Febrile Seizures

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Practice Essentials

Febrile seizures are the most common type of seizures observed in the pediatric age group. Febrile seizures are categorized into the following two types[1, 2] :

Complex febrile seizures may indicate a more serious disease process, such as meningitis, abscess, or encephalitis.

Signs and symptoms

The underlying cause of the fever should be sought. A careful physical examination often reveals otitis media, pharyngitis, or a viral exanthem.

See Presentation for more detail.

Diagnosis

Laboratory studies

Routine laboratory studies usually are not indicated for febrile seizure unless they are performed as part of a search for the source of a fever.

Imaging studies

A computed tomography (CT) scan should not be performed in the evaluation of a child with a first simple febrile seizure; however, CT should be considered in patients with complex febrile seizures. 

See Workup for more detail.

Management

Patients with active seizures should be treated with airway management, high-flow oxygen, supportive care, and anticonvulsants as necessary.

Patients who are postictal should receive supportive care and antipyretics as appropriate.

See Treatment and Medication for more detail.

Background

Although described by the ancient Greeks, it was not until the 20th century that febrile seizures were recognized as a distinct syndrome separate from epilepsy. In 1980, a consensus conference held by the National Institutes of Health described a febrile seizure as, "An event in infancy or childhood usually occurring between three months and five years of age, associated with fever, but without evidence of intracranial infection or defined cause."[3] It does not exclude children with prior neurological impairment and neither provides specific temperature criteria nor defines a "seizure." Another definition from the International League Against Epilepsy (ILAE) is "a seizure occurring in childhood after 1 month of age associated with a febrile illness not caused by an infection of the central nervous system (CNS), without previous neonatal seizures or a previous unprovoked seizure, and not meeting the criteria for other acute symptomatic seizures."[4]

Pathophysiology

Febrile seizures occur in young children at a time in their development when the seizure threshold is low. This is a time when young children are susceptible to frequent childhood infections such as upper respiratory tract infection, otitis media, and viral syndrome, and they respond with comparably higher temperatures. Animal studies suggest a possible role of endogenous pyrogens, such as interleukin 1beta, that, by increasing neuronal excitability, may link fever and seizure activity.[5] Preliminary studies in children appear to support the hypothesis that the cytokine network is activated and may have a role in the pathogenesis of febrile seizures, but the precise clinical and pathological significance of these observations is not yet clear.[6, 7]

Febrile seizures are divided into 2 types: simple febrile seizures (which are generalized, last < 15 min and do not recur within 24 h) and complex febrile seizures (which are prolonged, recur more than once in 24 h, or are focal).[1] Complex febrile seizures may indicate a more serious disease process, such as meningitis, abscess, or encephalitis. Febrile status epilepticus, a severe type of complex febrile seizure, is defined as single seizure or series of seizures without interim recovery lasting at least 30 minutes.

Viral illnesses are the predominant cause of febrile seizures. Recent literature documented the presence of human herpes simplex virus 6 (HHSV-6) as the etiologic agent in roseola in about 20% of a group of patients presenting with their first febrile seizures. Other viruses that have been commonly implicated in febrile seizures are influenza viruses, adenoviruses, and parainfluenza viruses.[2]  Shigella gastroenteritis also has been associated with febrile seizures. One study suggests a relationship between recurrent febrile seizures and influenza A.[8, 9]

Febrile seizures tend to occur in families. In a child with febrile seizure, the risk of febrile seizure is 10% for the sibling and almost 50% for the sibling if a parent has febrile seizures as well. Although clear evidence exists for a genetic basis of febrile seizures, the mode of inheritance is unclear.[10]

Whereas polygenic inheritance is likely, a small number of families are identified with an autosomal dominant pattern of inheritance of febrile seizures, leading to the description of a "febrile seizure susceptibility trait" with an autosomal dominant pattern of inheritance with reduced penetrance. Although the exact molecular mechanisms of febrile seizures are yet to be understood, underlying mutations have been found in genes encoding the sodium channel and the gamma amino-butyric acid A receptor.[11, 12, 13]

Etiology

Risk factors for developing febrile seizures are as follows[14, 15, 16, 17] :

Interestingly, no data support the theory that a rapid rise in temperature is a cause of febrile seizures.

