Treatment and prognosis of febrile seizures

INTRODUCTION — Febrile seizures are the most common neurologic disorder of infants and young children, occurring in 2 to 4 percent of children younger than five years of age. They are an age-dependent phenomenon with a strong genetic predisposition. While often frightening to parents, caregivers, and witnesses, febrile seizures are a mostly benign occurrence and are associated with a low risk for future epilepsy. Approximately one-third of children will have recurrent febrile seizures during early childhood, and the risk is increased in association with certain clinical features, including young age, low fever, family history of febrile seizures, and abnormal development at the time of first seizure.

Febrile seizures are described as being simple or complex. Simple febrile seizures are the most common type and are characterized by a single generalized seizure lasting less than 10 to 15 minutes. Complex febrile seizures include those that are focal, prolonged, or recurrent within a 24-hour period. (See "Clinical features and evaluation of febrile seizures".)

While simple febrile seizures have typically spontaneously resolved by the time the child is evaluated and do not need to be treated, prolonged seizures may require abortive treatment with benzodiazepines in the ambulance or in the emergency department. Prophylactic antiseizure medications can decrease the risk of recurrent febrile seizures, but given the benign nature of most seizures, the risks of side effects generally outweigh the benefits.

This topic will review the treatment and prognosis of febrile seizures, including febrile status epilepticus. Management of afebrile seizures and epilepsy in infants and children are discussed separately. (See "Seizures and epilepsy in children: Initial treatment and monitoring".)

INITIAL ASSESSMENT — The initial evaluation of children with seizure in the setting of fever must distinguish febrile seizure from alternative and more serious etiologies such as central nervous system infection. This can be accomplished with a thorough history and physical examination in most cases, along with neuroimaging and lumbar puncture in selected circumstances. Children with focal or prolonged febrile seizures may require more extensive evaluation than those with simple febrile seizures, particularly at the time of the first seizure. Therapies discussed below assume that such etiologies have been ruled out and that the diagnosis of febrile seizure has been established. (See "Clinical features and evaluation of febrile seizures".)

ACUTE MANAGEMENT

Emergency rescue therapy — The majority of febrile seizures have ended spontaneously by the time the child is first evaluated, and the child is rapidly returning to a normal baseline. In such cases, active treatment with benzodiazepines is not necessary. Fever should be treated symptomatically with antipyretics.

As with afebrile seizures, febrile seizures that continue for more than five minutes should be treated. Intravenous benzodiazepines (diazepam 0.1 to 0.2 mg/kg or lorazepam 0.05 to 0.1 mg/kg) are effective in aborting seizure in many cases. If the seizure persists, an additional dose may be given. The child's respiratory and circulatory status should be monitored carefully and an advanced airway intervention (eg, bag-mask ventilation, laryngeal mask airway, definitive artificial airway) undertaken if the ventilatory status becomes inadequate. (See "Basic airway management in children" and "Technique of emergency endotracheal intubation in children".)

The efficacy and safety of intravenous benzodiazepines as first-line agents for the treatment of seizures in children has been demonstrated in several randomized trials, primarily in children with afebrile seizures or status epilepticus. A 2018 meta-analysis concluded that intravenous lorazepam was as effective as intravenous diazepam and that both were associated with similar rates of respiratory depression [1]. In a randomized trial of 273 children with status epilepticus, intravenous lorazepam and intravenous diazepam had similar efficacy, but lorazepam-treated children were more likely to be sedated (67 versus 50 percent) [2]. Rates of intubation were similar (16 to 17 percent). (See "Management of convulsive status epilepticus in children", section on 'Benzodiazepine efficacy and pharmacokinetics'.)

When intravenous access is unavailable or cannot be achieved, buccal midazolam is an effective alternative [1]; a typical dose is 0.2 mg/kg, maximum dose 10 mg. Intranasal lorazepam is also an option. A systematic review and meta-analysis of 18 trials including 2199 children concluded that buccal or intranasal antiseizure medications were as effective as intravenous antiseizure medications in treating status epilepticus, but there was only low-quality evidence comparing buccal midazolam with rectal diazepam [1]. Respiratory complications requiring assisted ventilation are similar, regardless of administration route. (See "Seizures and epilepsy in children: Refractory seizures", section on 'Home rescue therapy (transmucosal antiseizure medications)'.)

