Neutrophil Extracellular Traps and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage. (17th May 2022)

• Record Type: Journal Article
• Authors: Witsch, Jens; Spalart, Valérie; Martinod, Kimberly; Schneider, Hauke; Oertel, Joachim; Geisel, Jürgen; Hendrix, Philipp; Hemmer, Sina
• Is Part Of: Critical care explorations. Volume 4:Number 5(2022)
• Page Start: e0692
• Publication Date: 2022-05-17
• Subjects: extracellular traps -- intracranial aneurysm -- ischemic stroke -- neutrophils -- subarachnoid hemorrhage
• DOI: 10.1097/CCE.0000000000000692
• Languages: English
• ISSNs: 2639-8028

Abstract

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.