Over the past decade, there has been a proliferation of new therapies for the treatment of epilepsy. Faced with this growing list of options, clinicians must decide what therapy, or combination of ...therapies, is best for a given individual. Although controlled clinical trials exist for each treatment option, the answer to these questions may remain unclear. In 2000, a survey of expert opinion was done to address questions concerning which treatment options might be best in a number of clinical situations. We surveyed a group of US epileptologists again in 2004 and compared the results of the two surveys.
We sent a questionnaire on the treatment of adolescent and adult epilepsy syndromes to a group of opinion leaders in the field of epilepsy. The questions were formatted to simulate real-world clinical situations in the treatment of symptomatic localization related epilepsy (SLRE) and idiopathic generalized epilepsy (IGE). The experts were asked to rate treatment options based on a modified RAND 9-point scale (with “9” most appropriate and “1” least appropriate). Statistical analysis of data was performed as defined by the expert consensus method. The results were used to develop user-friendly recommendations concerning overall treatment strategies and choice of specific medications.
Of the 48 experts to whom the survey was sent, 43 (90%) responded; 29 (67%) of the respondents had also participated in the first survey. For initial monotherapy for IGE (generalized tonic-clonic GTC, absence, and myoclonic seizures), valproate was rated as treatment of choice. For IGE-GTC seizures, lamotrigine and topiramate were also identified as usually appropriate for initial monotherapy. For IGE-absence seizures, ethosuximide was also a treatment of choice, and lamotrigine was usually appropriate. For SLRE, the experts were again asked to rate treatment options based on seizure type: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized tonic-clonic seizures (SGTC). In SLRE-SPS and SLRE-SGTC, carbamazepine and oxcarbazepine were treatments of choice, with lamotrigine and levetiracetam also usually appropriate. In SLRE-CPS, carbamazepine, lamotrigine. and oxcarbazepine were treatments of choice, while levetiracetam was also usually appropriate. For women who are pregnant or trying to conceive, lamotrigine was treatment of choice for both syndrome types. In the elderly, whether medically stable or ill, the treatment of choice was lamotrigine, while levetiracetam was also usually appropriate (along with gabapentin for persons with comorbid medical illness). In persons with HIV and epilepsy, lamotrigine and levetiracetam were usually appropriate. In people with both epilepsy syndromes who have depression, lamotrigine was treatment of choice. In a person with seizures and renal disease, lamotrigine was usually appropriate for both syndromes, with valproate also usually appropriate for IGE. In patients with hepatic disease, levetiracetam and lamotrigine were usually appropriate for IGE; in SLRE, levetiracetam was treatment of choice, with gabapentin also usually appropriate.
Although the panel of experts reached consensus on many treatment options, there are limitations to these types of data. Despite this, the expert consensus method concisely summarizes expert opinion, and this opinion may be helpful in situations in which the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.
Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior ...cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.
Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ...ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols.
Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued.
Three groups were studied: (1) normal controls, (2) subjects with coryzal symptoms and (3) adult patients with chronic lung disease who were admitted to hospital with an infective exacerbation. Each group received oxygen therapy, NIV using a vented mask system and a modified circuit with non-vented mask and exhalation filter, and nebulised saline. The patient group had a period of standardised chest physiotherapy treatment. Droplet counts in mean diameter size ranges from 0.3 to > 10 µm were measured with an counter placed adjacent to the face and at a 1-m distance from the subject/patient, at the height of the nose/mouth of an average health-care worker.
NIV using a vented mask produced droplets in the large size range (> 10 µm) in patients (p = 0.042) and coryzal subjects (p = 0.044) compared with baseline values, but not in normal controls (p = 0.379), but this increase in large droplets was not seen using the NIV circuit modification. Chest physiotherapy produced droplets predominantly of > 10 µm (p = 0.003), which, as with NIV droplet count in the patients, had fallen significantly by 1 m. Oxygen therapy did not increase droplet count in any size range. Nebulised saline delivered droplets in the small- and medium-size aerosol/droplet range, but did not increase large-size droplet count.
