Neurological diseases in pregnancy

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Neurological diseases during
pregnancy
By
Ahmed Elbohoty MD, MRCOG
Assistant professor of obstetrics and gynecology
Ain Shams University
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Neurologic complications of pregnancy
and Delivery
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Causes of maternal death
0.00
0.50
1.00
1.50
2.00
2.50
OtherIndirectcauses
Cardiacdisease
Neurological
Throm
bosis
PsychiatriccausesGenitaltractsepsis
Haem
orrhage
Pre-eclam
psia
Am
nioticfluid
em
bolism
Earlypregnancydeaths
AnaesthesiaIndirectm
alignancies
Rateper100,000maternities
Solid bars show indirect causes, hatched bars show direct causes
Maternal deaths have decreased from 11 (2006-2008) to 10 (2010-2012) in 100000
maternaties3/24/20 ELBOHOTY 3
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Neurological causes of maternal deaths
Epilepsy:
14 deaths
0.4 per 100000 maternities
Stroke:
26 deaths
Mostly haemorrhagic
0.75 per 100000
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STROKE
Haemorrhage:
• 13 women with subarachnoid
haemorrhage,
• 13 with intracranial
haemorrhage
• The majority presented with
sudden collapse no warning i.e.
no opportunity for intervention
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2013-2015
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December 2018 (2014-16)
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Indirect causes: 56% Direct causes: 44%
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Causes of maternal death 2015-2017
in UK
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Epilepsy
• Epilepsy commonest serious
neurological disease
• Epilepsy is one of the most common
neurological conditions in pregnancy,
with a prevalence of 0.5–1%
• Seizure related deaths more common
in pregnant women
• Mortality 0.4 per 100000 pregnancies
ELBOHOTY
• The death rate from epilepsy in pregnancy (0.40 per 100 000) is now higher
than the death rate from hypertensive disorders in pregnancy (0.38 per 100
000)3/24/20 12
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Maternal mortalities from epilepsy
• The risk of death is increased ten-fold in pregnant
WWE compared with those without the condition.
• Fourteen maternal deaths that occurred between
2009 and 2012 were attributed to epilepsy in the
2014 MBRRACE-UK (Confidential Enquiries into
Maternal Deaths and Morbidity) report.
• Twelve of these 14 deaths were classified as SUDEP
(sudden unexpected death in epilepsy),with poorly
controlled seizures being the main contributory
factor
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SUDEP
• Uncontrolled tonic-clonic seizures are the strongest
risk factor for SUDEP, which are the main cause of
death in pregnant WWE.
• SUDEP is defined as
– sudden, unexpected, witnessed or unwitnessed,
nontraumatic and nondrowning death in patients with
epilepsy, with Evidence or without evidence for a seizure
and excluding documented status epilepticus, in which
postmortem examination does not reveal a toxicologic
or anatomic cause for death.
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Aetiology
• Idiopathic
– 30% family history
• Secondary epilepsy
– Brain trauma or surgery
– Intracranial lesion
– Antiphospholipid syndrome
– Gestational epilepsy
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Definitions
• Epilepsy: predisposition to generate ≥ 2 epileptic
seizures, unprovoked by any immediate identifiable
cause.
• Status epilepticus: a single seizure lasting more than 20
min or recurrent seizures without recovery of
consciousness in between
• Status epilepticus is dangerous for both mother and
fetus and should be treated vigorously. Fortunately this
complicates 2 % of pregnancies.
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ILAE Classification of Seizures
Seizures
Partial Generalized
Simple Partial
Complex Partial
Secondarily
Generalized
Absence
Myoclonic
Atonic
Tonic
Tonic-Clonic
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• Epilepsy represents a medical emergency and most
fits are tonic-clonic.
• During the tonic phase:
– the contraction of the respiratory muscles results in
reduced maternal oxygenation, leading to fetal hypoxia.
• During the clonic phase:
– metabolic acidosis occurs.
– Rhabdomyolysis may precipitate acute renal failure.
ELBOHOTY
Fits
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Diagnosis
• Clinical diagnosis by should be made by a medical
practitioner with expertise in epilepsy, usually a
neurologist.
• Most women with epilepsy in pregnancy have
already been diagnosed, but when a first seizure
can occur in pregnancy but needs exclusion of other
causes.
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Assessment
• Blood pressure, urinalysis, platelet count, clotting
screen, blood film
• Blood glucose, serum calcium, serum sodium, liver
function tests
• EEG is used to support the diagnosis of epilepsy but
should not be used to make or exclude the
diagnosis of epilepsy.
• EEG can help to determine seizure type and risk of
recurrence of seizures.
• MRI is used to identify structural abnormalities that
can cause epilepsy
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DD of fits during pregnancy
• In pregnant women presenting with seizures in the
second half of pregnancy which cannot be clearly
attributed to epilepsy
– immediate treatment should follow existing protocols
for eclampsia management until a definitive diagnosis is
made by a full neurological assessment.
– Other cardiac, metabolic and intracranial conditions
should be considered in the differential diagnosis.
– Neuropsychiatric conditions including non-epileptic
attack disorder should also be considered.
– The diagnosis may be dependent on past history of
epilepsy or on risk factors for developing pre-eclampsia
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vasovagal syncope
– This is the most common attack disorder presenting to
hospital emergency departments
– It may be confused with seizures particularly if there is
stiffening and jerking during the episode (convulsive
syncope).
– Features such as
• a prior history of fainting
• a postural trigger
• a warning of lightheadedness and/or visual symptoms
• a brief duration of irregular jerking (less than one minute)
• a rapid recovery without postictal confusion should raise
suspicion of convulsive syncope.
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Cardiac syncope
– This is an uncommon but important cause of confusion
with epilepsy
– this diagnosis should not be missed due to the risk of
sudden death from cardiac arrhythmia.
– Collapse with syncopal features but without warning,
particularly if occurring on exercise, or in the context of
a personal or family history of either congenital heart
disease or sudden death, should raise suspicion of
cardiac syncope.
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Other DD
• Eclampsia
• Cerebral vein thrombosis (CVT)
• Thrombotic thrombocytopenic purpura (TTP)
• Stroke (risk is increased in pregnancy and 4% have seizures)
• Subarachnoid haemorrhage
• Drug (e.g cocain, amphetamine) and alcohol withdrawal
• Hypoglycaemia (diabetes, hypoadrenalism, hypopituitarism, liver failure)
• Hypocalcaemia (magnesium sulphate therapy, hypoparathyroidism)
• Hyponatraemia (hyperemesis, hypoadrenalism, pre-eclampsia)
• Infections (tuberculoma, toxoplasmosis)
• Postdural puncture. Seizures are rare and preceded by typical postdural
puncture headache and other neurological symptoms. Seizures occur
typically four to seven days after dural puncture
• pseudo fits characterized by
– Prolonged/repeated seizures without cyanosis
– Resistance to passive eye-opening
– Down-going plantar reflexes
– Persistence of a positive conjunctival reflex.
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Epilepsy management
• The decision to start antiepileptic drugs should
be made by the patient and an epilepsy
specialist.
• Antiepileptic drugs should be offered after a first
tonic-clonic seizure if:
– the patient has had previous myoclonic, absence or
focal seizures
– the EEG shows unequivocal epileptic discharges
– the patient has a structural cerebral disorder
– the patient considers the risk of recurrence
unacceptable.
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AE choice
• Focal onset seizures
– lamotrigine is the drug of choice.
– 2nd choice: carbamazepine and levetiracetam
• Genetic generalised epilepsy or unclassified
epilepsy:
– sodium valproate is the most effective antiepileptic drug.
– 2nd choice: lamotrigine and topiramate
– In women of childbearing age, levetiracetam or
lamotrigine may be a reasonable alternative.
• Routine switching between different manufacturers
of antiepileptic drugs should be avoided.
• The adverse effect and interaction profiles should
direct the choice of drug for the individual patient.3/24/20 ELBOHOTY 27
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Adverse effects and follow up
• Patients should be warned of common potential
adverse effects and given clear instructions to seek
medical attention urgently for symptoms including
rash, bruising or somnolence with vomiting
especially in the first weeks of treatment.
• Dietary and other lifestyle advice to minimise the
risk of osteoporosis.
• The potential negative psychotropic effects.
• Antiepileptic drug treatment should be used with
caution in those with pre-existing behavioural or
psychiatric conditions and epilepsy.
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Antiepileptic Drug Interactions
s AEDs that may induce metabolism of other drugs:
s carbamazepine, phenytoin, phenobarbital, primidone
s AEDs that are highly protein bound:
s valproate, phenytoin, tiagabine
s carbamazepine, oxcarbazepine
s topiramate is moderately protein bound
ELBOHOTY
Gabapentin, lamotrigine, levetiracetam and vigabatrin have no antifolate effects
