- Email: [email protected]
Epidemiology of febrile seizures in Singapore children
seizures were documented in 17 infants (17%), 12 (71%) of whom had grade 4 IVH, 2 (12%) with grade 3, and 3 (18%) with grade 2. Five and a half percent of the surviving patient population developed chronic seizure disorder: four patients with grade 4 and 1 patient with grade 3 IVH. Infants with grade 4 IVH are at a higher risk than infants with grades 1-3 IVH for developing acute seizures. All infants with IVH who survive the neonatal period are at a relatively low risk for developing a chronic seizure disorder.
277. DIFFERENCES IN FACTORS INFLUENCING THE FAMILY AGGREGATION OF FEBRILE CONVULSION: MULTIVARIATE REGRESSION APPROACH USING GENERALIZED ESTIMATING EQUATIONS II Chao-Ching Huang, For-Wey Lung, Mei-Chih Huang, and Jing-Jane Tsai, Tainan, Taiwan Febrile convulsion (FC) has a tendency for familial aggregation. The genetic influence on family clustering may be different in the general population and hospital FC patients. Generalized estimating equations II (GEE2) are used to examine the effect of genetic and environmental factors on the familial aggregation of FC among siblings of probands in population and multicenter groups. Multicenter FC studies (n -- 364) were obtained from 10 major teaching hospitals, and the population FC (n = 85) collected by the proportional to size method followed by simple random sampling. Population controls (n = 87) were matched with population FC by age, sex, and living district. The covariates for analysis included socioeconomic status (SES), urbanization levels of living district, housing space, type of housing, previous infection rate, FC history from father, mother, siblings, uncles, aunts, and cousins. The presence of FC among proband siblings is considered to be a response variable. Among the population, there is no significant difference between population FC and controls on the response variable. The odds ratio of FC in siblings is 6:1 (P > .05) (the odds ratios reflecting the risk associated with having one affected relative). However, lower SES has significant influence on the presence of FC. Among the multicenter, SES has no influence on FC. However, FC histories in the father and paternal cousins of the proband have significant influence on response variables (P < .05, P < .01, respectively). The odds ratio of FC in siblings is 12:1 (P < .0001). The result from this model suggests that the risk of a family member is increased by a factor of 12 if his/her relative is affected rather than unaffected. Our findings suggest the heterogeneity of genetic influence on familial aggregation in different patients sources. (Supported by NSC 80-0412-B006-02)
278. RISK OF AFEBRILE SEIZURES AFTER FEBRILE SEIZURES IN A MULTIRACIAL ASIAN POPULATION Wei Ling Lee, Kwok Chan Lun, Poh Sim Low, and Uma Rajan, Singapore The risk of afebrile seizures (AFS) and epilepsy after febrile seizures (FS), as well as prognostic factors, has been defined in many comprehensive population-based studies in western countries [1-4]. No similar studies have been published from Asian countries other than Japan [5]. During an epidemiologic study of seizure disorders in Singapore children, 909 were hospitalized at the time of their first FS and had well-documented records. FS
158 PEDIATRICNEUROLOGY Vol. 11 No. 2
was defined as a seizure that occurred with fever but without incidence of intracranial infection or defined cause. Seizures with fever in children with previous unprovoked afebrile seizure were excluded. Age was not included in the definition, but the study was limited to patients younger than the age of 13 years. There were 527 males and 382 females; age at first seizure ranged from 18 days to 12 years. Twenty-three (2.5%) subsequently developed AFS. On univariate (Kaplan-Meier) analysis, FS with focal features, duration more than 30 min, more than 1 seizure in 24 hours, family history of nonfebrile seizures, developmental delay at the time of first febrile seizure, age younger than 6 months, recurrent FS, and ethnic origin from the Indian subcontinent were all associated with increased risk of AFS. Sex was not a risk factor. On multivariate (Cox regression) analysis, developmental delay, family history of nonfebrile seizures, and 2 or more complex FS were significant risk factors. The characteristics of complex FS: focal, prolonged, multiple in a day, when occurring together significantly increased the risk. Race, sex, age, and recurrence of FS were not significant risk factors. However, a subgroup of patients, females younger than the age of 6 months, had an increased risk. The risk of AFS following FS in this Asian population is very similar to that found in western countries (2.5%) and the risk factors are also similar. References: [1] Nelson KB, Ellenberg JH. Predictors of epilepsy in patients who have experienced febrile seizures. N Engl J Med 1976;295:1029-33. [2] Nelson KB, Ellenberg JH. Prognosis in patients with febrile seizures. Pediatrics 1978;61:720-7. [3] Annergers JF, Hauser WA, Elveback LR, Kurland LT. The risk of epilepsy following febrile convulsions. Neurology 1979;29:297303. [4] Annergers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Meal 1987;316:493-8. [5] Tsuboi T, Endo S. Febrile convulsions followed by non-febrile convulsions. A clinical, electroencephalographic and follow-up study. Neuropaediatrie 1977;8:209-23.
