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Biomedical subjects

Alison M Pack

Publications and source records attributed to Alison M Pack.

10 recordsLinked to original sources

Therapy insight: clinical management of pregnant women with epilepsy.

In pregnant women with epilepsy who are being treated with antiepileptic drugs (AEDs), careful clinical management is vital because seizure frequency can change during pregnancy, and both seizure activity and AED treatment can have consequences for the developing fetus. Complications of epilepsy and AED treatment include stillbirths, prematurity, low birth weight, major and minor malformations, and cognitive delay later in life. Certain AEDs probably have more adverse effects than others; data from prospective studies indicate that phenobarbital and valproate are associated with significant increases in major malformations, and retrospective studies show lower verbal IQs and greater need for extra assistance in school for children whose mothers received valproate during pregnancy. Monitoring of AED levels and dosage adjustment are warranted throughout pregnancy, and vitamin K(1) at a dose of 10 mg/day should be given in the last month, particularly when cytochrome P450 enzyme-inducing AEDs are being administered. In the postpartum period, breastfeeding is recommended; however, there is differential transfer of individual AEDs in breast milk, and the infant should be observed clinically. For all women of reproductive age, preconceptual counseling is important, and includes optimization of the AED regimen and advising the mother to take supplemental folic acid.

Abnormalities, Drug-Induced↗

Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy.

Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.

Adolescent↗

Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs.

Women with epilepsy are believed to be at risk for sexual dysfunction. Disorders of sexual desire and sexual arousal, including dyspareunia, vaginismus, and lack of lubrication, affect an estimated 30 to 60% of women with epilepsy. In this study, 57 reproductive-aged women with either localization related (LRE) or primary generalized epilepsy (PGE) on antiepileptic drug (AED) monotherapy and 17 nonepileptic controls completed questionnaires examining sexual experience, arousability, anxiety, and symptoms, as well as an inventory of depression. An endocrine assessment was performed during the early follicular phase of the menstrual cycle. Sexual dysfunction was more common in women with LRE, in women receiving phenytoin, in women with low levels of estradiol and dehydroepiandrosterone sulfate, and in women with self-reported symptoms of mild depression. The mechanisms of sexual dysfunction in women with epilepsy are multifactorial, but AED choice appears to be one cause that is modifiable.

Adolescent↗

Epilepsy and common comorbidities: improving the outpatient epilepsy encounter.

Epilepsy is a chronic disorder that has been associated with other specific health problems. Evidence from recent clinical and basic investigations indicates that aspects of cerebral dysfunction associated with a lowered seizure threshold may also predispose toward other disorders such as depression, cognitive impairment, sleep disorders, and migraine. Similarly, certain types of brain injury may also increase the risk of adverse antiepileptic drug (AED) effects. For example, a history of febrile seizures is associated with a three fold increase in the occurrence of negative psychiatric effects of two newer AEDs. Poor fitness and obesity are also reported at higher rates in epilepsy. Some comorbid conditions in epilepsy, such a depression and anxiety, may have a greater influence on subjective health status than does seizure rate. Management strategies employed in the outpatient clinic to maximize overall health outcomes should include screening and treatment for the commonly coexistent conditions in persons with epilepsy.

Comorbidity↗

Bone disease in epilepsy.

Recent literature demonstrates an association between antiepileptic drugs (AEDs) and bone disease. Decreased bone mineral density (BMD) has been found in adults and children receiving both enzyme-inducing AEDs and valproate, which is an enzyme-inhibiting AED. Biochemical abnormalities include hypocalcemia, elevated parathyroid hormone, and elevated markers of bone formation and resorption. Although patients in earlier studies had evidence of decreased vitamin D, low BMD has been found to be independent of abnormal vitamin D chemistries in more recently published studies. Multiple mechanisms have been postulated to explain AED-associated bone disease, but no single mechanism fully explains all the abnormalities seen. Therapies are available for bone disease. However, few studies have evaluated the effects of treatment in bone disease associated with AEDs.

Anticonvulsants↗

Epilepsy and bone health in adults.

Adults taking antiepileptic drugs (AEDs) have an augmented risk for osteopenia and osteoporosis because of abnormalities of bone metabolism associated with AEDs. The increased fracture rates that have been described among patients with epilepsy may be related both to seizures and to AEDs. The hepatic enzyme-inducing AEDs phenytoin, phenobarbital, and primidone have the clearest association with decreased bone mineral density (BMD). Carbamazepine, also an enzyme-inducing drug, and valproate, an enzyme inhibitor, may also adversely affect bone, but further study is needed. Little information is available about specific effects of newer AEDs on bone. Physicians are insufficiently aware of the association between AEDs and bone disease; a survey found that fewer than one-third of neurologists routinely evaluated AED-treated patients for bone disease, and fewer than 10% prescribed prophylactic calcium and vitamin D. Physicians should counsel patients taking AEDs about good bone health practices, and evaluation of bone health by measuring BMD is warranted after 5 years of AED treatment or before treatment in postmenopausal women.

Adult↗

Bone disease associated with antiepileptic drugs.

Antiepileptic drugs (AEDs) are associated with bone disease. Early reports found rickets in children and osteomalacia in adults, but those reports were primarily in institutionalized persons. Studies in ambulatory adults and children taking AEDs do not reveal rickets or osteomalacia but do report abnormalities in biochemical indexes of bone mineral metabolism and density. In addition, fracture rates are increased in AED-treated patients. AEDs that induce the cytochrome P450 enzyme system are most commonly associated with abnormalities in bone. Emerging data suggest that valproate, an enzyme inhibitor, may also affect bone, and there is limited information on the newer AEDs. Several theories on the mechanism of AED-associated bone disease have been proposed, but no single one explains all the reported findings. Identifying AED-treated patients who are at risk for or have bone disease is important, as multiple therapies are available.

Adult↗

Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs.

Antiepileptic drug (AED) use is identified as being associated with increased fracture risk. AEDs commonly associated with osteopathies are inducers of the hepatic cytochrome p450 enzyme system (EIAEDs). We performed a retrospective cross-sectional study assessing bone mineral density (BMD) in an adult outpatient population receiving EIAEDs. Patients were routinely referred for dual-energy X-ray absorptiometry to evaluate BMD. BMD was measured at the femoral neck of hip and lumbar spine. Results were presented as absolute BMD (g/cm(2)), T score, and Z score. T and Z scores were used in this analysis. As a group, those with BMD measurements represent people with intractable epilepsy. There were no statistically significant differences found in the T or Z scores by gender; therefore all analyses combined both men and women. Significant reductions in both T and Z scores were present in men and women <50 and >or=50.

Absorptiometry, Photon↗

Treatment of women with epilepsy.

Epilepsy is equally prevalent in men and women. However, for women there are unique concerns related to hormone effects on seizures and the effects of seizures and antiepileptic drugs (AEDs) on reproductive health. Steroid hormones affect neuronal excitability and seizure frequency. Some AEDs reduce the efficacy of oral contraceptive agents, increasing the probability of unplanned pregnancies. AEDs affect bone density. AEDs may alter reproductive hormones resulting in polycystic-appearing ovaries, anovulatory cycles, and infertility. Seizure frequency may change during pregnancy, seizures may cause pregnancy complications, some AEDs are teratogenic, and many cross into breast milk. The treatment of a woman with epilepsy must consider all these issues.

Anticonvulsants↗