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Drugs that may decrease the efficacy of
oral contraceptive pills:
– Phenytoin
– Carbamazepine
– Phenobarbital
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s Lamotrigine and hormonal contraception:
s Oral contraceptive pills can decrease lamotrigine levels by 50%
s Lamotrigine levels will increase significantly during the placebo week, possibly
leading to toxicity
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Can we stop AE?
• This should be discussed with people with epilepsy
who are at least two years seizure free, so that they
can make an informed choice.
• Factors to be discussed should include driving,
employment, fear and risks of further seizures and
concerns about prolonged antiepileptic drug
treatment.
• The rate of withdrawal of antiepileptic drugs should
be slow, usually over a few months, and longer with
barbiturates and benzodiazepines.
• One drug should be withdrawn at a time.3/24/20 ELBOHOTY 32
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Management of status epilepticus
• As soon as possible:
– secure airway
– give oxygen
assess cardiac and respiratory function
– secure Iv access in large veins.
• Patients with prolonged tonic-clonic seizures that
have lasted five minutes or more should be given:
– midazolam 10 mg buccally or intranasally, or
– lorazepam 4 mg IV if midazolam is unavailable, or
– diazepam 10 mg IV or rectally if midazolam and
lorazepam are unavailable.ELBOHOTY3/24/20 33
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Pre-conception counselling
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• As good seizure control during pregnancy is more
likely in women whose seizures are controlled
prior to becoming pregnant an effort should be
made to optimise seizure control prior to
pregnancy (particularly for generalised tonic-clonic
seizures).
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• WWE who are planning their pregnancy should have a
clinician competent in the management of epilepsy
take responsibility for sharing decisions around choice
and dose of AEDs, based on the risk to the fetus and
control of seizures.
• WWE should be reassured that most mothers have
normal healthy babies and the risk of congenital
malformations is low if they are not exposed to AEDs in
the periconception period.
• Women should be informed that the risk of congenital
abnormalities in the fetus is dependent on the type,
number and dose of AEDs.
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Fertility
• Women with epilepsy have a higher incidence of
subfertility.
• The aetiology is multifactorial:
– lowered libido, dysparunia, reduced
lubrication/vaginismus – antiepileptic drugs may
contribute to sexual dysfunction by direct cortical effects
or secondarily through alterations in the hormone
effects on sexual behaviour social/genetic factors
– Sodium valproate is particularly associated with
polycystic ovaries
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Contraception
• WWE should be offered effective contraception to
avoid unplanned pregnancies.
• The risks of contraceptive failure and the short- and
long-term adverse effects of each contraceptive
method should be carefully explained to the
woman.
• Effective contraception is extremely important with
regard to stabilization of epilepsy and planning of
pregnancy to optimise outcomes.
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UKEC
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Women should be counselled that the efficacy of oral contraceptives
(combined hormonal contraception, progestogen-only pills),
transdermal patches, vaginal ring and progestogen-only implants may
be affected if they are taking enzyme-inducing AEDs
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ON Enzyme inducers therapy
– Cupper IUD
– the levonorgestrel intrauterine system may be used
without restriction
– depot injections of progestogen may be used without
restriction and with no alteration to the normal
dosing/replacement interval
– progestogen-only oral contraceptives are not
recommended
– progestogen implants (levonorgestrel and etonogestrel)
are not recommended
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• if there is no alternative to a CoCP, the CoCP should contain at least
50 micrograms daily of oestrogen; if the CoCP contains less
oestrogen, the woman should be warned that the efficacy is reduced
and additional barrier methods should be used
• If breakthrough bleeding occurs withaCoCP containing 50
microgramsofoestrogen,theCoCP dose should be increased to a
maximum of 70 micrograms and ‘tricycling’ should be considered
• if the antiepileptic drug is withdrawn, it is important to note that
enzyme induction persists for up to four weeks. Contraceptive cover
should be ensured during this time.
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Unusual Alternative (NOT IMPORTANT)
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non-enzyme-inducing AEDs
• All methods of contraception may be offered
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women with epilepsy receiving lamotrigine:
• can use progestogen-only contraceptives without
restriction.
• combined hormonal contraceptives should be counselled
about the reduction in circulating lamotrigine
concentrations and the potential for, consequences of,
increased seizure activity and possibility of increasing the
lamotrigine dose
• Woman should be warned about signs and symptoms of
lamotrigine toxicity if the CHC is withdrawn.
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emergency contraception
• Not taking antiepileptic drugs, or who are taking non-enzyme
inducing antiepileptic drugs
– can use emergency contraception as for the general population.
• Using enzyme-inducing antiepileptic drugs, or who have
stopped taking these within the last 28 days:
– Should be offered insertion of a non-hormonal
intrauterine device within 5 days of intercourse as an
alternative option. (IUD is the preferred choice for
emergency contraception).
– Emergency contraception pills with levonorgestrel and ulipristal
acetate are affected by enzyme-inducing AEDs.
– She may be prescribed a single dose of levonorgestrel 3 mg (as
opposed to 1.5 mg), ideally as soon as possible, and within 72
hours of unprotected intercourse
– should not be offered ulipristal acetate (ellaOne®) because of a risk of reduced
efficacy
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• WWE should be informed that two-thirds will not
have seizure deterioration in pregnancy.
• In women who were seizure free for at least 9
months to 1 year prior to pregnancy, 74–92%
continued to be seizure free in pregnancy
• The risk of seizures is highest peripartum; 1–2% of
women with epilepsy will have a seizure in labour
and 1–2% will have a seizure within 24 hours of
delivery.
ELBOHOTY
Effect of pregnancy on epilepsy
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Effect of epilepsy on pregnancy
• Seizures:
– Fetal hypoxia if status epilepticus
– Abdominal trauma
• Increased fetal congenital anomaly due to the use of
AED
• Increased risk of epilepsy in offspring
– One parent=4%
– Both parents=15%
– One sibling affected=10%
– Risk increased if mother had onset before 10 years age
• Maternal death
• Miscarriage: no difference
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• reasons for a pregnancy-related increase in seizure
activity include:
– non-compliance with medication – either due to
reluctance to accept the diagnosis of epilepsy or fear of
causing harm to their baby
– sleep deprivation
– alteration in antiepileptic drug pharmacokinetics –
decreased protein binding (phenytoin, carbamazepine,
valproate), increased liver metabolism (phenytoin,
phenobarbitone, primidone, carbemazepine,
topiramate), increased drug clearance (lamotrigine)
– weight gain
– hyperemesis gravidarum
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Additional counselling
• Most women with epilepsy have normal children
• Risk of fetal malformations is increased with AED exposure
• AED teratogenicity is related to exposure in the first
trimester of pregnancy
• Planning should begin well before pregnancy
• Seizures may be deleterious to the fetus
• Compliance with AED treatment is important
• Prenatal diagnosis of fetal malformations is possible
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Fetal anomalies
• Untreated epilepsy does not appear to be associated with an
increased risk of CM, but major and minor fetal malformations occur
more commonly in infants exposed 3 to AEDs during pregnancy.
• The overall risk of major congenital malformation (MCM) in the
general population is approximately 2%.
• The risk increases in women taking a single AED or multiple AEDs
• over 90% on AED have normal children
• Risk less:
– Monotherapy vs polytherapy
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The major malformations caused by
AEDs are:
• Highest risk and Urogenital defects with valproate
• Neural tube defects [particularly valproate (1–3.8%) and
carbamazepine (0.5– 1%)
• Orofacial clefts (particularly phenytoin, carbamezepine,
phenobarbitone)
• Congenital heart defects (particularly phenytoin,
phenobarbitone and valproate).
• Newer drugs
– Lamotrigine: Possibly safe
– Levetiracetam, gabapentin, tiagabine (no risk in animals)
– Topiramate: shows risk ELBOHOTY3/24/20 51
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Minor malformations (fetal
anticonvulsant syndrome)
• Dysmorphic features (V-shaped eyebrows, low-set
ears, broad nasal bridge, irregular teeth)
• Hypertelorism
• Hypoplastic nails and distal digits
• Hypoplasia of the midface could be a marker for
cognitive dysfunction.
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• The risk increases with the number of drugs, so for
those taking two or more AEDs, the risk is 10% to 15%
