Simple and Complex Febrile Seizures (6 mos - 5 years) - Curbside
Simple and Complex Febrile Seizures (6 mos - 5 years)
Editors: Dan Imler, MD, Elizabeth Mayne, Sarah Lee, & 1 more...
Inclusion Criteria  (All criteria are present)
  • ≥ 1 seizure accompanied by fever (T >/= 38C) or parental report of fever within 24 hours
Exclusion Criteria
  • Toxic appearing
  • Previous afebrile seizure
  • Oncologic patient or Immunodeficiency
  • Trauma
  • VP shunt, previous neurosurgery, structural brain abnormality or intracranial mass
  • Ingestion
  • Developmental delay, complex genetic or metabolic disorder or any other history making a full neurologic exam complex

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Evidence
Total Notes: 9
Evidence

1 Simple febrile seizures

Systematic review of existing trials showed no reduction in recurrence of febrile seizures when children were treated prophylactically with antipyretics.



References:
  1. Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized controlled trials and meta-analysis.
    Rosenbloom E, Finkelstein Y, Adams-Webber T, Kozer E,
    Eur. J. Paediatr. Neurol. 2013 Nov;17(6):585-8.

2 Diagnostic Yield of LP in Simple Febrile Seizure

Although patients with fever and seizure are at risk of meningitis, only few of them will have this diagnosis. The 2011 AAP guidelines recommend LP only for patients with clinical concern for meningitis as identified by the history and physical.

 



References:
  1. Neurodiagnostic evaluation of the child with a simple febrile seizure.

    Pediatrics 2011 Feb;127(2):389-94.

3 Simple febrile seizure

The 2011 AAP guidelines recommend against LP, bloodwork, and imaging in children with simple febrile seizure. Risk of meningitis and diagnostic yield of LP are minimal in infants and children with simple febrile seizure. Diagnostic yield of neuroimaging is minimal absent other symptoms suggestive of intracranial mass or bleed



References:
  1. Risk of Bacterial Meningitis in Children 6 to 11 Months of Age With a First Simple Febrile Seizure: A Retrospective, Cross-sectional, Observational Study.
    Guedj R et al
    Acad Emerg Med. 2015 Nov;22(11):1290-7
  2. Utility of lumbar puncture for first simple febrile seizure among children 6 to 18 months of age.
    Kimia AA, Capraro AJ, Hummel D, Johnston P, Harper MB,
    Pediatrics 2009 Jan;123(1):6-12.
  3. Risk of bacterial meningitis in young children with a first seizure in the context of fever: a systematic review and meta-analysis.
    Najaf-Zadeh A, Dubos F, Hue V, Pruvost I, Bennour A, Martinot A,
    PLoS ONE 2013;8(1):e55270.
  4. Febrile seizures: treatment and prognosis.
    Knudsen FU,
    Epilepsia 2000 Jan;41(1):2-9.
  5. Predictors of recurrent febrile seizures. A prospective cohort study.
    Berg AT, Shinnar S, Darefsky AS, Holford TR, Shapiro ED, Salomon ME, Crain EF, Hauser AW,
    Arch Pediatr Adolesc Med 1997 Apr;151(4):371-8.
  6. A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations.
    de Haan GJ, van der Geest P, Doelman G, Bertram E, Edelbroek P,
    Epilepsia 2010 Mar;51(3):478-82.

4 EEG is not useful in first complex febrile seizure

EEGs done in the acute setting of a complex febrile seizure typically show non-specific findings. The predictive value of those findings for identifying children at greatest risk of developing subsequent epilepsy is poor. EEG should not be part of the routine ED evaluation for first complex febrile seizure.



References:
  1. Risk for developing epilepsy and epileptiform discharges on EEG in patients with febrile seizures.
    Wo SB, Lee JH, Lee YJ, Sung TJ, Lee KH, Kim SK,
    Brain Dev. 2013 Apr;35(4):307-11.
  2. Studies in febrile seizures. V. Clinical and electroencephalographic study in unselected patients.
    MILLICHAP JG, MADSEN JA, ALEDORT LM,
    Neurology 1960 Jul;10:643-53.
  3. Early postictal electroencephalography and correlation with clinical findings in children with febrile seizures.
    Jeong KA, Han MH, Lee EH, Chung S,
    Korean J Pediatr 2013 Dec;56(12):534-9.
  4. EEG characteristics predict subsequent epilepsy in children with febrile seizure.
    Kanemura H, Mizorogi S, Aoyagi K, Sugita K, Aihara M,
    Brain Dev. 2012 Apr;34(4):302-7.

