kafr El Sheikh general hospital Copy epilepsy Women with WWE Can you answer these questions 1Is epilepsy affected by menstruation and why 2What 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 ID: 735149
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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 Slide9Slide10
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.Slide33Slide34Slide35
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