• An association between maternal valproate use and
impaired psychomotor development, and additional
educational needs and reduced verbal IQ in the
children.
• In utero exposure to sodium valproate is associated
with increased rates of childhood autism (adjusted
hazard ratio 2.9)
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• Based on limited evidence, in utero exposure to
carbamazepine and lamotrigine does not appear to
adversely affect neurodevelopment of the offspring.
• There is very little evidence for levetiracetam and
phenytoin.
• Parents should be informed that evidence on long-
term outcomes is based on small numbers of
children.
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Discontinuing AEDs if possible
Specialist decision and supervision
Seizure freedom for ³ 2 -5 years implies overall >60%
chance of successful withdrawal in some epilepsy
syndromes
s Favorable factors
– Control achieved easily on one drug at low dose
– No previous unsuccessful attempts at withdrawal
– Normal neurologic exam and EEG
s Consider relative risks/benefits (e.g., driving,
pregnancy)
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Antiepileptic Drug Monotherapy if
possible
Specialist decision and supervision
Simplifies treatment
Reduces adverse effects and risk of congenital
malformation
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AED Serum Concentrations
s Serum concentrations are useful when optimizing
AED therapy, assessing compliance, monitoring
during pregnancy or oral contraceptive use, or
teasing out drug-drug interactions.
s Individual patients define their own “therapeutic”
and “toxic” ranges.
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Adverse Effects of AEDs: Common
Typically dose-related in all AEDs :
Dizziness , Fatigue , Ataxia, Diplopia
Weight gain
s valproate (also associated with polycystic ovarian syndrome )
s carbamazepine, gabapentin, pregabalin
Aplastic anemia: carbamazepine
Rash
lamotrigine, phenytoin, zonisamide, carbamazepine
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Stevens-Johnson Syndrome (SJS) and
Toxic Epidermal Necrolysis (TENS)
s severe life threatening allergic reaction
s blisters and erosions of the skin, particularly palms/soles and mucous membranes
s fever and malaise
s rare: severe risk roughly 1-10/10,000 for many AEDs
s rapid titration of lamotrigine especially in combination with valproate increases
risk
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Pre pregnancy
• Multidiscipline approach: specialised consultant, specialised nurse, neurologist
• Information:
– Proper counselling
– Benefits of seizure control outweigh risks
– Avoid factors precipitating seizures
– advice on smoking cessation for women with epilepsy who smoke, as smoking in this
population is associated with a substantially higher risk of premature contractions, pre
term labour and delivery compared with women with epilepsy who do not smoke.
• Advice on contraception according to the control and specialist advice
• Supplements of folic acid:
– 400 micrograms daily for:
• women with epilepsy not receiving antiepileptic drug treatment
– 5 mg daily for:
• women with epilepsy receiving antiepileptic drug treatment
• women with epilepsy not on antiepileptic drug treatment, but with a family history of or a
previous child with a neural tube defect
• women with epilepsy not on antiepileptic drug treatment, but with a BMI >30.
• AED
– Lowest possible dose/serum level
– Divided doses, slow release
– Avoid valproate and consider to change to lamotorgine or carbamazepine
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Individual Assessment
• Any assessment of the condition in pregnancy should
include duration and severity, frequency and type of
seizures, and impact of epilepsy on the mother such as
driving, accidents, family life and employment.
• A drug history of effective and ineffective medications
is relevant, including a history of adverse effects.
• Women with a history of epilepsy who are not
considered to have a high risk of unprovoked seizures
can be managed as low-risk women in pregnancy.
– Women who have remained seizure-free for at least 10 years
(with the last 5 years off AEDs) and those with a childhood
epilepsy syndrome who have reached adulthood seizure- and
Evidence treatment-free are considered no longer to have
epilepsy.
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Benefits of folic acid
• Folic acid preconceptually and for at least the first
12 weeks of pregnancy may reduce the incidence of
major congenital malformations in the offspring of
women with epilepsy, particularly those receiving
AED treatment
• In women receiving sodium valproate, folic acid
may also significantly reduce the rate of
spontaneous miscarriage, with a non-significant
reduction for carbamazepine.
• A prospective multicentre study of cognitive outcomes at age six in children of women
prescribed sodium valproate, lamotrigine, carbamazepine or phenytoin monotherapy,
reported that mean IQs were higher in children whose mothers had taken
preconceptual folate, than in those who had not, but concluded that these results
should be interpreted with caution as information on folate was obtained from mothers
via a retrospective interview
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Genetic counselling
• A clinical genetics service, with expertise in the
genetics of epilepsy, should be available to patients
with a very strong family history of epilepsy, or
with a clinical phenotype suggestive of a
monogenic epilepsy syndrome.
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RISKS of INHERITING EPILEPSY
• Mothers with epilepsy have higher rates of having
affected offspring (2.8–8.7%) compared to fathers with
epilepsy (1.0–3.6%).
• The risks of passing on epilepsy are higher for mothers
with genetic than with symptomatic epilepsies.
• Parental age at onset of epilepsy also predicts risk to
offspring.
– Parents with onset of epilepsy before the age of 20 have a
2.3–6% risk of having offspring with epilepsy; onset after age
20 confers a 1.0–3.6% risk.
– No increased risk to offspring of individuals has been found
with epilepsy beginning after age 35.
• The risk increases with the number of affected
individuals in each family, and is also raised if there are
specific EEG abnormalities in family members.
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FOCAL EPILEPSIES
• In relatives of patients with non-genetic focal
epilepsy, there is no evidence for a significantly
increased risk of epilepsy.
• In genetic focal epilepsies the risks are higher.
• For example, in parents with autosomal dominant
nocturnal frontal lobe epilepsy the risk of a child
developing this disorder may be up to 50%,
depending on penetrance
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FEBRILE CONVULSIONS
• Susceptibility to febrile convulsions also follows a
multifactorial polygenic mode of inheritance with a
maternal preponderance in transmission.
• There is a 27% risk in a child with an affected
mother and 6% with an affected father.
• 2–7% of children with febrile seizures will go on to
develop epilepsy with afebrile seizures, the risk
being higher with complicated febrile convulsions.
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Antenatal management
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Settings of care
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Multi-disciplinary and expert care
• Pregnant women with epilepsy need prompt and responsive epilepsy
care, including for new referrals
• Usual out-patient waiting times may not be appropriate
• Other barriers may prevent prompt engagement (chaotic lifestyle,
language problems)
• Pregnant women with epilepsy should be seen promptly by an
epilepsy specialist as soon as possible
• Value of Epilepsy nurse specialists increasingly recognised
• Ideally placed to integrate with a number of different disciplines
• Emphasis on psychosocial outcomes
• Reduce admissions
• Improve medication compliance
• More responsive service
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High risk patients
• Women with epilepsy require diligent medical and nursing
care during hospital admissions
• A policy of never nursing women with epilepsy in single
rooms may be life saving
• Medical and nursing teams should always be aware of the
potential effects of pregnancy and its complications on a
woman’s epilepsy
• Pregnant women with epilepsy are still not routinely
identified as a high risk group, both in outpatient and
inpatient settings
ELBOHOTY3/24/20 71
71
• Multidisciplinary approach
• General advice:
– Shower no baths
– Women should be advised about the importance of proper sleep and medication compliance, particularly in the
last trimester, when AED levels tend to be lowest
– Relatives/partners education
• Drugs:
– Folic acid 5 mg/day or 400 mg
– antenatal corticosteroids if needed: Don’t double the dose
– All infants of women with epilepsy should be offered vitamin K1, 1 mg intramuscularly at birth, unless there are
contraindications.
– There is insufficient evidence to recommend routine maternal use of oral vitamin K to prevent haemorrhagic
disease of the newborn in WWE taking enzyme-inducing AEDs
– There is insufficient evidence to recommend giving vitamin K to WWE to prevent postpartum haemorrhage.
• SCAN:
– At the end of 1st trimester scan
– Detailed ultrasound assessment of the fetus at 18 – 20 weeks gestation (looking particularly for heart, renal and
neural tube defects)
• Ensure the request form for obstetric ultrasound includes details of all antiepileptic drugs the woman is
taking
• AED
– Continue even if she is controlled on valproate
– Monitor plasma anticonvulsant levels (not useful for valproate) every 1 to 2 months. If there is deterioration in
seizure control, adjust dose accordingly
–
ELBOHOTY3/24/20 72
72

