title: Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light.
abstract: Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that S-NF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further studies, with volume quantification of axonal injury, and a prolonged sampling time, in order to better determine the connection between NF-L and DAI.
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Faiez
authors.initials: F
authors.lastname: Al Nimer
authors.affiliation: Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Thelin
authors.affiliation: Department of Clinical Neuroscience, Section of Neuroradiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Harriet
authors.initials: H
authors.lastname: Nyström
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dring
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Svenningsson
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Department of Physiology and Pharmacology, Section of Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden.
authors.forename: David W
authors.initials: DW
authors.lastname: Nelson
authors.affiliation: Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bo-Michael
authors.initials: BM
authors.lastname: Bellander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001369:Axons / Q000473:pathology; D001925:Brain Damage, Chronic / Q000453:epidemiology / Q000209:etiology; D001930:Brain Injuries / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D015600:Glasgow Coma Scale; D023261:Glasgow Outcome Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood* / Q000134:cerebrospinal fluid*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011379:Prognosis; D012025:Reflex, Pupillary; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D014057:Tomography, X-Ray Computed; D015599:Trauma Severity Indices
chemical_list: D002556:Cerebrospinal Fluid Proteins; D016900:Neurofilament Proteins; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C044882:neurofilament protein L; D010751:Phosphopyruvate Hydratase