Utility of neuron-specific enolase in traumatic brain injury; relations to S100B levels, outcome, and extracranial injury severity.
BACKGROUND
In order to improve assessment and outcome prediction in patients suffering from traumatic brain injury (TBI), cerebral protein levels in serum have been suggested as biomarkers of injury. However, despite much investigation, biomarkers have yet to reach broad clinical utility in TBI. This study is a 9-year follow-up and clinical experience of the two most studied proteins, neuron-specific enolase (NSE) and S100B, in a neuro-intensive care TBI population. Our aims were to investigate to what extent NSE and S100B, independently and in combination, could predict outcome, assess injury severity, and to investigate if the biomarker levels were influenced by extracranial factors.


METHODS
All patients treated at the neuro-intensive care unit at Karolinska University Hospital, Stockholm, Sweden between 2005 and 2013 with at least three measurements of serum S100B and NSE (sampled twice daily) were retrospectively included. In total, 417 patients fulfilled the criteria. Parameters were extracted from the computerized hospital charts. Glasgow Outcome Score (GOS) was used to assess long-term functional outcome. Univariate, and multivariate, regression models toward outcome and what explained the high levels of the biomarkers were performed. Nagelkerke's pseudo-R(2) was used to illustrate the explained variance of the different models. A sliding window assessed biomarker correlation to outcome and multitrauma over time.


RESULTS
S100B was found a better predictor of outcome as compared to NSE (area under the curve (AUC) samples, the first 48 hours had Nagelkerke's pseudo-R(2) values of 0.132 and 0.038, respectively), where the information content of S100B peaks at approximately 1 day after trauma. In contrast, although both biomarkers were independently correlated to outcome, NSE had limited additional predictive capabilities in the presence of S100B in multivariate models, due to covariance between the two biomarkers (correlation coefficient 0.673 for AUC 48 hours). Moreover, NSE was to a greater extent correlated to multitrauma the first 48 hours following injury, whereas the effect of extracerebral trauma on S100B levels appears limited to the first 12 hours.


CONCLUSIONS
While both biomarkers are independently correlated to long-term functional outcome, S100B is found a more accurate outcome predictor and possibly a more clinically useful biomarker than NSE for TBI patients.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. eric.thelin@ki.se.
Eric Peter
EP
Thelin
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Emma
E
Jeppsson
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Arvid
A
Frostell
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
Mikael
M
Svensson
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
Stefania
S
Mondello
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
Bo-Michael
BM
Bellander
Department of Physiology and Pharmacology, Section of Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden.
David W
DW
Nelson
D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D000070642:Brain Injuries, Traumatic / Q000453:epidemiology; D005260:Female; D015600:Glasgow Coma Scale / Q000706:statistics & numerical data; D023261:Glasgow Outcome Scale / Q000706:statistics & numerical data; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010751:Phosphopyruvate Hydratase / Q000032:analysis* / Q000097:blood; D011379:Prognosis; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000032:analysis* / Q000097:blood; D013548:Sweden / Q000453:epidemiology
D015415:Biomarkers; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D010751:Phosphopyruvate Hydratase
Biomarkers; Neuron-specific enolase; Outcome; S100B; Traumatic brain injury