Febrile status epilepticus — Patients with prolonged or repetitive seizures despite initial benzodiazepine administration (ie, febrile status epilepticus) should be treated promptly with additional antiseizure medications, as are other patients with status epilepticus. The most commonly used drug in this setting is fosphenytoin (20 mg phenytoin equivalents [PE]/kg intravenously). Efforts should be made to lower fever with antipyretics and a cooling blanket. The management of status epilepticus in children is discussed in more detail separately. (See "Management of convulsive status epilepticus in children" and "Fever in infants and children: Pathophysiology and management", section on 'Management of fever'.)

Febrile status epilepticus rarely stops spontaneously and often requires more than one medication to control [3,4]. It is more common in young children and is focal in two-thirds of cases [3,5]. In a prospective cohort study of 119 children presenting with prolonged febrile seizures (>30 minutes), 70 percent of children required more than one antiseizure medication, and delays in antiseizure medication administration were associated with longer seizure duration [3]. Important clinical clues that a seizure has ended include the presence of closed eyes and a deep breath. Children with persistently open and deviated eyes may still be seizing, even if convulsive motor activity has stopped. (See "Clinical features and evaluation of febrile seizures", section on 'Febrile status epilepticus'.)

Prehospital treatment — Treatment of prolonged seizures by paramedics with either intramuscular midazolam or intravenous lorazepam appears to be safe and effective in children with status epilepticus [6], and limited data support out-of-hospital treatment for prolonged febrile seizures as well [5]. The ability of emergency medical services (EMS) to administer antiseizure medications varies by region, however. (See "Management of convulsive status epilepticus in children", section on 'Prehospital treatment'.)

In a prospective study of children presenting to the emergency department with prolonged febrile seizure (>15 minutes), 11 percent of those receiving rectal diazepam in the ambulance responded, compared with 58 percent of patients treated with intravenous diazepam [5]. In a larger prospective study, earlier onset of treatment was associated with shorter total seizure duration of febrile status epilepticus and better outcomes [3]. Similarly in the United Kingdom, an epidemiological study strongly supported prehospital treatment with buccal midazolam as a widely used but unlicensed option in the community [7].

DISCHARGE DISPOSITION — Most children with simple febrile seizures do not require hospital admission and can be discharged safely to home once they have returned to a normal baseline and parents and caregivers have been educated about the risk of recurrent febrile seizures. (See 'Recurrent febrile seizures' below.)

Children with focal or prolonged seizures may require a more extended period of observation, particularly if there is delayed recovery to baseline or postictal focality. The normal duration of the postictal phase is not well defined, but available studies suggest that return to cognitive baseline typically occurs within five minutes [8]. Failure to return to cognitive baseline within five minutes or the presence of focal postictal weakness (Todd paralysis) would constitute delayed recovery. A Todd paralysis may last up to 24 hours.

In addition, children with focal or prolonged seizures are at higher risk of having multiple seizures within the index illness. In a retrospective study of 228 presenting to an emergency department with febrile seizure, the cumulative probability of early recurrence was 9 percent within 6 hours, 13 percent within 12 hours, and 16 percent within 24 hours [9]. Ninety percent of recurrences occurred within the first 24 hours. Risk factors for early recurrence were focal seizure and prolonged seizure (>15 minutes).

Additional factors to consider when deciding whether to admit a child include the confidence with which outpatient follow-up can be arranged (for focal or prolonged seizures), comfort level of the parents or caregivers, and severity of the underlying febrile illness (eg, hydration status, ability to take oral fluids).

RECURRENT FEBRILE SEIZURES — Children with febrile seizures are at risk for developing recurrent febrile seizures with future illnesses during early childhood.

Risk factors for recurrence — The overall recurrence rate is approximately 30 to 35 percent [10,11]. However, the values vary with age, from as high as 50 to 65 percent in children who are younger than one year of age at the time of the first seizure, to as low as 20 percent in older children [12]. A major factor influencing the recurrence rate is the age of the infant at the time of the first seizure.

