Brain injury markers in blood associate with generalised oedema on computed tomography after cardiac arrest

Introduction. According to the 2021 ERC/ESICM guideline recommen-
dations, elevated neuron-specific enolase [NSE] levels as well as diffuse
and extensive anoxic damage on neuroimaging are predictors of poor
neurological outcome after cardiac arrest.(1) We previously described
that NSE is elevated in patients with generalised oedema on com-
puted tomography [CT]. (2).
Objectives. In this study, we aim to examine the novel brain injury
markers serum neurofilament light [NFL], glial fibrillary acidic protein
[GFAP] and total-tau [tau] to predict the presence of generalised brain
oedema.
Methods. Retrospective analysis of patients examined with CT on
clinical indication within the Target Temperature Management after
out-of-hospital cardiac arrest [TTM] trial. (2,3) Serum samples from
the biobank sub study were prospectively collected at 48 h post arrest
and analysed after trial completion as published. (4–7) The neuronal
marker NSE, the neuroaxonal injury markers NFL and tau and the
astrocytic injury marker GFAP were correlated with the presence of
generalised oedema on CT, assessed by local radiologists through vis-
ual evaluation. The prognostic accuracy of NSE ≥ 60 ug/l for predicting
generalised oedema was also analysed.
Results. 192 patients had data available on all four biomarkers at 48 h
and were examined with CT < 168 h post arrest. Brain injury markers
were significantly higher in patients with generalised oedema as com-
pared to patients without oedema on CT scans performed 24–168 h
after ROSC (p < 0.001) (Fig. 1A–D). For CT scans performed < 24 h, only
NSE levels showed a significant correlation (p < 0.05). Biomarkers pre -
dicted generalised oedema with area under the receiver operating
characteristics curve [AUC] 67.5–73.2% for CT scans performed < 24 h
(n = 111), with no statistically significant difference between the
markers ( Fig. 2A). For scans performed 24–168 h (n = 81) AUC for pre -
dicting generalised oedema was 78.1%-82.9%, with no statistically
significant difference between the markers. NSE ≥ 60 ug/l at 48 h, as
recommended by guidelines, predicted generalised oedema with 81%
(95%CI 67–90%) sensitivity and 77% (95%CI 62–87%) specificity.Conclusion. Concentrations of all evaluated brain injury markers
were significantly higher in patients with generalised oedema on CT
performed after the first 24 h post arrest. Biomarker concentrations
indicate whether generalised oedema on CT is likely and may thus be
clinically useful for deciding if a CT scan is sufficient for prognostica-
tion or if a MRI is more appropriate.