Clinical features and evaluation of febrile seizures

INTRODUCTION — Febrile seizures are the most common neurologic disorder of infants and young children. They are an age-dependent phenomenon, occurring in 2 to 4 percent of children younger than five years of age.

Simple febrile seizures, defined as generalized seizures lasting less than 15 minutes and not recurring during a 24-hour period, represent the majority of febrile seizures. While they eventually recur in approximately one-third of children during early childhood, they are an otherwise benign phenomenon and are associated with a risk of future epilepsy that is only slightly higher than the general population. Febrile seizures that are focal, prolonged, or multiple within the first 24 hours are defined as complex. Complex febrile seizures are a more heterogeneous group, associated with a higher risk of recurrence during early childhood and an increased likelihood of future afebrile seizures.

The risk factors, clinical features, and diagnostic evaluation of febrile seizures are reviewed here. Treatment and prognosis of febrile seizures, including the risk of recurrent febrile seizure and future epilepsy, are discussed separately. (See "Treatment and prognosis of febrile seizures".)

The evaluation and management of nonfebrile seizures and status epilepticus in neonates, infants, and children are also discussed separately. (See "Clinical features, evaluation, and diagnosis of neonatal seizures" and "Seizures and epilepsy in children: Clinical and laboratory diagnosis" and "Clinical features and complications of status epilepticus in children" and "Management of convulsive status epilepticus in children".)

DEFINITIONS — A febrile seizure refers to an event in infancy or childhood, usually occurring between six months and five years of age, associated with fever but without evidence of intracranial infection or defined cause [1]. Seizures with fever in children who have suffered a previous nonfebrile seizure are excluded from this definition. Febrile seizures are not considered a form of epilepsy, which is characterized by recurrent nonfebrile seizures [1,2].

Generally accepted criteria for febrile seizures include [3-5]:

●A convulsion associated with an elevated temperature greater than 38°C

●A child older than six months and younger than five years of age

●Absence of central nervous system (CNS) infection or inflammation

●Absence of acute systemic metabolic abnormality that may produce convulsions

●No history of previous afebrile seizures

Febrile seizures are further divided into two categories, simple or complex, based on clinical features [6].

●Simple febrile seizures, the most common type, are characterized by seizures that are generalized, last less than 15 minutes, and do not recur in a 24-hour period. Since most simple febrile seizures last less than five minutes, a cutoff of 10 minutes has been proposed as a more appropriate threshold for distinguishing between simple and complex [7].

●Complex febrile seizures are characterized by episodes that have a focal onset (eg, shaking limited to one limb or one side of the body), last longer than 15 minutes, or occur more than once in 24 hours [8].

Note that these definitions cannot be accurately applied with regard to seizure duration if treatment (eg, rectal diazepam) is given after five minutes.

The distinction between simple and complex has prognostic implications, with most studies indicating that patients with complex features have a higher risk of recurrent febrile seizures and a slightly higher risk of future nonfebrile seizures. (See 'Diagnostic evaluation' below and "Treatment and prognosis of febrile seizures", section on 'Recurrent febrile seizures' and "Treatment and prognosis of febrile seizures", section on 'Subsequent epilepsy'.)

EPIDEMIOLOGY — Febrile seizures are the most common neurologic disorder of infants and young children. They occur in approximately 2 to 4 percent of children younger than five years of age, with a peak incidence between 12 and 18 months. A higher prevalence has been reported in certain regions, such as Japan Mariana Islands. There is a slight male predominance, with an estimated male-to-female ratio of 1.6:1 [9].

RISK FACTORS — Febrile seizures are an age-dependent phenomenon, likely related to a vulnerability of the developing nervous system to the effects of fever in combination with an underlying genetic susceptibility. Aside from age, the most commonly identified risk factors include high fever, viral infection, recent immunization, and a family history of febrile seizures.

High fever — Although the issue is debated, the maximum height of a fever, rather than the rate of rise, may be the main determinant of risk in febrile seizures. This has been demonstrated in animals and confirmed in clinical studies [10-12]. In a study of 110 children with febrile seizures, the mean of 110 recordings with seizures was significantly higher than the mean of the 51 highest fevers unassociated with seizures (104.0 versus 103.3°F, p<0.001) [10].

