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      Clinical, Neuroimaging, and Neurophysiological Findings in Children with Microcephaly Related to Congenital Zika Virus Infection

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          Abstract

          Zika virus (ZIKV) infection appeared in Brazil in 2015, causing an epidemic outbreak with increased rates of microcephaly and other serious birth disorders. We reviewed 102 cases of children who were diagnosed with microcephaly at birth and who had gestational exposure to ZIKV during the outbreak. We describe the clinical, neuroimaging, and neurophysiological findings. Most mothers (81%) reported symptoms of ZIKV infection, especially cutaneous rash, during the first trimester of pregnancy. The microcephaly was severe in 54.9% of the cases. All infants presented with brain malformations. The most frequent neuroimaging findings were cerebral atrophy (92.1%), ventriculomegaly (92.1%), malformation of cortical development (85.1%), and cortical–subcortical calcifications (80.2%). Abnormalities in neurological exams were found in 97.0% of the cases, epileptogenic activity in 56.3%, and arthrogryposis in 10.8% of the infants. The sensorineural screening suggested hearing loss in 17.3% and visual impairment in 14.1% of the infants. This group of infants who presented with microcephaly and whose mothers were exposed to ZIKV early during pregnancy showed clinical and radiological criteria for congenital ZIKV infection. A high frequency of brain abnormalities and signs of early neurological disorders were found, and epileptogenic activity and signs of sensorineural alterations were common. This suggests that microcephaly can be associated with a worst spectrum of neurological manifestations.

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          A report: the definition and classification of cerebral palsy April 2006.

          For a variety of reasons, the definition and the classification of cerebral palsy (CP) need to be reconsidered. Modern brain imaging techniques have shed new light on the nature of the underlying brain injury and studies on the neurobiology of and pathology associated with brain development have further explored etiologic mechanisms. It is now recognized that assessing the extent of activity restriction is part of CP evaluation and that people without activity restriction should not be included in the CP rubric. Also, previous definitions have not given sufficient prominence to the non-motor neurodevelopmental disabilities of performance and behaviour that commonly accompany CP, nor to the progression of musculoskeletal difficulties that often occurs with advancing age. In order to explore this information, pertinent material was reviewed on July 11-13, 2004 at an international workshop in Bethesda, MD (USA) organized by an Executive Committee and participated in by selected leaders in the preclinical and clinical sciences. At the workshop, it was agreed that the concept 'cerebral palsy' should be retained. Suggestions were made about the content of a revised definition and classification of CP that would meet the needs of clinicians, investigators, health officials, families and the public and would provide a common language for improved communication. Panels organized by the Executive Committee used this information and additional comments from the international community to generate a report on the Definition and Classification of Cerebral Palsy, April 2006. The Executive Committee presents this report with the intent of providing a common conceptualization of CP for use by a broad international audience.
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            The Zika Virus Epidemic in Brazil: From Discovery to Future Implications

            The first confirmed case of Zika virus infection in the Americas was reported in Northeast Brazil in May 2015, although phylogenetic studies indicate virus introduction as early as 2013. Zika rapidly spread across Brazil and to more than 50 other countries and territories on the American continent. The Aedes aegypti mosquito is thought to be the principal vector responsible for the widespread transmission of the virus. However, sexual transmission has also been reported. The explosively emerging epidemic has had diverse impacts on population health, coinciding with cases of Guillain–Barré Syndrome and an unexpected epidemic of newborns with microcephaly and other neurological impairments. This led to Brazil declaring a national public health emergency in November 2015, followed by a similar decision by the World Health Organization three months later. While dengue virus serotypes took several decades to spread across Brazil, the Zika virus epidemic diffused within months, extending beyond the area of permanent dengue transmission, which is bound by a climatic barrier in the south and low population density areas in the north. This rapid spread was probably due to a combination of factors, including a massive susceptible population, climatic conditions conducive for the mosquito vector, alternative non-vector transmission, and a highly mobile population. The epidemic has since subsided, but many unanswered questions remain. In this article, we provide an overview of the discovery of Zika virus in Brazil, including its emergence and spread, epidemiological surveillance, vector and non-vector transmission routes, clinical complications, and socio-economic impacts. We discuss gaps in the knowledge and the challenges ahead to anticipate, prevent, and control emerging and re-emerging epidemics of arboviruses in Brazil and worldwide.
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              Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

              Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem.
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                Author and article information

                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                23 January 2019
                February 2019
                : 16
                : 3
                : 309
                Affiliations
                [1 ]Post-graduate Programme in Health Sciences, Federal University of Bahia School of Medicine, Praça XV de Novembro—Largo do Terreiro de Jesus, 40025-010 Bahia, Brazil; nascimentocarvalho@ 123456hotmail.com
                [2 ]Pediatric Rehabilitation Centre, Salvador Hospital, SARAH Network of Rehabilitation Hospitals, Avenida Tancredo Neves, Caminho das Árvores, Salvador, 41820-900 Bahia, Brazil; 13110@ 123456sarah.br (A.L.d.C.); 701064@ 123456sarah.br (P.A.V.); 11786@ 123456sarah.br (T.B.T.); 400868@ 123456sarah.br (A.S.F.); 701053@ 123456sarah.br (S.F.P.)
                [3 ]Diagnostic Imaging Department, Salvador Hospital, SARAH Network of Rehabilitation Hospital, Avenida Tancredo Neves, Caminho das ÁrvoresSalvador, 41820-900 Bahia, Brazil; 700991@ 123456sarah.br
                [4 ]Bahiana School of Medicine, Bahiana Foundation for Science Development, Dom João VI, Salvador, 40290-000 Bahia, Brazil; ccclr1@ 123456gmail.com (C.L.R.)
                [5 ]Departament of Paediatrics, Federal University of Bahia School of Medicine, Praça XV de Novembro—Largo do Terreiro de Jesus, 40025-010 Bahia, Brazil
                Author notes
                [* ]Correspondence: marylulage@ 123456hotmail.com ; Tel.: +55-217-198-424-0808
                Author information
                https://orcid.org/0000-0001-5571-8640
                Article
                ijerph-16-00309
                10.3390/ijerph16030309
                6388186
                30678125
                ae70218d-e1f8-4503-83d3-802a0eef0f77
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 November 2018
                : 21 January 2019
                Categories
                Article

                Public health
                zika virus,microcephaly,neuroimaging,neurologic examination
                Public health
                zika virus, microcephaly, neuroimaging, neurologic examination

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