A prospective cohort study of 428 children with a first febrile seizure defined other features and factors influencing recurrences [10]. Approximately one-third of the children had at least one recurrence, 17 percent had one recurrence, 9 percent had two recurrences, and approximately 6 percent had three or more recurrences. The majority of recurrences (50 to 75 percent) took place within one year of the initial seizure, and almost all occurred within two years [13]. Four factors in the prospective cohort study increased the recurrence risk [10]:

●Young age at onset

●History of febrile seizures in a first-degree relative

●Low degree of fever while in the emergency department

●Brief duration between the onset of fever and the initial seizure

Children who had all four factors were much more likely to have a recurrent febrile seizure than were those with none (≥70 versus ≤20 percent). Complex features were not associated with the risk of recurrence. These findings were confirmed in another prospective study [14].

Other factors identified in different studies have been abnormal development before the first febrile seizure, a history of afebrile seizures in parents and siblings, recurrence of seizures within the same illness, and the number of subsequent febrile illnesses [11,13-16]. Among children who have had one recurrence, younger age at the time of the first recurrence and a family history of epilepsy are predictors of subsequent recurrences [10,14]. Another risk factor is an unprovoked seizure after a febrile seizure; such children are at substantial risk for further seizures with fever (rate ratio 3.47 after adjusting for the above risk factors, p = 0.0015) [17].

Provision of home benzodiazepines — In children with a history of prolonged febrile seizure, including febrile status epilepticus (FSE), diazepam rectal gel (0.5 mg/kg) can be administered by parents or caregivers at home if the episode lasts longer than five minutes [18]. Parents and caregivers can be taught to safely give the medication at home, and one dose administered rectally will not lead to respiratory depression.

Where available, midazolam nasal spray is an alternative to rectal diazepam for home use. A comparison of midazolam nasal spray and rectal diazepam solution for residential treatment of seizure exacerbations found that midazolam was equal in efficacy to diazepam, and drowsiness occurred in more than 50 percent of administrations for both drugs [19]. The majority of patients and caregivers preferred the nasal spray to rectal formulations.

Factors helpful in predicting future prolonged febrile seizures are focality and history of prolonged febrile seizure, including FSE [20]. There appears to be a strong correlation between focality and prolonged duration of both first and recurrent febrile seizures [18]. In children with recurrent febrile seizures, those with long duration (defined as lasting longer than 10 minutes) tend to have similar features in repeat episodes. Similarly, children who have multiple risk factors for recurrent febrile seizures (focal onset, multiple seizures during the episode) and have a prolonged febrile seizure often have prolonged recurrent febrile seizures [10]. This is a group of children for whom rectal therapy at the time of occurrence should be strongly considered.

Role of preventive therapy — Prophylactic antiseizure medications can decrease the risk of recurrent febrile seizures, but given the benign nature of most seizures, the risks of side effects generally outweigh the benefits [16,21,22]. Use of antipyretics at the first sign of fever does not prevent recurrent febrile seizures.

Antiseizure therapy — Children with febrile seizures are at increased risk for recurrent febrile seizures as well as the development of afebrile seizures, suggesting a role for prophylactic treatment with chronic antiseizure medications. However, given the benign nature of recurrent febrile seizures, there is general consensus that risks of antiseizure medication treatment outweigh potential benefits for most patients [21,23].

The effectiveness of antiseizure medications was evaluated in a meta-analysis of studies for the prevention of recurrent febrile seizures [24]. While treatment with phenobarbital or intermittent oral or rectal diazepam was associated with reduced risk of recurrent seizures in the short term (six months to two years), this was also associated with a risk of adverse effects in up to 30 percent of children [24-27]. The use of chronic antiseizure medications or the prevention of recurrent febrile seizures is not associated with a reduced risk of epilepsy [16,21].

A clinical practice guideline developed by the Committee on Quality Improvement, Subcommittee on Febrile Seizures of the American Academy of Pediatrics concludes that neither continuous nor intermittent anticonvulsive therapy is recommended for children with one or more simple febrile seizures, based on the risks and benefits of effective therapies [21]. The guideline also recognizes that recurrent episodes of febrile seizures can create anxiety in some parents, caregivers, and affected children and as such, appropriate educational and emotional support should be provided.

This guideline does not address children with complex febrile seizures in whom the risk of future afebrile seizures is higher than in those with simple febrile seizures. In some children, a febrile seizure may represent the first presentation of epilepsy. Treatment decisions in such cases should be individualized based upon underlying risk factors, but there is no evidence that supports treatment in any one subset of patients. However, careful clinical history and review of the electroencephalogram (EEG) in cases of complex febrile seizures or febrile status epilepticus may reveal characteristics of an underlying epilepsy syndrome or risk factors for later development of temporal lobe epilepsy, such as acute focal slowing on EEG or subsequent mesial temporal sclerosis on magnetic resonance imaging (MRI) [28,29]. The benefits of antiseizure medication therapy may outweigh risks in such cases, particularly if caregiver concern about recurrent seizures is high and the risks of antiseizure medication therapy are carefully considered.

