Title: MRI and Clinical Variables for Prediction of Outcomes After Pediatric Severe Traumatic Brain Injury
Legend: Table, Multiple-Predictor Models for GOSE-Peds Score – Mixed Ordinal Logistic Regression, adjusted for age, sex and GOSE-Peds timepoint. AIC, Akaike Information Criterion; DAI, diffuse axonal injury; ICH, intracerebral hemorrhage; GOSE-Peds, Glasgow Outcome Scale–Extended for Pediatrics; ICH, intracerebral hemorrhage; mGCS, motor component of the Glasgow Coma Scale. *Significant improvement over clinical-only model (p<0.001). Figure, Predictive Model AUROC Comparisons – The discriminative ability of each model for favorable or unfavorable outcome (Glasgow Outcome Scale – Extended for Pediatrics [GOSE-Peds] score of 1-3 vs 4-7) is shown for 3, 6, and 12 months after injury. The mean AUROC was determined in a 10-fold cross-validation with 20 random partitions of the data, and the 95% CI was determined in 1000 bootstrap samples. The dashed vertical line at 0.5 AUROC indicates a discriminative ability no better than random assignment.
Citation: Ferrazzano, P. A., Rebsamen, S., Field, A. S., Broman, A. T., Mayampurath, A., Rosario, B., Buttram, S., Willyerd, F. A., Rathouz, P. J., Bell, M. J., Alexander, A. L., & ADAPT MRI Investigators (2024). MRI and Clinical Variables for Prediction of Outcomes After Pediatric Severe Traumatic Brain Injury. JAMA network open, 7(8), e2425765. https://doi.org/10.1001/jamanetworkopen.2024.25765
Abstract: Importance – Traumatic brain injury (TBI) is a leading cause of death and disability in children, and predicting functional outcome after TBI is challenging. Magnetic resonance imaging (MRI) is frequently conducted after severe TBI; however, the predictive value of MRI remains uncertain. Objectives – To identify early MRI measures that predict long-term outcome after severe TBI in children and to assess the added predictive value of MRI measures over well-validated clinical predictors. Design, setting, and participants – This preplanned prognostic study used data from the Approaches and Decisions in Acute Pediatric TBI (ADAPT) prospective observational comparative effectiveness study. The ADAPT study enrolled 1000 consecutive children (aged <18 years) with severe TBI between February 1, 2014, and September 30, 2017. Participants had a Glasgow Coma Scale (GCS) score of 8 or less and received intracranial pressure monitoring. Magnetic resonance imaging scans performed as part of standard clinical care within 30 days of injury were collected at 24 participating sites in the US, UK, and Australia. Summary imaging measures were correlated with the Glasgow Outcome Scale-Extended for Pediatrics (GOSE-Peds), and the predictive value of MRI measures was compared with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) core clinical predictors. Data collection, image analysis, and data analyses were completed in July 2023. Exposures – Pediatric severe TBI with an MRI scan performed as part of clinical care. Main outcomes and measures – All measures were selected a priori. Magnetic resonance imaging measures included contusion, ischemia, diffuse axonal injury, intracerebral hemorrhage, and brainstem injury. Clinical predictors included the IMPACT core measures (GCS motor score and pupil reactivity). All models adjusted for age and sex. Outcome measures included the GOSE-Peds score obtained at 3, 6, and 12 months after injury. Results – This study included 233 children with severe TBI who were enrolled at participating sites and had an MRI scan and preselected clinical predictors available. Their median age was 6.9 (IQR, 3.0-13.3) years, and more than half of participants (134 [57.5%]) were male. In a multivariable model including MRI measures and IMPACT core clinical variables, contusion volume (odds ratio [OR], 1.13; 95% CI, 1.02-1.26), brain ischemia (OR, 2.11; 95% CI, 1.58-2.81), brainstem lesions (OR, 5.40; 95% CI, 1.90-15.35), and pupil reactivity were each independently associated with GOSE-Peds score. Adding MRI measures to the IMPACT clinical predictors significantly improved model fit and discrimination between favorable and unfavorable outcomes compared with IMPACT predictors alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72-0.85 vs 0.67; 95% CI, 0.61-0.76 for GOSE-Peds score >3 at 6 months after injury). Conclusions and relevance – In this prognostic study of children with severe TBI, the addition of MRI measures significantly improved outcome prediction over well-established and validated clinical predictors. Magnetic resonance imaging should be considered in children with severe TBI to inform prognosis and may also promote stratification of patients in future clinical trials.
Investigator: Peter Ferrazzano, MD
About the Lab: By identifying MRI biomarkers in animal models of pediatric brain injury, the Ferrazzano Research Group hopes to provide a means for selecting the patients most likely to benefit from a particular neuroprotective intervention in subsequent clinical trials. Basing patient selection on the physiologic target of therapy rather than simply the disease state will reduce the sample size needed, increase the likelihood of observing a drug effect, and facilitate the translation of promising neuroprotective interventions into clinical use.