About one third of all children with a first febrile seizure experience recurrent seizures.[18]  Risk factors for recurrent febrile seizures include the following[19, 20] :

Patients with all 4 risk factors have greater than 70% chance of recurrence. Patients with no risk factors have less than a 20% chance of recurrence.

Regarding vaccination and risk of febrile seizures, Administration of the first dose of MMRV vaccine at age 12-15 months carries a slight increase risk of febrile seizure (0.05%, approximately 1 in 2000), from day 5 through 12 following receipt of the vaccine. However, the risk is not higher in older children receiving the second dose of MMRV.[21]  A study by Macartney et al evaluated the risk of febrile seizures after a second dose of MMRV vaccine at 18 months. The study reported no increased risk of febrile seizures (RI, 1.08; 95% CI, 0.55-2.13) in the 5 to 12 days following MMRV vaccine given as the second MCV to toddlers.[22]

In a Danish study, DTaP-IPV-Hib vaccination was associated with an increased risk of febrile seizures on the day of first and second vaccinations, although the absolute risk was small. A higher risk for febrile seizures was found on the day of first vaccination (hazard ratio [HR], 6.02; 95% confidence interval [CI], 2.86-12.65), as well as on the day of the second vaccination (HR, 3.94; 95% CI, 2.18-7.10), but higher risk was not seen on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) when compared with the reference group. Vaccination with DTaP IPV-Hib was not associated with an increased risk of epilepsy.[23]

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 MMR or MMRV vaccine beyond the age of 15 months may more than double the risk of postvaccination seizures in the second year of life.[24, 25]

A study by Duffy et al sought to determine whether concomitant administration of trivalent inactivated influenza vaccine (IIV3) with other vaccines affects the febrile seizure risk. The study found that the administration of IIV3 on the same day as either pneumococcal conjugate vaccine or a diphtheria-tetanus-acellular-pertussis-containing vaccine was associated with a greater risk of febrile seizure than when IIV3 was given on a separate day. However, the absolute risk of postvaccination febrile seizure with these vaccine combinations was small.[26, 27]

Epidemiology

United States statistics

Between 2% and 5% of children have febrile seizures by their fifth birthday.[14]

International statistics

A similar rate of febrile seizures is found in Western Europe. The incidence elsewhere in the world varies between 5% and 10% for India, 8.8% for Japan, 14% for Guam,[28] 0.35% for Hong Kong, and 0.5-1.5% for China.[29]

Race-, sex-, and age-related demographics

Race

Febrile seizures occur in all races.

Sex

Some studies demonstrate a slight male predominance.

Age

By definition, febrile seizures occur in children aged 3 months to 5 years. The highest incidence of febrile seizures has been reported in children aged 12-18 months.[30]

Prognosis

Simple febrile seizures may slightly increase the risk of developing epilepsy,[31]  but they have no adverse effects on behavior, scholastic performance, or neurocognition. The risk of developing epilepsy is increased further in children with a history of complex febrile seizures.[14, 32, 33, 34] ​

A strong association exists between febrile status epilepticus or febrile seizures characterized by focal symptoms and later development of temporal lobe epilepsy.[31, 35]

Children with febrile seizures have a slightly higher incidence of epilepsy compared with the general population (2% vs 1%).

Risk factors for epilepsy later in life include complex febrile seizure, family history of epilepsy or neurologic abnormality, and developmental delay. Patients with 2 risk factors have up to a 10% chance of developing afebrile seizures.[36]

Morbidity/mortality

Children with simple febrile seizures do not have increased mortality risk. However, seizures that were complex, occurred before age 1 year, or were triggered by a temperature of less than 39°C were associated with a 2-fold increased mortality rate during the first 2 years after seizure occurrence.[37]

Children with febrile seizures have a slightly higher incidence of epilepsy compared with the general population (2% vs 1%).[38]  Risk factors for epilepsy later in life include complex febrile seizure, family history of epilepsy or neurologic abnormality, and developmental delay. Patients with 2 risk factors have up to a 10% chance of developing afebrile seizures.[39, 40]

Patient Education

Parents should be taught what to do if their child has another seizure.

