Pediatric febrile seizures, which represent the most common childhood seizure disorder, exist only in association with an elevated temperature. Evidence suggests, however, that they have little connection with cognitive function, so the prognosis for normal neurologic function is excellent in children with febrile seizures.[1]
Epidemiologic studies have led to the division of febrile seizures into 3 groups, as follows:
Simple febrile seizures
Complex febrile seizures
Symptomatic febrile seizures
Essential update: Starting MMR/MMRV vaccination earlier may reduce seizure risk
In a case-series analysis of a cohort of 323,247 US children born from 2004 to 2008, Hambidge et al found that delaying the first dose of measles-mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMRV) vaccine beyond the age of 15 months may more than double the risk of postvaccination seizures in the second year of life.[2, 3]
In infants, there was no association between vaccination timing and postvaccination seizures.[3] In the second year of life, however, the incident rate ratio (IRR) for seizures within 7-10 days was 2.65 (95% confidence interval [CI], 1.99-3.55) after first MMR doses at 12-15 months of age, compared with 6.53 (95% CI, 3.15-13.53) after first MMR doses at 16-23 months. For the MMRV vaccine, the IRR for seizures was 4.95 (95% CI, 3.68-6.66) after first doses at 12-15 months, compared with 9.80 (95% CI, 4.35-22.06) for first doses at 16-23 months.
Signs and symptoms
Simple febrile seizure
The setting is fever in a child aged 6 months to 5 years
The single seizure is generalized and lasts less than 15 minutes
The child is otherwise neurologically healthy and without neurologic abnormality by examination or by developmental history
Fever (and seizure) is not caused by meningitis, encephalitis, or any other illness affecting the brain
The seizure is described as either a generalized clonic or a generalized tonic-clonic seizure
Complex febrile seizure
Age, neurologic status before the illness, and fever are the same as for simple febrile seizure
This seizure is either focal or prolonged (ie, >15 min), or multiple seizures occur in close succession, i.e. within the same fever episode
Symptomatic febrile seizure
Age and fever are the same as for simple febrile seizure
The child has a preexisting neurologic abnormality or acute illness
See Clinical Presentation for more detail.
Diagnosis
No specific laboratory studies are indicated for a simple febrile seizure. Physicians should instead focus on diagnosing the cause of fever. Other laboratory tests may be indicated by the nature of the underlying febrile illness. For example, a child with severe diarrhea may benefit from blood studies for electrolytes.
With regard to lumbar puncture, the following should be kept in mind:
Strongly consider lumbar puncture in children younger than 12 months, because the signs and symptoms of bacterial meningitis may be minimal or absent in this age group
Lumbar puncture should be considered in children aged 12-18 months, because clinical signs and symptoms of bacterial meningitis may be subtle in this age group
In children older than 18 months, the decision to perform lumbar puncture rests on the clinical suspicion of meningitis
See Workup for more detail.
Management
On the basis of risk/benefit analysis, neither long-term nor intermittent anticonvulsant therapy is indicated for children who have experienced 1 or more simple febrile seizures.
If, however, preventing subsequent febrile seizures is essential, oral diazepam would be the treatment of choice. It can reduce the risk of febrile seizure recurrence and, because it is intermittent, probably has the fewest adverse effects.[4]
Antipyretics have typically been suggested with a primary goal of comfort in mind, as it has been uncertain whether antipyretics can impact the occurrence of further febrile seizures. However a randomized controlled trial published in 2018 suggested that rectal acetaminophen given every 6 hours may prevent febrile seizure recurrence within the same febrile episode.[5]
Febrile seizures are the most common seizure disorder in childhood. Since early in the 20th century, people have debated about whether these children would benefit from daily anticonvulsant therapy. Epidemiologic studies have led to the division of febrile seizures into 3 groups, as follows: simple febrile seizures, complex febrile seizures, and symptomatic febrile seizures.
Simple febrile seizure
See the list below:
The setting is fever in a child aged 6 months to 5 years.
The single seizure is generalized and lasts less than 15 minutes.
The child is otherwise neurologically healthy and without neurological abnormality by examination or by developmental history.
Fever (and seizure) is not caused by meningitis, encephalitis, or other illness affecting the brain.
Complex febrile seizure
See the list below:
Age, neurological status before the illness, and fever are the same as for simple febrile seizure.
This seizure is either focal or prolonged (ie, >15 min), or multiple seizures occur in close succession i.e. during the same febrile episode.
Symptomatic febrile seizure
See the list below:
Age and fever are the same as for simple febrile seizure.
The child has a preexisting neurological abnormality or acute illness.
This is a unique form of seizures that occurs in early childhood and only in association with an elevation of temperature. The underlying pathophysiology is unknown, but genetic predisposition clearly contributes to the occurrence of this disorder.[6]
Febrile seizures occur in 2-5% of children aged 6 months to 5 years in industrialized countries. Among children with febrile seizures, about 70-75% have only simple febrile seizures, another 20-25% have complex febrile seizures, and about 5% have symptomatic febrile seizures.
Children with a previous simple febrile seizure are at increased risk of recurrent febrile seizures; this occurs in approximately one third of cases.