Antipyretics — For children who have had febrile seizures, treatment with antipyretics at the time of a febrile illness may allay discomfort and reduce the recurrence of febrile seizures during the same fever episode [30], but it does not appear to affect the recurrence rate of febrile seizures in subsequent fever episodes [21,24,27].

An open-label trial from Japan found that acetaminophen reduced febrile seizure recurrence during the same fever episode [30]. The trial enrolled over 400 children who presented to the hospital with febrile seizures and randomly assigned them to acetaminophen (10 mg/kg by suppository every six hours until 24 hours after febrile seizure onset if temperature remained >38.0° C) or to no antipyretic treatment. The rate of febrile seizure recurrence during the same fever episode was lower in the group assigned to rectal acetaminophen compared with the group assigned to no antipyretics (9 versus 24 percent). There were no serious adverse events related to acetaminophen.

However, antipyretic treatment does not appear to affect the recurrence rate of febrile seizures in subsequent fever episodes. A 2013 systematic review and meta-analysis that included three randomized controlled trials in 540 patients with febrile seizure also concluded that antipyretics (acetaminophen, ibuprofen, or diclofenac) were ineffective in reducing the rate of recurrent febrile seizures, compared with placebo [31]. The risk of recurrent febrile seizure was 23 percent in the antipyretics group and 24 percent in the placebo group during a one to two-year follow-up period.

There are several potential physiologic reasons why antipyretics may not prevent febrile seizures. Antipyretics facilitate heat loss but do not retard temperature elevation or lower the threshold convulsive temperature during the initial stage of fever that triggers a seizure [32]. Heat production is not inhibited by antipyretics, but heat dissipation is augmented by increased peripheral blood flow and sweating [33].

Both acetaminophen and barbiturates cause a fall in body temperature by depression of the central temperature regulatory mechanism. Phenobarbital inhibits heat production during the pyrogenic stage of the fever, whereas acetaminophen facilitates heat loss at the height of the fever or during its defervescence. The mechanism whereby phenobarbital reduces febrile seizure recurrence may be related to both an antipyretic and anticonvulsant effect [32].

The role of antipyretics in the management of fever in children is discussed separately. (See "Fever in infants and children: Pathophysiology and management", section on 'Management of fever'.)

PROGNOSIS — The prognosis for children with febrile seizures is favorable. While early reports had suggested that febrile seizures were associated with an increased risk of sudden death, the results from a large population-based study indicate that the small excess in mortality among children with febrile seizures is restricted to those with complex febrile seizures [34]. Furthermore, the increased risk in those patients is explained, at least in part, by preexisting neurologic abnormalities and subsequent epilepsy. In six cases of sudden unexplained death in toddlers with febrile seizures, hippocampal abnormalities were identified in one of three with available autopsy [35]. Inheritance was autosomal dominant. The interval from the last febrile seizure to death ranged from three weeks to six months.

Neurologic outcomes — Neurologic sequelae, including new neurologic deficits, intellectual impairment, and behavioral disorder, are rare following febrile seizures. In a case-control study in which 159 children with febrile seizures were compared with 142 controls, performance on measures of cognition, motor ability, and adaptive behavior were similar at one month after a first febrile seizure and one year later [36].

Most reports documenting neurologic complications have been anecdotal and derived from biased populations consisting of children assessed in hospitals or clinics; in some cases, they may reflect preexisting abnormalities. When new deficits were reported, they occurred only after complex or prolonged febrile seizures. In a small study, face recognition memory was impaired after prolonged febrile seizures, and the deficit was linked to the size of the hippocampi when tested one year later [37].

In general, population-based studies do not corroborate anecdotal reports of neurologic complications. In the National Collaborative Perinatal Project (NCPP), approximately 5 percent of children had febrile seizures lasting longer than 30 minutes. None of these children sustained permanent motor deficits and none had impaired mental development unless they developed afebrile seizures [15]. Similar findings were noted in a population-based study of 381 children with febrile convulsions in the United Kingdom [38]. The children were assessed when they were 10 years old, and children who had neurologic and developmental problems prior to the first febrile seizure were excluded. No difference was found in measurements of academic progress in children with febrile seizures, whether simple, complex, or recurrent, compared with a controlled cohort. There was also no difference in behavior between the two groups. Finally, among 18,000 Danish conscripts aged 18 to 20 years old, there was no association found between febrile seizures and cognitive function [39].

