September 1999
CHICAGO - Based on the risks and benefits of the effective therapies, neither continuous or intermittent anticonvulsant therapy is recommended for children with one or more simple febrile seizures, according to the American Academy of Pediatrics (AAP) Committee on Quality Improvement, Subcommittee on Febrile Seizures.
There is no convincing evidence that treating children who have febrile seizures will decrease epilepsy later in their lives, or that febrile seizures cause structural damage and decrease cognition, according to the recommendations published recently in Pediatrics
Although effective therapies that prevent reoccurrence exist, their potential adverse effects do not equal their benefits. "We recognize that recurrent episodes of febrile seizures can cause great anxiety in some parents and young children, and we suggest that appropriate educational and emotional support be provided," said Patricia Duffner, MD, chairwoman of the AAP committee that drafted the recommendations.
The AAP defines a simple febrile seizure as a brief (less than 15 minutes), generalized seizure occurring once during a 24-hour period in a febrile child who does not have an intracranial infection or severe metabolic disturbance.
These recommendations are not intended for patients who have had complex febrile seizures in whom a seizure lasts more than 15 minutes, is focal, or recurs during a 24-hour period. Nor are they intended for children who have previous neurologic insults, known central nervous system (CNS) abnormalities, or a history of afebrile seizures.
"These distinctions are important because complex febrile seizures are extremely different, both in terms of the potential for recommendations in the future and in terms of neurodiagnostic evaluations and perhaps even in terms of recommendations regarding treatment," said Duffner at the AAP Spring Session held here.
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To recommend treatment or no treatment, the risks to a child who has recurrent febrile seizures have to be analyzed, said Duffner, who is also professor of neurology and pediatrics at the State University of New York at Buffalo, Buffalo, N.Y.
The committee determined that the four theoretical risks of febrile seizures were: the potential for epilepsy; the potential that the current seizures might effect cognition in the long run; the potential that there might be an association with premature death; and, the potential that there might be a risk of recurrence.
Regarding treatment of febrile seizures in children to decrease their risk of developing epilepsy later in life, the AAP stated that children with simple febrile seizures are at a slightly greater risk for developing epilepsy by age 25, compared with the 1% risk of the general population.
"Many recent studies demonstrate no evidence that treating children with simple febrile seizures will prevent this slightly increased risk of developing epilepsy as an adult," said Duffner.
Will learning cognition be negatively effected by simple febrile seizures? asked Duffner. "I think the answer is pretty much unequivocal. The answer is no."
Two very large studies addressed this risk by looking at more than 700 children with simple febrile seizures and comparing them with sibling controls or age-matched controls. "There was no difference in learning or IQ in either study," said Duffner.
As for the risk of premature death, Duffner said she was unaware of any child dying suddenly from a simple febrile seizure. It is, of course, possible that a child having a febrile seizure is aspirated or injured from a fall, but these risks must be exceedingly low, she said.
The final risk factor reviewed by the committee - the potential for recurrence - was found to be high. "There is indeed a very high risk of having recurrent seizures if you have had one," said Duffner.
One study found that of all children with febrile seizures, 30% will have one recurrence. She said that children who have one recurrence, then have a 50% chance of having a second, third, or fourth recurrence, and children younger than 12-15 months automatically have a 50% chance of recurrence.
Can continuous anticonvulsant therapy prevent simple febrile seizure recurrence? asked Duffner. "I will say the answer is yes." The potential adverse effects of such therapy, however, are not commensurate with the benefit, according to the AAP.
The AAP cited a double-blind controlled study in which daily therapy with phenobarbital reduced subsequent febrile seizures from 25 to 100 subjects per year to five to 100 subjects per year.
"Most studies have shown that you can prevent recurrence with continuous phenobarbital 90% of the time," said Duffner. The caveat, however, is that the phenobarbital levels must be therapeutic. In the therapeutic range, it can prevent febrile seizures most of the time, she said.
Valproic acid (Depakene, Abbott), said Duffner, is also quite effective. In most studies, it is at least as effective as phenobarbital, and in some studies it is more effective if the levels are therapeutic, she said.
