Journal http://jcn.sagepub.com/ of Child Neurology
Relationship Between Common Viral Upper Respiratory Tract Infections and Febrile Seizures in Children From Suzhou, China Jihong Tang, Wenhua Yan, Yan Li, Bingbing Zhang and Qing Gu J Child Neurol published online 21 January 2014 DOI: 10.1177/0883073813515074 The online version of this article can be found at: http://jcn.sagepub.com/content/early/2014/01/20/0883073813515074 A more recent version of this article was published on - Sep 20, 2014
Published by: http://www.sagepublications.com
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Original Article
Relationship Between Common Viral Upper Respiratory Tract Infections and Febrile Seizures in Children From Suzhou, China
Journal of Child Neurology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813515074 jcn.sagepub.com
Jihong Tang, MD1, Wenhua Yan, MS2, Yan Li, BS1, Bingbing Zhang, MS1, and Qing Gu, MS1
Abstract This study aimed to determine the potential predisposing factors for the development of febrile seizures among children with upper respiratory tract infection in the eastern Chinese region. Participants were individuals aged 6 months and 6 years (n ¼ 189) who were diagnosed with febrile seizure, complicated with upper respiratory tract infection, and 174 age-matched children who had upper respiratory tract infection without seizures as controls. The viral antigens including influenza A and B, parainfluenza, adenovirus, and respiratory syncytial virus were detected from nasopharyngeal aspirates. The incidence of influenza A infection was much higher in patients with febrile seizure than controls, especially those children aged >36 months. Patients with influenza A infection had higher body temperatures at seizure occurrence, shorter seizure duration, and shorter fever duration before seizure onset. Influenza A infections are frequently associated with febrile seizure in children with upper respiratory tract infection. During an influenza epidemic, effective vaccination of children, especially those with a past history of febrile seizure, may minimize the development of febrile seizure. Keywords children, common respiratory viruses, febrile seizures, upper respiratory tract infections Received September 16, 2013. Received revised October 14, 2013. Accepted for publication November 04, 2013.
Febrile seizure is the most common type of seizures in children between 6 months and 6 years of age.1,2 Most are benign with little evidence of any adverse effects on brain development. However, febrile seizure in children is a traumatic and frightening experience for their parents. The risk of epilepsy after febrile seizure is 4 to 5 times higher than that in the general population.3 The pathogenesis of febrile seizure remains poorly understood. A multifactorial model including genetic factors, fever component, and neurotropic viruses are all thought to be involved in the etiology.4 Viral infections have been implicated as a cause of febrile seizure.2 Primary human herpesvirus 6 infection acquired mainly during the first 2 years of life is often associated with febrile seizure.5 Influenza virus, enterovirus, and adenovirus are the other viruses associated with febrile seizure.6 Febrile seizure is regarded as a complication of influenza A infection. Chiu et al2 had shown that the risk of developing febrile seizure following influenza A infection was higher compared with other respiratory viruses. A comparison of the relative risk of developing febrile seizure with 5 common viral infections and their subsequent risk of recurrence was reported by Chung et al.7 The risk of developing febrile seizure was found to be similar with influenza, adenovirus, or parainfluenza, though
it was higher than respiratory syncytial virus or rotavirus.7 The relationship between upper respiratory tract infections with common respiratory viruses and febrile seizure in children is seldom reported. Clinical presentations and epidemiologic characteristics of viral upper respiratory tract infection can vary among different populations, seasons, and regions. Suzhou, located in the temperate southeast of China, has a subtropical maritime monsoon climate with a high prevalence of respiratory infections during the winter and spring seasons. This study aimed to examine the role of common respiratory viruses associated with febrile seizure in children with upper respiratory tract infections from the Suzhou area and identify the
1
Department of Neurology, Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China 2 Department of Respiratory Medicine, Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China Corresponding Author: Yan Li, BS, Department of Neurology, Children’s Hospital Affiliated to Soochow University, Suzhou 215003, China. Email: [email protected]
Downloaded from jcn.sagepub.com at UNIV OF UTAH SALT LAKE CITY on November 28, 2014
2
Journal of Child Neurology
predisposing factors and special characteristics of febrile seizure in children with viral infections.
Methods Study Design and Settings This prospective study was conducted between June 2010 and June 2011 at the Department of Neurology, Children’s Hospital Affiliated to Soochow University, Suzhou, China.
