Seizures, Febrile

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Basics

Description

Febrile seizures occur in children ages 6 months to 5 years with fever ≥100.4°F (38°C) and absence of underlying neurologic abnormality, metabolic condition, or intracranial infection. Three types (1,2):

  • Simple febrile seizure (SFS) (70–75%; must meet all criteria)
    • Generalized clonic or tonic–clonic seizure activity without focal features
    • Duration <15 minutes
    • Does not recur within 24 hours
    • Resolves spontaneously
    • No history of previous afebrile seizure, seizure disorder, or other neurologic problem
  • Complex (CFS) (20–25%; only one criterion must be met)
    • Partial seizure, focal activity
    • Duration >15 minutes but <30 minutes
    • Recurrence within 24 hours
    • Postictal focal neurologic abnormalities (e.g., Todd paralysis) (3)
  • Febrile status epilepticus (FSE) (5%)
    • Lasts >30 minutes

Epidemiology

Incidence
  • About 500,000 febrile seizures occur in the United States annually
  • Peak incidence is 18 months of age (3).
  • Only 6% of febrile seizures occur before age 6 months, and 4% occur after age 3 years (4).
  • Bimodal seasonal pattern that mirrors peaks of febrile respiratory (November to January) and gastrointestinal infections (June to August) (3)

Prevalence
  • 2–5% of children in the white population ages 6 months to 3 years in United States and Western Europe (4)
  • Cumulative incidence varies in other populations (0.5–14%) (2)

Etiology and Pathophysiology

Cause of febrile seizures is likely multifactorial (1):

  • Lower baseline seizure threshold in affected age group
  • Familial genotypes may influence seizure thresholds.
  • Fever may alter ion channel activity, causing increased neuronal excitability.
  • Cytokines released in infection increase neuronal activity.
Genetics

Evidence for genetic association:

  • Greater concordance in monozygotic than dizygotic twins
  • 25–40% of cases have positive family history (4).
  • Previously affected sibling increases risk
  • Having two affected parents doubles a child’s risk
  • Mode of inheritance is multifactorial, although autosomal dominant inheritance reported (3)
  • Several rare familial epileptic syndromes present with febrile seizure

Risk Factors

  • Any condition causing fever. Height of temperature elevation increases risk.
  • Risk increases with number of affected first-degree (O.R. = 4.5%) and second-degree relatives (O.R. = 3.6%) (1)
  • Risk is increased for males (2)
  • Recent vaccination
    • Possible increased risk with MMR and DTaP vaccinations, but it’s unclear (4), and absolute vaccination-associated risk is very low. As febrile seizures are benign, benefits of vaccination outweigh risks.
    • No evidence of increased risk with influenza vaccination (1)
  • Prenatal exposure to alcohol and tobacco, child care center attendance, premature birth, developmental delay, and prolonged NICU stay
  • Perhaps increased risk with iron deficiency anemia (5)

General Prevention

Prevention is not usually indicated given the benign nature of this condition, lack of effective interventions, and side effects of prophylactic medications.

Commonly Associated Conditions

  • Viral infections: human herpesvirus 6 (HHV-6), influenza, parainfluenza, adenovirus, and respiratory syncytial virus (RSV)
    • HHV-6 infection found in 30% of FSE in one study (4)
  • Bacterial infections: otitis media, pharyngitis, urinary tract infection (UTI), pneumonia, and gastroenteritis (specifically with Shigella)

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Basics

Description

Febrile seizures occur in children ages 6 months to 5 years with fever ≥100.4°F (38°C) and absence of underlying neurologic abnormality, metabolic condition, or intracranial infection. Three types (1,2):

  • Simple febrile seizure (SFS) (70–75%; must meet all criteria)
    • Generalized clonic or tonic–clonic seizure activity without focal features
    • Duration <15 minutes
    • Does not recur within 24 hours
    • Resolves spontaneously
    • No history of previous afebrile seizure, seizure disorder, or other neurologic problem
  • Complex (CFS) (20–25%; only one criterion must be met)
    • Partial seizure, focal activity
    • Duration >15 minutes but <30 minutes
    • Recurrence within 24 hours
    • Postictal focal neurologic abnormalities (e.g., Todd paralysis) (3)
  • Febrile status epilepticus (FSE) (5%)
    • Lasts >30 minutes

Epidemiology

Incidence
  • About 500,000 febrile seizures occur in the United States annually
  • Peak incidence is 18 months of age (3).
  • Only 6% of febrile seizures occur before age 6 months, and 4% occur after age 3 years (4).
  • Bimodal seasonal pattern that mirrors peaks of febrile respiratory (November to January) and gastrointestinal infections (June to August) (3)

Prevalence
  • 2–5% of children in the white population ages 6 months to 3 years in United States and Western Europe (4)
  • Cumulative incidence varies in other populations (0.5–14%) (2)

Etiology and Pathophysiology

Cause of febrile seizures is likely multifactorial (1):

  • Lower baseline seizure threshold in affected age group
  • Familial genotypes may influence seizure thresholds.
  • Fever may alter ion channel activity, causing increased neuronal excitability.
  • Cytokines released in infection increase neuronal activity.
Genetics

Evidence for genetic association:

  • Greater concordance in monozygotic than dizygotic twins
  • 25–40% of cases have positive family history (4).
  • Previously affected sibling increases risk
  • Having two affected parents doubles a child’s risk
  • Mode of inheritance is multifactorial, although autosomal dominant inheritance reported (3)
  • Several rare familial epileptic syndromes present with febrile seizure

Risk Factors

  • Any condition causing fever. Height of temperature elevation increases risk.
  • Risk increases with number of affected first-degree (O.R. = 4.5%) and second-degree relatives (O.R. = 3.6%) (1)
  • Risk is increased for males (2)
  • Recent vaccination
    • Possible increased risk with MMR and DTaP vaccinations, but it’s unclear (4), and absolute vaccination-associated risk is very low. As febrile seizures are benign, benefits of vaccination outweigh risks.
    • No evidence of increased risk with influenza vaccination (1)
  • Prenatal exposure to alcohol and tobacco, child care center attendance, premature birth, developmental delay, and prolonged NICU stay
  • Perhaps increased risk with iron deficiency anemia (5)

General Prevention

Prevention is not usually indicated given the benign nature of this condition, lack of effective interventions, and side effects of prophylactic medications.

Commonly Associated Conditions

  • Viral infections: human herpesvirus 6 (HHV-6), influenza, parainfluenza, adenovirus, and respiratory syncytial virus (RSV)
    • HHV-6 infection found in 30% of FSE in one study (4)
  • Bacterial infections: otitis media, pharyngitis, urinary tract infection (UTI), pneumonia, and gastroenteritis (specifically with Shigella)

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