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01-02-2018 | Original Article

Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations

Authors: Romuald Girard, Hussein A. Zeineddine, Maged D. Fam, Anoop Mayampurath, Ying Cao, Changbin Shi, Robert Shenkar, Sean P. Polster, Michael Jesselson, Ryan Duggan, Abdul-Ghani Mikati, Gregory Christoforidis, Jorge Andrade, Kevin J. Whitehead, Dean Y. Li, Issam A. Awad

Published in: Translational Stroke Research | Issue 1/2018

Abstract

The clinical course of cerebral cavernous malformations (CCMs) is highly variable. Based on recent discoveries implicating angiogenic and inflammatory mechanisms, we hypothesized that serum biomarkers might reflect chronic or acute disease activity. This single-site prospective observational cohort study included 85 CCM patients, in whom 24 a priori chosen plasma biomarkers were quantified and analyzed in relation to established clinical and imaging parameters of disease categorization and severity. We subsequently validated the positive correlations in longitudinal follow-up of 49 subjects. Plasma levels of matrix metalloproteinase-2 and intercellular adhesion molecule 1 were significantly higher (P = 0.02 and P = 0.04, respectively, FDR corrected), and matrix metalloproteinase-9 was lower (P = 0.04, FDR corrected) in patients with seizure activity at any time in the past. Vascular endothelial growth factor and endoglin (both P = 0.04, FDR corrected) plasma levels were lower in patients who had suffered a symptomatic bleed in the prior 3 months. The hierarchical clustering analysis revealed a cluster of four plasma inflammatory cytokines (interleukin 2, interferon gamma, tumor necrosis factor alpha, and interleukin 1 beta) separating patients into what we designated “high” and “low” inflammatory states. The “high” inflammatory state was associated with seizure activity (P = 0.02) and more than one hemorrhagic event during a patient’s lifetime (P = 0.04) and with a higher rate of new hemorrhage, lesion growth, or new lesion formation (P < 0.05) during prospective follow-up. Peripheral plasma biomarkers reflect seizure and recent hemorrhagic activity in CCM patients. In addition, four clustered inflammatory biomarkers correlate with cumulative disease aggressiveness and predict future clinical activity.

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Title: Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations
Authors: Romuald Girard
Hussein A. Zeineddine
Maged D. Fam
Anoop Mayampurath
Ying Cao
Changbin Shi
Robert Shenkar
Sean P. Polster
Michael Jesselson
Ryan Duggan
Abdul-Ghani Mikati
Gregory Christoforidis
Jorge Andrade
Kevin J. Whitehead
Dean Y. Li
Issam A. Awad
Publication date: 01-02-2018
Publisher: Springer US
Published in: Translational Stroke Research / Issue 1/2018
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-017-0561-3

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Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations

Abstract

Keynote webinar | Spotlight on medication adherence

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