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Pregnancy Might Protect Against Seizures For Women with Catemenial Epilepsy

Fitzgerald, Susan

doi: 10.1097/01.NT.0000452486.08116.53
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In a new study, investigators reported that women with catamenial epilepsy had fewer seizures during pregnancy than women with non-catamenial epilepsy. The researchers believe hormonal changes may be associated with the reduction in seizures.

Most women with catamenial epilepsy tend to be seizure-free during pregnancy, while pregnant women with non-catamenial epilepsy are much more likely to have seizures, according to a new study that tracked more than 250 women in Italy. Hormonal changes related to pregnancy may provide a protective effect for women whose seizures are related to their menstrual cycles, the researchers concluded in the study published June 18 in the online edition of Neurology.

“We were surprised by the extent of the reduction of seizure rate in catamenial epilepsy patients,” lead researcher Claudia Cagnetti, MD, PhD, a neurologist at Marche Polytechnic University in Ancona, told Neurology Today. “The catamenial pattern may truly represent a favorable prognostic factor for seizure control in pregnancy, even considering the poor seizure control known to exist in catamenial epilepsy in non-pregnant patients.”

Doctors generally are supportive of women with epilepsy who want to pursue pregnancy. Still, “treatment of epilepsy during pregnancy represents a major clinical challenge since the potential adverse affects and teratogenic risks of antiepileptic drugs (AEDs) must be balanced with both maternal and fetal risks of poor seizure control,” the researchers noted in their study. They said that any number of factors might influence the level of seizure activities during pregnancy, including hormonal changes, the pharmacokinetics of AEDs, poor drug compliance, sleep deprivation, and physical and mental stress during labor.

This new study provides added information to doctors and patients by focusing specifically on catamenial epilepsy, which accounts for about one-third of all epilepsy in women.

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The study included 59 women with catamenial epilepsy (CE) and 215 with non-catamenial epilepsy (NCE) who had been referred for pregnancy planning to the Epilepsy Center of the Ospedali Riuniti of Ancona from January 1999 to 2011. The researchers prospectively followed the patients from pre-pregnancy until the end of pregnancy.

For the CE group, the researchers included only women with a perimenstrual catamenial pattern, which they defined as a two-fold or greater increase in seizure frequency during the perimenstrual phase (three days before the onset of menses until three days afterward). All the participants had been seen at least 24 months prior to pregnancy and had a documented history of at least three seizures. The women, who were on average 30.5 years old at the time of pregnancy, typically had had epilepsy since about the age of 15–16.

As of part of the study, the women were evaluated every three months from enrollment until the end of pregnancy. They were all assigned to take folate prophylaxis (5 mg daily) through the first trimester of pregnancy.

Of the total of 274 women in the study, 34.7 percent were seizure-free throughout pregnancy. Seizure frequency decreased in 17.5 percent of the women and declined by at least half in 14.6 percent. Seizure frequency increased in 23.4 percent of women and increased by at least 50 percent in 9.1 percent of them. The median number of seizures during pregnancy was 1.

The CE group fared better during pregnancy compared to the NCE group. Among the differences: 79.7 percent of women with CE remained seizure-free during pregnancy, compared to 22.3 percent of those with NCE; there was a reduction of seizures in 50.8 percent of women with CE compared with 8.4 percent of those with NCE. And there was decrease of at least 50 percent in seizure activity in 44.1 percent of CE women and 6.5 percent of NCE women. Seizure frequency increased in 16.9 percent of the CE group and 25.1 percent of the NCE group. It increased greater than 50 percent in 5.1 percent of the CE group and 10.2 percent in the NCE group.

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“Patients with perimenstrual catamenial epilepsy were more than twice as likely to be seizure-free or have reduced seizure frequency throughout the pregnancy,” the researchers concluded.

“The absence of cyclical hormone variations and the increase in circulating progesterone levels accompanying pregnancy may be involved in the underlying mechanism for this change,” the researchers reported. They noted that the theory is supported by evidence that non-pregnant women with CE can benefit from progesterone replacement therapy.

