Febrile Seizures


Febrile Seizures

Hanalise V. Huff, MD, MPH, and Kenneth R. Huff, MD


A 12-month-old girl is brought to the emergency department by paramedics because she is having a seizure. She is unresponsive and hypertonic, with arched trunk and extended arms and legs that are jerking rhythmically. Her eyes are open, but her gaze is directed upward. She has bubbles of saliva around her lips as well as circumoral cyanosis. Her vital signs are a respiratory rate of 60 breaths/minute, heart rate of 125 beats/minute, blood pressure of 130/78 mm Hg, and temperature of 41.0°C (105.8°F). An assessment of her respiratory status shows that she is moving air in all lung fields, and no evidence exists of upper airway obstruction.

The paramedics inform you that the girl has been convulsing with varying intensity of tone and movements but has remained unresponsive for approximately 6 minutes. Glucometer testing reveals a normal serum glucose level. Blood samples for other tests are sent to the laboratory, and urine is collected. An intravenous (IV) line is started, and the girl is given lorazepam by IV push. Within 2 minutes the movements cease, and her respirations become slow and even. No signs of trauma are evident on physical examination. Her only abnormality other than her unresponsive mental status is an inflamed and bulging right tympanic membrane.

The girl’s parents tell you that she has had a mildly stuffy nose for 2 days but has been afebrile and has seemed to be her usual self. While she was playing she became irritable, and her parents put her in her crib for her nap. Thirty minutes later they heard grunting noises, found her in the midst of a seizure, and called the paramedics. This is the girl’s first seizure. Her father recalls that his mother once told him that he had several “fever seizures” as an infant.


1. What are the characteristics of simple febrile seizures versus complex febrile seizures?

2. What is the appropriate evaluation of the child with febrile seizure, whether it is the first or a recurrence?

3. What is the recurrence risk for febrile seizure and the risk of developing unprovoked seizures after a febrile seizure?

4. What are the management options for the child with febrile seizure?

Febrile seizures are easily recognized, dramatic, generalized con-vulsions. A febrile seizure is defined by the presence of a fever or an acute inflammatory illness (often sudden) from a source outside the nervous system; patient age of approximately 5 years or younger; absence of chronic brain pathology, including developmental delay; absence of metabolic or structural abnormalities of the brain; and absence of previous nonfebrile seizures. Frequently, familial predisposition to similar seizures or a history of similar events in other family members is present. Despite the relatively uniform presentation of the seizure, other factors, such as genetic abnormalities in channels, neurotransmitter receptors, or hippocampal damage may influence prognosis, and individual clinical variables and social factors may influence management.


Febrile seizures occur in children between 6 months and approximately 5 years of age, but they are more common in children younger than 3 years. Some studies indicate that as many as 5% of all children in the United States experience at least 1 febrile seizure, and the prevalence is higher in the Asian population (eg, 6%–9% in Japan). The recurrence rate is 30% to 50% in children younger than 1 year, drops to 25% between 1 and 3 years of age, and falls to 12% after age 3 years. Seizures are associated with a higher maximum temperature and may occur with the rise in temperature and often so suddenly that the febrile illness is not recognized by the family prior to the seizure. Frequently, the febrile illness eventually is diagnosed as an upper respiratory tract or influenza infection or follows immunization. Human herpesvirus 6 infections may be associated with one-third of first-time febrile seizures and a somewhat higher rate of complex febrile seizures. Febrile seizures often occur in children with a first-degree relative who experienced the problem at the same age.

Clinical Presentation

A simple febrile seizure is characterized by a single episode of generalized, symmetric, tonic posturing and clonic movements of a few minutes’ duration that occurs suddenly in the child whose developmental progress is generally normal. Fever or an acute inflammatory illness is present, although it may not have been recognized before the seizure, and its source is outside the nervous system. A short time after the seizure (typically after 1–2 hours of postictal sleepiness), the child returns to a normal neurologic state (Box 69.1).

Box 69.1. Diagnosis of Febrile Seizure in the Pediatric Patient

Sudden unresponsiveness, tonic posturing, and generalized rhythmic jerking

Fever or acute inflammatory illness source outside nervous system

Age 6 months to approximately 5 years

Normal neurodevelopmental history

The recently described generalized epilepsy with febrile seizures plus (GEFS+) is characterized by the association of generalized febrile seizures after age 6 years and afebrile generalized convulsions, a positive family history of epilepsy with variable phenotypes, and a benign prognosis in most cases. The same families may have simple febrile seizures, febrile seizures after age 6 years, febrile seizures and absences, atonic or myoclonic seizures, and myoclonicastatic epilepsy or Dravet syndrome.


The susceptibility of young children to febrile seizures may be related to an increased incidence of sudden high fevers in this age group, a developmental genetic factor that may lower the seizure threshold, or both. Animal models indicate that the immature brain has a lower seizure threshold than the adult brain, and seizures in the immature brain are more likely to occur by a mechanism different from that in the adult. Febrile seizure has a mild association with prenatal nicotine exposure, iron insufficiency, and atopic conditions. A sudden increase in temperature to a sufficiently high level can provoke seizure regardless of age. Cultured neurons subjected to hyperthermia show epileptiform activity. Seizures occur more frequently with fever in many seizure-prone patients who have seizures of different etiologies, including genetic epilepsies. It may be that circulating pyrogens or interleukins interact with a brain cellular circuitry mechanism or susceptible ion channels, causing hypersynchronous depolarization and seizure. The commonly noted multigenerational familial history is suggestive of a dominantly expressed genetic transmission with reduced penetrance or a polygenic model. Different families have different loci linkages.

