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Thromb Haemost 2021; 121(11): 1476-1482
DOI: 10.1055/s-0041-1726094
Stroke, Systemic or Venous Thromboembolism

Matrix Metalloproteinase-9 Levels are Associated with Brain Lesion and Persistent Venous Occlusion in Patients with Cerebral Venous Thrombosis

Diana Aguiar de Sousa 
1   Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria/CHULN, Universidade de Lisboa, Lisbon, Portugal
2   Institute of Anatomy, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal
3   Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
,
Maria Conceição Pereira-Santos
3   Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
,
Ana Serra-Caetano
3   Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
,
Lia Lucas Neto
2   Institute of Anatomy, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal
4   Department of Neuroradiology, Hospital de Santa Maria - CHULN, Universidade de Lisboa, Lisbon, Portugal
,
Ana Luísa Sousa
5   Department of Neurology, Centro Hospitalar de Entre Douro e Vouga, Santa Maria da Feira, Portugal
,
Denis Gabriel
6   Department of Neurology, Centro Hospitalar Universitário do Porto - Hospital Santo António, Porto, Portugal
,
Manuel Correia
6   Department of Neurology, Centro Hospitalar Universitário do Porto - Hospital Santo António, Porto, Portugal
,
Raquel Gil-Gouveia
7   Department of Neurology, Hospital da Luz, Lisbon, Portugal
,
Renato Oliveira
7   Department of Neurology, Hospital da Luz, Lisbon, Portugal
,
Sara Penas
2   Institute of Anatomy, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal
,
Mariana Carvalho Dias
1   Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria/CHULN, Universidade de Lisboa, Lisbon, Portugal
,
Manuel A. Correia
4   Department of Neuroradiology, Hospital de Santa Maria - CHULN, Universidade de Lisboa, Lisbon, Portugal
,
Marta Carvalho
8   Department of Neurology, Centro Hospitalar Universitário de São João, Faculty of Medicine, University of Porto, Porto, Portugal
,
Ana E. Sousa
3   Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
,
Patrícia Canhão
1   Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria/CHULN, Universidade de Lisboa, Lisbon, Portugal
3   Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
,
José M. Ferro
1   Department of Neurosciences and Mental Health (Neurology), Hospital de Santa Maria/CHULN, Universidade de Lisboa, Lisbon, Portugal
3   Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
› Author Affiliations Funding This study was supported by 11° Bolsa de Investigação Fundação AstraZeneca - Faculdade de Medicina Universidade de Lisboa, D. Manuel de Mello grant, and Fundação Amélia de Mello. D.A.S. was supported by a doctoral grant SFRH/SINTD/92677/2013 from Fundação para Ciência e Tecnologia.
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Abstract

Background Elucidating mechanisms of brain damage in cerebral venous thrombosis (CVT) would be instrumental to develop targeted therapies and improve prognosis prediction. Matrix metalloproteinase-9 (MMP-9), a gelatinase that degrades major components of the basal lamina, has been associated to blood–brain barrier disruption. We aimed to assess, in patients with CVT, the temporal change in serum concentrations of MMP-9 and its association with key imaging and clinical outcomes.

Methods Pathophysiology of Venous Infarction—PRediction of InfarctiOn and RecanalIzaTion in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Serial collection of peripheral blood samples performed on day 1, 3, and 8, and standardized magnetic resonance imaging on day 1, 8, and 90. MMP-9 was quantified using enzyme-linked immunosorbent assay in 59 patients and 22 healthy controls. Primary outcomes were parenchymal brain lesion, early evolution of brain lesion, early recanalization, and functional outcome on day 90.

Results CVT patients with parenchymal brain lesion had higher baseline concentrations of MMP-9 compared with controls (adjusted p = 0.001). The area under receiver operating characteristic curve value for MMP-9 for predicting brain lesion was 0.71 (95% confidence interval [CI]: 0.57–0.85, p = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 (p = 0.021). Higher MMP-9 on day 8 was associated with persistent venous occlusion (odds ratio: 1.20 [per 20 ng/mL], 95% CI: 1.02–1.43, p = 0.030).

Conclusion We report a novel relationship among MMP-9, parenchymal brain damage, and early venous recanalization, suggesting that circulating MMP-9 is a dynamic marker of brain tissue damage in patients with CVT.

Keywords

cerebral venous thrombosis - blood–brain barrier - infarction - recanalization - prognosis

Supplementary Material



Publication History

Received: 26 April 2020

Accepted: 30 January 2021

Article published online:
23 March 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
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