Dr Paula VoinescuPaula Voinescu, MD, PhD
At the 72nd American Epilepsy Society’s (AES) annual meeting, held in New Orleans, Louisiana, Paula E. Voinescu, MD, PhD, junior faculty at Brigham and Women’s Hospital and instructor at Harvard Medical School, shared data from a study analysis that found that women with focal epilepsy have higher rates of seizure worsening during pregnancy compared to women with generalized epilepsy. In addition, women with frontal lobe epilepsy have particularly elevated rates of seizure worsening during the pregnancy and postpartum period.

Voinescu explained that while it’s unknown why these women experience a worsening of seizure frequency during pregnancy, clinicians need to carefully monitor this patient population especially during the second and third trimester where the women are at particularly high risk.

To dive more into the results of the analysis, NeurologyLive sat down with Voinescu at the AES meeting.

NeurologyLive: Is increased seizure frequency during pregnancy or postpartum period more likely in a specific type of epilepsy?

Paula E. Voinescu, MD, PhD: In caring for these women we noticed that women with frontal lobe epilepsy tend to have a dramatic increase in their seizure frequency, so we wanted to verify more thoroughly whether this is true or just a random observation in clinic. Since 2013 we have a clinical Microsoft Access database that gathers information on all pregnant women with epilepsy seen at Brigham and Women's Hospital both in the epilepsy and obstetrics clinic. The data has been gathered prospectively and we have information on their medications, their seizure frequency, and similarly, we follow them in clinic and document that in their chart. This analysis was done by using this clinical database that we have and corroborating it with the information available in the patient's chart.

From 2013–2018 we have tracked over a hundred pregnancies, more precisely 114 pregnancies and among these pregnancies we noticed that as it has been reported previously in the literature, patients with focal epilepsy are doing worse compared to patients with generalized epilepsy—so that was not a new finding—but prior publications have not looked at the localization of the seizure onset zone to see whether that was important in further stratifying this risk of seizure worsening during pregnancy.

We showed that within our patient populations women with focal epilepsy have a higher risk, but also women with frontal lobe epilepsy have a significantly higher risk even within the focal epilepsy group with an odds ratio of 8, which was statistically significant. We also noticed that women on polytherapy had a similar odds ratio of 8 for an increase in their seizure frequency during pregnancy but even when correcting for polytherapy, women with focal epilepsy and women with frontal lobe epilepsy were doing significantly worse.

The postpartum data was not that different between these women, we don't seem to have met the statistical significance there, but there was a difference when looking at the ratio of women who experienced an increase in seizure frequency postpartum within the generalized epilepsy group compared to the focal group.

The women with generalized epilepsy had an increase in the percentage of women who experienced seizure frequency worsening postpartum compared to the focal epilepsy group were there was a decrease, overall the percentage of women experiencing seizure worsening postpartum was still higher within the focal group, but the trend was definitely different postpartum for the 2 categories.

Another thought was to look into the therapeutic dose monitoring, because our work has previously shown that ratio to target threshold of 65% is significant for seizure worsening—and I should pause and say that when I'm saying ratio to target concentration, I'm referring to the concentration of the antiepileptic medication in the patient's serum at the certain time in pregnancy compared to a preconception baseline—so we obtained to these ratio to target concentrations for all patients with seizure worsening and they showed that the frontal focal epilepsy group with seizure worsening had adequate adjustments in their antiepileptic therapy and their ratios were frequently higher than other women with focal epilepsy within that group. Despite adequate dose adjustments during pregnancy, these women have an increase in their seizure frequency.

What should clinicians treating this patient population be on the lookout for?

We don't quite know why women with frontal lobe epilepsy are more likely to experience a worsening of their seizure frequency during pregnancy, so I think these women need to be more carefully monitored clinically during pregnancy. What we notice is that in a bunch of this women, we had to escalate not only the dose of their initial medication but also add other therapeutic methods. One of our patients even got TMS during pregnancy with hope of getting her seizures under control.

Is there a difference of seizure worsening between trimesters?

That’s a good question. We actually show that the majority of women experiencing worsening during pregnancy have seizure worsening starting at around 20 weeks of gestation, so the second and third but mostly the second trimester seems to be particularly high risk for these women.

Do you have any future study plans?

The first step would be to look a little more into other different antiepileptic therapies that may also play a role in seizure worsening. Our first analysis did not seem point to that as being the main trigger, but we need to confirm. We also need to think a little deeper into the physiological explanations for frontal lobe epilepsy and patients having seizure worsening during pregnancy, whether it's related to the different response to the rising sex hormones, or the different distribution of receptors for neurosurrogates in the frontal lobe—again all this is speculative at the moment.

Transcript edited for clarity.