A key variable that modulates the impact of fever is seizure threshold, which varies by individual and with age and maturation. Seizure threshold is lower in infants and is modified by certain medications and water and electrolyte imbalances, especially hyponatremia [9].

Infection — Viral infections are commonly identified in association with febrile seizures, whereas bacterial infections are infrequent [13]. Febrile seizures are not thought to be viral specific, but rather dependent upon the degree of temperature elevation. Viral infections associated with high fever, such as human herpesvirus 6 (HHV-6) and influenza, appear to pose the highest risk.

HHV-6 is the virus most frequently associated with febrile seizures in the United States and has been identified in one-third of all first-time febrile seizures in United States children up to two years of age [14]. In a European study, HHV-6 was isolated in 35 percent of children with febrile seizures, adenovirus in 14 percent, respiratory syncytial virus in 11 percent, herpes simplex virus (HSV) in 9 percent, cytomegalovirus in 3 percent, and HHV-7 in 2 percent [15].

The preponderance of HHV-6-associated febrile seizures is linked to the unusually high fevers associated with HHV-6 infection [16]. The mean maximum fever in infants with primary HHV-6 infection is generally 39.5°C (103°F) or higher, and the incidence of febrile seizures associated with primary infection has been estimated to be as high as 36 percent in the 12- to 15-month age group [14]. This may be an overestimate of the actual risk, however, since children with milder infections were likely underrepresented in the sampled emergency department population. In one community-based cohort study in which children's saliva was tested weekly for HHV-6 DNA for the first 24 months of life, only one-third of children with a well-defined acquisition were seen by a clinician [17]. Febrile seizures associated with HHV-6 have been associated with an increased rate of complex features, recurrence, and febrile status epilepticus (FSE) [14,18-20]. (See "Human herpesvirus 6 infection in children: Clinical manifestations, diagnosis, and treatment", section on 'Acute febrile illness' and 'Febrile status epilepticus' below.)

In Asia, influenza A virus is most commonly isolated in children with febrile seizures, accounting for 20 percent of cases in a Hong Kong study [21]. Parainfluenza (12 percent) and adenovirus (9 percent) were also common. In a separate hospital-based case-control study, the incidence of febrile seizures in children requiring admission for a viral illness was similar with influenza, adenovirus, and parainfluenza infections (6 to 18 percent), and somewhat less common with respiratory syncytial virus and rotavirus (4 to 5 percent) [22]. These viral infections were the cause of fever in children with febrile seizures, and they occurred with the same frequency in a control group of patients with fever but without seizures.

Except for the common association of HHV-6 or influenza A virus, the type of viral infection is not important in predicting future recurrence of a febrile seizure or a complex febrile seizure [23]. A specific neurotropism or central nervous system (CNS)-invasive property of HHV-6 and influenza A viruses and bacterial neurotoxin (Shigella dysenteriae) are implicated but unproven [23]. COVID-19 may cause a febrile illness in children but is not reported as a common cause of febrile seizures. In a study that reviewed the electronic health record data of 8854 children 0 to 5 years of age diagnosed with COVID-19, only 0.5 percent were also diagnosed with febrile seizures [24]. Seizure recurrence may be caused by a reactivation of the HHV-6 virus and a mild and transitory encephalitis, a theory that is an exception to the accepted definition of a febrile seizure. Multiple factors may be involved, including a proinflammatory cytokine and immune response to infection [22].

Breastfeeding is reported as a protective factor. In an observational study of a large Korean cohort, the risk of febrile seizures was lower with partial or exclusive breastfeeding compared with exclusive formula feeding up to the age of 2.5 years [25]. After 2.5 years, the risk difference was no longer significant.

Immunization — The risk of febrile seizures is increased after administration of certain vaccines, including diphtheria, tetanus toxoid, and whole-cell pertussis (DTwP); and measles, mumps, and rubella (MMR), although the absolute risk is small. The risk varies according to vaccine preparation and the age of the child when the vaccine is administered (table 1). Genetic susceptibility may also play a role. (See 'Genetic susceptibility' below.)

For children who have a febrile seizure within a few days following a vaccination, decisions about repeat vaccination should be individualized contingent upon the assessment of risks and benefits. In many cases, the benefits outweigh the risks. These issues are discussed in greater detail elsewhere. (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age", section on 'Contraindications and precautions' and "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'Adverse effects'.)

