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Febrile seizures occur in children aged 6 months to 5 years with fever ≥100.4°F (38°C) and absence of underlying neurologic abnormality, metabolic condition, or intracranial infection. Three distinct categories (1):
- Simple febrile seizure (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 or seizure disorder
- 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 neurologic abnormalities (e.g., Todd paresis) (2)
- Febrile status epilepticus (FSE) (5%)
- Lasts >30 minutes
- Approximately 500,000 febrile seizures occur in the United States annually.
- Peak incidence is 18 months of age (2).
- Only 6% of febrile seizures occur before age 6 months, and 4% of febrile seizures occur after age 3 years (3).
- Bimodal seasonal pattern that mirrors peaks of febrile respiratory (November to January) and gastrointestinal infections (June to August) (2)
Etiology and Pathophysiology
A variety of mechanisms have been proposed:
- A lower baseline seizure threshold in the age group affected by febrile seizures
- Familial genotypes may influence seizure thresholds.
- Fever may alter ion channel activity, resulting in increased circuit excitability.
- Cytokines released secondary to infection, specifically interleukin (IL)-1β, increase neuronal activity.
- Evidence for genetic association:
- Greater concordance in monozygotic than dizygotic twins
- 25–40% of cases have positive family history (3).
- Risk of febrile seizure with a previously affected sibling is increased.
- Having two affected parents doubles a child’s risk of febrile seizure.
- Mode of inheritance is multifactorial, although autosomal dominant inheritance reported (2).
- Several rare familial epileptic syndromes present with febrile seizure.
- Any condition causing fever
- Risk increases with the number of affected first-degree relatives.
- Risk is increased for male children (1).
- Recent vaccination
- As febrile seizures are a benign entity, the benefits of vaccination outweigh the risk.
- Possible increased risk with vaccinations, mainly MMR and DTaP, is a matter of much debate (3), and absolute vaccination-associated risk is very low.
- Prenatal exposure to alcohol and tobacco, daycare attendance, premature birth, developmental delay, and prolonged NICU stay
- Children with iron deficiency anemia may have increased risk for febrile seizures. Consider checking for anemia if the history suggests a risk for iron deficiency (4)[C].
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: Common pathogens include human herpesvirus 6 (HHV-6), influenza, parainfluenza, adenovirus, and respiratory syncytial virus (RSV).
- HHV-6 infection found in 30% of FSE in one study (3)
- Bacterial infections: Frequently associated infections include otitis media, pharyngitis, urinary tract infection (UTI), pneumonia, and gastroenteritis (specifically with Shigella).