Abstract:Summary:Purpose: On the basis of the neuroactive properties of estradiol and progesterone and the menstrually related cyclic variations of their serum concentrations, we propose the existence of three hormonally based patterns of seizure exacerbation. Because previous reports both support and refute the concept of catamenial epilepsy, we test the hypothesis by charting seizures and menses and measuring midluteal serum progesterone levels to estimate the frequency of epileptic women with catamenial seizure exac… Show more
“…It is known that sex hormones and their metabolites can modulate the GABA-receptor complex (GRC) (38). For example, estradiol is known to inhibit GABA and to promote kindling (39) and the occurrence of seizures in both experimental and clinical settings (40). In contrast, progesterone reduces neuronal metabolism, suppresses kindling and epileptiform discharges, and decreases the occurrence of seizures (2,(40)(41)(42).…”
Summary:Purpose: To evaluate the effects of sex and estrus cycle on biphasic anticonvulsant and proconvulsant modulation of seizure threshold by morphine.Methods: The threshold for the clonic seizures (CST) induced by acute intravenous administration of γ -aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice. Estrus cycle was assessed by vaginal smears. The effect of removing circulating sex hormones was assessed by gonadectomy.Results: At baseline, diestrus females had a higher CST compared with males and estrus females. Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect. Morphine at higher doses (30 and 60 mg/kg) significantly decreased CST in males and diestrus females, with less relative effect in estrus mice. In both phases, morphine exerted stronger effects in males compared with females. Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine.Conclusions: The biphasic modulation of seizure threshold is subject to both constitutive sex differences in sensitivity to morphine and hormonal fluctuations during the estrus cycle.
“…It is known that sex hormones and their metabolites can modulate the GABA-receptor complex (GRC) (38). For example, estradiol is known to inhibit GABA and to promote kindling (39) and the occurrence of seizures in both experimental and clinical settings (40). In contrast, progesterone reduces neuronal metabolism, suppresses kindling and epileptiform discharges, and decreases the occurrence of seizures (2,(40)(41)(42).…”
Summary:Purpose: To evaluate the effects of sex and estrus cycle on biphasic anticonvulsant and proconvulsant modulation of seizure threshold by morphine.Methods: The threshold for the clonic seizures (CST) induced by acute intravenous administration of γ -aminobutyric acid (GABA)-antagonist pentylenetetrazole (PTZ) was assessed in male and female mice. Estrus cycle was assessed by vaginal smears. The effect of removing circulating sex hormones was assessed by gonadectomy.Results: At baseline, diestrus females had a higher CST compared with males and estrus females. Morphine at lower doses (0.5-3 mg/kg) had a significant anticonvulsant effect in males and estrus females compared with that in vehicle-treated controls, whereas female mice in diestrus phase showed a relative subsensitivity to this effect. Morphine at higher doses (30 and 60 mg/kg) significantly decreased CST in males and diestrus females, with less relative effect in estrus mice. In both phases, morphine exerted stronger effects in males compared with females. Ovariectomy brought the baseline CST to the male level and resulted in significant expression of both phases of morphine effect but did not abolish the sex difference in responsiveness to morphine.Conclusions: The biphasic modulation of seizure threshold is subject to both constitutive sex differences in sensitivity to morphine and hormonal fluctuations during the estrus cycle.
“…Thus, it has been suggested that women with epilepsy, who have an increase in seizures during the periovulatory period of their menstrual cycle (Catamenial Epilepsy, Type I; [147]) might do so because of the rapid rise in estradiol before ovulation. It is also possible, although less commonly discussed, that seizures that occur during the perimenstrual period could be due to an elevation of estradiol, because estradiol does increase during the luteal phase and this could elevate BDNF.…”
Section: Epilepsymentioning
confidence: 99%
“…It is also possible, although less commonly discussed, that seizures that occur during the perimenstrual period could be due to an elevation of estradiol, because estradiol does increase during the luteal phase and this could elevate BDNF. Alternatively, and more widely accepted, is the view that waning progesterone at the time of menses leads to a disinhibition, and this lack of inhibition leads to increased seizure frequency [147].…”
In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy.
“…However, in addition to the finding that the HCs were less likely than the LCs to have complex partial seizures, it is also worth noting that there was a trend for greater proportion of women in the LC than HC group to report menstruation as a seizure precipitant ( 2 ס 2.91, df 1, p ס 0.088). Herzog et al (33), reviewing classifications of catamenial epilepsy, suggested that about a third of women with intractable complex partial seizures have seizures related to their menstrual cycle. It is possible that this biologic relationship between complex partial seizures and menstruation makes them seem less controllable.…”
Summary:Purpose: To define behaviours and to identify psychological, demographic, and epilepsy-related variables associated with high as opposed to low perceived self-control of seizures.Method: In a semistructured interview, 100 adults with intractable seizures were asked about their seizure precipitants and attempts at self-control of seizures. They also completed four psychological questionnaires. Latent Class Analysis was used to analyse the interview data to create two groups, High Controllers and Low Controllers, who were then compared on demographic, epilepsy, and psychological characteristics.Results: Being able to identify and seeking out low-risk-forseizure situations, avoiding high-risk-for-seizure situations, and making attempts at seizure inhibition were seizure behaviours that discriminated High from Low Controllers. The general probability of being a High Controller was greater than that of being a Low Controller. Perceived high self-control of seizures was associated with low chance-health locus of control. For Low Controllers, current age, age at onset of seizures, and duration of epilepsy history were related to psychological variables. A significantly higher proportion of the Low Controllers than High Controllers were women.Conclusions: Many people with intractable seizures do not accept their epilepsy as a condition over which they have no control. Perceived self-control of seizures, however, involves a complex interaction between epilepsy and psychological factors, with health locus of control an apparently important discriminator between High and Low Controllers.
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