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The primary risk factors for a first febrile seizure are day care center attendance, developmental delay, having a first- or second-degree relative with a history of febrile seizure, and a neonatal nursery stay of more than 30 days.4 Case-control studies5 have found the male to female ratio to be 1.4:1. Children with any two of the four risk factors have a 28 percent chance of experiencing at least one febrile seizure. For children with a febrile illness, the prime risk factors are the height of the fever and a family history of febrile seizures. Specifically, 10 percent of siblings and 10 percent of offspring of a person who had a childhood febrile seizure also will have seizures with fever.5 In one study,6 mean ferritin levels were lower in children who had a seizure with fever, suggesting a possible factor in febrile seizures.

The risk factors for recurrent seizures are provided in Table 2.4 Ethnicity, sex, neurodevelopmental abnormality, and a complex febrile seizure with one or more complex features are not risk factors for the recurrence of febrile seizures. The risk factors for the development of afebrile seizures (i.e., epilepsy) after an episode of febrile seizure are listed in Table 3.4 In one study,5 investigators found that 10 percent of children with febrile seizures subsequently developed an afebrile seizure disorder.

Ethnicity, sex, family history of febrile seizures, age at first febrile seizure, and height of fever are not risk factors for the subsequent development of epilepsy. Investigators in a 12-year study7 found no association between mesial temporal sclerosis and single or complex seizures with fever. Mesial temporal sclerosis is the most common lesion found in patients with temporal lobe epilepsy. The presence or absence of the above-mentioned risk factors is important for reassuring the parents, identifying patients who might warrant additional evaluation, and assessing the patient who has experienced a repeat seizure with fever.

The acute component of the evaluation of the febrile child with a seizure is the same as for any child with a fever.1,8-11 Measures include clinical history, presence of chronic illness, recent antibiotic therapy, recent immunizations,12 and day care attendance. As many as 10 percent of infants younger than three months who appear to be well and have a temperature above 100.4° F (38° C) have a serious bacterial infection or meningitis. Two percent of infants and children older than three months with a temperature above 102.2° F (39° C) are found to have bacteremia.

The authors of one retrospective study13 in children presenting with a febrile seizure examined the incidence of bacterial infections, including unsuspected meningitis. Bacteremia with Streptococcus pneumoniae was noted in 3 percent of the patients, urinary tract infection in 1 percent, and none of the patients had bacterial meningitis. Children with more than 8 white blood cells per mL of cerebral spinal fluid, known seizure disorder or other chronic neurologic disorder, or who had a documented immunodeficiency were excluded from the study.

In another retrospective study14 focusing on only simple febrile seizures, investigators found a 1.3 percent incidence of bacteremia with S. pneumoniae, a 6 percent incidence of urinary tract infection, and no meningitis. Patients who were unarousable or comatose after seizure were excluded from the study, which may account for the low incidence of meningitis. Streptococcal bacteremia and meningitis will become less common as the prevalence of immunization increases.

Current recommendations include consideration of a lumbar puncture, especially in children younger than 18 months, because meningeal signs are less reliable in this group.15 The prevalence of meningitis among patients with a febrile seizure was 1 to 2 percent, and the absence of any remarkable findings on the history or physical examination makes bacterial meningitis unlikely as the cause of the fever and seizure.16 Other laboratory studies,1,17 such as measurement of serum electrolyte levels, are most beneficial in situations with clear symptoms or signs of a concurrent illness, such as diarrhea or vomiting.

Neuroimaging (i.e., cranial magnetic resonance imaging [MRI] or computed tomography) is indicated in the child with a febrile seizure and evidence of increased intracranial pressure, history or examination suggestive of trauma, or a possible structural defect (in cases of microcephaly or spasticity).1,18 If a neuroimaging study is obtained, MRI is the preferred modality.19 Results of prospective studies2,18 have not found electroencephalography to be helpful in predicting the likelihood of developing afebrile seizure disorders later in life. Consultation with a neurology subspecialist rarely is needed for the child with a febrile seizure, especially a simple febrile seizure.