The authors did note some limitations of the study. It involved a relatively small number of patients. Also, plasma levels of AED and sex hormones were not collected during the pregnancies, information that could have provided more insight.

Also, because the CE group included only women “with a perimenstrual seizure pattern, presumably the most strictly connected to progesterone levels and its withdrawal, we cannot exclude the possibility that other patterns of catamenial seizure exacerbations may respond differently to pregnancy and its hormone variations,” they wrote.

The published study, while noting the percentage of women taking certain AED drugs did not specify how the drugs were dosed during pregnancy.

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Cynthia Harden, MD, a professor of neurology at Hofstra North Shore-Long Island Jewish School of Medicine, said the new study findings should provide some added reassurance for epilepsy patients contemplating pregnancy.

“Usually women do quite well during pregnancy especially if they come to pregnancy seizure-free,” Dr. Harden said. She said the findings from the new study make the added point that “if you have a catamenial pattern, there's a good chance you will stop having those tendencies during pregnancy,” while women with NCE “may have to be more vigilant.”

She said the theory that hormonal changes may act as a protective effect for women with CE is supported by findings from her research that indicate that women with CE fewer seizures after menopause.

Alison M. Pack, MD, an associate professor of neurology at Columbia University, told Neurology Today that previous research from Europe had indicated that overall about 50 percent of women with epilepsy are seizure-free during pregnancy — a higher percentage than the roughly 35 percent noted in the study from Italy.

According to that new data, “a sizable number of women who didn't have catamenial epilepsy were seizing during pregnancy,” (almost 78 percent of them), she said, noting that the unanswered question is “why?” Dr. Pack said more research is needed to understand the specific factors that make some epilepsy patients more at risk for seizures during pregnancy.

Dr. Cagnetti told Neurology Today that her research team would like to do further research to collect AED and sex hormone levels in women with perimenstrual CE as well as women with other CE patterns. That added information might help answer the question of whether it might be possible to reduce the use of AEDs in pregnant women with CE.

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Ongoing research has focused on the issue of whether the use of AED drugs during pregnancy increase the risk of major congenital malformations and long-term neurocognitive problems in children born to women with epilepsy. Low birthweight is another concern.

A practice parameter issued by the AAN in 2009 recommends that practitioners avoid the use of valproate and AED polytherapy during the fist trimester of pregnancy to decrease the risk of major congenital malformations. It also recommends avoiding the use of valproate or polytherapy, as well as phenytoin and phenobarbital, throughout pregnancy to reduce the likelihood of cognitive problems in babies.

Kimford J. Meador, MD, FAAN, a professor of neurology and neurological sciences at Stanford University, is one of the principal investigators for the MONEAD study (Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs), an ongoing research project by the National Institutes of Health. He said the study from Italy adds to other research that shows that women with epilepsy, under proper medical guidance, can have safe pregnancies and good outcomes with their babies.

“Many women come in scared,” Dr. Meador said “The general message I try to give women is that if we manage the pregnancy right, the vast majority of women will have a safe pregnancy and a healthy, normal baby.' There is no reason they can't have a child if they want one.'”

The NEAD researchers published a study in June in JAMA Pediatrics that found no deleterious effect on the neurocognitive of babies who are breastfed by mothers taking AEDs. In fact, the breastfed babies had, on average, an IQ advantage of 4 points when assessed at six years of age, Dr. Meador said.

—Susan Fitzgerald

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•. Cagnetti C, Lattanzi S, Foschi N, et al. Seizure course during pregnancy in catamenial epilepsy. Neurology 2014; Epub 2014 Jun 18.
    •. Meador KJ, Baker GA, Browning N, et al. for the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study Group. Breastfeeding in children of women taking antiepileptic drugs: Cognitive outcomes at age 6 years. JAMA Pediatr 2014; Epub 2014 Jun 16.
      •. Harden CL, Meador KJ, Pennell PB, et al. Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009 73:133–141; Epub 2009 Apr 27.
        •. Neurology archive on management of women with epilepsy:
          •. Neurology Today archive on management of women with epilepsy:
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