The parent should be advised to call for assistance if the seizure lasts longer than 10 minutes or if the postictal period lasts longer than 30 minutes.

Parents should be counseled on the benign nature of febrile seizures.

Parents should be reassured that simple febrile seizures do not lead to neurologic problems or developmental delay.

History

The type of seizure (generalized or focal) and its duration should be described to help differentiate between simple and complex febrile seizures.

Focus on the history of fever, duration of fever, and potential exposures to illness.

A history of the cause of fever (eg, viral illnesses, gastroenteritis) should be elucidated.

Recent antibiotic use is particularly important because partially treated meningitis must be considered.

A history of seizures, neurologic problems, developmental delay, or other potential causes of seizure (eg, trauma, ingestion) should be sought.

Physical Examination

The underlying cause for the fever should be sought.

A careful physical examination often reveals otitis media, pharyngitis, or a viral exanthem.

Serial evaluations of the patient's neurologic status are essential.

Check for meningeal signs as well as for signs of trauma or toxic ingestion.

Laboratory Studies

In children under the age of 5 with complex febrile seizures, over one-third of experienced pediatric emergency physicians would do extensive workup, nearly half would admit, but variability exists in the approach to optimal management of patients with CFS. Past studies support more aggressive workup for patients under the age of 18 months, but future prospective studies on this subject are warranted.[41]

Routine laboratory studies usually are not indicated for febrile seizure unless they are performed as part of a search for the source of a fever. The American Academy of Pediatrics (AAP) Section on Emergency Medicine does not recommend ordering laboratory testing for a child with a simple febrile seizure whose mental status has returned to baseline.[42]

Electrolytes assessments are rarely helpful in the evaluation of febrile seizures.[1]

Patients with febrile seizures have an incidence of bacteremia similar to patients with fever alone.[43]

A study found the European children with febrile seizures have lower ferritin than those with fever alone, and iron deficiency, but not anemia, is associated with recurrence. The study also suggested that iron status screening should be considered to help determine which children with febrile seizures may be at risk for recurrence.[44]

Imaging Studies

A CT scan should not be performed in the evaluation of a child with a first simple febrile seizure. The AAP also advises against ordering a CT scan of the head for a child with a simple febrile seizure whose mental status has returned to baseline.[42]

A CT scan should be considered in patients with complex febrile seizures. However, a study by Teng et al analyzed data in 71 children with first complex febrile seizure.[45] Fifty-one (72%) had a single complex feature (20 focal, 22 multiple, and 9 prolonged), and 20 (28%) had multiple complex features. None of the 71 patients (1-sided 95% confidence interval, 4%) had intracranial pathologic conditions that required emergency neurosurgical or medical intervention. Forty-six had normal acute scans; the rest were normal on clinical follow up without a scan. The confidence interval means that this study cannot exclude a risk of intracranial pathology of 4% or less.

Kimia et al reported a retrospective cohort review in children presenting with first complex febrile seizure (CFS). Of 526 subjects with CFS, 268 had emergent head imaging: 4 had a clinically significant finding; 2 had intracranial hemorrhage; 1 had acute disseminated encephalomyelitis; and 1 patient had focal cerebral edema (1.5%; 95% CI, 0.5-4%). Assigning low risk to patients not imaged and not returning to the emergency department within a week of the original visit, the risk of intracranial pathology was 4 (0.8%; 95% CI, 0.2-2.1%). Three of these 4 patients had other obvious findings (nystagmus, emesis, and altered mental status; persistent hemiparesis; bruises suggestive of inflicted injury). In the absence of other sign and symptoms, patients presenting with CFS are at very low risk for intracranial pathology.[46]

