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Neurofilament light predicts neurological outcome after subarachnoid haemorrhage

Neurofilament light predicts neurological outcome after subarachnoid haemorrhage
Neurofilament light predicts neurological outcome after subarachnoid haemorrhage
To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on days 1-3 post-SAH strongly predicted modified Rankin score at six months, independent of WFNS. NF-L from day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L’s relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus controls, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood-brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to WFNS, and is a promising surrogate endpoint in clinical trials.
0006-8950
761–768
Garland, Patrick
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Morton, Matthew
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Zolnourian, Ardalan
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Durnford, Andrew
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Gaastra, Benjamin
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Toombs, Jamie
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Heslegrave, Amanda J.
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More, John
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Zetterberg, Henrik
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Bulters, Diederik O.
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Galea, Ian
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Garland, Patrick
1d24a0cc-81f2-4ef1-82bd-77d2510e59d6
Morton, Matthew
4a178059-af3c-4de6-9d69-4024ea6178dc
Zolnourian, Ardalan
5e8d4881-cdfd-4cb1-8eae-b98b13104648
Durnford, Andrew
e915b595-7dee-40c6-901d-c9845a7e4f54
Gaastra, Benjamin
f48eac25-66e4-4e0b-8325-d4e4b9558d8f
Toombs, Jamie
87de1750-c129-4ea3-b2e2-4b898ca5846b
Heslegrave, Amanda J.
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More, John
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Zetterberg, Henrik
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Bulters, Diederik O.
a0586d7d-a447-464d-9ec6-fe151a22babe
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b

Garland, Patrick, Morton, Matthew, Zolnourian, Ardalan, Durnford, Andrew, Gaastra, Benjamin, Toombs, Jamie, Heslegrave, Amanda J., More, John, Zetterberg, Henrik, Bulters, Diederik O. and Galea, Ian (2021) Neurofilament light predicts neurological outcome after subarachnoid haemorrhage. Brain, 144 (3), 761–768. (doi:10.1093/brain/awaa451).

Record type: Article

Abstract

To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on days 1-3 post-SAH strongly predicted modified Rankin score at six months, independent of WFNS. NF-L from day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L’s relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus controls, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood-brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to WFNS, and is a promising surrogate endpoint in clinical trials.

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Garland et al 2020 - Accepted Manuscript
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Accepted/In Press date: 11 October 2020
e-pub ahead of print date: 31 January 2021
Published date: 1 March 2021

Identifiers

Local EPrints ID: 445225
URI: http://eprints.soton.ac.uk/id/eprint/445225
ISSN: 0006-8950
PURE UUID: 886b0e5a-03e1-447e-aabb-e518bb59ad09
ORCID for Matthew Morton: ORCID iD orcid.org/0000-0003-1986-0863
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

Catalogue record

Date deposited: 25 Nov 2020 17:33
Last modified: 22 Nov 2021 02:49

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Contributors

Author: Patrick Garland
Author: Matthew Morton ORCID iD
Author: Ardalan Zolnourian
Author: Andrew Durnford
Author: Benjamin Gaastra
Author: Jamie Toombs
Author: Amanda J. Heslegrave
Author: John More
Author: Henrik Zetterberg
Author: Diederik O. Bulters
Author: Ian Galea ORCID iD

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