Clinical and neurodevelopmental features in children with cerebral palsy and probable congenital Zika

Carvalho, Alessandra; Brites, Carlos; Mochida, Ganeshwaran H.; Ventura, Paloma; Fernandes, Adriana; Lage, Maria Lucia Costa; Taguchi, Tânia; Brandi, Ivar Viana; Silva, Alfredo; Franceschi, Giulia; Lucena, Pedro H.; Lucena, Rita

doi:10.1016/j.braindev.2019.03.005

Cited by 64 publications

(131 citation statements)

References 29 publications

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“…1,2,[23][24][25] Consistent with our ndings, a 2019 Brazilian investigation assessing children with cerebral palsy and probable CZS, of whom 97.5% had microcephaly, using the Bayley Scale of Infant and Toddler Development III (Bayley-III) reported scores below 70 (i.e., suggesting severe developmental delays) for almost all participants across all three scales: cognitive, 95.1%; language, 97.6%; motor, 97.6%. 23 A case series study assessing 24 children with ZIKV-related microcephaly in Northeast Brazil using the Denver Developmental Screening Test II also found a high degree of impairment for neuropsychomotor development. The study reported that children with a mean age of 19.9 months scored, on average, development milestones equivalent of ages 2.1 to 3.4 months, across the domains of language, motor, and personal/social skills.…”

Section: Discussionsupporting

confidence: 83%

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Silva

Eickmann

Ximenes

et al. 2020

Preprint

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Background: The implications of congenital Zika Virus (ZIKV) infections for pediatric neurodevelopment and behavior remain inadequately studied. The aim of this study is to investigate patterns of neurodevelopment and behavior in groups of children with differening severities of ZIKV-related microcephaly and children with prenatal ZIKV exposure in the absence of microcephaly.Methods: We conducted a cross-sectional study, nested in a cohort, of 274 children (aged 10-45 months) who were born during the peak and decline of the microcephaly epidemic in Northeast Brazil. Participants were evaluated between February 2017 and August 2019 at two tertiary care hospitals in Recife, Pernambuco, Brazil. We analyzed the children in four groups assigned based on clinical and laboratory criteria: Group 1 had severe microcephaly; Group 2 had moderate microcephaly; Group 3 had prenatal ZIKVexposure confirmed by maternal RT-PCR testing but no microcephaly; and Group 4 was a neurotypical control group. Groups were evaluated clinically for neurological abnormalities and compared using the Survey of Wellbeing of Young Children (SWYC), a neurodevelopment and behavior screening instrument validated for use in Brazil. Children with severe delays underwent further evaluation with an adapted version of the SWYC.Results: Based on the SWYC screening, we observed differences between the groups for developmental milestones but not behavior. Among the 114 children with severe microcephaly of whom 98.2% presented with neurological abnormalities, 99.1% were ‘at risk of development delay’ according to the SWYC instrument. Among the 20 children with moderate microcephaly of whom 60% presented with neurological abnormalities, 65% were ‘at risk of development delay’. For children without microcephaly, the percentages found to be ‘at risk of developmental delay’ were markedly lower and did not differ by prenatal ZIKV exposure status: Group 3 (N=94), 13.8%; Group 4 (N=46), 21.7%.Conclusions: Among children with prenatal ZIKV exposure, we found a gradient of risk of development delay according to head circumference. Children with severe microcephaly were at highest risk for delays, while normocephalic ZIKV-exposed children had similar risks to unexposed control children. We propose that ZIKV-exposed children should undergo first-line screening for neurodevelopment and behavior using the SWYC instrument. Early assessment and follow-up will enable at-risk children to be referred to a more comprehensive developmental evaluation and to multidisciplinary care management.

