Recurrence of febrile convulsions after the first diphtheria-pertussis-tetanus vaccination and measles vaccination in children with febrile convulsions: a questionnaire survey in Takamatsu City

A questionnaire about convulsions and other adverse events after vaccination was sent to doctors who administered a diphtheria-pertussis-tetanus (DPT) vaccine (the first dose) or a measles vaccine between April 1, 1995 and December 31, 1997 in Takamatsu City to children with convulsions. DPT and measles vaccines were administered to 300 and 339 such children, respectively. Many of them had febrile seizures, the last of which had occurred before more than 1 year. Among them, 175 cases were administered with DPT and 180 with measles vaccine. There were recurrences of febrile convulsions after immunization in 2 (1.1%) of the cases given DPT and 3 (1.7%) of those given measles vaccination. According to the data of the Monitoring System for Adverse Events Following Immunization (the Ministry of Health and Welfare of Japan), the incidence of convulsion after immunization in healthy children between April 1, 1996 and September 30, 1997 was 0.4% after the first dose of DPT vaccination and 0.3% after measles vaccination. In comparison, the incidence was higher in children who had had febrile convulsions before more than one year. Especially, the rate of convulsions after measles vaccinations was significantly higher (p < 0.05) in children with febrile convulsions. These results suggest that the measles vaccination should be administered with caution to the children with previous febrile convulsions.     

Late febrile convulsions: a clinical follow-up

A joint study was performed on patients from the Pediatric Clinics of Catania and Modena. Two hundred and twenty-two children who presented with febrile convulsions (FC) after the age of six years (LFC) were followed up in order to evaluate the risk of recurrence and type of convulsions. The overall results showed that 94 patients out of 222 (42.3%) had subsequent fits, both febrile and afebrile. The present study suggests that the risk of subsequent afebrile crises in LFC is higher (15.8%) than observed after "simple" FC (2-3%) and similar to that reported after "complex" FC (13-17%).     

Vasopressin may mediate febrile convulsions

The possibility that arginine vasopressin (AVP) is involved in the etiology of febrile convulsions was investigated by experiments on hyperthermia-induced convulsions in rats. Homozygous Brattleboro rats, which genetically lack AVP, and Long Evans rats, which were passively immunized by intracerebroventricular anti-AVP antiserum, either convulsed at higher body temperatures than untreated Long Evans rats or did not convulse at all. This indicates that a lack of AVP increases the threshold for the convulsions. High blood levels of AVP in hyperthermic convulsing rats compared to hyperthermic non-convulsive rats support the hypothesis that AVP may mediate febrile convulsions.     

Neurologic sequelae of experimental febrile convulsions

A study was designed to investigate the effects of experimentally produced hyperthermic seizures on the brain of the developing rat. Severty-nine newborn Sprague-Dawley white rats were divided into five groups and exposed to one of the following: Nonseizure-producing hyperthermia at 5 or 15 days (febrile controls), seizure-producing hyperthermia at 5 or 15 days, or no hyperthermia (afebrile controls). As the animals matured, seven developmental reflexes were tested and there were no differences found among the five groups in the ages at which these reflexes were acquired. At age 3 1/2 months, the ability of rats to adapt to a maze, and later to solve 12 maze problems, was studied. Although there was no significant difference in the amount of time required for any of the groups to adapt to the maze, there was a significant difference in the number of maze errors made by the different groups of rats. The mean error score for the control group was 118.5, compared with 183.0 (p less than 0.001), for rats with seizures at 5 days and 161.4 (p less than 0.001), for rats which convulsed at 15 days. It is apparent that experimental induction of a single hyperthermic seizure in the young rat interferes significantly with the animal's maze-solving ability at a later age.     

Unprovoked seizures after complex febrile convulsions

Children with complex febrile convulsions bear a higher risk of developing epilepsy than children with simple febrile convulsions. Complex febrile convulsions are defined by the presence of prolonged seizures, partial seizures and multiple seizures occurring during the same day. The aim of this study is to delineate the relative significance of each of the three criteria defining complex febrile convulsions. Fifty-seven out of 477 children (12%) admitted for febrile convulsions had complex febrile convulsions and normal neurological examination. Follow-up was available for 48 (84%) of them. Thirteen of these 48 (27%) had epilepsy at follow-up. The mean age of seizure onset among the patients with subsequent afebrile seizures was significantly lower than the rest (10.8 months versus 16.8 months). The patients with partial febrile convulsions showed a trend toward a higher risk (45%) of developing epilepsy than the patients with multiple febrile convulsions (21%).     

Lymphocytes subsets in children with febrile convulsions

In this study, lymphocytes subsets including blood CD3, CD4, CD8, CD16, CD19, and CD56 values were analyzed in children with febrile convulsion (FC) to determine whether there was the association of lymphocytes subsets in the pathogenesis of FC. The study includes 48 children with FC, and 55 healthy age matched control subjects, followed in Yüzüncü Yil University, Faculty of Medicine, Department of Pediatrics between October 2003 and June 2004. Blood CD3, CD4, CD8, CD16, CD19, and CD56 values were examined in the study and control groups. The analyses were performed in the Hematology Laboratory, Yüzüncü Yil University Faculty of Medicine, with flow cytometer device (Coulter Epics XL2, Flow Cytometer). A total of 48 children [17 girls (35.5%) and 31 boys (64.5%)], aged 6 months to 60 months (mean 22.20 +/- 13.75 months) with FC and 55 healthy children [28 girls (51%) and 27 boys (49%)], aged 6 months to 60 months (mean 28.87 +/- 17.04 months) were included in the study. When compared with the control group, the study found significantly decreased blood CD3 and CD4 values in the study group (p <.05). However, there was not significant difference in CD8, CD16, CD19, and CD56 values between the control and study groups (p >.05). When comparing the children with and without positive family history for FC, the study did not find any difference for all CD values between the groups (p >.05). Similarly, there was not significant difference in CD values between the children with simple and complex FC (p >.05). The findings suggested that decreased blood CD3 and CD4 values might be responsible for the infections connected with FC or that they might be related to the pathogenesis of FC in some children.     

