ArticleTranslational stroke research2018
Plasma Biomarkers of Inflammation Reflect Seizures and Hemorrhagic Activity of Cerebral Cavernous Malformations.
Article in Translational stroke research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Imaging markers and circulating biomarkers for predicting hemorrhage from cerebral cavernous malformations: A systematic review.Neurosurgical review · 2026Pooled it
- Molecular Pathways and Circulating Biomarkers in Cerebral Cavernous Malformations-A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Cerebral cavernous malformations: epidemiology, molecular pathogenesis, diagnosis and therapy.Molecular biomedicine · 2026Review
- Leukocytosis at Presentation Is an Independent Predictor for Hemorrhage in Cerebral Cavernoma.Diagnostics (Basel, Switzerland) · 2026Article
- Familial Cerebral Cavernous Malformations: Pathophysiology, Genetics, Biomarkers, and Treatment Perspectives.Journal of neurochemistry · 2026Review
- Plasma biomarkers in patients with familial cavernous malformation and their first-degree relatives: a cross-sectional study.Scientific reports · 2025Observational
- Stereotactic radiosurgery for haemorrhagic cerebral cavernous malformation: a multi-institutional, retrospective study.Stroke and vascular neurology · 2024Article
- Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs).International journal of molecular sciences · 2024Article
- Mammalian STE20-like kinase 1 inhibits synoviocytes activation in rheumatoid arthritis through mitochondrial dysfunction mediated by SIRT3/mTOR axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Circulating biomarkers in familial cerebral cavernous malformation.EBioMedicine · 2024Article
- Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain.Nature medicine · 2023Article
- Inflammatory Mechanisms in a Neurovascular Disease: Cerebral Cavernous Malformation.Brain sciences · 2023Review
- PCMT1 is a potential target related to tumor progression and immune infiltration in liver cancer.European journal of medical research · 2023Article
- Circulating Plasma miRNA Homologs in Mice and Humans Reflect Familial Cerebral Cavernous Malformation Disease.Translational stroke research · 2023Article
- Plasma metabolites with mechanistic and clinical links to the neurovascular disease cavernous angioma.Communications medicine · 2023Article
- A feasibility study for quantitative assessment of cerebrovascular malformations using flutriciclamide ([Frontiers in medicine · 2023Article
- Dysregulated Hemostasis and Immunothrombosis in Cerebral Cavernous Malformations.International journal of molecular sciences · 2022Review
- mPR-Specific Actions Influence Maintenance of the Blood-Brain Barrier (BBB).International journal of molecular sciences · 2022Article
- Next-Generation Sequencing Advances the Genetic Diagnosis of Cerebral Cavernous Malformation (CCM).Antioxidants (Basel, Switzerland) · 2022Article
- Cerebral Cavernous Malformation Pathogenesis: Investigating Lesion Formation and Progression with Animal Models.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
16 authors.
Funding
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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