Childhood-onset epilepsy with and without preceding febrile seizures

OBJECTIVE: To identify characteristics in children with epilepsy that differ between those who did versus did not have a history of preceding febrile seizures. BACKGROUND: Febrile seizures precede epilepsy in 10 to 15% of children. Little is known about the specific types of epilepsy associated with febrile seizures. METHODS: In a community-based, prospectively identified cohort of children, the association between prior febrile seizures and characteristics of the children's epilepsy (seizure type, epilepsy syndrome, age at onset, underlying etiology, family history) were examined for 524 of the children who were aged > or =1 year at onset of epilepsy. RESULTS: Seventy-three (13.9%) had febrile seizures. Children with febrile seizures were more likely to have a first-degree or a second-higher-degree relative with febrile seizures and less likely to have childhood absence epilepsy and absence seizures compared with children without febrile seizures. This was especially true for simple febrile seizures. There was no specific association with localization-related forms of epilepsy. Complex, but not simple, febrile seizures were associated with younger age at onset of epilepsy. There was no evidence that focal or prolonged febrile seizures were associated with localization-related epilepsy or temporal lobe epilepsy per se. Of the three children whose initial MRIs demonstrated hippocampal atrophy, none had a history of febrile seizures. CONCLUSIONS: At the time of diagnosis, febrile seizures are not specifically related to temporal lobe epilepsy or localization-related epilepsy in general. A genetic component for febrile seizures is suggested by its positive associations with family history, especially for simple febrile seizures. Complex febrile seizures represent an underlying age-dependent susceptibility.     

Cognitive skills in children with intractable epilepsy: comparison of surgical and nonsurgical candidates

PURPOSE: To compare neuropsychological performance of two groups of children with intractable epilepsy: those who are surgical candidates, and those who are not. METHODS: Intelligence, verbal memory, visual memory, academic skills, and sustained attention were measured in children aged 6-18 years. The effects of number of antiepileptic drugs (AEDs), seizure frequency, age at seizure onset, and duration of seizure disorder were examined. RESULTS: Both groups had high rates of impairment. Group differences were found only on the verbal memory task. Children who experienced seizures in clusters had higher IQ, reading comprehension, and arithmetic scores. Age at seizure onset and proportion of life with seizures were related to IQ. Performance did not vary with AED monotherapy versus polytherapy. CONCLUSIONS: Few differences exist in cognitive performance between children with intractable seizures who are and those who are not surgical candidates. These findings suggest that children who are not surgical candidates can serve as good controls in studies on cognitive outcome of surgery.     

Seizures in rural Zambia

PURPOSE: To describe the period prevalence of epilepsy and febrile seizures in a bush hospital and discuss the medical sequelae and social impact of seizures in this population. METHODS: For 13 weeks, an evaluation of inpatients was made at Chikankata Hospital in rural Zambia. Inpatients identified as having seizures, "fits," "spells," or "fainting," were evaluated by a medical records review, basic demographic data, a neurological history and physical examination, and a treatment history. A semistructured questionnaire was administered to evaluate the social impact of seizures and assess factors associated with delayed care seeking. RESULTS: Seizures composed 44% of all inpatient neurologic disease and resulted in 84 admissions. Epilepsy patients received treatment primarily from traditional healers; only 31% reported ever receiving antiepileptic drugs (AEDs). Among those who had received treatment, AEDs were frequently underdosed. Patients with epilepsy had significantly less education than their sex-matched siblings. Patients with untreated epilepsy for >2 years were more likely to have experienced serious burns or falls requiring hospitalization. Children with febrile seizures whose parents held supernatural beliefs regarding seizures were more likely to be treated with traditional medicines, had higher malarial parasite counts, and required longer hospitalizations than children with febrile seizures whose parents recognized the association between seizures and hyperthermia. CONCLUSIONS: Epilepsy and febrile seizures are responsible for a significant burden of disease in rural Zambia. Serious medical complications often result from seizures, especially if untreated for >2 years. Social stigma decreases educational opportunities and misperceptions regarding seizures may result in delayed care for children with febrile seizures. Some evidence suggests that epilepsy is underreported, underrecognized, and undertreated in this population.     

