Criteria for a Clinically Informative Serum Biomarker in Acute Ischaemic Stroke: A Review of S100B

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Abstract

Background and Purpose: Serum S100B has been widely studied as a biomarker in acute ischaemic stroke. The main objective of this review was to appraise the published literature on S100B and determine its clinical applicability. Methods: Medline was searched to identify studies on S100B (or S-100B) in acute ischaemic stroke. The authors have proposed the criteria for a clinically informative serum biomarker for acute ischaemic stroke, and relevant articles relating to these criteria were then selected. Results: Studies have shown that S100B has a low specificity for acute ischaemic stroke because of its tendency to be raised from extracranial sources. Data regarding S100B kinetics compiled from 6 longitudinal studies show that serum levels are not raised immediately following acute ischaemic stroke and peak 3 days after symptom onset. However, serum S100B levels correlate well with infarct volume and are higher in stroke patients at risk of malignant infarction or haemorrhagic transformation after thrombolysis. In addition, serum S100B levels correlate well with functional outcome. Conclusion: The evidence suggests that S100B is not a valuable biomarker for diagnosing acute ischaemic stroke. Instead, it may have a more promising role in non-specialist hospitals, as an additional tool for identifying patients at increased risk of specific early neurological complications after stroke and as a surrogate marker of cerebral damage and functional outcome, particularly in a research setting.

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A soluble protein characteristic of the nervous system.

Bethany B. Moore (1965)

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Comparison of MRI and CT for detection of acute intracerebral hemorrhage.

Jeffrey L Saver, Nathaniel Davis, Margaret Tremwel … (2004)

Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

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Evidence for a wide extra-astrocytic distribution of S100B in human brain

Johann Steiner, Hans-Gert Bernstein, Hendrik Bielau … (2007)

Background S100B is considered an astrocytic in-situ marker and protein levels in cerebrospinal fluid (CSF) or serum are often used as biomarker for astrocytic damage or dysfunction. However, studies on S100B in the human brain are rare. Thus, the distribution of S100B was studied by immunohistochemistry in adult human brains to evaluate its cell-type specificity. Results Contrary to glial fibrillary acidic protein (GFAP), which selectively labels astrocytes and shows only faint ependymal immunopositivity, a less uniform staining pattern was seen in the case of S100B. Cells with astrocytic morphology were primarily stained by S100B in the human cortex, while only 20% (14–30%) or 14% (7–35%) of all immunopositive cells showed oligodendrocytic morphology in the dorsolateral prefrontal and temporal cortices, respectively. In the white matter, however, most immunostained cells resembled oligodendrocytes [frontal: 75% (57–85%); temporal: 73% (59–87%); parietal: 79% (62–89%); corpus callosum: 93% (86–97%)]. S100B was also found in ependymal cells, the choroid plexus epithelium, vascular endothelial cells, lymphocytes, and several neurones. Anti-myelin basic protein (MBP) immunolabelling showed an association of S100B with myelinated fibres, whereas GFAP double staining revealed a distinct subpopulation of cells with astrocytic morphology, which solely expressed S100B but not GFAP. Some of these cells showed co-localization of S100B and A2B5 and may be characterized as O2A glial progenitor cells. However, S100B was not detected in microglial cells, as revealed by double-immunolabelling with HLA-DR. Conclusion S100B is localized in many neural cell-types and is less astrocyte-specific than GFAP. These are important results in order to avoid misinterpretation in the identification of normal and pathological cell types in situ and in clinical studies since S100B is continuously used as an astrocytic marker in animal models and various human diseases.

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Author and article information

Journal

Journal ID (publisher-id): CED

Journal ID (nlm-ta): Cerebrovasc Dis

Journal ID (doi): 10.1159/issn.1015-9770

Title: Cerebrovascular Diseases

Publisher: S. Karger AG

ISSN (Print): 1015-9770

ISSN (Electronic): 1421-9786

Publication date Subscription-year: 2009

Publication date (Print): March 2009

Publication date (Electronic): 06 February 2009

Volume: 27

Issue: 3

Pages: 295-302

Affiliations

^aStroke Research Group and ^bDepartment of Neuroimmunology, UCL Institute of Neurology, National Hospital of Neurology and Neurosurgery, London, UK

Article

Publisher ID: 199468 Other ID: Cerebrovasc Dis 2009;27:295–302

DOI: 10.1159/000199468

PubMed ID: 19202335

SO-VID: 5925d009-fd9c-484c-a000-4c2c7d65bd2a

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 03 July 2008

Date accepted : 14 November 2008

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Figures: 1, Tables: 1, References: 40, Pages: 8

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Criteria for a Clinically Informative Serum Biomarker in Acute Ischaemic Stroke: A Review of S100B

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Karger: Neurology and Neuroscience

Most cited references 25

A soluble protein characteristic of the nervous system.

Comparison of MRI and CT for detection of acute intracerebral hemorrhage.

Evidence for a wide extra-astrocytic distribution of S100B in human brain

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Cited by 38

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