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Transcript
A 30 year-old female patient has
been maintained on phenytoin
100 mg TID for the past 5 years
with good control of her
idiopathic generalized seizure.
She is 3 months pregnant when
she visited your clinic.
MISSING DATA
• (+) / (-)
Frequency and Severity
Associated with:
•Subtherapeutic anticonvulsant levels
•Nausea and vomiting leads to missed
doses
•Expanded intravascular volume lowers
serum drug levels
•Hepatic, plasma and placental enzymes
increase drug metabolism
•Increased glomerular filtration hastens
drug clearance
• (+) / (-)
Frequency and Severity
Associated with:
•Lower seizure threshold
•“Exhaustion from sleep deprivation”
•(+) / (-) Diabetes
•(+) / (-) Hypertension
•(+) / (-) Intake of folic acid
SALIENT FEATURES
•30 year old, female
•1st trimester pregnancy
•Phenytoin 100 mg TID for the past 5
years
CLINICAL IMPRESSION
IDIOPATHIC GENERALIZED
SEIZURE DISORDER
GENERALIZED SEIZURES
GENERALIZED TONIC-CLONIC SEIZURE
• Prodromal symptoms
• Involve both hemispheres of the brain
– Occurring hours or days before a seizure
simultaneously
and may be preceded by an
– Mood changes, sleep disturbances, lightheadedness,
auraanxiety,
before
an abrupt
lossconcentrating
of consciousness
irritability,
difficulty
and,
•
rarely, an ecstatic feeling, abdominal pain, facial
pallor, or headache. Most patients lose
Strong
hereditary
component
consciousness
without
any premonitory symptoms
– Patients with generalized tonic-clonic seizures do not
have auras. An aura represents a simple partial
seizure
GENERALIZED SEIZURES
GENERALIZED TONIC-CLONIC SEIZURE
• The patient
have completelyofnonfocal
• Involve
bothmayhemispheres
the brain
findings on neurologic examination when not
simultaneously and may be preceded by an
having seizures. Seizures typically are divided
aura
before
an
abrupt
loss
of
consciousness
into tonic, clonic, and postictal phases
– Tonic phase
The tonic phase begins with flexion of the trunk and
• Strong• hereditary
component
elevation and abduction of the elbows. Subsequent
extension of the back and neck is followed by extension of
arms and legs. This can be accompanied by apnea, which
is secondary to laryngeal spasm.
GENERALIZED SEIZURES
GENERALIZED TONIC-CLONIC SEIZURE
•Autonomicboth
signs arehemispheres
common during this
• Involve
ofphase
theand brain
include increase in pulse rate and blood pressure,
simultaneously
and may be preceded by an
profuse sweating, and tracheobronchial hypersecretion
aura
before
an bladder
abruptpressure
loss ofrises,
consciousness
•Although
urinary
voiding does
not occur because of sphincter muscle contraction
•This stage lasts for 10-20 seconds
• Strong hereditary component
GENERALIZED SEIZURES
GENERALIZED TONIC-CLONIC SEIZURE
– Clonic phase
• The tonic stage
gives way
to clonic convulsive of
movements,
• Involve
both
hemispheres
the in brain
which the tonic muscles relax intermittently, lasting for a variable
period of time.
simultaneously
and may be preceded by an
• A generalized tremor occurs at a rate of 8 tremors per second,
aura
before
an
abrupt
of per
consciousness
which
may slow
down
to aboutloss
4 tremors
second. Each
•
spasm is accompanied by pupillary contraction and
dilation. Some patients may have tongue or cheek bites
• The atonic periods gradually become longer until the last spasm.
Strong
Voidinghereditary
may occur at thecomponent
end of the clonic phase as sphincter
muscles relax. The atonic period lasts about 30 seconds. The
patient continues to be apneic during this phase
• The convulsion, including tonic and clonic phases, lasts for 1-2
minutes.
GENERALIZED SEIZURES
GENERALIZED TONIC-CLONIC SEIZURE
– Postictal state
• Involve both hemispheres of the brain
• A variable period of unconsciousness during which the
simultaneously
and and
may
be preceded
patient becomes quiet
breathing
resumes. by an
aura
an abrupt
loss often
of consciousness
• Thebefore
patient gradually
awakens,
after a period of
•
stupor or sleep, and often is confused, with some
automatic behavior.
Strong
hereditary
component
• Headache
and muscular
pain are common. The patient
does not recall the seizure itself.
GENERALIZED SEIZURES
GENERALIZED TONIC-CLONIC SEIZURE
• Most both
generalized
epilepsiesof
are the brain
• Involve
hemispheres
idiopathic, but
locus
simultaneously
anda definite
may be genetic
preceded
by an
beenanfound
forloss
some
of these
aurahas
before
abrupt
of consciousness
generalized types of epilepsy.
• Strong hereditary component
HISTORY
• Unusual sensations suggesting an aura
• Seizure manifestations
SUBTYPE
MANIFESTATIONS
Absence seizure
Brief staring spells with arrest of
activity, often w/ eye fluttering,
which just last a few seconds
Myoclonic seizure
Very brief isolated body jerks
that tend to occur in the
morning
Generalized tonic-clonic
seizure
Convulsions of the whole body
lasting 1-2 minutes
HISTORY
• Ask about the first and any subsequent
seizures
• Duration
• Frequency
• Sequential evolution
• Longest & shortest interval between seizures
• Aura
• Postictal state
• Precipitating factors
HISTORY
• Risk factors
• Prior head trauma or CNS infection
• Drug use or withdrawal
• Alcohol withdrawal
• Non-adherence to anticonvulsants
• Family history of seizures or neurologic disorders
• Rare triggers
• Repetitive sounds
• Flashing lights
• Touching certain parts of the body
• Sleep deprivation
• Can lower the seizure threshold
PHYSICAL EXAM
• A bitten tongue, incontinence (eg, urine or feces in
clothing), or, in patients who have lost consciousness,
prolonged confusion, suggest seizure.
