Epilepsy in children with Congenital Zika Syndrome: A systematic review and meta‐analysis

Abstract

Objectives: To estimate the overall frequency of epilepsy in children with congenital Zika syndrome (CZS) and describe the profile of seizures and the response rate to anti-epileptic treatment in this group of patients. Methods: A systematic review and meta-analysis were conducted following the Cochrane Handbook and preferred reporting items for systematic reviews and metaanalyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Cochrane Library, SciELO, and LILACS were searched until June 23, 2020. Observational studies that evaluated the frequency of epilepsy in children diagnosed with CZS according to international criteria were included in the study. Results: Fourteen studies evaluating 903 patients diagnosed with CZS were pooled in a meta-analysis. All studies were conducted in Brazil, with reports published between 2016 and 2020, and included children diagnosed with CSZ from 0 to 40 months of age. The overall rate of epilepsy in children diagnosed with CZS was estimated at 60% (95% confidence interval [CI] 0.51-0.68). The studies included in this review show that the frequency of epilepsy in patients with CSZ varies with age, with higher rates in older children. Epileptic spasms was the primary type of seizure observed in this group, followed by focal and generalized crisis. The response rate to antiepileptic drugs was considerably low, ranging from 20% of seizure control in the first year and 30% in the second year. Significance: Children with CZS presented a high cumulative incidence of epilepsy episodes with increased severity and a low response to anti-epileptic therapy, which is associated with the extensive damage caused by the Zika virus on the cortical structures of patients. K E Y W O R D Santi-epileptic agents, congenital infection, cortical malformations, seizures, Zika virus (ZIKV) | METHODSA systematic review and meta-analysis were conducted following the Cochrane Handbook guidelines. 23 The searching, selection, extraction, and analysis of the data of interest were performed according to the Preferred Reporting Items Key points• The overall rate of epilepsy in children diagnosed with congenital Zika syndrome (CZS) was estimated at 60% (95% confidence interval [CI] 0.51-0.68) • The rate of epilepsy in children with CZS is considerably higher than that observed in congenital infections with syphilis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex (STORCH) pathogens • Epileptic spasms were the primary type of seizure observed in this group, followed by focal and generalized crisis • The response rate to anti-epileptic drugs was considerably low (20% of seizure control in the first year and 30% in the second year)

Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects

“…Abnormal background (100%) and focal epileptiform activity (54%) were the most frequent findings after the first year of life in children with CZS (Maia et al, 2021). In a series of 55 children, a pattern of continuous or almost continuous epileptiform discharges during sleep was seen in The response to anti-epileptic drugs is generally low, ranging from only 20% seizure control in the first year to 30% seizure control in the second year (Maia et al, 2021).…”

“…Although identified less often, hypsarrhythmia (11%) and burst suppression (8%) patterns were associated with a higher risk of drug resistance ( van der Linden et al, 2018 ). Abnormal background (100%) and focal epileptiform activity (54%) were the most frequent findings after the first year of life in children with CZS ( Maia et al, 2021 ). In a series of 55 children, a pattern of continuous or almost continuous epileptiform discharges during sleep was seen in 40% of the cases, and it was correlated with the presence of subcortical calcifications and multifocal epileptiform discharges from the previous EEG showing ( van der Linden et al, 2020b ).…”

“…In a series of 55 children, a pattern of continuous or almost continuous epileptiform discharges during sleep was seen in 40% of the cases, and it was correlated with the presence of subcortical calcifications and multifocal epileptiform discharges from the previous EEG showing ( van der Linden et al, 2020b ). The response to anti-epileptic drugs is generally low, ranging from only 20% seizure control in the first year to 30% seizure control in the second year ( Maia et al, 2021 ).…”

Congenital Zika Syndrome: Genetic Avenues for Diagnosis and Therapy, Possible Management and Long-Term Outcomes

“…In children with minor morphological damage, the main neurological problems are infantile cerebral palsy, epilepsy (the extensive damage caused by the Zika virus on the cortical structures of patients can lead to higher cumulative incidence of epilepsy episodes of higher severity, in addition to a worse response to anti-epileptic treatment [ 59 ]) and neurodevelopmental repercussions [ 60 , 61 ]. Wheeler et al, in a 30-months follow-up study of 121 children affected by congenital ZIKV infection, reported global developmental delay in almost all specific domains (in particular, cognition, fine motor skills and expressive language).…”

Perinatal characteristics and longer-term outcomes in Brazilian children with confirmed or suspected congenital Zika infection: ZIKAction Paediatric Registry

“…Children exposed in utero to ZIKV can be seriously affected, with neurological abnormalities including microcephaly, hydrocephalus, extrapyramidal movements, hemiparesis, hyperexcitability, hyperirritability, and epilepsy. 3,6,7 Microcephaly, the most prominent feature of CZS, occurs in some fetuses but not others, with some studies describing infants with definite or probable CZS who presented with normal head circumference (HC) at birth. 3,4 Reduced fetal movement subsequent to ZIKV-related brain damage can result in arthrogryposis and other congenital contractures.…”