Indian Pediatrics 2001; 38: 733-740
the Division of Pediatric Neurology and Neuro Developmental Unit, Department
of Pediatrics, PGIMER, Chandigarh 160 012, India.
Febrile seizures are the most frequent neurologic disorder in children. There have been a number of controversies regarding their management, recurrence risk and long term outcome. Recently the American Academy of Pediatrics (AAP) has set guidelines for management of simple febrile seizures in childhood(l). This article provides an update on the current status and management practices of febrile seizures.
Febrile seizures are defined as an event in neurologically healthy infants and children between 6 months and 5 years of age, associated with fever >38ºC rectal temperature but without evidence of intracranial infection as a defined cause and with no history of prior afebrile seizures(2). Febrile seizures are to be distinguished from epilepsy which is characterized by recurrent nonfebrile seizures. All seizures with fever are not febrile seizures. Convulsions in children with fever due to pyogenic meningitis, hypernatremic dehydra-tion or other metabolic disorders are not included. Generally, febrile seizures occur during early phase of rising temperature and are uncommon after 24 hours of onset of fever(3).
Simple febrile seizures are generalized seizures, lasting less than 15 min, not recurring within 24 hours, and with no postictal neuro-logical abnormalities.
Complex febrile seizures are focal, prolonged or recurrent within 24 hours or associated with postictal neurological abnor-malities including Todd paresis. These seizures constitute around 15% of febrile seizures.
Febrile status is seizure duration of 30 min. or more, either one long lasting or a series of shorter seizures without regaining conscious-ness interictally.
Febrile seizures occur in 3-4% of children under the age of 5 years(3). Usually, they do not occur beyond the age of 5 years implying a specific vulnerability of young children to fever as a precipitant. The medium age of occurrence is 18-22 months(4).
It has been recognized that there is significant genetic component for suscepti-bility to febrile seizures. Two putative febrile seizure (FS) loci, FEB1 (chromosome 8q13-q2l) and FEB2 (chromosome 19P) have been mapped. Furthermore, a mutation in the voltage gated sodium (Na+) channel beta subunit gene (SCN1B) at chromosome 19ql3.1 was identified in a family with clinical subset, termed generalized epilepsy with febrile seizures plus syndrome (GE FS(+)). Studies have also linked the susceptibility of febrile seizures to a gene on chromosome 5ql4-ql5 (FEB4)(5). The risk of another child having febrile seizure is one in five with one affected sibling and one in three if both parents and a previous child have had febrile seizures(6).
Risk Factors for Recurrence of Febrile Seizures
The determinants for recurrent febrile seizures and for later epilepsy are different. The average recurrence rate after a first febrile seizure is 30-40% but this is dependent on complex interplay between the genetic and environmental factors. Recurrence risk is related to various risk factors, which may include the type of treatment. One study found a total of five risk factors for recurrent febrile seizures when no prophylaxis was given(7). In order of predictive power it included young age at onset (<15 months), epilepsy in first degree relative, febrile seizures in first degree relatives, many subsequent febrile episodes and a first complex febrile seizure. The higher the number of risk factors, the higher the recurrence rate and vice versa. Untreated children with no risk factors have a very low recurrence rate (10%); children with one or two risks have an intermediate risk (25-50%) and those with 3 or more factors have a very high recurrence rate (50-100%). In a similar group of children with febrile seizures, given intermittent diazepam prophylaxis at the time of fever, all risk groups had a low recurrence rate (12%). This intermittent prophylaxis reduced recurrence risk in those with one or more risks. The higher the recurrence risk, the better the seizure control during prophy-laxis(7). A meta-analysis of 14 studies found mainly 2 factors associated with recurrence of febrile seizures: (i) younger age of onset, and (ii) family history of febrile seizures(8). Subsequently, two more factors have been associated: (i) lower temperature at the time of febrile seizure(9) and shorter duration of temperature before the onset of seizure(10). In another meta-analysis by Offringa et al. young age at onset (<12 months), a history of febrile or unprovoked seizure in first degree relative and a rectal temperature less than 40ºC at the time of febrile seizure were associated with a significantly increased recurrence rate(11).
Age of onset is perhaps the single strongest and most consistent predictor of recurrent febrile seizures: the younger the child, the greater the risk (50% in <1 year old versus 20% in >3 years old)(4). The higher recurrence risk associated with early age at onset may indicate increased vulnerability to febrile seizure or may simply be a function of greater remaining risk period available in which to have a recurrence. The younger the child at second or third febrile seizure, the higher the likelihood of further recurrences. The associa-tion between complex febrile seizures and recurrences though seen in some studies(7) has not been consistently proven(8,11,12). However, in children with recurrent febrile seizures, complex features tend to repeat(12). The recurrence hazard is highest in the first 6 to 12 months after an initial seizure(11). The important risk factors are summarized in Table I.
The most crucial risk factors for febrile status include young age at onset, family history of unprovoked seizure and an initial partial febrile seizure(11,12). Risk factors for the first febrile seizure comprise the height of the temperature and family history of febrile seizure(13).