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37
Vitamin K use
• All babies born to WWE taking enzyme-inducing
AEDs should be offered 1 mg of intramuscular
vitamin K to prevent haemorrhagic disease of the
newborn.
3/24/20 ELBOHOTY 73
73
3/24/20 ELBOHOTY 74
74

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38
Anti-epileptic drugs
• Previous enquiries have demonstrated a
relationship between lamotrigine and
maternal death
• Possible co-factors could include epilepsy
syndrome, falls in lamotrigine levels during
pregnancy, or direct effect of the drug itself
• Greater understanding of metabolism and
effects of AEDs in pregnancy required
ELBOHOTY3/24/20 75
75
• WWE taking AEDs who become unexpectedly pregnant
should be able to discuss therapy with an epilepsy
specialist on an urgent basis.
• It is never recommended to stop or change AEDs
abruptly
without an informed discussion.
• timing of screening for detection of fetal abnormalities:
• Early pregnancy can be an opportunity to screen for structural
abnormalities.
• The fetal anomaly scan P at 18+0–20+6 weeks of gestation can
identify major cardiac defects in addition to neural tube defects.
• All WWE should be offered a detailed ultrasound in line
with the National Health Service Fetal Anomaly
Screening Programme standards.
3/24/20 ELBOHOTY 76
76

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39
• In pregnancy, dosing adjustment for the majority of antiepileptic drugs (with
the exception of lamotrigine and levetiracetam) should only be considered if
there is a change in seizure frequency or if toxicity is suspected.
• Healthcare professionals should be aware that the dose of lamotrigine may
need to be increased during pregnancy.
• To avoid postpartum neurotoxicity, the lamotrigine dose should be reduced
early in the puerperium.
• If seizure control deteriorates during pregnancy, other factors affecting AED
levels in pregnancy should be considered (for example vomiting, interactions
with other medication).
• For pregnant women with epilepsy, routine monitoring of AED concentrations
is not indicated. However, the measurement of AED concentrations can be
useful in the following circumstances: for adjustment of phenytoin dose,
assessment of AED adherence and suspected AED toxicity.
• The interpretation of AED blood levels is best performed by an epilepsy
specialist
• Issues relating to AED blood level monitoring must be discussed with the
patient.
3/24/20 ELBOHOTY 77
77
3/24/20 ELBOHOTY
Treatment Malformations (%)
Women without AED 2.7 (comparable to general population 2)
Monotherapy
Carbamazepine 4.62
Lamotrigine 2.91
Phenobarbital 4.91
Phenytoin 7.36
Sodium valproate 10.73
Polytherapy
Two or more anticonvulsants 7.1–11.5
Three or more anticonvulsants 8.5–25.0
78
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40
3/24/20 ELBOHOTY 79
79
• All pregnant WWE should be provided with
information about the UK Epilepsy and Pregnancy
Register and invited to register.
3/24/20 ELBOHOTY 80
80

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41
Carbamazepine
• Large peak-trough fluctuations can be minimised by
using a controlled-release formulation but this may
require higher doses
• Pregnancy may cause a small decrease in the
concentration of carbamazepine; consideration should
be given to monitoring levels
• Associated with major malformations including neural
tube defects in up to 1 % of exposed pregnancies, heart
defects, inguinal hernia, hypospadias and hip
dislocations
• Craniofacial abnormalities and developmental delay
have been associated in some but not all studies with
the use of carbamazepine both alone or with other
anticonvulsants ELBOHOTY3/24/20 81
81
Lamotrigine
• Lamotrigine clearance may be increased in pregnancy, leading to a
reduction in lamotrigine concentrations and potential loss of
seizure control
• Lamotrigine levels should be monitored in pregnancy and the dose
adjusted accordingly
• Doses of lamotrigine may need to be increased two- to three-fold
during pregnancy.
• To date data suggest that lamotrigine has not been shown to
increase the risk of major birth defects however there are
conflicting reports of an association with the increased risk of oral
facial clefts
• the incidence of SUDEP in women with epilepsy taking lamotrigine
is higher (2.5 per 1000 patient years) than in those taking other
AEDS (0.5–1.0 per 1000 patient years)
ELBOHOTY3/24/20 82
82

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42
Sodium valproate
• Divided doses are preferred to avoid high peaks in serum concentrations
• Therapeutic range not closely correlated with efficacy – drug level
monitoring is of limited value apart from suspected toxicity or non-
compliance
• Exposure to valproate during early pregnancy is associated with a 1 to 2 %
incidence of neural tube defects, especially with doses > 1,000 mg / day
• Other defects include cardiovascular complications, urogenital
malformations, skeletal defects; and facial dysmorphic patterns
• The incidence of congenital malformations in children exposed to valproic
acid during pregnancy ranging from 5 to 18 %
• In utero exposure to sodium valproate is associated with increased rates of
childhood autism 2.9
• Emerging evidence suggests that valproate exposure in pregnancy may lead
to neurodevelopmental delay (including decreased mental development,
intelligence quotient (IQ) and cognition, and autism spectrum disorder)
ELBOHOTY3/24/20 83
83
Phenobarbital and Primidone
• Barbiturates are now less frequently prescribed due
to their tendency to produce sedation and impaired
cognitive function
• Associated with congenital heart defects and facial
clefts
• Infants born after exposure to phenobarbitone or
primidone in utero should be monitored for
withdrawal symptoms for up to 6 weeks after birth
ELBOHOTY3/24/20 84
84

