Laboratory biomarkers of delayed cerebral ischemia after subarachnoid hemorrhage: a systematic review

  • Ramazan JabbarliEmail author
  • Daniela Pierscianek
  • Marvin Darkwah Oppong
  • Tako Sato
  • Philipp Dammann
  • Karsten H. Wrede
  • Klaus Kaier
  • Martin Köhrmann
  • Michael Forsting
  • Christoph Kleinschnitz
  • Andreas Roos
  • Ulrich Sure


Delayed cerebral ischemia (DCI) is a severe complication of subarachnoid hemorrhage (SAH). Clinical and radiographic features of SAH may be helpful in identification of individuals prone to DCI. The aim of this systematic review was to analyze the present evidence on predictive value of blood and cerebrospinal fluid (CSF) biomarkers of DCI after SAH. We systematically searched in PubMed, Scopus, Web of Science, and Cochrane Library databases for publications before July 15, 2018, reporting correlations between blood/CSF biomarkers and occurrence of DCI and/or vasospasm in SAH patients. Included studies underwent quality assessment according to QUIPS and STARD guidelines. Level of evidence (I–IV) for each of tested biomarkers was assessed according to GRADE guidelines. Of 2181 unique records identified in four databases, 270 original articles and 5 meta-analyses were included to this review. Of 257 blood and CSF parameters analyzed in 16.914 SAH patients, there was no biomarker with positive association with DCI/vasospasm showing level I evidence. Twenty-one biomarkers achieved level II evidence and could be confirmed as predictive biomarkers. In this review, six single nucleotide polymorphisms (for EET metabolic pathways, COMT, HMGB1, ACE, PAI-1 promoter, and Hp genes) and 15 non-genetic biomarkers (pNF-H, ADAMTS13, NPY, Copeptin, HMGB1, GFAP, periostin, Tau, BNP, NT pro-BNP, hs-TnT, PA-TEGMA, MPV:PLT, NLR, and PLR) were selected as predictive DCI biomarkers. We propose that a panel analysis of the selected genetic and protein biomarker candidates would be needed for further validation in a large SAH cohort.


DCI Vasospasm SAH Biomarkers Proteomics Genomics 


Compliance with ethical standards

Conflict of interest

RJ, DP, MDO, PD, KHW, and US are the members of the Editorial Board of Neurosurgical Review.

Ethical approval

Ethical approval is not required for this type of study.

Informed consent

Informed consent is not required for this type of study.

Supplementary material

10143_2018_1037_MOESM1_ESM.docx (147 kb)
ESM 1 (DOCX 147 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ramazan Jabbarli
    • 1
    Email author
  • Daniela Pierscianek
    • 1
  • Marvin Darkwah Oppong
    • 1
  • Tako Sato
    • 1
  • Philipp Dammann
    • 1
  • Karsten H. Wrede
    • 1
  • Klaus Kaier
    • 2
  • Martin Köhrmann
    • 3
  • Michael Forsting
    • 4
  • Christoph Kleinschnitz
    • 3
  • Andreas Roos
    • 5
  • Ulrich Sure
    • 1
  1. 1.Department of NeurosurgeryUniversity Hospital of EssenEssenGermany
  2. 2.Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical CenterUniversity of FreiburgFreiburgGermany
  3. 3.Clinic for NeurologyUniversity Hospital of EssenEssenGermany
  4. 4.Institute for Diagnostic and Interventional RadiologyUniversity Hospital of EssenEssenGermany
  5. 5.Leibniz Institute for Analytical Sciences - ISAS - e.V.DortmundGermany

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