Pediatric Annals

CME 

Febrile Seizures

Janet L. Patterson, MD; Stephanie A. Carapetian, MD; Joseph R. Hageman, MD; Kent R. Kelley, MD

Abstract

CME Educational Objectives

1. Discuss the classification, epidemiology, and pathophysiology of febrile seizures in children.

Review the evaluation, management, and prognosis of febrile seizures.

Understand the long-term outcomes and implications for follow-up management and parental education of febrile seizures.

Febrile seizures are the most common form of childhood seizures, affecting 2% to 5% of children. They are considered benign and self-limiting; however, a febrile seizure is a terrifying event for most parents, and is one of the most common causes of trips to the emergency room.

A febrile seizure is “an event in infancy or childhood, usually occurring between 3 months and 5 years of age, associated with fever but without evidence of intracranial infection or defined cause.” This definition excludes seizures with fever in children who have had a prior afebrile seizure. In 2011, The American Academy of Pediatrics (AAP) published a clinical practice guideline defining a febrile seizure as “a seizure accompanied by fever (temperature ≥ 100.4°F or 38°C by any method), without central nervous system infection, that occurs in infants and children 6 through 60 months of age.” Febrile seizures are further classified as simple or complex. This article reviews the evaluation, management, and prognosis of simple and complex seizures, including febrile status epilepticus.

Abstract

CME Educational Objectives

1. Discuss the classification, epidemiology, and pathophysiology of febrile seizures in children.

Review the evaluation, management, and prognosis of febrile seizures.

Understand the long-term outcomes and implications for follow-up management and parental education of febrile seizures.

Febrile seizures are the most common form of childhood seizures, affecting 2% to 5% of children. They are considered benign and self-limiting; however, a febrile seizure is a terrifying event for most parents, and is one of the most common causes of trips to the emergency room.

A febrile seizure is “an event in infancy or childhood, usually occurring between 3 months and 5 years of age, associated with fever but without evidence of intracranial infection or defined cause.” This definition excludes seizures with fever in children who have had a prior afebrile seizure. In 2011, The American Academy of Pediatrics (AAP) published a clinical practice guideline defining a febrile seizure as “a seizure accompanied by fever (temperature ≥ 100.4°F or 38°C by any method), without central nervous system infection, that occurs in infants and children 6 through 60 months of age.” Febrile seizures are further classified as simple or complex. This article reviews the evaluation, management, and prognosis of simple and complex seizures, including febrile status epilepticus.

Febrile seizures are the most common form of childhood seizures, affecting 2% to 5% of children. They are considered benign and self-limiting, however, a febrile seizure is a terrifying event for most parents, and is one of the most common causes of trips to the emergency room (ER).

Characteristics and Classification

Febrile seizures are classified as simple or complex based on duration, physical characteristics, and recurrence patterns (Table 1). A self-limited, short (< 15 minutes), generalized, tonic-clonic seizure that does not recur within the same illness and is not associated with post-ictal pathology is classified as a simple febrile seizure (SFS). Febrile seizures that do not meet all criteria for SFS are classified as complex febrile seizures (CFS). A prolonged febrile seizure (PFS) is a complex seizure that lasts longer than 15 minutes, and a febrile seizure that continues longer than 30 minutes is classified as febrile status epilepticus (FSE).5 FSE accounts for 5% to 9% of all febrile seizures6,7 and 25% of all episodes of status epilepticus occurring in children.8,9 In the second year of life, two-thirds of all cases of status epilepticus are FSE.10 FSE is considered a medical emergency.

Classification of Febrile Seizures

Table 1.

Classification of Febrile Seizures

Despite the common belief that febrile seizures occur with rise in temperature, there is no evidence to support this. Febrile seizures usually develop in the first 24 hours of the illness,8,11 with 21% of children manifesting a seizure within an hour of fever onset.11 The fever associated with febrile seizures is typically higher than in children with similar fever-related illness who do not experience a seizure,1 and the height of the fever is often at least 39°C at the time of the seizure.11 The seizure itself is the first sign of febrile illness in 25% to 50% of cases, and seizures that occur 3 or more days after the onset of fever should be considered unlikely to be a febrile seizure.11

Incidence

In the United States and Western Europe, 2% to 5% of all children experience a febrile seizure. The incidence varies in other parts of the world; for example, 5% to 10% in India, 8.8% in Japan, and 14% in Guam.8 The first febrile seizure occurs commonly between 6 months and 3 years of age, with the peak incidence at 18 months.1,11 They are complex in 9% to 35% of cases, and the incidence in boys is slightly higher than in girls.

