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%).     

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.     

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.     

Episousse: incidence of newly presenting seizures in children in the Region of Sousse, Tunisia

PURPOSE: To evaluate the incidence of newly presenting seizures in children in the area of Sousse, Tunisia. METHODS: From June 1, 1998, to May 31, 1999, all children aged 1 month to 15 years with first provoked and unprovoked seizures were included. Children with febrile seizures were excluded. All suspected cases were systematically referred to the Department of Functional Explorations of the Nervous System where a detailed questionnaire was filled out by a neurologist. All the patients underwent an EEG. Only 12 patients had a computed tomography (CT) scan. RESULTS: A total of 175 patients were included. Eighteen (10.3%) patients had acute symptomatic seizures, and 157 patients had unprovoked seizures. The incidence rate of first unprovoked seizures was 102.1/100,000. In this latter group, some epileptic syndromes were individualized on strict electroclinical criteria. CONCLUSIONS: However, nearly 75% of the cases remained cryptogenic, one of the major reasons that no predominant risk factor was identified in this population.     

Status epilepticus in children with newly diagnosed epilepsy.

Status epilepticus (SE) constitutes a neurological emergency and may be of prognostic value in individuals with epilepsy. Little is known about the associations between other prognostic factors in epilepsy and the occurrence of SE. The following study examines associations between clinical characteristics of children with newly diagnosed epilepsy and the occurrence of SE when epilepsy is first diagnosed. Children were recruited prospectively from the practices of physicians throughout Connecticut. Information was collected via standardized interviews with parents and review of pertinent records. Analyses were performed for any SE, unprovoked SE only, and previous provoked SE. Of 613 children, 56 (9.1%) had one or more episodes of SE by the time the diagnosis of epilepsy was established. Factors correlated with SE during an unprovoked seizure were partial seizures and previous craniotomy. For SE during a provoked seizure, correlates were primarily young age at onset of epilepsy and nonidiopathic epilepsy syndrome. To date, subsequent SE has occurred in 4.3% of children without and in 19.6% of those with SE at diagnosis. By the time epilepsy is first diagnosed in children, SE has already occurred in a substantial minority. It is correlated with specific clinical characteristics in the children, which differ depending on whether the SE was provoked or unprovoked. SE has a high risk of recurring.     

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.     

Retrospective study of late febrile seizures.

This retrospective study documents the clinical features, electroencephalographic data, and outcome of 50 children with a history of seizures with fever that occurred after 5 years of age. Children with afebrile seizures before the onset of febrile seizures were excluded. Outcome was based on a cross-sectional survey and the follow-up period was 1-13 years. Of the 50 children, 40 had two or fewer febrile seizures after 5 years of age, and febrile seizures did not occur after 10 years of age. Twenty had complex febrile seizures, and 16 had a first-degree relative with febrile seizures. Five developed afebrile seizures, and 18 had educational difficulties. Epileptiform electroencephalographic abnormalities were observed in 22 but were not predictive of later afebrile seizures. Febrile seizures that occur after 5 years of age recur infrequently and cease by 10 years of age. The risk of developing afebrile seizures in this group is small.     

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.     

Results of computed tomography in "neurologically normal" children after initial onset of seizures

A combined retrospective and prospective study assessed the results of computed tomographic (CT) scans in infants and children without neurologic deficit who presented with initial onset of seizures. Of 101 pediatric patients, 81 had afebrile seizures and 20 had complicated febrile seizures (i.e., focal, multiple, or prolonged). Seven children (7%), 6 with afebrile and 1 with a febrile seizure, had CT abnormalities. Four patients (4%) required further diagnostic workup including angiography and/or surgery. Children with afebrile focal seizures were more likely to have an abnormality than those with afebrile generalized seizures without focal components (13% and 4.9%, respectively). This study demonstrated a lower percentage of overall CT abnormalities, yet a similar percentage of "therapeutically important" abnormalities, in neurologically normal children with new onset of seizures when compared to previous reports of children with chronic seizures. Although an abnormal CT was more likely to be associated with an abnormal electroencephalogram, a normal result did not eliminate the possibility of an abnormal CT.     

