Prognostic Models for Global Functional Outcome and Post-Concussion Symptoms Following Mild Traumatic Brain Injury: A Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study

Abstract

After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3-week post-concussion and mental health symptoms. Predictors were selected based on Akaike's Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.

Keywords: Glasgow Outcome Scale Extended; biomarkers; mild traumatic brain injury; post-concussion symptoms; predictors; prognostic model.

FIG. 1.

Modeling strategy.

FIG. 2.

The Core and Clinical models for prediction of Glasgow Outcome Scale Extended (GOSE) and Rivermead Post-Concussion Symptom Questionnaire (RPQ). Black circles indicate selected predictors based on Akaike's Information Criterion. Black triangles indicate pre-specified core predictors. Alcohol, alcohol intoxication; ASA-PS, American Society of Anesthesiologists Physical Status; Cause, cause of injury; GCS, Glasgow Coma Scale; ISS, Injury Severity Score Total; Neuropain H, history of migraines/headaches; PreTBI, prior traumatic brain injury; PsychiatricH, psychiatric history; PTA, post-traumatic amnesia; LOC, loss of consciousness.

FIG. 3.

The Clinical+ symptoms, computed tomography (CT), biomarkers models for prediction of Glasgow Outcome Scale Extended (GOSE), and Rivermead Post-Concussion Symptom Questionnaire (RPQ). Black circles indicate selected predictors based on Akaike's Information Criterion. Black triangles indicate pre-specified core predictors. ASA-PS, American Society of Anesthesiologists Physical Status; Cause, cause of injury; CisternalComp, cisternal compression; GCS, Glasgow Coma Scale; Hem, hematoma; Intox, intoxication; ISS, Injury Severity Score Total; Neuropain H, history of migraines/headaches; PsychiatriH, psychiatric history; TAI, traumatic axonal injury; tSah, traumatic subarachnoid hemorrhage.

FIG. 4.

The Clinical +2-3–week symptoms models for prediction of Glasgow Outcome Scale Extended (GOSE) and Rivermead Post-Concussion Symptom Questionnaire (RPQ). Black circles indicate selected predictors based on Akaike's Information Criterion. Black triangles indicate pre-specified core predictors. ASA-PS, American Society of Anesthesiologists Physical Status; Cause, cause of injury; GAD-7, Generalized Anxiety Disorder 7-item scale (GAD-7); GCS, Glasgow Coma Scale; ISS, Injury Severity Score Total; Neuropain H, history of migraines/headaches; PCL-5, Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM)-5; PHQ-9, Patient Health Questionnaire; PsychiatricH, psychiatric history; wk, week.