Genetic susceptibility — A genetic predisposition to febrile seizures has long been recognized, although the exact mode of inheritance is not known in most cases. Among first-degree relatives of children with febrile seizures, 10 to 20 percent of parents and siblings also have had or will have febrile seizures. In addition, monozygotic twins have a higher concordance rate than do dizygotic twins [26], in whom the rate is similar to that of other siblings.

Susceptibility to febrile seizures has been linked to several genetic loci in different families, including the long arm of chromosome 8q13-21 (FEB1) [27], chromosome 19p (FEB2) [28,29], chromosome 2q23-24 (FEB3) [30], and other loci [31-36]. The trait is transmitted in an autosomal dominant pattern with reduced penetrance or as a polygenic or multifactorial model [37]. In one study, heterogeneous R43Q mutations of the GABRG2 gene, located on the long arm of chromosome 5, occurred significantly more often in patients with febrile seizures than controls (36 versus 2 percent) [38]. Family history of febrile seizures and epilepsy was significantly higher in the study group than in controls, but the homozygous mutation carrier status was not different.

In a large genome-wide association study, isolated febrile seizures were associated with common genetic variants in loci containing the sodium channel genes, SCN1A and SCN1B, among others [39]. In the same study, two loci were specifically associated with MMR-related febrile seizures, including one locus containing an interferon-stimulated gene and another correlating with the measles-specific immune response.

In some patients and families, the propensity for febrile seizures is an early manifestation of generalized epilepsy with febrile seizures plus (GEFS+), a genetic epilepsy for which a variety of causative mutations has been identified. Severe myoclonic epilepsy of infancy (Dravet syndrome) is another genetic epilepsy with a well-known preponderance for seizures with fever in early childhood. (See 'Genetic epilepsies with febrile seizures' below.)

Hippocampal abnormalities are identified in some patients and families with febrile seizures and may be a link to genetic factors and risk of future temporal lobe epilepsy [40]. Developmental abnormalities of the hippocampus, including hippocampal malrotation, have also been reported in 10.5 percent of children presenting with FSE [41]. (See "Treatment and prognosis of febrile seizures", section on 'Febrile status epilepticus'.)

Others — Prenatal exposure to nicotine, but not alcohol or coffee consumption, has been associated with a slightly increased risk of febrile seizures [42,43].

Iron deficiency has been suggested as a possible risk factor or pathogenic mechanism [44,45]. In a prospective study of 150 children, mean ferritin levels were significantly lower in children with a first febrile seizure than in matched controls with febrile illness but no convulsions (29.5 versus 53.3 mcg/L) [46]. Plasma ferritin levels ≤30 mcg/L occurred in a significantly greater proportion of children with seizures than in controls (65 versus 32 percent).

Incidence of allergic rhinitis is higher in children with febrile seizures than in controls without seizures. The association with allergic rhinitis is stronger in children with more than three febrile seizures [47]. Children with febrile seizures also have a higher association with other atopic diseases, including asthma. Allergies and immune reactions are proposed as possible factors in the cause of febrile seizures [9].

CLINICAL FEATURES

Presentation — Febrile seizures occur in children between the ages of six months and five years, with the majority occurring in children between 12 and 18 months of age. Febrile seizures have been reported in children over five years of age, but in older children, febrile seizures should be considered a diagnosis of exclusion, as they are more likely than younger children with febrile seizures to have subsequent afebrile seizures [48].

The majority of children have their febrile seizures on the first day of illness, and in some cases, it is the first manifestation that the child is ill. The degree of fever associated with febrile seizures is variable and is dependent on the child's threshold convulsive temperature. While measured fever is most often at or above 39ºC, approximately 25 percent of events occur when the temperature is between 38 and 39ºC. Seizures are often seen as the temperature is increasing rapidly, but the degree of fever, not the rate of temperature rise, is the precipitating stimulus [10].

Seizure characteristics

Simple febrile seizures — Simple febrile seizures are generalized, last less than 15 minutes, and do not recur in a 24-hour period. The most common seizure type is generalized tonic-clonic, but atonic and tonic spells are also seen. The facial and respiratory muscles are commonly involved. Although by definition the duration of a simple febrile seizure can be as long as 15 minutes, most simple febrile seizures are much shorter, with a median duration of three to four minutes [7].