Febrile seizures and behavioural and cognitive outcomes in preschool children: the Generation R Study

Aim  General developmental outcome is known to be good in school‐aged children who experienced febrile seizures. We examined cognitive and behavioural outcomes in preschool children with febrile seizures, including language and executive functioning outcomes. Method  This work was performed in the Generation R Study, a population‐based cohort study in Rotterdam from early fetal life onwards. Information about the occurrence of febrile seizures was collected by questionnaires at the ages of 1, 2, and 3 years. At the age of 3 years, behaviour and emotion were assessed using the Child Behavior Checklist. Information on expressive language development was obtained by the Language Development Survey at the age of 2 years 6 months. To assess executive functioning, parents completed the Behaviour Rating Inventory of Executive Function – Preschool Version when their children were 4 years old. Final analyses were based on 3157 children. Results  No associations were found between febrile seizures and the risk of behavioural problems or executive functioning. In contrast to single febrile seizures, recurrent febrile seizures were significantly associated with an increased risk of delayed vocabulary development (odds ratio 3.22, [95% confidence interval 1.30–7.94]). Interpretation  Febrile seizures are not associated with problem behaviour or executive functioning in preschool children, but the results suggest that children with recurrent febrile seizures might be at risk for delayed language development.     

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.     

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.     

Seizures with Fever After Unprovoked Seizures: An Analysis in Children Followed from the Time of a First Febrile Seizure

Summary: Purpose: To determine how the onset of unprovoked seizures influences recurrence of seizures with fever in children followed from the time of a first febrile seizure.
Methods: In a prospective cohort of children (n = 428) identified at the time of a first febrile seizure, predictors of a second seizure with fever were identified. The occurrence of a first unprovoked seizure was treated as a time-dependent covariate in a Cox regression model rather than as a censoring point as it traditionally has been in the past.
Results: One hundred forty-three (33.4%) children had further seizures. Seven had further seizures with fever only after onset of unprovoked seizures. After adjustment was made for the four previously described predictors of recurrent febrile seizures (age at onset, family history, height of fever, and duration of fever), the onset of unprovoked seizures was associated with a rate ratio of 3.47 (p = 0.0015), indicating a large increase in the risk of further seizures with fever after onset of unprovoked seizures.
Conclusions: Young children who develop unprovoked seizures after a febrile seizure are at substantial risk for further seizures with fever. This may represent part of the spectrum of benign febrile seizures or it may represent the so-called "epilepsy triggered by fever" spectrum. It affects only a small proportion of children with febrile seizures; however, in some children, it may be useful information to consider when making treatment decisions.     

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.     

Epilepsy After Febrile Seizures: Twins Suggest Genetic Influence

BackgroundA history of complex febrile seizures can increase the risk of epilepsy, but the role of genetic factors is unclear. This analysis evaluated the relationship between febrile seizures and epilepsy.MethodsInformation on the history of seizures was obtained by a questionnaire from twin pairs in the Mid-Atlantic, Danish, and Norwegian Twin Registries. The information was verified using medical records and detailed clinical and family interviews. The initial study evaluated the genetic epidemiology of febrile seizures in this population. Further information was analyzed and used to evaluate genetic associations of different febrile seizure subtypes.ResultsHistories of febrile seizures were validated in 1051 twins in 900 pairs. The febrile seizure type was classified as simple, complex, or febrile status epilepticus. There were 61% simple, 12% complex, and 7% febrile status epilepticus. There were 78 twins who developed epilepsy. The highest rate of epilepsy (22.2%) occurred in the febrile status epilepticus group. Concordance was highest in simple group.ConclusionA twin with febrile status epilepticus is at the highest risk of developing epilepsy, but simple febrile seizures gave the highest risk for the unaffected twin to develop seizures or other neurological issues. These results are consistent with previous findings. There is a subgroup of febrile seizures that can be associated with long-term consequences. This subgroup can be associated with a significant financial and emotional burden. It is currently not possible to accurately identify which children will develop recurrent febrile seizures, epilepsy, or neuropsychological comorbidities.     

