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Neurofilament light predicts neurological outcome after subarachnoid haemorrhage.

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 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. 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 control subjects, 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 the WFNS score, and is a promising surrogate end point in clinical trials.

SUBMITTER: Garland P

PROVIDER: S-EPMC8041040 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Neurofilament light predicts neurological outcome after subarachnoid haemorrhage.

Garland Patrick P Morton Matt M Zolnourian Ardalan A Durnford Andrew A Gaastra Ben B Toombs Jamie J Heslegrave Amanda J AJ More John J Zetterberg Henrik H Bulters Diederik O DO Galea Ian I

Brain : a journal of neurology 20210401 3

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 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L f ...[more]

PMID: 33517369

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Project description:BackgroundDisease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome.MethodsData were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24-48 h, 6-8 days, 12-15 days and 6-12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models.FindingsIn the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24-48 h after admission (2.23 (1.23-3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122-0·594), p < 0·001, median with 95%CI). A multivariate logistic regression model revealed power for BBBD in combination with RMS at 24-48 h in predicting outcome (ROC area under the curve = 0·829, p < 0·001).InterpretationWe suggest that early identification of BBBD may serve as a key predictive biomarker for neurological outcome in aSAH. FUND: Dr. Dreier was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (DFG DR 323/5-1 and DFG DR 323/10-1), the Bundesministerium für Bildung und Forschung (BMBF) Center for Stroke Research Berlin 01 EO 0801 and FP7 no 602150 CENTER-TBI. Dr. Friedman was supported by grants from Israel Science Foundation and Canada Institute for Health Research (CIHR). Dr. Friedman was supported by grants from European Union's Seventh Framework Program (FP7/2007-2013; grant #602102).

Dataset Information

Neurofilament light predicts neurological outcome after subarachnoid haemorrhage.

Publications

Neurofilament light predicts neurological outcome after subarachnoid haemorrhage.

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