RESUMO
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 meta-analyses (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 anti-epileptic 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.
Assuntos
Epilepsia/epidemiologia , Epilepsia/virologia , Infecção por Zika virus/congênito , Infecção por Zika virus/complicações , Criança , Humanos , IncidênciaRESUMO
The chronic dysfunction of neuronal cells, both central and peripheral, a characteristic of neurological disorders, may be caused by irreversible damage and cell death. In 2016, more than 276 million cases of neurological disorders were reported worldwide. Moreover, neurological disorders are the second leading cause of death. Generally, the etiology of neurological diseases is not fully understood. Recent studies have related the onset of neurological disorders to viral infections, which may cause neurological symptoms or lead to immune responses that trigger these pathological signs. Currently, this relationship is mostly based on epidemiological data on infections and seroprevalence of patients who present with neurological disorders. The number of studies aiming to elucidate the mechanism of action by which viral infections may directly or indirectly contribute to the development of neurological disorders has been increasing over the years but these studies are still scarce. Comprehending the pathogenesis of these diseases and exploring novel theories may favor the development of new strategies for diagnosis and therapy in the future. Therefore, the objective of the present study was to review the main pieces of evidence for the relationship between viral infection and neurological disorders such as Alzheimer's disease, Parkinson's disease, Guillain-Barré syndrome, multiple sclerosis, and epilepsy. Viruses belonging to the families Herpesviridae, Orthomyxoviridae, Flaviviridae, and Retroviridae have been reported to be involved in one or more of these conditions. Also, neurological symptoms and the future impact of infection with SARS-CoV-2, a member of the family Coronaviridae that is responsible for the COVID-19 pandemic that started in late 2019, are reported and discussed.
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COVID-19/patologia , Doenças do Sistema Nervoso/virologia , Tropismo Viral/fisiologia , Doença de Alzheimer/virologia , COVID-19/virologia , Epilepsia/virologia , Flaviviridae/metabolismo , Síndrome de Guillain-Barré/virologia , Herpesviridae/metabolismo , Humanos , Esclerose Múltipla/virologia , Doenças do Sistema Nervoso/patologia , Orthomyxoviridae/metabolismo , Doença de Parkinson/virologia , Retroviridae/metabolismo , SARS-CoV-2/metabolismoRESUMO
PURPOSE: Our objective is to describe the most prevalent electroencephalographic findings in COVID-19 hospitalized patients, and to determine possible predictors of mortality including EEG and clinical variables. METHODS: A multicentric prospective observational study in patients with COVID-19 requiring EEG during hospitalization. RESULTS: We found 94 EEG from 62 patients (55 % men, mean age 59.7 ± 17.8 years) were analyzed. Most frequent comorbidity was cardiac (52 %), followed by metabolic (45 %) and CNS disease (39 %). Patients required ICU management by 60 %, with a mortality of 27 % in the whole cohort. The most frequent EEG finding was generalized continuous slow-wave activity (66 %). Epileptic activity was observed in 19 % including non-convulsive status epilepticus, seizures and interictal epileptiform discharges. Periodic patterns were observed in 3 patients (3.2 %). Multivariate analysis found that cancer comorbidity and requiring an EEG during the third week of evolution portended a higher risk of mortality CONCLUSION: We observed that the most prevalent EEG finding in this cohort was generalized continuous slow-wave activity, while epileptic activity was observed in less than 20 % of the cases. Mortality risk factors were comorbidity with cancer and requiring an EEG during the third week of evolution, possibly related to the hyperinflammatory state.
