You may be surprised to learn that 2-5% of all infants worldwide will experience at least one fever-induced (febrile) seizure. And yet most parents probably don’t even know what a febrile seizure is. According to the International League Against Epilepsy (ILAE), a febrile seizure is:

“[a] seizure occurring in childhood after age 1 month, associated with a febrile illness not caused by an infection of the CNS, without previous neonatal seizures or a previous unprovoked seizure, and not meeting criteria for other acute symptomatic seizures”.

To put it more plainly, it’s a seizure that occurs during a fever in infancy that isn’t otherwise due to a brain infection (meningitis, encephalitis), brain injury, toxic insults, or an already-established form of epilepsy. In short, it’s the brain’s reaction to its own changes during fever-associated infection.

The majority of these seizures occur in infants between 6 months and 3 years of age, peaking around 18 months. Approximately 2-4% of infants who experience febrile seizures (FS) go on to develop epilepsy (i.e., afebrile seizures), but the majority of kids have no further seizures and no obvious lasting impairment. Infants who experience seizures lasting greater than 10 minutes duration, in contrast to those with seizures lasting less than 10 minutes, are more likely to exhibit motor delay prior to the FS, suggesting a neurological vulnerability to fever-induced excitation. In addition, these same infants with motor delay are more likely to experience FS at a younger age (15 months vs. 19 months) [1]. In general, infants who are at higher risk for developing epilepsy following FS:

1) tend to exhibit developmental delay prior to the first FS,
2) experience FS lasting 10 minutes or more, or
3) have a family history of epilepsy.

In general, FS that are considered “complex” rather than “simple”– not to be confused with terms like “complex partial seizure” or “simple partial seizure”– often confer poorer outcome. Complex FS refers to:

• febrile seizures that last more than 10 minutes,
• febrile seizures that recur within 24 hours or during the same period of illness,
• when the child does not recover from the febrile seizure within an hour,
• febrile seizures that are partial or focalized in nature, such that only part of the body might shake during a fit.

Though these types of seizures are associated with fever, fever-reducing medications such as aspirin don’t appear to prevent the FS, suggesting that the fever itself doesn’t cause the seizure. Instead, the causal mechanism is probably something that accompanies the fever. For instance, it has been suggested that the pyrogen (fever-inducing substance), Interleukin-1, not only induces fever but increases neuronal excitability, lowering the threshold for seizures in animal models [2]. There are probably also other immune-related factors that get released during fever that affect the excitatory-inhibitory balance of the infant brain, though they’ve been poorly studied by comparison.

Although any infection that causes a feverish rise in body temperature could be a potential stimulus for FS, not all infections are the same and some infections seem to be better at inducing this transient condition. The Influenza A virus, for instance, appears to be particularly adept at causing higher fevers in infants as compared to other illnesses. In one study by Kwong et al. (2006), they reported that Influenza A infection was linked not only with higher fever, but with shorter duration time between fever onset and seizures, and increased occurrence of partial seizures (i.e., complex FS).

Electron micrograph of Influenza A.

Vaccinations have also been linked with the induction of FS, though the severity and timing vary by the specific inoculation just as they vary by type of infection. Infants who experience FS following DPT vaccination tend to experience seizures within the first 24-72 hours. Meanwhile, infants exposed to MMR tend not to experience fever until 7-10 days following inoculation, and therefore FS following MMR may not occur until up to two weeks after vaccination. One study by Klein et al. (2010) also reported a higher incidence of FS when MMR was combined with the varicella vaccine. The researchers reported finding that when MMR was combined with varicella, there was one additional occurrence of FS for every 2,300 doses, as compared to infants who received separate doses of MMR and varicella, suggesting that combining vaccinations may not be advisable for vulnerable populations, e.g., infants with a family history of epilepsy and/or febrile seizures.

A few weeks ago, I wrote about why regressive autism occurs when it does. To recap a little bit, one form of regressive syndromic autism, known as Dravet Syndrome, is particularly vulnerable to FS. (For a moving personal story on Dravet Syndrome, read Kennedy’s Story.) Approximately 2/3rds of infants with Dravet Syndrome develop FS, which is often the first signs of this severe seizure disorder. About 1/3rd experience FS following vaccination. Although vaccination certainly affects the timing of the onset of the condition, ultimately the outcome of these children do not differ from counterparts who do not experience FS following inoculation. In addition to seizures, about 1/4th of those with Dravet Syndrome develop autism.

In the general autism population, it appears that FS are also not uncommon. According to one study by Parmeggiani et al. (2010), approximately 8.5% of their autism sample experienced FS. Meanwhile, another study by Matsuo et al. (2011) reported that of those autistic individuals with complex partial seizures, 33% were reported to have experienced febrile seizures in infancy, once again suggesting a strong link between seizure susceptibility and FS.

Both autism and epilepsy are strongly tied to the excitability of the brain. It seems as though fever-associated infection or inoculation may lower the threshold for excitation, leading to increased risk for seizures. In those infants who already have a lowered threshold due to other inherited or environmental factors, FS may be more likely. It is uncertain whether FS in these cases ultimately affects the outcome of these children or whether epilepsy may have been inevitable given enough time. Further research is definitely needed in this area.

For those parents who are concerned about the safety of vaccinations and who have an infant who has already experienced complex FS following illness or vaccination, who is developmentally delayed, or who has a family history of epilepsy or autism, talk to your doctor about splitting vaccine combinations such as is recommended with the MMR + varicella or to postpone the typical vaccination schedule until an older age. It is not recommended to permanently forgo vaccination without consulting your child’s pediatrician. Research indicates that the infections that these inoculations are meant to protect against are just as capable of inducing FS, if not with greater frequency and severity than the inoculations themselves. Therefore, vaccination should only be refused under select, and well-reasoned, circumstances. If you feel that your doctor refuses to discuss vaccination options with you, don’t refuse vaccines– find a new doctor.