Epilepsy in Pregnancy

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The physiological changes that occur during pregnancy result in altered distribution and elimination of AEDs. This may interfere with seizure control, particularly in women who were already poorly controlled before conception. Increased plasma estrogens, water and sodium retention, vomiting, poor compliance with AEDs, anxiety, and sleep irregularities are some of the factors that may affect seizure frequency during pregnancy.

There are several aspects to consider when planning AED therapy during pregnancy. These include preconceptional coun-

KEYPOINTS

■ CT or MRI can be used to assist antiepileptic treatment. Resolution of epileptogenicity is often accompanied by disappearance of the active cyst.

■ The finding of calcifications on CT at the time of seizure onset suggests a chronic condition, and prognosis for drug withdrawal is poorer than when active cysts are seen.

■ The argument against antiparasitic treatment is that acute cysts resolve without this intervention, while antiparasitic agents, such as albendazole, accelerate the release of toxic substances, increasing the risk for more severe seizures and increased intracranial pressure.

■ Where neither CT nor X-ray are available and other tests are either negative or not possible to perform, relatively little is lost by opting not to introduce the risk and cost of another drug regimen.

■ The diagnosis of neurocysticercosis or findings of small calcifications in patients presenting with acute seizures does not necessarily mean that the seizures are due to this disturbance.

■ Most specialists recommend not treating viable asymptomatic cysts.

KEYPOINTS

■ When evaluating a patient thought to have eclampsia, it is important to ask specific questions about a history of prior epileptic seizures, because a history of epilepsy may not have been disclosed to those delivering obstetrical care, especially among women recently wed who have not revealed their seizure disorder to their husban's family.

■ Vitamin K1 (10 mg/day by mouth) during the last few weeks of pregnancy reduces the chances of neonatal intracerebral hemorrhage when mothers are on enzyme-inducing AEDs.

seling, choice of drug, adjustment of the AED regimen throughout gestation, and delivery planning. When it is possible to adjust the AED regimen before conception, attempts should be made to ensure the best possible control with monotherapy at the minimum effective dosages, and folate supplementation should be started. In developing countries, limited access to public health systems may reduce the chances of precon-ceptional counseling, although public campaigns in this regard should be instituted. Although no AED is yet proven to be absolutely free of teratogenic effects, some of the newer drugs may have a relatively lower risk than commonly used older ones. If possible, valproic acid should be avoided because of an apparently greater risk of causing neural tube defects, especially in the presence of a positive family history of ter-atogenic drug effects.

The increase in the volume of distribution of most AEDs in the third trimester may lead to seizure recurrence due to reduced serum levels. The latter should be checked and dosage adjusted accordingly, particularly in patients who experienced difficulties in seizure control before conception and in those who already had seizures during pregnancy. Pregnancy also is associated with reduced serum protein and a resultant increase in the free fraction of protein-bound AEDs. This, in turn, causes increased renal clearance and lower total serum levels, but the amount of unbound drug available to the brain remains the same. If serum drug levels fall during pregnancy as a result of decreased protein binding, increasing the drug dosage may not be necessary and, indeed, may increase the risk of toxicity. Vitamin K1 (10 mg/day by mouth) during the last few weeks of pregnancy reduces the chances of neonatal intracerebral hemorrhage when mothers are on enzyme-inducing AEDs. All these measures highlight the pivotal role of good quality prenatal care in the outcome of pregnancies of women with epilepsy, and no specific management guidelines substitute for that. Neurologists from developing countries should work in concert with gynecologists and policy-makers to improve the quality of prenatal care for pregnant women with epilepsy.

There is a two- to threefold increase in the incidence of major malformations and minor anomalies among babies born to mothers with epilepsy. The use of AEDs during pregnancy plays a major role in the increased risk of abnormalities like cleft lip, cleft palate, congenital heart disease, and neural tube defects. The risk increases with the number of AEDs used during pregnancy, which makes a strong case for monotherapy. However, more than 90% of women with epilepsy treated during pregnancy can be expected to have an uneventful pregnancy and a normal healthy baby.

Although women with epilepsy who are taking AEDs excrete these drugs in their milk, this is not a contraindication to nursing. Nursing babies should be watched, however, to make sure that there is no sedative effect that suppresses the nursing reflex.

Eclampsia is the occurrence of seizures in women (with no prior history of epilepsy) during pregnancy in a setting of pre-eclamp-sia (proteinurea, edema, and high blood pressure after the 20th week of gestation). The causes of eclampsia and seizures during that period are poorly understood and are believed to be multifactorial. If seizures during eclampsia are not controlled quickly, there is significant maternal as well as fetal mortality. Eclampsia is a common cause of maternal and fetal mortality in developing countries because most of the pregnancies and subsequent deliveries are still not conducted under the supervision of trained personnel. The diagnosis of eclamptic seizures is mainly established by the clinical setting. When evaluating a patient thought to have eclampsia, it is important to ask explicit questions privately of the family members to confirm that indeed the patient does not have a history of prior epileptic seizures, because a history of epilepsy may not have been disclosed to those delivering obstetrical care, especially among women recently wed who have not revealed their seizure disorder to their husband's family. Magnesium sulfate has been the standard treatment for both pre-eclampsia and eclampsia. Magnesium sulfate acts by various mechanisms, but is not effective in seizures due to epilepsy. Magnesium sulfate can cause sedation in the mother, and hypotonia and lethargy in the newborn.

Other drugs that have been used in eclampsia include phenytoin and diazepam. Phenytoin can be used for status epilepticus (15 mg per kg loading dose followed by maintenance dose). The best treatment for eclampsia, however, is delivery of the baby.

Sexually active women who do not wish to become pregnant should know that many enzyme-inducing AEDs (carbamazepine, oxcarbazepine, phenytoin, primidone, and phenobarbital) can decrease the efficacy of oral contraceptives taken by women with epilepsy. This problem can partially be overcome by taking a contraceptive pill with higher estrogen content. Barrier methods are particularly useful adjuncts to oral contraception. Benzodiazepines, gabapentin, lam-otrigine, levetiracetam, tiagabine, and val-proate do not influence the efficacy of oral contraceptives.

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