TY - JOUR
T1 - Matrix metalloproteinase-9 levels are associated with brain lesion and persistent venous occlusion in patients with cerebral venous thrombosis
AU - Sousa, Diana Aguiar de
AU - Pereira-Santos, Maria Conceição
AU - Serra-Caetano, Ana
AU - Neto, Lia Lucas
AU - Sousa, Ana Luísa
AU - Gabriel, Denis
AU - Correia, Manuel A.
AU - Gil-Gouveia, Raquel
AU - Oliveira, Renato
AU - Penas, Sara
AU - Dias, Mariana Carvalho
AU - Correia, Manuel A.
AU - Carvalho, Marta
AU - Sousa, Ana E.
AU - Canhão, Patrícia
AU - Ferro, José M.
N1 - Publisher Copyright:
© 2021. Thieme. All rights reserved.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - Blood-brain barrier
KW - Cerebral venous thrombosis
KW - Infarction
KW - Prognosis
KW - Recanalization
UR - http://www.scopus.com/inward/record.url?scp=85103436255&partnerID=8YFLogxK
U2 - 10.1055/s-0041-1726094
DO - 10.1055/s-0041-1726094
M3 - Article
C2 - 33759145
SN - 0340-6245
VL - 121
SP - 1476
EP - 1482
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 11
ER -