Behavioral outcomes in children exposed prenatally to lamotrigine, valproate, or carbamazepine.

OBJECTIVES: To evaluate adaptive behavior outcomes of children prenatally exposed to lamotrigine, valproate, or carbamazepine, and to determine if these outcomes were dose-dependent. METHODS: Data were collected from women enrolled in the North American Anti epileptic Drug (AED) Pregnancy Registry who had taken lamotrigine, valproate, or carbamazepine monotherapies throughout pregnancy to suppress seizures. The adaptive behavior of 252 exposed children (including 104 lamotrigine-exposed, 97 carbamazepine-exposed, and 51 valproate-exposed), ages 3- to 6-years-old, was measured using the Vineland-II Adaptive Behavior Scales, administered to each mother by telephone. Mean Adaptive Behavior Composite (ABC), domain standard scores for communication, daily living, socialization and motor skills, and adaptive levels were analyzed and correlated with first trimester drug dose. RESULTS: After adjusting for maternal age, education, folate use, cigarette and alcohol exposure, gestational age, and birth weight by propensity score analysis, the mean ABC score for valproate-exposed children was 95.6 (95% CI [91, 101]), versus 100.8 (95% CI [98, 103]) and 103.5 (95% CI [101, 106]) for carbamazepine- and lamotrigine-exposed children, respectively (ANOVA; p=0.017). Significant differences were observed among the three drug groups in the ABC (p=0.017), socialization (p=0.026), and motor (p=0.018) domains, with a trend toward significance in the communication domain (p=0.053). Valproate-exposed children scored lowest and lamotrigine-exposed children scored highest in every category. Valproate-exposed children were most likely to perform at a low or moderately low adaptive level in each category. Higher valproate dose was associated with significantly lower ABC (p=0.020), socialization (p=0.009), and motor (p=0.041) scores before adjusting for confounders. After adjusting for the above variables, increasing VPA dose was associated with decreasing Vineland scores in all domains, but the relationships were not statistically significant. No dose effect was observed for carbamazepine or lamotrigine. CONCLUSIONS: Unlike carbamazepine and lamotrigine, prenatal valproate exposure was associated with adaptive behavior impairments with specific deficits in socialization and motor function, along with a relative weakness in communication. Increasing valproate dose was associated with a decline in adaptive functioning. This finding of a linear dose-dependent teratogenic effect suggests that valproate should be avoided at any dose during pregnancy. However, some women with epilepsy controlled only by valproate will decide, in consultation with their provider, that the benefits of continuing valproate during pregnancy outweigh the fetal risks. Faced with difficult choices, clinicians should be supportive as these patients consider their options.

Lamotrigine dosing for pregnant patients with bipolar disorder.

OBJECTIVE: Little information is available on the need for dosage changes for lamotrigine in pregnant women with bipolar disorder. The authors present new data on serial serum levels of lamotrigine in pregnant patients on lamotrigine monotherapy. They also review the epilepsy literature on use of lamotrigine during pregnancy. METHOD: Lamotrigine serum samples were obtained from eight mother-infant pairs at different time points during pregnancy and the postpartum period. RESULTS: All of the women were taking lamotrigine throughout pregnancy. Serum-level-to-dose ratios were lower during pregnancy than the postpartum period. Lamotrigine was taken once daily in doses ranging from 100 mg to 300 mg. Three patients had an increase of 50 mg to their daily dose across pregnancy. The change in serum lamotrigine levels in the postpartum period ranged from a 30% decrease to a 640% increase compared with the first level obtained during pregnancy. Level-to-dose ratios obtained within 4 weeks after delivery reflected a mean level 402% greater than the baseline level during gestation. Compared with the third trimester, lamotrigine serum concentration increased an average of 154% within 5 weeks after delivery. The most dramatic increase in lamotrigine serum level early after delivery occurred at 1.5 weeks. The mean infant cord level was 66% of the maternal serum level at delivery. The mean breast-fed infant serum level was 32.5% of the maternal serum levels. CONCLUSIONS: The pattern of lamotrigine changes during pregnancy in these women with bipolar disorder was consistent with that described in the epilepsy literature.

Peripheral nerve disease in pregnancy.

