Recurrence of febrile convulsions in a population-based cohort

The risk of recurrence after an initial febrile seizure was 25% in a population-based cohort of 639 children followed from their first febrile seizure. Prognostic factors were an increasing risk of recurrence with younger age at first febrile seizure, a first degree relative with febrile seizures and complex features of the first febrile seizure. The effect of complex features was modified by age at first febrile seizure and family history in that complex features alone did not increase risk of recurrence but further increased the risk for children under 18 months at first seizure and/or with a positive family history. The prognostic factors for all febrile convulsions recurrences were also prognostic for having subsequent complex febrile convulsions. Children with none of the prognostic factors had only a 3% risk of a future complex febrile seizure while children under 18 months at first febrile convulsion and a positive family history or complex features had about a 20% risk of a subsequent complex febrile seizure.     

Efficacy of a diazepam suppository at preventing febrile seizure recurrence during a single febrile illness

Purpose: To assess the efficacy of diazepam suppositories at preventing febrile seizure recurrence during a single febrile illness to determine how to treat children with a febrile seizure on presentation at the hospital. Methods: We studied 203 children with febrile seizures from December 2004 through March 2006. On admission between December 2004 and May 2005, a diazepam suppository was administered to the patients. Patients seen between June 2005 and March 2006 were not treated with antiepileptic drugs on admission. Results: We saw a significant difference in the rate of recurrence of febrile seizures between children treated with diazepam and those who were not. Recurrences were observed in 2 (2.1%) of 95 children treated with diazepam and in 16 (14.8%) of 108 untreated children. For the 108 untreated patients, the median age was 22.8 months in those with recurrences and 30.6 months in those without, confirming that a younger age was related to a recurrence. Conclusions: A diazepam suppository after a febrile seizure will reduce the incidence of recurrent febrile seizures during the same febrile illness. However, a diazepam suppository after a febrile seizure should be used after carefully considering the benefits and potential adverse effects.     

Fieberkrämpfe

Febrile seizures are the most common seizure type in man and may be classified as simple or complex. The overall recurrence rate is 30–35%. Predictors of recurrence include a family history of febrile seizures, age at onset of less than 18 months, and a relatively low body temperature at the time of the seizure. The risk of subsequent epilepsy is only slightly elevated in children with simple febrile seizures. Factors that increase epilepsy risk are complex febrile seizures, abnormal neurological development, and a family history of epilepsy. While older studies did not report increased mortality in children with frebrile seizures, a recent large population-based study found increased mortality during the first 2 years after a febrile seizure in children with complex febrile seizures, seizure onset in the first year of life as well as seizures triggered by a body temperature of less than 39°C. Semiology and prognosis of febrile seizures are heterogeneous. Simple febrile seizures have a good prognosis with diagnostic and therapeutic procedures being uniform at the international level. Children with complex febrile seizures have a poorer prognosis, concerning both risk of epilepsy and mortality within the first 2 years after the first febrile seizure. In these children, decisions concerning diagnostic work-up and medical management are based on the risk profile of the individual patient.     

Are febrile seizures an indication for intermittent benzodiazepine treatment,and if so,in which cases?

Febrile seizures occur in ～4% of children. After a first febrile seizure, the risk of recurrence is ～40%, but excellent studies document that febrile seizures do not cause brain damage or deficits in cognition or behaviour. The risk of subsequent epilepsy is 2–4%. Prolonged febrile seizures are of concern because a child may later develop mesial temporal sclerosis and intractable epilepsy in rare cases. Most prolonged febrile seizures represent the first febrile seizure and cannot be anticipated. A first prolonged febrile seizure does not increase the risk of recurrence, but if there is a recurrence, it is more likely to be prolonged. Prevention of recurrent febrile seizures is difficult. Antipyretics are ineffective. Daily AED treatment is not often justified. Intermittent oral diazepam at the time of illness is not very successful and has significant side effects. The most optimistic study found that the number of subjects required to treat in order to prevent one recurrence was 14. Intermittent clobazam has fewer side effects than diazepam and may be somewhat effective. Rescue benzodiazepines given outside health care facilities may be effective in selected patients to prevent prolonged recurrences, although this has not been proven with rectal diazepam which has been more extensively studied than buccal or nasal midazolam. Currently, we suggest that, for children with febrile seizures, candidates for consideration for rescue benzodiazepines are those with a prolonged febrile seizure or poor access to medical care. It is possible that the use of a rescue benzodiazepine may alleviate severe parental anxiety, but this remains to be established.     

