Family history of convulsions and use of pertussis vaccine

To evaluate the risk of neurologic events after vaccination with diphtheria-tetanus-pertussis (DTP) vaccine, we used data from the Centers for Disease Control Monitoring System for Adverse Events Following Immunization to compare the family history of convulsions in persons reporting neurologic events with that in persons reporting nonneurologic events; these events have an onset within 3 days of immunization with DTP vaccine, given either alone or with oral poliovirus vaccine. Persons reporting neurologic events were 6.4 times more likely to report a prior personal history of convulsions than those reporting nonneurologic events (95% confidence interval 4.7 to 8.8), and were 2.4 times more likely to report a history of convulsions in first-degree family members, that is, siblings or parents (95% confidence interval 1.7 to 3.4). Similar risks were noted for subgroup analyses controlling for type of event (febrile vs nonfebrile convulsion), age at immunization, source of report, number of previous doses of DTP vaccine, and day of onset. Because the Centers for Disease Control monitoring system receives reports on a nonrandom sample of all adverse events after immunization, selection bias could not be ruled out. On the basis of these data, we conclude that children with a family history of seizures are at increased risk of neurologic events, primarily febrile convulsions, after DTP vaccination. However, this increase in risk may reflect a nonspecific familial tendency for convulsions rather than a specific vaccine effect. Considering the rare occurrence of neurologic events after DTP vaccination, the generally benign outcome of febrile convulsions (which make up the majority of these neurologic events), and the possible increased risk of pertussis in the general population if the estimated 5% to 7% of persons with a first-degree family history of convulsions were exempted from pertussis vaccination, we further conclude that a history of convulsions in siblings or parents should not be a contraindication to pertussis vaccination. Special care in the prevention of postvaccination fever may be warranted in children with a family history of seizures.     

Lower degree of fever at the initial febrile convulsion is associated with increased risk of subsequent convulsions.

We studied 132 children admitted consecutively with their first febrile convulsion to assess whether the degree of fever at the onset of the convulsion can predict the risk of subsequent convulsions. The children studied were reviewed at least 2 years after the initial febrile convulsion to determine the number of children who had recurrences of febrile convulsions and/or afebrile convulsions. Children with body temperatures below 39 degrees C at the onset of their initial febrile convulsion (Group 1) were two and half times more likely to experience multiple convulsions within the same illness than those with body temperatures above 39 degrees C (Group 2). This occurred when the body temperature rose above that which had triggered the initial febrile convulsion. Children in Group 1 were also over three times more likely to experience recurrent febrile convulsion in subsequent illnesses than those in Group 2. As for subsequent development of afebrile convulsion or epilepsy, although the risk was low, it only occurred in Group 1. It is suggested that the known association between multiple convulsions, recurrent febrile convulsions and epilepsy may be due to the single predisposing factor of a low degree of fever at the onset of febrile convulsion. Each child with febrile convulsion may have his own threshold for eliciting a convulsion with fever; the lower this threshold is, the more likely are subsequent convulsions.     

Nonfebrile seizures after febrile convulsions: possible role of chronic cytomegalovirus infection

Twelve hundred children with convulsions when feverish were studied during a period of five years. Among them 52 subjects (4.33%) developed nonfebrile seizures after a period of eight months to five years from the first febrile convulsion (group A). Twenty-three children had neither afebrile seizures nor EEG abnormalities during the period of observation (group B). The two groups were comparable for age of the first febrile convulsion onset, sex, and socioeconomic status. None had risk factors for subsequent epilepsy or clinical signs of congenital cytomegalovirus infection. The isolation rate of CMV from urine was 53.84% in patients of group A, 26.09% in children of group B, and 26.83% in healthy control children. Twelve CMV-positive children from group A were followed for one to more than three years. In five of seven children with persisting EEG abnormalities, cytomegaloviruria was still present 13 to 41 months after the first isolation, whereas none of five patients with normal electroencephalograms had viruria after a comparable period. We found that CMV-positive children generally lacked cell-mediated immunity to the virus, whereas CMV-negative patients had positive reactions. Our data suggest a correlation between persistence of neurologic abnormalities and CMV excretion in children with nonfebrile seizures and CMV infection.     