According to the AAP, in randomized, controlled studies, only 4% of children taking valproate (Depacon, Abbott) as opposed to 35% of control subjects had a subsequent febrile seizure.
Neither carbamazepine or phenytoin (Dilantin, Parke-Davis), however, can prevent febrile seizures, even when levels are therapeutic, she said. "They are ineffective in study after study."
"We know, therefore, that if you elect to treat, you can effectively prevent recurrence with either continuous phenobarbital or valproic acid." To do so, however, requires the child to undergo a year or two of continuous anticonvulsant therapy, said Duffner. Anticonvulsants, however, present risks.
Phenobarbital results in major behavioral problems, said Duffner, including hyperactivity and hypersensitivity reactions. Study after study of children taking phenobarbital has shown 20% to 45% of them having significant behavior disturbances including hyperactivity, attention deficit disorder and irritability.
Phenobarbital does not effect bone marrow and only uncommonly effects the liver, she said. "What has concerned people most is the effect of phenobarbital on cognition."
One study, which compared children being tested on phenobarbital with other anticonvulsants, found that children being treated with phenobarbital performed less desirably on tests of neuropsychologic function.
"I would suggest that the data stating that these are all long-term effects of phenobarbital on cognition after you stop the drug are very weak," said Duffner. There, however, is no question that while on phenobarbital, children do not test or perform as well, she said.
Duffner said that valproic acid should not be given. "It should not even be considered to be given because the fatal hepatotoxicity that occurs with valproic acid, occurs in the very young child. It occurs in the child 2-3 years of age, which is when you would consider using the drug."
In addition, said Duffner, valrpoic acid is associated with pancreatitis, weight loss, weight gain, thrombocytopenia and gastrointestinal disturbances.
Intermittent oral diazepam administered at the onset of illness may be effective in preventing recurrence and alleviating parental anxiety, but this too has some risks, she said.
There are two approaches to intermittent therapy, said Duffner, and those are treating with antipyretic agents, in particular acetometaphin, or diazepam. Unfortunately, said Duffner, acetaminophen does not prevent recurrence.
"We all take children with febrile seizures and tell the families to give them acetaminophen every four hours if they are sick, but the fact is that we are kidding ourselves." The children may feel better, but the acetaminophen does not protect them, she said.
Duffner cited a study showing acetaminophen and a placebo administered every four hours to be ineffective. "It is only when it is coupled with continuous phenobarbital that you can prevent the recurrent febrile seizures."
Without anticonvulsants, antipyretic agents are not effective against recurrent febrile seizures, according to the AAP. If a sufficiently large dose of diazepam is given correctly, said Duffner, it will prevent recurrence.
A double-blind, controlled study in which children with a history of febrile seizures were administered oral diazepam at the time of fever or illness showed a 44% reduction in the recurrence of febrile seizures, according to the AAP.
Oral diazepam is a difficult regimen to follow because a seizure could occur before a fever is noticed. Many families say that the first time they knew their child was sick was when they convulsed, said Duffner.
"The fever goes up quickly, the child has a seizure and you already lost the chance," she said.
Although it is only given for 48 hours, said Duffner, it is associated with ataxia, lethargy, irritability, and sleep disorders during that 48 hours. "I guess our greatest concern was that diazepam has the potential to mask an underlying CNS infection."
If the parents are concerned their child looks febrile and administers diazepam, they could attribute lethargy or irritability to the drug rather than to something serious. Parents think these are effects from the diazepam and do not pay attention to them, said Duffner.
Febrile seizures are the most common convulsive disorders in children; between 2% and 5% of children worldwide have them, said Duffner "Despite the markable frequency of this problem, there has been little unanimity of opinion, particularly in the United States, regarding the neurodiagnostic approach to these children and whether or not they require long-term anticonvulsant therapy."
For more information:
- Duffner P. Febrile seizures: Current treatment. Plenary session. Presented at the American Academy of Pediatrics Spring Session. April 17-20. Chicago.
- American Academy of Pediatrics Committee on Quality Improvement, Subcommittee on Febrile Seizures. Practice parameter: Long-term treatment of the child with simple febrile seizures. Pediatrics.1999;103(6):1307-1309.
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