Subsequent epilepsy — Epilepsy occurs more frequently in children who have had febrile seizures than in the general population. In a normal child with a simple febrile seizure, the risk is approximately 1 to 2 percent, only slightly above that of the general population [40]. For children with complex febrile seizures, an abnormal developmental history, or a family history of epilepsy, the risk is closer to 5 to 10 percent.

Epidemiologic studies have identified risk factors for epilepsy among children with febrile seizures:

●In the NCPP, children with abnormal neurologic development and whose first seizure was complex (focal, multiple, or longer than 15 minutes) had a 9.2 percent incidence of afebrile seizures by seven years of age, a risk 18 times higher than that in children with no history of febrile seizures (0.5 percent) and more than eight times higher than that in normal children with a noncomplex first febrile seizure (1.1 percent) [40].

●In Rochester, Minnesota, 687 children with a history of febrile seizures were observed into adulthood [41]. Three risk factors for developing epilepsy were identified: focal seizures, prolonged seizures, and repeated episodes within 24 hours during the same illness. The risk of developing epilepsy was 2.4, 6 to 8, 17 to 22, and 49 percent in children with no, one, two, or three of these risk factors, respectively.

●A population-based study in Denmark also followed children with febrile seizures into adulthood [42]. The cumulative incidence of epilepsy was 6.9 percent at 23 years, and the relative risk associated with febrile seizures was 5.4. The risk of epilepsy was higher in those with a family history of epilepsy, cerebral palsy, or low Apgar scores at five minutes.

●Long-term risk of developing epilepsy in a median 21-year follow-up UK study of 181 infants with a first febrile seizure was 6 percent [43]. The risk of developing epilepsy decreased with time.

●Another cohort study of 181 children with febrile seizure found that the risk of epilepsy was highest in the first five years and appeared to decrease over time [43]. Overall, individuals aged 15 to 19 years with a history of febrile seizure appeared to have a similar risk of epilepsy compared with controls; however, subgroups of children with febrile seizures who might be at higher risk of epilepsy were not compared.

●A prospective study of 501 children with a first febrile seizure found a 5.4 percent risk of occurrence of epilepsy during a 30-month follow-up period. Significant prognostic markers for subsequent epilepsy included a family history of epilepsy (especially maternal), complex febrile seizure, focal febrile seizure, Todd's paresis, short fever duration before the seizure, late onset of febrile seizure (>3 years old), and multiple febrile seizure recurrences. Multiple febrile seizures increased the risk of epilepsy 10 times [44].

Electroencephalogram and risk of epilepsy — While electroencephalogram (EEG) is not useful in determining the risk of recurrent febrile seizures, it is often performed in the outpatient setting to identify children at increased risk for future epilepsy, in combination with other risk factors.

The evidence to support the utility of EEG in this setting is mixed, however. In one small study, 25 percent of children (9 of 36) with epileptiform discharges on EEG after febrile seizure developed epilepsy, compared with 2 percent of controls with a normal EEG [45]. The rate of recurrent febrile seizures was similar (33 and 26 percent, respectively). In a larger study that included 154 children with a first complex febrile seizure who underwent EEG, 13 percent of children developed epilepsy with a minimum of two years of follow up [46]. Epileptiform EEGs were noted in 20 percent of those who developed epilepsy and 13 percent of those who did not, resulting in a positive predictive value of only 15 percent. In a later report of 243 children, the presence of interictal epileptiform discharges on EEG following one or more episodes of complex febrile seizures was associated with an increased risk of future epilepsy (odds ratio 3.7, 95% CI 1.37-10.43) [47]. As in the earlier study [46], interictal epileptiform discharges on EEG were noted in 12 of 60 patients (20 percent) of those who developed epilepsy and 23 of 183 (13 percent) of those who did not, giving the same positive predictive value of 15 percent.

