. 2023 Aug 15;23(1):304.

doi: 10.1186/s12883-023-03284-6.

Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury

Iftakher Hossain^#^{1

2

3

4}, Mehrbod Mohammadian^#^{5

6}, Henna-Riikka Maanpää^{7

5

6}, Riikka S K Takala⁸, Olli Tenovuo⁶, Mark van Gils⁹, Peter Hutchinson¹⁰, David K Menon¹¹, Virginia F Newcombe¹¹, Jussi Tallus^{5

6

12}, Jussi Hirvonen¹², Timo Roine^{13

14}, Timo Kurki^{5

6}, Kaj Blennow^#^{15

16}, Henrik Zetterberg^#^{15

16

17

18

19}, Jussi P Posti^#^{7

5

6}

Affiliations

¹ Department of Neurosurgery, Neurocenter, Turku University Hospital, Turku, Finland. ifthos@utu.fi.
² Turku Brain Injury Center, Turku University Hospital, Turku, Finland. ifthos@utu.fi.
³ Department of Clinical Neurosciences, University of Turku, Turku, Finland. ifthos@utu.fi.
⁴ Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ifthos@utu.fi.
⁵ Turku Brain Injury Center, Turku University Hospital, Turku, Finland.
⁶ Department of Clinical Neurosciences, University of Turku, Turku, Finland.
⁷ Department of Neurosurgery, Neurocenter, Turku University Hospital, Turku, Finland.
⁸ Intensive Care Medicine and Pain Management, Perioperative Services, Turku University Hospital and University of Turku, Turku, Finland.
⁹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁰ Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
¹¹ Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
¹² Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland.
¹³ Turku Brain and Mind Center, University of Turku, Turku, Finland.
¹⁴ Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Turku, Finland.
¹⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁷ Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
¹⁸ UK Dementia Research Institute at UCL, University College London, London, UK.
¹⁹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.

^# Contributed equally.

PMID: 37582732
PMCID: PMC10426141
DOI: 10.1186/s12883-023-03284-6

Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury

Iftakher Hossain et al. BMC Neurol. 2023.

. 2023 Aug 15;23(1):304.

doi: 10.1186/s12883-023-03284-6.

Authors

Affiliations

¹ Department of Neurosurgery, Neurocenter, Turku University Hospital, Turku, Finland. ifthos@utu.fi.
² Turku Brain Injury Center, Turku University Hospital, Turku, Finland. ifthos@utu.fi.
³ Department of Clinical Neurosciences, University of Turku, Turku, Finland. ifthos@utu.fi.
⁴ Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ifthos@utu.fi.
⁵ Turku Brain Injury Center, Turku University Hospital, Turku, Finland.
⁶ Department of Clinical Neurosciences, University of Turku, Turku, Finland.
⁷ Department of Neurosurgery, Neurocenter, Turku University Hospital, Turku, Finland.
⁸ Intensive Care Medicine and Pain Management, Perioperative Services, Turku University Hospital and University of Turku, Turku, Finland.
⁹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁰ Department of Clinical Neurosciences, Neurosurgery Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
¹¹ Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
¹² Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland.
¹³ Turku Brain and Mind Center, University of Turku, Turku, Finland.
¹⁴ Department of Neuroscience and Biomedical Engineering, Aalto University School of Science, Turku, Finland.
¹⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁷ Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
¹⁸ UK Dementia Research Institute at UCL, University College London, London, UK.
¹⁹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.

^# Contributed equally.

PMID: 37582732
PMCID: PMC10426141
DOI: 10.1186/s12883-023-03284-6

Abstract

Background: It is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI.

Methods: Ninety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups.

Results: The levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001-p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found.

Conclusion: In patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

Keywords: Diffusion tensor imaging; Diffusion-weighted magnetic resonance imaging; Neurofilament light protein.

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Conflict of interest statement

Iftakher Hossain has no financial disclosures; Mehrbod Mohammadian has no financial disclosures; Henna-Riikka Maanpää has no financial disclosures; Riikka S.K. Takala has no financial disclosures. RSKT has received speakers fee from Abbott, Fresenius-Kabi, Orion and UCB, conference funding from Pfizer and Steripolar and is stockholder of Orion; Olli Tenovuo has no financial disclosures; Mark van Gils has no financial disclosures; Peter J. Hutchinson is supported by the UK NIHR and Royal College of Surgeons of England; David K. Menon reports collaborative research or consultancy agreements with GlaxoSmithKline Ltd; Ornim Medical; Shire Medical; Calico Inc; Pfizer Ltd; Pressura Ltd; Glide Pharma Ltd; NeuroTraumaSciences LLC; Lantasman AB; Virginia F. Newcombe holds a grant with Roche Pharmaceuticals; Jussi Tallus has no financial disclosures; Jussi Hirvonen has no financial disclosures; Timo Roine has no financial disclosures; Timo Kurki has no financial disclosures; Henrik Zetterberg has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Annexon, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Pinteon Therapeutics, Red Abbey Labs, Passage Bio, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program; Kaj Blennow has served as a consultant or at advisory boards for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program; Jussi P. Posti has no financial disclosures. JPP has received speaker’s fees from Orion corporation and Finnish Medical Association.

Figures

**Fig. 1**
Diffusion tensor imaging (DTI) metrics values for the different mild traumatic brain injury (mTBI) subgroups. Computed tomography positive = CT-positive, computed tomography negative = CT-negative, Glasgow Outcome Scale Extended (GOSE) 8 = complete recovery, and Glasgow Outcome Scale Extended (GOSE) 1–7 = incomplete recovery. FA = fractional anisotropy, MD = mean diffusivity, AD = axial diffusivity, RD = radial diffusivity

**Fig. 2**
Levels of NF-L in patients dichotomized based on CT findings (A) or their outcome (B). Computed tomography positive = CT-positive, computed tomography negative = CT-negative, Glasgow Outcome Scale Extended (GOSE) 8 = complete recovery, and Glasgow Outcome Scale Extended (GOSE) 1–7 = incomplete recovery

See this image and copyright information in PMC

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Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury

Affiliations

Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury

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