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43
AED with congenital malformation
3/24/20 ELBOHOTY 85
85
• Fetus
– End of 1st trimester
– Anomaly scan 18-21 weeks
– Fetal cardiac scan
• Serial growth scans are required for detection of
small-for-gestational-age babies and to plan
further management in WWE exposed to AEDs.
• There is no role for routine antepartum fetal
surveillance with cardiotocography in WWE
taking AEDs.
ELBOHOTY3/24/20 86
86

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Sudden Unexplained
Death in Epilepsy (SUDEP)
• SUDEP remains predominant
cause of death in epilepsy
• Antenatal and postpartum
• Estimated risk of SUDEP higher
than expected in pregnancy than
expected
• Women and their families should
be expressly counselled regarding
risk
• Modifiable factors (first aid,
recovery position, not sleeping
alone, AED compliance) should
addressed, including in the post-
partum period
ELBOHOTY3/24/20 87
87
Bathing and
drowning
• Death by drowning still occurs
• 2 deaths in this series due to
drowning (including one
washing hair over edge of bath)
• Entirely preventable
• All women need robust advice
regarding risks of bathing
A woman was found kneeling on the bathroom floor
having drowned with her head in a bath of water.
She had been washing her hair, and showed signs of
having had a generalised seizure.
ELBOHOTY3/24/20 88
88

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45
• Women with epilepsy who are pregnant or
who have recently been pregnant and who
require hospital admission should not be
placed in a single room.
3/24/20 ELBOHOTY 89
89
INTRAPARTUM MANAGEMENT
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90

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46
• Most women with epilepsy will have a normal labour and a vaginal
delivery at term.
• Stress, pain, sleep deprivation, overbreathing and dehydration
increase the risk of seizures during labour and birth. If tonic-clonic
seizures occur during labour, maternal hypoxia, fetal hypoxia and
acidosis may result.
• Women with epilepsy should be delivered in a consultant-led
maternity unit.
• When a woman with epilepsy presents in the early stages of
labour, a low threshold for admission to the maternity unit should
be adopted.
• During labour, one-to-one midwifery care should be given.
• Factors predisposing to increased risk of seizures in labour should
be reduced as much as possible and there should be a low
threshold for epidural anaesthesia.
• The usual oral antiepileptic drug should be continued during
labour and in the postnatal period. Every effort should be made
to ensure that no doses are missed.
• In women with epilepsy who are unable to tolerate oral
medication, the antiepileptic drug can be given by other routes.3/24/20 ELBOHOTY 91
91
• Adequate analgesia and appropriate care in labour
should be provided to minimise risk factors for P
seizures such as insomnia, stress and dehydration.
• Long-acting benzodiazepines such as clobazam
can be considered if there is a very high risk of
seizures in the peripartum period.
• AED intake should be continued during labour. If
this cannot be tolerated orally, a parenteral
alternative P should be administered.
3/24/20 ELBOHOTY 92
92

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47
• Timing:
– In women with epilepsy, induction of labour should be
offered for standard obstetric indications.
• Mode:
– A history of epilepsy alone is not an indication for
delivery by Caesarean section.
– Elective Caesarean section should be considered if there
have been frequent tonic-clonic or prolonged focal
seizures during the third trimester of pregnancy in
order to avoid adverse outcomes associated with
intrapartum seizures.
• Place:
– Hospital: should not be left unattended
– Early pain relief
ELBOHOTY3/24/20 93
93
• Continuous fetal monitoring is recommended
in women at high risk of a seizure in labour,
and following an intrapartum seizure.
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94

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48
methods of analgesia in labour
• Pain relief in labour should be prioritised in
WWE, with options including transcutaneous
electrical P nerve stimulation (TENS), nitrous
oxide and oxygen (Entonox®), and regional
analgesia.
• Pethidine should be used with caution in
WWE for analgesia in labour. Diamorphine
should be used in preference to pethidine.
3/24/20 ELBOHOTY 95
95
Care
• Most women with epilepsy will have a normal
uncomplicated vaginal birth
• Two to four percent of women with epilepsy will have a
tonic-clonic seizure during labour or in the first 24
hours after labour
• Tonic clonic seizures may result in fetal hypoxia
• Birth should be arranged in a hospital with facilities for
emergency caesarean section and maternal and
neonatal resuscitation
• Continue oral anticonvulsants
• Ensure intravenous access , presence ready airway
• Paediatrician / neonatologist at birth
ELBOHOTY3/24/20 96
96

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49
management of epileptic seizures in
labour?
• Every obstetric unit should have written
guidelines on the management of seizures in
labour.
• Seizures in labour should be terminated as
soon as possible to avoid maternal and fetal
hypoxia and fetal acidosis. Benzodiazepines
are the drugs of choice
3/24/20 ELBOHOTY 97
97
When to use IV antiepleptics
• Phenytoin and phenobarbitone are the only parenteral antiepileptics
• Women will not usually need parenteral anticonvulsants in labour
unless they are vomiting and unable to take their usual anti-
convulsant medication
• Women who have missed their anticonvulsant doses for more than
12 hours may need a parenteral dose. Consult a physician or
neurologist.
• For women already on oral phenytoin, continue the same dose
intravenously (divided doses)
• If the woman is on a different anticonvulsant, she will require a
phenytoin loading dose (15 – 20 mg / kg) followed by maintenance
doses of 8 mg / kg / day, approximately 300 mg, twice daily
intravenously or orally
• Intravenous diazepam 5-10 mg can be used for acute seizure
management in women on other anti-epileptic drugsELBOHOTY3/24/20 98
98

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50
SEIzURES IN LABOUR
• Approximately 3.5–5% of women with epilepsy will
have a seizure during labour and birth.
• Intrapartum seizures are more common in those
with antenatal seizures and occur more frequently
in women with primary generalised seizures than in
women with focal-onset seizures.
3/24/20 ELBOHOTY 99
99
Management of Intrapartum fits
• In those with intravenous access, lorazepam given as an
intravenous dose of 0.1 mg/kg (usually a mg bolus, with a
further dose after 10−20 minutes) is preferred. Diazepam 5–
10 mg administered slowly intravenously is an alternative.
• If there is no intravenous access, diazepam 10−20 mg rectally
repeated once 15 minutes later if there is a continued risk of
status epilepticus, or midazolam 10 mg as a buccal
preparation are suitable.
• If seizures are not controlled, consider administration of
phenytoin.
• The loading dose of phenytoin is 10–15 mg/kg by intravenous
infusion, with the usual dosage for Evidence an adult of about
1000 mg
3/24/20 ELBOHOTY 100
100

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51
• If the seizure persists, this should be managed as
for status epilepticus.
– Maternal airway and oxygenation should be maintained
at all times.
– If there is doubt whether a seizure in labour is due to
eclampsia or epilepsy, a slow intravenous bolus of 4 g
magnesium sulphate over five minutes followed by 1
g/hour for 24 hours is recommended in addition to
midazolam, lorazepam or diazepam.
– Following a generalised tonic-clonic seizure during
labour (irrespective of aetiology) delivery should be
expedited once the maternal condition is stable.
– Neonatal expertise should be available.
101
POSTNATAL MANAGEMENT
ELBOHOTY3/24/20 102
102