Factors associated with ambulance requests for febrile seizures

The objective of this study was to determine factors associated with ambulance requests for febrile seizures. This study retrospectively investigated medical records of patients who visited the Emergency Care Unit at Tokyo Metropolitan Toshima Hospital in the 5-year period after April 2001. Subjects' basic characteristics (e.g., age and sex), medical history of febrile seizures, sibling and parental medical history of febrile seizures, and distance from hospital were investigated. In total, 310 subjects used ambulances, and 106 came to the hospital without requesting ambulances. The results of binomial logistic analysis indicated that factors associated with ambulance requests included patient's and parents' medical history of febrile seizures. Increasing awareness of febrile seizures and provision of a general public educational campaign are possible strategies to help decrease unnecessary ambulance requests. However, a medical history of febrile seizures among siblings revealed no association, indicating the need to conduct repeated early-stage interventions.     

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.     

Determinants of IQ Profile in Children Generalized Epilepsy

To determine the IQ profile of children with epilepsy and the influence of various epilepsy-related variables on IQ scores, we studied 50 children with idiopathic generalized epilepsy of > 1-year duration, 25 of their siblings, and 30 healthy controls. IQ assessments were made with Malin's Indian modification of the Wechsler Intelligence Scale for Children. The mean +/- SD IQ scores of children with epilepsy (85.6 +/- 12) and their siblings (93.2 +/- 11) were significantly lower than those of the controls (101.6 +/- 9). The IQ scores of the children with epilepsy were also significantly lower than those of their siblings (p < 0.05). The IQ scores showed a significant correlation with socioeconomic status (SES) score (r = 0.33), a history of status epilepticus (r = -0.38), duration of seizure disorder (r = -0.31), and total number of seizures (r = -0.31). On multiple regression analysis, status epilepticus emerged as the most significant variable, accounting for 14% variance, followed by SES score (9% variance), duration of seizure disorder (6% variance), and sex of the child (5% variance). Genetic or environmental factors that probably lead to cognitive deficit in children with epilepsy and their siblings require further study.     

Prenatal Stress and Risk of Febrile Seizures in Children: A Nationwide Longitudinal Study in Denmark

We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year before the pregnancy and they were included in the exposed group. The exposed children had a risk of febrile seizures similar to that of the unexposed children (hazard ratio (HR) 1.00, 95% CI 0.94–1.06). The HRs did not differ according to the nature or timing of bereavement. Our data do not suggest any causal link between exposure to prenatal stress and febrile seizures in childhood.     

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.     

Febrile seizures and risk of schizophrenia

BACKGROUND: Febrile seizure is a benign condition for most children, but experiments in animals and neuroimaging studies in humans suggest that some febrile seizures may damage the hippocampus, a brain area of possible importance in schizophrenia. METHODS: A population-based cohort of all children born in Denmark between January 1977 and December 1986 was followed until December 2001 by using data from nationwide registries. RESULTS: We followed 558,958 persons including 16,429 with a history of febrile seizures for 2.8 million person-years and identified 952 persons who were diagnosed with schizophrenia. A history of febrile seizures was associated with a 44% increased risk of schizophrenia [relative risk (RR)=1.44; 95% confidence interval (CI), 1.07-1.95] after adjusting for confounding factors. The association between febrile seizures and schizophrenia remained virtually unchanged when restricting the analyses to people with no history of epilepsy. A history of both febrile seizures and epilepsy was associated with a 204% increased risk of schizophrenia (RR=3.04; 95% CI, 1.36-6.79) as compared with people with no such history. CONCLUSIONS: We found a slightly increased risk of schizophrenia among persons with a history of febrile seizures. The association may be due to a damaging effect of prolonged febrile seizures on the developing brain, shared etiological factors, or confounding by unmeasured factors.     

