan,
  • Lynnette Murray,
  • Nandesh Nair,
  • Ancuta Negru,
  • David Nelson,
  • Daan Nieboer,
  • József Nyirádi,
  • Matej Oresic,
  • Fabrizio Ortolano,
  • Olubukola Otesile,
  • Aarno Palotie,
  • Paul M. Parizel,
  • Jean-François Payen,
  • Natascha Perera,
  • Vincent Perlbarg,
  • Paolo Persona,
  • Wilco Peul,
  • Anna Piippo-Karjalainen,
  • Matti Pirinen,
  • Dana Pisica,
  • Horia Ples,
  • Suzanne Polinder,
  • Inigo Pomposo,
  • Jussi P. Posti,
  • Louis Puybasset,
  • Andreea Rădoi,
  • Arminas Ragauskas,
  • Rahul Raj,
  • Malinka Rambadagalla,
  • Isabel Retel Helmrich,
  • Jonathan Rhodes,
  • Sylvia Richardson,
  • Sophie Richter,
  • Samuli Ripatti,
  • Saulius Rocka,
  • Cecilie Roe,
  • Olav Roise,
  • Jonathan Rosand,
  • Jeffrey Rosenfeld,
  • Christina Rosenlund,
  • Guy Rosenthal,
  • Rolf Rossaint,
  • Sandra Rossi,
  • Daniel Rueckert,
  • Martin Rusnák,
  • Juan Sahuquillo,
  • Oliver Sakowitz,
  • Renan Sanchez-Porras,
  • Janos Sandor,
  • Nadine Schäfer,
  • Silke Schmidt,
  • Herbert Schoechl,
  • Guus Schoonman,
  • Rico Frederik Schou,
  • Elisabeth Schwendenwein,
  • Ranjit D. Singh,
  • Charlie Sewalt,
  • Toril Skandsen,
  • Peter Smielewski,
  • Abayomi Sorinola,
  • Emmanuel Stamatakis,
  • Simon Stanworth,
  • Robert Stevens,
  • William Stewart,
  • Ewout W. Steyerberg,
  • Nino Stocchetti,
  • Nina Sundström,
  • Riikka Takala,
  • Viktória Tamás,
  • Tomas Tamosuitis,
  • Mark Steven Taylor,
  • Braden Te Ao,
  • Olli Tenovuo,
  • Alice Theadom,
  • Matt Thomas,
  • Aurore Thibaut,
  • Dick Tibboel,
  • Marjolijn Timmers,
  • Christos Tolias,
  • Tony Trapani,
  • Cristina Maria Tudora,
  • Andreas Unterberg,
  • Peter Vajkoczy,
  • Egils Valeinis,
  • Shirley Vallance,
  • Zoltán Vámos,
  • Mathieu van der Jagt,
  • Joukje van der Naalt,
  • Gregory Van der Steen,
  • Jeroen T.J.M. van Dijck,
  • Inge A. van Erp,
  • Thomas A. van Essen,
  • Wim Van Hecke,
  • Caroline van Heugten,
  • Dominique Van Praag,
  • Ernest van Veen,
  • Roel P.J. van Wijk,
  • Thijs Vande Vyvere,
  • Alessia Vargiolu,
  • Emmanuel Vega,
  • Kimberley Velt,
  • Jan Verheyden,
  • Paul M. Vespa,
  • Anne Vik,
  • Rimantas Vilcinis,
  • Victor Volovici,
  • Nicole von Steinbüchel,
  • Daphne Voormolen,
  • Peter Vulekovic,
  • Kevin K.W. Wang,
  • Eveline Wiegers,
  • Guy Williams,
  • Stefan Winzeck,
  • Stefan Wolf,
  • Zhihui Yang,
  • Peter Ylén,
  • Alexander Younsi,
  • Frederick A. Zeiler,
  • Veronika Zelinkova,
  • Agate Ziverte,
  • Tommaso Zoerle

Journal volume & issue
Vol. 107
p. 105298

Abstract

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Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

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