Risk of Epilepsy (Table II)
Population based studies have shown that the risk of epilepsy after febrile convulsion varies from 2-2.5%. A history of febrile convulsions is present in 10 to 15% of people with epilepsy or unprovoked seizure(14), several times higher than the 2 to 4% seen in the general population. Among children with febrile seizure three factors have been well established as predictors of later epilepsy(15): (i) A family history of epilepsy, (ii) Pre-existing neurologic or developmental abnormalities and (iii) Complex febrile seizures, each complex feature of febrile seizures is an independent predictor of later afebrile seizures.
Table II - Risk Factors for Epilepsy After a Febrile Seizure
Type of Epilepsy
Different types of seizures (generalized tonic clonic, absence, complex partial) may occur in those children who develop epilepsy after previous febrile seizures. In rare cases multiple febrile recurrences are followed by severe myoclonic epilepsy(16). Contrary to earlier belief, only a small proportion of children with febrile seizures go on to develop temporal lobe epilepsy(17). The relationship between febrile seizures in childhood, complex partial seizures, temporal lobe epilepsy and mesial temporal sclerosis in particular has long been assumed based upon associations seen among these and other factors in adults as well as children, largely with refractory epilepsy. While one study had shown strong association between prior febrile seizures and temporal but not extra temporal lobe epilepsy(14) another noted that there is no evidence that prior febrile seizures were associated with complex partial seizures, localization-related epilepsy, or specifically with temporal lobe epilepsy or with hippocampal atrophy or other potentially related findings in the temporal lobe(18). In selected families, prolonged febrile seizures were found to have a strong association with temporal lobe epilepsy(19). Thus, the relation-ship between febrile seizures and mesial temporal sclerosis is till date inconclusive. Mesial temporal sclerosis has been reported both before and after febrile seizures. There is evidence demonstrating that mesial temporal sclerosis is both a result and a cause of seizures(20).
Intellectual and Motor Functions
There is no evidence that simple febrile seizures cause any structural damage to the brain or that children with simple febrile seizures are at risk for cognitive decline. Population based studies have shown that febrile seizures in early childhood do not have adverse effects on behavior, scholastic performance and neurocognitive attention(21).
Management of a Child With Febrile Seizure
Long Term Management
The primary goal of long-term manage-ment of febrile seizure is to prevent recurrences. Treatment options include: (a) prolonged daily prophylaxis with phenobarbi-tone or valproate; and (b) intermittent prophylaxis with diazepam or other benzo-diazepines.
Phenobarbital is effective in preventing the recurrence of simple febrile seizures(33). In a controlled double blind study, daily therapy with Phenobarbital reduced the rate of subsequent febrile seizure from 25 per 100 subjects/years to 5 per 100 subjects/year(34). The adverse effects include behavioral problems such as hyperactivity and hyper-sensitivity reactions. Long-term phenobarbital treatment appears to influence cognition and behavior, a large price for prevention of benign condition.
Valproate is as effective as phenobarbitone in preventing recurrent, simple febrile seizures. In randomized, controlled studies, only 4% of children taking valproate as opposed to 35% of control subjects had a subsequent febrile seizure(35). Drawbacks to therapy with valproate include its rare association with fatal hepatotoxicity, thrombocytopenia, weight loss and gain, gastrointestinal disturbances and pancreatitis.
Neither Phenobarbital or Valproate is effective in reducing the risk of epilepsy in children with febrile seizure.
Intermittent Diazepam Prophylaxis
Diazepam administered intermittently either rectally as suppositories, or solution or orally at the onset of fever has been shown to be effective in preventing recurrence of febrile seizures(36). By either route, generally a dose of 0.3 to 0.5 mg/kg (max 10 mg) is used and repeated every 8-12 hours if temperature is 38ºC or more. A maximum of 4-5 doses are given per illness. Intermittent clobazam (1mg/kg/day) given orally has also been found to be useful in preventing febrile seizure recur-rences(37). A potential drawback to inter-mittent medication is that seizure could occur before fever is noticed. Adverse effects of oral diazepam include lethargy, drowsiness and ataxia(36). The sedation associated with this therapy could mask evolving signs of meningitis. It must however be remembered that this therapy does not decrease the incidence of later epilepsy in children with febrile seizures(38).
This perhaps is the most important (and often neglected) aspect of management of febrile seizures. As seizures in their child can be very frightening for the parents they should be counselled properly with particular emphasis on: (i) The benign nature of the febrile seizures; (ii) That febrile seizures do not lead to neurological problems or develop-mental delay; (iii) What they should do immediately if their child has another seizure; (iv) A doctor should be consulted if the seizure lasts for more than 15 min. or if the post ictal drowsiness persists for more than 30 min.
Febrile seizures in children are benign events that do not have any long term neurological sequalae, and neither long term daily phenobarbitone nor intermittent diazepam have any role in the management of these children with simple febrile seizures(39). Appropriate education and emotional support should be provided to parents. In situations where severe parental anxiety is associated with febrile seizures, intermittent therapy may be advised; continuous antiepileptic therapy is rarely used. Recent epidemiologic studies have also confirmed that the vast majority of children with febrile seizures have a benign prognosis and a normal long term outcome(40,41).
Contributors: PD conceptualized and drafted the manuscript, she will act as the guarantor. SM helped in literature review and drafting.