Other Tests

An electroencephalogram (EEG) is not necessary in the routine evaluation of a child with a simple febrile seizure. In a prospective study, Nordli et al recruited 199 children with febrile status epilepticus (severe type of complex febrile seizure) within 72 hours of presentation. Of these, 45.2 % had an abnormal EEG with focal slowing and attenuation seen maximally over the temporal areas in almost all cases and were highly associated with MRI evidence of hippocampal injury.[47]

Procedures

Lumbar puncture

Controversy exists regarding the need for a lumbar puncture in a child presenting with a simple febrile seizure. Lumbar puncture is not needed for young children with first simple febrile seizure.[48]

Certainly, meningitis can present with a seizure, although the seizure usually is not the only sign of meningitis. Patients who have a first-time febrile seizure and do not have a rapidly improving mental status (short postictal period) should be evaluated for meningitis.

Several reviews of the medical literature report less than 5% incidence of meningitis in children presenting with seizures and fever.

Hom and Medwid, in an evidence-based review, examined the risk of bacterial meningitis as diagnosed by lumbar puncture in children presenting to the emergency department with a simple febrile seizure. The study population consisted of fully immunized children aged 6-18 months with an unremarkable history and normal physical examination. Of 461 children, 150 enrolled for febrile seizure underwent lumbar puncture to rule out meningitis. The rate of bacterial meningitis was 0% (95% CI, 0-3%).[49] Fletcher and Sharieff also determine that acute bacterial meningitis (ABM) is rare in patients presenting with a first complex febrile seizure. Patients presenting only with 2 short febrile seizures within 24 hours may be less likely to have ABM, and may not require lumbar puncture without other clinical symptoms of neurological disease.[50]

Risk factors for meningitis in patients presenting with seizure and fever include the following:

In 1996, the American Academy of Pediatrics (AAP) recommended that a lumbar puncture be strongly considered in patients younger than 12 months presenting with fever and seizure.[4] The AAP also recommended that a lumbar puncture be considered in patients aged 12-18 months. A lumber puncture is not routinely necessary in patients older than 18 months. This recommendation is conservative, but it takes into account the difficulty in recognizing meningitis in infants and young children and the range of experience in the evaluation of pediatric patients among healthcare providers.

In 2011, the AAP revised this guideline. It no longer recommends routine lumbar puncture in well-appearing, fully immunized children who present with a simple febrile seizure and makes lumbar puncture an option in infants age 6-12 months who are deficient in Haemophilus influenzae or Streptococcus pneumoniae immunizations or when immunization status cannot be established.[51]

Prehospital Care

Patients with active seizures should be treated with airway management, high-flow oxygen, supportive care, and anticonvulsants as necessary. Acute treatment such as rectal diazepam (0.5 mg/kg) and buccal 0.4-0.5 mg/kg) or intranasal (0.2 mg/kg) are effective and can be given at home for a seizure lasting longer than 5 minutes.[52, 53, 54]

Patients who are postictal should receive supportive care and antipyretics as appropriate.

Emergency Department Care

Patients presenting with status epilepticus should be treated with airway management and anticonvulsants as necessary.

Patients presenting with history and physical examination findings consistent with a simple febrile seizure should have frequent neurologic examinations to monitor mental status.

Other causes of seizure should be ruled out.

The cause of the febrile illness should be sought and treated.

Antipyretics should be considered. Acetaminophen (Tylenol) and ibuprofen (Motrin) are often used.

Parental anxiety and fear that their child may die or will develop brain damage needs to be addressed with reassurance and education.

Further Care

Further outpatient care

Arrange for medical reevaluation of discharged patients and parental education in a follow-up appointment within 24-48 hours.

Further inpatient care

The decision to admit should be individualized, but admission usually is not necessary for patients with febrile seizure.

Most patients should be observed in the ED until awake and alert.