Subjects and Selection Criteria Children who were diagnosed with febrile seizure, complicated with upper respiratory tract infection, and aged between 6 months and 6 years (n ¼ 189) were enrolled in this study. Febrile seizure was defined according to diagnostic standards8,9 and classified into simple and complex. The following clinical features were considered as simple febrile seizure: (1) sudden occurrence of seizure with generalized tonic-clonic, tonic, or clonic components; (2) seizure duration of less than 15 minutes; and (3) no recurrence of seizure within 24 hours. The following clinical features that exhibited atypical symptoms were considered as complex febrile seizure: (1) partial seizures, (2) seizures lasting for more than 15 minutes, and (3) multiple seizures within a short period (seizures more than 2 times in 1 febrile period). Patients who had central nervous system infection, acute electrolyte imbalance, metabolic disorder, afebrile seizure, and infection other than upper respiratory tract infection such as bronchiolitis, pneumonia, bronchitis, asthma exacerbation, acute gastroenteritis, exanthema subitum, or erysipelas were excluded from the study. The diagnosis of upper respiratory tract infection was based on the definitions in Practical Pediatrics by Zhu Futang (seventh edition).10 At the same time, children who were febrile without seizures, complicated with upper respiratory tract infection, and aged between 6 months and 6 years (n ¼ 174) were selected as the control group.
Sample Collection and Testing Nasal aspirate samples (2 mL each) were obtained from each patient within 24 hours of inpatient admission by introducing a sterile disposable catheter into the lower part of the pharynx through the nasal cavity. The samples were then centrifuged and stored at –80 C until tested for the detection of 7 common respiratory viruses such as respiratory syncytial virus; adenovirus; influenza viruses A and B; and parainfluenza viruses 1, 2, and 3 using a direct immunofluorescence assay as described in earlier reports.11-13 Antigen detection was carried out using a Light Diagnostics Respiratory Panel I Viral Screening and Identification Kit (Chemicon International Inc, Temecula, CA) according to the manufacturer’s instructions. Slides were examined by fluorescence microscopy (Leica 020-518.500, Germany). Blood samples (4 mL each) were also obtained to determine the following: leukocyte count; C-reactive protein; bacterial culture; and serological tests for hepatitis viruses, mycoplasma, chlamydia, and salmonella. Mycoplasma pneumoniae and Chlamydia pneumoniae were detected and quantified with enzyme-linked immunosorbent assay. Stool enzyme immunoassays (for rotavirus) and urine culture were performed whenever there was clinical suspicion of gastroenteritis and urinary tract infection, respectively. Human herpesvirus-6 serology and polymerase chain reaction were not routinely performed in the microbiology laboratory, and a diagnosis of roseola infantum was based on clinical findings.
Clinical Data Collection During inpatient admission to the department, the medical history and physical examination details of the children were recorded systematically by 2 physicians. The following clinical data were obtained for each patient from their hospital records: (1) patient demographics such as age on admission and gender; (2) history of febrile seizure and other nervous system diseases; (3) birth information such as birth order, parity, full term or premature, delivery pattern, and birth weight; (4) history of seizures in first-degree relatives; (5) seizures characteristics such as duration from pyrexia to seizures, body temperature at febrile seizure, maximum body temperature during a febrile episode (fever peak), seizure duration, frequency, and febrile seizure manifestations; (6) auxiliary examination characteristics such as cranial computed tomography (CT) or magnetic resonance imaging (MRI) scan on the first day of admission to exclude the presence of intracranial spaceoccupying lesions, encephalomalacia, or cerebrovascular disease; and (7) electroencephalogram in all patients on the next day to exclude the presence of epileptic discharges. Additionally, the data of cerebrospinal fluid examination of 27 children with complex febrile seizure and 2 control patients, who were suspected of infections in the central nervous system, were also recorded.
Statistical Analysis Statistical analyses were performed using SPSS version 10.0 software (SPSS, Inc, Chicago, IL). Data of normal distribution were expressed as mean + SD and analyzed using t test. Data other than normal distribution were expressed as median (and interquartile ranges, 25%, 75%) and analyzed using rank sum tests. An unpaired t test was used to compare the mean of the age, maximum temperature, and temperature at the time of seizures of children with febrile seizure infected with different respiratory viruses. Grouped data and rate comparison were conducted using w2 test. A value of P 36 months (older patients) and 132 were aged
Relationship Between Common Viral Upper Respiratory Tract Infections and Febrile Seizures in Children From Suzhou, China Jihong Tang, Wenhua Yan, Yan Li, Bingbing Zhang and Qing Gu J Child Neurol published online 21 January 2014 DOI: 10.1177/0883073813515074 The online version of this article can be found at: http://jcn.sagepub.com/content/early/2014/01/20/0883073813515074 A more recent version of this article was published on - Sep 20, 2014
Published by: http://www.sagepublications.com
Additional services and information for Journal of Child Neurology can be found at: Email Alerts: http://jcn.sagepub.com/cgi/alerts Subscriptions: http://jcn.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
Version of Record - Sep 20, 2014 >> OnlineFirst Version of Record - Jan 21, 2014 What is This?