Children typically return to baseline quickly after a simple febrile seizure. As with nonfebrile seizures, the postictal phase can be associated with confusion or agitation and drowsiness. Prolonged drowsiness is not typical for simple febrile seizure and should prompt consideration of an alternative etiology (eg, meningitis, structural brain pathology) or ongoing seizure activity. Similarly, the presence of persistently open and deviated eyes is an important clinical feature of ongoing seizure activity. (See 'Febrile status epilepticus' below.)

Complex febrile seizures — Complex febrile seizures (focal onset, prolonged, or recurrent within 24 hours) are less prevalent, making up approximately 20 percent of febrile seizures in most series. Prolonged seizures occur in less than 10 percent and focal features in less than 5 percent of children with febrile seizures. An initial simple febrile seizure may be followed by complex seizures, but the majority of children who develop complex febrile seizures do so with their first seizure. However, an initial complex febrile seizure does not necessarily indicate that all subsequent seizures will be complex.

Transient hemiparesis following a febrile seizure (Todd paresis), usually of complex or focal type, is rare, occurring in 0.4 to 2 percent of cases [9,49].

Children with complex febrile seizures are often younger and more likely to have abnormal development. In one study of 158 children with a first febrile seizure, prolonged seizures (>10 minutes) occurred in 18 percent and were associated with developmental delay and younger age at first seizure [7].

Febrile status epilepticus — Some patients present in febrile status epilepticus (FSE), ie, continuous seizures or intermittent seizures without neurologic recovery. Historically, FSE was defined as seizures lasting 30 minutes or longer; the definition was updated in 2015 to include continuous seizures lasting five minutes or longer [50]. (See "Clinical features and complications of status epilepticus in children", section on 'Definition'.)

In up to one-third of cases of FSE, the actual seizure duration is underestimated in the emergency department [51]. 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 be experiencing an ongoing focal seizure, even if convulsive motor activity has stopped.

A multicenter prospective cohort study (FEBSTAT) described the characteristics of prolonged (>30 minutes) febrile seizures in 119 children, aged one month through five years, as follows [19,51]:

●The median duration was 68 minutes

●The seizures were convulsive in all but one child

●The seizures were continuous in 52 percent and intermittent in 48 percent

●Two-thirds of seizures were partial

●This was the first febrile seizure in 76 percent of children

●Primary or reactivated human herpesvirus 6B (HHV-6B) infection was found in 32 percent of children

The clinical setting in which FSE occurs is not clearly different than that of shorter febrile seizures. In the FEBSTAT cohort, the median peak temperature was 103ºF (39.4ºC), most patients had a defined viral or bacterial illness, and there was a higher-than-expected family history of epilepsy [51]. In another series, patients with FSE were more likely to have a family history of epilepsy than children who presented with briefer febrile seizures; they also had a higher prevalence of baseline neurologic disease and a personal history of epilepsy [52].

By definition, FSE does not include episodes of status epilepticus in children with fever due to meningitis, but the distinction may not be possible based only on clinical features at the time of initial presentation, and lumbar puncture (LP) should be more carefully considered in patients. In one large single-center study of 381 consecutive cases of status epilepticus with fever, FSE accounted for the majority of diagnoses (82 percent), followed by known epilepsy (7.6 percent), encephalitis/encephalopathy (6.6 percent), and bacterial meningitis (0.8 percent) [20]. (See 'Central nervous system infection' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of febrile seizure includes nonepileptic events or movements, provoked seizures from central nervous system (CNS) infection (eg, meningitis or encephalitis), and rare forms of genetic epilepsy in which seizures are particularly common with fever.

Shaking chills — Involuntary movements can occur in sick children and can be confused with seizures. Shaking chills are usually readily distinguished from seizures. Chills are common and are characterized by fine rhythmic oscillatory movements about a joint. They rarely involve facial or respiratory muscles, which frequently occur during febrile seizures. In addition, chills usually involve both sides of the body simultaneously and are not associated with loss of consciousness, in contrast to children with generalized seizures. Thus, bilateral manifestations without apparent unconsciousness strongly suggest that the movements are not epileptic. Any repetitive movements of concern should also be evaluated by touch, since seizures should not be suppressible.