Conditions requiring admission of the patient include the following:

Medication Summary

Patients presenting in status epilepticus can be treated with routine seizure medications, including benzodiazepines, phenytoin, and phenobarbital. For further discussion on the treatment of seizures, see Pediatrics, Status Epilepticus.

Discharge medications include antipyretics and, if indicated, antibiotics (eg, otitis media, pneumonia).

Prophylactic use of antipyretics and sedatives/anticonvulsants for possible recurrence of febrile seizure has not shown to be effective.

Regular or sporadic administration of antipyretics during febrile illness is generally safe, but no study has shown them to be effective in reducing recurrence of febrile seizures.[55, 56]  Acetaminophen and ibuprofen are no better than placebo for preventing recurrences of febrile seizures . [57]

Phenobarbital and valproic acid can be given daily and are effective, but they are associated with multiple adverse effects. Carbamazepine and phenytoin are not effective in preventing recurrent febrile seizures. Citing a preponderance of harm over benefit, the 2008 Clinical Practice Guideline for the Long-Term Management of the Child with Simple Febrile Seizures recommends neither continuous nor intermittent use of anticonvulsants for children with one or more simple febrile seizures.[56]

Some studies report that diazepam, given orally or rectally every 8 hours during febrile illnesses, is effective in preventing recurrence of febrile seizures.[58, 59] . However, these benzodiazepines can cause lethargy, drowsiness, and ataxia, and sedation could mask an evolving central nervous system infection. The AAP guideline released in 2008 does not recommend prophylactic use of diazepam as the risk outweighs the benefits.[56]

Given a more established role of influenza A in the etiology of febrile seizure, both acute and recurrent, vaccination against influenza A in the flu season may have a role in preventing development of both acute and recurrent febrile seizures.[9]

Acetaminophen (Tylenol)

Clinical Context:  Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body heat via vasodilation and sweating.

Ibuprofen (Advil, Motrin)

Clinical Context:  One of the few NSAIDs indicated for reduction of fever. Inhibits the formation of prostaglandins.

Class Summary

Antipyretics should be used in patients who appear uncomfortable secondary to fever. Antipyretics do not appear to prevent recurrence of febrile seizures.

Diazepam (Valium, Diastat)

Clinical Context:  Can decrease number of subsequent febrile seizures when given with each febrile episode. Modulates postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. Also has been found to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops to 20% of Cmax.

Individualize dosage and increase cautiously to avoid adverse effects. Available as IV, PO, and PR dosage forms.

Lorazepam (Ativan)

Clinical Context:  Sedative hypnotic with short onset of effects and relatively long half-life.

By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

Important to monitor patient's blood pressure after administering dose. Adjust as necessary.

Class Summary

Prophylactic treatment with an anticonvulsant agent may be considered for subsequent fever episodes.

Author

Nooruddin R Tejani, MD, Assistant Professor, Department of Emergency Medicine, SUNY Health Sciences Center Brooklyn; Director, Pediatric Emergency Medicine, Downstate Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Wayne Wolfram, MD, MPH, Professor, Department of Emergency Medicine, Mercy St Vincent Medical Center; Chairman, Pediatric Institutional Review Board, Mercy St Vincent Medical Center, Toledo, Ohio

Disclosure: Nothing to disclose.

Chief Editor

Kirsten A Bechtel, MD, Associate Professor of Pediatrics, Section of Pediatric Emergency Medicine, Yale University School of Medicine; Co-Director, Injury Free Coalition for Kids, Yale-New Haven Children's Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Debra Slapper, MD, Physician, Southwest Washington Free Clinic System-Urgent Care; Former FEMA Physician and Military Contractor; Former Associate Professor, University of Miami, Leonard M Miller School of Medicine and University of South Florida Morsani College of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, William T Zempsky, MD, to the development and writing of this article.

