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Cerebral venous thrombosis : from pathophysiology to therapeutics

datacite.subject.fosCiências Médicas::Medicina Clínicapt_PT
dc.contributor.advisorFerro, José Manuel Morão Cabral
dc.contributor.advisorCanhão, Patrícia Martins
dc.contributor.authorde Sousa, Diana Aguiar
dc.date.accessioned2021-06-11T16:39:24Z
dc.date.available2021-06-11T16:39:24Z
dc.date.issued2020-07
dc.date.submitted2020-02
dc.description.abstractCerebral Venous Thrombosis (CVT) is a less common form of stroke that mostly affects young women. Despite the great progress made in the last decades, significant evidence gaps persist in the understanding of the pathophysiology of brain damage, the mechanisms underlying the benefit of the available treatment strategies and the management of secondary prophylaxis. This work was focused on two of these questions, namely: (1) the mechanisms underlying the pathogenesis of brain lesion and their evolution in relation with the therapeutic intervention; and (2) the risk of pregnancy-related venous thrombotic events and unfavourable foetal outcomes in women with history of CVT, and the most appropriate approach to prevent them. We have performed two systematic reviews (and one systematic review update) and three original studies. The available evidence was appraised in the systematic reviews and the main research gaps were identified. To further address the first aim, we have conducted a multicenter prospective cohort study of patients treated with anticoagulation that included serial standard magnetic resonance imaging and blood collection at several time-points, in order to assess early venous recanalization and biomarkers of blood-brain barrier (BBB) disruption and inflammation. We found an association between persistent venous occlusion and early worsening of brain lesions and diffusion restriction was often associated with tissue recovery in patients with early recanalization. Patients with CVT and parenchymal brain lesions had abnormal levels of matrix metalloproteinase 9 (MMP-9) and the levels of this marker of BBB disruption following treatment start were related with the early recanalization status. Patients with CVT had higher levels of Interleukin-6 (IL-6) and this was a predictor of unfavourable functional outcome at 90-days. Also, we have pooled two registries in order to describe that a MRI marker of hypoperfusion and dilated collateral circulation, the brush sign, can be identified in CVT and is associated with brain lesion and others makers of severity. For the second aim, we performed a follow-up study of women at fertile age with history of CVT and assessed recurrent venous thrombotic events and foetal outcomes, according to antithrombotic prophylaxis. Our results add new evidence on the mechanisms of disease, providing insights into the role of early venous recanalization in the progression and recovery of brain lesions associated with CVT in patients treated with anticoagulation, and indicating new promising markers, as the brush sign, MMP-9 and IL-6. We also collected substantial evidence that support the use of antithrombotic prophylaxis to reduce the pregnancy-related venous thrombotic events and miscarriage among women with history of CVT.pt_PT
dc.identifier.tid101454015pt_PT
dc.identifier.urihttp://hdl.handle.net/10451/48477
dc.language.isoengpt_PT
dc.relationTROMBOSE VENOSA CELEBRAL: DA FISIOPATOLOGIA À TERAPÊUTICA
dc.subjectTrombose venosa cerebralpt_PT
dc.subjectTerapêutica antitrombóticapt_PT
dc.subjectBiomarcadorespt_PT
dc.subjectRecanalizaçãopt_PT
dc.subjectGravidezpt_PT
dc.subjectCerebral venous thrombosispt_PT
dc.subjectAntithrombotic treatmentpt_PT
dc.subjectBiomarkerspt_PT
dc.subjectRecanalizationpt_PT
dc.subjectPregnancypt_PT
dc.subjectTeses de doutoramento - 2020pt_PT
dc.titleCerebral venous thrombosis : from pathophysiology to therapeuticspt_PT
dc.typedoctoral thesis
dspace.entity.typePublication
oaire.awardNumberSFRH/SINTD/92677/2013
oaire.awardTitleTROMBOSE VENOSA CELEBRAL: DA FISIOPATOLOGIA À TERAPÊUTICA
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FSINTD%2F92677%2F2013/PT
person.familyNameAguiar de Sousa
person.givenNameDiana
person.identifier574112
person.identifier.ciencia-id571C-121A-5CCB
person.identifier.orcid0000-0002-6702-7924
person.identifier.ridJ-4105-2013
person.identifier.scopus-author-id55781226000
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typedoctoralThesispt_PT
relation.isAuthorOfPublication1d984575-dd95-4ca1-9092-bf6f9914ba63
relation.isAuthorOfPublication.latestForDiscovery1d984575-dd95-4ca1-9092-bf6f9914ba63
relation.isProjectOfPublicationff685705-7ef3-4e39-83ef-dc69c8d23772
relation.isProjectOfPublication.latestForDiscoveryff685705-7ef3-4e39-83ef-dc69c8d23772
thesis.degree.nameTese de doutoramento, Medicina (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2020pt_PT

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