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%).     

Complex Febrile Seizures

In the context of a prospective cohort study, we examined the associations between individual complex features of both first (n = 428) and recurrent (n = 240) febrile seizures and factors shown to predict outcome in children with febrile seizures. Thirty-five percent of first and 33% of recurrent febrile seizures had one or more complex features (focal onset, duration ≥10 min, or multiple seizures during the illness episode). There were strong correlations between focality and prolonged duration for both first and recurrent febrile seizures. A low fever at the time of the seizure was marginally associated with prolonged duration. Most factors associated with either recurrent febrile seizures or subsequent unprovoked seizures were not associated with either the initial seizure being complex or the likelihood that a recurrence would be complex. However, in children with recurrent febrile seizures, complex features tended to repeat. This factor was statistically significant and particularly striking for prolonged duration. Genetic or other constitutional factors may explain why the prolonged feature recurs. Eleven (2.5%) children had three or four risk factors for recurrent febrile seizures and a first febrile seizure that was prolonged. Eight (72.7%) of them experienced a recurrent febrile seizure that was prolonged. This very small group of children may be candidates for abortive therapy to be administered at the onset of a recurrent seizure.     

The value of early postictal EEG in children with complex febrile seizures

PURPOSE: To assess the usefulness of an early postictal EEG in neurologically normal children with complex febrile seizures. METHODS: We conducted a retrospective chart review of all neurologically normal children who were hospitalized over a period of 2.5 years after complex febrile seizures, and had an EEG up to 1 week after the seizure. RESULTS: Thirty-three patients (mean age, 17.8 months) qualified for inclusion into the study. Twenty-four patients were qualified as complex cases based on one factor (prolonged in 9, repetitive in 13, and focal in 2). Nine other patients had two complex factors: in six patients, the seizures were long and repetitive; in two patients, the seizures were focal and repetitive; and in one patient, the seizures were long, focal, and repetitive. Thirteen (39%) patients experienced prior febrile seizures. All 33 patients had a normal postictal sleep EEG. Our results indicate with a 95% probability that the true rate of abnormalities in an early postictal EEG performed on otherwise normal children with complex febrile seizures is 8.6% or less. CONCLUSIONS: The yield of abnormalities of an early postictal EEG in this population is low and similar to the reported rate of abnormalities in children with simple febrile seizures. The routine practice of obtaining an early EEG in neurologically normal children with complex febrile seizures is not justified.     

Nonfebrile Illness Seizures: A Unique Seizure Category?

PURPOSE: To describe the clinical characteristics of children with a first-time nonfebrile seizure in the setting of mild illness and to test the hypothesis that these seizures are associated with illness characterized by diarrhea. METHODS: This retrospective cohort study was performed in a pediatric emergency department. Patients ages 6 months to 6 years who were evaluated with first-time seizures were eligible for inclusion. Subjects were divided into three groups on the basis of symptoms accompanying their seizure: febrile (temperature, >38.0 degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile illness (no fever at the time of seizure, but other symptoms of illness present). RESULTS: Of the 323 children with first-time seizures, 247 (76%) had febrile seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness seizures. Children with nonfebrile illness seizures were more likely than children with febrile seizures to have diarrheal illnesses accompanying their seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not differ significantly between children with febrile and nonfebrile illness seizures. Diagnostic testing for infectious etiologies was not performed frequently in either group. CONCLUSIONS: Nonfebrile illness seizures may represent a distinct group of seizures with unique epidemiology. Further study to define this seizure group better is warranted.     

Pathogenetic role of monoamine metabolism in complex febrile seizures.

