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Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light.

Al Nimer F, Thelin E, Nyström H, Dring AM, Svenningsson A, Piehl F, Nelson DW, Bellander BM - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus

Serum NF-L levels by patient.Every line (separate color) represents an individual patient. Generally, even if there were differences in concentration between patients they were limited over time for the individual patient.
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pone.0132177.g002: Serum NF-L levels by patient.Every line (separate color) represents an individual patient. Generally, even if there were differences in concentration between patients they were limited over time for the individual patient.

Mentions: Between 1 and 3 samples were collected per patient, as available (Fig 1A and 1B). In total, 439 serum-, and 167 CSF samples, of NF-L were acquired. There was a general upward trend of s-NF-L at the group level over time (Fig 1C and 1D), but differences on an individual basis were often less pronounced (Fig 2). Since mixed models were not applicable, and as intra-individual changes were limited, data was reduced to mean and max per patient. Additionally two variables were derived: a variability parameter of the standard deviation per patient and a time parameter stratifying samples to early (1–5) and late (5–15) sample days, respectively. The analyses of these two parameters are affected by missing data points and should be considered as exploratory.


Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light.

Al Nimer F, Thelin E, Nyström H, Dring AM, Svenningsson A, Piehl F, Nelson DW, Bellander BM - PLoS ONE (2015)

Serum NF-L levels by patient.Every line (separate color) represents an individual patient. Generally, even if there were differences in concentration between patients they were limited over time for the individual patient.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489843&req=5

pone.0132177.g002: Serum NF-L levels by patient.Every line (separate color) represents an individual patient. Generally, even if there were differences in concentration between patients they were limited over time for the individual patient.
Mentions: Between 1 and 3 samples were collected per patient, as available (Fig 1A and 1B). In total, 439 serum-, and 167 CSF samples, of NF-L were acquired. There was a general upward trend of s-NF-L at the group level over time (Fig 1C and 1D), but differences on an individual basis were often less pronounced (Fig 2). Since mixed models were not applicable, and as intra-individual changes were limited, data was reduced to mean and max per patient. Additionally two variables were derived: a variability parameter of the standard deviation per patient and a time parameter stratifying samples to early (1–5) and late (5–15) sample days, respectively. The analyses of these two parameters are affected by missing data points and should be considered as exploratory.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus