Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations.
Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations.
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DOI：
10.1007/s12975-017-0561-3
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发表时间：
2018-03
影响因子：
6.9
通讯作者：
Awad IA
中科院分区：
文献类型：
--
作者：
Girard R;Zeineddine HA;Fam MD;Mayampurath A;Cao Y;Shi C;Shenkar R;Polster SP;Jesselson M;Duggan R;Mikati AG;Christoforidis G;Andrade J;Whitehead KJ;Li DY;Awad IA
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, 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 4 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, 4 clustered inflammatory biomarkers correlate with cumulative disease aggressiveness, and predict future clinical activity.
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影响因子：
2.6
作者：
Matsuo R;Ago T;Kamouchi M;Kuroda J;Kuwashiro T;Hata J;Sugimori H;Fukuda K;Gotoh S;Makihara N;Fukuhara M;Awano H;Isomura T;Suzuki K;Yasaka M;Okada Y;Kiyohara Y;Kitazono T
通讯作者：
Kitazono T
影响因子：
3.2
作者：
London NR;Li DY
通讯作者：
Li DY
影响因子：
6.3
作者：
Mikati, Abdul G.;Khanna, Omaditya;Awad, Issam A.
通讯作者：
Awad, Issam A.
影响因子：
2.2
作者：
Amur, Shashi G.;Sanyal, Sarmistha;Buckman-Garner, ShaAvhree Y.
通讯作者：
Buckman-Garner, ShaAvhree Y.
影响因子：
2.2
作者：
Girard, Romuald;Khanna, Omaditya;Awad, Issam A.
通讯作者：
Awad, Issam A.