Neuroimagem na síndrome congênita do zika vírus: do diagnóstico ao monitoramento de sequelas neurológicas
Data
2024-06-13
Orientadores
Moll, Fernanda Freire Tovar 
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A trajetória do Zika vírus, desde sua origem na isolada Floresta Zika até se tornar um patógeno com impacto profundo na saúde mundial, ilustra a dinâmica complexa das doenças infecciosas emergentes e a necessidade de vigilância constante, pesquisa e cooperação internacional para enfrentar desafios que transcendem fronteiras. Em face dos desafios impostos pela síndrome congênita do Zika, a necessidade de pesquisa contínua é evidente. Esta tese investiga o papel da neuroimagem no diagnóstico e acompanhamento dos pacientes acometidos pelo Zika vírus, através de estudos desenvolvidos pelo grupo de pesquisa, cujo objetivo geral foi caracterizar as alterações morfológicas relacionadas a infecção congênita pelo vírus Zika e os objetivos específicos foram: caracterizar os aspectos de imagem das alterações do desenvolvimento fetal; descrever as características das imagens pós-natais com foco nas anomalias cranioencefálicas; correlacionar os aspectos morfológicos radiológicos com as alterações histopatológicas nos casos de autópsia; e correlacionar achados morfológicos com alterações do neurodesenvolvimento das crianças expostas à infecção congênita pelo vírus Zika. O resultado é demonstrado através da compilação dos nove artigos desenvolvidos pelo nosso grupo de pesquisa: 1) investigou a associação entre a infecção pelo vírus Zika e a microcefalia fetal, confirmando a transmissão vertical e descrevendo os aspectos de imagem através da avaliação por ultrassonografia de dois fetos acometidos pela infecção congênita, 2) documentou os achados de imagem característicos da infecção congênita pelo vírus Zika, tanto no período pré-natal quanto pós-natal através de uma abordagem multimodal, 3) descreveu a evolução pré-natal e os resultados perinatais através de uma abordagem clínica e radiológica completa do desenvolvimento e danos neurológicos associados à infeção pelo vírus Zika, 4) analisou a ativação imune no líquido amniótico de gestantes infectadas pelo vírus Zika, 5) revisão das alterações radiológicas do sistema nervoso central associados à infecção congênita pelo vírus Zika, utilizando diferentes métodos de imagem e a correlação destas com a fisiopatologia e mecanismo de ação, 6) investigou e detalhou os efeitos neuropatológicos do vírus Zika no sistema nervoso central através da avaliação post-mortem de neonatos infectados intraútero, 7) demonstrou os resultados da avaliação clínica de crianças em idade pré-escolar com síndrome congênita do Zika, identificando os principais sintomas neurológicos, suas correlações funcionais e comorbidades associadas, 8) abordou os resultados obstétricos e perinatais da coorte de pacientes gestantes cujos fetos foram acometidos pela síndrome congênita do Zika, observando as implicações clínicas da infecção pelo vírus Zika durante a gestação e no período perinatal, e 9) investigou e demonstrou os resultados de uma segunda gestação em mulheres que foram infectadas pelo vírus Zika em gestação prévia e cujos filhos anteriores nasceram com síndrome congênita do vírus Zika. O grupo de pesquisa foi o responsável pelo alerta mundial da transmissão vertical e o pioneiro na descrição dos dois primeiros casos de Zika congênita diagnosticados ainda na vida intrauterina, também propôs o termo "síndrome congênita do Zika", além de contribuições importantes como o estudo de neuropatologia com o maior número de neonatos avaliados post-mortem e o estudo dedicado a avaliação multimodal de neuroimagem com a descrições minuciosas do espectro de alterações radiológicas.
