Febrile Seizure

See Also

Unprovoked Seizure in Children

Definitions

Febrile Seizure
1. Seizure with fever (Temperature >100.4 F) in neurologically healthy child without CNS Infection

Epidemiology

Ages affected: 6 months to 5 years (peaks at age 2 years)
Most common Seizures of childhood
1. Occurs in 3-5% of children before age 5 years
Gender: 66% are male
Most common in winter and early spring
1. Corresponding to increased frequency of respiratory and gastrointestinal infections

Risk Factors
First Febrile Seizure

Low grade fever
1. High fever also is associated, raising Neuronal excitability and decreasing Seizure threshold
Day care attendance (OR 3.1)
Developmental Delay (OR 4.9)
Neonatal nursery hospitalization >28 days (OR 5.6)
Viral Infections (esp. those associated with high fever)
1. Primary human herpes 6 Infection (most common association)
  1. Laina (2010) Pediatr Neurol 42(1): 28-31 [PubMed]
2. Other infections
  1. Influenza Virus
  2. Adenovirus
  3. Parainfluenza Virus
  4. Chung (2007) Arch Dis Child 92(7): 589-93 [PubMed]
Family History
1. Up to 25-49% of those with Febrile Seizures have a Family History
2. Febrile Seizure in parent or sibling (10% risk, OR 4.5)
3. Febrile Seizure in second degree relative (OR 3.6)
Vitamin Deficiency
1. Iron Deficiency
  1. Hartfield (2009) Clin Pediatr 48(4): 420-6 [PubMed]
2. Zinc Deficiency
  1. Ganesh (2008) Clin Pediatr 47(2): 164-66 [PubMed]
Vaccinations
1. Background
  1. Prophylactic antipyretics did not reduce Seizure risk and may reduce immune response to Vaccination
  2. Prymula (2009) Lancet 374(9698): 1339-50 [PubMed]
2. Influenza Vaccine
  1. 2010 Southern Hemisphere seasonal trivalent Vaccine (Fluvax)
  2. Over the longterm, Influenza Vaccine has not been consistently associated with Febrile Seizures
3. DTP Vaccine
  1. Limited to within first 24 hours after Immunization
  2. DTaP is not associated with significantly increased risk
4. MMR Vaccine
  1. Related to fever from Vaccine (not Vaccine itself)
  2. Risk was 1 per 1000 if MMR given at age 16-23 months
    1. However risk drops to 4 in 10,000 (less than half), if Vaccine given at 12-15 months
  3. Increased risk only in the first 2 weeks after Vaccination
  4. Vestergaard (2004) JAMA 292(3): 351-7 [PubMed]

Risk Factors
Recurrent Febrile Seizure

Age of onset of first Seizure
1. First Seizure age 1 to 3 years
  1. Second Febrile Seizure: 30% risk
  2. Third Febrile Seizure: 15% risk
  3. More than 3 Febrile Seizures: <5% risk
2. First Seizure any other age
  1. Second Febrile Seizure: 50% risk of recurrence
High risk recurrence factors
1. Complex Febrile Seizure
2. Febrile Status Epilepticus
  1. Recurrence Febrile Seizure in 43%
  2. Recurrent febrile Status Epilepticus in 10%
Timing of recurrence
1. When Febrile Seizures recur, they do so in the first year in 75% of cases
Risk Scoring
1. Criteria: One point for each
  1. Age <18 months
  2. Short interval between fever onset and Seizure (<1 hour)
  3. Lower peak fever (<104 F or 40 C)
  4. First degree relative with Febrile Seizure
2. Risk of recurrence within 2 years
  1. Recurrence in 14% if 0 risk factors
  2. Recurrence in 24% if 1 risk factors
  3. Recurrence in 32% if 2 risk factors
  4. Recurrence in 63% if 3 risk factors
  5. Recurrence in 75% if 4 risk factors
3. References
  1. Berg (1997) Arch Pediatr Adolesc Med 151(4): 371-8 [PubMed]