Convulsive Status Epilepticus in Children

Summary: Status epilepticus (SE) occurs most commonly in infancy and childhood. Children with prior neurological abnormalities are most susceptible. More than 90% of cases are convulsive and the majority are generalized. SE may occur in the setting of an acute illness, in patients with established epilepsy or as a first unprovoked seizure. The etiology can be classified as idiopathic, remote symptomatic, febrile, acute symptomatic, or associated with a progressive encephalopathy. The morbidity and mortality of status have dramatically declined in recent years. Overall mortality in recent pediatric series was 3–10%, with almost all fatalities associated with acute central nervous system insults or progressive neurologic disorders. Neurological sequelae in children with idiopathic or febrile status are rare. Neurologically normal children with SE as their first unprovoked seizure have the same risk of experiencing subsequent seizures of any type as children who present with a brief first seizure. The risk of recurrent episodes of convulsive SE approaches 50% in neurologically abnormal children but is very low in neurologically normal children. The favorable outcome of SE in children may be related to advances in therapy and to the resistance of the immature brain to damage from seizures.     

gamma-Aminobutyric acid in CSF of children with febrile seizures

Previous studies have suggested that levels of cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) may be decreased in children with febrile seizures. We used gas chromatography and mass spectrometry to measure CSF GABA levels in 14 children with febrile seizures. The results were compared with the GABA levels in six children with first-time afebrile seizures, three with recurrent febrile seizures, and 13 controls (febrile children undergoing lumbar puncture to rule out meningitis). Children with central nervous system infections or known neurologic disease were excluded. The CSF GABA levels in children with febrile seizures were not significantly different from those in controls and children with afebrile or recurrent febrile seizures. In the control group, CSF GABA levels correlated with increasing age. There was no correlation with severity of febrile response in any group. The results indicated that the CSF GABA level may not be abnormal in patients with first-time febrile convulsions.     

A randomized study of carbamazepine versus no medication after a first unprovoked seizure in childhood

We randomized 31 children with a 1st afebrile unprovoked seizure to receive carbamazepine (CBZ) or no medication for 1 year or until the time of a 2nd seizure. All seizures had a focal onset or were generalized tonic-clonic. Overall, 2/14 randomized to CBZ and 9/17 with no medication had a recurrent afebrile seizure. Compliance with CBZ was excellent in 12/14, but noncompliance may have contributed to 1 of the recurrences with CBZ. Four discontinued CBZ because of side effects. Two additional children taking CBZ had a febrile seizure. Thus, only 6/14 taking CBZ had a year completely seizure-free with no unacceptable medication side effects. Of those taking no medication, 2 had a febrile recurrence, and 7/17 had a year completely-seizure free. Side effects and febrile recurrences may limit the value of CBZ for some children, although CBZ appears to reduce significantly recurrences after a 1st afebrile seizure.     

Febrile seizures

Febrile seizures are the most common form of childhood seizures, occurring in 2 to 5% of children in the United States. Most febrile seizures are considered simple, although those with focal onset, prolonged duration, or that occur more than once within the same febrile illness are considered complex. Risk factors for a first febrile seizure, recurrence of febrile seizures, and development of future epilepsy are identifiable and varied. Children with febrile seizures encounter little risk of mortality and morbidity and have no association with any detectable brain damage. Recurrence is possible, but only a small minority will go on to develop epilepsy. Although antiepileptic drugs can prevent recurrent febrile seizures, they do not alter the risk of subsequent epilepsy. This has led to a changing view of how we approach the treatment of these common and largely benign seizures. This chapter will review the current understanding of the prognosis and management of febrile seizures.     

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.     

Epilepsy can be diagnosed when the first two seizures occur on the same day

PURPOSE: Experts have suggested that when the first two (or more) unprovoked seizures occur on the same day, they should be considered as a single event and the diagnosis of epilepsy await a further seizure. We have studied the subsequent clinical course of children with their first two seizures on the same day ("same day" group) compared with children with their first two seizures separated by more than one day ("different day" group). METHOD: The Nova Scotia childhood epilepsy database documented all newly diagnosed children with epilepsy from 1977 to 1985 with follow-up in 1990 and 1991. Epilepsy was defined as two or more unprovoked seizures regardless of the interval between seizures provided that consciousness fully returned between seizures. All patients had their first seizure between the ages of 1 month and 16 years. Seizure types were restricted to partial, generalized tonic-clonic, and partial with secondary generalization. RESULTS: Of the 490 children with partial or generalized tonic-clonic seizures and follow-up of more than 2 years, 70 had their first two or more seizures on the same day and 420 had their first two seizures on different days. Eighty percent (56 of 70) of the "same day" group subsequently had one or more further seizures with (n = 14) or without (n = 42) medication; 80.9% (340 of 420) of the "different day" group had one or more further seizures with (n = 115) or without (n = 225) medication. Seizure types were nearly identical. Cause was the same (except for fewer idiopathic "genetic" cases in the "same day" group: 1 of 70 vs. 42 of 420; p = 0.02). Rates of mental handicap and previous febrile seizures were the same. Children in the "same day" group were younger on average (60 vs. 84 months; p = 0.001) and were somewhat more likely to have neurological impairment. Outcome after 7 years average follow-up was the same: 58% of the "same day" group and 56% of the "different day" group were in remission. CONCLUSION: If two or more unprovoked seizures (with normal consciousness between) occur on the same day, the child appears to have epilepsy and will have a clinical course identical to that of the child with a longer time interval between the first two seizures.     