5 Earlier intervention in febrile status epilepticus

About half of all febrile status epilepticus are focal (Shinnar et al). The majority of patients in FSE do not respond to the first dose of AED. Most children required at least 2 doses, and many required more than one AED (e.g., a benzo plus fospheny).

Because febrile status typically does not stop on its own, time to first AED is directly correlated with total duration of seizure. In the study by Seinfeld et al, there was a direct relationship between total seizure duration and time to first AED. However, there was not a relationship between time to first AED, and time from AED to seizure termination. Together, this suggests that the major contributor to the duration of FSE is time to first AED.



References:
  1. Emergency management of febrile status epilepticus: results of the FEBSTAT study.
    Seinfeld S, Shinnar S, Sun S, Hesdorffer DC, Deng X, Shinnar RC, O'Hara K, Nordli DR, Frank LM, Gallentine W, Mosh SL, Pellock JM, Pellock JM,
    Epilepsia 2014 Mar;55(3):388-95.
  2. Phenomenology of prolonged febrile seizures: results of the FEBSTAT study.
    Shinnar S, Hesdorffer DC, Nordli DR, Pellock JM, O'Dell C, Lewis DV, Frank LM, Mosh SL, Epstein LG, Marmarou A, Bagiella E, Bagiella E,
    Neurology 2008 Jul;71(3):170-6.

6 Patients with fever and seizure

Children having fever and seizure are common with 2-4 percent of all children less than 5 years having at least one episode with peak incidence at 12-18 months. Males have a 1.6:1 ratio. Certain populations have increase risk of febrile seizures: Japanese (7 percent) and the Pacific Mariana Islands (14 percent).

Risk factors

  • Family history of febrile seizures
  • High fever
  • Viral infection (HHV-6 most common ~ 1/3 of viral infections)
  • Recent immunization

Although the exact pathophysiology of febrile seizures is unknown it is believed to be a combination of genetic factors and the innate susceptibility of the developing brain.



References:
  1. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009.
    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Mosh SL, Nordli D, Plouin P, Scheffer IE,
    Epilepsia 2010 Apr;51(4):676-85.
  2. Predictors of epilepsy in children who have experienced febrile seizures.
    Nelson KB, Ellenberg JH,
    N. Engl. J. Med. 1976 Nov;295(19):1029-33.
  3. Distribution of febrile seizure duration and associations with development.
    Hesdorffer DC, Benn EK, Bagiella E, Nordli D, Pellock J, Hinton V, Shinnar S, Shinnar S,
    Ann. Neurol. 2011 Jul;70(1):93-100.
  4. Complex febrile seizures.
    Berg AT, Shinnar S,
    Epilepsia 1996 Feb;37(2):126-33.
  5. Studies in febrile seizures. I. Height of body temperature as a measure of the febrile-seizure threshold.
    MILLICHAP JG,
    Pediatrics 1959 Jan;23(1 Pt 1):76-85.
  6. Studies in febrile seizures. V. Clinical and electroencephalographic study in unselected patients.
    MILLICHAP JG, MADSEN JA, ALEDORT LM,
    Neurology 1960 Jul;10:643-53.
  7. Risk factors for a first febrile seizure: a matched case-control study.
    Berg AT, Shinnar S, Shapiro ED, Salomon ME, Crain EF, Hauser WA,
    Epilepsia 1995 Apr;36(4):334-41.
  8. Low risk of bacteremia in children with febrile seizures.
    Shah SS, Alpern ER, Zwerling L, Reid JR, McGowan KL, Bell LM,
    Arch Pediatr Adolesc Med 2002 May;156(5):469-72.
  9. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation.
    Hall CB, Long CE, Schnabel KC, Caserta MT, McIntyre KM, Costanzo MA, Knott A, Dewhurst S, Insel RA, Epstein LG,
    N. Engl. J. Med. 1994 Aug;331(7):432-8.
  10. A study of childhood febrile convulsions with particular reference to HHV-6 infection: pathogenic considerations.
    Bertolani MF, Portolani M, Marotti F, Sabbattini AM, Chiossi C, Bandieri MR, Cavazzuti GB,
    Childs Nerv Syst 1996 Sep;12(9):534-9.
  11. A population-based study of primary human herpesvirus 6 infection.
    Zerr DM, Meier AS, Selke SS, Frenkel LM, Huang ML, Wald A, Rhoads MP, Nguy L, Bornemann R, Morrow RA, Corey L,
    N. Engl. J. Med. 2005 Feb;352(8):768-76.
  12. Clinical characteristics of febrile convulsions during primary HHV-6 infection.
    Suga S, Suzuki K, Ihira M, Yoshikawa T, Kajita Y, Ozaki T, Iida K, Saito Y, Asano Y,
    Arch. Dis. Child. 2000 Jan;82(1):62-6.
  13. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study.
    Epstein LG, Shinnar S, Hesdorffer DC, Nordli DR, Hamidullah A, Benn EK, Pellock JM, Frank LM, Lewis DV, Moshe SL, Shinnar RC, Sun S, Sun S,
    Epilepsia 2012 Sep;53(9):1481-8.
  14. Influenza A infection is an important cause of febrile seizures.
    Chiu SS, Tse CY, Lau YL, Peiris M,
    Pediatrics 2001 Oct;108(4):E63.
  15. Relationship between five common viruses and febrile seizure in children.
    Chung B, Wong V,
    Arch. Dis. Child. 2007 Jul;92(7):589-93.
  16. Role of viral infections in the etiology of febrile seizures.
    Millichap JG, Millichap JJ,
    Pediatr. Neurol. 2006 Sep;35(3):165-72.
  17. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine.
    Barlow WE, Davis RL, Glasser JW, Rhodes PH, Thompson RS, Mullooly JP, Black SB, Shinefield HR, Ward JI, Marcy SM, DeStefano F, Chen RT, Immanuel V, Pearson JA, Vadheim CM, Rebolledo V, Christakis D, Benson PJ, Lewis N, Lewis N,
    N. Engl. J. Med. 2001 Aug;345(9):656-61.
  18. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B.
    Sun Y, Christensen J, Hviid A, Li J, Vedsted P, Olsen J, Vestergaard M,
    JAMA 2012 Feb;307(8):823-31.

