title: Validation of serum markers for blood-brain barrier disruption in traumatic brain injury.
abstract: The blood-brain barrier (BBB), which prevents the entry into the central nervous system (CNS) of most water-soluble molecules over 500 Da, is often disrupted after trauma. Post-traumatic BBB disruption may have important implications for prognosis and therapy. Assessment of BBB status is not routine in clinical practice because available techniques are invasive. The gold-standard measure, the cerebrospinal fluide (CSF)-serum albumin quotient (Q(A)), requires the measurement of albumin in CSF and serum collected contemporaneously. Accurate, less invasive techniques are necessary. The objective of this study was to evaluate the relationship between Q(A) and serum concentrations of monomeric transthyretin (TTR) or S100B. Nine subjects with severe traumatic brain injury (TBI; Glasgow Coma Scale [GCS] score < or =8) and 11 subjects with non-traumatic headache who had CSF collected by ventriculostomy or lumbar puncture (LP) were enrolled. Serum and CSF were collected at the time of LP for headache subjects and at 12, 24, and 48 h after ventriculostomy for TBI subjects. The Q(A) was calculated for all time points at which paired CSF and serum samples were available. Serum S100B and TTR levels were also measured. Pearson's correlation coefficient and area under the receiver operating characteristic (ROC) curve were used to determine the relationship between the serum proteins and QA. Seven TBI subjects had abnormal Q(A)'s indicating BBB dysfunction. The remaining TBI and control subjects had normal BBB function. No significant relationship between TTR and QA was found. A statistically significant linear correlation between serum S100B and Q(A) was present (r = 0.432, p = 0.02). ROC analysis demonstrated a significant relationship between Q(A) and serum S100B concentrations at 12 h after TBI (AUC = 0.800; SE 0.147, 95% CI 0.511-1.089). Using an S100B concentration cutoff of 0.027 ng=ml, specificity for abnormal Q(A) was 90% or higher at each time point. We conclude that serum S100B concentrations accurately indicate BBB dysfunction at 12 h after TBI.
authors.affiliation: Department of Emergency Medicine and Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Blyth
authors.forename: Arash
authors.initials: A
authors.lastname: Farhavar
authors.forename: Christopher
authors.initials: C
authors.lastname: Gee
authors.forename: Brendan
authors.initials: B
authors.lastname: Hawthorn
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.forename: Akshata
authors.initials: A
authors.lastname: Nayak
authors.forename: Veit
authors.initials: V
authors.lastname: Stöcklein
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bazarian
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000293:injuries*; D001930:Brain Injuries / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D011228:Prealbumin / Q000032:analysis; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012709:Serum Albumin / Q000032:analysis / Q000134:cerebrospinal fluid; D014696:Ventriculostomy; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D011228:Prealbumin; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D012709:Serum Albumin