Thalassemia major may decrease the frequency of febrile convulsions in children

Aim: We aimed to determine the relative frequency of febrile convulsion in children with major thalassemia to theorize that higher serum iron levels could reduce the incidence of febrile convulsion. Background: Febrile convulsion is the most common type of seizure in childhood that its causes are not fully understood. However, some risk factors have been cited such as the serum iron level. Materials and methods: Three hundred and fifty-nine children aged more than 5 years with major thalassemia who were receiving blood were enrolled as the case group. The control group consisted of 357 children without thalassemia aged 4–7 years (151 boys, 206 girls) who were referred to healthcare centers for routine health monitoring. Included data were the history of febrile convulsion, age of onset and type and the frequency of convulsions. Results: Children in control group significantly experienced more febrile convulsions than thalassemic children [4/359 (1.1%) in the thalassemic children and 14/357 (3.9%) in the control group had experienced febrile convulsions (P = 0.017)]. Conclusion: The frequency of febrile convulsion in children with major thalassemia is less than that of normal children. Children with thalassemia major may have higher serum levels of iron and such high serum iron levels might have a protective role in the children who have a vulnerability for febrile convulsions.     

Risk factors for recurrence of febrile convulsions

A cohort of hundred children with febrile convulsions, in the age group of 3 months to 5 years were followed up prospectively for one year to study the natural course of the illiness, and to determine if specific factors would increase the risk of recurrence of febrile convulsions. The risk factors studied were age of onset under one year, long duration of convulsion (more than 15 minutes), family history of febrile convulsion or epilepsy and combination of two or all of the above factors. Four groups of children with different risk factors were followed up for recurrence of convulsion, after the first attack. A group of children without any risk factor was considered as control and they were also followed up for recurrence of convulsions. Though all the groups with the risk factors, showed a trend towards a higher recurrence rate when compared to controls, the difference observed clinically was not significant statistically. This could be due to the small sample size of each group. A larger study could throw light on the predictive value of these risk factors and narrow down the use of long term anticonvulsant prophylaxis.     

Retrospective study of 160 children with febrile convulsions]

In a retrospective study of 411 children with cerebral convulsions over a period of 4 years, 160 patients with febrile seizures were found. This group consisted of 94 boys and 66 girls. The main purpose of this study was to establish the age of the first convulsive fit in each child. Febrile convulsions started in the first half year, increased in the second half year and culminated in the second year of life. This age dependent appearance was explained with passive immunization by maternal antibodies so that febrile convulsions appear when these antibodies decrease. The first occurrence of febrile convulsions appeared on an average of 22.9 months, in children with recurrent febrile convulsions a little earlier with 18.2 months. The most interesting fact was that children with a family history of febrile seizures showed an even earlier occurrence of the first seizure with 14.5 months. This tendency of early incidence of febrile convulsion in the group with family history and in the group of recurrent febrile convulsions could be shown as statistically significant respectively nearly significant in comparing with the group of retarded patients. A peculiar tendency for febrile convulsions seems to be documented by recurrent seizures in the patient himself, but also by a history of febrile convulsions in other family members. Both facts may lead to a very early incidence of febrile convulsions.     

Increased interleukin-1 (IL-1) production from LPS-stimulated peripheral blood monocytes in children with febrile convulsions

Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections (p less than 0.001), viral infections (p less than 0.005) or no infection (p less than 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL-1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions.     

幼儿急疹合并热性惊厥的临床特征

目的 探讨幼儿急疹合并热性惊厥的临床特征.方法 回顾性总结本院2005年1月至2008年2月确诊的幼儿急疹病例和热性惊厥病例,对幼儿急疹并热性惊厥的31例患儿的临床资料进行总结,与其他热性惊厥患儿及幼儿急疹未合并热性惊厥者对比,并结合文献进行分析.结果 幼儿急疹合并热性惊厥患儿占所有热性惊厥的17.1%(31/181),占2岁内热性惊厥的24.4%(31/127),占幼儿急疹患儿的15.7%(31/198);幼儿急疹并热性惊厥患儿出现热性惊厥的平均年龄为(0.85 4±0.38)岁,早于一般的热性惊厥患儿(2.41±1.30)岁,P<0.01;与不伴热性惊厥的幼儿急疹患儿比较,伴热性惊厥者的性别、年龄、最高体温、热程、出疹时间均无显著差别(P>0.05),而热性惊厥家族史有显著差别(P<0.05).结论 遗传因素是导致幼儿急疹并热性惊厥发作的一个危险因素;幼儿急疹并热性惊厥时一般预后良好,但要警惕发生严重中枢神经系统损伤的可能性,如癫痫.对于1岁内初次发热并出现热性惊厥的患儿要注意幼儿急疹的可能.     