Types
Febrile Seizure

Simple Febrile Seizure (65-90%)
1. Generalized Seizure
2. Seizure duration <15 minutes
3. Occurs once in 24 hour period
4. No prior neurologic conditions
5. Normal Neurologic Exam
Complex Febrile Seizure (20-25%)
1. Focal Seizure (most common reason for classifying as complex Seizure)
2. Seizure duration >15 minutes
3. Occurs more than once in a 24 hour period
4. Known neurologic condition (e.g. Cerebral Palsy)
5. Postictal neurologic abnormality (Todd's Paralysis)
6. May also be associated with prolonged postictal state
Febrile Status Epilepticus (5%)
1. Generalized Febrile Seizure lasting >30 minutes

Differential Diagnosis

See Seizure
Meningitis
Generalized Epilepsy with Febrile Seizure Plus (GEFS+)
1. Inherited mutation related to Neuronal voltage gated Sodium channel mutations (SCN1A, SCN1B, SCN1B)
Dravet Syndrome
1. Severe myoclonic Epilepsy
2. Rare, but severe degenerative neurologic condition

History

Seizure episode
1. Duration of Seizure (most Febrile Seizures last <7-8 minutes, typically much less than this)
2. Characteristics (generalized or focal findings)
3. Postictal signs and duration
4. Recurrence
Past medical history
1. Recent Infections or Antibiotic use
2. Recent head injuries
3. Prior Seizures
Immunization status
1. Recent Vaccinations (e.g. MMR)
2. Haemophilus Influenzae Type B Vaccine (Hib Vaccine)
3. Streptococcus Pneumoniae Vaccine (Prevnar)
Family History
1. Febrile Seizures
2. Seizure Disorder

Exam

Complete Neurologic Exam
1. Focal neurologic deficit (e.g. Todd Paralysis)
Identify source of fever
1. Simple Febrile Seizures are not associated with an increased risk of serious infection
  1. Well appearing children are not at higher risk of UTI, Pneumonia or Bacterial Meningitis
2. Consider Meningitis (for ill appearing children or those with complex Seizures)
  1. However, Meningitis rarely presents as Febrile Seizures (especially not simple Febrile Seizures)
  2. Those with Meningitis and Seizure, had other abnormalities (e.g. ALOC, Nuchal Rigidity, petechial rash)
  3. Green (1993) Pediatrics 92(4): 527-34 [PubMed]
3. Consider Bacteremia in Children (for ill appearing children or those with complex Seizures)
  1. Streptococcal Bacteremia (Streptococcus Pneumoniae)
  2. Urinary Tract Infection

Evaluation
Red Flags

Meningeal Signs
Complex Febrile Seizure
Altered Level of Consciousness
1. Patient should return to full alertness within one hour
2. Altered Level of Consciousness is present in 93% of patients with Meningitis
3. Green (1993) Pediatrics 92(4): 527-34 [PubMed]
Additional risks for serious Bacterial Infection cause
1. Age <6 months or >60 months with first-time Febrile Seizure
2. Age <12 months with inadequate or unknown Immunization history
3. Febrile Status Epilepticus

Labs

Well appearing children with simple Febrile Seizures do not require lab testing
1. In addition, well appearing children even with complex Febrile Seizures are unlikely to have abnormal labs
Finger stick Blood Sugar (bedside Glucose)
Consider Urinalysis
Consider serum Electrolytes if indicated by history
1. Example: Diarrhea or Vomiting
2. However lab testing is not routinely indicated (not recommended by AAP)
3. Consider basic chemistry panel (Serum Glucose, Serum Sodium, Serum Calcium, Serum Magnesium)

Diagnostics
Criteria for Lumbar Puncture (LP)

No LP if otherwise normal history and exam
1. Simple Febrile Seizures without other findings are not associated with Meningitis
2. Kimia (2009) Pediatrics 123(1): 6-12 [PubMed]
3. Guedj (2015) Acad Emerg Med 22(11): 1290-7 +PMID:26468690 [PubMed]
Atypical Seizure history
1. Complex Febrile Seizure alone does not mandate Lumbar Puncture
  1. Risk of Bacterial Meningitis as cause of complex Febrile Seizure is <1%
  2. Kimia (2010) Pediatrics 126(1): 62-9 [PubMed]
2. Focal Seizure
3. Prolonged Seizure exceeding 15 minutes
4. Multiple Seizures
Physical exam findings suggestive of intracranial abnormality or findings suggestive of Meningitis
1. Petechiae
2. Nuchal Rigidity (or Kernig Sign or Brudzinksi Sign)
3. Decreased Level of Consciousness or Coma
4. Hypotension
5. Focal neurologic deficit
Other possible indications
1. Pretreatment with Antibiotics or
2. Children 6-12 months of age with unknown or incomplete Vaccination series
  1. Haemophilus Influenzae type B Vaccine
  2. Streptococcus Pneumoniae Vaccine (Prevnar)
3. Lumbar Puncture is no longer routinely indicated for children under 18 months without other findings