Children younger than 12 months at the time of their first simple febrile seizure have a 50% probability of having a second seizure. After 12 months, the probability decreases to 30%.
Children who have simple febrile seizures are at a slightly increased risk for epilepsy. The rate of epilepsy by age 25 years is approximately 2.4%, which is about twice the risk in the general population.
The literature does not support the hypothesis that simple febrile seizures are associated with lower intelligence or learning disability or are associated with increased mortality[7] .
Sex
Males have a slightly (but definite) higher incidence of febrile seizures.
Age
Simple febrile seizures occur most commonly in children aged 6 months to 5 years.
Children with simple febrile seizures are neurologically and developmentally healthy before and after the seizure.
They do not experience a seizure in the absence of fever.
The seizure is described as either a generalized clonic or a generalized tonic-clonic seizure.
Signs of a focal seizure during the onset or in the postictal period (eg, initial clonic movements of 1 limb or of the limbs on 1 side, a weak limb postictally) would rule out a simple febrile seizure.
Similarly, simple febrile seizure activity does not continue for more than 15 minutes, although a postictal period of sleepiness or confusion can extend beyond the 15-minute maximum.
Simple febrile seizures often occur with the initial temperature elevation at the onset of illness. The seizure may be the first indication that the child is ill. While no clear cutoff is known, a rectal temperature under 38°C should raise concern that the event was not a simple febrile seizure.
Physical examination findings reveal a neurologically and developmentally healthy child. It is especially important that the child have no signs of meningitis or encephalitis (eg, stiff neck or persistent mental status changes).
Simple febrile seizures are considered a genetic disorder, but neither a specific locus nor a specific pattern of inheritance has been described. The mode of inheritance is likely to vary between families and may be multifactorial.
No specific studies are indicated for a simple febrile seizure.
Physicians should focus on diagnosing the cause of fever.
Other laboratory tests may be indicated by the nature of the underlying febrile illness. For example, a child with severe diarrhea may benefit from blood studies for electrolytes.
Neither computed tomography (CT) nor magnetic resonance imaging (MRI) is indicated in patients with simple febrile seizures. A prospective study on the outcomes of febrile status epilepticus (duration ≥30 minutes), named the Consequences of Prolonged Febrile Seizures in Childhood or FEBSTAT, has shown that febrile status epilepticus is more frequently associated with hippocampal abnormality as compared to patients with simple febrile seizure.[8]
EEG is not indicated in children with simple febrile seizures. Published studies demonstrate that the vast majority of these children have a normal EEG. In addition, some of those with an abnormal EEG have remained free of seizures for the duration of their follow-up. On the other hand, some of the children with a normal initial EEG have experienced 1 or more afebrile seizures subsequent to the EEG. Finally, no evidence indicates that beginning anticonvulsant therapy for a child with simple febrile seizures and an abnormal EEG will alter the child's eventual outcome.
Strongly consider lumbar puncture in children younger than 12 months, because the signs and symptoms of bacterial meningitis may be minimal or absent in this age group.
Lumbar puncture should be considered in children aged 12-18 months, because clinical signs and symptoms of bacterial meningitis may be subtle in this age group.
In children older than 18 months, the decision to perform lumbar puncture rests on the clinical suspicion of meningitis.
On the basis of risk/benefit analysis, neither long-term nor intermittent anticonvulsant therapy is indicated for children who have experienced 1 or more simple febrile seizures.
Continuous therapy with phenobarbital or valproate decreases the occurrence of subsequent febrile seizures.
Both therapies confer significant risks and potential adverse effects, whereas additional simple febrile seizures have no proven risk.
These medications are not recommended, since the potential benefits do not outweigh the potential risks.
No evidence suggests that any therapy administered after a first simple febrile seizure will reduce the risk of a subsequent afebrile seizure or the risk of recurrent afebrile seizures (ie, epilepsy).
Oral diazepam can reduce the risk of subsequent febrile seizures. Because it is intermittent, this therapy probably has the fewest adverse effects. If preventing subsequent febrile seizures is essential, this would be the treatment of choice.[4]
Although it has been felt that antipyretic therapy cannot prevent simple febrile seizures, it is desirable for other reasons, for instance comfort. A randomized controlled trial published in 2018 suggested that rectal acetaminophen 10 mg/kg given every 6 hours may prevent febrile seizure recurrence within the same febrile episode.[5]
Febrile status epilepticus (duration ≥30 minutes) occurs in 5 to 9% of children with first febrile seizure. Patients with febrile status epilepticus are at greater risk for subsequent febrile status epilepticus.[9] Many practitioners have prescribed rectal diazepam for patients with febrile seizures, particularly those with febrile seizures lasting more than 5 minutes. There is some literature supporting the safety and efficacy towards truncating the seizures. Following a review of 7 randomized studies, investigators concluded that the benzodiazepine midazolam, administered intranasally, is as safe and effective as intravenous or rectal diazepam in the treatment of acute pediatric seizure emergencies. Results were based on the administration of 0.2 mg/kg of intranasal midazolam versus 0.2-0.5 mg/kg of either intravenous (4 trials) or rectal (3 trials) diazepam, for the treatment of seizure emergencies having an onset of action of less than 5 minutes. Patients in the study were aged 18 years or younger. The 3 types of treatment produced only a few reports of respiratory depression.[10, 11, 12]
On the basis of risk/benefit analysis, neither long-term nor intermittent anticonvulsant therapy is indicated for children who have experienced 1 or more simple febrile seizures. In situations in which a child tends to have febrile seizures with frequent illnesses, and seizures tend to occur after the onset/recognition of fever, oral diazepam can be considered for the duration of the fever.