Risk Factors

The two most consistently identified risk factors for developing febrile seizures are the height of the temperature and a positive family history in first-degree relatives.8,11,12

Higher temperatures are associated with a higher likelihood of having a febrile seizure.11,12 The risk for febrile seizures increases with the number of relatives who have a history of febrile seizures.1,8 Sibling studies identify a risk of 10% to 45%.8,13

Other identified risk factors are a neonatal nursery stay of greater than 28 days, developmental delay, and day care attendance.2,14,15

Pathogenesis

Febrile seizures are strongly age-specific, and mechanisms of seizure development are related to the identified risk factors, environment (fever) and genetics. Animal models have shown that brain hyperthermia can lead to seizures in all species of rats and mice. Certain strains have different seizure - threshold temperatures, implying genetic influences on susceptibility.16

Several gene loci have been implicated in familial febrile seizures, including genes that code for GABA receptors and interleukins. SCN1A gene mutations are responsible for a spectrum of seizure disorders that often present initially as a febrile seizure. This spectrum of disorders ranges from SFS to generalized epilepsy with febrile seizures plus (GEFS+), and at the severe end, Dravet syndrome (or severe myoclonic epilepsy in infancy).17,18 Various mechanisms have been proposed in the pathogenesis of febrile seizures, including temperature sensitive ion channels altering neuronal function, and inflammatory processes promoting secretion of cytokines (known to increase neuronal excitability).11,16 Specific infectious etiologies have been associated with febrile seizures, such as human herpes simplex virus-6 (roseola infantum), accounting for as much as 20% of children presenting with first febrile seizures, shigella gastroenteritis, and influenza A.19–21 Immunizations, such as diphtheria-tetanus-pertussis and measles-mumps-rubella, are associated with significantly elevated risks of febrile seizures.22 It is unclear whether the association of infections and immunizations are related to the height of the fever or some other unidentified factor.11

Evaluation/Management

Simple Febrile Seizures

Children with SFS tend to present to the ER for medical care after resolution of the seizure. They may be post-ictal and appear irritable, confused, or lethargic. Gradual return to a normal level of alertness occurs within 1 hour, and there are no focal deficits. Transient hemiparesis (Todd’s paralysis) has been described with SFS but should always raise suspicion of focality and, therefore, complex classification.23

The medical history should include duration of fever, potential illness exposure, and recent antibiotic use. Neuro-developmental delay, possible metabolic disturbance, history of prior seizures, and other potential causes of seizures, such as trauma or accidental ingestion, should also be considered.

The diagnostic evaluation of a child with an SFS should clarify whether the child actually had a seizure and focus on identifying the source of fever. The 2011 AAP clinical practice guideline recommendations state, “meningitis should be considered in the differential diagnosis in any child with fever, and a lumbar puncture (LP) should be performed if there are any signs or symptoms of concern” (level B evidence). Level D evidence supports consideration of an LP in the evaluation of a younger child (6 to 12 months), a child who is underimmunized, of questionable vaccination status, or on prior antibiotics. Further investigations — such as blood studies, imaging studies, or EEGs —are not necessary, unless there are specific indications for concern based on the history and physical findings.4

The AAP guidelines were based on retrospective analyses of the risk for bacterial meningitis presenting as a SFS with no other symptoms of meningitis. In a 20-year review of 503 consecutive children with bacterial meningitis, no child presented solely with an SFS.24 A more recent study of 6- to 18-month-old children presenting with a first SFS found no cases of bacterial meningitis.25

Complex Febrile Seizures

CFS are heterogeneous in presentation, and no national practice guidelines are established. A survey of 353 pediatric emergency providers identified significant variability in the evaluation of children with CFS.26 One-third of febrile status epilepticus (FSE) cases are unrecognized in the ER.5,6 In a prospective study of 60 children presenting with prolonged febrile seizure (PFS), 70% went into FSE, irrespective of whether treatment was administered in the field.10 Treatment of an ongoing seizure consists of airway maintenance, oxygen, supportive care, and anticonvulsants. Rectal diazepam has been used at home and in the ER with dosing of 0.25 mg/kg to 0.5 mg/kg.15