Epilepsy and Mental Retardation Following Febrile Seizures In Childhood

ABSTRACT. In an unselected group of children who were seen following an initial febrile convulsion, the frequency of subsequent afebrile seizures was 3.5% and of mental retardation 1%. The most common afebrile seizure type was generalized major (86%). About 3/4 of the children who developed afebrile seizures did so by three years and all by five years following the initial febrile seizure. The children with afebrile seizures differed from those without afebrile seizures in the frequency of neonatal abnormality, family history of mental retardation, focal initial febrile convulsions, and delay in psychomotor milestones before the initial febrile seizure. Only about 1/3 of the children who developed afebrile seizures ever had a recurrent febrile convulsion and none had complex recurrent febrile seizures. Half the children with mental retardation had histories of delay in psychomotor milestones prior to the initial febrile seizure, and no child with mental retardation had any seizure longer than five minutes. The administration of daily phenobarbital did not reduce the frequency of epilepsy, in spite of a significant reduction in the incidence of recurrent febrile seizures. There remains no evidence that the prevention of recurrent febrile convulsions significantly decreases the frequency of afebrile seizures or mental retardation.     

Increased Interleukin-1 (IL-1) Production from LPS-Stimulated Peripheral Blood Monocytes in Children with Febrile Convulsions

ABSTRACT. Peripheral blood mononuclear cells (MNC) from 27 children with a febrile convulsion were tested for production of interleukin-1 (IL-1) in culture. MNC stimulated with lipopolysaccharide (LPS) showed a significantly increased production of IL-1 when compared to MNC from children without convulsions but with bacterial infections ( p < 0.001), viral infections ( p < 0.005) or no infection ( p < 0.005). Children who had experienced a febrile convulsion were retested several months later; this time the IL-1 production from LPS-stimulated MNC was not different from controls. These results demonstrate that MNC at the time of febrile convulsions have increased sensitivity to LPS and possibly to other IL-1 inducers; the resulting enhanced IL-1 response from sensitized MNC may have a role in the pathogenesis of febrile convulsions.     

Febrile convulsions and later development of epilepsy

A group of 172 epileptic children who had had prior febrile convulsions was compared with a group of 674 who had not. Children with epilepsy and prior febrile convulsions were similar in some respects (sex ratio, positive family history for seizures) to children with pure febrile convulsions and in most respects (type of epilepsy, mental status, initial EEG, and two- and four-year remission rates in the long-term outcome) to epileptic children without prior febrile convulsions. Our data do not support the current view that febrile convulsions, per se, are the main cause of mesial temporal sclerosis, le, temporal lobe epilepsy. Thus, our clinical findings support previously expressed doubts on the role of febrile seizures in temporal lobe epilepsy that were based on pathohistologic findings.     

Clinical characteristics of febrile convulsions during primary HHV-6 infection.

OBJECTIVE: To clarify clinical characteristics of children with febrile convulsions during primary human herpesvirus 6 (HHV-6) infection. SUBJECTS AND METHODS: The clinical characteristics of first febrile convulsion were compared between those with and without primary HHV-6 infection in 105 children. HHV-6 infection was verified by culture or acute/convalescent anti-HHV-6 antibody titres. RESULTS: Primary infection with HHV-6 was seen in 21 of 105 patients with febrile convulsions (3 upper respiratory infection, 1 lower respiratory infection, and 17 exanthem subitum). 13 of 23 patients < 1 year, 19 of 79 patients with first febrile convulsion, and 2 of 15 with second convulsion were infected with HHV-6. The median age of patients with first febrile convulsion and HHV-6 was significantly lower than those without infection. The frequency of clustering seizures, long lasting seizures, partial seizures, and postictal paralysis was significantly higher among those with primary HHV-6 infection than among those without. The frequency of atypical seizures in 19 patients with first febrile convulsion associated with primary infection was significantly higher than in 60 patients without primary infection. The frequency in infants younger than 1 year of age was also significantly higher than that in 10 age matched infants without primary infection. CONCLUSIONS: These findings suggest that primary infection with HHV-6 is frequently associated with febrile convulsions in infants and young children and that it often results in the development of a more severe form of convulsions, such as partial seizures, prolonged seizures, and repeated seizures, and might be a risk factor for subsequent development of epilepsy.     