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• Where seizure control is poor and/or social factors
have the potential to affect outcomes adversely, a
care management plan should be considered before
delivery. It should be ensured that health
professionals, both in the community and in
secondary care, are aware of the potential risks to
the woman and her baby.
• Advice should be given to new parents/child carers
on safety, particularly in relation to breastfeeding
and caring for the child.
103
• After the birth a review of the mother’s AED
therapy should be undertaken.
• If the AED dose was increased in pregnancy, it
should be reviewed within 10 days of delivery to
avoid postpartum toxicity.
• Postpartum safety advice and strategies should be
part of the antenatal and postnatal discussions
with the mother alongside breastfeeding, seizure
deterioration and AED intake.
104

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53
• Advice regarding contraception, the need for
planning future pregnancies, folic acid
requirements and risks associated with AEDs in
pregnancy should be offered at the postnatal visit.
• Extra support should be available to mothers who
have a physical or learning disability
105
• Lamotrigine, levetiracetam and topiramate transfer to a larger
extent to the child from breast milk compared with sodium
valproate, carbamazepine and phenytoin, which have minimal
transfer.
• Breastfeeding has not been shown to affect the cognitive
outcomes at 3 years of age in children who were exposed in
utero to lamotrigine, sodium valproate, phenytoin or
carbamazepine monotherapy
• the psychomotor development of the breastfed children was
better at 6 and 18 months compared with those who were
not breastfed or were breastfed for less than 6 months.
• Other options such as alternating breast and bottle milk could
be considered if there are any concerns about AED exposure.3/24/20 ELBOHOTY 106
106

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54
Depression screening
• WWE should be screened for depressive
disorder in the puerperium. Mothers should
be informed about the symptoms and
provided with contact details for any
assistance
107
breastfeeding
• All mothers should be encouraged to breastfeed and receive support from their health
visitor, midwife and GP.
• Most of the antiepileptic drugs cross into breast milk in an inverse relation to their
protein binding. Phenytoin, carbamazepine and valproate are highly protein bound and
found in low concentration in breast milk. Data suggest probable penetration into
breast milk of primidone and levetiracetam in amounts that may be clinically important
• As antiepileptic drugs are excreted in breast milk only in low concentrations encourage
breastfeeding
• If the mother is using antiepileptic drugs that are associated with drowsiness, monitor
the breastfed baby for prolonged sedation, disinterest in feeding and inadequate weight
gain, and ensure the mother is informed of safe sleeping practices
• Lamotrigine requires caution –If a rash occurs in the baby, breastfeeding should be
ceased and the cause of the rash urgently established.
• Valproate may be associated with jitteriness
• If maternal seizure control is poor there may be a risk of injury to the infant
• Parents should be made aware of signs of toxicity in infants of breastfeeding women
taking antiepileptic drugs. The possibility of sedation should be considered in infants
of mothers taking high dose antiepileptic drugs, polytherapy, or regimens including
primidone, levetiracetam, gabapentin, lamotrigine and topiramate.
•
ELBOHOTY3/24/20 108
108

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55
Epilepsy Action recommend the following
to women with newborn babies:
• if possible share the night feeds – for some women,
lack of sleep can trigger seizures.
• when feeding, sit on the floor surrounded by
cushions if possible
• never bathe the baby alone
• use a car seat when carrying the baby up or down
stairs.
ELBOHOTY3/24/20 109
109
Neonate
• The babies of patients treated with enzyme-inducing anticonvulsants
(carbamazepine, phenytoin, primidone, phenobarbitone) are at
increased risk of haemorrhagic disease of the newborn caused by
deficiency of vitamin K-dependent clotting factors
• Vit. K 1mg IM
• Observe baby closely for signs of respiratory depression
• Examine baby for signs of anticonvulsant and epilepsy-associated
dysmorphology
ELBOHOTY3/24/20 110
110

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56
Contraception
ELBOHOTY3/24/20 111
111
Suitability of contraception for women taking anticonvulsant therapy
Combined hormonal
methods
Not recommended for women using hepatic enzyme-inducing
antiepileptic drugs (carbamazepine, phenobarbitone, phenytoin,
primidone and topiramate)
If chosen by women using hepatic enzyme-inducing antiepileptic
drugs they should take 2 pills containing at least 50 microgram
estrogen (e.g. 20 and 30 microgram combined oral contraceptives)
and also use condoms
Estrogen reduces plasma concentrations of lamotrigine. Use of
combined hormone methods are not recommended in women on
lamotrigine monotherapy due to the risk of loss of seizure control
and the potential for toxicity in the combined hormone free week
Progesterone-only
pill/implant
Not recommended for women using hepatic enzyme-inducing
antiepileptic drugs
Progesterone only
injectable
Levonorgestrel-
releasing intrauterine
system (LNG-IUS)
Suitable for all women taking anticonvulsant therapy. Efficacy of
depot medroxyprogesterone acetate, norethisterone enantate and
LNG-IUS is unaffected by enzyme-inducing drugs
Non-hormonal
methods
Suitable for all women taking anticonvulsant therapy
Emergency
contraception
Women taking hepatic enzyme-inducing antiepileptic drugs should
be advised that an intrauterine device is the preferred optionELBOHOTY3/24/20 112
112

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57
Headache in pregnancy
113
INTRODUCTION
• Headaches are common in life and in pregnancy.
• Most headaches in pregnancy are benign
114

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58
Case 1
• Known migrain, seen at term complaining of
headache, blurred vision
• No documented neurology exam
• Re-admitted 1 week later, resuscitated by
paramedics-urgent C/S, diffuse SAH, died
• First presentation may have been a sentinel bleed?
• Importance of Liaison, equipment, Nimodipine
ELBOHOTY3/24/20 115
115
Case 2
• Admitted for induction
• BP 140/95
• Given Dinoprostone gel
• Syntometrine at delivery
• Sudden severe headache,
seizure, asystole-SAH
Oxytocin alone (without
ergometrine) is the drug of choice
for the routine active management
of the third stage of labour
NICE CG107, CG55
ELBOHOTY3/24/20 116
116

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Ischaemic Stroke
Rare
0.03 per 100 000 maternities
Neither pregnancy, caesarean
section delivery nor the immediate
post-partum state are absolute
contraindications to thrombolysis
(intravenous or intra-arterial), clot
retrieval or craniectomy.
ELBOHOTY3/24/20 117
117
KEY MESSAGES
• Pregnancy should not alter the standard of care for
stroke.
• All women, pregnant or not, should be admitted to a Hyperacute
Stroke Unit.
• Neurological examination including assessment for neck stiffness
is mandatory in all new onset headaches or headache with
atypical features, particularly focal symptoms.
• Neither pregnancy, caesarean section delivery nor the immediate
post-partum state are absolute contraindications to thrombolysis
(intravenous or intra-arterial), clot retrieval or craniectomy.
ELBOHOTY3/24/20 118
118

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• The International Classification of Headache
Disorders classifies 85 different types of headache,
many of which only rarely occur in young women
and approximately 90% of
• Headaches in pregnancy are
– migraine
– tension-type headaches
119
Pathophysiology of headache
• Pain of headaches arise from sensory fibers that
surrounds intracranial blood vessels from direct
pain or secondary inflammatory effects of
vasoactive neuropeptides released after stimulation
of the sensory fibres.
• These sensory fibers originate in trigeminal ganglia
• Sex hormones in particular estrogen ,influence this
system directly or in directly modifying cerebral
blood flow or neuropeptides.
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Types
• I: Primary headaches: migraine or tension
headaches – these are the common causes of
headaches in pregnant women
• II: Secondary headaches: headaches
secondary to trauma, vascular disorders, IIH,
infection, psychiatric problems
• III: Cranial neuralgias, central and primary
facial pain and other headaches
121
THE PRIMARY HEADACHES
• 1. MIGRAINE
• 2. TENSION-TYPE HEADACHE (TTH)
• 3. CLUSTER HEADACHE AND OTHER TRIGEMINAL
AUTONOMIC CEPHALALGIAS
• (uncommon in pregnancy )
• 4. OTHER PRIMARY HEADACHES
122