To investigate the pathogenetic role of monoamine metabolism for febrile seizures, concentrations of homovanillic acid and 5-hydroxyindoleacetic acid were evaluated in the lumbar cerebrospinal fluid of affected children. This series included children who underwent lumbar puncture within 4 hours after seizures, at which time the lumbar cerebrospinal fluid is presumed to represent a ventricular source of cerebrospinal fluid, without the consequence of a seizure. The subjects were 21 patients with simple febrile seizures, eight with complex febrile seizures, and eight control patients. The complex febrile seizure group had lower homovanillic acid and 5-hydroxyindoleacetic acid levels than the control group, whereas the simple febrile seizure group and control group did not have a significant difference. Although statistically not significant, the complex febrile seizure group was inclined toward lower homovanillic acid and 5-hydroxyindoleacetic acid levels than the simple febrile seizure group. These results implied that abnormal monoamine metabolism contributes to seizure susceptibility in the complex febrile seizure group. The simple febrile seizure group may be heterogeneous, and abnormal monoamine metabolism can play a role in seizure development for some children of this group.     

Febrile seizures: treatment and prognosis

Recent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal longterm outcome. A precise knowledge of the short- and long-term outcome with or without treatment, and short- and long-term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short-term or prophylactic treatment on the short- and long-term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long-term outcome as compared with short-term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long-term outcome, even without treatment. Many prefer a "wait and see" policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short-term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short-term seizure control of febrile status and careful parental counseling are the two most important targets of treatment.     

Influenza A and febrile seizures in childhood

The aims of the present study are to identify predisposing factors of febrile seizures in influenza A infection and to clarify the special characteristics of febrile seizures in children with influenza A infection. Between January and July 2005, children hospitalized because of febrile seizures and subsequently confirmed influenza A infection were enrolled as subjects. Age-matched control subjects were those admitted as a result of influenza A infection but no febrile seizures (control 1) and children who developed febrile seizures with negative viral studies (control 2). Significant factors for the development of febrile seizures include: history of febrile seizures, family history of seizure disorders, and coexisting gastroenteritis. Independent risk factor for febrile seizures was history of febrile seizures (odds ratio 7.58, 95% confidence interval CI 1.48 to 38.84, P = 0.015). When compared with children who developed febrile seizures with negative virus studies, children who developed febrile seizures in influenza A infection had a significantly higher maximum body temperature, shorter duration of fever before seizure onset, and more frequent occurrence of partial seizures. Current episode represented first seizure in 26.5% of children infected with influenza A as compared with 50% of children whose virus studies were negative (P = 0.04). The findings suggest that effective vaccination may prevent development of febrile seizures, especially in those patients with past history of febrile seizures. Rapid diagnostic testing for influenza infection in the management of complex febrile seizures, especially during influenza season, is cost-effective.     

Efficacy and tolerability of levetiracetam in children younger than 4 years: a retrospective review

PURPOSE: To review our experience of the efficacy and tolerability of levetiracetam (LEV) in children younger than 4 years. METHODS: We used retrospective chart review to identify 122 children with seizures who were younger than 4 years and followed for >or=6 months. Efficacy was evaluated on the basis of the occurrence and durability of seizure remission. Tolerability was based on parent- and patient-reported side effects. RESULTS: Seventy (57%) subjects achieved seizure remission, and 52 (43%) did not. In univariate analysis, those achieving seizure remission were more likely to have partial epilepsy, require lower maintenance doses of LEV, and have fewer than two seizures per month at initiation of the medication. Only seizure frequency at initiation of LEV remained significant in multivariate analysis. The median duration of seizure freedom (8.9 month) was not influenced by age, epilepsy type, gender, or pretreatment seizure frequency. The dose of LEV was the only significant predictor of the duration of seizure remission, with longer duration of seizure remission seen in those taking <30 mg/kg/day compared with those taking > 30 mg/kg/day (median, 12.8 months vs. 3 months; p<0.0001). Side effects of LEV occurred in 34% of subjects but required discontinuation in only 16%, most commonly because of behavioral disturbances. CONCLUSIONS: LEV is an effective medication in children younger than 4 years and at doses lower than previously reported. It also well tolerated, suggesting that it represents an important option for the treatment of epilepsy in this age group.     