The precise definitions of the genetic markers and mechanisms of generalized seizures in all cases are not yet fully understood. Recent work suggests possible mechanisms. Mutations in γ-aminobutyric acid (GABA)A receptor genes have been found to be associated with febrile seizures and GEFS+ pedigrees. The GABAA receptors transmit inhibitory signals and are composed of combinations of 5 subunits. The γ2 subunit is critical for receptor trafficking, clustering, and synaptic maintenance, and mutations in this subunit have been associated with febrile seizure families. It has also been found that the trafficking of mutant receptors with γ2 subunit mutations was more highly temperature dependent than mutations of other subunits and impaired membrane insertion or accelerated receptor endocytosis when brief increases of 37°C to 40°C (98.6°F to 104°F) occurred. In families with these mutations, febrile seizures may be caused by a fever-induced change in the status of a dynamic membrane receptor system, producing reduced numbers of available GABAA receptors.

In other families with GEFS+, it has been found that mutations in the SCN1A (sodium voltage-gated channel alpha subunit 1) gene have occurred. Mutations in this same gene may occur in sequences that encode for the critical “pore” region of the subunit protein that participates in ion selectivity and results in a more severe phenotype with early prolonged resistant seizures and later, intellectual and developmental disability and Dravet syndrome. A less severe GEFS+ phenotype is associated with a less functionally critical position of the missense mutation in the SCN1A gene. A rat model of hyperthermic seizures has a comparable mutation and may provide additional clues related to pathophysiology.

Differential Diagnosis

When a young child presents with a fever and a seizure, the possibility that the seizure is symptomatic of meningitis, encephalitis, or brain abscess must be considered, although other clinical signs are nearly always present. Signs of meningeal irritation may not be reliable in infants younger than 12 months, however, and these and other signs of the illness may be obscured in the postictal period. If a history of lethargy or persistent vomiting exists; the seizure is focal in onset or prolonged or multiple seizures occur; or the postictal depression is prolonged, an examination of the cerebrospinal fluid (CSF) should be done. In addition, if the patient is deficient in Haemophilus influenzae type b or Streptococcus pneumoniae immunizations or the patient has been pretreated with antibiotics, which could mask meningeal signs or symptoms, a CSF examination should be considered. It is rare that a febrile seizure would cause CSF pleocytosis (>10–20 white blood cells/mm3). The fever also could be provocative or coincidental to a seizure of different etiology, such as trauma, toxic ingestion, metabolic derangement, degenerative or neurocutaneous disorder, or stroke.

A useful concept for the physician caring for a child with a febrile seizure has been the differentiation of simple febrile seizure from complex febrile seizure (Table 69.1). A question with prognostic implications is whether a child in the appropriate age range has had a true febrile seizure or a seizure with fever, which may be an early fever-provoked episode of a nonfebrile seizure disorder. The factors that define a complex febrile seizure also predict an increased likelihood of later unprovoked nonfebrile seizures. A complex febrile seizure may last 15 minutes or longer. Most febrile seizures are shorter than 90 seconds, although a significant number present in status epilepticus. Recurrent febrile seizures are considered complex if more than 1 febrile seizure occurs during the same infectious illness or during the first 24-hour period following the initial seizure. Febrile seizures are also complex if there is a history of a focal or partial onset or the presence of postictal focal neurologic signs. An abnormal neurodevelopmental history prior to the febrile seizure or abnormal neurologic examination or brain imaging study before or after the seizure also is indicative of an increased likelihood of later unprovoked seizures.

Table 69.1. Simple Versus Complex Febrile Seizures




Onset of clonic movements




<15 minutes (usually <90 seconds)

≥15 minutes

Number of seizures per 24-hour febrile illness



Neurodevelopmental history



Parent or sibling history of febrile seizure

Often positive

Often negative



After the seizure has been controlled and the child has been stabilized, a more detailed history relating to the circumstances of the seizure should be obtained, including the child’s state leading up to the seizure; prenatal, birth, and developmental histories; and family seizure history (Box 69.2).

Physical Examination

The child should be examined thoroughly after stabilization, noting the possibility that the fever may be coincidental and signs from an unrelated cause inciting the seizure could be present. The physician should look for bruising, fracture, retinal hemorrhage, and other signs of trauma. The presence of dysmorphic features, enlarged organs, or bony changes should be noted. The skin should be examined for abnormal, pigmented, or textured spots. Lateralized signs of tone or strength should be assessed. An appropriate examination to determine the etiology of the fever should also be performed (see Chapter 67). Meningismus, bulging fontanelle, and prolonged postictal drowsiness should prompt consideration of meningitis or encephalitis.

Laboratory Tests

If the seizure is prolonged, focal, or multiple; if a history exists of lethargy, stupor, or persistent vomiting before the seizure; or if the patient remains ill-appearing after the postictal period, cultures should be obtained and metabolic and toxicologic blood and urine studies sent. A lumbar puncture for CSF examination for meningitis or encephalitis should be done unless signs exist of increased intracranial pressure or a lateralized neurologic examination, in which case antibiotics should be given and an imaging study obtained prior to the lumbar puncture.

Box 69.2. What to Ask

Febrile Seizure in the Pediatric Patient

What were the child’s symptoms for the few days before the seizure?

Where was the child, and what was the child doing immediately before the seizure?

Were there any pregnancy-related or perinatal complications?

Has the child’s development been normal or similar to that of siblings?

Have any other family members had seizures of any kind, including during infancy?

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Aug 28, 2021 | Posted by in PEDIATRICS | Comments Off on Febrile Seizures
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