Predicting recovery in patients with mild traumatic brain injury and a normal CT using serum biomarkers and diffusion tensor imaging (CENTER-TBI): an observational cohort study
Sophie Richter, Stefan Winzeck, Marta Correia, Endre Czeiter, Daniel Whitehouse, Evgenios Kornaropoulos, Guy Williams, Jan Verheyden, Tilak Das, Olli Tenovuo, Jussi P. Posti, Anne Vik, Kent Gøran Moen, Asta K. Håberg, Kevin Wang, Andras Buki, Andrew I.R. Maas, Ewout W. Steyerberg, David Menon, Virginia Newcombe, Krisztina Amrein, Nada Anđelić, Lasse Andreassen, Audny Anke, Philippe Azouvi, Bo‐Michael Bellander, Habib Benali, Andras Buki, Alessio Caccioppola, Emiliana Calappi, Marco Carbonara, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan Coles, Marta Correia, Endre Czeiter, Véronique De Keyser, Vincent Degos, Bart Depreitere, Live Eikenes, Erzsébet Ezer, Kelly Foks, Shirin Frisvold, Damien Galanaud, Alexandre Ghuysen, Ben Glocker, Asta K. Håberg, Iain Haitsma, Eirik Helseth, Peter J. Hutchinson, Evgenios Kornaropoulos, Noémi Kovács, Ana Kowark, Steven Laureys, Didier Ledoux, Hester F. Lingsma, Andrew I.R. Maas, Geoffrey T. Manley, David Menon, Tomas Menovsky, Benoît Misset, Visakh Muraleedharan, Ingeborg Nakken, Virginia Newcombe, Wibeke Nordhøy, József Nyirádi, Fabrizio Ortolano, Paul M. Parizel, Vincent Perlbarg, Paolo Persona, Wilco C. Peul, Jussi P. Posti, Louis Puybasset, Sophie Richter, Cecilie Røe, Olav Røise, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Ranjit D. Singh, Toril Skandsen, Abayomi Sorinola, Emmanuel A. Stamatakis, Ewout W. Steyerberg, Nino Stocchetti, Riikka Takala, Viktória Tamás, Olli Tenovuo, Zoltán Vámos, Gregory Van der Steen, Inge A. van Erp, Wim Van Hecke, Thijs Vande Vyvere, Jan Verheyden, Anne Vik, Victor Volovici, Lars T. Westlye, Daniel Whitehouse, Guy Williams
Abstract
Background: Even patients with normal computed tomography (CT) head imaging may experience persistent symptoms for months to years after mild traumatic brain injury (mTBI). There is currently no good way to predict recovery and triage patients who may benefit from early follow-up and targeted intervention. We aimed to assess if existing prognostic models can be improved by serum biomarkers or diffusion tensor imaging metrics (DTI) from MRI, and if serum biomarkers can identify patients for DTI. Methods: We included 1025 patients aged >18 years with a Glasgow Coma Score >12 and normal CT from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study which recruited between December 19,2014 and December 17, 2017 (NCT02210221). Biomarkers (GFAP, NFL, S100B) were obtained at a median of 8.8 h (Q1-Q3 4.2-16.7) and DTI at 13 days (3-19) after injury. DTI metrics were available in 153 patients for 48 white matter tracts (ICBM-DTI-81 atlas). Incomplete recovery at three months was defined as an extended Glasgow Outcome Scale score <8. Existing prognostic models were fitted with and without biomarkers, or with and without DTI, and internally validated using bootstrapping. Findings: 75% (39-100)]. The top three prognostic tracts were the left posterior thalamic radiation, left superior cerebellar peduncle and right uncinate fasciculus. Serum biomarkers could have avoided 1 in 5 DTI scans, with GFAP <12 h and NFL 12-24 h from injury performing best. Interpretation: DTI substantially improved existing prognostic models for functional outcome in patients with mTBI and a normal CT, and biomarkers could help select patients for MRI. If validated, DTI could allow for targeted follow-up and enrichment of clinical trials of early interventions to improve outcome. Funding: EU Seventh Framework Programme, Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, NeuroTrauma Sciences.