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COVID-19/mortalidade , Eletroencefalografia , SARS-CoV-2/patogenicidade , Convulsões/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Epilepsia/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Prognóstico , Convulsões/virologia , Estado Epiléptico/mortalidade , Estado Epiléptico/fisiopatologia , Estado Epiléptico/virologiaRESUMO
Clinical outcomes related to congenital Zika syndrome (CZS) include microcephaly accompanied by specific brain injuries. Among several CZS outcomes that have been described, epilepsy and motor impairments are present in most cases. Pharmacological treatment for seizures resulting from epilepsy is performed with anticonvulsant drugs, which in the long term are related to impairments in the child's neuropsychomotor development. Here, we describe the results from a two-year follow-up of a cohort of children diagnosed with CZS related to the growth of the head circumference and some neurological and motor outcomes, including the pharmacological approach, and its results in the treatment of epileptic seizures. This paper is part of a prospective cohort study carried out in the state of Mato Grosso Sul, Brazil, based on a Zika virus (ZIKV)-exposed child population. Our data were focused on the assessment of head circumference growth and some neurological and motor findings, including the description of seizure conditions and pharmacological management in two periods. Among the 11 children evaluated, 8 had severe microcephaly associated with motor impairment and/or epilepsy. Seven children were diagnosed with epilepsy. Of these, 3 had West syndrome. In four children with other forms of epilepsy, there was no pharmacological control.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Microcefalia/virologia , Espasmos Infantis/tratamento farmacológico , Infecção por Zika virus/patologia , Brasil , Pré-Escolar , Epilepsia/virologia , Feminino , Cabeça/anatomia & histologia , Humanos , Lactente , Recém-Nascido , Microcefalia/patologia , Hipertonia Muscular/virologia , Malformações do Sistema Nervoso/virologia , Paresia/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Reflexo Anormal/fisiologia , Espasmos Infantis/virologia , Zika virus/patogenicidadeRESUMO
Modulation of brain activity is one of the main mechanisms capable of demonstrating the synchronization dynamics of neural oscillations. In epilepsy, modulation is a key concept since seizures essentially result from neural hypersynchronization and hyperexcitability. In this study, we have introduced a time-dependent index based on the Kullback-Leibler divergence to quantify the effects of phase and frequency modulations of neural oscillations in neonatal mice exhibiting epileptiform activity induced by Zika virus (ZIKV) infection. Through this index, we demonstrate that fast oscillations (gamma and beta 2) are the more susceptible modulated rhythms in terms of phase, during seizures, whereas slow waves (delta and theta) mainly undergo changes in frequency. The index also allowed detection of specific patterns associated with the interdependent modulation of phase and frequency in neural activity. Furthermore, by comparing ZIKV modulations with the general computational model Epileptors, we verify different signatures related to the brain rhythms modulation in phase and frequency. These findings instigate new studies on the effects of ZIKV infection on neuronal networks from electrophysiological activities, and how different mechanisms can trigger epilepsy.
Assuntos
Ondas Encefálicas/fisiologia , Epilepsia/fisiopatologia , Neurônios/fisiologia , Infecção por Zika virus/virologia , Animais , Ritmo beta/fisiologia , Encéfalo/patologia , Encéfalo/virologia , Modelos Animais de Doenças , Epilepsia/complicações , Epilepsia/virologia , Ritmo Gama/fisiologia , Humanos , Camundongos , Neurônios/virologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/fisiopatologiaRESUMO
BACKGROUND: Zika virus (ZIKV) is a recently emerged arbovirus, which infection during pregnancy is associated with a series of congenital malformations, collectively denominated Congenital Zika Syndrome (CZS). Following infection, ZIKV RNA has a median duration period of 10 days in plasma and up to 6 months in semen in immunocompetent adult individuals. Moreover, ZIKV is able to replicate and persist in fetal brains and placentas, consequently, infection is associated with pregnancy loss, albeit the pathogenic mechanisms are still unknown. CASE PRESENTATION: Here we report a CZS case of an infant born during the ZIKV outbreak in northeast Brazil, the child presented recurrent episodes of seizures with prolonged presence of ZIKV RNA on the central nervous system (CNS) and blood. ZIKV RNA was identified and partially sequenced from a sample of cerebrospinal fluid (CSF) obtained from the infant with 6 months of life, and later from another sample after the infant completed 17 months of life. Commonly congenital infections were discarded based on STORCH (syphilis, toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus) negative laboratory results. Presence of specific ZIKV antibodies on both mother and children confirmed the association of severe microcephaly and ZIKV infection, diagnosed after birth. CONCLUSIONS: Altogether, our data raise the possibility that CZS cases may result in prolonged viral presence, these findings could be useful for therapy and diagnostic recommendations.