Imaging
Neuroimaging (MRI or CT) Indications

See Neuroimaging after First Seizure
General
1. No imaging is needed if otherwise normal history and exam
2. MRI Head is the preferred modality if imaging is absolutely required (no radiation)
  1. MRI in young children requires sedation and increased resource use
  2. Consult pediatric neurology if imaging may be deferred to follow-up or tertiary transfer
  3. Larger, tertiary facilities have T3 MRI allowing rapid sequences and shorter MRI time
Imaging Indications
1. Persistent neurologic deficits or Altered Mental Status
2. Cerebral Abscess risk
3. Increased Intracranial Pressure signs
4. Head Trauma
5. Suspected structural defect (e.g. Microcephaly)
6. Status Epilepticus
7. Complex Febrile Seizure
  1. Only obtain imaging if associated with other neurologic findings
  2. Complex Febrile Seizure alone is not associated with intracranial abnormality
  3. Teng (2006) Pediatrics 117(2): 304-8 [PubMed]
References
1. Offringa (2001) BMJ 323:1111-4 [PubMed]

Management
Seizure duration >15 minutes (Status Epilepticus)

See Status Epilepticus
Approach
1. Treated the same regardless of fever presence
2. Consider initiating Benzodiazepines for Seizure >5 minutes (as these are unlike to stop spontaneously)
3. ABC Management
4. Supplemental Oxygen, monitor and airway management
5. Benzodiazepines (Lorazepam, Diazepam, Midazolam) followed by Fosphenytoin, Levetiracetam or Phenobarbital
Emergency department
1. Lorazepam
  1. Preferred agent for acute tonic-clonic pediatric Seizures
  2. Dose: 0.1 mg/kg IV up to 4 mg
2. Diazepam
  1. Consider rectal form (Diastat) when no IV Access available
  2. Dose: 0.2 to 0.5 mg/kg IV (or rectally) q15 minutes
  3. Maximum cummulative dose: 5 mg for age <5 years
3. Midazolam
  1. Consider when no IV Access available (use IM)
  2. Dose: 0.2 mg/kg IM of the IV formulation up to 10 mg
4. Fosphenytoin (preferred over Phenytoin)
  1. Indicated for Seizure refractory to Benzodiazepine
Home environment (emergency prescription)
1. Agents
  1. Diazepam gel (buccal Diazepam) - preferred over rectal formulation
  2. Diazepam rectal suppository (Diastat)
2. Dosing
  1. Diazepam 0.5 mg/kg for single dose (age 2-5 years)
3. Protocol
  1. Parents would have available at home for prn use
  2. Give for Seizure lasting longer than 15 minutes
  3. Immediate ER evaluation for prolonged Seizure
References
1. Offringa (2001) BMJ 323:1111-4 [PubMed]

