Medications for Neonatal Seizures and Infantile Spasms

Doctors face special challenges when treating children with epilepsy because of the limited data available to help determine the best use of medications for children of different ages with various types of epilepsy. Recently, however, progress has been made in understanding the use of antiepileptic drugs (AEDs) for treating neonatal seizures and infantile spasms, seizure disorders that occur in the first year of life. The effectiveness of AEDs in treating these conditions has been controversial, and predicting the outcome of these disorders for each child has been difficult, so this kind of progress is welcome.

Treating neonatal seizures
Phenobarbital is the most commonly used AED for treating neonatal seizures. The dosage aims at reaching a level in the baby's blood (a free plasma concentration) of at least 25 micrograms per milliliter (mcg/mL). Dilantin (phenytoin) is the second most commonly used medication. Doses of Dilantin are calculated to produce plasma concentrations of 3 mcg/mL. A study in 1999 showed that these two AEDs worked equally well when given to newborns with frequent seizures resulting from reduced blood flow and oxygen in the brain. Unfortunately, when either drug was given alone, seizures were controlled in fewer than half of these babies, even when high doses were used. Specifically, seizures were controlled in 13 of 30 newborns who received phenobarbital (43%) and 13 of 29 who received Dilantin (45%). When combined treatment was considered, seizure control was achieved in 57% of the babies who received phenobarbital first and 62% of those who received Dilantin first.

Treating infantile spasms (West syndrome)
In the late 1990s, several studies shed light on the safety and effectiveness of the drug Sabril (vigabatrin) in treating infantile spasms (also known as West syndrome), an unusual form of epilepsy that begins between 3 and 12 months of age. Sabril was shown to be highly effective, achieving spasm-free rates of 48%. Most of the patients responded to the medication within 3 days. Unfortunately, FDA approval of Sabril for sale in the United States was derailed by a 1999 study that found evidence of a high risk of damage to the retina of the eye in patients who were treated with it. (Sabril is being used in Canada and Europe as a first-line medication for the initial treatment of infantile spasms in children with tuberous sclerosis, however.) With the disappointing news about Sabril, a renewed search has been undertaken for another potential first-line medication for treating infantile spasms.

One promising AED for infantile spasms is Zonegran (zonisamide)—a Japanese-manufactured medication that became available in the U.S. in 2000. Two small Japanese studies in the late 1990s found that it was effective in stopping seizures within several days in 33-36% of these babies. The EEG pattern became normal in a few of these babies. The seizures returned later in some of the children, however, so Zonegran may be best regarded as a short-term therapy. No adverse side effects were noted.

Zonegran is not the only AED under investigation for treating infantile spasms. As research continues, we are sure to expand the arsenal of drug therapies available for infantile spasms, neonatal seizures, and other pediatric epilepsy syndromes.

Look for more information at PubMed, a service of the National Library of Medicine: www.ncbi.nlm.nih.gov/pubmed/

Here are links to some studies mentioned here:

Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med 1999 Aug 12;341(7):485-9. PMID: 10441604.

Vigevano F, Cilio MR. Vigabatrin versus ACTH as first-line treatment for infantile spasms: a randomized, prospective study. Epilepsia 1997 Dec;38(12):1270-4. PMID: 9578521.

Chiron C, Dumas C, Jambaque I, Mumford J, Dulac O. Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res 1997 Jan;26(2):389-95. PMID: 9095401.