References

  1. [Guideline] Subcommittee on Febrile Seizures, American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011 Feb. 127 (2):389-94. [View Abstract]
  2. Eilbert W, Chan C. Febrile seizures: A review. J Am Coll Emerg Physicians Open. 2022 Aug. 3 (4):e12769. [View Abstract]
  3. Consensus statement. Febrile seizures: long-term management of children with fever-associated seizures. Pediatrics. 1980 Dec. 66(6):1009-12. [View Abstract]
  4. [Guideline] Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia. 1993 Jul-Aug. 34(4):592-6. [View Abstract]
  5. Matsuo M, Sasaki K, Ichimaru T, Nakazato S, Hamasaki Y. Increased IL-1beta production from dsRNA-stimulated leukocytes in febrile seizures. Pediatr Neurol. 2006 Aug. 35(2):102-6. [View Abstract]
  6. Gatti S, Vezzani A, Bartfai T. Mechanisms of fever and febrile seizures: putative role of the interleukin-1 system. Baram TZ, Shinnar S. Febrile Seizures. San Diego, Ca: Academic Press; 2002. 169-88.
  7. Haspolat S, Mihci E, Coskun M, Gumuslu S, Ozben T, Yegin O. Interleukin-1beta, tumor necrosis factor-alpha, and nitrite levels in febrile seizures. J Child Neurol. 2002 Oct. 17(10):749-51. [View Abstract]
  8. Millichap JG, Millichap JJ. Role of viral infections in the etiology of febrile seizures. Pediatr Neurol. 2006 Sep. 35(3):165-72. [View Abstract]
  9. Kwong KL, Lam SY, Que TL, Wong SN. Influenza A and febrile seizures in childhood. Pediatr Neurol. 2006 Dec. 35(6):395-9. [View Abstract]
  10. Audenaert D, Van Broeckhoven C, De Jonghe P. Genes and loci involved in febrile seizures and related epilepsy syndromes. Hum Mutat. 2006 May. 27(5):391-401. [View Abstract]
  11. Iwasaki N, Nakayama J, Hamano K, Matsui A, Arinami T. Molecular genetics of febrile seizures. Epilepsia. 2002. 43 Suppl 9:32-5. [View Abstract]
  12. Hirose S, Mohney RP, Okada M, Kaneko S, Mitsudome A. The genetics of febrile seizures and related epilepsy syndromes. Brain Dev. 2003 Aug. 25(5):304-12. [View Abstract]
  13. Nakayama J, Arinami T. Molecular genetics of febrile seizures. Epilepsy Res. 2006 Aug. 70 Suppl 1:S190-8. [View Abstract]
  14. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from birth. I--Prevalence and recurrence in the first five years of life. Br Med J (Clin Res Ed). 1985 May 4. 290(6478):1307-10. [View Abstract]
  15. van Esch A, Steyerberg EW, van Duijn CM, Offringa M, Derksen-Lubsen G, van Steensel-Moll HA. Prediction of febrile seizures in siblings: a practical approach. Eur J Pediatr. 1998 Apr. 157(4):340-4. [View Abstract]
  16. Bethune P, Gordon K, Dooley J, Camfield C, Camfield P. Which child will have a febrile seizure?. Am J Dis Child. 1993 Jan. 147(1):35-9. [View Abstract]
  17. Vestergaard M, Basso O, Henriksen TB, Ostergaard JR, Olsen J. Risk factors for febrile convulsions. Epidemiology. 2002 May. 13(3):282-7. [View Abstract]
  18. Offringa M, Bossuyt PM, Lubsen J, Ellenberg JH, Nelson KB, Knudsen FU. Risk factors for seizure recurrence in children with febrile seizures: a pooled analysis of individual patient data from five studies. J Pediatr. 1994 Apr. 124(4):574-84. [View Abstract]
  19. Waruiru C, Appleton R. Febrile seizures: an update. Arch Dis Child. 2004 Aug. 89(8):751-6. [View Abstract]
  20. Berg AT, Shinnar S, Darefsky AS, Holford TR, Shapiro ED, Salomon ME. Predictors of recurrent febrile seizures. A prospective cohort study. Arch Pediatr Adolesc Med. 1997 Apr. 151(4):371-8. [View Abstract]
