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- Title
ASPECTE HORMONALE ALE EPILEPSIEI CATAMENIALE LA ADOLESCENTE.
- Authors
David, Dana Liana; Velea, Iulian P.; Paul, Corina
- Abstract
In ancient times, catamenial epilepsy was attributed to the moon, giving rise to the word, "lunatic" ("mooon - struck"). The word, "catamenial," derives from the Greek word katomenios, meaning "monthly." Catamenial epilepsy describes seizures that are clustered around specific points in the menstrual cycle, usually during the perimenstrual or periovulatory intervals. The diagnosis of catamenial epilepsy is based on demonstrating the temporal relationship between menstruation and seizure activity; a 2-fold or greater increase in seizure frequency during a particular phase of the menstrual cycle generally is considered as evidence of catamenial epilepsy. Catamenial seizures are associated with every type of epilepsy but are more common among women with focal epilepsy (e.g., temporal lobe epilepsy) than in those with generalized epilepsy. Their specific cause is still unclear. Puberty relative to childhood is a time of marked hormonal fluctuations. Seizures disorders become evident for the first time during puberty, whereas others remit, perhaps due to the hormonal changes occurring during puberty. Cyclic changes in estrogen and progesterone across the menstrual cycle are widely regarded as playing a central role. Estrogens generally are considered as proconvulsant, although their effects depend on the duration of treatment, dosage, the mode of administration, and the seizure model. Estrogens affect neuronal excitability via modulation of gene expression, regulation of neurotransmitter release, and direct interaction with neurotransmitter receptors. Estrogen acts on neurons within the limbic system, cerebral cortex and other regions important for seizure susceptibility. Estrogen also interacts with neurotrophins, which enhance hippocampal excitability. In women with epilepsy, seizure susceptibility correlates with the estrogen/progesterone ratio, which peaks in the premenstrual and preovulatory intervals. Although serum estradiol concentrations in girls with catamenial epilepsy are similar to those in normal controls across the menstrual cycle, evidence suggests that progesterone levels are lower and estrogen/progesterone ratios are higher. Seizure frequency decreases during the midluteal phase when progesterone levels are highest and increases in the premenstrual phase when progesterone levels fall and the estrogen/progesterone ratio increases. Progesterone generally is considered to have an anticonvulsant action, by lowering seizure susceptibility. Changes in serum progesterone levels have been correlated directly with catamenial seizures, and evidence from studies in mice supports the concept that 5a-reduced metabolites of progesterone, particularly allopregnanolone, are responsible for its antiseizure activity. Neurosteroids like allopregnanolone are synthesized locally within the brain, both de novo and from circulating steroid precursors, and modulate neural excitability. Allopregnanolone potentiates the action of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, via modulation and direct interaction with GABA-A receptors. The interactions between gonadal steroid hormones, seizures, and antiepileptic drugs are complex. Whereas gonadal steroid hormones can affect seizure susceptibility, seizures may disrupt patterns of steroid hormone secretion, and antiepileptic drugs can affect sex steroid hormone levels by altering their metabolism. In adolescents with epilepsy, the incidence of generalized tonic-clonic seizures often increases during puberty, when the levels of steroid hormones increase and menses begin. The prevalence of menstrual disorders is increased, and fertility is decreased among women with epilepsy, suggesting that seizures may predispose to reproductive dysfunction, possibly by altering the pattern of hypothalamic GnRH release. The association between epilepsy and reproductive dysfunction also might reflect the effects of antiepileptic drugs on steroid hormone metabolism. Diagnosis is confirmed by assessment of menstrual and seizure diaries and characterisation of cycle type and duration. Checking midluteal serum progesterone (21day) is important. Checking AED levels on day 22 to day 1 if the woman has perimenstrual seizure exacerbation. Some adolescent girls with epilepsy appear to be at increased risk of ovulatory dysfunction. Currently there is no specific treatment for catamenial epilepsy. Antiepileptic drugs are the mainstay for its management. However, approximately one-third of women with catamenial seizures require treatment with more than one drug, partly because catamenial epilepsy often proves refractory to conventional medications. Drugs, such as phenytoin, carbamazepine, and phenobarbital, induce hepatic cytochrome P450 enzymes, which can accelerate the metabolism of steroid hormones that share common metabolic pathways. They also can increase serum SHBG concentrations, thereby further decreasing the concentrations of free or biologically active steroids. At least in theory, gabapentin, levetiracetam, tiagabine, zonisamide, and pregabalin are attractive choices, because they do not induce hepatic enzymes. Other antiepileptic drugs, such as sodium valproate, inhibit hepatic enzymes, which may increase bioactive steroid hormone levels. Acetazolamide, a potent inhibitor of carbonic anhydrase, has been used empirically for years in the treatment of catamenial epilepsy, but there are few direct studies attesting to its effectiveness drug tolerance, requiring progressive dosage escalation, is a common problem. Hormonal therapies for the management of catamenial seizures also deserve consideration, particularly for women who prove resistant to antiepileptic drugs. Treatment with depot-medroxyprogesterone acetate in doses that typically eliminate menses (e.g., 150 mg intramuscularly every 3 months) can improve seizure control in many women. Cyclic natural progesterone also has been demonstrated effective for the treatment of catamenial seizures; 100-200 mg, administered orally or vaginally three times daily between days 15 and 28 of the cycle, decreased seizure frequency by approximately 50-75%.- Evidence from studies in animal models and clinical data suggest the anti seizure effects of progesterone derive from its metabolic conversion to neurosteroids, primarily allopregnanolone. Ganaxolone, a synthetic neurosteroid (a 3ß-methyl analog of allopregnanolone) that has shown promise in preclinical models of catamenial epilepsy and preliminary investigations in women, is now available Continuous oral contraceptives, the progestin-only minipill, and GnRH agonists with add-back estrogen/progestin therapy also have demonstrated some effectiveness in small numbers of women with catamenial epilepsy. However, there is no direct evidence linking catamenial epilepsy with specific antiepileptic drugs. Conventional antiepileptic drugs are not effective in most patients with catamenial seizures, possibly because they can alter sex steroid concentrations and metabolism. Hormonal therapies such as progesterone, oral contraceptives, and GnRH agonists, have proven efficacy. Finally, newly developed synthetic neurosteroids have shown considerable promise. The extent to which all of these competing mechanisms contribute to catamenial epilepsy remains to be determined. Conclusion: One-third of adolescent girls with epilepsy have hormone-sensitive seizures, that occurs during entering puberty and adolescent age. The role of estrogen, progesterone and endogenous neurosteroids in the etiopatology of catamenial epilepsy is clear. They are not studies that demonstrate abnormalities in hormonal dynamics that predispose to catamenial epilepsy. Various treatment approaches have been proposed. The efficacy is based on small, uncontrolled series and observations. Epilepsy, antiepileptic drugs and gonadal hormones have complex interactions. Hormones may alter seizure threshold, and change frequency and severity of seizures. Epilepsy and/or antiepileptic drugs can compromise the reproductive hormonal and sexual functions in women.
- Subjects
TEENAGE girls; EPILEPSY in adolescence; MENSTRUAL cycle; DIAGNOSIS of epilepsy; SPASMS; ESTROGEN; ANTICONVULSANTS; DISEASES
- Publication
Jurnalul Pediatrului, 2014, Vol 17, p14
- ISSN
2360-4557
- Publication type
Article