Physical examination rarely indicates
the cause when seizures are
idiopathic but may provide clues
when seizures are symptomatic.
Intellectual
functions, neurologic
exam and imaging
(MRI) are normal.
Diagnostic evaluation must
determine whether the event was a
seizure vs. pseudoseizure or
syncope.
ELECTROENCEPHALOGRAM
(EEG)
• The only definitive test to confirm the
diagnosis.
• Represents a recurrent, sudden,
excessive discharge of cortical neurons
• When abnormal, it’s very characteristic:
• Interictal symmetric bursts of 4- to
7-Hz epileptiform activity
• Interictal spike-and-wave
abnormalities without any clinical
seizure activity
ELECTROENCEPHALOGRAM OF SUBTYPES
SUBTYPE
Absence seizure
EEG CHANGES
Very characteristic
pattern wave complexes
Myoclonic seizure
Bilateral polyspike and
wave abnormality at a
rate of 4- to 6-Hz
Generalized tonic-clonic Can show either of the
seizure
above patterns or
generalized spikes
SEIZURE & PREGNANCY
• A woman with a seizure disorder can
carry a pregnancy safely.
• Seizures can harm the developing
fetus by reducing the blood supply to
the placenta.
• For most pregnant women who have
epilepsy, seizures remain the same.
For a few, seizures become less
frequent. For others — particularly
women who have poorly controlled
epilepsy — pregnancy increases the
number of seizures.
COMPLICATIONS
• Severe morning sickness
• Anemia
• Vaginal bleeding during
and after pregnancy
• Abruptio placenta
• Pre-eclampsia
• Premature baby
• LBW baby
The occurrence of seizures in the first
trimester poses the greatest risk of
congenital malformation and
developmental delay in the offspring.
For babies whose mothers take seizure
medication, the risk of birth defects is
4 to 8 percent — compared with 2 to 3
percent for all babies.
An antifolate effect on blood
and interference with vitamin K
metabolism have been reported,
for which reason pregnant women taking
phenytoin should
be given vitamin K before delivery and
the newborn infant should
receive vitamin K as well to prevent
bleeding.
The obstetrician and neurologist should
work together prior to conception and
throughout the pregnancy to closely
monitor seizures and contributing factors
(eg, sleep deprivation and medication
compliance).
AEDs & PREGNANCY
Phenytoin
• fetal hydantoin syndrome
– craniofacial anomalies, distal digital
hypoplasia, epicanthal folds,
hypertelorism, low-set ears, and
developmental delay
• mothers received phenytoin
monotherapy during pregnancy
demonstrated slightly delayed
locomotor development
Phenobarbital
• fetal hydantoin syndrome and
fetal alcohol syndrome
Valproic Acid
• syndrome of specific craniofacial
abnormalities and long, thin
digits with hyperconvex nails
• neural tube defects
Carbamazepine
• craniofacial abnormalities and
hypoplastic nails
• neural tube defects and cardiac
abnormalities
Trimethadione
• epicanthal folds, low-set ears,
microcephaly, short stature, and
irregular teeth
• rarely used in the treatment of
epilepsy and should certainly be
discontinued during pregnancy
PREVENTION &TREATMENT
Phenytoin: Fetal Hydantoin Syndrome
A 30 year-old female patient has been maintained on phenytoin 100 mg TID for the past 5 years with good
control of her idiopathic generalized seizure. She is 3 months pregnant when she visited your clinic.
Because exposure to multiple antiepileptic drugs
(AEDs) seems to be more teratogenic than
monotherapy, patients are advised to switch to
a single AED prior to conception and taper to the
lowest possible dose.
Supplemental folate has been shown to
decrease neural tube defects in patients
without epilepsy and decrease other
congenital anomalies in women with epilepsy.
4 mg of folic acid should be taken daily
starting two to three months prior to
pregnancy and be continued through the first
trimester.
A fetal echocardiogram should be performed
at 19 to 20 weeks’ gestation with careful
attention to cardiac anomalies.
Because of the increased risk neural tube
defects, a maternal serum AFP and
acetylcholinesterase screening test should be
offered.
Preconceptual management of women
with epilepsy
• Attempt to decrease pharmacotherapy to
monotherapy.
• Taper dosages of AEDs to the lowest possible dose.
• In women who have not had a seizure for 2-5 years,
attempt complete withdrawal of pharmacotherapy.
• Establish the level of total and free AEDs necessary
for achieving good clinical control.
• Consider preconceptual genetic counseling.
• Supplement the diet with folate at 4 mg/d.
Management of women with
epilepsy during pregnancy
• Check total and free levels of AEDs monthly.
• Consider early genetic counseling.
• Check maternal MSAFP levels and perform a
level II fetal survey and ultrasonography at 1920 weeks' gestation.
• Consider amniocentesis for alpha-fetoprotein
and acetylcholinesterase.
Gabapentin, lamotrigine, felbamate,
topiramate, and oxcarbazepine
These newer anticonvulsants have not been
studied extensively in pregnancy, though the use of
pregnancy registries for AEDs are providing larger sample
sizes.
The benefits and risks between congenital
anomalies and seizure control needs to be considered
when preparing the women with epilepsy for pregnancy.
The new anticonvulsants generally have a better
pharmokinetic profile and are not metabolized to known
teratogens.
All of these anticonvulsants are considered US
Food and Drug Administration pregnancy category C. Of
note, they are still known to both cross the placenta and
into breast milk.