Brain biomarkers and pre-injury cognition are associated with long-term cognitive outcome in children with traumatic brain injury

Abstract

BackgroundChildren with traumatic brain injury (TBI) are frequently at risk of long-term impairments of attention and executive functioning but these problems are difficult to predict. Although deficits have been reported to vary with injury severity, age at injury and sex, prognostication of outcome remains imperfect at a patient-specific level. The objective of this proof of principle study was to evaluate a variety of patient variables, along with six brain-specific and inflammatory serum protein biomarkers, as predictors of long-term cognitive outcome following paediatric TBI.MethodOutcome was assessed in 23 patients via parent-rated questionnaires related to attention deficit hyperactivity disorder (ADHD) and executive functioning, using the Conners 3rd Edition Rating Scales (Conners-3) and Behaviour Rating Inventory of Executive Function (BRIEF) at a mean time since injury of 3.1 years. Partial least squares (PLS) analyses were performed to identify factors measured at the time of injury that were most closely associated with outcome on (1) the Conners-3 and (2) the Behavioural Regulation Index (BRI) and (3) Metacognition Index (MI) of the BRIEF.ResultsHigher levels of neuron specific enolase (NSE) and lower levels of soluble neuron cell adhesion molecule (sNCAM) were associated with higher scores on the inattention, hyperactivity/impulsivity and executive functioning scales of the Conners-3, as well as working memory and initiate scales of the MI from the BRIEF. Higher levels of NSE only were associated with higher scores on the inhibit scale of the BRI.ConclusionsNSE and sNCAM show promise as reliable, early predictors of long-term attention-related and executive functioning problems following paediatric TBI.

Interleukin-8 Predicts Fatigue at 12 Months Post-Injury in Children with Traumatic Brain Injury

“…In this study we determined that increased concentrations of serum NSE and decreased expression of soluble neuron cell adhesion molecule (sNCAM) was associated with long-term cognitive/behavioural outcomes (attention, executive function and memory). 33 The current study therefore builds on this earlier work, in selected specific proteins sensitive to injury to the cells of the neurovascular unit is as well as marking neuro-inflammation. To our knowledge, research examining serum biomarkers in association with fatigue is limited.…”

“…The prognostic value of paired severity (based on GCS) and IL-8 data in our study confirms prior findings, 57 hyperactivity/impulsivity and executive functioning on behavioral questionnaires at 3 year follow-up. 33 Attentional vigilance has been implicated as a contributor to post-TBI fatigue This paper has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.…”

Early predictors of perinatal brain damage: the role of neurobiomarkers

“…In children, NSE increases in both CSF and blood after impairment of the blood-brain barrier and brain injury [114][115][116]. Few studies have investigated the role of NSE in neonates.…”

Derivation of a Three Biomarker Panel to Improve Diagnosis in Patients with Mild Traumatic Brain Injury

“…Finally, because the biomarkers selected for this investigation may not be equally present in the pediatric population, a cohort not studied in our investigation, the utility in children younger than 18 will need to be determined. Published evidence does suggest that NSE is a useful biomarker predicting neurocognitive deficits after pediatric TBI ( 46 ).…”