Downloaded from jcn.sagepub.com at UNIV OF UTAH SALT LAKE CITY on November 28, 2014
Original Article
Relationship Between Common Viral Upper Respiratory Tract Infections and Febrile Seizures in Children From Suzhou, China
Journal of Child Neurology 1-6 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073813515074 jcn.sagepub.com
Jihong Tang, MD1, Wenhua Yan, MS2, Yan Li, BS1, Bingbing Zhang, MS1, and Qing Gu, MS1
Abstract This study aimed to determine the potential predisposing factors for the development of febrile seizures among children with upper respiratory tract infection in the eastern Chinese region. Participants were individuals aged 6 months and 6 years (n ¼ 189) who were diagnosed with febrile seizure, complicated with upper respiratory tract infection, and 174 age-matched children who had upper respiratory tract infection without seizures as controls. The viral antigens including influenza A and B, parainfluenza, adenovirus, and respiratory syncytial virus were detected from nasopharyngeal aspirates. The incidence of influenza A infection was much higher in patients with febrile seizure than controls, especially those children aged >36 months. Patients with influenza A infection had higher body temperatures at seizure occurrence, shorter seizure duration, and shorter fever duration before seizure onset. Influenza A infections are frequently associated with febrile seizure in children with upper respiratory tract infection. During an influenza epidemic, effective vaccination of children, especially those with a past history of febrile seizure, may minimize the development of febrile seizure. Keywords children, common respiratory viruses, febrile seizures, upper respiratory tract infections Received September 16, 2013. Received revised October 14, 2013. Accepted for publication November 04, 2013.
Febrile seizure is the most common type of seizures in children between 6 months and 6 years of age.1,2 Most are benign with little evidence of any adverse effects on brain development. However, febrile seizure in children is a traumatic and frightening experience for their parents. The risk of epilepsy after febrile seizure is 4 to 5 times higher than that in the general population.3 The pathogenesis of febrile seizure remains poorly understood. A multifactorial model including genetic factors, fever component, and neurotropic viruses are all thought to be involved in the etiology.4 Viral infections have been implicated as a cause of febrile seizure.2 Primary human herpesvirus 6 infection acquired mainly during the first 2 years of life is often associated with febrile seizure.5 Influenza virus, enterovirus, and adenovirus are the other viruses associated with febrile seizure.6 Febrile seizure is regarded as a complication of influenza A infection. Chiu et al2 had shown that the risk of developing febrile seizure following influenza A infection was higher compared with other respiratory viruses. A comparison of the relative risk of developing febrile seizure with 5 common viral infections and their subsequent risk of recurrence was reported by Chung et al.7 The risk of developing febrile seizure was found to be similar with influenza, adenovirus, or parainfluenza, though
it was higher than respiratory syncytial virus or rotavirus.7 The relationship between upper respiratory tract infections with common respiratory viruses and febrile seizure in children is seldom reported. Clinical presentations and epidemiologic characteristics of viral upper respiratory tract infection can vary among different populations, seasons, and regions. Suzhou, located in the temperate southeast of China, has a subtropical maritime monsoon climate with a high prevalence of respiratory infections during the winter and spring seasons. This study aimed to examine the role of common respiratory viruses associated with febrile seizure in children with upper respiratory tract infections from the Suzhou area and identify the
1
Department of Neurology, Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China 2 Department of Respiratory Medicine, Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China Corresponding Author: Yan Li, BS, Department of Neurology, Children’s Hospital Affiliated to Soochow University, Suzhou 215003, China. Email: [email protected]
Downloaded from jcn.sagepub.com at UNIV OF UTAH SALT LAKE CITY on November 28, 2014
2
Journal of Child Neurology
predisposing factors and special characteristics of febrile seizure in children with viral infections.
Methods Study Design and Settings This prospective study was conducted between June 2010 and June 2011 at the Department of Neurology, Children’s Hospital Affiliated to Soochow University, Suzhou, China.