Current guidelines2,3,20 do not recommend the use of continuous or intermittent therapy with neuroleptics or benzodiazepines after a simple febrile seizure. No medication has been shown to reduce the risk of an afebrile seizure (i.e., epilepsy) after a simple febrile seizure. Intense routine use of antipyretic agents has been no more effective in reducing the incidence of recurrent febrile seizures than the intermittent use of the antipyretic agents when a febrile episode is noted.18 Although valproic acid (Depakene), diazepam (Valium), lorazepam (Ativan), and fosphenytoin (Cerebyx) are indicated for the management of seizures, they have not been indicated explicitly for the management of febrile seizures.

The use of phenobarbital (5 to 8 mg per kg of weight per day for children two to 24 months of age, and 3 to 5 mg per kg per day for children older than two years) and valproic acid (10 to 15 mg per kg per day in divided doses, with a maximal dosage of 60 mg per kg per day) on a continuous basis reduces the risk of recurrent febrile seizures but has significant side effects. Phenobarbital is associated with transient sleep disturbances, decreased memory, and reduced concentration. Valproic acid therapy is associated with hematopoietic disruptions, renal toxicity, pancreatitis, and fatal hepatotoxicity.

The use of intermittent oral diazepam also has been found to reduce the risk of recurrent febrile seizures, but the effectiveness is limited. In one randomized controlled trial,3 recurrence was noted in 15 percent of patients receiving diazepam and 18 percent of patients receiving placebo. One reason for this limited effectiveness was that nearly one half of patients in the oral diazepam and placebo groups experienced febrile seizure as the first sign of a febrile illness. Hyperactivity was the most common side effect in the oral diazepam group, and other side effects included lethargy, ataxia, and drowsiness. Concern has been expressed that the latter side effects could mask an evolving infection of the central nervous system.

For patients who have an ongoing seizure at the time of assessment (i.e., febrile status epilepticus), intravenous diazepam (0.2 to 0.5 mg per kg of weight intravenously every 15 minutes for a cumulative dosage of 5 mg in children one month to five years of age) often is effective. For the pre-hospital treatment of a seizure or for patients in whom intravenous access is limited, rectal diazepam (a single dose of 0.5 mg per kg for children two to five years of age) or diazepam gel is an option.4 Lorazepam (0.1 mg per kg up to 4 mg) is another intravenous medication, and it has a longer duration of action compared with diazepam.

Finally, if the seizure continues after an adequate dose of diazepam (or other benzodiazepine) is administered, a full status epilepticus treatment protocol is indicated.21 Fosphenytoin has several theoretic and clinical advantages compared with phenytoin (Dilantin): a more convenient, rapid route of intravenous administration; the ability to reach therapeutic levels more quickly; the availability for intramuscular injection; and a relatively low potential for adverse local reactions at injection sites. If this additional measure is not successful, intubation and anesthesia are the recommended final measures.

The author thanks R. Michael Morse, M.D., John W. Tipton, M.D., Charles E. Henley, D.O., and Karen F. Malnar, R.N., for providing critical appraisal and suggestions for revision of the manuscript.

Members of various family medicine departments develop articles for "Practical Therapeutics." This article is one in a series coordinated by the Department of Family Medicine at the University of Oklahoma-Tulsa College of Medicine, Tulsa, Okla. Coordinator of the series is John W. Tipton, M.D.

JAMES S. MILLAR, M.D., is associate professor and medical director in the Department of Family Medicine at the University of Oklahoma-Tulsa College of Medicine. He received his medical degree from the University of Oklahoma College of Medicine, Oklahoma City, and completed a residency in family medicine at the University of Oklahoma-Tulsa.

Address correspondence to James S. Millar, M.D., Department of Family Medicine, University of Oklahoma-Tulsa, 1111 S. St. Louis Ave., Tulsa, OK 74120 (e-mail: james-millar@ouhsc.edu ). Reprints are not available from the author.

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