Assuntos
Microcefalia/virologia , Infecção por Zika virus/congênito , Infecção por Zika virus/complicações , Adulto , Brasil , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Microcefalia/patologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , RNA Viral/isolamento & purificação , Índice de Gravidade de Doença , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/patologiaRESUMO
Zika virus 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 (P < 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.
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Surtos de Doenças , Epilepsia/etiologia , Microcefalia/etiologia , Convulsões/etiologia , Infecção por Zika virus/complicações , Zika virus/fisiologia , Brasil/epidemiologia , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/virologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Microcefalia/tratamento farmacológico , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Convulsões/tratamento farmacológico , Convulsões/epidemiologia , Convulsões/virologia , Infecção por Zika virus/congênito , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologiaRESUMO
Initial reports of congenital Zika virus (ZIKV) infection focused on microcephaly at birth with severe brain anomalies; the phenotype has broadened to include microcephaly that develops after birth and neurodevelopmental sequelae. In this narrative review, we summarize medical literature describing motor abnormalities and epilepsy in infants with evidence of congenital ZIKV infection and provide information on the impact of these conditions. Specific scenarios are used to illustrate the complex clinical course in infants with abnormalities that are consistent with congenital Zika syndrome. A search of the English-language medical literature was done to identify motor abnormalities and epilepsy in infants with evidence of congenital ZIKV infection by using Medline and PubMed, Embase, Scientific Electronic Library Online, Scopus, the OpenGrey Repository, and the Grey Literature Report in Public Health. Search terms included "Zika" only and "Zika" in combination with any of the following terms: "epilepsy," "seizure," "motor," and "cerebral palsy." Clinical features of motor abnormalities and epilepsy in these children were reviewed. Thirty-six publications were identified; 8 were selected for further review. Among infants with clinical findings that are consistent with congenital Zika syndrome, 54% had epilepsy and 100% had motor abnormalities. In these infants, impairments that are consistent with diagnoses of cerebral palsy and epilepsy occur frequently. Pyramidal and extrapyramidal motor abnormalities were notable for their early development and co-occurrence. Prompt identification of potential disabilities enables early intervention to improve the quality of life for affected children. Long-term studies of developmental outcomes and interventions in children with congenital ZIKV infection are needed.
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Epilepsia/diagnóstico por imagem , Transtornos Motores/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Infecção por Zika virus/diagnóstico por imagem , Zika virus , Criança , Epilepsia/etiologia , Epilepsia/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/complicações , Microcefalia/diagnóstico por imagem , Microcefalia/virologia , Transtornos Motores/etiologia , Transtornos Motores/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Infecção por Zika virus/complicações , Infecção por Zika virus/virologiaRESUMO
Cerebrospinal fluid (CSF) and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/tropical spastic paraparesis), six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control) from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA). All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG). In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response) were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.
Assuntos
Epilepsia/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Paraparesia Espástica Tropical/líquido cefalorraquidiano , Brasil , Diagnóstico Diferencial , Epilepsia/sangue , Epilepsia/imunologia , Epilepsia/virologia , Anticorpos Anti-HTLV-I/sangue , Anticorpos Anti-HTLV-I/líquido cefalorraquidiano , Humanos , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Esclerose Múltipla/virologia , Paraparesia Espástica Tropical/sangue , Paraparesia Espástica Tropical/imunologia , Paraparesia Espástica Tropical/virologiaRESUMO
Amostras do líquido cefalorraquidiano (LCR) e soro de 17 pacientes brasileiros com HAM/TSP, seis com esclerose múltipla e seis com epilepsia idiopática (controle nao-inflamatório) foram analisadas para a presença de anticorpos para o vírus de sarampo, rubéola, varicela zoster e herpes simples pelo método de ELISA. Todos os casos de HAM/TSP e esclerose múltipla tinham resposta imune poliespecífica intratecal para sarampo e rubéola. Anticorpos específicos para sarampo e rubéola (resposta MRZ) foram observados em todos os pacientes com esclerose múltipla, mas nao nos controles com epilepsia idiopática. A relevância das respostas poliespecífica e monoespecífica é discutida para essas doenças neurológicas crônicas.