If the decision is made to obtain an EEG, the optimal timing is also uncertain. Abnormalities are more likely to be found when the test is performed shortly after the seizure and when convulsions are of long duration and have focal features. Transient slow wave abnormality up to 10 days after recovery from a febrile seizure is reported in 50 percent of patients [48]. Multiple seizures within 24 hours are predictive of abnormal EEG, and abnormalities are more common in children with complex than simple febrile seizures (43 versus 28 percent) [49]. Some studies suggest that certain abnormal EEG findings may be more strongly associated with the risk of epilepsy than others, but the EEG alone should not be used as a basis for treatment decisions [50].

Focal EEG slowing or attenuation on an EEG obtained within 72 hours of febrile status epilepticus is a potential biomarker for later development of epilepsy, and such changes are highly associated with MRI evidence of acute hippocampal injury [28]. (See 'Febrile status epilepticus' below.)

Subsequent temporal lobe epilepsy — Although a variety of seizure types follow febrile seizures, whether prolonged febrile seizures lead to the development of temporal lobe epilepsy is controversial. Reports of patients with refractory temporal lobe epilepsy considered for surgery often find an association with febrile convulsions in infancy, particularly prolonged seizures [51]. In addition, studies assessing hippocampal volume in adults with epilepsy have found an association between a smaller hippocampus and a history of febrile seizures [52,53]. Data are conflicting as to whether a correlation exists between the duration of epilepsy and a reduction in hippocampal volume [54]. Hippocampal abnormalities have also been associated with familial febrile seizures [55].

The possibility of hippocampal injury induced by febrile seizures was assessed by MRI in infants who had had complex febrile seizures [56]. Abnormalities were found in the children with focal and prolonged complex febrile seizures but not in those with generalized febrile seizures. In a few children who had significantly longer seizures, MRI suggested acute edema of the hippocampus, a finding noted in other case series as well [57,58]. Follow-up imaging studies in these children may show hippocampal atrophy or abnormal apparent diffusion coefficient measurements. Another study found that hippocampal atrophy and other MRI characteristics of hippocampal sclerosis were more common in adults with a history of febrile seizures in childhood than those without [59]. Although these observations suggest acute injury to the hippocampus during a febrile seizure, the possibility of preexisting lesions leading to susceptibility to injury is not excluded.

Studies based mainly upon imaging results and patients being considered for epilepsy surgery suggest an association between febrile seizures and temporal lobe epilepsy. Some clinical studies reached a similar conclusion. In one, patients presenting to an epilepsy clinic because of a previous diagnosis of epilepsy or recent onset of seizures were prospectively questioned about febrile seizures and their characteristics [60]. Febrile seizures were reported by 13.2 percent of the patients. Temporal lobe epilepsy was more likely to be preceded by febrile convulsions than by other types of epilepsy (25.2 versus 5.6 percent, respectively). Prolonged duration was the most common feature of the complex febrile seizure associated with temporal lobe epilepsy, although patients with generalized epilepsy were more likely to have had simple febrile seizures.

However, carefully performed community-based epidemiologic studies have not been able to confirm this association. In one, the characteristics of epilepsy were evaluated in 524 children who were one year of age or older at the onset of epilepsy [51]. Febrile seizures were present in 14 percent of the patients. Complex febrile seizures were associated with a younger age at onset of the epilepsy, but there was no specific association with localization-related forms of epilepsy. No evidence that focal or prolonged febrile seizures were associated with temporal lobe epilepsy was found; three children had hippocampal atrophy demonstrated on their initial MRI, but none had a history of febrile seizures.

In summary, febrile seizures do not appear to cause temporal lobe epilepsy. The association may represent an inherent susceptibility in some children who are predisposed to prolonged febrile seizures and epilepsy simultaneously.

Febrile status epilepticus — Febrile status epilepticus (FSE) is a subset of complex febrile seizures, and as such is associated with an increased risk of recurrent febrile seizures, as well as future afebrile seizures. However, the magnitude of the elevation in risk is not well-defined.

Clinical follow–up of a large prospective cohort of children with febrile status epilepticus (FEBSTAT) is in progress [4]. Children with febrile status epilepticus are more likely to have hippocampal imaging abnormalities at the time of presentation compared with those with simple febrile seizures, including abnormal hippocampal T2 hyperintensity in 11.5 percent and developmental abnormalities of the hippocampus in 10.5 percent [4,29]. The majority of children with abnormal hippocampal T2 hyperintensity at baseline had evidence of decreased hippocampal volume one year later, but the implications of this finding in terms of long-term seizure risk are not yet known [61]. Compared with children with a first simple febrile seizure, children with FSE are also at an increased risk for subsequent FSE, particularly those with a baseline MRI abnormality [20].