279. EPIDEMIOLOGY OF FEBRILE SEIZURES IN SINGAPORE CHILDREN Wei Ling Lee, Poh Sim Low, Uma Rajan, and Belinda Murugasu, Singapore In the United States [1], South America [2], and Western Europe [3], 2-5% of all children experience febrile seizures (FS) before age 5. Estimates of the frequency of FS are much higher in Japan [4] (8%) and the Mariana Islands [5] (15%). It is not clear whether these differences are accurate and due to genetic or environmental factors, or spurious from differences in methodology between different studies. Singapore is a small, multiracial country (Chinese 78%, Malaysians 14%, Indians 7%, other races 1%) with a relatively uniform environment. Differences in incidence of FS between the different races is most likely due to genetic differences. The population base of the study included 30,763 children born in 2 government hospitals between January 1, 1980 and December 31, 1982 followed up to age 6 years. All records of admissions to government hospitals for seizures were reviewed; when the patient was 6 years of age, parents were sent a questionnaire asking whether the child ever had seizures of any type. FS was defined as a seizure that occurs in association with fever but without evidence of intracranial infection or defined cause. Seizures with fever in children who have suffered a previous unprovoked afebrile seizure were excluded. The cumula-
tive incidence of FS by age 6 years was 4.48% (5.15% in males; 3.76% in females). There were no significant differences between the races. The slightly higher rate in males was found for all 3 races. FSs are seen in all races. There are no significant differences in incidence between Chinese, Malaysians, and Indians in Singapore. References: [1] Annegers JF, Hauser WA, Elveback LR, Kurland LT. The risk of epilepsy following febrile convulsions. Neurology 1979;29:297-303. [2] Chiofalo N, Kirschbaum A, Fuentes A, Cordero ML, Madsen J. Prevalence of epilepsy in children of Mekipilla, Chile. Epilepsia 1979;20: 261-6. [3] Cooper JE. Epilepsy in a longitudinal survey of 5,000 children. Br Med J 1965;1:1020-2. [4] Tsuboi T. Epidemiology of febrile and afebrile convulsions in children in Japan. Neurology 1984;34:175-81. [5] Stanhope JM, Brody JA, Brink E, Morris CE. Convulsions among the Chamorro people of Guam, Mariana Islands. II. Febrile convulsions. Am J Epidemiol 1972;95: 299-304. Table 279-1. age 6
All races Chinese Malaysian Indian
Race and sex-specific cumulative incidence of FS by
Both Sexes
Male
Female
4.48% 4.10% 4.48% 4.70%
5.15% 5.21% 4.81% 5.12%
3.76% 4.06% 2.89% 3.26%
280. ARE COMMON PROBLEMS FOLLOWING ECMO RELATED TO JUGULAR BULB THROMBOSIS? Theodore J. Tarby and Janie Waggoner, Phoenix, Arizona
Extracorporeal membrane oxygenation (ECMO) is a rescue intervention for newborn infants with acute respiratory failure that has not responded to maximal conventional treatment. ECMO involves cardiopulmonary bypass using either venoarterial or venovenous circuits. In either case, the right internal jugular vein is cannulated and subsequently ligated. Infants who survive ECMO frequently feed poorly despite quite adequate alertness and a vigorous nonnutritive suck. They exhibit suck-swallow incoordination. Many infants are hoarse following ECMO and there have been case reports alleging a surgical cause for right vocal fold paralysis following ECMO. We examined infants surviving ECMO with MRI and MR venography. In the first 30 infants reviewed, 22 had thrombosis or at least absence of flow in the right jugular bulb. Jugular bulb thrombosis has resulted in isolated dysphagia, hoarseness, and trapezius-sternomastoid weakness in adults. In our own clinical experience, one adolescent male with a traumatic jugular bulb thrombosis complained of not being able to swallow and an infant displayed a similar problem after Broviac catheter placement. We propose that jugular bulb thrombosis is involved in lower cranial nerve dysfunction following ECMO and that this dysfunction is clinically significant.
