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

Iftakher Hossain; Mehrbod Mohammadian; Henna Riikka Maanpää; Riikka S.K. Takala; Olli Tenovuo; Mark van Gils; Peter Hutchinson; David K. Menon; Virginia F. Newcombe; Jussi Tallus; Jussi Hirvonen; Timo Roine; Timo Kurki; Kaj Blennow; Henrik Zetterberg; Jussi P. Posti

doi:10.1186/s12883-023-03284-6

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

Iftakher Hossain, Mehrbod Mohammadian, Henna Riikka Maanpää, Riikka S.K. Takala, Olli Tenovuo, Mark van Gils, Peter Hutchinson, David K. Menon, Virginia F. Newcombe, Jussi Tallus, Jussi Hirvonen, Timo Roine, Timo Kurki, Kaj Blennow, Henrik Zetterberg, Jussi P. Posti

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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.

Original language	English
Article number	304
Journal	Bmc Neurology
Volume	23
Issue number	1
Early online date	15 Aug 2023
DOIs	https://doi.org/10.1186/s12883-023-03284-6
Publication status	Published - 2023
Publication type	A1 Journal article-refereed

Funding

This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), The Integra EANS Research Grant (IH), The Finnish Medical Foundation (IH), The Päivikki and Sakari Sohlberg Foundation (IH), The Paulo Foundation (IH), The Finnish Cultural Foundation (IH), University of Turku Graduate School funding (MM), Academy of Finland (#17379, JPP), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland) (JPP), Maire Taponen Foundation sr (JPP), personal grants from Emil Aaltonen Foundation sr (TR), and the Finnish Cultural Foundation (TR), and NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Scholarship and grants from the Swedish and European Research Councils (HZ), and grants from the Swedish Research Council and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986) (KB).

Keywords

Diffusion tensor imaging
Diffusion-weighted magnetic resonance imaging
Neurofilament light protein

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Clinical Neurology

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Hossain, I., Mohammadian, M., Maanpää, H. R., Takala, R. S. K., Tenovuo, O., van Gils, M., Hutchinson, P., Menon, D. K., Newcombe, V. F., Tallus, J., Hirvonen, J., Roine, T., Kurki, T., Blennow, K., Zetterberg, H., & Posti, J. P. (2023). Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury. Bmc Neurology, 23(1), Article 304. https://doi.org/10.1186/s12883-023-03284-6

@article{14152807e31044f7b4feab2a4d998a37,

title = "Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury",

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",

author = "Iftakher Hossain and Mehrbod Mohammadian and Maanp{\"a}{\"a}, {Henna Riikka} and Takala, {Riikka S.K.} and Olli Tenovuo and {van Gils}, Mark and Peter Hutchinson and Menon, {David K.} and Newcombe, {Virginia F.} and Jussi Tallus and Jussi Hirvonen and Timo Roine and Timo Kurki and Kaj Blennow and Henrik Zetterberg and Posti, {Jussi P.}",

note = "Funding Information: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), The Integra EANS Research Grant (IH), The Finnish Medical Foundation (IH), The P{\"a}ivikki and Sakari Sohlberg Foundation (IH), The Paulo Foundation (IH), The Finnish Cultural Foundation (IH), University of Turku Graduate School funding (MM), Academy of Finland (#17379, JPP), Government{\textquoteright}s Special Financial Transfer tied to academic research in Health Sciences (Finland) (JPP), Maire Taponen Foundation sr (JPP), personal grants from Emil Aaltonen Foundation sr (TR), and the Finnish Cultural Foundation (TR), and NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Scholarship and grants from the Swedish and European Research Councils (HZ), and grants from the Swedish Research Council and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986) (KB). Publisher Copyright: {\textcopyright} 2023, BioMed Central Ltd., part of Springer Nature.",

year = "2023",

doi = "10.1186/s12883-023-03284-6",

language = "English",

volume = "23",

number = "1",

}

Hossain, I, Mohammadian, M, Maanpää, HR, Takala, RSK, Tenovuo, O, van Gils, M, Hutchinson, P, Menon, DK, Newcombe, VF, Tallus, J, Hirvonen, J, Roine, T, Kurki, T, Blennow, K, Zetterberg, H & Posti, JP 2023, 'Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury', Bmc Neurology, vol. 23, no. 1, 304. https://doi.org/10.1186/s12883-023-03284-6

TY - JOUR

T1 - Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury

AU - Hossain, Iftakher

AU - Mohammadian, Mehrbod

AU - Maanpää, Henna Riikka

AU - Takala, Riikka S.K.

AU - Tenovuo, Olli

AU - van Gils, Mark

AU - Hutchinson, Peter

AU - Menon, David K.

AU - Newcombe, Virginia F.

AU - Tallus, Jussi

AU - Hirvonen, Jussi

AU - Roine, Timo

AU - Kurki, Timo

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Posti, Jussi P.

N1 - Funding Information: This work was partially funded by the European Commission under the 7th Framework Programme (FP7-270259-TBIcare), The Integra EANS Research Grant (IH), The Finnish Medical Foundation (IH), The Päivikki and Sakari Sohlberg Foundation (IH), The Paulo Foundation (IH), The Finnish Cultural Foundation (IH), University of Turku Graduate School funding (MM), Academy of Finland (#17379, JPP), Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland) (JPP), Maire Taponen Foundation sr (JPP), personal grants from Emil Aaltonen Foundation sr (TR), and the Finnish Cultural Foundation (TR), and NIHR Research Professorship and the NIHR Cambridge BRC (PJH), NIHR Research UK (through a Senior Investigator Award and the Cambridge Biomedical Research Centre) (DKM), Academy of Medical Sciences / The Health Foundation Clinician Scientist Fellowship (VFN); Wallenberg Scholarship and grants from the Swedish and European Research Councils (HZ), and grants from the Swedish Research Council and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986) (KB). Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Diffusion tensor imaging

KW - Diffusion-weighted magnetic resonance imaging

KW - Neurofilament light protein

U2 - 10.1186/s12883-023-03284-6

DO - 10.1186/s12883-023-03284-6

M3 - Article

C2 - 37582732

AN - SCOPUS:85168063555

SN - 1471-2377

VL - 23

JO - Bmc Neurology

JF - Bmc Neurology

IS - 1

M1 - 304

ER -

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

Abstract

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