Mortality in Patients with a First Unprovoked Seizure

Summary:  Purpose: The mortality after a first epileptic seizure is affected by the source of cases, the intensity of the diagnostic work-up, the type and the presumed etiology of the seizure, the length of follow-up, and the modalities of data collection (retrospective vs. prospective). We review the four studies of this topic.
Methods: Four studies have been identified which focused on the mortality of the first unprovoked seizures or the first afebrile (provoked or unprovoked) seizure. These included two population-based surveys, one clinic-based community survey, and a randomized clinical trial on the treatment of the first unprovoked generalized tonic–clonic seizure.
Results: A standardized mortality ratio (SMR) of 2.3 (95% confidence interval, CI 1.5–3.3) for unprovoked first seizures was found in a retrospective cohort study in the population of Rochester, Minnesota. The SMR was higher during the first year after the seizures to progressively decrease thereafter. Acute symptomatic seizures carried the higher risk, followed by remote symptomatic seizures, while idiopathic and cryptogenic seizures carried no risk. The increased SMR found in women and in patients aged 0–19 years enrolled in the randomized trial differs from that seen in other mortality studies in epilepsy (SMR being highest in the youngest age groups) and may be a chance finding.
Conclusions: Mortality is increased in patients with a first unprovoked seizure, particularly during the first year after the seizure. This increased mortality is associated with known etiology of the seizure, and is not present when etiology is unknown.     

A comparative study of febrile and afebrile seizures associated with mild gastroenteritis

Purpose: Seizures associated with mild gastroenteritis have been increasingly reported. We analyzed the clinical characteristics of febrile and afebrile seizures associated with mild gastroenteritis, and attempted to determine the influence of fever in these two groups. Methods: We reviewed the medical records of 59 children presenting with seizures during a mild gastroenteritis episode. They were classified into an afebrile group (n = 27) and a febrile group (n = 32). We compared the age of onset, sex, seizure semiology, frequency, duration, family history, and prior history of seizures between the two groups. Results: The mean age, family history, seizure semiology, and frequency of seizures were not significantly different between the two groups. However, more patients in the afebrile group experienced ?2 seizures/day than in the febrile group (63% vs. 38%, p = 0.051). The febrile patients had a tendency of experiencing prolonged seizures lasting ?5 min compared with the afebrile group (34% vs. 11%, p = 0.063). Prior febrile seizures were noted in 5 of the 32 patients (15.6%) in the febrile group, while none of the 27 patients in the afebrile group had a history of prior seizures (p = 0.056). Conclusions: It seems that the presence of fever may influence the clinical characteristics of seizures associated with mild gastroenteritis. We suggest that afebrile seizures associated with gastroenteritis may be regarded as a distinct condition from those associated with fever, and it needs to be clarified by a further large sample study.     

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.     

The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.     

The Prevalence and Incidence of Convulsive Disorders in Children

Summary: Each year, about 150,000 children and adolescents in the United States will come to medical attention for evaluation of a newly occurring seizure disorder of some type. Between 2% and 4% of all children in Europe and the United States experience at least one convulsion associated with a febrile illness before the age of 5 years. The cumulative incidence of febrile convulsions among children ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak incidence of a first febrile convulsion occurs in the second year of life. Between 0.5% and 1% of children and adolescents experience a seizure associated with other acute metabolic or neurologic insults; most of these occur in the neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in children and adolescents seems relatively consistent across all populations studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in the first year of life. West syndrome accounts for about 2% of all childhood epilepsy, Lennox-Gastaut syndrome for 1–2%, childhood absence epilepsy (pyknolepsy) for 10–15%, juvenile myoclonic epilepsy for 5%, and idiopathic localization-related epilepsy for 10%. Between 0.5 and 1% of children experience a nonrecurrent, single, unprovoked convulsive episode. Following are the estimated numbers of children and adolescents with newly diagnosed convulsive disorders in the United States for the year 1990: febrile seizures, 100,000; neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked seizures, 10,000; and epilepsy, 30,000.