Central nervous system infection — Provoked seizures from meningitis or encephalitis are the main concerns in a child presenting with fever and seizures. A thorough evaluation by an experienced clinician almost always will detect the child with meningitis. Although as many as 40 percent, particularly younger infants, who have seizures as an initial manifestation of meningitis do not have meningeal signs, they have other symptoms and findings (eg, altered consciousness, petechial rash) that strongly suggest the correct diagnosis [53].

It is exceedingly rare for bacterial meningitis to be detected on the basis of doing a "routine" evaluation of the cerebrospinal fluid (CSF) after a simple febrile seizure. When the only indication for performing a lumbar puncture (LP) is the seizure, meningitis will be found in less than 1 percent of patients and less than one-half of these will have bacterial meningitis [54-56]. Meningitis itself has also become increasingly less common with widespread Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) immunization practices. (See 'Lumbar puncture' below.)

Children with status epilepticus and fever may be more likely to have bacterial meningitis than those with a short seizure, although estimates of risk vary, and bacterial meningitis itself has become less common with widespread vaccination. In one prospective population-based cohort in England that included 95 children with status epilepticus and fever between the years 2002 and 2004, 11 children (11.6 percent) had acute bacterial meningitis [57]. By contrast, the rate of bacterial meningitis was only 0.8 percent in a retrospective cohort of 381 consecutive cases of convulsive status epilepticus and fever presenting to a single tertiary care center in Japan between the years 2010 and 2014 [20]. In addition to lower rates of bacterial meningitis over time, another potential explanation for the disparity is that the former study included both in-hospital and out-of-hospital presentations, whereas the latter study included only cases presenting to the emergency department.

The emergent evaluation and management of the child with suspected meningitis is discussed separately. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Evaluation'.)

The manifestations of viral meningitis or encephalitis are generally similar to those of bacterial meningitis but may be less severe. The diagnosis is made by clinical features, CSF examination, and viral studies. (See "Viral meningitis in children: Clinical features and diagnosis" and "Acute viral encephalitis in children: Clinical manifestations and diagnosis".)

Genetic epilepsies with febrile seizures — In some patients, the propensity for febrile seizures is an early manifestation of generalized epilepsy with febrile seizures plus (GEFS+), a genetic epilepsy for which a variety of causative mutations has been identified. Aside from typical febrile seizures, the most common phenotype of GEFS+ consists of seizures with fever in early childhood that, unlike typical febrile seizures, continue beyond six years of age or are associated with afebrile tonic-clonic seizures [41,58-60]. The phenotypic spectrum is broader than initially thought and includes a small number of individuals who have only focal seizures, leading to a proposal that the syndrome be renamed genetic (rather than generalized) epilepsy with febrile seizures plus [60]. The epilepsy typically remits by mid-adolescence but can persist into adulthood.

GEFS+ is usually associated with an autosomal dominant inheritance pattern. SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene identified for GEFS+. Family members who inherit the mutation may only have nonfebrile seizures [41,60]. Additional families have been identified with mutations in genes encoding voltage-gated sodium, calcium, and potassium channels; ligand-gated ion channels; nicotinic cholinergic receptor; various subunits of the gamma-aminobutyric acid receptor (GABA)-2; the GABA vesicular transporter (SLC32A1); and syntaxin 1B (STX1B) [36,61-73]. GEFS+ has been described as an evolving composite of many syndromes with shared genetic susceptibility [74].

Severe myoclonic epilepsy of infancy (Dravet syndrome) is a rare genetic epilepsy that can resemble complex febrile seizures in the first year [75]. Mutations in SCN1A, encoding for the alpha subunit of the voltage-gated sodium channel, are identified in approximately 70 to 80 percent of patients; the majority are de novo rather than germline mutations. Patients with Dravet syndrome typically present in the first year of life with prolonged, often febrile, generalized clonic or hemiclonic seizures in the setting of normal cognitive and motor development prior to the onset of seizures. The most common precipitants for seizures in children with Dravet syndrome are fever/illness and vaccination, although the first seizure is afebrile at least one-third of the time [76]. Most patients have refractory seizures and poor neurodevelopmental outcomes and are thereby easily distinguished from patients with febrile seizures with time. (See "Dravet syndrome: Genetics, clinical features, and diagnosis".)

