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.     

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.     

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.     

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.     

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.     

Double-blind, randomized trial of diazepam versus placebo for prevention of recurrence of febrile seizures

The aim of this study was to evaluate the efficacy and tolerance of intermittent oral administration of diazepam during hyperthermia for reducing the recurrence of febrile seizure: 185 children, between 8 months and 3 years of age, with a first febrile seizure and normal neurologic development, were randomly assigned in a double-blind fashion to receive orally administered diazepam (0.5 mg/kg, then 0.20 mg/kg, every 12 hours) or placebo, whenever the rectal temperature was more than 38 degrees C. The main criterion of efficacy was the seizure recurrence rate 1 year after the first seizure. The duration of the study was 3 years; eight different centers in France participated. There were 462 febrile episodes and 1000 days with prophylactic treatment. The recurrence rates did not differ between the diazepam group (16%) and the placebo (19.5%) group. The children with recurrent seizures were significantly younger at the time of the first seizure (17 +/- 6.9 months) than children without a recurrent seizure (21 +/- 8.5 months). In children with recurrent seizures, prophylactic treatment was correctly administered to only 1 of 15 children in the diazepam group and to 7 of 18 children in the placebo group. The following were the reasons for this poor cooperation: convulsion being the first manifestation of the fever (seven cases in each group), parents neglecting to give treatment (nine cases), and refusal to take treatment by two children. Side effects were similar in the two groups except for hyperactivity, which was more frequent in the diazepam (138 days) than in the placebo (34 days) group. Intermittent oral administration of diazepam at the onset of fever offered no advantage over placebo in preventing recurrence of seizure. This finding probably reflects a lack of efficacy of the intermittent method rather than of diazepam itself.     

Evaluation of Selenium Levels and Mean Platelet Volume in Patients with Simple Febrile Convulsion

Objective: This study aimed to evaluate serum selenium levels and mean platelet volume in children who experience simple febrile convulsion. Methods: The study comprised 42 patients diagnosed with simple febrile convulsions and a control group of 30 healthy children. Blood samples were taken following a febrile convulsion. Selenium levels in the serum of both the patients and control subjects were measured with the hydride formation method on an atomic absorption spectrometry device and mean platelet volume was evaluated. Findings: When the mean values of the febrile convulsion patients were compared with those of the control group, the mean selenium levels and thrombocyte count were found to be statistically significantly low (P=0.002, P=0.01 respectively) and the mean platelet volume values were statistically significantly high (P=0.002). Conclusion: While low serum selenium levels cause the onset of a febrile seizure in patients with simple febrile convulsion, it is thought that the increased mean platelet volume shows infection activity causing febrile convulsion.Key Words: Febrile Convulsion, Selenium, Platelet: Mean Platelet Volume, Antioxidant     

Sodium valproate versus phenobarbital in the prophylactic treatment of febrile convulsions in childhood

Phenobarbital has been shown to offer effective prophylaxis against childhood febrile convulsions. However, a high percentage of children do not tolerate phenobarbital, mainly due to behavioral changes. Valproate, due to its low toxicity, appears to be an attractive alternative to phenobarbital treatment. Ninety children admitted with their first febrile convulsion were offered prophylactic treatment with either phenobarbital 3–5 mg/kg/day or valproate 20–30 mg /kg/day. Twenty-five children whose parents refused prophylactic treatment make up an untreated control group. Serum levels of the appropriate drug were measured at each follow-up visit. The three groups appear to be comparable. Twenty-one per cent of the phenobarbital treated children required discontinuation of the drug due to side effects. All the children tolerated valproate therapy.Twelve out of 25 untreated children suffered recurrences. Eight out of 33 children treated with phenobarbital suffered recurrences. Four out of 32 children on valproate therapy had recurrences. The difference between valproate treatment and no therapy at all is highly significant (P<0.0001). Phenobarbital did not reduce the risk of recurrence. We now recommend prophylactic treatment with valproate to children with febrile seizures.     