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THE SECONDARY HEADACHES
• 5. HEADACHE ATTRIBUTED TO HEAD AND/OR NECK TRAUMA
• 6. HEADACHE ATTRIBUTED TO CRANIAL OR CERVICAL VASCULAR DISORDER
( imminent Eclampsia , sub arachnoid hemorrhage, acute ischaemic stroke
,cerebral vein thrombosis)
• 7. HEADACHE ATTRIBUTED TO NON-VASCULAR INTRACRANIAL DISORDER
(idiopathic Intra cranial hypertension, tumors, post dural puncture,)
• 8. HEADACHE ATTRIBUTED TO A SUBSTANCE OR ITS WITHDRAWAL
• 9. HEADACHE ATTRIBUTED TO INFECTION
• 10. HEADACHE ATTRIBUTED TO DISORDER OF HOMOEOSTASIS (
hypoglycemia, hypoxia)
• 11. HEADACHE OR FACIAL PAIN ATTRIBUTED TO DISORDER OF CRANIUM,
NECK, EYES, EARS, NOSE, SINUSES, TEETH, MOUTH OR OTHER FACIAL OR
CRANIAL STRUCTURES
• 12. HEADACHE ATTRIBUTED TO PSYCHIATRIC DISORDER
123
Headache
124

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63
125
126

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64
127
Assessment
128

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129
130

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Headache may be the only symptom of
cerebral venous thrombosis
Neurological conditions were the third
most common cause of death and ahead of
sepsis in the Confidential Enquiries into
Maternal Deaths in the United Kingdom
2006–2008 report (when considering direct
and indirect causes).
131
MIGRAIN
what happens during migraine ?
132

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67
However, pregnancy itself leads to a reduction in the
frequency and severity of attacks of migraine without
aura.
A migraine is classically:
_ unilateral
_ pulsating
_ builds up over minutes to hours
_ moderate to severe in intensity
_ associated with nausea and/or vomiting and/or
photophobia, phonophobia (sensitivity to light and/or
sensitivity to sound) disabling aggravated by routine
physical activity.
133
134

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Migraine -visual aura
135
Bright shimmering 'stars' seen falling across
the image (telischopsia).
Bright-edged castellated line (fortification spectrum).
Scintilating Scotoma: A blind spot surrounded by a bright
starburst. It is often mobile.
Loss, blanking or darkening of one half of the field of
vision (Hemianopia)
136

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137
Women who experience migraines have
a more than two-fold increased risk of
pre-eclampsia compared with women
who do not .
Migraine was associated with a 17-fold
increased risk of stroke and a four-fold
increased risk of acute myocardial
infarction.
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Typically, aura involves fully reversible
phenomena of vision, sensation, motor
power, balance and speech.
The symptoms include flickering lights,
spots, zigzag lines (fortification spectrum),
tingling, numbness and visual holes
(scotoma).
Symptoms evolve over more than 5
minutes and resolve within 60 minutes and
may occur in succession3/24/20 ELBOHOTY 139
139
Avoidance of precipitants, rest, hydration, regular meals and
relaxation.
Paracetamol and anti-emetics may be all that is required but
further analgesia or specific anti-migraine preparations may
be needed.
A non-steroidal anti-inflammatory drug (in the first and
second trimesters)
Use of Triptans in pregnancy is reserved for severe migraine that is
refractory to other treatments
Treatment
140

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71
prophylactic treatment
Women experiencing three to four headaches a
month
when the headache is unresponsive to simple
analgesia.
propranolol (10–40 mg three times a day) has the
best evidence of safety in pregnancy and lactation.
Amitriptyline in the lowest effective dose (25–50 mg
at night) may also be used
141
Idiopathic intracranial hypertension
• is a rare condition but more prevalent in obese
women
• pre-existing disease tends to worsen during
pregnancy.
142

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Presentation
• The headache is generalised, non-throbbing,
aggravated by coughing or straining and is
associated with diplopia (38%) and visual loss (31%)
with papilloedema.
• Signs and symptoms of increased intracranial
pressure: headaches, nausea, vomiting, transient
obscurations of vision, papilloedema
• No localising neurologic signs otherwise, with the
single exception being unilateral or bilateral sixth
nerve paresis
143
Diagnosis
• Diagnosis requires excluding other causes and
finding abnormally elevated cerebrospinal fluid
pressure (>20 cmH2O) on lumbar puncture
• Cerebrospinal fluid can show increased pressure,
but no cytologic or chemical abnormalities
otherwise
• Normal to small symmetric ventricles must be
demonstrated (originally required ventriculography,
but now demonstrated by computed tomography
scan)3/24/20 ELBOHOTY 144
144

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Papilledema & visual field affection
145
Effect of pregnanacy
• Pre-existing IIH tends to worsen in pregnancy,
probably as a result of the weight gain.
• Visual outcome for pregnant women with IIH is
similar to that for non-pregnant women.
• Subsequent pregnancy is not implicated as a risk
factor for recurrence of IIH.
146

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• The course of IIH is variable in pregnancy. Women
with IIH who are planning pregnancy will benefit
from prepregnancy counselling.
• Review of medication and weight loss will help to
reduce complications in pregnancy.
Multidisciplinary care is essential in managing
pregnant women with IIH.
• The investigation and treatment modalities are safe
in pregnancy. IIH is not associated with adverse
pregnancy outcome and vaginal delivery is possible
in women with the condition.
147
Lumbar puncture
• The lumbar CSF opening pressure should be greater
than 250 mmH2O measured with the patient in the
lateral decubitus position.
• The CSF opening pressure measurements and
constituent assay are vital to confirm the diagnosis.
• Repeated lumbar puncture is safe and can be done
at any time during the pregnancy to reduce the CSF
opening pressure.
• Repeated lumbar puncture has been proven to
improve visual symptoms and headache
148

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Monitoring
• multidisciplinary team
– Neurology and ophthalmology reviews must be
undertaken regularly in pregnancy.
– Review in an obstetric anaesthetic clinic is
recommended to discuss the implications of analgesia in
labour.
• The frequency of visual field testing depends on the
symptoms.
• If the patient’s visual symptoms are stable, visual
field testing may be done every 2–3 months.
However, any change in vision should be brought to
immediate medical attention.3/24/20 ELBOHOTY 149
149
Diuretics
• no adverse effects when acetazolamide was used in
pregnancy including the first trimester. Loop
diuretics act by inhibiting cerebrospinal fluid
production.
• There are no adverse fetal effects associated with
loop diuretics when used for a short period of time.
• Thiazide diuretics such as hydrochlorothiazide
should be avoided due to risks of fetal growth
restriction
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• Analgesics
– Simple analgesics such as paracetamol are safe to use in
pregnancy
• Steroids
– Corticosteroids are used occasionally in the treatment of
IIH, but their mechanism of action is not clear.
– It is recommended that corticosteroids be used only in
an acute clinical presentation to minimise any potential
side effects
151
Current surgical treatment
• options include optic nerve sheath fenestration,
and CSF shunting via the lumboperitoneal or
ventriculoperitoneal route.
152

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Delivery
• The increase in intracranial pressure that
occurs during labour is transient and is not
harmful to the mother or baby.
• A caesarean section is not routinely required.
The mode of delivery needs to be determined
by obstetric factors only.
153
Anaestheisa
• Spinal anaesthesia is safe
• Epidural anaesthesia carries a potential risk of
increasing intracranial pressure with a large volume of
drugs in the epidural space.
• Particular attention must be paid to women with a
lumboperitoneal shunt who need regional anaesthesia.
• There is a potential risk of shunt damage.
• Prior imaging is recommended because there is a risk
of shunt entanglement.
• General anaesthesia carries a risk of increasing
intracranial pressure with rapid sequence induction3/24/20 ELBOHOTY 154
154