7 Differentiating febrile seizures

Idiopathic febrile seizures are generally grouped into 3 different groups with specific criteria.

  • Simple febrile seizures
  • Complex febrile seizures (20 percent of febrile seizures)
  • Febrile status epilepticus (uncommon)

By using clinical criteria to identify the different types of febrile seizures the provider can risk stratify their patient.



References:
  1. Distribution of febrile seizure duration and associations with development.
    Hesdorffer DC, Benn EK, Bagiella E, Nordli D, Pellock J, Hinton V, Shinnar S, Shinnar S,
    Ann. Neurol. 2011 Jul;70(1):93-100.
  2. Prognosis in children with febrile seizures.
    Nelson KB, Ellenberg JH,
    Pediatrics 1978 May;61(5):720-7.
  3. Phenomenology of prolonged febrile seizures: results of the FEBSTAT study.
    Shinnar S, Hesdorffer DC, Nordli DR, Pellock JM, O'Dell C, Lewis DV, Frank LM, Mosh SL, Epstein LG, Marmarou A, Bagiella E, Bagiella E,
    Neurology 2008 Jul;71(3):170-6.
  4. Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study.
    Epstein LG, Shinnar S, Hesdorffer DC, Nordli DR, Hamidullah A, Benn EK, Pellock JM, Frank LM, Lewis DV, Moshe SL, Shinnar RC, Sun S, Sun S,
    Epilepsia 2012 Sep;53(9):1481-8.
  5. Short-term outcomes of children with febrile status epilepticus.
    Shinnar S, Pellock JM, Berg AT, O'Dell C, Driscoll SM, Maytal J, Moshe SL, DeLorenzo RJ,
    Epilepsia 2001 Jan;42(1):47-53.

8 Antipyretics

Although they may help symptomatically, antipyretics have not been shown to prevent simple febrile seizure episodes. Antipyretics do not stop temperature elevation or lower the threshold convulsive temperature during the initial stage of fever which is thought to trigger the seizure. Antipyretics carry the potential for overdose so judicial use should be recommended.



References:
  1. Febrile seizures: clinical practice guideline for the long-term management of the child with simple febrile seizures.

