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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finding the most appropriate contraceptive method for retarded or developmentally delayed young people poses a tremendous challenge to family planning nurse practitioners. Retarded young people have the same sex drive and are influenced by the same pressures affecting sexual decision making as every adolescent. The crucial difference is the retarded person's lack of appropriate information about physical and emotional changes of adolescence, sexuality, and birth control. Since retarded teenagers struggle to be accepted, they tend to be compliant and thus vulnerable to sexual exploitation. Parents are generally more concerned about sexuality in retarded daughters than sons, and many request to have their child sterilized. Mentally retarded teens usually lack the motor skills and motivation to use barrier methods consistently. Long-acting injectable contraceptives such as Depo-Provera offer the greatest protection against pregnancy and have the highest satisfaction rate among parents and caretakers of retarded young people; however, side effects can include depression and weight gain. If hormonal contraception is selected, its effects on seizure activity must be carefully evaluated. In addition, may epileptic teens may be on anticonvulsants or other medications that interfere with the effectiveness of hormonal methods. Sterilization must be approved by the courts and is difficult to obtain if a young woman demonstrates enough comprehension and competence to one day marry and have a family.
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PMID:Physically, mentally disabled teens require special contraceptive care. 1226 27

Norplant, Depo-Provera, and the progestin-only pill are good for 35-50 year old women, since they are safe and have low failure rates. A beneficial feature of progestin-only contraceptives is the lack of thrombotic complications. They are good for couples considering sexual sterilization. Neither antibiotics nor antiseizure medicines reduce Depo-Provera's effectiveness. The only drug which reduces its effectiveness is aminoglutethimide (Cytadren), used to suppress adrenal function in some people with Cushing syndrome. Research indicates that Depo-Provera even reduces the frequency of seizures. Antiseizure medicines (except valproic acid) and the antibiotic, rifampin, greatly reduce the effectiveness of Norplant to prevent pregnancy. Antiseizure drugs increase hepatic enzymes, resulting in the breakdown of levonorgestrel. In those cases where women who already have Norplant need an antiseizure drug or rifampin, family planning practitioners should advise them to use another contraceptive. Many women using Depo-Provera experience amenorrhea (30-50% at 1 year, 70% at 2 years, and 80% at 5 years), but most find it to be a benefit. The most undesirable side effect of Depo-Provera is weight gain (5.4-16.5 lbs. after 1-6 years use, respectively), likely due to increased appetite. Women who use Norplant for 5 years gain on average a little less than 5 lbs. Once a woman is injected with Depo-Provera, she cannot immediately discontinue it, and its effects cannot be stopped. It takes 6 to 8 months to clear the body. Only 2 women have experienced anaphylactic reactions to Depo-Provera. Despite this rare event, it is important for practitioners to have epinephrine, steroids, and diphenhydramine to treat severe allergic reactions. A study finds reduced bone density among longterm Depo-Provera users, but it did not match for parity or smoking and did not determine bone density prior to injections of Depo-Provera. Further research on bone density and progestin-only contraceptives is needed.
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PMID:Ask the experts: progestin-only contraceptives. 1228 99

Anticonvulsant drugs used to treat epilepsy have been linked to an increased risk of birth defects among infants of epileptic mothers. Thus, effective contraception for epileptic women is especially important. Copper IUDs, voluntary sterilization, and correct use of barrier methods have been suggested. Most hormonal methods raise concerns, however. Some antiepileptic drugs (e.g., phenytoin, phenobarbital, carbamazepine, and paramethadione) may cause more rapid metabolism of the progestin or estrogen component of combined oral contraceptives. This, in turn, may reduce contraceptive effectiveness, resulting in pregnancy and exposure of the fetus to the potential teratogenic properties of the anti-seizure drug. Since anticonvulsant drugs also speed the metabolism of levonorgestrel, Norplant is not recommended for epileptic women. Depo-Provera is an appropriate method for epileptic women and may reduce seizure frequency.
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PMID:Epilepsy drugs may reduce method effectiveness. 1229 55

