The Glasgow Outcome Scale (GOS) and its most recent revision, the GOS-Extended (GOS-E), provide the gold standard for measuring traumatic brain injury (TBI) outcome. The GOS-E exhibits validity when used with adults and some adolescents, but validity with younger children is not established. Because the GOS-E lacks the developmental specificity necessary to evaluate children, toddlers, and infants, we modified the original version to create the GOS-E Pediatric Revision (GOS-E Peds), a developmentally appropriate structured interview, to classify younger patients. The criterion, predictive, and discriminant validity of the GOS-E Peds was measured in 159 subjects following TBI (mild: 36%; moderate: 12%; severe: 50%) at 3 and 6 months after injury. Participants were included from two studies completed at the Pediatric Neurotrauma Center at Children's Hospital of Pittsburgh. We assessed the relationship among GOS-E Peds, the GOS, and the Vineland Adaptive Behavior Scales as well as other standardized measures of functional, behavioral, intellectual, and neuropsychological outcome. Premorbid function was assessed 24-36 h after injury. The GOS-E Peds showed a strong correlation with the GOS at 3 and 6 month time points. Criterion-related validity was also indicated by GOS-E Peds' association with most measures at both time points and at injury severity levels. The 3 month GOS-E Peds was associated with the 6 month GOS-E Peds, everyday function, behavior, and most cognitive abilities. Discriminant validity is suggested by weak correlations between both 3 and 6 month GOS-E Peds and premorbid measures. The GOS-E Peds is sensitive to severity of injury and is associated with changes in TBI sequelae over time. This pediatric revision provides a valid outcome measure in infants, toddlers, children, and adolescents through age 16. Findings support using the GOS-E Peds as the primary outcome variable in pediatric clinical trials.

Serum NSE, S100B, or myelin basic protein are increased in the majority of children with acute nTBI and iTBI, including well-appearing children with iTBI in whom the diagnosis might otherwise have been missed. Differences in the time course of NSE, S100B, and myelin basic protein after nTBI and iTBI may provide insight into the pathophysiology of iTBI. These serum markers should be prospectively evaluated in a target population of infants.

ABSTRACT. Background. Traumatic brain injury (TBI) is a leading cause of death and disability in children. Considerable insight into the mechanisms involved in secondary injury after TBI has resulted from analysis of ventricular cerebrospinal fluid (CSF) obtained in children with severe noninflicted and inflicted TBI (nTBI and iTBI, respectively). Neuron-specific enolase (NSE) is a glycolytic enzyme that is localized primarily to the neuronal cytoplasm. S100B is a calcium-binding protein localized to astroglial cells. In adults, CSF and serum concentrations of NSE and S100B have served as markers of neuronal damage after TBI. Neither NSE nor S100B has previously been studied in CSF after TBI in infants or children.Objective. To compare the time course and magnitude of neuronal and astroglial death after nTBI and iTBI by measuring CSF concentrations of NSE and S100B using a rapid enzyme-linked immunosorbent assay.Methods. Severe nTBI and iTBI were defined by strict clinical criteria. Serial ventricular CSF samples (n ‫؍‬ 35) were obtained from children 1.5 to 9 years with severe nTBI (n ‫؍‬ 5) and children 0.2 to 1.5 years (n ‫؍‬ 5) with severe iTBI. Lumbar CSF samples from 5 children 0.1 to 2.3 years evaluated for meningitis were used as a comparison group. CSF NSE and S100B concentrations were quantified by an enzyme-linked immunosorbent assay (SynX Pharma Inc, Ontario, Canada).Results. There was no difference in age between patients with iTBI (median [ ]). The initial Glasgow Coma Scale score was higher in the iTBI group (9 [4 -14]) versus the nTBI group (3 [3-7]). NSE was increased in TBI versus the comparison group in 34 of 35 samples. Mean NSE was markedly increased (mean ؎ SEM, 117.1 ؎ 12.0 ng/mL vs 3.5 ؎ 1.4 ng/mL). After nTBI, a transient peak in NSE was seen at a median of 11 hours after injury (range: 5-20 hours). After iTBI, an increase in admission NSE was followed by a sustained and delayed peak at a median of 63 hours after injury (range: 7-94). The magnitude of peak NSE was similar in nTBI and iTBI. S100B was increased versus the comparison group in 35 of 35 samples. Mean S100B was markedly increased in TBI versus the comparison group (1.67 ؎ 0.2 ng/mL vs 0.02 ؎ 0.0 ng/mL). S100B showed a single peak at 27 hours (range: 5-63 hours) after both nTBI and iTBI. The mean S100B concentration, peak S100B concentration, and the time to peak were not associated with mechanism of injury.Conclusions. Markers of neuronal and astroglial death are markedly increased in CSF after severe nTBI and iTBI. ITBI produces a unique time course of NSE, characterized by both an early and late peak, presumably representing 2 waves of neuronal death, the second of which may represent apoptosis. Delayed neuronal death may represent an important therapeutic target in iTBI. NSE and S100B may also be useful as markers to identify occult iTBI, help differentiate nTBI and iTBI, and assist in determining the time of injury in cases of iTBI. Pediatrics 2002;109(2). URL: http://www.pediatrics.org/ cgi/content/full/109/2/e31; head t...

Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. The study objective was to assess whether biomarkers concentrations obtained at the time of injury are associated with outcome. Serial serum concentrations of neuron-specific enolase (NSE), S100B and myelin basic protein (MBP) were measured in 152 children with acute TBI. Outcome was assessed with the Glasgow Outcome Scale (GOS) score and/or GOS-Extended Pediatric (GOS-E Peds). Spearman's rank correlation and binary logistic regression assessed the relationship between biomarker concentrations and outcome. For all biomarkers and time points, higher biomarker concentrations were associated with worse outcome. Initial and peak NSE concentrations and initial MBP concentrations were more strongly correlated with outcome in children < or =4 years compared with those >4 years of age. Using binary logistic regression to evaluate the simultaneous affect of all biomarkers on outcome, there was significant overall model fit predicting a dichotomous GOS from biomarker concentrations with a 77% correct classification rate and a negative and positive predictive value of 97% and 75%, respectively. We conclude that NSE, S100B, and MBP concentrations obtained at the time of TBI may be useful in predicting outcome. Future studies should focus on assessing the differential benefit of biomarkers compared with clinical variables and in assessing a continuous rather than categorical outcome variable.