Subjects and Selection Criteria Children who were diagnosed with febrile seizure, complicated with upper respiratory tract infection, and aged between 6 months and 6 years (n ¼ 189) were enrolled in this study. Febrile seizure was defined according to diagnostic standards8,9 and classified into simple and complex. The following clinical features were considered as simple febrile seizure: (1) sudden occurrence of seizure with generalized tonic-clonic, tonic, or clonic components; (2) seizure duration of less than 15 minutes; and (3) no recurrence of seizure within 24 hours. The following clinical features that exhibited atypical symptoms were considered as complex febrile seizure: (1) partial seizures, (2) seizures lasting for more than 15 minutes, and (3) multiple seizures within a short period (seizures more than 2 times in 1 febrile period). Patients who had central nervous system infection, acute electrolyte imbalance, metabolic disorder, afebrile seizure, and infection other than upper respiratory tract infection such as bronchiolitis, pneumonia, bronchitis, asthma exacerbation, acute gastroenteritis, exanthema subitum, or erysipelas were excluded from the study. The diagnosis of upper respiratory tract infection was based on the definitions in Practical Pediatrics by Zhu Futang (seventh edition).10 At the same time, children who were febrile without seizures, complicated with upper respiratory tract infection, and aged between 6 months and 6 years (n ¼ 174) were selected as the control group.
Sample Collection and Testing Nasal aspirate samples (2 mL each) were obtained from each patient within 24 hours of inpatient admission by introducing a sterile disposable catheter into the lower part of the pharynx through the nasal cavity. The samples were then centrifuged and stored at –80 C until tested for the detection of 7 common respiratory viruses such as respiratory syncytial virus; adenovirus; influenza viruses A and B; and parainfluenza viruses 1, 2, and 3 using a direct immunofluorescence assay as described in earlier reports.11-13 Antigen detection was carried out using a Light Diagnostics Respiratory Panel I Viral Screening and Identification Kit (Chemicon International Inc, Temecula, CA) according to the manufacturer’s instructions. Slides were examined by fluorescence microscopy (Leica 020-518.500, Germany). Blood samples (4 mL each) were also obtained to determine the following: leukocyte count; C-reactive protein; bacterial culture; and serological tests for hepatitis viruses, mycoplasma, chlamydia, and salmonella. Mycoplasma pneumoniae and Chlamydia pneumoniae were detected and quantified with enzyme-linked immunosorbent assay. Stool enzyme immunoassays (for rotavirus) and urine culture were performed whenever there was clinical suspicion of gastroenteritis and urinary tract infection, respectively. Human herpesvirus-6 serology and polymerase chain reaction were not routinely performed in the microbiology laboratory, and a diagnosis of roseola infantum was based on clinical findings.
Clinical Data Collection During inpatient admission to the department, the medical history and physical examination details of the children were recorded systematically by 2 physicians. The following clinical data were obtained for each patient from their hospital records: (1) patient demographics such as age on admission and gender; (2) history of febrile seizure and other nervous system diseases; (3) birth information such as birth order, parity, full term or premature, delivery pattern, and birth weight; (4) history of seizures in first-degree relatives; (5) seizures characteristics such as duration from pyrexia to seizures, body temperature at febrile seizure, maximum body temperature during a febrile episode (fever peak), seizure duration, frequency, and febrile seizure manifestations; (6) auxiliary examination characteristics such as cranial computed tomography (CT) or magnetic resonance imaging (MRI) scan on the first day of admission to exclude the presence of intracranial spaceoccupying lesions, encephalomalacia, or cerebrovascular disease; and (7) electroencephalogram in all patients on the next day to exclude the presence of epileptic discharges. Additionally, the data of cerebrospinal fluid examination of 27 children with complex febrile seizure and 2 control patients, who were suspected of infections in the central nervous system, were also recorded.
Statistical Analysis Statistical analyses were performed using SPSS version 10.0 software (SPSS, Inc, Chicago, IL). Data of normal distribution were expressed as mean + SD and analyzed using t test. Data other than normal distribution were expressed as median (and interquartile ranges, 25%, 75%) and analyzed using rank sum tests. An unpaired t test was used to compare the mean of the age, maximum temperature, and temperature at the time of seizures of children with febrile seizure infected with different respiratory viruses. Grouped data and rate comparison were conducted using w2 test. A value of P 36 months (older patients) and 132 were aged
