Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children.
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 [range]: 0.2 years [0.2-1.8]), nTBI (2.0 years [1.5-9]), and the comparison group (0.2 years [0.2-1.8]). 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.
Berger
Rachel Pardes
RP
Department of Pediatrics, Pittsburgh Child Advocacy Center, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 5213, USA. rberger@pitt.edu
Pierce
Mary Clyde
MC
Wisniewski
Stephen R
SR
Adelson
P David
PD
Clark
Robert S B
RS
Ruppel
Randy A
RA
Kochanek
Patrick M
PM
D000328:Adult; D000367:Age Factors; D017209:Apoptosis; D001253:Astrocytes / Q000473:pathology; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000201:enzymology / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000134:cerebrospinal fluid*; D016923:Cell Death; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007223:Infant; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid*; D009457:Neuroglia / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins
D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D010751:Phosphopyruvate Hydratase