DIAGNOSTIC EVALUATION — Febrile seizure is a clinical diagnosis, defined by the following features:

●A convulsion associated with an elevated temperature greater than 38°C

●A child older than six months and younger than five years of age

●Absence of central nervous system (CNS) infection or inflammation

●Absence of acute systemic metabolic abnormality that may produce convulsions

●No history of previous afebrile seizures

In children with a typical history for simple febrile seizure and a reassuring and nonfocal exam, diagnostic testing is unnecessary in most cases [77]. The evaluation should focus on assessment and diagnosis of the underlying febrile illness and parent or caregiver education about risk of recurrent febrile seizures and the low risk of future epilepsy. (See "Treatment and prognosis of febrile seizures".)

Children presenting with prolonged or focal febrile seizures, particularly if it is the first, require a more individualized approach since the likelihood of an alternative etiology such as meningitis or an underlying structural or metabolic cause is higher (although still quite low), and there is a slightly higher risk of future afebrile seizures. Electroencephalography (EEG) and magnetic resonance imaging (MRI) in the outpatient setting may help further stratify risk of future epilepsy in children with complex febrile seizures but are not usually necessary in the acute setting. The approach to outpatient evaluation of complex febrile seizures is not standardized, and a specific plan for each patient must be developed by the treating clinician, usually in consultation with a pediatric neurologist for interpretation of abnormal testing results.

Children younger than 12 months of age also warrant special consideration since signs and symptoms of meningitis may be more subtle in this age group. The threshold for performing a lumbar puncture (LP) in these patients should be lower, particularly if immunizations for Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae are not up to date or cannot be verified. (See 'Lumbar puncture' below.)

History — Key elements of the seizure history in a child presenting with a febrile seizure include seizure characteristics, duration of the seizure, and presence of focal features (eg, shaking limited to one limb or one side of the body). A witness to the seizure should be interviewed if possible, keeping in mind that seizures are frightening to many witnesses, and details of the seizure, including exact duration, may be difficult to elicit or unreliable.

A careful history must identify any underlying medical or neurologic conditions that increase the child's risk of serious infection or underlying structural abnormality. The history should include an assessment of immunization status, personal or family history of seizure, and history of neurologic problems or developmental delay. A child with a known neurologic condition may be more likely to experience a seizure with fever, which would not be classified as a simple febrile seizure. (See "Seizures and epilepsy in children: Clinical and laboratory diagnosis".)

Physical examination — A general physical and neurologic examination should include attention to vital signs, level of consciousness, presence or absence of meningismus, a tense or bulging fontanelle, and focal differences in muscle tone, strength, or spontaneous movements. The presence of any of these signs should prompt consideration of an alternative etiology such as meningitis or an underlying structural abnormality. Likewise, children with febrile seizures are typically well appearing, and postictal drowsiness usually resolves within 5 to 10 minutes, depending upon the duration and type of seizure. Encephalopathy beyond this time period should prompt increased suspicion for possible CNS infection or severe systemic infection. (See 'Lumbar puncture' below and 'Neuroimaging' below.)

Close attention may be necessary to detect ongoing or recurrent focal seizures in children presenting with complex febrile seizures, including febrile status epilepticus (FSE). In a prospective cohort study of more than 100 children presenting with FSE, the median seizure duration was 72 minutes, seizures were intermittent in half of the cases, and chart reviews suggested that status epilepticus was often not recognized by the emergency department staff, perhaps contributing to the long duration of the seizure [51,78]. 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 'Febrile status epilepticus' above.)

In well-appearing children without an obvious source of infection, attention to abnormal vital signs and physical findings, including tachypnea or hypoxemia, lesions in the oropharynx, or a viral exanthem, may help identify a specific etiology, which is most often viral. (See "Fever without a source in children 3 to 36 months of age: Evaluation and management", section on 'Well-appearing patients'.)

Lumbar puncture — The need for an LP and cerebrospinal fluid (CSF) examination to exclude meningitis or encephalitis in children with a febrile seizure is based mainly on clinical signs. Approximately 25 percent of children with meningitis will have seizures at or before the initial presentation, but virtually all of them will have other signs and symptoms of meningitis (eg, altered consciousness, nuchal rigidity, petechial rash) [53]. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Clinical features'.)