To determine whether maintained estrogen or progesterone levels affect kainic acid (KA) seizure patterns or the susceptibility of hippocampal neurons to death from seizures, ovariectomized Sprague-Dawley rats were implanted with estrogen pellets, 0.1 or 0.5 mg, that generated serum levels of 42.4 +/- 6.6 (mean +/- SEM) and 242.4 +/- 32.6 pg/ml or one to six capsules of progesterone that generated serum levels of 11.00 +/-.72 to 48.62 +/- 9.4 ng/ml. Seven days later, the rats were administered KA (8.5mg/kg, ip) and scored for seizure activity; 96 h later, the rats were killed and their brains processed for localization of neuron nuclear antigen (NeuN), a general neuronal marker. The hippocampus was scored for spread (the number of separate regions showing cell loss), and the area within the CA fields occupied by NeuN immunoreactivity was measured (indicating surviving neurons). Administration of estrogen or progesterone (independent of dose) significantly reduced mortality from KA seizures. Progesterone reduced seizure severity in animals that received one to four implants; compared with controls, no difference in seizure severity was noted for animals with six progesterone implants. The reduced seizures in progesterone-treated animals were accompanied by a reduction in the spread of hippocampal damage (r(2) = 0.87; P < 0.05). Likewise, in progesterone-treated rats, neuron survival and reduction in seizure scores were correlated (r(2) = 0.76; P < 0.0001). Estrogen had no effect on seizure severity (P > 0.05), but reduced both the spread (P < 0.05) and degree of neuronal loss (P < 0.05). Indeed, in the estrogen-treated rats, neuronal death was significantly lower than that observed in progesterone-treated animals with equally severe seizures (P < 0.05). These data are consistent with the hypothesis that progesterone produces its effects by reducing seizures, whereas estrogen has little beneficial effect on seizure behavior but protects the hippocampus from the damage seizures produce.
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PMID:Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment. 1282 82

Many of the biological actions of progesterone are mediated through the progesterone receptor (PR), a nuclear transcription factor. Progesterone is well recognized to protect against seizures in animal models. Although this activity has been attributed to the progesterone metabolite allopregnanolone, a GABAA receptor-modulating neurosteroid with anticonvulsant properties, PRs could also play a role. Here, we used PR knockout (PRKO(-/-)) mice bearing a targeted deletion of the PR gene that eliminates both isoforms of the PR to investigate the contribution of the PR to the anticonvulsant activity of progesterone. The protective activity of progesterone was examined in female and male homozygous PRKO mice and isogenic wild-type controls in the pentylenetetrazol (PTZ), maximal electroshock, and amygdala-kindling seizure models. In all three models, the anticonvulsant potency of progesterone was undiminished in PRKO mice compared with control mice. On the contrary, there was a substantial increase in the anticonvulsant potency of progesterone in the PTZ and kindling models. The antiseizure activity of progesterone in PRKO mice was reversed by pretreatment with finasteride, a 5alpha-reductase inhibitor that blocks the metabolism of progesterone to allopregnanolone. Unlike progesterone, the neurosteroids allopregnanolone and allotetrahydrodeoxycorticosterone exhibited comparable anticonvulsant potency in PRKO and wild-type mice. The basis for the heightened progesterone responsiveness of PRKO mice is not attributable to pharmacokinetic factors, because the plasma allopregnanolone levels achieved after progesterone administration were not greater in the PRKO mice. These studies provide strong evidence that the PR is not required for the antiseizure effects of progesterone, which mainly occurs through its conversion to the neurosteroid allopregnanolone.
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PMID:Anticonvulsant activity of progesterone and neurosteroids in progesterone receptor knockout mice. 1498 69

