Validation of the GCS-Pupil Scale in Traumatic Brain Injury: Incremental Prognostic Value of Pupillary Reactivity with GCS in the Prospective Observational Cohorts CENTER-TBI and TRACK-TBI

To compare the incremental prognostic value of pupillary reactivity captured as part of the Glasgow Coma Scale-Pupils (GCS-P) score or added as separate variable to the GCS+P, in traumatic brain injury (TBI). We analyzed patients enrolled between 2014 and 2018 in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI, n = 3521) and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI, n = 1439) cohorts. Logistic regression was utilized to quantify the prognostic performances of GCS-P (GCS minus number of unreactive pupils) and GCS+P versus GCS alone according to Nagelkerke's R². End-points were mortality and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-4) at 6 month post-injury. We estimated 95% confidence intervals (CIs) with bootstrap resampling to summarize the improvement in prognostic capability. In a meta-analysis of CENTER-TBI and TRACK-TBI, GCS as a linear score had a R² of 25% (95% CI 19-31%) for mortality and 33% (4-41%) for unfavorable outcome. Pupillary reactivity as a separate variable improved the R² by an absolute value of 6% (4.0-7.7%) and 2% (1.2-3.0%) for mortality and unfavorable outcome, respectively, while comparatively half of this improvement was captured by the GCS-P score (3% [2.1-3.3%], 1% [1-1.7%], respectively). GCS-P showed a stronger association with 6-month outcome after TBI than GCS alone and provides a single integrated score. However, this comes at a loss of clinical and prognostic information compared with GCS+P. For prognostic models, inclusion of GCS and pupillary reactivity as separate factors may be preferable to using a GCS-P summary score.