    Pediatrics 2008 Jun;121(6):1281-6.
  2. Prophylactic drug management for febrile seizures in children.
    Offringa M, Newton R,
    Cochrane Database Syst Rev 2012;4:CD003031.
  3. Treatment of febrile seizures: historical perspective, current opinions, and potential future directions.
    Lux AL,
    Brain Dev. 2010 Jan;32(1):42-50.
  4. Paracetamol for treating fever in children.
    Meremikwu M, Oyo-Ita A,
    Cochrane Database Syst Rev 2002(2):CD003676.
  5. Effect of acetaminophen and of low intermittent doses of diazepam on prevention of recurrences of febrile seizures.
    Uhari M, Rantala H, Vainionp L, Kurttila R,
    J. Pediatr. 1995 Jun;126(6):991-5.
  6. Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial.
    Strengell T, Uhari M, Tarkka R, Uusimaa J, Alen R, Lautala P, Rantala H,
    Arch Pediatr Adolesc Med 2009 Sep;163(9):799-804.
  7. Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized controlled trials and meta-analysis.
    Rosenbloom E, Finkelstein Y, Adams-Webber T, Kozer E,
    Eur. J. Paediatr. Neurol. 2013 Nov;17(6):585-8.

9 Prognosis

The prognosis of simple febrile seizures is very good, with only a slight increase in the baseline risk of epilepsy. Children with complex febrile seizures do have an increased risk of epilepsy (5 to 10 percent vs. 1 to 2 percent in the general population).



References:
  1. Death in children with febrile seizures: a population-based cohort study.
    Vestergaard M, Pedersen MG, Ostergaard JR, Pedersen CB, Olsen J, Christensen J,
    Lancet 2008 Aug;372(9637):457-63.
  2. Inheritance of febrile seizures in sudden unexplained death in toddlers.
    Holm IA, Poduri A, Crandall L, Haas E, Grafe MR, Kinney HC, Krous HF,
    Pediatr. Neurol. 2012 Apr;46(4):235-9.
  3. Longitudinal assessment of skill development in children with first febrile seizure.
    Leaffer EB, Hinton VJ, Hesdorffer DC,
    Epilepsy Behav 2013 Jul;28(1):83-7.
  4. Recognition memory is impaired in children after prolonged febrile seizures.
    Martinos MM, Yoong M, Patil S, Chin RF, Neville BG, Scott RC, de Haan M,
    Brain 2012 Oct;135(Pt 10):3153-64.
  5. Long-term intellectual and behavioral outcomes of children with febrile convulsions.
    Verity CM, Greenwood R, Golding J,
    N. Engl. J. Med. 1998 Jun;338(24):1723-8.
  6. Febrile seizures and cognitive function in young adult life: a prevalence study in Danish conscripts.
    Nrgaard M, Ehrenstein V, Mahon BE, Nielsen GL, Rothman KJ, Srensen HT,
    J. Pediatr. 2009 Sep;155(3):404-9.
  7. Predictors of epilepsy in children who have experienced febrile seizures.
    Nelson KB, Ellenberg JH,
    N. Engl. J. Med. 1976 Nov;295(19):1029-33.
  8. Factors prognostic of unprovoked seizures after febrile convulsions.
    Annegers JF, Hauser WA, Shirts SB, Kurland LT,
    N. Engl. J. Med. 1987 Feb;316(9):493-8.
  9. The long-term risk of epilepsy after febrile seizures in susceptible subgroups.
    Vestergaard M, Pedersen CB, Sidenius P, Olsen J, Christensen J,
    Am. J. Epidemiol. 2007 Apr;165(8):911-8.
  10. Long-term risk of developing epilepsy after febrile seizures: a prospective cohort study.
    Neligan A, Bell GS, Giavasi C, Johnson AL, Goodridge DM, Shorvon SD, Sander JW,
    Neurology 2012 Apr;78(15):1166-70.
  11. Prognostic factors for subsequent epilepsy in children with febrile seizures.
    Pavlidou E, Panteliadis C,
    Epilepsia 2013 Dec;54(12):2101-7.
  12. Risk for developing epilepsy and epileptiform discharges on EEG in patients with febrile seizures.
    Wo SB, Lee JH, Lee YJ, Sung TJ, Lee KH, Kim SK,
    Brain Dev. 2013 Apr;35(4):307-11.


  13. Childhood-onset epilepsy with and without preceding febrile seizures.
    Berg AT, Shinnar S, Levy SR, Testa FM,
    Neurology 1999 Nov;53(8):1742-8.
  14. Phenomenology of prolonged febrile seizures: results of the FEBSTAT study.
    Shinnar S, Hesdorffer DC, Nordli DR, Pellock JM, O'Dell C, Lewis DV, Frank LM, Mosh SL, Epstein LG, Marmarou A, Bagiella E, Bagiella E,
    Neurology 2008 Jul;71(3):170-6.