Another study followed 44 children with FSE, most of whom were followed prospectively [62]. After a mean follow-up of 28 months, the risk of recurrent seizures (febrile and afebrile) was increased only in those who had prior neurologic abnormalities. This finding is similar to that seen in patients with febrile seizures without status. Other case series have found that EEG studies, performed within one week after status, show focal slowing in one-third [63], a finding that has been associated with a higher risk of epilepsy in some studies. (See 'Electroencephalogram and risk of epilepsy' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in children".)

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●Beyond the Basics topic (see "Patient education: Febrile seizures (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Description – Febrile seizures occur in children with fever, usually in the setting of systemic bacterial or viral infection. Affected patients are typically between the ages of six months and five years of age and do not have epilepsy, central nervous system infection or inflammation, or other triggers for seizures. (See "Clinical features and evaluation of febrile seizures", section on 'Definitions'.)

●Initial evaluation – The initial evaluation must distinguish febrile seizure from alternative and more serious etiologies such as central nervous system infection. In most cases, this can be accomplished with a thorough history and physical examination, as discussed in detail separately. (See "Clinical features and evaluation of febrile seizures", section on 'Diagnostic evaluation'.)

●Acute management – Fever should be treated symptomatically with antipyretics. (See 'Acute management' above.)

•Seizure ended – The majority of febrile seizures have ended spontaneously by the time the child is first evaluated, and the child is rapidly returning to a normal baseline. In such cases, active treatment with benzodiazepines is not necessary. (See 'Emergency rescue therapy' above.)

•Seizure prolonged or ongoing – In children with febrile seizures that continue for more than five minutes, we recommend treatment with intravenous (IV) benzodiazepines (diazepam 0.1 to 0.2 mg/kg or lorazepam 0.05 to 0.1 mg/kg) (Grade 1B). Buccal midazolam (0.2 mg/kg, maximum 10 mg) is an alternative when IV access is unavailable. Patients with continued seizures despite initial benzodiazepine administration (ie, febrile status epilepticus) should be treated promptly with additional antiseizure medications, as are other patients with status epilepticus. (See 'Emergency rescue therapy' above and 'Febrile status epilepticus' above.)

•Disposition – Most children with simple febrile seizures do not require hospital admission and can be discharged safely to home once they have returned to a normal baseline and parents and caregivers have been educated about the risk of recurrent febrile seizures. Children with focal or prolonged seizures may require a more extended period of observation, particularly if there is delayed recovery to baseline or focal postictal weakness. (See 'Discharge disposition' above.)

●Recurrent febrile seizures

•Risk factors – Children with febrile seizures are at risk for recurrent febrile seizures, particularly if they have a young age of onset, a family history of febrile seizures, brief latency between onset of fever and seizures, and a relatively low fever. (See 'Risk factors for recurrence' above.)

•Home benzodiazepines – In children with a history of prolonged febrile seizure, benzodiazepines (eg, diazepam rectal gel 0.5 mg/kg) can be administered at home by parents or caregivers if the seizure lasts longer than five minutes. (See 'Provision of home benzodiazepines' above.)

•Limited role of antiseizure prophylaxis

-For simple febrile seizures – We suggest not treating patients with simple febrile seizures with antiseizure medication therapy (Grade 2B). While antiseizure medications may decrease the risk of recurrent febrile seizures, the prevention of febrile seizures is generally not considered worth the potential adverse effects of treatment. The available evidence suggests that the use of chronic antiseizure medications does not reduce the risk of epilepsy. (See 'Role of preventive therapy' above.)

-For complex febrile seizures – The use of antiseizure medication prophylaxis in children with complex febrile seizures is individualized based upon underlying risk factors. (See 'Antiseizure therapy' above.)

●Risk of epilepsy – Epilepsy occurs more frequently in children who have had febrile seizures than in the general population. In a normal child with a simple febrile seizure, the risk is only slightly above that of the general population. Children with complex febrile seizures, an abnormal developmental history, or a family history of epilepsy have an increased risk. (See 'Subsequent epilepsy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges J Gordon Millichap, MD, FRCP, who contributed to an earlier version of this topic review.