Of the many people that have epilepsy, only about 70% achieve seizure control with traditional pharmacotherapies. Steroids have long been known to influence ictal activity and may have a therapeutic role. This review summarizes recent investigations that have enhanced knowledge of the effects and mechanisms of gonadal, adrenal, and neuroactive steroids on seizure processes. Progesterone, which varies across reproductive cycles, pregnancy, and as a function of aging, has been shown to have anti-seizure effects among women with epilepsy and in animal models of epilepsy. Further, data suggest that progesterone's anti-seizure effects may involve its metabolism to the neuroactive steroid, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), and its subsequent actions at GABA(A) receptors. Androgens also have anti-seizure effects. Androgens' anti-seizure effects may be mediated, in part, through actions of the testosterone metabolite, and neuroactive steroid, 5 alpha-androstane-3 alpha,17 alpha-diol (3 alpha-diol) at GABA(A) receptors. Stress can alter seizure susceptibility, suggesting a role of adrenal steroids on seizure processes. In animal models of epilepsy, acute or chronic stress can increase ictal activity. Notably, stress and seizures can alter levels of gonadal, adrenal, and neuroactive steroids, which may then influence subsequent seizure activity. Thus, this review summarizes recent progress in the role of gonadal, adrenal, and/or neuroactive steroids in seizure processes which suggest that greater understanding of these steroids' effects and mechanisms may ultimately lead to improved seizure control for people with epilepsy.
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PMID:Gonadal, adrenal, and neuroactive steroids' role in ictal activity. 1505 47

Asphyxia in utero in pre-term fetuses is associated with evolving hypoperfusion of the gut after the insult. We examined the role of the sympathetic nervous system (SNS) in mediating this secondary hypoperfusion. Gut blood flow changes were also assessed during postasphyxial seizures. Preterm fetal sheep at 70% of gestation (103-104 days, term is 147 days) underwent sham asphyxia or asphyxia induced by 25 min of complete cord occlusion and fetuses were studied for 3 days afterwards. Phentolamine (10 mg bolus plus 10 mg h(-1)i.v.) or saline was infused for 8 h starting 15 min after the end of asphyxia or sham asphyxia. Phentolamine blocked the fall in superior mesenteric artery blood flow (SMABF) after asphyxia and there was a significant decrease in MAP for the first 3 h of infusion (33 +/- 1.6 mmHg versus vehicle 36.7 +/- 0.8 mmHg, P < 0.005). During seizures SMABF fell significantly (8.3 +/- 2.3 versus 11.4 +/- 2.7 ml min(-1), P < 0.005), and SMABF was more than 10% below baseline for 13.0 +/- 1.7 min per seizure (versus seizure duration of 78.1 +/- 7.2 s). Phentolamine was associated with earlier onset of seizures (5.0 +/- 0.4 versus 7.1 +/- 0.7 h, P < 0.05), but no change in amplitude or duration, and prevented the fall in SMABF. In conclusion, the present study confirms the hypothesis that postasphyxial hypoperfusion of the gut is strongly mediated by the SNS. The data highlight the importance of sympathetic activity in the initial elevation of blood pressure after asphyxia and are consistent with a role for the mesenteric system as a key resistance bed that helps to maintain perfusion in other, more vulnerable systems.
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PMID:The role of the sympathetic nervous system in postasphyxial intestinal hypoperfusion in the pre-term sheep fetus. 1507 76

Catamenial epilepsy is a menstrual cycle-related seizure disorder characterized by an increase in seizures at the time of menstruation. Catamenial epilepsy affects up to 70% of women with epilepsy. Catamenial seizures are common among women with focal or generalized epilepsy, which affects an estimated 1 million women in the United States. Presently, there is no specific, FDA-approved drug treatment for catamenial epilepsy. Despite the increased use of wide-ranging antiepileptic and hormonal drugs, catamenial seizures are often refractory to many treatments. Recent studies have provided an improved understanding of the pathophysiology of catamenial epilepsy. Cyclical changes of ovarian hormones estrogens and progesterone are now widely believed to be essential for the genesis of catamenial seizures. Generally, progesterone has antiseizure effects, while estrogens facilitate seizure susceptibility. The progesterone metabolite allopregnanolone has been identified as a key endogenous neurosteroid with powerful antiseizure activity. Allopregnanolone is a potent, positive allosteric modulator of GABA(A) receptors. Progesterone and allopregnanolone exposure and withdrawal affects GABA(A) receptor plasticity. In animal models, withdrawal from chronic progesterone and, consequently, of allopregnanolone levels in brain, has been shown to increase seizure susceptibility. Natural progesterone therapy is proven to be effective in women with epilepsy. Consequently, synthetic neurosteroids that are devoid of hormonal side effects represent a novel class of antiepileptic drugs for women with catamenial epilepsy. Our studies suggest that ganaxolone, a GABA(A) receptor-modulating synthetic neuroactive steroid, is a particularly promising treatment for catamenial epilepsy. Future studies are clearly warranted to determine the molecular pathophysiology and an effective treatment of catamenial epilepsy.
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PMID:Pharmacology of catamenial epilepsy. 1553 44