Psychological functioning in children and adolescents with Sturge-Weber syndrome

Previous studies of individuals with Sturge-Weber syndrome have focused on the medical aspects of this syndrome, but little has been known about the affective and behavioral correlates. We collected psychological and medical data from parents and teachers for 79 children and adolescents with Sturge-Weber syndrome and a group of their siblings. We also obtained the results of intellectual assessment for a subset of the Sturge-Weber syndrome group. The young people with Sturge-Weber syndrome exhibited more problems than the group of siblings across a number of behavioral domains: intellectual/academic, social skills, mood, and compliance. Those children most at risk for psychological problems were those with lower levels of intellectual functioning, those with seizure disorders, and those with more frequent seizures. Larger port-wine stains were also associated with an increase in mood and social problems but only for older children. Increased age was not associated with lower levels of intellectual or academic functioning, but mood and social problems were more common in older children.     

Unconsciousness and delirious behavior in children with febrile seizures

The aim of this study is to clarify the incidence and clinical features of prolonged unconsciousness and delirious behavior in children with febrile seizures. We studied 213 consecutive febrile seizures during 208 febrile episodes in 203 patients. The seizure manifestations, the duration of seizures, the duration of unconsciousness, and the presence or absence of delirious behavior were determined on the basis of interviews with the parents with the assistance of medical records. The duration of seizures was less than 5 minutes in 90.2% of the seizures. The duration of unconsciousness was less than 30 minutes in 93% of the seizures. Delirious behavior was observed in 2.0% of the patients. Delirious behavior appeared before febrile seizures, and its duration was not long. On multiple regression analysis, nongeneralized seizures, seizures of ≥5 minutes, and intravenous diazepam were demonstrated to be independently associated with prolonged unconsciousness. In conclusion, prolonged unconsciousness and delirious behavior are rare in children with febrile seizures. Careful diagnostic evaluation is necessary when a child with febrile seizures has associated prolonged unconsciousness or delirious behavior. Okumura A, Uemura N, Suzuki M, Itomi K, Watanabe K. Unconsciousness and delirious behavior in children with febrile seizures.     

Treatment of children with simple febrile seizures: the AAP practice parameter. American Academy of Pediatrics

Febrile seizures are the most common seizure disorder in childhood, occurring in 2-5% of children. Despite their frequency, there has been little unanimity of opinion regarding the need for long-term antiepileptic therapy. As such, the American Academy of Pediatrics formulated a subcommittee to study the subject. A Practice Parameter was developed that addressed the issue of whether continuous or intermittent antiepileptic therapy is necessary for children with simple febrile seizures. The committee determined that with the exception of a high rate of recurrence, no long-term adverse effects of simple febrile seizures have been identified. The risk of developing epilepsy is extremely low and, even in those patients who do, there is no evidence that recurrent simple febrile seizures produce structural central nervous system damage. Also, there is no evidence that recurrent simple febrile seizures cause either learning problems or premature death. The committee concluded that although there is the evidence that continuous antiepileptic therapy with phenobarbital or valproic acid and intermittent therapy with diazepam are effective in reducing the risk of recurrence, the potential toxicities associated with antiepileptic therapy outweigh the relatively minor risks associated with simple febrile seizures. As such, long-term treatment is not recommended.     

Febrile seizures in a South Indian district: incidence and associations

One thousand four hundred and three children participated in a home-based survey of psychiatric disorders in 8- to 12- year-old children in Calicut District, Kerala, India. One thousand one hundred and ninety-two consecutive children underwent neurological and psychometric assessments. The projected number of children with a history of febrile seizures was 120 giving a lifetime incidence of 10.1%. Recurrent febrile seizures predominated and these were strongly associated with a history of perinatal adversity. Febrile seizures were independently associated with indices of infective illness and mothers' education. Epilepsy developed in 2.7% of children with febrile seizures, but no evidence was found that febrile seizures had adverse intellectual or behavioural sequelae.