Transcript epilepsy and woman

Women with epilepsy
(WWE(
BY
GAMAL YOUSOF
MD.NEUROLOGY
KAFR EL SHEIKH
GENERAL HOSPITAL
COPY
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 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.
.
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 epilepsy
Menstrual 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)
Estrogen is epileptogenic
Estrogen is epileptogenic 
but progesterone is
antiepileptic
Catamenial epilepsy
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.
patterns of Catamenial epilepsy
1-Perimenstrual (both are low(
2-Periovulatory(estrogen and progestrone )
3-Inadequate luteal phase(inadequate progestrone)
inadequate luteal
periovulatory
perimenstrual
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.
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
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.
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 this
population 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 more
difficult
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 related
to specific anti-epileptic drugs
women should not
be discouraged from becoming pregnant
During pregnancy
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
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 family
Folic 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.
Starting a family
Folic acid
There is some evidence, however, that folic acid
can interact with phenytoin and primidone,
MAKING THEM LESS EFFECTIVE.
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.
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 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.
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 a
particular drug is difficult.
Valproic acid is associated with a greater incidence
of MCAs than other AEDs.
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.
drugs
Carbamazepine (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 major 
anomalies, 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
– Ultrasound High resoultion at 11-13 weeks
-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
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 normal 
labour and delivery. 
• Anti-epileptic drugs (AEDs) should be taken as 
The usual schedule during labor
-I.V or-I.M forms may be needed)BZD.PHYENTOIN)
-2-4 weeks after delivery AEDs doses may return to
normal.
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. 
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 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 
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 include
condoms, diaphragms and caps. These
methods are not affected by taking AEDs.
Intrauterine devices (IUDs) and
intrauterine 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.
Contraception
There is no evidence that the contraceptive pill
affects epilepsy or AEDs. But some AEDs can
affect how well the pill works. This depends on
which 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 what
contraception is chosen.
Contraception
• Non enzyme-inducing AEDs (valproate sodium,
benzodiazepines, ethosuximide, and
levetiracetam) do not show any interactions with
the 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 OCS
The combined oral contraceptive pill
'
• Enzyme-inducing AEDs cause the hormones in
the pill to be broken down more quickly, so the
pill is less effective.
• If a woman is taking an enzyme-inducing AED
she may be given the pill with a higher amount
of 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.
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
experience improved seizure control after menopause.
to
 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 miss ‫اميرة‬
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?
miss ‫مروة‬
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
miss ‫مروة‬
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?
Antiepileptic Drug Effects on Oral
Contraceptives
Antiepileptic Drug Effects on Oral 
Contraceptives 
• Agents that induce liver enzymes and may compromise Oral 
Contraceptive efficacy 
– Carbamazepine 
– Felbamate 
– Phenytoin 
– Phenobarbital 
– Primidone 
– Oxcarbazepine 
– Topiramate 
• Agents that do not compromise Oral Contraceptive efficacy 
– Gabapentin 
– Levetiracetam 
– Lamotrigine 
– Tiagabine 
– Valproate 
– Zonisamide 