Febrile seizure

Viral infections triggering fever are the most common cause, with bacteremia as an infrequent cause.[10][11][14][15][16]

A retrospective cohort study of more than 900 febrile seizures showed the risk of developing febrile seizures is similar with influenza, adenovirus, or parainfluenza and is lower with respiratory syncytial virus or rotavirus. The type of viral infection was not important in predicting complex features or future recurrences.[17] The frequency of these infections was not significantly different in a control group of patients with fever but without seizures.

A prospective multicenter study of children with prolonged febrile seizures found human herpesvirus (HHV)-6 infection to be commonly associated with febrile status epilepticus; HHV-7 infection was less frequently associated, but together they accounted for one third of febrile status epilepticus.[18]

The International League Against Epilepsy described a monogenic etiology that may cause a spectrum of mild to severe epilepsies, such as SCN1A mutations, which are associated with Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+). There is an increasing tendency to define newly described epileptic disorders primarily in genetic terms, with clinical features being linked to genotypes.[19] In the future, the diagnosis of febrile seizures may be influenced by a greater understanding of the genetic epilepsies.[20]

Febrile seizures are dependent upon a threshold temperature and this seems to vary from one individual to another.[12][21][22] Age plays an important role in the susceptibility of febrile seizures; the risk of recurrence of seizure declines with growing older. If there is an individual temperature threshold level above which a febrile seizure will develop, this threshold is influenced by age: as the child grows older, the higher the threshold, the lower the risk.[23] The minimum temperature increase required to diagnose fever varies according to scientific societies and measuring methods, and has changed over time. Fever is generally defined as a temperature of ≥100.4°F (38.0°C).[1]

A specific neurotropism or central nervous system-invasive property of certain viruses (e.g., human herpesvirus-6 [HHV-6], influenza A), and bacterial neurotoxin (Shigella dysenteriae) has been implicated, but the evidence is inconclusive.[11] In some cases, HHV-6 may invade the brain during the acute viremic phase of exanthem subitum. Exanthem subitum, otherwise known as roseola or sixth disease, is a febrile illness often accompanied by a rash, lymphadenopathy, and gastrointestinal or respiratory symptoms. Seizure recurrence may be associated with reactivation of the HHV-6 virus. The definition of febrile seizure may need to be modified to include a mild encephalitis or encephalopathy in these cases. The type - simple or complex - may be related to a viral neurotropism or to the severity of a cytokine immune response to infection.[24]

Febrile seizures may be classified as simple or complex depending on clinical features, duration, and recurrence.

Simple febrile seizures are usually defined as primary generalized seizures lasting less than 15 minutes, resolving spontaneously, and not recurring during a 24-hour period.[1][2][4] Results of the FEBSTAT study, a prospective multicenter study of 158 children with a first febrile seizure, have suggested that an upper time limit of 10 minutes' duration may be more appropriate for the definition of simple febrile seizures.[5] The widely accepted definition of simple febrile seizures still includes a seizure duration of up to 15 minutes; however, the majority of febrile seizures last less than 10 minutes.[4]

Complex febrile seizures are defined by one or more of the following features: a focal onset or focal features during the seizure, prolonged duration (greater than 10-15 minutes), recurrence within 24 hours or within same febrile illness, or incomplete recovery.[1][2][4][6]

Between 9% and 35% of all first febrile seizures are complex.[6]

Pathophysiology

Classification