CFS and FSE are more frequently associated with meningitis than SFS.24,27 CNS infections are unlikely, however, unless there are accompanying clinical findings, such as decreased level of consciousness, meningeal signs, or toxic appearance.25,28 An LP is frequently unnecessary unless the patient is under the age of 12 months (limiting confidence in physical exam), displays signs of CNS infection, or does not return to baseline mental status.29 About one in four children with meningitis present with a seizure,15 and bacterial meningitis occurs in up to 18% of children with CFS.27

Imaging studies are not indicated in most well-appearing children with first CFS.29 In a recent review of children with a first CFS, no child had intracranial pathology.30 High resolution brain MRI should be considered in the follow up of focal, PFS, and FSE due to the association of FSE with hippocampal injury, mesial temporal sclerosis, and temporal lobe epilepsy.5,31,32

An EEG is not usually indicated for evaluations of CFS with the exception of FSE. EEG may be considered in follow-up if there are recurrences without fever or evidence of developmental delay or neurologic deficits.33

A prospective, multicenter study (Consequences of Prolonged Febrile Seizures in Childhood, or FEBSTAT) was initiated to examine the association between PFS, FSE, and the development of hippocampal sclerosis. The FEBSTAT study followed children aged 1 month to 6 years who presented with an episode of FES, documenting periodic imaging and EEGs.5 The FEBSTAT study findings identified 90 of 119 EEGs obtained in the first 72 hours after FSE as abnormal, with focal slowing or attenuation primarily over the temporal area. These preliminary findings (currently at the 5-year mark) were highly associated with MRI evidence of acute hippocampal injury and may indicate a marker for injury associated with FSE.5

Prognosis

Recurrence Risk

One in three children with a febrile seizure will have another, and age (< 15 months) appears to be the most consistent risk factor associated with recurrence.1,8 If recurrence occurs, half will recur within the first year and 90% will occur within 2 years.8 Other associated factors include epilepsy or febrile seizures in first-degree relatives, first CFS, and day care exposure. As the number of risk factors increase, the recurrence risk increases;34 the presence of three or more risk factors is associated with 80% to 100% recurrence. Higher recurrence risk has also been associated with seizures that occur at lower-peak temperatures or within an hour of fever onset.35

Epilepsy Risk

Although children with febrile seizures are at increased risk of developing epilepsy compared to healthy controls,36,37 most children with febrile seizures (97%) will never develop epilepsy.1

Risk factors for developing epilepsy following SFS is 1% to 2.4% (compared to 0.5% in the general population) and 4% to 6% following CFS.36 The National Cooperative Perinatal project identified idiopathic or genetic epilepsy in a first-degree relatives, abnormal neurodevelopmental status prior to seizure onset, and CFS as independent risk factors.37 Population-based studies identified cerebral palsy, low apgar score, PFS, focal seizures, and recurrent febrile seizures with increased epilepsy risk.38

PFS have been associated with increased risk of recurrent febrile seizures, epilepsy, and FSE.10 Hersdorffer7 noted that defining PFS at 10 minutes or greater, instead of 15, is associated with prior developmental delay and younger age at first seizure.

Mortality and Morbidity

Population-based studies have shown no association between any type of febrile seizure, including FSE, and the later development of neurological deficits or impaired cognitive functioning.39 Children with febrile seizures do not have a higher risk of mortality.11

Prevention

There is no evidence to support the use of antipyretics for the prevention of recurrent seizures, although they may be helpful in relieving the discomfort of a febrile child.15

Although studies have shown efficacy in reducing the recurrence rate of febrile seizures by treating with continuous antiepileptic therapy, both the Royal College of Pediatrics and Child Health and the AAP do not recommend the use of prophylactic oral antiepileptic medication in children with either SFS or CFS due to significant associated side effects.1,23

Education

Despite the benign nature and excellent prognosis of febrile seizures, they are a cause of high anxiety among parents. When a seizure is first witnessed, parents may think that the child is dying, and parental reactions to febrile seizures include anxiety in reference to recurrence and fear of subsequent development of epilepsy, physical disabilities, mental retardation, and learning dysfunction. In light of the high incidence of recurrence, parents need specific information on appropriate first aid techniques and reassurance that febrile seizures are not associated with death, development of neurological deficits, or impaired cognitive functioning. (Table 2)

Talking Points

Table 2.

