By Gamal Yousof md.neurology - PowerPoint Presentation

Slide1

By Gamal Yousofmd.neurologykafr El Sheikh general hospitalCopy

epilepsy

Women with

(

(WWESlide2

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?Slide3

Epilepsy and hormonal cycleThe 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.

.Slide4

PubertyPuberty is a common time for epilepsy to start.Slide5

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 pubertySlide6

At menarche-pituitary gonadotropins (FSH and LH) and ovarian steroids (estrogen and progesterone) increase in overall concentrationSlide7

Catamenial epilepsyMenstrual cycles and periodsSome 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)Slide8

Estrogen is epileptogenicEstrogen is epileptogenic but progesterone is antiepileptic Slide9
Slide10

Catamenial epilepsyWhen women have seizures only during theirperiods and at no other time, this is calledcatamenial epilepsy. Women with catamenialepilepsy might benefit from taking an extra type

of medication during the week before and for the

first few days of their period.Slide11

patterns of Catamenial epilepsy(1-Perimenstrual (both are low2-Periovulatory(estrogen and progestrone )

3-Inadequate

luteal

phase(inadequate

progestrone

)

periovulatory

inadequate

luteal

perimenstrualSlide12

Treatment1-Increase AEDs doses2-Add acetazolamid (cidamex)3-Premenstrual BZD4-Pthers OCS natural progesterone, and estrogen receptor antagonist clomiphen, or hysterectomy and oophorectomy.Slide13

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

valproateSlide14

FertilityEpilepsy and antiepileptic drug-related changesin hypothalamic, pituitary, and gonadal hormoneshave been associated with:increased rates of infertility,anovulatory cycles,menstrual irregularity,polycystic ovaries.Slide15

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.Slide16

PCOSFor 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.Slide17

PCOSPCOS can cause– irregular or infrequent periods– weight gain– increased hair growth.– It may also make becoming pregnant moredifficultSlide18

PCOsValproate, may directly cause PCOS or indirectly lead to the disorder by causing weight gain that triggers insulin resistance, increased testosterone levels, and other reproductive abnormalitiesSlide19

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 drugsSlide20

women should notbe discouraged from becoming pregnant

the major risks to mother and

child result from loss of seizure control

an elevated risk of major congenital

malformations due to antiepileptic drug treatment

During pregnancySlide21

PregnancyThe goal of the antiepileptic drugs is to achieve good control of seizures with minimal side effects for fetus and motherAny change of AEDs should Be before getting pregnant Slide22

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, some

doctors suggest that any woman with epilepsy

who could become pregnant should take 5mg of

folic acid daily all the time.Slide23

Starting a familyFolic acidThere is some evidence, however, that folic acidcan interact with phenytoin and primidone,making them less effective.Slide24

Once your pateint get pregnantCurrent 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 during

pregnancy.Slide25

PregnancyDuring 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 complicationSlide26

PregnancyThe 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.Slide27

Pregnancy Increased incidence of IUGR, cognitive dysfunction, microcephaly and perinatal mortality (1.2 - 3 times normal). Slide28

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 drugsBecause 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.

Valproic

acid is associated with a greater incidence

of MCAs than other AEDs.Slide29

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, 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.Slide30

drugsCarbamazepine (goody)Sodium Valproate (baddy)Lamotrigine (goody/baddy)Slide31

Pregnancy• Fetal valproate syndrome results from in uteroexposure to valproic acid. It is• Characterized by a distinctive facialappearence, a cluster of minor and majoranomalies, and central nervous systemdysfunction.Slide32

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.Slide33
Slide34
Slide35

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.Slide36

Low birth weightSlide37

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.Slide38

Pregnancy• InvestigationsHigh 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 controlSlide39

The last monthsThird 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

).Slide40

Labor Slide41

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.Slide42

-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, so

long as the mother does not over-breathe when

using it, since over-breathing can trigger

seizures in some people.Slide43

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 usualSlide44

A nice girl from your nice managementSlide45

lactationSlide46

Breast-feeding• The decision whether to breast-feed is up to themother. Unless the baby is born prematurely, thesmall amount of anti-epileptic drug (AED) thatgets into breast milk is very unlikely to affect thebaby.• In prematures it is advisable to discuss breastfeedingwith your baby's paediatrician

, because

some AEDs may accumulate in the baby's body

and may cause them problemsSlide47

He searchs for his food in spite of your preventionSlide48

ContraceptionThere 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 epilepsySlide49

Barrier methods

Barrier

methods of contraception

include

condoms, diaphragms and caps. These

methods are not affected by taking AEDs.Slide50

Intrauterine devices (IUDs) andintrauterine systems (IUSs)• IUCDs (often called 'the coil').• The Mirena coil is an IUSs which contains thehormone progesterone (in a slow release formcalled levonorgestrel). Like barrier methods such

as condoms and diaphragms,

IUDs

and IUSs

are not affected by AEDs.Slide51

ContraceptionThere 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 takenSlide52

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

contraception is chosen.Slide53

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

[doses

above 200 mg/day], and

oxcarbazepine

) and

also

lamotrigine

.

-. 5 to 6 folds failure rate of OCSSlide54

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 pill

can still be unreliable.

• To be effective it is often best to use other

methods of contraception.Slide55

ContraceptivesLamotrigen is exception of EIAED LTG OCsSlide56

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

.Slide57

Sleep is forbiddenSleep for babies onlySlide58

What is Menopause?Some prefer to define menopause as a roseSlide59

but some prefer to define menopause like that Slide60

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.Slide61

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.Slide62

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 degreeSlide63

Bone health Calcium supplements are most helpful when used in conjunction with vitamin C (which promotes absorption of calcium) and vitamin DSlide64

اميرة Advice for pregnancy for missOne 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?Slide65

مروةmiss 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 pregnancySlide66

مروةmiss Had 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?Slide67

Antiepileptic Drug Effects on OralContraceptivesAntiepileptic 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