Effectiveness of intermittent diazepam prophylaxis in febrile seizures: long-term prospective controlled study

The efficacy of intermittent rectal diazepam prophylaxis is assessed in the prevention of febrile seizures. In a prospective randomized cohort trial, 139 children (77 girls, 62 boys) who experienced a first febrile seizure were allocated to two groups: group A, which received intermittent diazepam (n = 68), and group B, which received no prophylaxis (n = 71). All children had a 3-year follow-up. The inclusion criteria were no personal history of afebrile seizures, normal neurodevelopment, no previous anticonvulsant therapy, and age between 6 months and 3 years. Each group was stratified to low, intermediate, and high risk according to the available clinical data. The 36-month recurrence rates in the no-prophylaxis group were 83% in high-risk patients, 55% in intermediate-risk patients, and 46% in low-risk patients. In the prophylaxis group, the recurrence rates were reduced in all risk groups: 38%, 35%, and 33%, respectively. Intermittent diazepam prophylaxis reduces the recurrence rate mainly in high-risk children provided that sufficient doses are given on time and adequately.     

Home use of rectal diazepam to prevent status epilepticus in children with convulsive disorders

Thirty families were taught to administer rectal liquid diazepam to their children to stop a seizure at home. Twelve children had previous prolonged afebrile seizures, and 18 had either prolonged or repeated febrile seizures. During follow-up, 17 of the 30 families administered the rectal diazepam an average of three times per child with no complications. Fifteen of 17 families reported prompt cessation of the seizure, while in two the rectal diazepam was unsuccessful and hospital treatment was needed. We conclude that rectal diazepam is a useful adjunctive home treatment for children at risk for prolonged seizures. Hospitalization is decreased and parental confidence increased. Without our knowledge, twelve families taught others how to give the rectal diazepam, a practice that might be hazardous and should be anticipated.     

Seizure Recurrence After A First Febrile Seizure: A Multivariate Approach

The results are presented of a follow-up study of 155 Dutch children after the first febrile seizure. Of these initially untreated children 37 per cent had had at least one, 30 per cent at least two and 17 per cent at least three subsequent seizures. The vulnerable period for recurrent seizures after the first febrile seizure was between 12 and 24 months, whereafter the risk was four to five times lower; after any seizure the risk was highest within the first six months, declining steadily after six months without seizures. A first-degree family history of any type of seizure predicted multiple recurrences; an age of at least 30 months and a temperature of greater than or equal to 40 degrees C at initial seizure were associated with reduced risk. Factors in combination influenced the risk of recurrent seizures, sometimes in opposite ways.     

Levetiracetam monotherapy for late poststroke seizures in the elderly

Stroke is the most common cause of seizures in the elderly. Antiepileptic drugs are used to treat most patients with late poststroke seizures. The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) in patients aged 60 or older with late-onset poststroke seizures. This prospective study evaluated patients 60 years of age or older, who had at least two late-onset poststroke seizures and were given LEV monotherapy. Demographic data and seizure and stroke characteristics were recorded. Outpatient visits were made after 2, 4, 6, 9, and 12 months and every 3 months thereafter, and the effectiveness and tolerability of LEV were investigated. Thirty-four patients with a mean age of 69.76+/-6.41 were included in this study. Average seizure frequency before treatment was 3.61+/-3.02/month. Mean follow-up time was 17.68+/-3.24 months. At daily doses of 1000-2000 mg, 82.4% of the patients were seizure free, and 7 patients (20.6%) had side effects. LEV was discontinued in one patient because of severe somnolence. Two patients were switched to another antiepileptic drug because of uncontrolled seizures despite an increase in dose up to 3000 mg/day. LEV monotherapy can be effective and well tolerated in elderly patients with late-onset poststroke seizures.     