Osmolality and electrolytes in cerebrospinal fluid and serum of febrile children with and without seizures

Abstract During acute febrile diseases mild disturbances of water and electrolyte balance occur frequently. It has been suggested that changes in electrolyte balance, in particular hyponatraemia, might predispose a child to convulsions during febrile illness; however, the changes of electrolytes in the CSF are not known.We have studied the effects of fever and convulsions on water and electrolyte balance in CSF and serum by measuring osmolality and electrolyte concentrations in children. The febrile population consisted of 60 children, 36 of whom had seizures during fever. Twenty-one children without convulsions and nine children with epileptic symptoms were nonfebrile controls. We noticed that CSF is subject to changes in osmolality and electrolyte concentration during fever, while convulsions do not exhibit such changes. CSF osmolality and sodium concentrations were lower in febrile children than in nonfebrile controls. The osmolality in febrile children with convulsions was 3.8% (P<0.01) and without seizures 3.5% (P<0.01) lower than in nonfebrile nonconvulsive children. The changes in CSF sodium concentration, and to a lesser extent potasium and chloride concentrations, paralleled those of CSF osmolality. A positive correlation was observed between the CSF and serum osmolatities (r=0.73,P<0.0001), and sodium concentrations (r=0.63,P<0.0001). A negative correlation between the body temperature and both CSF osmolality (r=–0.66,P<0.0001) and sodium concentration (r=–0.59,P<0.0001) exhibits also the important regulative role of increased body tmeperature.Conclusion Fever is an important factor for disturbances in fluid and electrolyte balance. The alterations in CSF osmolality and sodium concentration do not, however, give an unambiguous explanation for the susceptibility to simple febrile seizures.     

Continuous phenobarbital treatment after a 'simple febril convulsion'

In only a small proportion of young children with brief, generalized, febrile convulsions do afebrile seizures develop, but this fraction is several times the prevalence of epilepsy in an unselected population. The risk of another febrile convulsion is approximately 30%. Febrile status epilepticus during a subsequent infection is a potential source of serious morbidity and mortality. Intermittent phenobarbital administration during subsequent, febrile illnesses confers little protection against recurrent, febrile convulsions. Continuous phenobarbital administration during the preschool years is indicated for most children who have had a simple febrile convulsion.     

Duration of admission for febrile convulsions?

Records of 199 children aged 5 to 71 months (mean 22.8) admitted after febrile convulsion were examined. Although 32 had recurrent convulsions (some before admission) none suffered a convulsion more than 24 hours after hospital admission.     

Clinical characteristics of febrile convulsions during primary HHV-6 infection

OBJECTIVE—To clarify clinical characteristics of children with febrile convulsions during primary human herpesvirus 6 (HHV-6) infection.SUBJECTS AND METHODS—The clinical characteristics of first febrile convulsion were compared between those with and without primary HHV-6 infection in 105 children. HHV-6 infection was verified by culture or acute/convalescent anti-HHV-6 antibody titres.RESULTS—Primary infection with HHV-6 was seen in 21 of 105 patients with febrile convulsions (3 upper respiratory infection, 1 lower respiratory infection, and 17 exanthem subitum). 13 of 23 patients < 1 year, 19 of 79 patients with first febrile convulsion, and 2 of 15 with second convulsion were infected with HHV-6. The median age of patients with first febrile convulsion and HHV-6 was significantly lower than those without infection. The frequency of clustering seizures, long lasting seizures, partial seizures, and postictal paralysis was significantly higher among those with primary HHV-6 infection than among those without. The frequency of atypical seizures in 19 patients with first febrile convulsion associated with primary infection was significantly higher than in 60 patients without primary infection. The frequency in infants younger than 1 year of age was also significantly higher than that in 10 age matched infants without primary infection.CONCLUSIONS—These findings suggest that primary infection with HHV-6 is frequently associated with febrile convulsions in infants and young children and that it often results in the development of a more severe form of convulsions, such as partial seizures, prolonged seizures, and repeated seizures, and might be a risk factor for subsequent development of epilepsy.     

