Andrew Wilner

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

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy. Methods: Systematic review of relevant articles published between January 1985 and June 2007. Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. Recommendations: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C).

Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first‐trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1‐minute Apgar score of <7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes.

Efficacy and Tolerability of the New Antiepileptic Drugs, II: Treatment of Refractory Epilepsy. Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society

Summary:u2003 Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.

Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Obstetrical complications and change in seizure frequency Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy in WWE compared to other women, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. Methods: A 20-member committee including general neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and February 2008. Results: For WWE taking antiepileptic drugs, there is probably no substantially increased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84%–92%) of remaining seizure-free during pregnancy. Recommendations: Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84%–92%) of remaining seizure-free during pregnancy (Level B). However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy (Level C).

Practice Parameter update: Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society

Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid use, prenatal vitamin K use, risk of hemorrhagic disease of the newborn, clinical implications of placental and breast milk transfer of antiepileptic drugs (AEDs), risks of breastfeeding, and change in AED levels during pregnancy. Methods: A 20-member committee evaluated the available evidence based on a structured literature review and classification of relevant articles published between 1985 and October 2007. Results: Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in amounts that may be clinically important. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. Recommendations: Supplementing women with epilepsy with at least 0.4 mg of folic acid before they become pregnant may be considered (Level C). Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered (Level B) and monitoring of levetiracetam and oxcarbazepine (as monohydroxy derivative) levels may be considered (Level C). A paucity of evidence limited the strength of many recommendations.

Management issues for women with epilepsy—Focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast‐milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4u2003mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.

Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): I. Obstetrical complications and change in seizure frequency: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure‐free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9u2003months prior to pregnancy is probably associated with a high likelihood (84–92%) of remaining seizure‐free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.

Incidence of spikes and paroxysmal rhythmic events in overnight ambulatory computer-assisted EEGs of normal subjects: A multicenter study

The incidences of spikes and paroxysmal rhythmic events (PREs) in 10-h overnight EEGs of normal adult volunteers (n=135) were studied at 11 sites with a computer-assisted ambulatory EEG monitoring system with automatic spike and PRE detection. Spikes were evident in the overnight EEG of 1 subject (0.7%), and PREs were apparent in the overnight EEG of the same subject (0.7%). The incidences of spikes of 24 other subjects with a history of migraine and/or a family history of epilepsy were 12.5 and 13.3%, respectively. The overnight EEGs of these subjects were significantly more likely to show spikes than the overnight EEGs of subjects without migraine or a family history of epilepsy.