  21. [Guideline] Committee on Infectious Diseases. Policy statement—Prevention of varicella: update of recommendations for use of quadrivalent and monovalent varicella vaccines in children. Pediatrics. 2011 Sep. 128(3):630-2. [View Abstract]
  22. Macartney K, Gidding HF, Trinh L, Wang H, Dey A, Hull B, et al. Evaluation of Combination Measles-Mumps-Rubella-Varicella Vaccine Introduction in Australia. JAMA Pediatr. 2017 Aug 14. [View Abstract]
  23. Sun Y, Christensen J, Hviid A, Li J, Vedsted P, Olsen J. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B. JAMA. 2012 Feb 22. 307(8):823-31. [View Abstract]
  24. Hand L. Delaying childhood vaccines ups postvaccine seizure risk. Medscape Medical News [serial online]. May 19, 2014;. Available at http://www.medscape.com/viewarticle/825333. Accessed: May 28, 2014.
  25. Hambidge SJ, Newcomer SR, Narwaney KJ, Glanz JM, Daley MF, Xu S, et al. Timely versus delayed early childhood vaccination and seizures. Pediatrics. 2014 Jun. 133(6):e1492-9. [View Abstract]
  26. Duffy J, Weintraub E, Hambidge SJ, et al. Febrile Seizure Risk After Vaccination in Children 6 to 23 Months. Pediatrics. Published Online: June 2016.
  27. Garcia J. Risk for Febrile Seizure After Multiple Vaccines Is Low. Medscape Medical News. Available at http://www.medscape.com/viewarticle/864323. June 06, 2016; Accessed: June 06, 2016.
  28. Hauser WA. The prevalence and incidence of convulsive disorders in children. Epilepsia. 1994. 35 Suppl 2:S1-6. [View Abstract]
  29. Chung B, Wat LC, Wong V. Febrile seizures in southern Chinese children: incidence and recurrence. Pediatr Neurol. 2006 Feb. 34(2):121-6. [View Abstract]
  30. Sawires R, Buttery J, Fahey M. A Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers. Front Pediatr. 2021. 9:801321. [View Abstract]
  31. Verity CM, Golding J. Risk of epilepsy after febrile convulsions: a national cohort study. BMJ. 1991 Nov 30. 303(6814):1373-6. [View Abstract]
  32. Berg AT. Febrile seizures and epilepsy: the contributions of epidemiology. Paediatr Perinat Epidemiol. 1992 Apr. 6(2):145-52. [View Abstract]
  33. Verity CM, Butler NR, Golding J. Febrile convulsions in a national cohort followed up from birth. II--Medical history and intellectual ability at 5 years of age. Br Med J (Clin Res Ed). 1985 May 4. 290(6478):1311-5. [View Abstract]
  34. Verity CM, Greenwood R, Golding J. Long-term intellectual and behavioral outcomes of children with febrile convulsions. N Engl J Med. 1998 Jun 11. 338(24):1723-8. [View Abstract]
  35. Tarkka R, Paakko E, Pyhtinen J, Uhari M, Rantala H. Febrile seizures and mesial temporal sclerosis: No association in a long-term follow-up study. Neurology. 2003 Jan 28. 60(2):215-8. [View Abstract]
  36. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med. 1976 Nov 4. 295(19):1029-33. [View Abstract]
  37. 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]
  38. Tsai JD, Mou CH, Chang HY, Li TC, Tsai HJ, Wei CC. Trend of subsequent epilepsy in children with recurrent febrile seizures: A retrospective matched cohort study. Seizure. 2018 Oct. 61:164-169. [View Abstract]
  39. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med. 1976 Nov 4. 295(19):1029-33. [View Abstract]
  40. Berg AT, Shinnar S. Unprovoked seizures in children with febrile seizures: short-term outcome. Neurology. 1996 Aug. 47(2):562-8. [View Abstract]
  41. Sales JW, Bulloch B, Hostetler MA. Practice variability in the management of complex febrile seizures by pediatric emergency physicians and fellows. CJEM. 2011 May. 13(3):145-9. [View Abstract]
