Management of Epilepsy and Pregnancy.(Review Article)

Byline: Sanjeev. Thomas

Epilepsy is recognized as the commonest serious neurological disorder in the world. Women with epilepsy (WWE) experience several gender-related physical and social problems. They constitute high obstetric risk because of reduced fertility, risk of seizures during pregnancy, and complications of pregnancy. Hormonal and other factors can alter the pharmacokinetics of antiepileptic drugs (AED) during pregnancy and puerperium. Antenatal exposure to AEDs, particularly at higher dosage and in polytherapy, increases the risk of fetal malformation. Recent reports raise the possibility of selective developmental language deficits and neurocognitive deficits with antenatal exposure to AEDs. There are concerns regarding the effect of traces of AEDs that pass to the infant during breast-feeding. The pre conception management is the cornerstone for epilepsy care in WWE. A careful reappraisal of each case should ascertain the diagnosis, the need for continued AED therapy, selection of appropriate AEDs, optimization of the dosage, and prescription of folic acid. During pregnancy, the fetal status needs to be monitored with estimation of serum a-feto-protein and ultrasound screening for malformations. The dosage of AEDs can be adjusted according to clinical requirement and blood levels of AEDs. Several institutions recommend oral vitamin K toward the end of pregnancy when enzyme-inducing AEDs are prescribed because the latter may potentially predispose the new born to hemorrhagic disease, but recent reports indicate that such a risk is practically negligible. WWE who are using enzyme-inducing AEDs (phenobarbitone, primidone, phenytoin, carbamazepine, and oxcarbazepine) need to know that these AEDs may lead to failure of oral contraception.

Epilepsy is a common neurological disorder with a prevalence rate of approximately 0.5% in most communities. It is estimated that there are over 2.5 million women with epilepsy (WWE) in India,[1] with up to 52% of them being in the reproductive age group.[2] People with epilepsy, especially women, experience tremendous social stigma and alienation in life. Despite progress in medical and surgical therapy, better social acceptance, and favorable legal stand, WWEs are less, often married (59%), when compared with others in the community (65%).[3],[4] Neurologists and obstetricians are increasingly faced with WWE during pregnancy, but apparently are not adequately informed about their optimal management.[5],[6] Several important aspects need to be attended to, which manage pregnancy in WWE: Pregnancy influences the natural history of epilepsy and seizures are likely to worsen in about one-third of them; the bioavailability of antiepileptic drugs (AEDs) may change considerably owing to alterations in its pharmacodynamics and kinetics and most AEDs are potentially teratogenic and hence may increase the risk of fetal malformations.

Effect of Pregnancy on Epilepsy

Hormonal aspects of epilepsy Experimental and clinical studies have shown that seizures are influenced by the female sex hormones estrogen and progesterone.[7],[8] In general, estrogen lowers the seizure threshold and progesterone elevates it. In most experimental animal models, estrogen lowers the threshold for seizures induced by electroshock, kindling, pentylenetetrazol, and other agents. Topical brain application or intravenous administration of estradiol in rabbits increases spontaneous paroxysmal spike discharges, especially when there is a pre-existing cortical lesion.[9] Progesterone, on the other hand, reduces spontaneous and induced epileptiform discharges.[10] Similar observations have been made in human beings also. Conjugated estrogen, when administered intravenously, activated epileptiform discharges in 11 of 16 women with clinical seizures.[11] In another study, four of seven women with partial epilepsy showed significant reduction in interictal spike frequency when progesterone was infused intravenously.[12]

Epileptic syndromes during pregnancy Several mechanisms, including syndromes[13] such as metabolic derangement, eclampsia, and cerebral venous sinus thrombosis, can induce seizures during pregnancy and postpartum period, epilepsy being the commonest amongst them. Majority of WWE have had seizures even before pregnancy. Rarely, some WWE may experience seizures only during pregnancy, which is termed gestational epilepsy . Such women would be seizure-free between pregnancies. Another subgroup (gestational onset epilepsy) may have their first seizure during pregnancy and thereafter may continue to get spontaneous recurrent seizures. Approximately 1-2% of WWE may experience status epilepticus (SE) during pregnancy, which is associated with high morbidity and mortality.

Effect of pregnancy on seizure frequency Pregnancy has a variable effect on seizure frequency. Seizure frequency may remain unchanged or decreases in two-third of WWE, whereas it may increase in others.[14] Seizure frequency may also vary between pregnancies in the same woman. There can be diverse patterns of seizure frequency during pregnancy. WWE may have a stable pattern with seizure frequency remaining more, less, or unchanged throughout the entire period of pregnancy. Others may have an unstable pattern wherein the seizure frequency may vary widely and often unpredictably during different months of pregnancy. In a recent study it was observed that nearly 61% patients had a stable pattern and 39% women had an unstable pattern.[15] Approximately 1% of them had SE. Diverse …