Blanca Vazquez

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).

Nonepileptic seizures and childhood sexual and physical abuse

Nonepileptic seizures (NES) must be distinguished from epilepsy to avoid the adverse effects of unnecessary antiepileptic drugs and to initiate appropriate psychiatric treatment. A higher frequency of prior sexual abuse has been suspected in NES, although no prospective controlled study has compared patients with NES and epilepsy, A series of patients with conversion disorder presenting as epilepsy and 140 patients with complex partial epilepsy (CPE) without evidence of conversion were selected from a series of consecutive admissions to a comprehensive epilepsy center. The groups did not differ with respect to age, years of education, race, or marital status, but the percentage of women was greater in the conversion NES group (73.2%) than in the CPE control group (50.7%; p < 0.002). The frequency of a history of sexual or physical abuse was greater in the NES group (32.4%) than in the CPE controls (8.6%; p < 0.000). Severity of sexual but not physical abuse was significantly greater in the NES group relative to controls (p < 0.05). There was a trend for a closer relationship of the perpetrator of sexual abuse to the victim among the NES patients compared with CPE controls (p < 0.1). These results support the impression that childhood abuse is more common among patients with conversion NES than with epilepsy, and suggests that in some cases childhood abuse may be a contributory pathogenetic factor.

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.

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.

Differential cognitive and behavioral effects of carbamazepine and lamotrigine

Background: The relative cognitive and behavioral effects of lamotrigine compared with the older standard antiepileptic drugs (AED) are uncertain. Objective: To directly compare the cognitive and behavioral effects of carbamazepine and lamotrigine. Methods: The cognitive and behavioral effects of carbamazepine and lamotrigine were assessed in 25 healthy adults using a double-blind, randomized crossover design with two 10-week treatment periods. During each treatment condition, subjects received either lamotrigine (150 mg/day) or carbamazepine (mean 696 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean 7.6 μg/mL). Subjects were tested at the end of each AED treatment period and in three drug-free conditions (two pretreatment baselines and a final posttreatment period [1 month after last AED]). The neuropsychological test battery included 19 measures yielding 40 total variables. Results: Direct comparison of the two AED revealed significantly better performance on 19 (48%) variables for lamotrigine but none for carbamazepine. Differences spanned both objective cognitive and subjective behavioral measures, including cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood factors, sedation, perception of cognitive performance, and other quality-of-life perceptions. Comparison of carbamazepine with the nondrug average revealed significantly better performance for nondrug average on 24 (62%) variables but none for carbamazepine. Comparison of lamotrigine with nondrug average revealed better performance on one (2.5%) variable for nondrug average and on one (2.5%) variable for lamotrigine. Conclusion: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects than carbamazepine at the dosages used in this study.

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 0.4 mg 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.

Dissociation in Epilepsy and Conversion Nonepileptic Seizures

Summary: Purpose: We examined the dimensionality of the item content of the Dissociative Experiences Scale (DES) in relation to the clinical diagnosis of conversion nonepileptic seizures (C‐NES) versus complex partial epilepsy (CPE).

Clinical profile of patients with epileptic and nonepileptic seizures

Epileptic seizures (ES) and nonepileptic seizures (NES) often coexist in patients with treatment-refractory seizures. There are few data on ictal features of these different seizure types in the same patient. We identified 20 patients with ES from a group of 99 NES patients (ES/NES) and compared this group with patients with only ES or NES. All 20 ES/NES patients developed NES after ES. Clinical features of NES clearly differed from ES in 18 of 20 cases. In patients with ES/NES their ES were similar to seizures in patients with only ES, and their NES were similar to spells in patients with only NES. ES/NES patients were similar to ES patients in electrodiagnostic and neuroimaging studies, and similar to NES patients in psychiatric interviews and inventories. The clinical manifestations of ES and NES in the same patient are usually different. Both types of events may be stereotypic and can be distinguished and characterized during video-EEG recording. Determining what events are more prevalent or disturbing is critical. Psychiatric and antiepileptic drug treatment may be provided accordingly. NEUROLOGY 1996;46: 1530-1533

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 9 months 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.