LP is unnecessary in most well-appearing children who have returned to a normal baseline after a febrile seizure [3,4]. We agree with the American Academy of Pediatrics (AAP) recommendations regarding the performance of LP in the setting of febrile seizures, which include the following [3]:

●LP should be performed when there are meningeal signs or symptoms or other clinical features that suggest a possible meningitis or intracranial infection

●LP should be considered in infants between 6 and 12 months if the immunization status for Hib or Streptococcus pneumoniae is deficient or undetermined

●LP should be considered when the patient is on antibiotics because antibiotic treatment can mask the signs and symptoms of meningitis

LP should also be considered when febrile seizures occur after the second day of illness or when, based on history or examination, the clinician remains concerned about possible CNS infection. Based on case series, but not included in the AAP guidelines, FSE may be another possible indication for LP [57,79,80]. (See 'Central nervous system infection' above.)

The low yield of LP in children presenting with a simple febrile seizure has been confirmed in several studies [81,82]. A retrospective cohort review of 704 patients aged 6 to 18 months who presented with a first simple febrile seizure revealed that 38 percent underwent LP [82]. There were no diagnoses of bacterial meningitis made in children in whom this was not otherwise suspected clinically; leukocytosis was present in 3.8 percent. CSF cultures revealed no pathogens, but in 10 cases (3.8 percent) a contaminant grew. Similarly, a study of 205 children aged 6 to 12 months with a simple febrile seizure and no clinical signs of meningitis found no cases of meningitis among 30 percent of children who underwent LP [81].

A separate study in 526 children with complex febrile seizures revealed similar findings, although the rate of LP was higher (64 percent) and bacterial meningitis was diagnosed in three patients (0.9 percent) [56]. In these three patients, there was reason to suspect CNS infection; one was clinically nonresponsive, one had a bulging fontanelle and apnea, and the other appeared well but had a positive blood culture for Streptococcus pneumoniae and did not have confirmatory CSF. Another study corroborated these findings and also confirmed the low utility of testing for herpes simplex virus (HSV) encephalitis: out of 839 patients presenting with a complex febrile seizure, the rates of bacterial meningitis and HSV encephalitis were 0.7 and 0 percent, respectively, and all five patients with meningitis had a clinical examination suggestive of infection [83]. Four out of the five cases of bacterial meningitis were in children <12 months of age, highlighting the importance of considering LP in infants with a prolonged febrile seizure, abnormal examination, and incomplete or unknown immunization status.

A finding of pleocytosis in the CSF in a patient with a febrile seizure should be considered a sign of bacterial meningitis until proven otherwise, indicating further evaluation with cultures and in certain cases empiric antimicrobial therapy. While pleocytosis in the CSF has been attributed to an epileptic seizure in some cases, this is rare in the setting of febrile seizure and should be considered a diagnosis of exclusion [84].

Other laboratories — A complete blood count and measurement of serum electrolytes [85], blood sugar, calcium, and urea nitrogen is of very low yield in patients with simple febrile seizures; these parameters should be measured only when the patient has a history of vomiting, diarrhea, and abnormal fluid intake, or when physical findings of dehydration or edema exist [3]. If a decision to perform an LP has been made, blood culture and serum glucose testing should be performed concurrently.

In children presenting with complex febrile seizures, hyponatremia is more common and has been associated with risk for recurrent seizure during the index illness [11]. For this reason, aggressive hydration with hypotonic fluids should generally be avoided in children with febrile seizures. In a prospective study of 69 children with febrile seizures, 52 percent had serum sodium levels <135 mmol/L; the mean level of serum sodium (134.4 mmol/L) was significantly lower compared with controls without fever but with convulsions. Measurement of the serum sodium was considered a valuable investigation in the child with a febrile seizure; the lower the serum sodium, the higher the probability of a recurrence of the seizure and the need to admit the child for management [86,87].

Neuroimaging — Neuroimaging with computed tomography (CT) or MRI is not required for children with simple febrile seizures [3,80,88]. The incidence of intracranial pathology in children presenting with complex febrile seizures also appears to be very low [55,89]. Urgent neuroimaging (CT with contrast or MRI) should be done in children with abnormally large heads, a persistently abnormal neurologic examination, particularly with focal features, or signs and symptoms of increased intracranial pressure [80,88,89].