The risk of epilepsy following febrile convulsions

A cohort of 666 children who had convulsions with fever were followed to determine the risks of subsequent epilepsy. High risks were found in children with preexisting cerebral palsy or mental retardation. Other major risk factors were atypical features of the febrile convulsions (such as focal seizures) and duration of febrile seizures for 10 minuts or more. The risk of developing epilepsy by age 20 was about 6 percent for all children who had experienced febrile convulsions. However, this risk figure consisted of a combination of 2.5 percent of children without prior neurologic disorder or atypical or prolonged seizures, and 17 percent of those with such complications.     

Risk factors for recurrences of febrile convulsions

Risk factors for predicting recurrences of febrile seizures were studied in an unselected series of 169 children after their first febrile seizure. Follow-up data covering 2.1–6.8 (mean 3.8) years from the first febrile seizure were available from 167 of them (98.8%) including 72 girls. Altogether 35/167 (21.0%, 95% confidence intervals (CI) 14.6% to 29.1%) had further febrile seizures, and multivariate logistic regression analysis showed the number of febrile episodes (p = 0.011) and the occurrence of such seizures among first degree relatives (p = 0.015, relative risk 3.75, CI 1.22 to 11.5) to be significant risk factors for recurrences. Our findings indicate that more emphasis should be placed on preventing febrile episodes rather than concentrating only on preventing seizures with antiepileptic therapy.     

Intermittent treatment of febrile convulsions with nitrazepam

Intermittent oral or rectal administration of diazepam for the prophylactic treatment of febrile convulsions has given results comparable to the continuous use of phenobarbital while limiting side effects and risks of toxicity. Since we believe that nitrazepam is a better anticonvulsant than diazepam, we performed a study to evaluate the effectiveness of this medication in the prophylactic treatment of febrile convulsions. Nitrazepam was given only when the children had fever and almost exclusively in children with a high risk of recurrence (less than 12 months of age at first convulsion; atypical convulsion; one or several previous convulsions). Thirty one children with a high risk of recurrence received nitrazepam. The rate of recurrence in this group was 19.3% after a follow-up of 16 months, compared to 45.8% in 24 children who also had a high risk of recurrence but in whom the parents refused the medication or gave it inadequately (p less than 0.05). Fifty one children with a low risk of recurrence also were evaluated and followed for at least 12 months (mean 15.4 months). Six were treated with nitrazepam, mostly because of parental anxiety, and none had a recurrence; of the 45 untreated children in this group, 6 (13.6%) had another convulsion. These results show the efficiency of nitrazepam in the prophylactic treatment of febrile convulsions.     

A genetic study of febrile convulsions.

307 probands with febrile convulsions classed as the simple type (131 children) and the complicated type (176 children) were genetically analyzed. There was a tendency toward familial aggregation of febrile convulsions, and genetic involvement was suggested. The multifactorial mode of inheritance best agreed with the observations. (1) The ratio of incidence of febrile convulsions in siblings of probands in the present study (19.9%) to the incidence in the general population (2.9%), i.e., 6.85, was rather close to the expected ratio of 5.87 from the multifactorial inheritance system. (2) The incidence in siblings tended to be higher when either or both of their parents had a history of febrile convulsions. In 2-child families where the first child was affected, the incidence in the second child tended to increase in parallel with the increasing incidence in parents. (3) The incidence in siblings was higher if probands were males. (4) The heritability, when estimated by Falconer's procedure, was as high as 76%, showing that febrile convulsions are strongly genetically predisposed. These findings were more distinctly observed in the simple type than in the complicated type.     

Association of developing childhood epilepsy subsequent to febrile seizure: A population-based cohort study

Purpose

Epilepsy is an important neurological condition that frequently associated with neurobehavioral disorders in childhood. Our aim was to identify the risk of developing epilepsy subsequent to febrile seizure and the association between epilepsy risk factors and neurobehavioral disorders.

Evidence favoring genetic heterogeneity for febrile convulsions

PURPOSE: Two large Canadian kindreds appearing to segregate febrile convulsions as an autosomal dominant trait were evaluated for linkage to three known FC loci, as well as other epilepsy loci. METHODS: Members of the two families were genotyped with microsatellite markers linked to the previously identified febrile convulsion loci, FEB1, FEB2, and GEFS+, and we performed two-point linkage analyses by assuming an autosomal dominant mode of inheritance. RESULTS: We report the exclusion of the FC trait in our families to FEB1 on 8q13-21 and to a second febrile convulsion locus on 19p13. Furthermore, we also excluded the GEFS+ locus on 19q13.1 as the cause of febrile convulsions in both kindreds. Microsatellite markers linked to juvenile myoclonic epilepsy (EJM1), benign neonatal familial convulsions EBN1 and EBN2, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), idiopathic generalized epilepsy (EGI), progressive myoclonic epilepsy of Unverricht-Lundborg (EPM1), and partial epilepsy with auditory features (EPT), were also excluded as potential loci linked to the FC trait in our families. CONCLUSIONS: These findings favor considerable genetic heterogeneity for febrile convulsions.