Clinical Context:
Oral diazepam can decrease number of subsequent febrile seizures when given with each febrile episode. Many practitioners will prescribe rectal diazepam, particularly to patients who have had prolonged febrile seizures, in order to prevent future episodes of febrile status epilepticus. By increasing activity of GABA, a major inhibitory neurotransmitter, diazepam depresses all levels of CNS, including limbic and reticular formation.
A study reported in New England Journal of Medicine gave oral diazepam 0.33 mg/kg per dose, every 8 hours throughout the febrile illness, until the child was afebrile for 24 hours. However, this dosage was frequently associated with side effects such as imbalance, lethargy, and irritability.
Prognosis for normal neurologic function is excellent.
About one third of children who experience a single simple febrile seizure will have another.
The lifetime rate of epilepsy in these children is slightly above that of the general population.[1]
A Danish population-based study by Norgaard et al found little association between febrile seizures and cognitive function. Data linked from health-care databases and conscript records of Danish men born from 1977-1983 showed that, of the 18,276 eligible conscripts, 507 (2.8%) had a record of hospitalization with febrile seizures and no known history of epilepsy. Compared with conscripts with no record of febrile seizures, the adjusted prevalence ratio for having a Boerge Prien intelligence test score in the bottom quartile was 1.08 (95% confidence index [CI], 0.94-1.25). The adjusted prevalence ratios were 1.38 (95% CI, 1.07-1.79) for febrile seizures with an onset age of 3 months to < 1 year, 0.98 (95% CI, 0.80-1.18) for febrile seizures with an onset age of 1-2 years, and 1.14 (95% CI, 0.79-1.66) for an onset age of 3-5 years.[16]
What are pediatric febrile seizures?How are pediatric febrile seizures categorized?How does the timing of the first measles-mumps-rubella (MMV) or measles-mumps-rubella-varicella (MMRV) vaccine affect the risk for pediatric febrile seizures?What are the signs and symptoms of a simple febrile seizure?What are the signs and symptoms of a complex febrile seizure?What are the signs and symptoms of a symptomatic febrile seizure?How are pediatric febrile seizures diagnosed?When should lumbar puncture be considered in diagnosis of pediatric febrile seizures?What is the role of anticonvulsant therapy in the treatment of pediatric febrile seizures?What are pediatric febrile seizures?How is simple febrile seizure characterized?How is complex febrile seizure characterized?How is symptomatic febrile seizure characterized?What is the pathophysiology of pediatric febrile seizures?How common are pediatric febrile seizures in the US?Which health risks are increased in children with febrile seizures?Which sex has a higher risk for pediatric febrile seizures?What is the risk factor for pediatric febrile seizures by age?Which history is characteristic of pediatric febrile seizures?Which physical findings are characteristic of pediatric febrile seizures?What causes pediatric febrile seizures?What are the differential diagnoses for Pediatric Febrile Seizures?What is the role of lab studies in the diagnosis of pediatric febrile seizures?What is the role of imaging studies in the diagnosis of pediatric febrile seizures?What is the role of EEG in the diagnosis of pediatric febrile seizures?What is the role of lumbar puncture in the diagnosis of pediatric febrile seizures?What are the treatment options for pediatric febrile seizures?How is febrile status epilepticus managed in children with febrile seizures?What activity restrictions are included in the treatment of pediatric febrile seizures?Which medications are used in the treatment of pediatric febrile seizures?Which medications in the drug class Benzodiazepines are used in the treatment of Pediatric Febrile Seizures?What is the prognosis of pediatric febrile seizures?What should be included in parent education about pediatric febrile seizures?
Robert J Baumann, MD, Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Disclosure: Nothing to disclose.
Chief Editor
Amy Kao, MD, Attending Neurologist, Children's National Medical Center
Disclosure: Have stock (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.
Additional Contributors
James J Riviello, Jr, MD, George Peterkin Endowed Chair in Pediatrics, Professor of Pediatrics, Section of Neurology and Developmental Neuroscience, Professor of Neurology, Peter Kellaway Section of Neurophysiology, Baylor College of Medicine; Chief of Neurophysiology, Director of the Epilepsy and Neurophysiology Program, Texas Children's Hospital
Disclosure: Partner received royalty from Up To Date for section editor.
Brooks M. Intranasal Midazolam Works for Seizure Emergencies in Kids. Medscape Medical News. Nov 5 2013. Available at http://www.medscape.com/viewarticle/813827. Accessed: 11/12/13.
