Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI
Authors: Howe Emilie Isager , Andelic Nada , Brunborg Cathrine , Zeldovich Marina , Helseth Eirik , Skandsen Toril , Olsen Alexander , Fure Silje C. R. , Theadom Alice , Rauen Katrin , Madsen Benedikte Å. , Jacobs Bram , van der Naalt Joukje , Tartaglia Maria Carmela , Einarsen Cathrine Elisabeth , Storvig Gøril , Tronvik Erling , Tverdal Cathrine , von Steinbüchel Nicole , Røe Cecilie , Hellstrøm Torgeir ,   CENTER-TBI Participants and Investigators, Åkerlund Cecilia , Amrein Krisztina , Andreassen Lasse , Anke Audny , Antoni Anna , Audibert Gérard , Azouvi Philippe , 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 , Calv Maria Rosa , Cameron Peter , Lozano Guillermo Carbayo , 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 , Dawes Helen , DeKeyser Véronique , Degos Vincent , Corte Francesco Della , Boogert Hugo den , 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 PedroA. , Gravesteijn Johannes Gratz Benjamin , Grossi Francesca , Gruen RussellL. , Gupta Deepak , Haagsma JuanitaA. , Haitsma Iain , Helbok Raimund , Horton Lindsay , Huijben Jilske , Hutchinson PeterJ. , Jankowski Stefan , Jarrett Mike , Jiang Ji-yao , Johnson Faye , Jones Kelly , Karan Mladen , Kolias AngelosG. , 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 AndrewI. 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 , Rusnák Daniel Rueckert 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. , 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 MarkSteven , Thibaut Aurore , Ao Braden Te , Tenovuo Olli , Thomas Matt , Tibboel Dick , Timmers Marjolein , Tolias Christos , Trapani Tony , Tudora CristinaMaria , Unterberg Andreas , Vajkoczy Peter , Vallance Shirley , Valeinis Egils , Vámos Zoltán , van der Jagt Mathieu , Van der Steen Gregory , van Dijck Jeroen T. J. M. , van Erp Inge A. M. , van Essen Thomas A. , VanHecke Wim , van Heugten Caroline , 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 , Voormolen Daphne , Vulekovic Petar , Wang KevinK. W. , Whitehouse Daniel , Wiegers Eveline , Williams Guy , Wilson Lindsay , Winzeck Stefan , Wolf Stefan , Yang Zhihui , Ylén Peter , Zeiler Frederick A. , Zelinkova Veronika , Ziverte Agate , TommasoZoerle  
Published: March 2024

Abstract
Background
Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury.

Methods
A large patient sample from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study was used. Patients were stratified based on their clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU) in the acute phase. Headache was assessed using a single item from the Rivermead Post-Concussion Symptoms Questionnaire measured at baseline, 3, 6 and 12 months after injury. Mixed-effect logistic regression analyses were applied to investigate changes in headache frequency and associated predictors.

Results
A total of 2,291 patients responded to the headache item at baseline. At study enrolment, 59.3% of patients reported acute headache, with similar frequencies across all strata. Female patients and those aged up to 40 years reported a higher frequency of headache at baseline compared to males and older adults. The frequency of severe headache was highest in patients admitted to the ICU. The frequency of headache in the ER stratum decreased substantially from baseline to 3 months and remained from 3 to 6 months. Similar trajectory trends were observed in the ICU and ADM strata across 12 months. Younger age, more severe TBI, fatigue, neck pain and vision problems were among the predictors of more severe headache over time. More than 25% of patients experienced headache at 12 months after injury.

Conclusions
Headache is a common symptom after TBI, especially in female and younger patients. It typically decreases in the first 3 months before stabilising. However, more than a quarter of patients still experienced headache at 12 months after injury. Translational research is needed to advance the clinical decision-making process and improve targeted medical treatment for headache.

Trial registration
ClinicalTrials.gov NCT02210221.