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Febrile Seizure

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Febrile Seizure, Febrile Convulsion

  • Definition
  1. Febrile Seizure
    1. Seizure with fever (Temperature >100.4 F) in neurologically healthy child without CNS Infection
  • Epidemiology
  1. Ages affected: 6 months to 5 years (peaks at age 2 years)
  2. Most common Seizures of childhood
    1. Occurs in 3-5% of children before age 5 years
  3. Gender: 66% are male
  4. Most common in winter and early spring
    1. Corresponding to increased frequency of respiratory and gastrointestinal infections
  • Risk Factors
  • First Febrile Seizure
  1. Low grade fever
    1. High fever also is associated, raising Neuronal excitability and decreasing Seizure threshold
  2. Day care attendance (OR 3.1)
  3. Developmental Delay (OR 4.9)
  4. Neonatal nursery hospitalization >28 days (OR 5.6)
  5. 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]
  6. 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)
  7. 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]
  8. 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
  1. 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
  2. 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%
  3. Timing of recurrence
    1. When Febrile Seizures recur, they do so in the first year in 75% of cases
  4. 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
  1. 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
  2. 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
  3. Febrile Status Epilepticus (5%)
    1. Generalized Febrile Seizure lasting >30 minutes
  • Differential Diagnosis
  1. See Seizure
  2. Meningitis
  3. Generalized Epilepsy with Febrile Seizure Plus (GEFS+)
    1. Inherited mutation related to Neuronal voltage gated Sodium channel mutations (SCN1A, SCN1B, SCN1B)
  4. Dravet Syndrome
    1. Severe myoclonic Epilepsy
    2. Rare, but severe degenerative neurologic condition
  • History
  1. 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
  2. Past medical history
    1. Recent Infections or antibiotic use
    2. Recent head injuries
    3. Prior Seizures
  3. Immunization status
    1. Recent Vaccinations (e.g. MMR)
    2. HaemophilusInfluenzae Type B Vaccine (Hib Vaccine)
    3. Streptococcus PneumoniaeVaccine (Prevnar)
  4. Family History
    1. Febrile Seizures
    2. Seizure Disorder
  • Exam
  1. Complete Neurologic Exam
    1. Focal neurologic deficit (e.g. Todd Paralysis)
  2. 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
  1. Meningeal Signs
  2. Complex Febrile Seizure
  3. 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]
  4. 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
  1. 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
  2. Finger stick Blood Sugar (bedside Glucose)
  3. Consider Urinalysis
  4. 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)
  1. 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]
  2. 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
  3. 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
  4. Other possible indications
    1. Pretreatment with antibiotics or
    2. Children 6-12 months of age with unknown or incomplete Vaccination series
      1. HaemophilusInfluenzae type B Vaccine
      2. Streptococcus PneumoniaeVaccine (Prevnar)
    3. Lumbar Puncture is no longer routinely indicated for children under 18 months without other findings
  • Imaging
  • Neuroimaging (MRI or CT) Indications
  1. General
    1. No imaging if otherwise normal history and exam
    2. MRI Head is the preferred modality if imaging is absolutely required (no radiation)
  2. Criteria
    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]
  3. References
    1. Offringa (2001) BMJ 323:1111-4 [PubMed]
  1. See Status Epilepticus
  2. 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
  3. 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
  4. 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
  5. References
    1. Offringa (2001) BMJ 323:1111-4 [PubMed]
  • Management
  • General
  1. 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
  2. Plan follow-up
    1. All children discharged from Emergency Department after Febrile Seizure in 1-2 days in clinic
  3. 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]
  4. 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]
  5. 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
  6. 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
  1. May offer parent some sense of control
  2. 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
  3. Intermittent dose for fever >38.5
    1. Not recommended unless high risk of recurrence
    2. Diazepam (adjust dosing per age)
  4. 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
  1. Not recommended in simple Febrile Seizures
  2. Complex Febrile Seizure
  3. Abnormal findings on examination or diagnostics
  • Management
  • Outpatient EEG
  1. 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]
  2. 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
  1. Mortality is rare with complex Febrile Seizures and non-existant in simple Febrile Seizures
  2. Normal school progression expected
    1. Verity (1998) N Engl J Med 338(24): 1723-8 [PubMed]
  3. Seizure remission expected
    1. No further Seizures after age 5 years in 98% children
  • Prognosis
  • Predictors of continued Epilepsy
  1. Neurodevelopmental disorder
    1. Developmental Delay
    2. Cerebral Palsy
    3. Hydrocephalus
    4. Abnormal Neurologic Exam
  2. Fever duration less than 1 hour before Seizure onset
  3. Age >3 years at time of Febrile Seizure
  4. Multiple Febrile Seizures at age <1 year
  5. Febrile Seizure with Eye Deviation, lip smacking or prolonged motor movement >15 min
  6. Family History of Epilepsy in first degree relative
  7. 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
  8. References
    1. Shinnar (2002) J Child Neurol 17(suppl 1): S44-S52 [PubMed]