epilepsy Women with ( (WWE

1. epilepsyWomen with((WWE By GamalYousof md.neurology kafr El Sheikh general hospital Copy

2. Can you answer these questions? 1-Is epilepsy affected by menstruation and why? 2-What to do when your patient wants to get pregnant, stop drugs ,reduce dose ,or change the drug . or what else ,how to protect the fetus? 3-How to prepare your patient for delivery. are there any precautions to do ,what? 4-Is there any care for the newborn of epileptic mother? 5-Can epileptic mother lactate her baby while she is taking AEDs?

3. Epilepsy and hormonal cycle The hormones estrogen and progesterone are produced in a woman's body at puberty. • There are times in a woman's life when changes in hormone levels and hormone balance happen: – during her periods, – during pregnancy – throughout the menopause. .

4. Puberty Puberty is a common time for epilepsy to start.

5. Menarche -Certain genetically determined epilepsies (i.e., JAE and JME) will present around puberty, -some nongenetic partial epilepsies may worsen causing them to come to medical attention at this time.  • -Childhood absenceand benign rolandic epilepsymay remit at puberty

6. Atmenarche -pituitary gonadotropins (FSH and LH) and ovarian steroids (estrogen and progesterone) increase in overall concentration

7. CatamenialepilepsyMenstrual cycles and periods Some women find their seizures often happen just before and during their period. Others may find their seizures regularly occur at another particular time during their cycle, such as at cycle (ovulation)

8. Estrogen is epileptogenic Estrogen is epileptogenic but progesterone is antiepileptic

10. Catamenialepilepsy When women have seizures only during their periods and at no other time, this is called catamenial epilepsy. Women with catamenial epilepsy might benefit from taking an extra type of medication during the week before and for the first few days of their period.

11. patterns of Catamenialepilepsy (1-Perimenstrual (both are low 2-Periovulatory(estrogen and progestrone ) 3-Inadequate luteal phase(inadequate progestrone) inadequate luteal perimenstrual periovulatory

12. Treatment 1-Increase AEDs doses 2-Add acetazolamid (cidamex) 3-Premenstrual BZD 4-Pthers OCS natural progesterone, and estrogen receptor antagonist clomiphen, or hysterectomy and oophorectomy.

13. Fertility  Fluctuations of luteinizing hormone and pulsatile release of prolactin and sex steroids have been observed in temporal relation to some seizures The most common symptoms are – hyperandrogenism, – menstrual disorders with ovulatory failure, – polycystic ovary-appearing ovaries or polycystic ovary syndrome, and hyperinsulinemia • These symptoms may be secondary to epilepsy or to AED treatment, particularly with valproate

14. Fertility Epilepsy and antiepileptic drug-related changes in hypothalamic, pituitary, and gonadal hormones have been associated with: increased rates of infertility, anovulatory cycles, menstrual irregularity, polycystic ovaries.

15. polycystic ovarian syndrome Polycystic ovarian syndrome is widely believed to be common in women withepilepsy, but the actual prevalence and the pathogenesis of PCOS in this population are disputed.

16. PCOS For women with PCOS, ova are not released and they stay in the ovary and form cysts. This syndrome also causes a higher level of the hormone testosterone than normal.

17. PCOS PCOS can cause – irregular or infrequent periods – weight gain – increased hair growth. – It may also make becoming pregnant more difficult

18. PCOs Valproate, may directly cause PCOS or indirectly lead to the disorder by causing weight gain that triggers insulin resistance, increased testosterone levels, and other reproductive abnormalities

19. Preconception Starting a family • Pre-conception counselling • Risks during pregnancy, associated with epilepsy and anti-epileptic drugs • Risks of major congenital malformations related to specific anti-epileptic drugs

20. women should notbe discouraged from becoming pregnant the major risks to mother and child result from loss of seizure control During pregnancy an elevated risk of major congenital malformations due to antiepileptic drug treatment

21. Pregnancy The goal of the antiepileptic drugs is to achieve good control of seizures with minimal side effects for fetus and mother Any change of AEDs should Be before getting pregnant

22. Starting a family Folic acid • Folic acid supplements of 800umg up to 5mg a day should bebtakenby women with epilepsy who are planning a family. • These should start before conception and be continued throughout the first three months of pregnancy. • As accidental pregnancies are common, some doctors suggest that any woman with epilepsy who could become pregnant should take 5mg of folic acid daily all the time.

23. Starting a family Folic acid There is some evidence, however, that folic acid can interact with phenytoin and primidone, making them less effective.

24. Once your pateint get pregnant Current evidence suggests that unborn babies are only very rarely harmed by their mothers' seizures, unless the mother falls and injures the baby. For this reason, it is a good idea to aim to have as few seizures as possible during pregnancy.

25. Pregnancy During pregnancy, the seizure frequency was unchanged, or the change was for the better in the majority (83%) of the patient No significant differences between Women With Active Epiepsy and controls in the incidence of preeclampsia, preterm labor, or in the rates of caesarean sections, perinatal mortality, But some said that there may be increase of the incidence of these complication

26. Pregnancy The rate of small-for-gestational-age infants was significantly higher, and the head circumference was significantly smaller in WWAE. The frequency of major malformations was 4.8% in the 127 children of WWAE.

