Acute physiologic prediction of pediatric post-traumatic epilepsy

Abstract

Objective: Post-traumatic epilepsy (PTE) is a known complication of traumatic brain injury (TBI). Limited physiologic biomarkers have been investigated in relation to pediatric PTE. Our aim is to identify clinical, physiologic and neuroimaging biomarkers predictive of pediatric PTE arising during the acute care phase after injury.

Methods: We performed a retrospective analysis from a prospectively collected clinical database of pediatric patients who underwent multimodality neurologic monitoring that included continuous electroencephalography and intracranial pressure (ICP) monitoring. Biomarkers included hemodynamic vital signs, model-based indices of cerebrovascular pressure reactivity (CVPR) and autonomic function (AF), electroencephalographic abnormalities, and neuroimaging abnormalities on the initial CT scan on day of imaging. Our primary outcome, PTE, was classified as the presence of unprovoked seizures 2 months post-injury or the continued need for antiseizure medications at 12-month post-injury. We utilized univariate logistic regression to identify biomarkers associated with PTE.

Results: 61 surviving patients were included in this study, among which 10 (16.4%) developed PTE. We identified that PTE was associated with increased ICP (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.02-1.52), increased pressure reactivity indices (92.53, 2.84->999.99), increased wavelet pressure reactivity indices (121.76, 2.84->999.99), increased CT Marshall scores (1.76, 1.13-2.74), decreased HRsd (0.54, 0.33-0.87) and the presence of epileptiform discharges (8.06, 1.85-35.17), and abnormal sleep spindles (4.88, 1.18-20.00). Whereas early post-traumatic seizures within the first 7 days post-injury were associated with PTE development (7.58, 1.81-39.68), this association was significant for such seizures occurring between 24 and 168 h post-injury (21.47, 4.18-110.38), and not for seizures occurring within 24 h post-injury. Among patients experiencing early post-traumatic seizures, increased time with seizures on surface electroencephalography was associated with PTE development (7.28, 2.05-73.14). We also identified that development of PTE was associated with worsened functional outcomes identified by increased Glasgow Outcome Scale - Extended Pediatric (GOSE-PEDs) scores (3.18, 1.68-8.01).

Conclusion: Pediatric PTE development is associated with increased ICP, impaired CVPR, low heart rate variability, worsened neuroimaging findings, and electroencephalographic abnormalities identified during intensive care. Further studies are needed to investigate strategies to mitigate pediatric PTE development.

Keywords: Early post-traumatic seizures; Intracranial pressure; Pediatric traumatic brain injury; Pediatrics; Post-traumatic epilepsy.