Neuropathies during pregnancy and the postpartum period are common and are usually due to compression around pregnancy and childbirth. The most common peripheral neuropathies are Bell's palsy, carpal tunnel syndrome (CTS), and lower extremity neuropathies. Although most neuropathies are usually reversible, associated disabilities or morbidities can limit functioning and require therapy. Nerve conduction study tests and imaging should only be considered if symptoms are unusual or prolonged. Some neuropathies may be associated with preeclampsia or an inherent underlying neuropathy that increases the risk of nerve injury. All neuropathies in pregnancy should be followed as some may be persistent and require follow-up.

Neuroimaging in pregnancy: a review of clinical indications and obstetric outcomes.

OBJECTIVE: To determine indications and outcomes of pregnant women requiring neurologic imaging at a tertiary care center. METHODS: We reviewed medical records of women receiving magnetic resonance (MR) head imaging during pregnancy to determine indications for such imaging and their pregnancy outcomes. RESULTS: Between April 2007 and December 2008, 60 pregnant women presented to Brigham and Women's Hospital with severe headache or other acute neurologic complaint and underwent head imaging. Two patients were found to have significant findings considered to be neurologic emergencies: a right thalamic hemorrhage and a subarachnoid hemorrhage. Nine patients had abnormal findings not requiring immediate intervention but deeming further evaluation. Sixteen patients had abnormal findings determined to be incidental and unrelated to their indication for imaging. Thirty-three patients had unremarkable imaging studies. The most common presenting symptoms included headache (70%) and visual disturbances (48%). The most common imaging studies obtained were MR brain without contrast (87%) and MR angiography head without contrast (73%). The majority of patients (96%) delivered in the third trimester without significant complications. CONCLUSIONS: Most women who receive head imaging in pregnancy do not have adverse findings and have good obstetrical outcomes.

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.

Epilepsy cases in pregnant and postpartum women: a practical approach.

Approximately one million women with epilepsy in the United States are in their active reproductive years. Many women with epilepsy require treatment during pregnancy, and many antiepileptic drugs (AEDs) are potential teratogens. Unfortunately, many pregnancies are often not identified until after organ formation has occurred. However, most women with epilepsy will have a normal pregnancy and a favorable outcome. Effective control of maternal seizures with the least risk to the fetus is ideal, but maternal and fetal risks are still likely increased over the general population. In 2009, the American Academy of Neurology (AAN) and the American Epilepsy Society (AES) published Practice Parameter Updates on the pregnant woman with epilepsy. These guidelines reviewed medications, teratogenicity, obstetric outcomes, vitamins, breastfeeding, and other management issues in the pregnant woman with epilepsy. Through a case-based approach, these guidelines will be reviewed, and approaches to diagnosis and management of the pregnant woman with epilepsy will be discussed.

Early postpartum headache: case discussions.

Headaches are a common complaint for most women during their lifetime, including gestation and puerperium. Tension-type headaches and migraine flare-ups are the most common headache complications after delivery, but the differential diagnosis of postpartum headache is broad. The clinician must distinguish common headache syndromes from dangerous causes of postpartum headache. We will focus on early postpartum headaches in the form of case discussions that will include clinical presentation, diagnostic criteria, and treatment.

The neuroprotective role of creatine.

Significant progress has been made in identifying neuroprotective agents and their translation to patients with neurological disorders. While the direct causative pathways of neurodegeneration remain unclear, they are under great clinical and experimental investigation. There are a number of interrelated pathogenic mechanisms triggering molecular events that lead to neuronal death. One putative mechanism reported to play a prominent role in the pathogenesis of neurological diseases is impaired energy metabolism. If reduced energy stores play a role in neuronal loss, then therapeutic strategies that buffer intracellular energy levels may prevent or impede the neurodegenerative process. Recent studies suggest that impaired energy production promotes neurological disease onset and progression. Sustained ATP levels are critical to cellular homeostasis and may have both direct and indirect influence on pathogenic mechanisms associated with neurological disorders. Creatine is a critical component in maintaining cellular energy homeostasis, and its administration has been reported to be neuroprotective in a wide number of both acute and chronic experimental models of neurological disease. In the context of this chapter, we will review the experimental evidence for creatine supplementation as a neurotherapeutic strategy in patients with neurological disorders, including Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease, as well as in ischemic stroke, brain and spinal cord trauma, and epilepsy.