  42. American Academy of Pediatrics Section on Emergency Medicine. Choosing Wisely: Five Things Physicians and Patients Should Question in the Practice of Pediatric Emergency Medicine. AAP. Available at https://downloads.aap.org/AAP/PDF/Choosing%20Wisely/CWEmergencyMedicine.pdf. 2022 Dec 01; Accessed: July 18, 2023.
  43. Chamberlain JM, Gorman RL. Occult bacteremia in children with simple febrile seizures. Am J Dis Child. 1988 Oct. 142(10):1073-6. [View Abstract]
  44. Papageorgiou V, Vargiami E, Kontopoulos E, Kardaras P, Economou M, Athanassiou-Mataxa M, et al. Association between iron deficiency and febrile seizures. Eur J Paediatr Neurol. 2015 Jun 12. [View Abstract]
  45. Teng D, Dayan P, Tyler S, Hauser WA, Chan S, Leary L. Risk of intracranial pathologic conditions requiring emergency intervention after a first complex febrile seizure episode among children. Pediatrics. 2006 Feb. 117(2):304-8. [View Abstract]
  46. Kimia AA, Ben-Joseph E, Prabhu S, Rudloe T, Capraro A, Sarco D. Yield of emergent neuroimaging among children presenting with a first complex febrile seizure. Pediatr Emerg Care. 2012 Apr. 28(4):316-21. [View Abstract]
  47. Nordli DR Jr, Moshé SL, Shinnar S, Hesdorffer DC, Sogawa Y, Pellock JM, et al. Acute EEG findings in children with febrile status epilepticus: results of the FEBSTAT study. Neurology. 2012 Nov 27. 79(22):2180-6. [View Abstract]
  48. Kimia AA, Capraro AJ, Hummel D, Johnston P, Harper MB. Utility of lumbar puncture for first simple febrile seizure among children 6 to 18 months of age. Pediatrics. 2009 Jan. 123(1):6-12. [View Abstract]
  49. Hom J, Medwid K. The low rate of bacterial meningitis in children, ages 6 to 18 months, with simple febrile seizures. Acad Emerg Med. 2011 Nov. 18(11):1114-20. [View Abstract]
  50. Fletcher EM, Sharieff G. Necessity of lumbar puncture in patients presenting with new onset complex febrile seizures. West J Emerg Med. 2013 May. 14(3):206-11. [View Abstract]
  51. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011 Feb. 127(2):389-94. [View Abstract]
  52. McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005 Jul 16-22. 366(9481):205-10. [View Abstract]
  53. Bhattacharyya M, Kalra V, Gulati S. Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol. 2006 May. 34(5):355-9. [View Abstract]
  54. Sadleir LG, Scheffer IE. Febrile seizures. BMJ. 2007 Feb 10. 334(7588):307-11. [View Abstract]
  55. van Stuijvenberg M, Derksen-Lubsen G, Steyerberg EW, Habbema JD, Moll HA. Randomized, controlled trial of ibuprofen syrup administered during febrile illnesses to prevent febrile seizure recurrences. Pediatrics. 1998 Nov. 102(5):E51. [View Abstract]
  56. [Guideline] Steering Committee on Quality Improvement and Management, Subcommittee on Febrile Seizures American Academy of Pediatrics. 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]
  57. Strengell T, Uhari M, Tarkka R, Uusimaa J, Alen R, Lautala P. Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial. Arch Pediatr Adolesc Med. 2009 Sep. 163(9):799-804. [View Abstract]
  58. Autret E, Billard C, Bertrand P, Motte J, Pouplard F, Jonville AP. Double-blind, randomized trial of diazepam versus placebo for prevention of recurrence of febrile seizures. J Pediatr. 1990 Sep. 117(3):490-4. [View Abstract]
  59. Rosman NP, Colton T, Labazzo J, Gilbert PL, Gardella NB, Kaye EM. 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]