Pediatric Febrile Seizures

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Practice Essentials

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:

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

Complex febrile seizure

Symptomatic febrile seizure

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:

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]

See Treatment and Medication for more detail.

Background

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:

Complex febrile seizure

See the list below:

Symptomatic febrile seizure

See the list below:

Pathophysiology

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]

Frequency

United States

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.

Mortality/Morbidity

See the list below:

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.

History

See the list below:

Physical

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).

Causes

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.

Laboratory Studies

See the list below:

Imaging Studies

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]

Other Tests

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.

Procedures

See the list below:

Medical Care

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.

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]

Activity

No activity restrictions are necessary.

Guidelines Summary

The reader is referred to several published clinical "guidelines" or practice parameters.[13, 14, 15]

Medication Summary

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.

Diazepam (Diastat Pediatric, Valium)

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.

Class Summary

These agents have antiseizure activity and act rapidly in acute seizures.

Prognosis

Prognosis for normal neurologic function is excellent.

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]

Patient Education

See the list below:

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?

Author

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.

References

  1. Verity CM, Golding J. Risk of epilepsy after febrile convulsions: a national cohort study. BMJ. 1991 Nov 30. 303(6814):1373-6. [View Abstract]
  2. Hand L. Delaying childhood vaccines ups postvaccine seizure risk. Medscape Medical News. May 19, 2014.
  3. Hambidge SJ, Newcomer SR, Narwaney KJ, Glanz JM, Daley MF, Xu S, et al. Timely Versus Delayed Early Childhood Vaccination and Seizures. Pediatrics. 2014 May 19. [View Abstract]
  4. Rosman NP, Colton T, Labazzo J, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med. 1993 Jul 8. 329(2):79-84. [View Abstract]
  5. Murata S, Okasora K, Tanabe T, et al. Acetaminophen and febrile seizure recurrences during the same fever episode. Pediatrics. 2018 Nov. 142(5):[View Abstract]
  6. Winawer M, Hesdorffer D. Turning on the heat: the search for febrile seizure genes. Neurology. 2004 Nov 23. 63(10):1770-1. [View Abstract]
  7. Vestergaard M, Pedersen MG, Ostergaard JR, Pedersen CB, Olsen J, Christensen J. Death in children with febrile seizures: a population-based cohort study. Lancet. 2008 Aug 9. 372(9637):457-63. [View Abstract]
  8. Lewis DV, Shinnar S, Hesdorffer DC, et al. Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study. Ann Neurol. 2014. 75:178-185. [View Abstract]
  9. Hesdorffer DC, Shinnar S, Lax DN et al. Risk factors for subsequent febrile seizures in the FEBSTAT study. Epilepsia. 2016 July. 57(7):1042-1047. [View Abstract]
  10. 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.
  11. Lahat E, Goldman M, Barr J, Bistritzer T, Berkovitch M. Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomised study. BMJ. 2000 Jul 8. 321(7253):83-86. [View Abstract]
  12. Holsti M, Dudley N, Schunk J, et al. Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Arch Pediatr Adolesc Med. 2010. 164(8):747-753. [View Abstract]
  13. [Guideline] Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics. 2008 Jun. 121(6):1281-6. [View Abstract]
  14. [Guideline] Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. American Academy of Pediatrics. Provisional Committee on Quality Improvement, Subcommittee on Febrile Seizures. Pediatrics. 1996 May. 97(5):769-72; discussion 773-5. [View Abstract]
  15. [Guideline] Riemenschneider TA, Baumann RJ, Duffner PK, et al. Practice parameter: the neurodiagnostic evaluation of the child with a first simple febrile seizure. American Academy of Pediatrics. Provisional Committee on Quality Improvement, Subcommittee on Febrile Seizures. Pediatrics. 1996 May. 97(5):769-72; discussion 773-5. [View Abstract]
  16. Nørgaard M, Ehrenstein V, Mahon BE, Nielsen GL, Rothman KJ, Sørensen HT. Febrile seizures and cognitive function in young adult life: a prevalence study in Danish conscripts. J Pediatr. 2009 Sep. 155(3):404-9. [View Abstract]