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women with epilepsy.. treatment and special considerations
- 1. الرحيم الرحمن هللا بسم LA9/19/2020
- 3. Important considerations Contraception Reproductive disoredrs Teratogenicity Changes of AED and seizures during pregnancy.. Catamenial epilepsy LA9/19/2020
- 4. Contraception • Bi-directional effect. • 3% to 6% failure rate. • In OCP >> The progestin component is responsible for the contraceptive effect. • Enzyme inducers >> CYP3A4 induction >> lower P level. • Breakthrough bleeding (mid-cycle bleeding) is a useful sign of inadequate estrogenic effect. LA9/19/2020
- 5. LA9/19/2020
- 6. Affected .. • The progesterone-only pill (the ‘mini- pill’). • Post-coital contraception (the morning after pill). • Levonorgestrel subdermal capsules. Not affected .. • Medroxyprogesterone acetate (Depo- Provera®). (used every 10 weeks in women using enzyme-inducing AEDs, as opposed to the recommended 12-week intervals for women in the general population) • Intra-uterine contraception (coils). LA9/19/2020
- 7. Changes during pregnancy • In most women, pregnancy has no effect or a protective effect on their seizure frequency. • Best predictor of seizure recurrence >> Having a seizure disorder that was active in the year before pregnancy. • The most common cause of seizure recurrence >> Reduced plasma concentration of antiepileptic drugs and changes in antiepileptic drug metabolism. • ANN guidelines recommend checking antiepileptic drug levels at baseline before conception and monthly thereafter. LA9/19/2020
- 8. Dose adjustments Stable level Maintain efficacy Especially in women taking: lamotrigine, oxcarbazepine, levetiracetam, carbamazepine, and phenytoin. LA9/19/2020
- 10. LA9/19/2020
- 11. New-onset epilepsy • Gestational epilepsy >> a rare pattern. • Epilepsy can be the presenting symptom of many conditions associated with pregnancy: Meningiomas. Arteriovenous malformations. Ischemic stroke. Hematological diseases. Cerebral venous thrombosis. Eclampsia and pre-eclampsis. LA9/19/2020
- 12. -The cause of most new-onset seizures in the late stages of pregnancy. -Can be severe and progress rapidly to status. -Rx: magnesium sulphate: Dose >> IV infusion of 4 g over 5–15 minutes followed by an IV infusion of 1 g/hr for 24 hours. If seizures recur, an additional 2 g dose should be given by IV infusion. Pre-eclampsia • Hypertension • proteinuria • Oedema • abnormalities of hepatic function, platelets and clotting parameters Eclampsia • encephalopathy • Confusion • Stupor • focal neurological signs • Cerebral hemorrhage • seizures LA9/19/2020
- 13. Catamenial epilepsy • Def : cyclic exacerbation of seizures at certain points in the menstrual cycle that are attributed to fluctuations in their sex hormones. • Prevalence : reported in at least one-third of women with epilepsy. • Diagnosis : by using seizure diaries and charting the time of ovulation and menstruation for three cycles. If most seizures (twofold or higher) occur during one of the cycle periods, a diagnosis of catamenial epilepsy is made. • Mechanism: RULE >> estrogens are proconvulsant and progesterone anticonvulsant. LA9/19/2020
- 14. LA9/19/2020
- 15. • Treatment : -No specific treatment is approved by the FDA. -Divided into hormonal and nonhormonal. LA9/19/2020
- 16. Reproductive disorders • Polycystic ovary syndrome. • Infertility. • AEDs are known to cause endocrine side effects (ex, valproic acid) resulting in abnormalities in fertility, thyroid hormones, sexual function, and bone health. LA9/19/2020
- 17. LA9/19/2020
- 18. LA9/19/2020
- 19. References: • Hand book of epilepsy treatment – Simon D Shorvon. • Treatment of women with epilepsy – continuum 2019. 9/19/2020 LA
Editor's Notes
- Failure is 1% in general population topiramate are less potent hepatic enzyme inducers and can cause contraceptive failure at higher doses
- plasma AED concentration fluctuates during pregnancy because of several physiologic reasons, including increased renal clearance, altered hepatic absorption, increased plasma volume of distribution, and hepatic enzyme induction by steroid hormones
- Risk includes: malformations, intra uterine fetal death, neurodevelopmental adverse effects (lower IQ, language deficits, autism, and attention deficit hyperactivity disorder)
- meningiomas grow in size faster during pregnancy owing to oestrogenic stimulation. Arteriovenous malformations are also said to present more commonly in pregnancy although evidence for this is weak The risk of ischaemic stroke increases 10-fold in pregnancy. The underlying causes include arteriosclerosis, cerebral angiitis, moya-moya disease, Takayasu’s arteritis, embolic disease from a cardiac or infective source, and primary cardiac disease. Haematological diseases can also present as stroke, including sickle cell disease, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, and deficiencies in antithrombin, protease C and S, and factor V Leiden.
- charting the time of ovulation (by using basal body temperature or ovulation kits) Progesterone’s reduced metabolite, allopregnanolone, is a potent positive allosteric modulator of γ-aminobutyric acid type A (GABA-A) neurotransmission, Estradiol may potentiate seizures by increasing the density of dendritic spines and N-methyl- D-aspartate (NMDA) receptor–containing excitatory synapses in the hippocampus.