Duration of fever prior to onset of a simple febrile seizure: a predictor of significant illness and neurologic course

This study tested the hypothesis that the duration of fever prior to the onset of a simple febrile seizure may be an important clinical variable with respect to patient outcome. The duration of fever prior to seizure according to patient history was defined as either long (greater than or equal to 24 hours) or short (less than 24 hours). We hypothesized that simple febrile seizures which occur with a history of a fever of long duration (LDF) are more likely to be associated with a significant illness at presentation or a subsequent neurologically abnormal course than are simple febrile seizures which occur with a history of a fever or short duration (SDF). Of 100 cases which met study criteria for simple febrile seizures, nine had a LDF and 91 had a SDF prior to the development of a seizure. No statistical differences in age, sex, maximum fever recorded in the emergency department, duration of seizure, WBC, or electrolytes were found between patients with SDF and LDF (P less than 0.01). Of the nine patients with a LDF, all had either a significant illness at the time of initial visit or a subsequent neurologically abnormal course. Of the 91 patients with a SDF, 88 had a good outcome, while two had a significant illness at the time of visit, and one had a subsequent neurologically abnormal course. These results suggest that children with a history of LDF prior to the occurrence of a simple febrile seizure are more likely to have a serious illness at presentation or a subsequent neurologically abnormal course than are children with seizures which occur with a history of SDF.     

Zinc in CSF of patients with febrile convulsion

OBJECTIVE: This prospective study was carried out from July-December 1999 to see the status of zinc in CSF of children with febrile convulsion and to compare this to that of control. METHODS: Forty-two cases of febrile convulsion and 30 controls (fever without convulsion) were enrolled into the study. CSF zinc was estimated by atomic absorption spectrophotometry (AAS) in Atomic Energy Center, Dhaka and compared between the two groups. RESULTS: The mean zinc level in CSF in the study sample was 40.19mgm/L and that in control was 74.98mgm/L. This difference was statistically significant (p<0.001). CONCLUSION: The study concludes that a significantly lower of zinc exists in CSF of children with febrile. However no relationship was found between CSF zinc status with age, sex, degree & duration of fever and time of lumbar puncture after convulsion.     

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.     

Late cognitive effects of early treatment with phenobarbital.

We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile 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.     

Febrile seizures.

Febrile seizures are the most frequent of seizure disorders in childhood. Febrile seizures are most common in children between 6 months and 3 years of age, with a peak incidence at about 18 months. Approximately 30% to 40% of children who experience a febrile seizure will have a recurrence. The majority of febrile seizures occur within 24 hours of the onset of the fever. Febrile seizures can be simple or complex. Diagnostic studies are usually not necessary. Febrile seizures usually are self-limited, and intervention to stop the seizure often is unnecessary. When possible, the cause of the fever should be treated. Continuous preventative anticonvulsant therapy is not recommended for children with either simple or complex febrile seizures. The use of intermittent anticonvulsant therapy is not routinely indicated. Parental educational and counseling is important. The prognosis is excellent.     

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.     

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.     

Frequency of fever episodes related to febrile seizure recurrence

The aim of this study was to assess the number of fever episodes as a risk factor for febrile seizure recurrence during the first 6 months after the last previous febrile seizure. In a 6-month follow-up study of 155 children, aged 3 months to 5 y, with a first or a recurrent febrile seizure, the occurrence of fever episodes and febrile seizure recurrences was prospectively documented. Using logistic regression analysis the association between the baseline characteristics and the number of fever episodes and the outcome, a febrile seizure recurrence, was studied. In total, 260 fever episodes were registered; 29 children experienced 1 or more febrile seizure recurrence during follow-up. Two factors were associated with febrile seizure recurrence: the number of fever episodes [odds ratio (OR) = 1.8; 95% confidence interval (CI): 1.4-2.4)] and age at study entry (OR = 0.6; 95% CI: 0.3-1.1). In a multivariable model, only the number of fever episodes remained significant. In conclusion, the number of fever episodes increases the risk of a febrile seizure recurrence with a factor of 1.8 per fever episode in the first 6 months after a febrile seizure.     

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.     

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.