erythematosus (SLE) who presented in status epilepticus. Upon admission, she was hypertensive, but had a normal neurologic examination after seizures stopped. Cranial MRI disclosed diffuse gray and white matter lesions which markedly improved after treatment with methylprednisolone. The results of undetectable CSF C a and C4 and low serum C a complements were obtained much later and together with MRI findings supported the diagnosis of CNS lupus. There is no single test specific for CNS lupus. Usually, a battery of tests, including EEG, CSF examination, and various CSF and serum antibody titers are performed. However, the latter are not readily available in the initial assessment of the patient and therapeutic decision. In such situations, MRI offers a rapid and sensitive tool in detecting focal and diffuse lesions in SLE patients with acute neurologic presentation and in determining clinical outcome.
282. C-FOS GENE EXPRESSION IN AUDIOGENIC SEIZURE-PRONE RAT BRAIN Wei-Song Shan, Bao-Qiang Yuan, and Xi-Ru Wu, Beijing, China
We studied the basal and stimulated c-fos gene expression of audiogenic seizure-prone rat (P77PMC) brain during development in vivo and in fetal brain primary cell cultures. The results revealed: (1) In primary cultures of fetal rat cerebral cortical neurons, exogenous NMDA-induced c-fos mRNA expression exhibits dose- and time-dependent changes. These changes can be prevented by competitive or noncompetitive antagonists; during the development of cortical neurons, NMDA-induced c-fos mRNA expression increased on day 18 in vitro, reaching a maximum at day 24; NMDA-induced c-fos mRNA expression in cultured cortical neurons of P77PMC rats was higher than that of controls during 6-24 days in vitro with significant differences (P < .05) on day 18. (2) The basal c-fos mRNA expression level in brain of P77PMC rats was rapidly increased on day 14 after birth and was the highest on day 21; the content of c-fos mRNA in brain of adult P77PMC rats rose dramatically after seizures and reached a peak level at 30 min, decreased to the same as the control level by 4 or 24 hours after seizure; brain slices showed that c-fos mRNA distributed throughout the motor cortex, somatosensory cortex, hippocampus, dentate gyms, thalamus, inferior colliculus, etc. Based on the above results, we considered that there is indeed some close relationship between c-fos gene and the seizure susceptibility of P77PMC rats. Mechanisms by which seizure-induced increased expression of c-fos mRNA could lead to short- and long-term changes in regional excitability and thereby could contribute to susceptibility for further seizure activity will be discussed. (The project was supported by the National Nature Sciences Foundation of China.)