Infants and children with convulsions and hypotonic-hyporesponsive episodes following diphtheria-tetanus-pertussis immunization: follow-up evaluation

In a prior prospective study, we evaluated the nature and rates of adverse reactions occurring within 48 hours following 15,752 diphtheria-tetanus-pertussis (DTP) immunizations. Nine children had convulsions, and nine had hypotonic-hyporesponsive episodes. After an interval of 6 to 7 years, we were successful in contacting the families of 16 of these children to determine whether any had evidence of neurologic impairment too subtle to have been detected at the time of initial evaluation. All 16 were considered normal by their parents and were doing well in school. A complete neurologic and psychometric evaluation was performed on 13 of these children. No child had significant neurologic deficit, although four had minor neurologic abnormalities. Psychometric testing revealed normal performance IQ scores (104.3 +/- 15.8) but low verbal IQ scores (91.8 +/- 18.4); however, these lower verbal IQ scores can be explained by the proportion of Hispanic and bilingual children in this sample. Therefore, there is no evidence that any of these 16 children have any serious neurologic damage as a result of a convulsion or a hypotonic-hyporesponsive episode temporally associated with a prior diphtheria-tetanus-pertussis immunization.     

Epilepsy and mental retardation following febrile seizures in childhood

In an unselected group of children who were seen following an initial febrile convulsion, the frequency of subsequent afebrile seizures was 3.5% and of mental retardation 1%. The most common afebrile seizure type was generalized major (86%). About 3/4 of the children who developed afebrile seizures did so by three years and all by five years following the initial febrile seizure. The children with afebrile seizures differed from those without afebrile seizures in the frequency of neonatal abnormality, family history of mental retardation, focal initial febrile convulsions, and delay in psychomotor milestones before the initial febrile seizure. Only about 1/3 of the children who developed afebrile seizures ever had a recurrent febrile convulsion and none had complex recurrent febrile seizures. Half the children with mental retardation had histories of delay in psychomotor milestones prior to the initial febrile seizure, and no child with mental retardation had any seizure longer than five minutes. The administration of daily phenobarbital did not reduce the frequency of epilepsy, in spite of a significant reduction in the incidence of recurrent febrile seizures. There remains no evidence that the prevention of recurrent febrile convulsions significantly decreases the frequency of afebrile seizures or mental retardation.     

Serum sodium levels and probability of recurrent febrile convulsions

In a prospective study of 69 children with febrile convulsions, serum sodium levels were often lower than normal (52% had levels <135 mmol/l). The mean level (134.4±0.4 mmol/l) was significantly lower as compared to a group of children without fever (140.6±0.4 mmol/l,n=23) and as compared to a group with fever but without convulsions (137.6±0.6 mmol/l,n=31). The probability of a repeat convulsion within the same febrile period appeared to be significantly related to the serum sodium level.Conclusion Measurement of the serum sodium is a valuable investigation in the child with a febrile convulsion. The lower the serum sodium level, the higher the probability of a repeat convulsion. This knowledge may be of practical value in deciding whether to admit the child or allow it to return home and in advising parents or carers of the risk of a repeat convulsion.     

Convulsions in childhood shigellosis. Clinical and laboratory features in 153 children

We studied 153 children who experienced convulsions associated with shigellosis. The male-female ratio was 1.2:1.0. Thirty-six children had a previous history of febrile convulsions, and 31 children had a family history of convulsive disorder. Most of the children were 0.5 to 3 years of age, although 49 (32%) were older than 3 years of age and 20 (13.1%) were older than 5 years of age. All children were febrile; in 75% of the children, the temperature was over 39 degrees C. The majority of the children had generalized, self-limited convulsions, which lasted less than ten minutes. In 30 children the seizures were categorized as complex; ten of them had recurrent episodes, although none had any residual neurologic deficit. The total leukocyte count was usually within normal limits, but the differential count characteristically showed a marked increase in the number of band forms. Hypocalcemia (blood calcium level, less than 9.01 mg/dL [less than 2.25 mmol/L]) was observed in four patients; hyponatremia (blood sodium level, 130 mEq/L [130 mmol/L]), in 11 patients; and hypernatremia (blood sodium level, 157 mEq/L [157 mmol/L]), in one patient. Electroencephalographic (EEG) studies were performed in ten children, and lumbar punctures were performed in 34 children; both procedures usually yielded normal results. Shigella sonnei was isolated from 69% of the children; Shigella flexneri from 25%; Shigella boydii from 5%; and Shigella dysenteriae from 1%. Due to the benign and self-limited nature of most of the convulsions, neither diagnostic procedures, nor drug therapy, are usually necessary. These measures should, however, be considered in complicated cases characterized by focal or prolonged seizures.