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Frontal Lobe Epilepsy Tied to Higher Seizure Risk in Pregnancy

NEW ORLEANS — Compared to women with other types of epilepsy, those with frontal lobe epilepsy have the highest risk of seizures worsening during pregnancy, new research shows.

Investigators found that 53% of women with frontol lobe epilepsy experienced an increase in the frequency of seizures during pregnancy compared with before they became pregnant.

“We showed for the first time that women with frontal focal epilepsy have a high risk for seizure worsening during pregnancy, which indicates the need for closer monitoring of these women during pregnancy,” author Paula Voinescu, MD, PhD, attending neurologist, Division on Epilepsy, Department of Neurology, Brigham and Women’s Hospital, and instructor, Harvard Medical School, Boston Massachusetts, told Medscape Medical News.

The study also showed that although women with generalized epilepsy tend to do better during pregnancy, their condition may worsen in the postpartum period.

The study was presented here at the American Epilepsy Society (AES) 72nd Annual Meeting 2018.

Voinescu said she and her colleagues observed that several of their pregnant patients with frontal focal epilepsy experienced an increase in the frequency of seizures compared to preconception baseline.

“We aimed to assess whether increased seizure frequency during pregnancy and the postpartum period is more likely in women with focal or generalized epilepsy and whether it differs by the localization of seizure onset zone,” she said.

A secondary aim of the study was to determine whether the antiepileptic medication regimen influences this worsening.

A worsening of seizures during pregnancy has been reported more often in women with focal epilepsy, but so far, there has not been a distinction among sites.

At Brigham and Women’s Hospital, women with epilepsy are referred to the Epilepsy-Obstetrics Clinic for preconception counseling and epilepsy management during pregnancy and the postpartum period.

Since 2013, researchers have prospectively tracked pregnant women at the clinic. Information on antiepileptic drug (AED) regimens, seizure frequency, and pregnancy outcome is kept in a clinical database.

The researchers corroborated this information retrospectively with patient charts that routinely document epilepsy type/syndrome, seizure types and frequency, changes in AED regimens, and pregnancy outcomes.

Seizure Worsening

The study included data on 114 pregnancies in 99 women with epilepsy who were followed from 2013 to 2018. The patients included 37 women with generalized epilepsy, 62 women with focal epilepsy, 15 with frontal focal epilepsy, and 47 with other focal epilepsy. The mean age of the cohort was 31 years, and most were white.

The investigators recorded seizure frequency during a 9-month period before conception, during pregnancy, and 9 months post partum. For each participant, all seizures were totalled for each 9-month interval.

The researchers defined a worsening of seizure frequency during pregnancy or the postpartum period as any increase above preconception levels.

The analysis showed that seizures were more frequent during pregnancy compared to the prepregnancy period in 5.5% of women with generalized epilepsy; 22.6% of women with focal epilepsy; and 53% of women with frontal lobe epilepsy.

Women with generalized epilepsy had significantly lower odds of experiencing seizure worsening in pregnancy compared with women with focal epilepsy (odds ratio [OR], 0.213; 95% confidence interval [CI], 0.045 – 0.998; P = .0497).

Among women with focal epilepsy, those with frontal focal epilepsy had significantly higher odds of experiencing seizure worsening in pregnancy compared to those with any other type of focal epilepsy (OR = 8.000; 95% CI, 2.191 – 29.210; P = .0017).

About 94.6% of the women with generalized epilepsy were receiving polytherapy, defined as therapy with more than two AEDs, at the time of conception, as were 20% of those with frontal focal epilepsy and 10.6% of those with other focal epilepsy.

After adjusting for polytherapy, women with frontal focal epilepsy had significantly higher odds of experiencing seizure worsening in pregnancy compared to women with any other type of focal epilepsy (OR = 8.3964; 95% CI, 2.0614 – 34.1991; P = .0030).

Age was not a significant covariate for seizure worsening during pregnancy, said Voinescu. Given the predominantly white population, the investigators were unable to assess whether race was a contributing factor for seizure worsening. In addition, the researchers did not evaluate socioeconomic status as a variable.

Risk Reversal

The investigators hypothesize that pregnancy has a particular impact on women with frontal lobe epilepsy.

“We believe that some of the physiological changes in pregnancy lead to a temporary worsening of their seizures. We don’t know what the molecular underpinnings of these changes are, but we plan to investigate this in further studies,” said Voinescu.

Next research steps for the team include trying to better understand the role of hormonal changes during pregnancy on different epilepsy types.

The new results highlight the need for closer monitoring of women with frontal lobe epilepsy during pregnancy, said Voinescu.

The analysis showed that seizures were more frequent during the postpartum period compared to the prepregnancy period in 12.12% of women with generalized epilepsy; in 7.14% of women with focal epilepsies; and in 20% of women with frontal lobe epilepsy.

“In the postpartum period, women with focal epilepsy tend to do better than women with generalized epilepsy, although our numbers did not reach statistical significance” (P = .480), said Voinescu.

Other studies have shown that overall, patients with focal epilepsy are at a higher risk for seizure worsening compared to patients with generalized epilepsy.

“But we draw attention to a tendency of a risk reversal in the postpartum period, with women with generalized epilepsy having more frequent seizures,” said Voinescu.

Close Monitoring Warranted

Commenting for Medscape Medical News, James Valeriano, MD, chairman, Department of Neurology, Allegheny Health Network, professor of neurology, Temple University School of Medicine, and director, Comprehensive Epilepsy Program, Allegheny General Hospital, Pittsburgh, Pennsylvania, noted the many factors that may influence seizure frequency both during pregnancy and the postpartum period.

“This would include hormonal fluctuations, sleep deprivation, psychological stress that can accompany pregnancy and caring for a newborn,” he said.

Levels of almost all AEDs may decrease during pregnancy, said Valeriano, who treats adult women as well as men with epilepsy in his practice.

“Close monitoring of anticonvulsant levels, at least on a monthly basis during the second half of pregnancy, is warranted,” he said.

Physicians should explain to their epilepsy patients the risk factors during pregnancy “and make sure that any correctable issues are addressed,” said Valeriano.

Dr Voinescu has received support from the American Brain Foundation, the American Epilepsy Society, and the Epilepsy Foundation through the Susan Spencer Clinical Research Fellowship. Dr Valeriano has disclosed no relevant financial relationships.

American Epilepsy Society (AES) 72nd Annual Meeting 2018. Abstract 3.236,presented December 3, 2018.

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