281. MRI IN CNS LUPUS Maria A. Gieron-Korthals, Susan Khoromi, and Alfonso Campos, Tampa, Florida
283. MOLECULAR NEUROBIOLOGY STUDY ABOUT CANDIDATE GENES RELEVANT TO PATHOGENESIS OF EPILEPSY Xi-Ru Wu, Z h a o - H u i W a n g , W e i - S o n g Shan, BaoChang Yuen, Wei-Lan Liang, and Hong Pan, Beijing, China
There is limited information on an MRI pattern in childhood CNS lupus. We report a 10-year-old girl with systemic lupus
The pathogenesis of bursting neurons in epileptic brain may be controlled by multiple genetic loci. We utilized domestic audio-
PEDIATRIC NEUROLOGY Vol. 11 No. 2 159
277. DIFFERENCES IN FACTORS INFLUENCING THE FAMILY AGGREGATION OF FEBRILE CONVULSION: MULTIVARIATE REGRESSION APPROACH USING GENERALIZED ESTIMATING EQUATIONS II Chao-Ching Huang, For-Wey Lung, Mei-Chih Huang, and Jing-Jane Tsai, Tainan, Taiwan Febrile convulsion (FC) has a tendency for familial aggregation. The genetic influence on family clustering may be different in the general population and hospital FC patients. Generalized estimating equations II (GEE2) are used to examine the effect of genetic and environmental factors on the familial aggregation of FC among siblings of probands in population and multicenter groups. Multicenter FC studies (n -- 364) were obtained from 10 major teaching hospitals, and the population FC (n = 85) collected by the proportional to size method followed by simple random sampling. Population controls (n = 87) were matched with population FC by age, sex, and living district. The covariates for analysis included socioeconomic status (SES), urbanization levels of living district, housing space, type of housing, previous infection rate, FC history from father, mother, siblings, uncles, aunts, and cousins. The presence of FC among proband siblings is considered to be a response variable. Among the population, there is no significant difference between population FC and controls on the response variable. The odds ratio of FC in siblings is 6:1 (P > .05) (the odds ratios reflecting the risk associated with having one affected relative). However, lower SES has significant influence on the presence of FC. Among the multicenter, SES has no influence on FC. However, FC histories in the father and paternal cousins of the proband have significant influence on response variables (P < .05, P < .01, respectively). The odds ratio of FC in siblings is 12:1 (P < .0001). The result from this model suggests that the risk of a family member is increased by a factor of 12 if his/her relative is affected rather than unaffected. Our findings suggest the heterogeneity of genetic influence on familial aggregation in different patients sources. (Supported by NSC 80-0412-B006-02)
278. RISK OF AFEBRILE SEIZURES AFTER FEBRILE SEIZURES IN A MULTIRACIAL ASIAN POPULATION Wei Ling Lee, Kwok Chan Lun, Poh Sim Low, and Uma Rajan, Singapore The risk of afebrile seizures (AFS) and epilepsy after febrile seizures (FS), as well as prognostic factors, has been defined in many comprehensive population-based studies in western countries [1-4]. No similar studies have been published from Asian countries other than Japan [5]. During an epidemiologic study of seizure disorders in Singapore children, 909 were hospitalized at the time of their first FS and had well-documented records. FS
158 PEDIATRICNEUROLOGY Vol. 11 No. 2
was defined as a seizure that occurred with fever but without incidence of intracranial infection or defined cause. Seizures with fever in children with previous unprovoked afebrile seizure were excluded. Age was not included in the definition, but the study was limited to patients younger than the age of 13 years. There were 527 males and 382 females; age at first seizure ranged from 18 days to 12 years. Twenty-three (2.5%) subsequently developed AFS. On univariate (Kaplan-Meier) analysis, FS with focal features, duration more than 30 min, more than 1 seizure in 24 hours, family history of nonfebrile seizures, developmental delay at the time of first febrile seizure, age younger than 6 months, recurrent FS, and ethnic origin from the Indian subcontinent were all associated with increased risk of AFS. Sex was not a risk factor. On multivariate (Cox regression) analysis, developmental delay, family history of nonfebrile seizures, and 2 or more complex FS were significant risk factors. The characteristics of complex FS: focal, prolonged, multiple in a day, when occurring together significantly increased the risk. Race, sex, age, and recurrence of FS were not significant risk factors. However, a subgroup of patients, females younger than the age of 6 months, had an increased risk. The risk of AFS following FS in this Asian population is very similar to that found in western countries (2.5%) and the risk factors are also similar. References: [1] Nelson KB, Ellenberg JH. Predictors of epilepsy in patients who have experienced febrile seizures. N Engl J Med 1976;295:1029-33. [2] Nelson KB, Ellenberg JH. Prognosis in patients with febrile seizures. Pediatrics 1978;61:720-7. [3] Annergers JF, Hauser WA, Elveback LR, Kurland LT. The risk of epilepsy following febrile convulsions. Neurology 1979;29:297303. [4] Annergers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Meal 1987;316:493-8. [5] Tsuboi T, Endo S. Febrile convulsions followed by non-febrile convulsions. A clinical, electroencephalographic and follow-up study. Neuropaediatrie 1977;8:209-23.