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Section: Discussionsupporting

confidence: 83%

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Silva

Eickmann

Ximenes

et al. 2020

Preprint

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“…putamen and caudate) on MRI, as well as calcification on neuropathology. Calcification in subcortical areas have been reported in several studies of confirmed and suspected congenital Zika syndrome cases in humans 21,44,70 . These findings as well as the smaller cerebellum GM volumes may explain the increased incidents of balance loss seen amongst the ZIKV-infected infant RMs during their exploration of a novel social environment.…”

Section: Discussionmentioning

confidence: 88%

“…Infants born with this syndrome can develop seizures, hearing and vision problems, feeding difficulties, and gross motor abnormalities 17 . Importantly, recent reports have documented the postnatal onset of microcephaly, neurologic dysfunction, and neurodevelopmental abnormalities in infants infected prenatally but without overt symptoms at birth [18][19][20][21][22] , highlighting the potential of ZIKV to cause ongoing damage in the postnatal period.…”

Section: Mainmentioning

confidence: 99%

Long-term alterations in brain and behavior after postnatal Zika virus infections in infant macaques

Raper

Kovacs-Balint

Mavinger

et al. 2019

Preprint

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Considering the impact that Zika virus (ZIKV) infection has on the fetal nervous system and given that the postnatal period is also a time of rapid brain growth, it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Using a rhesus macaque (RM) model, we showed that postnatal ZIKV infection resulted in long-term behavioral changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant RMs had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior and cognitive function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection of infants in this model has long lasting neurodevelopmental consequences.

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“…Some extrinsic causes in CNS‐linked AMC have been identified, especially congenital infections. Today the most frequent viral infection causing AMC and CNS anomalies is maternal Zika virus infection during pregnancy (C Lage et al, ; Carvalho et al, ). Up to 30% of all newborns present with AMC, with bilateral or unilateral hip, knee, hand and/or feet involvement.…”

Section: Clinical Syndromes and Geneticsmentioning

confidence: 99%

Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes, diagnosis, and care

Dieterich

Kimber

Hall

2019

American J of Med Genetics Pt C

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Arthrogryposis or AMC, arthrogryposis multiplex congenita, is defined as multiple congenital joint contractures in more than two joints and in different body areas. The common cause of all AMC is lack of movement in utero, which in turn can have different causes, one of which is CNS involvement. Intellectual disability/CNS involvement is found in approximately 25% of all AMC. AMC with CNS involvement includes a large number of genetic syndromes. So far, more than 400 genes have been identified as linked to AMC, with and without CNS involvement. A number of neonatally lethal syndromes and syndromes resulting in severe disability due to CNS malfunction belong to this group of syndromes. There are several X-linked disorders with AMC, which are primarily related to intellectual disability. A number of neuromuscular disorders may include AMC and CNS/brain involvement. Careful clinical evaluation by a geneticist and a pediatrician/pediatric neurologist is the first step in making a specific diagnosis.Further investigations may include MRI of the brain and spinal cord, electroencephalogram, blood chemistry for muscle enzymes, other organ investigations (ophtalmology, cardiology, gastrointestinal, and genitourinary systems). Nerve conduction studies, electromyogram, and muscle pathology may be of help when there is associated peripheral nervous system involvement. But most importantly, genetic investigations with targeted or rather whole exome or genome sequencing should be performed. A correct diagnosis is important in planning adequate treatment, in genetic counselling and also for future understanding of pathogenic mechanisms and possible new treatments.A multidiciplinary team is needed both in investigation and treatment. K E Y W O R D Sarthrogryposis multiplex congenita, neonatally lethal AMC syndromes, central nervous system involvement, multi-organ involvement, intellectual disability

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Clinical and neurodevelopmental features in children with cerebral palsy and probable congenital Zika

Cited by 64 publications

References 29 publications

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Pediatric neurodevelopment by prenatal Zika virus exposure: A cross-sectional study of the Microcephaly Epidemic Research Group Cohort

Long-term alterations in brain and behavior after postnatal Zika virus infections in infant macaques

Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes, diagnosis, and care

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