Abstracts

Rationale: Epilepsy is a major clinical concern in children with prenatal Zika virus (ZIKV) exposure. The teratogenicity of ZIKV is well established; ZIKV is able to cross the placental barrier, disseminate to the fetus, and target cortical progenitors, potentially leading to malformations of cortical development (MCD). ZIKV-associated MCDs can be severe and visually obvious, such as microcephaly, but also focal and radiographically occult. Epilepsy is detected in 48% to 96% of Zika-exposed children (ZEC) with microcephaly [1]. Epilepsy rates in normocephalic ZEC are unknown, despite evidence for ZIKV-associated structural brain damage in the absence of microcephaly [2]. This project involved epilepsy surveillance in a cohort of children born during the 2016-2017 ZIKV outbreak in Grenada, West Indies. We aimed to compare the epilepsy incidence rate in our cohort to the global epilepsy incidence rate in the first year of life (approximately 0.1%) [3]. Methods: Mothers were recruited from public health centers across Grenada during and immediately following the ZIKV outbreak (April 2016 to March 2017). 384 mothers consented to participate and had serum tested for prior flavivirus exposure with immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). The children of 206 mothers (208 children, two twin births) were assessed for general health, serum flavivirus status, neurodevelopmental outcomes, anthropometry, and epilepsy at one year of age. Epilepsy surveillance consisted of a pediatric epilepsy screening questionnaire [4] and electroencephalography (EEG). EEG was measured in a non-specialized clinical facility using a multi-channel, wireless microEEG® system, with a standard 10-20 electrode configuration for a minimum of 20 minutes along with a video recording of participant behavior time-locked to the EEG recording. EEGs were interpreted independently by at least two board certified epileptologists via a remote telemedicine platform. Clinical diagnosis of epilepsy was based on ILAE criteria [5]. Results: Maternal serum testing revealed that 99% had prior flavivirus exposure. Child assessments revealed four cases of epilepsy (1.9%; CI: 0.6% to 5.2%) with seizure onset in the first year of life. Of these, one child was microcephalic, one child had an enlarged cranium with MRI evidence for lobar holoprosencephaly, and two children were normocephalic. Three of the four children with epilepsy had an EEG that was interpreted as abnormal with focal epileptiform discharges in two cases and diffuse moderate slowing in the third. Focal epileptiform discharges were independently observed on EEG in one additional normocephalic child although there was no parental report of seizures. Conclusions: The epilepsy incidence rate of 1.9% observed in our cohort in the first year of life is higher than global incidence rates. This suggests that the risk of developing epilepsy may be increased in children with prenatal flavivirus exposure; however, study limitations warrant caution. The maternal serum assays we utilized are sensitive to prior ZIKV and dengue virus infection, which are both endemic to the region, and the child’s virologic status is not yet confirmed. To overcome these limitations, we plan to probe maternal and child serum using a multiplexed assay on a plasmonic-gold platform for measuring IgG antibodies, which enables specific diagnosis of ZIKV infection over other flaviviral infections [6].1. Oliveira-Filho J et al. Am J Trop Med Hyg. 2018; 98(6):1860-622. Adams Waldorf KM et al. Nat Med 2018; 24(3):368-3743. Camfield P, Camfield C. Epileptic Disord 2015; 17(2):117-1234. Fisher RS et al. Epilepsia 2014; 55:475-825. Patel AA, et al. Epilepsy Behav 2016; 59:57-616. Zhang B et al. Nat Med 2017; 23(5):548-50 Funding: Research supported by: USAID AID-OAA-A-14-00028 (KB, RW, BL, ADL); NIH R21HD093551-01 (KB, RW, BL); Stanford Child Health Research Institute (ADL)