279. EPIDEMIOLOGY OF FEBRILE SEIZURES IN SINGAPORE CHILDREN Wei Ling Lee, Poh Sim Low, Uma Rajan, and Belinda Murugasu, Singapore In the United States [1], South America [2], and Western Europe [3], 2-5% of all children experience febrile seizures (FS) before age 5. Estimates of the frequency of FS are much higher in Japan [4] (8%) and the Mariana Islands [5] (15%). It is not clear whether these differences are accurate and due to genetic or environmental factors, or spurious from differences in methodology between different studies. Singapore is a small, multiracial country (Chinese 78%, Malaysians 14%, Indians 7%, other races 1%) with a relatively uniform environment. Differences in incidence of FS between the different races is most likely due to genetic differences. The population base of the study included 30,763 children born in 2 government hospitals between January 1, 1980 and December 31, 1982 followed up to age 6 years. All records of admissions to government hospitals for seizures were reviewed; when the patient was 6 years of age, parents were sent a questionnaire asking whether the child ever had seizures of any type. FS was defined as a seizure that occurs in association with fever but without evidence of intracranial infection or defined cause. Seizures with fever in children who have suffered a previous unprovoked afebrile seizure were excluded. The cumula-
tive incidence of FS by age 6 years was 4.48% (5.15% in males; 3.76% in females). There were no significant differences between the races. The slightly higher rate in males was found for all 3 races. FSs are seen in all races. There are no significant differences in incidence between Chinese, Malaysians, and Indians in Singapore. References: [1] Annegers JF, Hauser WA, Elveback LR, Kurland LT. The risk of epilepsy following febrile convulsions. Neurology 1979;29:297-303. [2] Chiofalo N, Kirschbaum A, Fuentes A, Cordero ML, Madsen J. Prevalence of epilepsy in children of Mekipilla, Chile. Epilepsia 1979;20: 261-6. [3] Cooper JE. Epilepsy in a longitudinal survey of 5,000 children. Br Med J 1965;1:1020-2. [4] Tsuboi T. Epidemiology of febrile and afebrile convulsions in children in Japan. Neurology 1984;34:175-81. [5] Stanhope JM, Brody JA, Brink E, Morris CE. Convulsions among the Chamorro people of Guam, Mariana Islands. II. Febrile convulsions. Am J Epidemiol 1972;95: 299-304. Table 279-1. age 6
All races Chinese Malaysian Indian
Race and sex-specific cumulative incidence of FS by
Both Sexes
Male
Female
4.48% 4.10% 4.48% 4.70%
5.15% 5.21% 4.81% 5.12%
3.76% 4.06% 2.89% 3.26%
280. ARE COMMON PROBLEMS FOLLOWING ECMO RELATED TO JUGULAR BULB THROMBOSIS? Theodore J. Tarby and Janie Waggoner, Phoenix, Arizona
Extracorporeal membrane oxygenation (ECMO) is a rescue intervention for newborn infants with acute respiratory failure that has not responded to maximal conventional treatment. ECMO involves cardiopulmonary bypass using either venoarterial or venovenous circuits. In either case, the right internal jugular vein is cannulated and subsequently ligated. Infants who survive ECMO frequently feed poorly despite quite adequate alertness and a vigorous nonnutritive suck. They exhibit suck-swallow incoordination. Many infants are hoarse following ECMO and there have been case reports alleging a surgical cause for right vocal fold paralysis following ECMO. We examined infants surviving ECMO with MRI and MR venography. In the first 30 infants reviewed, 22 had thrombosis or at least absence of flow in the right jugular bulb. Jugular bulb thrombosis has resulted in isolated dysphagia, hoarseness, and trapezius-sternomastoid weakness in adults. In our own clinical experience, one adolescent male with a traumatic jugular bulb thrombosis complained of not being able to swallow and an infant displayed a similar problem after Broviac catheter placement. We propose that jugular bulb thrombosis is involved in lower cranial nerve dysfunction following ECMO and that this dysfunction is clinically significant.
