Page 99 - NNS 2014 Program & Abstract Book

B4-22
SALIVARY BIOMARKERS OF STRESS REACTIVITY FOL-
LOWING PEDIATRIC TRAUMATIC BRAIN INJURY
Ewing-Cobbs, L., Prasad, M.R., Juranek, J., Cox, C.S., Swank, P.S.
Children’s Learning Insititue, University of Texas Health Science
Center, Houston, USA
Very little is known about how traumatic brain injury (TBI) may
impact stress systems. The objective of this study is to identify rela-
tions between biomarkers of stress reactivity, as measured by salivary
cortisol and alpha-amylase, and psychological health outcomes fol-
lowing pediatric TBI.
Participants were drawn from a longitudinal prospective study
composed of three groups of children ages 8–16: 1) mild, moderate,
and severe TBI (n = 18) extracranial injury (n = 8), and healthy com-
parison children (n = 18). Cortisol and alpha amylase samples were
collected at 5 time intervals before and after stress induction using the
Trier Social Stress Test. The TSST is an established laboratory pro-
cedure involving oral speaking and mathematical calculation that
typically produces time-linked elevation in both cortisol and alpha
amylase. Psychological health outcomes included the Child Behavior
Checklist Internalizing (anxiety, depression) and Externalizing (rule
breaking, aggressive behavior) T-scores. Biomarkers and outcomes
were assessed 6 months after injury.
Following assays of the salivary samples, cortisol and alpha amylase
data were aggregated across time using area under the curve method-
ology. Spearman correlation coefficients examined the relations be-
tween each biomarker and psychological outcomes. For the total
sample, cortisol levels were not significantly correlated with indices of
psychological health. Alpha amylase was positively correlated with
Externalizing (r =.41, p < .01) behavior problems. Within the TBI
group, the Externalizing score was positively correlated with alpha
amylase (r = .69, p < .01). Alpha amylase levels tended to be related to
Internalizing scores for the total sample and the TBI subgroup.
Cortisol, a marker of hypothalamic-pituitary-adrenal axis function,
did not correlate significantly with psychological health outcomes.
Elevated levels of alpha amylase, a marker of adrenergic sympathetic
nervous system stress reactivity, were significantly related to parent
ratings of increased externalizing behavior problems. Following TBI,
dysregulation of the autonomic nervous stress system may place
children at risk for post-traumatic stress symptoms and contribute to
dysregulation of emotions and behavior.
Key words
alpha amylase, cortisol, post-traumatic stress, psychological outcome,
stress reactivity
B4-23
PEDIATRIC PATIENTS IN THE TRACK TBI TRIAL - TESTING
COMMON DATA ELEMENTS IN CHILDREN
Duhaime, A.C.1, Hotz, G.A.2 , Wittkampf, F.1, Haire, S.W.1 , Costine,
B.A.1
1Harvard University, Boston, MA
2University of Miami, Miami, USA
In 2009, the NINDS and other agencies convened an effort to create a
set of common data elements (CDE) for use in research in traumatic
brain injury that would standardize definitions and data collection
across centers, facilitate data sharing, and expand evidence for treat-
ment evaluations. A parallel effort ensured that elements appropriate
for children were included. TRACK TBI (Transforming Research and
Acquiring Clinical Knowledge in TBI) is an 11-center, NIH-funded
observational study which utilizes the CDE approach to enable
comparative effectiveness research in TBI. We report here the de-
velopment and use of the CDE platform for pediatric patients enrolled
in TRACK TBI.
General and pediatric CDE consulting groups created recommen-
dations for specific domains including demographics, clinical as-
sessment, neuroimaging, biomarkers, and outcome measures; a second
phase further refined elements deemed most important for specific
patient groups or research areas. A 4-center pilot phase of TRACK
TBI ensued which piloted the CDE’s in adult patients. These elements
were further expanded for TRACK TBI, an 11-center study involving
3000 TBI patients, so that pediatric patients could be readily
Specific pediatric considerations were necessary in all domains of
data, including demographics (development, parent information,
school setting), acute assessment (neurologic assessment tools for
preverbal children), biomarkers and genetics (weight-based blood
limits), imaging (rapid MRI protocols for unsedated young children),
and validated, age-specific outcome measures. In all instances, choos-
ing measures which could be compared both within and across age
groups was prioritized. Consideration for age-specific consent/assent
procedures, release of study-related results, recruitment incentives, and
family concerns were addressed, in concert with participating centers’
Institutional Review Boards.
Successful enrollment and followup of infants and older children
into a large comprehensive database has been accomplished, and the
CDE/TRACK TBI model may serve as a platform for other pediatric
TBI clinical research studies.
Key words
biomarkers, clinical trial, comparative effectiveness, imaging, out-
comes, pediatric
B4-24
THROMBIN AND PROTEASE-ACTIVATED RECEPTOR-1
ARE ACTIVATED IN INTRACTABLE EPILEPSY IN
CHILDREN
Piao, C.S.1,2, Wadhwani, N.1,2, Koh, S.1,2, Wainwright, M.S.1,2
1Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago,
USA
2Northwestern University Feinberg School of Medicine, Chicago,
USA
Disruption of the blood-brain barrier (BBB) has been implicated in the
mechanisms of epileptogenesis following brain injury. Compromise of
BBB integrity allows serum proteins including thrombin, access to the
brain parenchyma. In hippocampal slice preparations, exposure to
thrombin causes seizure-like activity via activation of the protease-
activated receptor (PAR)-1. The role of thrombin in epileptogenesis in
humans is not known.
We obtained resected brain tissues from 10 pediatric patients who
underwent surgery for treatment of intractable epilepsy, and from age-
matched postmortem controls. We used immunohistochemical methods
to access; (a) integrity of the BBB (IgG; tight junction protein ZO-1); (b)
expression of activated thrombin; and (c) PAR-1 receptor expression.
In the epileptic foci there was an increase in IgG immunoreactivity and
a decrease in ZO-1 expression consistent with the disruption of BBB
integrity. Expression of activated thrombin and PAR-1 was also in-
creased in the brains of patients with intractable epilepsy, and was most
prominent in white matter. Using double-labeling methods, we found that
activated thrombin and PAR-1 is mainly expressed on astrocytes.
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