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Systemic High-Mobility Group Box-1: A Novel Predictive Biomarker for Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage*

Chaudhry, Shafqat R., PharmD, MPhil1,2; Güresir, Agi, MD1; Stoffel-Wagner, Birgit, MD, PhD3; Fimmers, Rolf, PhD4; Kinfe, Thomas M., MD1; Dietrich, Dirk, MD, PhD1; Lamprecht, Alf, PhD2; Vatter, Hartmut, MD, PhD1; Güresir, Erdem, MD1; Muhammad, Sajjad, MD, PhD1,5

doi: 10.1097/CCM.0000000000003319
Online Clinical Investigations

Objectives: To investigate the release of proinflammatory damage-associated molecular pattern molecule “high-mobility group box-1” in the serum of patients after aneurysmal subarachnoid hemorrhage and its association with cerebral vasospasm.

Design: Retrospective observational study.

Setting: University hospital.

Patients: Aneurysmal subarachnoid hemorrhage patients admitted within 24 hours of ictus.

Interventions: Standard subarachnoid hemorrhage treatment after clipping or coiling of aneurysm.

Measurements and Main Results: We enrolled 53 aneurysmal subarachnoid hemorrhage patients from which peripheral venous blood was withdrawn on days 1, 3, 5, 7, 9, 11, and 13 and once from the controls to obtain the serum. Serum high-mobility group box-1 concentration was quantified by enzyme-linked immunosorbent assay. Serum interleukin-6 and peripheral blood leukocytes were also determined over the first 2 weeks after subarachnoid hemorrhage. Patients’ data were recorded prospectively. Serum high-mobility group box-1 was significantly elevated in subarachnoid hemorrhage patients from day 1 to day 13 when compared with nonsubarachnoid hemorrhage patients (p < 0.05). Patients with cerebral vasospasm showed significantly higher high-mobility group box-1 starting from day 1 to day 13 when compared with patients without cerebral vasospasm. Cumulative levels of high-mobility group box-1 showed significant correlation with peripheral blood leukocytes and interleukin-6 levels (p < 0.05). Receiver operating characteristic curve analysis showed that serum high-mobility group box-1 level at admission may be a predictive biomarker for cerebral vasospasm with a sensitivity of 59% and a specificity of 82% at a cutoff value of 5.6 ng/mL.

Conclusions: Serum high-mobility group box-1 is differentially elevated after subarachnoid hemorrhage. Serum high-mobility group box-1 levels were elevated early after subarachnoid hemorrhage (day 1) and remained significantly high until day 13 in patients who developed cerebral vasospasm. Our data suggest that serum high-mobility group box-1 may be a predictive biomarker for the detection of CVS.

1Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.

2Department of Pharmaceutics, University of Bonn, Bonn, Germany.

3Department of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.

4Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn, Bonn, Germany.

5Department of Neurosurgery, Helsinki University Hospital, Helsinki, Finland.

*See also p. 1883.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by grant from Stiftung Neurochirurgische Forschung (Deutsche Gesellschaft für Neurochirurgie [DGNC]) to Dr. Muhammad and Bonner Forschung (BONFOR) Program (Instrument V) to Dr. Muhammad and Dr. Dietrich.

Dr. Muhammad received support for article research from the German Society of Neurosurgery (DGNC) and BONFOR Programm of University Bonn. Dr. Dietrich’s institution received funding from Deutsche Forschungsgemeinschaft (DFG); he received support for article research from DFG; and he disclosed government work. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: ext-sajjad.muhammad@hus.fi

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