The trajectory of the Zika virus, from its origins in the isolated Zika Forest to becoming a pathogen with profound global health impact, illustrates the complex dynamics of emerging infectious diseases and the need for constant surveillance, research and international cooperation to tackle challenges that transcend borders. In light of the challenges posed by Zika congenital syndrome, the need for ongoing research is evident. This thesis investigates the role of neuroimaging in the diagnosis and follow-up of patients affected by the Zika virus, through studies conducted by the research group, the overall aim was to characterize the morphological alterations related to congenital Zika virus infection, with the specific objectives being: to characterize imaging aspects of fetal development abnormalities; to describe postnatal imaging features focusing on cranioencephalic anomalies; to correlate radiological morphological aspects with histopathological changes in autopsy cases; and to relate morphological findings with neurodevelopmental alterations in children exposed to congenital Zika virus infection. The results are demonstrated through the compilation of nine articles developed by our research group: 1) investigated the association between Zika virus infection and fetal microcephaly, confirming vertical transmission and describing the imaging aspects through ultrasound evaluation of two fetuses affected by congenital infection; 2) documented the characteristic imaging findings of congenital Zika virus infection, both prenatal and postnatal, using a multimodal approach; 3) described the prenatal evolution and perinatal outcomes through a comprehensive clinical and radiological approach to development and neurological damage associated with Zika virus infection; 4) analyzed immune activation in the amniotic fluid of pregnant women infected with Zika virus; 5) reviewed the radiological changes in the central nervous system associated with congenital Zika virus infection, utilizing different imaging methods and correlating them with pathophysiology and mechanisms of action; 6) investigated and detailed the neuropathological effects of Zika virus on the central nervous system through post-mortem evaluation of intrauterine-infected neonates; 7) demonstrated the results of clinical evaluations of preschool-aged children with congenital Zika syndrome, identifying the main neurological symptoms, their functional correlations and associated comorbidities; 8) addressed obstetric and perinatal outcomes of the cohort of pregnant patients whose fetuses were affected by congenital Zika syndrome, observing the clinical implications of Zika virus infection during pregnancy and the perinatal period; and 9) investigated and demonstrated the outcomes of a second pregnancy in women who were infected with Zika virus in a previous pregnancy and whose earlier children were born with congenital Zika syndrome. The research group was responsible for the worldwide alert on vertical transmission and was pioneering in the description of the first two cases of congenital Zika diagnosed still in utero. Additionally, proposed the term "congenital Zika syndrome" and made significant contributions, including the neuropathology study with the largest number of post-mortem evaluated neonates and a dedicated multimodal neuroimaging study with detailed descriptions of the spectrum of radiological changes.
The trajectory of the Zika virus, from its origins in the isolated Zika Forest to becoming a pathogen with profound global health impact, illustrates the complex dynamics of emerging infectious diseases and the need for constant surveillance, research and international cooperation to tackle challenges that transcend borders. In light of the challenges posed by Zika congenital syndrome, the need for ongoing research is evident. This thesis investigates the role of neuroimaging in the diagnosis and follow-up of patients affected by the Zika virus, through studies conducted by the research group, the overall aim was to characterize the morphological alterations related to congenital Zika virus infection, with the specific objectives being: to characterize imaging aspects of fetal development abnormalities; to describe postnatal imaging features focusing on cranioencephalic anomalies; to correlate radiological morphological aspects with histopathological changes in autopsy cases; and to relate morphological findings with neurodevelopmental alterations in children exposed to congenital Zika virus infection. The results are demonstrated through the compilation of nine articles developed by our research group: 1) investigated the association between Zika virus infection and fetal microcephaly, confirming vertical transmission and describing the imaging aspects through ultrasound evaluation of two fetuses affected by congenital infection; 2) documented the characteristic imaging findings of congenital Zika virus infection, both prenatal and postnatal, using a multimodal approach; 3) described the prenatal evolution and perinatal outcomes through a comprehensive clinical and radiological approach to development and neurological damage associated with Zika virus infection; 4) analyzed immune activation in the amniotic fluid of pregnant women infected with Zika virus; 5) reviewed the radiological changes in the central nervous system associated with congenital Zika virus infection, utilizing different imaging methods and correlating them with pathophysiology and mechanisms of action; 6) investigated and detailed the neuropathological effects of Zika virus on the central nervous system through post-mortem evaluation of intrauterine-infected neonates; 7) demonstrated the results of clinical evaluations of preschool-aged children with congenital Zika syndrome, identifying the main neurological symptoms, their functional correlations and associated comorbidities; 8) addressed obstetric and perinatal outcomes of the cohort of pregnant patients whose fetuses were affected by congenital Zika syndrome, observing the clinical implications of Zika virus infection during pregnancy and the perinatal period; and 9) investigated and demonstrated the outcomes of a second pregnancy in women who were infected with Zika virus in a previous pregnancy and whose earlier children were born with congenital Zika syndrome. The research group was responsible for the worldwide alert on vertical transmission and was pioneering in the description of the first two cases of congenital Zika diagnosed still in utero. Additionally, proposed the term "congenital Zika syndrome" and made significant contributions, including the neuropathology study with the largest number of post-mortem evaluated neonates and a dedicated multimodal neuroimaging study with detailed descriptions of the spectrum of radiological changes.
Descrição
Citação
SZEJNFELD, Patricia Soares de Oliveira. Neuroimagem na síndrome congênita do zika vírus: do diagnóstico ao monitoramento de sequelas neurológicas. 2024. 144 f. Dissertação (Doutorado em Radiologia Clínica) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP). São Paulo, 2024.