Early cognitive development in children born to women with epilepsy: A prospective report

Purpose: In this prospective study the early cognitive development of children born to women with epilepsy (n = 198) was assessed and compared to a group of children representative of the general population (n = 230). Methods: The children were assessed when younger than the age of 2 years using the Griffiths Mental Development Scales, either in their local participating hospital or in their home. The assessments were completed by an assessor who was blinded to whether the child’s mother had epilepsy and to antiepileptic drug type. Results: Children exposed to sodium valproate had a statistically significant increased risk of delayed early development in comparison to the control children. Linear regression analysis showed a statistically significant effect of sodium valproate exposure on the child’s overall developmental level that was not accounted for by confounding variables. Delayed early development is also noted for children within an ad hoc group of less commonly utilized antiepileptic drugs, although conclusions cannot be drawn due to the size of this group (n = 13). Children exposed to either carbamazepine or lamotrigine in utero did not differ significantly in their overall developmental ability. Differences noted in specific developmental areas for these two groups were not statistically significant after the control for confounders such as socioeconomic status and maternal IQ. Discussion: Women with epilepsy should be informed of the risks posed to their potential offspring prior to pregnancy to allow for informed decisions regarding treatment. Children exposed in utero to antiepileptic drugs should be monitored throughout childhood to allow for early intervention when necessary.     

The postpartum period in women with epilepsy

For women with epilepsy (WWE), the postpartum period is a vulnerable time owing to medication alterations, disrupted sleep, increased stress, and the challenges of breastfeeding. Sleep deprivation and the stress of having a new child can be challenging for WWE. Concerns over antiepileptic drugs (AEDs) in breast milk and sleep disruption associated with breastfeeding leads some WWE to discontinue breastfeeding. Adjustment of AEDs in the postpartum period can lead to difficulties in seizure control. Postpartum depression is increased in WWE, and patient education about newborn safety remains a concern. This article covers these important topics in postpartum WWE.     

Growth and lipid metabolism in girls and young women with epilepsy during pubertal maturation

Summary:  Purpose: To assess growth and the serum lipid profile in girls with epilepsy receiving monotherapy at a mean age of 12.6 years and approximately 6 years later.
Methods: A population-based cohort of 77 girls with epilepsy and 49 healthy controls participated in this follow-up study including two cross-sectional evaluations (age range, 8–18.5 years on the first evaluation, and 12.5–25.8 years on the second evaluation). Forty of the patients were initially taking valproate (VPA), 19, carbamazepine (CBZ), and 18, oxcarbazepine (OXC). Growth data were compiled, body mass index (BMI) was calculated, and serum total (TC), and high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol and triglyceride concentrations were analyzed.
Results: Linear growth and final height did not differ between the patients and the controls. At follow-up, the mean BMI of the patients who were off medication (61%) was similar to that of the controls, whereas the patients initially treated with VPA who were still taking any medication had a higher BMI. On the first evaluation, the patients taking VPA had low serum HDL-C, and those taking CBZ or OXC had high serum TC and LDL-C concentrations. At follow-up, serum lipid levels were similar in the patients off medication and the controls.
Conclusions: Neither epilepsy nor antiepileptic therapy affects linear growth or final height, but they may have unfavorable effects on body weight and serum lipid concentrations. Lipid-profile impairment seems to be transient if the medication is discontinued. Overweight is common in patients treated with VPA during puberty if epilepsy and medication continue into adulthood.     

西比灵治疗癫痫的临床研究

目的：研究西比灵（ＩＢＬ）辅助抗痫药（ＡＥＤｓ）在抗痫方面的临床价值。方法：将６８例癫痫（ＥＰ）分为甲、乙两组。第一阶段甲组作为治疗组，乙组作为对照组。治疗组在对照组基础上加用西比灵胶囊，每日 １０ ｍｇ，每晚一次，小儿按公斤体重给药，两组均用药３个月，然后评定其疗效。第二阶段乙组作为治疗组，第４个月开始，加用西比灵，用法同上，连用３个月，作同样观察，并以该组前３个月的观察结果用自身对照；同时还与连用６个月西比灵的甲组进行比较。结果：甲组（治疗组）加用西比灵后显效率与总有效率均明显优于对照组（Ｐ＜０．０１与Ｐ＜０．０５），甲组连用６个月西比灵，疗效进一步提高。西比灵对不同类型的ＥＰ均有效，而显效率有明显差别，特殊类型ＥＰ组优于全身大发作ＥＰ组（Ｐ＜０．０１）。结论：西比灵是一种安全有效抗ＥＰ的辅助新药，尤其对特殊类型ＥＰ更有应用前景。     

Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy

PURPOSE: This study evaluated obstetric and neonatal outcome in a community-based cohort of women with active epilepsy (WWAE) compared with the general pregnant population receiving modern obstetric care. METHODS: We reviewed the total population who gave birth between January 1989 and October 2000 at Kuopio University Hospital. Obstetric, demographic, and epilepsy data were collected prospectively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of unaffected controls. The obstetric data from the pregnancy register was supplemented with detailed neurologic data retrieved from the medical records. The data retrieved were comprehensive because of a follow-up strategy according to a predecided protocol. RESULTS: During pregnancy, the seizure frequency was unchanged, or the change was for the better in the majority (83%) of the patients. We found no significant differences between WWAE and controls in the incidence of preeclampsia, preterm labor, or in the rates of caesarean sections, perinatal mortality, or low birth weight. However, the rate of small-for-gestational-age infants was significantly higher, and the head circumference was significantly smaller in WWAE. Apgar score at 1 min was lower in children of WWAE, and the need for care in the neonatal ward and neonatal intensive care were increased as compared with controls. The frequency of major malformations was 4.8% (-0.6-10.2%; 95% confidence interval) in the 127 children of WWAE. CONCLUSIONS: Pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predecided protocol is used for the follow-up of WWAE in antenatal and neurologic care. Long-term follow-up of the neurologic and cognitive development of the children of WWAE is still needed.     

Seizure frequency and cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in women with epilepsy receiving antiepileptic drug treatment

PURPOSE: Hormonal changes occur in epilepsy because of seizures themselves and of antiepileptic drug (AED) effects on steroid production, binding, and metabolism. Conversely, steroids may influence neuron activity and excitability by acting as neuroactive steroids. This cross-sectional observational study aimed to evaluating cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in female epilepsy patients with different disease severity, as assessed by a seizure frequency score (SFS). METHODS: Morning serum levels of cortisol and DHEAS were assayed in 113 consecutive women, aged 16 to 47 years, with varied epilepsy syndromes, receiving mono- or polytherapy with enzyme-inducing and/or noninducing antiepileptic drugs (AEDs). Hormonal data were correlated with clinical parameters (age, body mass index, epilepsy syndrome, disease onset and duration, SFS, AED therapy, and AED serum levels) and compared with those of 30 age-matched healthy women. RESULTS: In epilepsy patients, cortisol levels and cortisol-to-DHEAS ratios (C/Dr) were significantly higher, whereas DHEAS levels were significantly lower than those in controls. Patients with more frequent seizures showed higher cortisol and C/Dr values and lower DHEAS levels than did those with rarer or absent seizures during the previous 6 months. SFS mainly explained the increase of cortisol levels and C/Dr in patients with more active disease. Changes in DHEAS levels correlated with SFS and epilepsy syndrome, as well as with AED treatments and ages. CONCLUSIONS: Women with more frequent seizures had alterations of their adrenal steroids characterized by an increase of cortisol and a decrease of DHEAS levels. Such hormonal changes might be relevant in seizure control and in patient health.     

癫痫患者经颅磁刺激运动诱发电位的研究

目的 探讨癫痫患者经颅磁刺激（ＴＭＳ）的运动诱发电位（ＭＥＰ）对癫痫的诊断价值。方法 对３５例癫痫患者和３０例正常对照组的脑运动皮质和第７颈椎和７颈椎水平神经根进行单脉冲磁刺激，引出ＭＥＰ。结果 与对照组比较，两组患者的皮质阈强度均增大，治疗组增大更明显；未治 的皮质潜伏期和中枢神经传导时间缩短，治疗组则无明显改变；三组的周围潜伏期无明显差异。癫痫类型，疗程，联合用药与否以及脑部病灶侧别对ＭＥＰ无     