NIV and chest physiotherapy are droplet (not aerosol)-generating procedures, producing droplets of > 10 µm in size. Due to their large mass, most fall out on to local surfaces within 1 m. The only device producing an aerosol was the nebuliser and the output profile is consistent with nebuliser characteristics rather than dissemination of large droplets from patients. These findings suggest that health-care workers providing NIV and chest physiotherapy, working within 1 m of an infected patient should have a higher level of respiratory protection, but that infection control measures designed to limit aerosol spread may have less relevance for these procedures. These results may have infection control implications for other airborne infections, such as severe acute respiratory syndrome and tuberculosis, as well as for pandemic influenza infection.
Epilepsy in women Morrell, Martha J
American family physician,
10/2002, Letnik:
66, Številka:
8
Journal Article
Recenzirano
Epilepsy in women raises special reproductive and general health concerns. Seizure frequency and severity may change at puberty, over the menstrual cycle, with pregnancy, and at menopause. Estrogen ...is known to increase the risk of seizures, while progesterone has an inhibitory effect. Many antiepileptic drugs induce liver enzymes and decrease oral contraceptive efficacy. Women with epilepsy also have lower fertility rates and are more likely to have anovulatory menstrual cycles, polycystic ovaries, and sexual dysfunction. Irregular menstrual cycles, hirsutism, acne, and obesity should prompt an evaluation for reproductive dysfunction. Children who are born to women with epilepsy are at greater risk of birth defects, in part related to maternal use of antiepileptic drugs. This risk is reduced by using a single antiepileptic drug at the lowest effective dose and by providing preconceptional folic acid supplementation. Breastfeeding is generally thought to be safe for women using antiepileptic medications.
Antiepileptic drugs (AEDs) were first associated with disorders of bone in both adults and children in the late 1960s. The most severe manifestations of these disorders are osteopenia/osteoporosis, ...osteomalacia and fractures. Bone disease has been described in several groups of patients receiving AEDs. Groups identified as being more vulnerable to AED-associated bone disease include institutionalised patients, postmenopausal women, older men and children. Radiological and histological evidence of bone disease is found in patients taking AEDs. Numerous biochemical abnormalities of bone metabolism have also been described. The severity of bone and biochemical abnormalities is thought to correlate with the duration of AED exposure and the number of AEDs used. In monotherapy, the AEDs most commonly associated with altered bone metabolism are phenytoin, primidone and phenobarbital (phenobarbitone). To date there have been no reports of altered bone metabolism in individuals receiving the newer anticonvulsants (specifically lamotrigine, topiramate, vigabatrin and gabapentin). The mechanisms of AED-associated bone disease are not clearly elucidated; however, several theories have been proposed to explain the link. No definitive guidelines for evaluation or treatment have yet been determined.
A review of literature referable to management issues for women with epilepsy (WWE) was undertaken for the development of a practice parameter.
Epilepsy is a common neurologic condition with ...gender-related management implications. Although reviews of this topic often focus on pregnancy-related issues for WWE, specific health concerns for WWE are present throughout all phases of reproductive life.
An OVID MEDLINE literature search was conducted for 1965 to 1997 using the following key words/phrases and cross referencing: epilepsy/ seizures and pregnancy, anticonvulsants, antiepileptic drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic acid, vitamin K, metabolic bone disease, and breast-feeding.
Pregnancy outcome literature for WWE spans several decades. Methodology varies and interpretation is complicated by modern management strategies. Contributions of socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to adverse pregnancy outcomes have not been clearly delineated. There is a biologic basis for recommendations concerning contraception, folate supplementation, vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial epilepsy, and reproductive endocrine disorders, but no outcome studies afford a strong evidence base for practice recommendation.
WWE face health issues for which there is no available outcome literature to guide decision making. The urgent need for studies in many of these areas is highlighted by expanded treatment options with new AEDs and epilepsy surgery.
Antiepileptic drugs (AEDs) may have adverse effects on bone mineral density (BMD) and metabolism. We previously reported biochemical evidence of increased bone turnover in premenopausal women with ...epilepsy on phenytoin monotherapy compared with those on carbamazepine, lamotrigine, and valproate. We therefore hypothesized that rates of bone loss would be higher in young women treated with phenytoin.