27. Pregnancy Increased incidence of IUGR, cognitive dysfunction, microcephaly and perinatal mortality (1.2 - 3 times normal).

28. Pregnancy Major Congenital Anomalies (MCA). Children who are born to women with epilepsy have a higher risk of birth defects, probably related to inuteroexposure to antiepileptic drugs Because available evidence does not suggest that epilepsy per se is associated with a major increase in the risk of Major Congenital Anomalies (MCA). Establishing definite evidence of teratogenicity with a particular drug is difficult. Valproicacid is associated with a greater incidence of MCAs than other AEDs.

29. Pregnancy Major Congenital Anomalies (MCA). • VPA has been associated with a variety of major and minor malformations, an increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism. • Polytherapy treatment in epileptic pregnant women increases the risk of teratogenicity in offspring Always use monotherapy when possible (tegretol) • There is an established relationship between VPA dose and adverse outcome.

30. drugs Carbamazepine (goody) Sodium Valproate (baddy) Lamotrigine (goody/baddy)

31. Pregnancy • Fetal valproate syndrome results from in utero exposure to valproic acid. It is • Characterized by a distinctive facial appearence, a cluster of minor and major anomalies, and central nervous system dysfunction.

32. Teratogenicity Antiepileptic drugs (AEDs) have the potential to produce both anatomic and behavioral teratogenesis. Mechanisms: 1-Direct drug toxicity: due to accumulation of the drug metabolites which are embryotoxic. 2-Antifolate effect: Phyntoins, carbamazepine & barbiturates impair folic acid absorption. Valproic acid interferes with the production of folinic acid. 3-Genetically determined deficiency of the detoxifying enzyme epoxidehydroxylase. 4-Possible genetic link between maternal epilepsy and malformations.

35. Specific Syndromes Of Malformations 1-Fetal Hydantoin Syndrome: • 11% of infants exposed will have the syndrome. • There is pre and postnatal growth deficiency, • dysmorphicfaciesmental retardation • Facial features of the fetal hydantoin syndrome. • Note broad, flat nasal ridge, epicanthic folds, • mild hypertelorism, and wide mouth • with prominent upper lip.. 3-Barbiturates Withdrawal Symptoms Starts 1 week after birth & includes restlessness, constant crying, irritability, difficult sleeping & vasomotor instability.

36. Low birth weight

37. Withdrawal of medication?!!!!!!!!! • Should she discontinue the carbamazepine? • If seizure free for two years (all types) withdrawal can be considered • Refer to neurologist if still want to consider drug withdrawal. Need to discuss risk/benefit in detail.

38. Pregnancy • Investigations High resoultion at 11-13 weeks– Ultrasound -Serum alpha fetoprotein at 16 weeks -Second trimester ultrasonic at 18-22 weeks -Amniocentesis and measuring alpha fetoprotein to exclude anomalies – Blood levels especially in women whose epilepsy is normally difficult to control

39. The last months Third trimester -Maximum dose can be used Last month -Monitoring of serum levels of the AEDs ----Vitamin K to mother to avoid vaginal bleeding and protect the infant against hemorrhagic disease of the mothers taking hepatic enzyme-inducing drugs (phenytoin, phenobarbitone, primidone, carbamazepine and topiramate - Not necessary with sodium valproate).

40. Labor

41. Giving birth • Epilepsy should not prevent having a normal labour and delivery. • Anti-epileptic drugs (AEDs) should be taken as The usual schedule during labor BZD.PHYENTOIN))-I.V or-I.M forms may be needed -2-4 weeks after delivery AEDs doses may return to normal.

42. -Giving birth • Epidural anaesthesia/analgesia can be used in labour. • Some doctors feel Pethidine is probably best avoided as this may trigger seizures. • Entanox, nitrous oxide and oxygen is safe, so long as the mother does not over-breathe when using it, since over-breathing can trigger seizures in some people.

43. At labor Start administration of vitamin K1 for the infant, and send the cord blood for clotting studies. Management of a pregnant patient in status epilepticus: Establish the ABCs, and check vital signs. Assess the fetal heart rate. Rule out eclampsia. Administer a bolus of lorazepam (0.1 mg/kg, ie, 5-(10 mg) at no faster than 2 mg/min. (ttt as usual

44. A nice girl from your nice management

45. lactation

46. Breast-feeding • The decision whether to breast-feed is up to the mother. Unless the baby is born prematurely, the small amount of anti-epileptic drug (AED) that gets into breast milk is very unlikely to affect the baby. • In prematures it is advisable to discuss breastfeeding with your baby's paediatrician, because some AEDs may accumulate in the baby's body and may cause them problems

47. He searchs for his food in spite of your prevention

48. Contraception There are many different methods of contraception to prevent pregnancy. There are no contraindications to the use of non hormonal methods of contraceptionin women with epilepsy

49. Barrier methods Barrier methods of contraception include condoms, diaphragms and caps. These methods are not affected by taking AEDs.

50. Intrauterine devices (IUDs) andintrauterine systems (IUSs) • IUCDs (often called 'the coil'). • The Mirena coil is an IUSs which contains the hormone progesterone (in a slow release form called levonorgestrel). Like barrier methods such as condoms and diaphragms, IUDs and IUSs are not affected by AEDs.