Therapy for neurobehavioral disorders in epilepsy

Neurobehavioral disorders commonly affect patients with epilepsy. In addition to the behavioral changes during and immediately after seizures, the epileptogenic disorder of function often extends further into the postictal and interictal period. Cognitive impairments commonly affect attention, memory, mental speed, and language, as well as executive and social functions. Reducing seizure frequency and the antiepileptic drug burden can reduce these problems. Attentional deficits may respond to therapies for attention-deficit/hyperactivity disorder, but apart from patients with this comorbid disorder, their efficacy is unproven in other epilepsy patients. No effective therapies are established for other cognitive problems, but pragmatic, compensatory strategies can be helpful. Behavioral disorders include fatigue, depression, anxiety, and psychosis. Many of these disorders usually respond well to pharmacotherapy, which can be supplemented by psychotherapy. Cognitive and behavioral disorders can be the greatest cause of morbidity and impaired quality of life, often overshadowing seizures. Yet these problems often go unrecognized and, even when identified, are often undertreated or untreated.     

Neurologic Care of Pregnant Women with Epilepsy

Summary: Epilepsy is a common neurologic condition in women of reproductive age. Although their risks are greater than those for women in the general population, the majority of women with epilepsy have a good pregnancy outcome. An understanding of the risks and appropriate management of both the pregnancy and epilepsy in these patients is essential for their physicians. Health-care providers should discuss contraception and reproductive issues with all of their female patients with epilepsy as they enter reproductive age. Optimal care requires prepregnancy counseling, including information about contraception, dietary folate supplementation, and the risks related to pregnancy. Although antiepileptic drugs (AEDs) have been implicated as the major cause of teratogenesis in infants born to mothers with epilepsy, uncontrolled epilepsy is also associated with maternal and fetal risk. Therefore, optimal seizure control during pregnancy remains an important goal for women with epilepsy. Women with epilepsy should be counseled about breast-feeding their infants and supported in their decision. The recommendations in this article reflect those of a Practice Parameter developed by the American Academy of Neurology Quality Standards Subcommittee.     

Malformation in index pregnancy in women with epilepsy is not followed by recurrence in subsequent pregnancy

Use of antiepileptic drugs (AEDs) in pregnant women with epilepsy (WWE) is associated with an increased risk of major congenital malformations (MCM). Previous studies have suggested that WWE who had a malformation in their index pregnancy were at an increased risk of recurrence in future pregnancies. We aimed to assess the risk of recurrence of MCM in 1,616 WWE from Kerala Registry of Epilepsy and Pregnancy. The pregnancy outcome of women (n = 246) with two prospective pregnancies in the registry were analyzed. They had partial seizures with or without generalization (57.3%) or generalized seizures (42.7%). Polytherapy was used in 26.4% (index pregnancy) and 23.6% (follow‐up pregnancy). The mean dosage of AED for valproate was 498 mg/day and carbamazepine was 555 mg/day. The malformation rate in the index pregnancy was 8.5% (21/246) and in the follow‐up pregnancy was 8.9% (22/246) with only one recurrence. There was no increased risk of MCM in follow‐up pregnancy for those who had MCM in the index pregnancy (p = 0.70; OR 0.49; 95% CI 0.06–3.80). The use of any specific drug, continuation of the same drug or a change in drug therapy between two pregnancies did not alter the recurrence risk.     

Response to sequential treatment schedules in childhood epilepsy: Risk for development of refractory epilepsy

PurposeTo investigate response to sequential treatment schedules and risk of development of refractory epilepsy in childhood.MethodsAll children younger than 14 years with two or more unprovoked seizures seen at our hospital between 1994 and 2004 were included and prospectively followed. “Seizure control” was defined as a 2-year seizure-free interval without further recurrences except those related to attempts of medication withdrawal and “refractory epilepsy” as failure of >2 drugs plus >1 seizure/month for ≥18 months.Results343 Patients were included, 191 males and 152 females. Mean age at diagnosis was 4y 10 mo (SD 3 year 10 month). Mean follow-up period was 76.2 mo (SD 35.2). The probability of achieving “seizure control” was 70% and 86% at 5 and 10 years. 59% of patients were “controlled” with the first drug used. Among patients failing the first, second and third therapeutic regimen due to lack of efficacy, 39%, 23% and 12% respectively were finally “controlled” with subsequent treatment schedules Risk of development of refractory epilepsy was 8% and 12% at 6 and 10 years.ConclusionAfter failing a first drug, a significant proportion of children can still be controlled with subsequent therapeutic schedules. Only a small proportion develops refractory epilepsy.