Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study
Authors: Howe Emilie Isager , Zeldovich Marina , Andelic Nada , von Steinbuechel Nicole , Fure Silje C. R. , Borgen Ida M. H. , Forslund Marit V. , Hellstrøm Torgeir , Søberg Helene L. , Sveen Unni , Rasmussen Mari , Kleffelgaard Ingerid , Tverdal Cathrine , Helseth Eirik , Løvstad Marianne , Lu Juan , Arango-Lasprilla Juan Carlos , Tenovuo Olli , Azouvi Philippe , Dawes Helen , Roe Cecilie ,   CENTER-TBI participants and investigators, Åkerlund Cecilia , Amrein Krisztina , Andreassen Lasse , Anke Audny , Antoni Anna , Audibert Gérard , Azzolini Maria Luisa , Bartels Ronald , Barzó Pál , Beauvais Romuald , Beer Ronny , Bellander Bo-Michael , Belli Antonio , Benali Habib , Berardino Maurizio , Beretta Luigi , Blaabjerg Morten , Bragge Peter , Brazinova Alexandra , Brinck Vibeke , Brooker Joanne , Brorsson Camilla , Buki Andras , Bullinger Monika , Cabeleira Manuel , Caccioppola Alessio , Calappi Emiliana , Calvi Maria Rosa , Cameron Peter , Carbayo Lozano Guillermo , Carbonara Marco , Cavallo Simona , Chevallard Giorgio , Chieregato Arturo , Citerio Giuseppe , Clusmann Hans , Coburn Mark , Coles Jonathan , Cooper Jamie D. , Correia Marta , Čović Amra , Curry Nicola , Czeiter Endre , Czosnyka Marek , Dahyot-Fizelier Claire , Dark Paul , De Keyser Véronique , Degos Vincent , Della Corte Francesco , den Boogert Hugo , Depreitere Bart , Đilvesi Đula , Dixit Abhishek , Donoghue Emma , Dreier Jens , Dulière Guy-Loup , Ercole Ari , Esser Patrick , Ezer Erzsébet , Fabricius Martin , Feigin Valery L. , Foks Kelly , Frisvold Shirin , Furmanov Alex , Gagliardo Pablo , Galanaud Damien , Gantner Dashiell , Gao Guoyi , George Pradeep , Ghuysen Alexandre , Giga Lelde , Glocker Ben , Golubovic Jagoš , Gomez Pedro A. , Gratz Johannes , Gravesteijn Benjamin , Grossi Francesca , Gruen Russell L. , Gupta Deepak , Haagsma Juanita A. , Haitsma Iain , Helbok Raimund , Horton Lindsay , Huijben Jilske , Hutchinson Peter J. , Jacobs Bram , Jankowski Stefan , Jarrett Mike , Jiang Ji-yao , Johnson Faye , Jones Kelly , Karan Mladen , Kolias Angelos G. , Kompanje Erwin , Kondziella Daniel , Kornaropoulos Evgenios , Koskinen Lars-Owe , Kovács Noémi , Kowark Ana , Lagares Alfonso , Lanyon Linda , Laureys Steven , Lecky Fiona , Ledoux Didier , Lefering Rolf , Legrand Valerie , Lejeune Aurelie , Levi Leon , Lightfoot Roger , Lingsma Hester , Maas Andrew I. R. , Castaño-León Ana M. , Maegele Marc , Majdan Marek , Manara Alex , Manley Geoffrey , Martino Costanza , Maréchal Hugues , Mattern Julia , McMahon Catherine , Melegh Béla , Menon David , Menovsky Tomas , Mikolic Ana , Misset Benoit , Muraleedharan Visakh , Murray Lynnette , Negru Ancuta , Nelson David , Newcombe Virginia , Nieboer Daan , Nyirádi József , Olubukola Otesile , Oresic Matej , Ortolano Fabrizio , Palotie Aarno , Parizel Paul M. , Payen Jean-François , Perera Natascha , Perlbarg Vincent , Persona Paolo , Peul Wilco , Piippo-Karjalainen Anna , Pirinen Matti , Pisica Dana , Ples Horia , Polinder Suzanne , Pomposo Inigo , Posti Jussi P. , Puybasset Louis , Radoi Andreea , Ragauskas Arminas , Raj Rahul , Rambadagalla Malinka , Helmrich Isabel Retel , Rhodes Jonathan , Richardson Sylvia , Richter Sophie , Ripatti Samuli , Rocka Saulius ,  Roise Olav , Rosand Jonathan , Rosenfeld Jeffrey V. ,  Rosenlund Christina ,  Rosenthal Guy , Rossaint Rolf , Rossi Sandra , Rueckert Daniel ,  Rusnák Martin , Sahuquillo Juan , Sakowitz Oliver , Sanchez-Porras Renan , Sandor Janos , Schäfer Nadine , Schmidt Silke , Schoechl Herbert , Schoonman Guus , Schou Rico Frederik , Schwendenwein Elisabeth , Sewalt Charlie , Singh Ranjit D. , Skandsen Toril , Smielewski Peter , Sorinola Abayomi , Stamatakis Emmanuel , Stanworth Simon , Stevens Robert , Stewart William , Steyerberg Ewout W. , Stocchetti Nino , Sundström Nina , Takala Riikka , Tamás Viktória , Tamosuitis Tomas , Taylor Mark Steven , Ao Braden Te , Theadom Alice , Thomas Matt , Tibboel Dick , Timmers Marjolein , Tolias Christos , Trapani Tony , Tudora Cristina Maria , Unterberg Andreas , Vajkoczy Peter , Vallance Shirley , Valeinis Egils , Vámos Zoltán , van der Jagt Mathieu , Van der Steen Gregory , van der Naalt Joukje , van Dijck Jeroen T. J. M. , van Erp Inge A. M. , van Essen Thomas A. , Van Hecke Wim , van Heugten Caroline , Van Praag Dominique , van Veen Ernest , Vyvere Thijs Vande , van Wijk Roel P. J. , Vargiolu Alessia , Vega Emmanuel , Velt Kimberley , Verheyden Jan , Vespa Paul M. , Vik Anne , Vilcinis Rimantas , Volovici Victor , von Steinbüchel Nicole , Voormolen Daphne , Vulekovic Petar , Wang Kevin K. W. , Whitehouse Daniel , Wiegers Eveline , Williams Guy , Wilson Lindsay , Winzeck Stefan , Wolf Stefan , Yang Zhihui , Ylén Peter , Younsi Alexander , Zeiler Frederick A. , Zelinkova Veronika , Ziverte Agate , Zoerle Tommaso 
Published: December 2022

Abstract
Background
Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury.

Methods
Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles.

Results
Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL.

Conclusions
Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach.

Trial registration
ClinicalTrials.gov NCT02210221.