BY GAMAL YOUSOFMD.NEUROLOGY

KAFR EL SHEIKH GENERAL HOSPITAL

COPY

epilepsy Women with((WWE

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?

Epilepsy and hormonal cycle

The hormones estrogen and progesterone areproduced in a woman's body at puberty.

•There are times in a woman's life when changesin hormone levels and hormone balance happen:

–during her periods, –during pregnancy

–throughout the menopause..

Puberty

Puberty is a common time for epilepsy to

start.

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 absence and benign rolandic epilepsy may remit at puberty

At menarche

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

Catamenial epilepsyMenstrual cycles and periods

Some women find their seizures often happenjust before and during their period .

Others may find their seizures regularly occur at another particular time during their cycle, such as at cycle (ovulation)

Estrogen is epileptogenic

Estrogen is epileptogenic but progesterone is

antiepileptic

Catamenial epilepsy

When women have seizures only during theirperiods and at no other time, this is calledcatamenial epilepsy. Women with catamenialepilepsy might benefit from taking an extra typeof medication during the week before and for thefirst few days of their period.

patterns of Catamenial epilepsy

(1-Perimenstrual (both are low2-Periovulatory(estrogen and progestrone )

3-Inadequate luteal phase(inadequate progestrone)

periovulatory

inadequate luteal

perimenstrual

Treatment

1-Increase AEDs doses2-Add acetazolamid (cidamex)

3-Premenstrual BZD4-Pthers OCS natural progesterone, and

estrogen receptor antagonist clomiphen, or hysterectomy and oophorectomy.

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 epilepsyor to AED treatment, particularly with valproate

Fertility

Epilepsy and antiepileptic drug-related changesin hypothalamic, pituitary, and gonadal hormoneshave been associated with:increased rates of infertility,anovulatory cycles,menstrual irregularity,polycystic ovaries.

polycystic ovarian syndrome

Polycystic ovarian syndrome is widely believed to be common in women with epilepsy, but the actual prevalence and the pathogenesis of PCOS in thispopulation are disputed.

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.

PCOS

PCOS can cause –irregular or infrequent periods

–weight gain –increased hair growth.

–It may also make becoming pregnant moredifficult

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

Preconception Starting a family

•Pre-conception counselling

•Risks during pregnancy, associated with epilepsy and anti-epileptic drugs

•Risks of major congenital malformations relatedto specific anti-epileptic drugs

women should notbe discouraged from becoming pregnant

the major risks to mother andchild result from loss of seizure control an elevated risk of major congenital

malformations due to antiepileptic drug treatment

During pregnancy

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

Starting a familyFolic acid

•Folic acid supplements of 800umg up to 5mg a day should bebtaken by 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, somedoctors suggest that any woman with epilepsywho could become pregnant should take 5mg offolic acid daily all the time.

Starting a familyFolic acidThere is some evidence, however, that folic acidcan interact with phenytoin and primidone,MAKING THEM LESS EFFECTIVE.

Once your pateint get pregnant

Current evidence suggests that unborn babiesare only very rarely harmed by their mothers'

seizures, unless the mother falls and injures thebaby. For this reason, it is a good idea to aim tohave as few seizures as possible duringpregnancy.

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

Pregnancy

The rate of small-for-gestational-age infants wassignificantly higher, and the head circumferencewas significantly smaller in WWAE.

The frequency of major malformations was 4.8%in the 127 children of WWAE.

Pregnancy

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

Pregnancy Major Congenital Anomalies (MCA).

Children who are born to women with epilepsy have a higher risk of birth defects, probably related to inutero exposure 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 aparticular drug is difficult.

Valproic acid is associated with a greater incidenceof MCAs than other AEDs.

Pregnancy Major Congenital Anomalies (MCA) .

•VPA has been associated with a variety of majorand minor malformations, an increase in neuraltube defects, cleft lip and palate, cardiovascularabnormalities, genitourinary defects, developmentaldelay, endocrinological disorders, limb defects, andautism.

•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 VPAdose and adverse outcome.

drugsCarbamazepine (goody)

Sodium Valproate (baddy)Lamotrigine (goody/baddy)

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 majoranomalies, and central nervous system

dysfunction.

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 epoxide hydroxylase.

4-Possible genetic link between maternal epilepsy and malformations.

Specific Syndromes Of Malformations

1-Fetal Hydantoin Syndrome:11% of infants exposed will have the syndrome.

There is pre and postnatal growth deficiency, dysmorphic facies mental 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.

Low birth weight

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.

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

epilepsyis normally difficult to control

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).

Labor

Giving birth

•Epilepsy should not prevent having a normallabour and delivery.

•Anti-epileptic drugs (AEDs) should be taken asThe 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.

-Giving birth

•Epidural anaesthesia/analgesia can be used inlabour.

•Some doctors feel Pethidine is probably bestavoided as this may trigger seizures.

•Entanox, nitrous oxide and oxygen is safe, solong as the mother does not over-breathe when

using it, since over-breathing can triggerseizures in some people.

