Seizures as a Complication of Congenital Zika Syndrome in Early Infancy

Abstract

transmission in Brazil was linked to a large outbreak of microcephaly but less is known about longer term anthropometric and neurological outcomes. We studied a cohort of infants born between October 31, 2015, and January 9, 2016, in a state maternity hospital, followed up for 101 ± 28 days by home visits. Microcephaly (< 2 standard deviations, Intergrowth standard) occurred in 62 of 412 (15%) births. Congenital Zika syndrome (CZS) was diagnosed in 29 patients. Among CZS patients, we observed a significant gain in anthropometric measures ( < 0.001) but no significant gain in percentile for these measures. The main neurological outcome was epilepsy, occurring in 48% of infants at a rate of 15.6 cases per 100 patient-months, frequently requiring multiple anti-seizure medications. The cumulative fatality rate was 7.4% (95% confidence interval: 2.1-23.4%). Health-care professionals should be alerted on the high risk of epilepsy and death associated with CZS in early infancy and the need to actively screen for seizures and initiate timely treatment.

Early epilepsy in children with Zika‐related microcephaly in a cohort in Recife, Brazil: Characteristics, electroencephalographic findings, and treatment response

“…With regard to the age groups, we hypothesized that a significant proportion of participants would present with early seizures in the first 2 months of life and develop an epileptic encephalopathy in the neonatal period, because lissencephaly, a common finding in these affected infants, is known to be an important cause of Ohtahara syndrome . Nevertheless, we did not observe any record of this syndrome in this ZIKV‐affected cohort, a finding consistent with previous studies . The largest proportion of epileptic seizures occurred between the third and ninth months of life, with incidence remaining high until the 15th month and very few new cases after this age.…”

“…At the end of 24 months, nearly three‐quarters of the monitored children had epileptic seizures, an incidence similar to that described in other studies of children with extensive lissencephaly . Other recent studies of microcephaly cases associated with congenital ZIKV infections have reported either similar or lower rates . Two factors may underlie the difference in rates.…”

“…11,28 Other recent studies of microcephaly cases associated with congenital ZIKV infections have reported either similar 15 or lower rates. 12,13,15,16 Two factors may underlie the difference in rates. The first is the age range assessed.…”

“…Of clinical significance, lissencephaly is considered to be a major contributor to pediatric epilepsy cases for which there is an early onset of seizures that are difficult to control with the use of antiseizure medications . As lissencephaly has been a common finding among the neuroimaging of patients with CZS, it is hypothesized that there may be an increased risk for the occurrence of early epilepsy in children with Zika‐related microcephaly, as suggested in the initial cases series . Using data collected from a cohort of children born with microcephaly during the 2015‐2016 ZIKV epidemic in northeast Brazil, this study aims to (1) estimate the incidence of epilepsy during the first 24 months of life, (2) characterize the associated clinical manifestations and electrographic findings, and (3) summarize the treatment responses.…”

Zika virus and the nonmicrocephalic fetus: why we should still worry

“…(43–47) While this particular type of brain injury could not be detected even with prenatal MRI, it would be expected to correlate with the reported early onset of seizures/epilepsy in human infants, perturbations to later learning and memory development, and potentially even later onset depression and age-related cognitive decline. (48–50) A recent study in infant nonhuman primates also correlated ZIKV infection with hippocampal growth arrest, dysfunctional connectivity by functional MRI, and abnormal socioemotional processing. (51) Longitudinal studies are needed to understand the implications of ZIKV-associated injury to neurogenic cells in the fetus or young children and whether this injury might result in a predisposition to learning disorders, developmental delay or mental illness in childhood and adolescence.…”