Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Jens Witsch; Valérie Spalart; Kimberly Martinod; Hauke Schneider; Joachim Oertel; Jürgen Geisel; Philipp Hendrix; Sina Hemmer

doi:10.1097/CCE.0000000000000692

Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Crit Care Explor. 2022 May 17;4(5):e0692. doi: 10.1097/CCE.0000000000000692. eCollection 2022 May.

Authors

Jens Witsch¹, Valérie Spalart², Kimberly Martinod², Hauke Schneider³, Joachim Oertel⁴, Jürgen Geisel⁵, Philipp Hendrix⁴, Sina Hemmer⁴

Affiliations

¹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
² Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
³ Department of Neurology, University Hospital Augsburg, Augsburg, Germany.
⁴ Department of Neurosurgery, Saarland University Medical Center, Homburg/Saar, Germany.
⁵ Department of Clinical Chemistry and Laboratory Medicine, Saarland University Medical Center, Homburg/Saar, Germany.

Abstract

Importance: Myeloperoxidase (MPO)-DNA complexes, biomarkers of neutrophil extracellular traps (NETs), have been associated with arterial and venous thrombosis. Their role in aneurysmal subarachnoid hemorrhage (aSAH) is unknown.

Objectives: To assess whether serum MPO-DNA complexes are present in patients with aSAH and whether they are associated with delayed cerebral ischemia (DCI).

Design setting and participants: Post-hoc analysis of a prospective, observational single-center study, with de novo serum biomarker measurements in consecutive patients with aSAH between July 2018 and September 2020, admitted to a tertiary care neuroscience ICU.

Main outcomes and measures: We analyzed serum obtained at admission and hospital day 4 for concentrations of MPO-DNA complexes. The primary outcome was DCI, defined as new infarction on brain CT. The secondary outcome was clinical vasospasm, a composite of clinical and transcranial Doppler parameters. We used Wilcoxon signed-rank-test to assess for differences between paired measures.

Results: Among 100 patients with spontaneous subarachnoid hemorrhage, mean age 59 years (sd ± 13 yr), 55% women, 78 had confirmed aSAH. Among these, 29 (37%) developed DCI. MPO-DNA complexes were detected in all samples. The median MPO-DNA level was 33 ng/mL (interquartile range [IQR], 18-43 ng/mL) at admission, and 22 ng/mL (IQR, 11-31 ng/mL) on day 4 (unpaired test; p = 0.015). We found a significant reduction in MPO-DNA levels from admission to day 4 in patients with DCI (paired test; p = 0.036) but not in those without DCI (p = 0.17). There was a similar reduction in MPO-DNA levels between admission and day 4 in patients with (p = 0.006) but not in those without clinical vasospasm (p = 0.47).

Conclusions and relevance: This is the first study to detect the NET biomarkers MPO-DNA complexes in peripheral serum of patients with aSAH and to associate them with DCI. A pronounced reduction in MPO-DNA levels might serve as an early marker of DCI. This diagnostic potential of MPO-DNA complexes and their role as potential therapeutic targets in aSAH should be explored further.

Keywords: extracellular traps; intracranial aneurysm; ischemic stroke; neutrophils; subarachnoid hemorrhage.