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.     

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.     

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.     

Effect of fever on recurrence rate of febrile convulsions.

We studied 154 children admitted consecutively with their first febrile convulsion to assess the influence of the temperature on the recurrence rate of convulsions. Those with temperatures of 40 degrees C or more were nine times less likely to have subsequent convulsions than those with temperatures of 38-38.9 degrees C.     

Recurrence rate of febrile convulsion related to the degree of pyrexia during the first attack

Ninety-four children consecutively admitted to the hospital between January 1980 and December 1982 with their first febrile convulsion (FC) were studied to assess the influence of the degree of pyrexia on the recurrence rate of FC. Thirty-eight of sixty-three children between 6 and 18 months of age (the peak incidence of FC) with fever above 40 degrees C were almost seven times less likely to have subsequent convulsions with fever, than those whose initial febrile convulsion was associated with a lower degree of pyrexia. It is suggested that the degree of pyrexia is a factor that influences the recurrence of FC. This may explain why some children have a reduced frequency of subsequent FC compared with others who appear to be at comparable risk.     

Spontaneous fits after convulsions with fever.

112 of an original sample of 134 children with febrile convulsions were reviewed between 8 years and 9 years 10 months after their initial attack. 17% of those followed up had had at least one spontaneous fit. A significant correlation was found with perinatal abnormalities. 12% had continuing recurrent fits. Persisting grand mal occurred most commonly in lower social class children who had had perinatal abnormalities and continued to have long-term neurological disorders. Psychomotor epilepsy correlated significantly with a prolonged or repeated initial convulsion with unilateral features. It is suggested that the development of grand mal and temporal lobe epilepsies after convulsions with fever are determined by different mechanisms.     

Febrile status epilepticus

As part of a study of status epilepticus in children (Maytal J, Shinnar S, Moshe SL, Alvarez LA. Pediatrics. 1989; 83:323-331); 44 children with febrile convulsions lasting more than 30 minutes were followed for a mean of 28 months (range 4 to 72). Thirty children were followed prospectively. Children with prior afebrile seizures or evidence of acute central nervous system infection were excluded. Nine (20%) children had prior neurological deficits. The duration of the febrile seizure was 0.5 to 1 hour in 41 cases (85%), 1 to 2 hours in 5 (10%), and greater than 2 hours in 2 children (5%). No child died or developed new neurological deficits following the seizures. The risk of recurrent seizures was increased, but only in the group with prior neurological abnormality. Six (66%) of these children had subsequent febrile seizures compared with 12 (34%) of the normal children (P = .08). Three (33%) had recurrent febrile status epilepticus compared with only 1 (3%) normal child (P = .023). The 2 children in the prospective arm of the study with recurrent febrile status epilepticus were both neurologically abnormal (P = .035). All 3 of the children who subsequently had afebrile seizures (2 prospective) were neurologically abnormal (P = .006 overall, P = .035 for prospective only). It is concluded that the occurrence of febrile status epilepticus in a neurologically impaired child is a risk factor for subsequent febrile as well as afebrile seizures. The occurrence of febrile status epilepticus in an otherwise normal child does not significantly increase the risk for subsequent febrile (brief or prolonged) or afebrile seizures in the first few years following the episode.     

History of convulsions and use of pertussis vaccine

Data on 2062 reports from the Monitoring System for Adverse Events Following Immunization, Centers for Disease Control (CDC), were analyzed to compare the risk of a personal or family history of convulsions in children who had a neurologic adverse event after receipt of diphtheria-tetanus-pertussis (DTP) vaccine with those who had a nonneurologic adverse event. Children with a neurologic event after DTP vaccine had a 7.2 times higher risk for personal history of convulsions (95% confidence limits 4.5 to 11.5) and a 4.5 times higher risk for family history of convulsions (95% confidence limits 3.1 to 6.7) than did children with an adverse event that did not affect the nervous system. Children with either a febrile or nonfebrile convulsion after receipt of DTP were significantly more likely to have a personal history of convulsions than children with a nonneurologic adverse event (P less than 0.0001). Children with a febrile convulsion after receipt of DTP but not children with nonfebrile convulsions were significantly more likely to have a family history of convulsions than those with a nonneurologic adverse event. It is recommended that pertussis vaccination be deferred in children with a personal history of a convulsion until it can be determined that an evolving neurologic disorder is not present. If such disorders are found, these children should be given the combined pediatric diphtheria and tetanus toxoids (DT) vaccine to complete the series.     

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.     

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.     

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.     

Long term outcome of prophylaxis for febrile convulsions

A cohort of 289 children with febrile convulsions who had been randomised in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) was followed up 12 years later. The study focused on the occurrence of epilepsy and on neurological, motor, intellectual, cognitive, and scholastic achievements in the cohort. At follow up the two groups were of almost identical age (14.0 v 14.1 years), body weight (58.2 v 57.2 kg), height (168.2 v 167.7 cm), and head circumference (55.9 v 56.2 cm). The occurrence of epilepsy (0.7% v 0.8%), neurological examination, fine and gross motor development on the Stott motor test, intellectual performance on the Wechsler intelligence scale for children verbal IQ (105 v 105), performance IQ (114 v 111), and full scale IQ (110 v 108), cognitive abilities on a neuropsychological test battery, including short and long term, auditory and visual memory, visuomotor tempo, computer reaction time, reading test, and scholastic achievement were also very similar. Children with simple and complex febrile convulsions had the same benign outcome. The long term prognosis in terms of subsequent epilepsy, neurological, motor, intellectual, cognitive, and scholastic ability was not influenced by the type of treatment applied in early childhood. Preventing new febrile convulsions appears no better in the long run than abbreviating them.     

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.     

THE EFFECTIVENESS OF PHENOBARBITAL IN THE PREVENTION OF RECURRENT FEBRILE CONVULSIONS IN CHILDREN WITH AND WITHOUT A HISTORY OF PRE-, PERI- AND POSTNATAL ABNORMALITIES

Abstract. Three hundred children who had an initial febrile convulsion were divided into two groups. In one group were children with a single brief generalized initial febrile seizure and no history of pre-, peri- or postnatal abnormalities which might suggest the possibility of brain damage and in the other group those with such abnormalities and/or a "severe" initial febrile convulsion. Daily phenobarbital produced a significant decrease in febrile seizure recurrences in both groups, as compared to children who received phenobarbital at the onset of fever and no phenobarbital prophylaxis. "Intermittent" phenobarbital given at the onset of fever did not produce a significant difference in recurrence rate as compared with no phenobarbital.     

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.     

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.     

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.     

CSF Glucose Concentrations in Infants with Febrile Convulsions and the Possible Effect of Acetaminophen

The present study was done to explore the relationship between the cerebrospinal fluid (CSF) glucose concentration, body temperature, seizure duration, and acetaminophen administration. Retrospective record review of 117 consecutive febrile convulsive infants aging 3 to 18 months admitted to Bahrami Children Hospital were studied. There was a positive correlation between CSF glucose level and body temperature in those who had not taken acetaminophen before admission (r = 0.515, n = 83). CSF glucose levels were significantly higher (P = 0.014) in febrile children (75.33 mg/dL, n =70) as compared with afebrile children (66.16 mg/dL, n = 13). In those administered acetaminophen there was a negative correlation between the CSF glucose level and body temperature (r = - 0.389, P = 0.023, n = 34). CSF glucose concentration was not significantly different (P = 0.076) in those who had taken acetaminophen than those who had not taken. Type of febrile seizure, fever, convulsion duration and multiplicity were not significantly correlated with CSF glucose concentration.     

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.     

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.