Management
General

Disposition to home criteria
1. Simple Febrile Seizure
  1. Return to baseline status, tolerating oral fluids, non-toxic in appearance
2. Complex Febrile Seizure
  1. Return to baseline with no persistent neurologic deficits
Plan follow-up
1. All children discharged from Emergency Department after Febrile Seizure in 1-2 days in clinic
Lowering Temperature with antipyretics (Tylenol and Ibuprofen)
1. Some stuides showed no reduced risk of Seizure (although may aid comfort)
  1. Strengell (2009) Arch Pediatr Adolesc Med 163(9): 799-804 [PubMed]
2. Other studies showed Acetaminophen reduced Seizure recurrence in first 24 hours
  1. Murata (2018) Pediatrics 142(5): e20181009 [PubMed]
Warn parents that recurrence is likely
1. See recurrence risk factors above
2. One third of children with febrile seziure will have another (75% within one year)
  1. Berg (1997) Arch Pediatr Adolesc Med 151(4): 371-8 [PubMed]
Discuss with parents general home measures during recurrent Seizure
1. Place child in safe position in left lateral decubitus position
2. Ensure unobstructed airway
3. Give emergency Seizure abortive medication (e.g. rectal Diazepam) if prescribed
4. Call 911 for prolonged Seizure or at parental discretion
5. Re-evaluation for new complex Seizure features, Seizure recurrence in 24 hours
Offer reassurance (key)
1. Children with Febrile Seizures have identical intellectual and behavioral development as with their peers
2. Simple Febrile Seizures are not associated with increased morbidity or mortality
3. Complex Febrile Seizures have a very rare mortality, nearly undetectable rate in the first 2 years after Seizure
4. Verity (1998) N Engl J Med 338(24): 1723-8 [PubMed]
5. Vestergaard (2008) Lancet 372(9637): 457-63 [PubMed]

Management
Prophylaxis

May offer parent some sense of control
Prophylaxis, however, is not recommended
1. Significant adverse effects (lethargy, irritability)
2. Does not affect future Seizure risk
3. Agents taken continuously have adverse effects
4. Agents taken intermittently (Diazepam) not protective
  1. Typically Seizure presents with fever onset
Intermittent dose for fever >38.5
1. Not recommended unless high risk of recurrence
2. Diazepam (adjust dosing per age)
Continuous Dosing (not recommended - adverse effects)
1. Phenobarbital
  1. Age 2-24 months: 5-8 mg/kg/day
  2. Age >2 years: 3-5 mg/kg/day
2. Valproic Acid 10-15 mg/kg/day (max 60 mg/kg) divided

Management
Neurology Consultation Indications

Not recommended in simple Febrile Seizures
Complex Febrile Seizure
Abnormal findings on examination or diagnostics

Management
Outpatient EEG

Precautions
1. AAP does not recommend for simple Febrile Seizures in neurologically healthy children
2. Electroencephologram (EEG) does not predict future Seizure Disorder
  1. (2011) Pediatrics 127(2):389-94 [PubMed]
Indications
1. History of neurologic or Developmental Disorders
2. Family History of Seizure Disorder
3. More than one feature characterizing Febrile Seizure as complex

Prognosis
Excellent

Mortality is rare with complex Febrile Seizures and non-existant in simple Febrile Seizures
Normal school progression expected
1. Verity (1998) N Engl J Med 338(24): 1723-8 [PubMed]
Seizure remission expected
1. No further Seizures after age 5 years in 98% children

Prognosis
Predictors of continued Epilepsy

Neurodevelopmental disorder
1. Developmental Delay
2. Cerebral Palsy
3. Hydrocephalus
4. Abnormal Neurologic Exam
Fever duration less than 1 hour before Seizure onset
Age >3 years at time of Febrile Seizure
Multiple Febrile Seizures at age <1 year
Febrile Seizure with Eye Deviation, lip smacking or prolonged motor movement >15 min
Family History of Epilepsy in first degree relative
Complex Febrile Seizure with multiple complex features (see type description above)
1. Two complex features: 17-22% chance of future Epilepsy
2. Three complex features: 49% chance of future Epilepsy
References
1. Shinnar (2002) J Child Neurol 17(suppl 1): S44-S52 [PubMed]

References

Homme (2017) Febrile Seizures, Mayo Clinical Reviews, Rochester, MN
Ruest et al (2016) Crit Dec Emerg Med 30(12): 13-9
Graves (2012) Am Fam Physician 85(2): 149-53 [PubMed]
Hampers (2011) Emerg Med Clin North Am 29(1): 83-93 [PubMed]
Millar (2006) Am Fam Physician 73(10):1761-6 [PubMed]
Smith (2019) Am Fam Physician 99(7): 445-50 [PubMed]
Shinnar (2002) J Child Neurol 17:S44-52 [PubMed]
Warden (2003) Ann Emerg Med 41:215-22 [PubMed]