Febrile seizures in southern Chinese children: incidence and recurrence

This study investigates the incidence, recurrence, and risk factors of febrile seizures in southern Chinese children. A retrospective study of a 5-year period (March 1998 through February 2003) was conducted for all children admitted with first febrile seizure to a university teaching hospital of Hong Kong, serving a population of 31,700 under 6 years. A total of 565 Chinese children (329 males, 236 females) were identified with mean age of 2.1 +/- 1.1 years. The annual incidence was 0.35%. Among them 16% (91/565) had complex febrile seizures. Family history of febrile and afebrile seizures was present in 17.5% and 2.7% respectively. The mean follow-up period was 2.33 +/- 1.69 years. Altogether 103 children (18%) had recurrence, and the cumulative rates by 1, 2, and 3 years were 12.7%, 18.7%, and 20.5% respectively. Three significant factors were identified for higher risk of recurrence: early age of onset, family history of febrile seizure, and complex febrile seizure. The incidence of first febrile seizure in Chinese children is low compared with the Western world and relatively similar to mainland China. Recurrence is also lower despite similarities in the predictive factors. Further epidemiologic and genetic studies will be necessary to confirm and explain this interethnic variation.     

Academic performance in children with new-onset seizures and asthma: a prospective study

The purpose of this study was to compare teachers' ratings of academic performance over 24 months between children with new-onset seizures (N=121) and those with new-onset asthma (N=54) aged 4 to 14. At each data collection point (baseline, 12 months, 24 months), children with seizures were placed into two groups according to their recurrent seizure status (yes/no) during that period. Longitudinal linear mixed models were used to explore differences between the asthma group and the two seizure groups and to determine if differences in teachers' ratings of performance in children with seizures were associated with age, gender, or use of medication. In the seizure sample, scores for children in both groups (with and without recurrent seizures) initially declined at 12 months; however, at 24 months, children who did not have recurrent seizures improved, whereas children who continued to have recurrent seizures declined. There was a trend for younger children to decline more than older children.     

Recommendations for the management of "febrile seizures" Ad hoc Task Force of LICE Guidelines Commission

Febrile seizures are the most common seizure disorder in childhood, affecting 2–5% of children. Simple febrile seizure is defined as a short (<15 min) generalized seizure, not recurring within 24 h, that occurs during a febrile illness not resulting from an acute disease of the nervous system in a child aged between 6 months and 5 years, with no neurologic deficits and no previous afebrile seizures. These recommendations address the instructions for management of the first febrile seizures, giving criteria for hospital admission, diagnosis, differential diagnosis, and treatment of a prolonged seizure. The authors stressed the benign prognosis of the majority of cases and the risk factors for recurrence of febrile seizures and appearance of epilepsy later on. Both continuous and intermittent anticonvulsant therapy are efficacious in preventing single febrile seizures, but side effects may be so important to overcome the benefits. These treatments are indicated in very selected patients.     

Febrile Seizures: Clinical Characteristics and Initial EEG

We examined the relationship between clinical characteristics and EEG classification in all children with febrile seizures examined at the University Pediatric Clinic, Skopje, Yugoslavia between 1982 and 1984. This is the only facility in Macedonia providing EEG or neurologic consultation for children. EEGs were classified as paroxysmally abnormal if they contained spikes, sharp waves, or spike-wave complexes considered abnormal for age. In all, 22% of the 676 children had an abnormal initial EEG. The most common basis for classification as abnormal was spike-wave complexes greater than 3 Hz; the next most common basis was the presence of spikes. Birth weight, gender, accompanying illness, and family history of seizures, and whether the index seizure was single or multiple were not associated with differences in rate of abnormal EEG. Clinically focal index seizures and longer duration were associated with EEG abnormality. Number of previous febrile seizures was associated with an increasing rate of EEG abnormality, from 18% in children with no previous seizures to 63% in those with four or more previous seizures. Age at EEG was linearly related to likelihood of paroxysmal EEG abnormality, both for the total cohort and for the 376 children with no previous seizures. In the total cohort, logistic regression identified leading predictors of abnormal initial EEG to be older age, number of previous febrile seizures, preexisting motor abnormality, and focal seizures. For children with a first febrile seizure, leading predictors were focal seizure, older age, and preexisting motor abnormality.