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.
Highlights
Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in young adults worldwide, and is increasing in the elderly population [1, 2]
The early Glasgow Coma Scale (GCS) distribution showed a bias towards lower scores, in part explained by many patients being sedated and intubated directly at the scene of accident
We only found a significant prediction between cerebrospinal fluid (CSF-)Neurofilament light (NF-L) and outcome in a univariate analysis, presumably because the material was underpowered for such an analysis
Summary
Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in young adults worldwide, and is increasing in the elderly population [1, 2]. Existing predictors of outcome include age, Glasgow Coma Scale (GCS), pupil response and grading of extent/type of TBI damage on imaging [2, 4, 5]. These factors have been included in predictive models with some success in estimating outcome, with limitations [2, 6]. As NSE is present in erythrocytes, its usefulness as a serum biomarker for brain damage is limited since hemolysis will provide elevated levels of non-cerebral origin [7, 20]. A more clinically useful marker for axonal injury is warranted
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