Ninety-three premenopausal women with epilepsy receiving a single AED (carbamazepine, lamotrigine, phenytoin, or valproate) participated. Subjects completed nutritional and physical activity questionnaires. Biochemical indices of bone and mineral metabolism and BMD of the proximal femur and lumbar spine were measured at baseline and 1 year.
Participants reported high calcium intake (>1,000 mg/day) and were physically active. Significant loss (2.6%) was seen at the femoral neck in the phenytoin group. BMD remained stable in the other AED groups. Bone turnover markers and calciotropic hormones were unchanged after 1 year in all groups except for a significant decline in urine N-telopeptide in the phenytoin group. In women receiving phenytoin, lower serum 25-hydroxyvitamin D concentrations were associated with higher parathyroid hormone, bone alkaline phosphatase, and urine N-telopeptide levels, a biochemical pattern consistent with secondary hyperparathyroidism and increased remodeling.
In this study, young women treated with phenytoin had significant femoral neck bone loss over 1 year. In contrast, those treated with carbamazepine, lamotrigine, and valproate did not have detectable adverse effects on bone turnover or bone mineral density. These results raise concerns about the long-term effects of phenytoin monotherapy on bone in young women with epilepsy.
As new antiepileptic drugs (AEDs) become available, physicians will define their appropriate use in particular patient populations. For women, the issues include gender-specific efficacy and ...tolerability, including the impact of the AED on reproductive health. Women with epilepsy who are treated with established AEDs appear to be at risk for compromised bone health, for disturbances in fertility, menstrual cyclicity, ovulatory function, and sexuality and, with some AEDs, for failure of hormonal contraception. Finally, pregnancy outcome may be adversely affected by the established AEDs, all of which are human teratogens. Felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were reviewed. The preclinical development process had not addressed all the issues of concern to women. Although gender-specific efficacy is routinely evaluated, impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM, and VGB have similar efficacy in women and men. It is not known whether the new AEDs will affect bone health, fertility, the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and probably VGB do not interfere with hormonal contraception. Whether these new AEDs are good choices for the pregnant woman with epilepsy awaits further experience in human pregnancy. However, animal reproductive toxicology studies appear promising. The limited number of human pregnancy exposures do not, thus far, signal a significant number or particular type of adverse outcomes. However, only with improved postmarketing surveillance can essential information about teratogenic effects by acquired in an acceptably short time.
Epilepsy is a common neurologic disorder affecting women during the reproductive years. Seizures and some antiepileptic drugs (AEDs) can compromise reproductive health, and some AEDs can adversely ...affect carbohydrate and bone metabolism. Women with epilepsy have lower birth rates and more frequent anovulatory menstrual cycles. This appears to be related to seizure‐ and AED‐associated reproductive endocrine disturbances. Carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PB) induce hepatic cytochrome P450 enzymes and lower endogenous estrogens, adrenal and ovarian androgens, and contraceptive steroids. Valproate (VPA) inhibits steroid hormone metabolism, elevates androgens, and predisposes to phenotypic signs of hyperandrogenism‐hirsutism, obesity, acne, and frequent anovulatory cycles. VPA is associated with weight gain, probably by altering insulin metabolism. CBZ, PHT, and VPA, but not lamotrigine (LTG), are associated with lower levels of calcium. PHT, but not VPA or LTG, appears to accelerate bone turnover. AED effects on bone mineral metabolism may explain the elevated risk of fracture described in women with epilepsy. Prospective pregnancy registries are beginning to provide information about AED‐associated teratogenesis. The North American Antiepileptic Drug Pregnancy Registry reports a 12% rate of major malformations after first trimester exposure to PB and an 8.6% rate after first trimester exposure to VPA. A prospective LTG‐specific registry reports a 1.8% chance of major malformations after the first trimester. The registries will continue to release information as data become significant. In the meantime, practitioners can be alert to signs and symptoms of reproductive or metabolic health disturbances and participate in pregnancy registry efforts.
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. Ann Neurol 2005;57:252–257
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