Catamenial epilepsy is a menstrual cycle-related seizure disorder that affects up to 70% of women with epilepsy. Catamenial epilepsy is characterized by an increase in seizures during particular phases of the menstrual cycle. Three distinct patterns of catamenial epilepsy - perimenstrual, periovulatory, and inadequate luteal phase - have been described. Currently, there is no specific treatment for catamenial epilepsy. The molecular mechanisms involved in the pathophysiology of catamenial epilepsy are not well understood. Recent studies suggest that cyclical changes of ovarian hormones estrogens (proconvulsant) and progesterone (anticonvulsant) appear to play a key role in the genesis of catamenial seizures. Progesterone reduces seizure susceptibility partly through conversion to neurosteroids such as allopregnanolone, which enhances GABA(A) receptor function and thereby inhibits neuronal excitability. In animal models, withdrawal from chronic progesterone and, consequently, of allopregnanolone levels in brain, has been shown to increase seizure susceptibility. Natural progesterone therapy has proven effective in women with epilepsy. Moreover, neurosteroids have been shown to be very effective inhibitors of catamenial seizures in animal models. Thus, synthetic neuroactive steroids, such as ganaxolone, which are orally active and devoid of hormonal side effects, represent a novel treatment strategy for catamenial epilepsy. However, their clinical efficacy in catamenial epilepsy has yet to be explored. A greater understanding of the molecular mechanisms is clearly needed for designing effective treatment and prevention strategies of catamenial epilepsy in women at risk.
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PMID:Role of neurosteroids in catamenial epilepsy. 1557 99

Progesterone has antiseizure effects, which may be due to the actions of its 5alpha-reduced metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP). Whether metabolism of progesterone to 3alpha,5alpha-THP in the hippocampus is essential for its antiseizure effects was investigated. In Experiment 1, ovariectomized rats were administered subcutaneous progesterone (500 microg) or vehicle (sesame oil), followed 1 hour later by subcutaneous administration of an inhibitor of the 5alpha-reductase enzyme, finasteride (50 mg/kg), or vehicle (90% sesame oil, 10% ethanol). Administration of progesterone increased the latency to, and decreased the number of, tonic seizures and increased hippocampal 3alpha,5alpha-THP levels, compared with vehicle. Administration of finasteride with progesterone attenuated progesterone's antiseizure effects and decreased levels of 3alpha,5alpha-THP in the hippocampus. Finasteride administration alone did not alter ictal behavior or 3alpha,5alpha-THP levels compared with vehicle. In Experiment 2, ovariectomized rats were administered subcutaneous progesterone (500 microg) or vehicle (sesame oil), followed 1 hour later by bilateral infusions of finasteride (10 microg) or vehicle (beta-cyclodextran) into the hippocampus. Administration of finasteride to the hippocampus of progesterone-primed rats significantly increased ictal activity and decreased hippocampal 3alpha,5alpha-THP levels, compared with progesterone administration alone. These data suggest that formation of 3alpha,5alpha-THP in the hippocampus is important for progesterone's antiseizure effects.
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PMID:Attenuating 5alpha-pregnane-3alpha-ol-20-one formation in the hippocampus of female rats increases pentylenetetrazole-induced seizures. 1571 Feb 96


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