Talking Points

Summary

In conclusion, febrile seizures are a common, benign disorder occurring in children between 6 months and 3 years of age, and most children have an excellent outcome with no long-term sequelae. Identifying the source of fever and parental education are the mainstays of management for children with SFS. Balancing the avoidance of unnecessary diagnostic and therapeutic interventions with practical approaches to long-term follow-up for CFS is crucial. The recognition, treatment, and prevention of FSE, as well as the understanding of long-term outcomes, will guide future management of PFS (Table 3).

Management of Febrile Seizures

Table 3.

Management of Febrile Seizures

References

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Classification of Febrile Seizures

Simple Febrile Seizure (all criteria must be met) Complex Febrile Seizure (one or more of the following)
Duration Short (< 15 minutes) Self - limiting Prolonged febrile seizure (> 15 minutes) Febrile status epilepticus (> 30 minutes)
Phenotype Generalized tonic-clonic Focal onset or features Clonic and/or tonic Loss of muscle tone Focal progressing to general Head/eye deviation to one side
Recurrence Frequency No recurrence in 24 hours Recurrence within the same febrile illness
Prior Neurologic Diagnosis None Present
Post-ictal Pathology None Present (unilateral paralysis, somnolence)

Talking Points

General information Simple Febrile Seizure (not harmful / does not cause death or brain damage) Complex Febrile Seizure (not harmful / does not cause death or brain damage)
Recurrence One-third have recurrence Increased risk if child:

Has family history of seizures

Is < 12 months

Has temperature < 102°

One-third have recurrence Increased risk if child:

Has family history of seizures

Is < 12 months

Has temperature < 102°

Has PFS

Management Important action points:

Remain calm

Place child on his / her side to prevent choking.

Do not put anything in the child’s mouth or try to restrain

Call 911 if seizure lasts longer than 5 minutes.

Important action points:

Remain calm

Place child on his / her side to prevent choking.

Do not put anything in the child’s mouth or try to restrain

Call 911 if seizure lasts longer than 5 minutes

Epilepsy Risk Most children never develop epilepsy. Risk is slightly higher than risk for all children. Most children never develop epilepsy. Higher epilepsy risk than SFS if child has:

Prior neurodevelopmental abnormality,

Positive family history

Onset prior to 1 year of age

Learning Risk No higher risk of learning difficulties or decreased IQ Learning risk is associated with familial seizure disorders
Prophylaxis Not indicated Rarely indicated (identified syndrome, PFS or FSE)

Management of Febrile Seizures

Diagnostic Criteria SFS (Simple) Short (< 15 minutes), self-limiting, tonic/clonic generalized, non-recurrent CFS (Complex) Does not meet criteria for “simple” PFS/FSE (Prolonged) >15 minutes
Acute Management Comfort measures Observe post-ictal state Investigate etiology of fever Comfort Measures Monitor post-ictal state Investigate etiology of fever Treat with antiepileptic Monitor post-ictal state Investigate etiology of fever
  LP Consider LP:

S/X of meningitis

Concern for exam reliability

Consider LP if:

S/X of meningitis

Non-return to baseline status

Concern for exam reliability

Consider LP if:

S/X of meningitis

Non-return to baseline status

Concern for exam reliability

  EEG NI NI NI unless S/X of space occupying lesion or bleed NI unless concern for ongoing seizure
  Imaging (CT) NI NI NI unless S/X of space occupying lesion or bleed
  Labs NI NI NI
Follow-Up Management Parental Education/Support Parental Education/Support Parental Education/Support
  EEG NI NI routinely, consider if:

> 1 complex feature

Abnormal neurodevelopmental status

History of family epilepsy

Indicated
  Imaging (MRI) NI NI Indicated
Prophylaxis NI NI Consider acute intermittent therapy
Authors

Janet L. Patterson, MD, is Assistant Professor of Clinical Pediatrics, Division of Child Development, University of Illinois College of Medicine at Peoria. Stephanie A. Carapetian, MD, is Pediatric Neurology Fellow, Division of Pediatric Neurology, University of Washington. Joseph R. Hageman, MD, is Senior Clinical Educator, Pritzker School of Medicine, University of Chicago, Department of Pediatrics, NorthShore University Health System. Kent R. Kelley, MD, is Clinical Assistant Professor, Pritzker School of Medicine, University of Chicago, Department of Pediatrics, NorthShore University Health System.

Address correspondence to: Janet L. Patterson, MD; University of Illinois College of Medicine, Peoria, University Child Development, 507 E. Armstrong Peoria, IL 61603; email: patters@uicomp.uic.edu.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00904481-20131122-09

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