While not necessary in the emergent setting, high-resolution MRI is often obtained in the outpatient setting in children with focal or prolonged febrile seizures, particularly those with a history of abnormal development, since these children have a higher risk of developing afebrile seizures [90].

Electroencephalography — Routine EEG is not warranted, particularly in the setting of a neurologically healthy child with a simple febrile seizure [3,4].

In children with complex febrile seizures, the need for an EEG depends on several factors and clinical judgement. A short, generalized seizure repeated twice in 24 hours is, by definition, complex but would not necessitate an EEG unless the neurologic examination were abnormal. A prolonged seizure, or one that has focal features, warrants an EEG and neurologic follow-up since the risk of future epilepsy (repeated afebrile seizures) is higher. The optimal timing of EEG is not well defined, but a study utilizing recordings performed within 72 hours of FSE suggest this may be a useful timeframe for prognostic purposes [91]. (See "Treatment and prognosis of febrile seizures", section on 'Electroencephalogram and risk of epilepsy'.)

Genetic testing — Genetic testing is not recommended in most children with febrile seizures, even those with a positive family history.

By contrast, genetic testing may be indicated when an alternative diagnosis such as Dravet syndrome is being considered on the basis of multiple prolonged focal febrile seizures and other seizure types before the age of 12 to 18 months; clinical presentations for which genetic testing is recommended are reviewed separately. (See "Dravet syndrome: Genetics, clinical features, and diagnosis", section on 'Genetic testing'.)

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".)

SUMMARY AND RECOMMENDATIONS

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

●Epidemiology and risk factors – Febrile seizures occur in 2 to 4 percent of children younger than five years of age, with a peak incidence between 12 and 18 months. Febrile seizures are an age-dependent phenomenon, likely related to a vulnerability of the developing nervous system to the effects of fever in combination with an underlying genetic susceptibility. Aside from age, the most commonly identified risk factors include high fever, viral infection, recent immunization, and a family history of febrile seizures. (See 'Epidemiology' above and 'Risk factors' above.)

●Presentation – The majority of children have their febrile seizures on the first day of illness and, in some cases, it is the first manifestation that the child is ill. (See 'Presentation' above.)

●Characteristics

•Simple febrile seizures – These are the most common type and are characterized by seizures that last less than 15 minutes, have no focal features, and occur once in a 24-hour period. These are mainly generalized tonic-clonic seizures but may also be atonic or tonic in character. (See 'Simple febrile seizures' above.)

•Complex febrile seizures – These are characterized by episodes that last more than 15 minutes, have focal features or postictal paresis, or occur more than once in 24 hours. (See 'Complex febrile seizures' above.)

●Differential diagnosis – The differential diagnosis of febrile seizure includes nonepileptic events or movements, CNS infection (eg, meningitis or encephalitis), and rare forms of genetic epilepsy in which seizures are particularly common with fever. While meningitis and encephalitis are the main concerns in a child presenting with fever and seizures, a thorough history and examination will almost always detect the child with meningitis. (See 'Differential diagnosis' above.)

●Evaluation – Febrile seizures are a clinical diagnosis. In children with a typical history and a reassuring and nonfocal exam, diagnostic testing is unnecessary in most cases. (See 'Diagnostic evaluation' above.)

•Role of lumbar puncture (LP) – An LP is unnecessary in most well-appearing children who have returned to a normal baseline after a febrile seizure. Postictal drowsiness typically resolved within 5 to 10 minutes, depending upon the duration and type of seizure. LP should be performed when there are meningeal signs or symptoms or other clinical features that suggest possible meningitis or intracranial infection. Additional circumstances that warrant consideration of LP include (see 'Lumbar puncture' above):

-Infants between 6 and 12 months of age, if the immunization status for Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae is deficient or undetermined

-Current treatment with antibiotics since antibiotics can mask the signs and symptoms of meningitis

-Febrile status epilepticus (FSE)

-Seizures that occur after the second day of a febrile illness

•Other tests – Laboratory testing, neuroimaging, and electroencephalography (EEG) are required only in specific circumstances. (See 'Other laboratories' above and 'Neuroimaging' above and 'Electroencephalography' above.)

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