erythematosus (SLE) who presented in status epilepticus. Upon admission, she was hypertensive, but had a normal neurologic examination after seizures stopped. Cranial MRI disclosed diffuse gray and white matter lesions which markedly improved after treatment with methylprednisolone. The results of undetectable CSF C a and C4 and low serum C a complements were obtained much later and together with MRI findings supported the diagnosis of CNS lupus. There is no single test specific for CNS lupus. Usually, a battery of tests, including EEG, CSF examination, and various CSF and serum antibody titers are performed. However, the latter are not readily available in the initial assessment of the patient and therapeutic decision. In such situations, MRI offers a rapid and sensitive tool in detecting focal and diffuse lesions in SLE patients with acute neurologic presentation and in determining clinical outcome.
282. C-FOS GENE EXPRESSION IN AUDIOGENIC SEIZURE-PRONE RAT BRAIN Wei-Song Shan, Bao-Qiang Yuan, and Xi-Ru Wu, Beijing, China
We studied the basal and stimulated c-fos gene expression of audiogenic seizure-prone rat (P77PMC) brain during development in vivo and in fetal brain primary cell cultures. The results revealed: (1) In primary cultures of fetal rat cerebral cortical neurons, exogenous NMDA-induced c-fos mRNA expression exhibits dose- and time-dependent changes. These changes can be prevented by competitive or noncompetitive antagonists; during the development of cortical neurons, NMDA-induced c-fos mRNA expression increased on day 18 in vitro, reaching a maximum at day 24; NMDA-induced c-fos mRNA expression in cultured cortical neurons of P77PMC rats was higher than that of controls during 6-24 days in vitro with significant differences (P < .05) on day 18. (2) The basal c-fos mRNA expression level in brain of P77PMC rats was rapidly increased on day 14 after birth and was the highest on day 21; the content of c-fos mRNA in brain of adult P77PMC rats rose dramatically after seizures and reached a peak level at 30 min, decreased to the same as the control level by 4 or 24 hours after seizure; brain slices showed that c-fos mRNA distributed throughout the motor cortex, somatosensory cortex, hippocampus, dentate gyms, thalamus, inferior colliculus, etc. Based on the above results, we considered that there is indeed some close relationship between c-fos gene and the seizure susceptibility of P77PMC rats. Mechanisms by which seizure-induced increased expression of c-fos mRNA could lead to short- and long-term changes in regional excitability and thereby could contribute to susceptibility for further seizure activity will be discussed. (The project was supported by the National Nature Sciences Foundation of China.)
281. MRI IN CNS LUPUS Maria A. Gieron-Korthals, Susan Khoromi, and Alfonso Campos, Tampa, Florida
283. MOLECULAR NEUROBIOLOGY STUDY ABOUT CANDIDATE GENES RELEVANT TO PATHOGENESIS OF EPILEPSY Xi-Ru Wu, Z h a o - H u i W a n g , W e i - S o n g Shan, BaoChang Yuen, Wei-Lan Liang, and Hong Pan, Beijing, China
There is limited information on an MRI pattern in childhood CNS lupus. We report a 10-year-old girl with systemic lupus
The pathogenesis of bursting neurons in epileptic brain may be controlled by multiple genetic loci. We utilized domestic audio-
PEDIATRIC NEUROLOGY Vol. 11 No. 2 159