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

A nice girl from your nice management

lactation

Breast-feeding

•The decision whether to breast-feed is up to themother. Unless the baby is born prematurely, the

small amount of anti-epileptic drug (AED) thatgets into breast milk is very unlikely to affect the

baby. •In prematures it is advisable to discuss

breastfeedingwith your baby's paediatrician, because

some AEDs may accumulate in the baby's bodyand may cause them problems

He searchs for his food in spite of your prevention

Contraception

There are many different methods of contraception to prevent pregnancy.

There are no contraindications to the use of non hormonal methods of contraception in women with epilepsy

Barrier methods

Barrier methods of contraception includecondoms, diaphragms and caps. Thesemethods are not affected by taking AEDs.

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 formcalled levonorgestrel). Like barrier methods suchas condoms and diaphragms, IUDs and IUSsare not affected by AEDs.

Contraception

There is no evidence that the contraceptive pillaffects epilepsy or AEDs. But some AEDs canaffect how well the pill works. This depends onwhich AED is being taken

Contraception

.AEDs can be divided into two groups, enzyme inducing drugs and non enzyme-inducing drugs.The AED that is being taken may affect whatcontraception is chosen.

Contraception

• Non enzyme-inducing AEDs (valproate sodium,benzodiazepines, ethosuximide, andlevetiracetam) do not show any interactions withthe combined oral contraceptive pill.

.Hepatic microsomal-inducing EIAEDs (phenytoin,barbiturates, carbamazepine, topiramate [dosesabove 200 mg/day], and oxcarbazepine) andalso lamotrigine.

.-5 to 6 folds failure rate of OCS

The combined oral contraceptive pill

'• Enzyme-inducing AEDs cause the hormones inthe pill to be broken down more quickly, so thepill is less effective.• If a woman is taking an enzyme-inducing AEDshe may be given the pill with a higher amountof estrogen. Even with this higher dose, the pillcan still be unreliable.• To be effective it is often best to use othermethods of contraception.

Contraceptives

Lamotrigen is exception of EIAED

LTG OCs

The combined oral contraceptive

'Usually when a woman's estrogen levels are high, there is a higher risk of seizures happening .

But when the levels of estrogen are higher because of the pill, the risk of seizures is not higher. This is because the body gets rid of the estrogen from the pill quickly.

If bleeding happens between periods, it means that the dose of estrogen is not enough and the pill may not be reliable against becoming pregnant.

Sleep is forbidden

Sleep for babies only

What is Menopause?

Some prefer to define menopause as a rose

but some prefer to define menopause like that

Menopause

menopause can alter seizure control. Women who have had reproducible catamenial patterns are more likely to experience improved seizure control after menopause.

perimenopausal time results in erratic fluctuations in gonadal steroids, which can temporarily worsen seizures. Once hormone levels stabilize, such effects should improve, but exogenous hormones and the increasing risk of cerebrovascular disease may obscure this benefit.

Postmenopausal estrogen replacement has been reported to exacerbate seizures in some women with epilepsy.

therapy (HRT) can be of benefit to them.

Bone health

AEDs may decrease bone mineral density and result in osteopenia, osteoporosis, and fractures.

 Although these risks are present in both men and women treated with AEDs for more than several years, postmenopausal women are especially susceptible due to the added risk factor of hormonal depletion.

Bone health

Cytochrome p-450 enzyme-inducing agents (phenytoin, phenobarbital, primidone, carbamazepine) increase vitamin-D metabolism, leading to decreased calcium absorption in the intestine, and increased parathyroid hormone, causing bone calcium stores to be mobilized.

 -Reports suggest that non-enzyme-inducing AEDs, such as valproate, may also result in decreased bone mineral density, though to a lesser degree

Bone health

Calcium supplements are most helpful when used in conjunction with vitamin C (which promotes absorption of calcium) and vitamin D

Advice for pregnancy for missاميرة

One and a half years her epilepsy is well-controlled – she has had one fit only since then. She and her husband want to start a family but she has come to you for advice – should she discontinue the carbamazepine?

missمروة

Has become unexpectedly pregnant while taking AEDs. She had a coil but unfortunately it fell out. What do you tell her and what care is she offered in pregnancy

missمروةHad a successful pregnancy and in the third trimester asks your advice about the birth. She has read that people can have fits during delivery and she is worried about this, and she is also concerned about breast feeding while taking medication. How might you advise her?

Antiepileptic Drug Effects on OralContraceptives

Antiepileptic Drug Effects on OralContraceptives

•Agents that induce liver enzymes and may compromise OralContraceptive efficacy

–Carbamazepine –Felbamate –Phenytoin

–Phenobarbital –Primidone

–Oxcarbazepine –Topiramate

•Agents that do not compromise Oral Contraceptive efficacy –Gabapentin

–Levetiracetam –Lamotrigine

–Tiagabine –Valproate –Zonisamide