Trajectory of Long-Term Outcome in Severe Pediatric Diffuse Axonal Injury: An Exploratory Study

Abstract

Introduction: Pediatric severe traumatic brain injury (TBI) is one of the leading causes of disability and death. One of the classic pathoanatomic brain injury lesions following severe pediatric TBI is diffuse (multifocal) axonal injury (DAI). In this single institution study, our overarching goal was to describe the clinical characteristics and long-term outcome trajectory of severe pediatric TBI patients with DAI. Methods: Pediatric patients (<18 years of age) with severe TBI who had DAI were retrospectively reviewed. We evaluated the effect of age, sex, Glasgow Coma Scale (GCS) score, early fever ≥ 38.5°C during the first day post-injury, the extent of ICP-directed therapy needed with the Pediatric Intensity Level of Therapy (PILOT) score, and MRI within the first week following trauma and analyzed their association with outcome using the Glasgow Outcome Score-Extended (GOS-E) scale at discharge, 6 months, 1, 5, and 10 years following injury. Results: Fifty-six pediatric patients with severe traumatic DAI were analyzed. The majority of the patients were >5 years of age and male. There were 2 mortalities. At discharge, 56% (30/54) of the surviving patients had unfavorable outcome. Sixty five percent (35/54) of surviving children were followed up to 10 years post-injury, and 71% (25/35) of them made a favorable recovery. Early fever and extensive DAI on MRI were associated with worse long-term outcomes. Conclusion: We describe the long-term trajectory outcome of severe pediatric TBI patients with pure DAI. While this was a single institution study with a small sample size, the majority of the children survived. Over one-third of our surviving children were lost to follow-up. Of the surviving children who had follow-up for 10 years after injury, the majority of these children made a favorable recovery.

Keywords: diffuse axonal injury (DAI); fever; intracranial hypertension (IH); outcome; pediatric; traumatic brain injury.

Figure 1

DAI Zone 1 (Superficial) MRI Findings. (A) axial diffusion weighted (DWI) and (B) axial T2^* weighted sequences show a punctate focus of restricted diffusion (A, white arrow) at the left parietal gray-white junction with associated susceptibility effect (B, solid white arrow). Additional foci of susceptibility within the frontal and parietal subcortical WM (B, broken white arrows).

Figure 2

DAI Zone 2 (Deep) MRI Findings. (A) axial diffusion weighted (DWI) and (B) axial T2^* weighted sequences show a focus of restricted diffusion (A, white arrow) at the midline splenium of the corpus callosum with associated susceptibility effect (B, white arrow). (C) axial DWI and (D) axial T2^* weighted from a different severe pediatric TBI patient with restricted diffusion (C, white arrow) and associated susceptibility effect (D, white arrow) in the left thalamus.

Figure 3

DAI Zone 3 (Posterior fossa) MRI Findings. (A) axial T2^* weighted image showing susceptibility effect in the right midbrain, and (B) axial T2^* weighted image in a different severe pediatric TBI patient showing susceptibility effect in the right pons.

Figure 4

Trajectory of Unfavorable Outcome (GOS-E 5-7) over time with respect to (A) Overall proportion of children. (B) GOS-E at Discharge. (C) Age Group. (D) Sex. (E) GCS. (F) Early Fever. (G) Number of DAI Zones Involved. ^***p < 0.001, ^**p < 0.01, ^*p < 0.05 represent differences in proportion of unfavorable outcomes between the groups at the follow-up times.