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78
postpartum
• Breastfeeding
– Acetazolamide can be continued during breastfeeding.
– analgesics (paracetamol and short-term use of
NSAIDs) are safe to use.
– Ibuprofen is the drug of choice if long-term use is
contemplated.
• Hormonal contraception
– There are case reports associating IIH and
progestogen-only contraceptives. The
recommendation is to liaise with neurologist and
ophthalmologist regarding progestogen only
contraception.
155
Posterior reversible encephalopathy
syndrome
• It is a clinical–neuroradiological entity associated
with pre-eclampsia .
• It is characterised by :
headache, vomiting, visual disturbances, seizures and
altered mental state, with radiological findings of
oedema in the posterior circulation of the brain.
156

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157
Reversible cerebral vasoconstriction
syndrome
• It is a cerebrovascular disorder associated with
multifocal arterial constriction and dilation.
• It has a significant association with the postpartum
period.
• It is characterized by recurrent sudden onset and
severe headaches over 1–3 weeks, often accompanied
by nausea, vomiting, photophobia, confusion and
blurred vision.
• Diagnosis requires the demonstration of diffuse arterial
beading on cerebral angiography with resolution within
1–3 months
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80
case
159
160

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81
Cerebral venous thrombosis
• Pregnancy is a recognised risk factor for the
uncommon but catastrophic event of cerebral
venous thrombosis (CVT), perhaps as a result of
prothrombotic changes and dehydration.
• Caesarean section, systemic infection, vomiting and
anaemia increase the risk.
• The greatest risk period is the third trimester and
the first 4 weeks postpartum
161
C/P
•Headache is the most frequently (80–90%) occurring
symptom in cerebral venous thrombosis and often the
first symptom reported by patients.
•More often other clinical manifestations present include
papilloedema, focal deficits, altered consciousness,
seizures and cranial nerve signs, in particular diplopia
caused by sixth nerve palsy.
•Psychosis, in conjunction with focal neurological signs,
has also been reported.
•The development of symptoms may occur over hours,
days or even weeks.
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82
•When CVT is suspected prompt referral to a
neurologist is advised.
•MRI or CT should be done
•Treatment – usually anticoagulation with low-
molecular-weight heparin – should be continued
typically for 6 months.
•CVT is not a contraindication for future
pregnancies but women should be counselled that
they are at risk of further venous thrombotic
events and will require prophylaxis with low-
molecular-weight heparin during pregnancy and
postpartum
163
164

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165
166

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84
Multiple Sclerosis
MS is an autoimmune disease that affects the CNS.
Diagnosis is clinical and based on neurological events separated by time and space.
167
ELBOHOTY3/24/20 168
168

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Effect of pregnancy on multiple
sclerosis
• The risk of relapse is reduced in pregnancy and is
increased significantly in the three months
postpartum. There is no long term effect of pregnancy
or breastfeeding on the progression of multiple
sclerosis.
• Women with MS may find that their pregnancy
aggravates pre-existing urinary/bowel dysfunction;
there is an associated increased risk of urinary tract
infections, with or without pyelonephritis
• Exacerbation of pre-existing motor problems
• Regional analgesia is not contraindicated – there is no
difference in relapse rates
• Breastfeeding may prevent postpartum relapse.
ELBOHOTY3/24/20 169
169
Effect of multiple sclerosis on the
pregnancy
• There is no increase in miscarriage, stillbirth or
congenital abnormality
• If one parent has MS the lifetime risk to the offspring of
developing MS is approximately 3% (compared with
0.1% in the general population)
• Postpartum relapse may interfere with maternal
bonding and the mother's ability to care for her infant
• Increased fatigue and maternal exhaustion in labour
may necessitate assisted delivery.
• Those with neuropathic bladder have increased UTI
ELBOHOTY3/24/20 170
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Management
• Steroids for relapses
• Disability: assistance
• Several disease-modifying drugs (DMD) including
interferon β (IFN-β) 1a and 1b, glatiramer acetate
(GA), natalizumab, mitoxantrone, and fingolimod
are licensed worldwide to reduce the frequency of
clinical attacks with the hope of slowing disability
progression. There is limited data on the risks to
the fetus of these drugs and they should be
avoided in pregnancy and during breast feeding.
ELBOHOTY3/24/20 171
171
Myasthenia gravis
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87
• Myasthenia gravis (MG) is an acquired, neuromuscular
autoimmune disease in which autoantibodies against
the acetylcholine receptor at the neuromuscular
junction cause impaired neuromuscular transmission. It
presents with weakness and fatigue of skeletal muscles.
• Its prevalence is between 1 in 10 000 and 1 in 50 000
and it affects twice as many women as men.
• Abnormalities of the thymus are found in most patients
with MG. Thymectomy results in remission in 35% of
patients and improvements in 50% of patients.
• Signs and symptoms:
• Ocular muscle weakness resulting in diplopia or ptosis
• Difficulty in chewing or talking
• Respiratory muscle weakness (advanced disease).
• Female:male 2:1
ELBOHOTY3/24/20 173
173
Effect of pregnancy
• The effect of pregnancy on MG is variable:
• Exacerbation 40%
• No change 30%
• Remission 30%
• Post partum exacerbation in 30%
• The course in one pregnancy does not predict the course in a subsequent
pregnancy.
• The risk of deterioration is highest in women who become pregnant within
12 months of diagnosis.
• Previous thymectomy reduces the likelihood of exacerbation in pregnancy.
30% of women experience an exacerbation postpartum.
• Disease can be precipitated by:
– emotional distress and anxiety
– intercurrent infection, e.g. pyelonephritis can precipitate a life-threatening
crisis
– increased temperature, e.g. hot weather
– sub-therapeutic levels of medication caused by pregnancy changes, e.g.
hyperemesis, increased circulating blood volume and renal clearance.
ELBOHOTY3/24/20 174
174

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88
Effect on pregnancy
• Pronged Second stage of labour
• Arthrogryposis multiplex congenital (AMC) can affect some infants. The
syndrome consists of nonprogressive congenital joint contractures,
secondary to reduced fetal movements in utero. Some infants survive;
others die in utero or in the neonatal period from pulmonary hypolasia. A
more complex phenotype is occasionally seen:
– dysmorphic facies
– abnormal genitalia
– CNS atrophy
– lung hypoplasia.
• There is a high risk of recurrence
• CTG, it is important to note that a reduction in both short term variability
and accelerations may be seen in fetuses of mothers with MG
ELBOHOTY3/24/20 175
175
Neonatal myasthenia
• 20% of neonates.
• Transient, resolves in 2 months
• Transplacental passage of Ig G antibodies
• Ttt anticholineesterase drugs
• Typical features of this condition
• Poor sucking
• Feeble cry
• Generalised hypotonia
• Swallowing difficulties
• Facial paresis/ptosis
• Respiratory depression.
• Symptoms usually start 12–48 hours after birth. Delayed onset may be due to the
transplacental passage of maternal anticholinesterase medication and α-FP. α-FP
inhibits the binding of the antibody to the acetylcholine receptor. Complete
recovery usually occurs within 2 months. Treatment is with anticholinesterase
drugs and supportive care
ELBOHOTY3/24/20 176
176

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Preconception counselling
• Effective contraception until disease control is
optimal
• Discuss the importance of close supervision in
pregnancy, possible adjustment of medication
and risk of exacerbation
• Provide information about neonatal risks of MG.
• Drugs
– Anticholineesterase: long acting, increase dose
– Corticosteroids
– Azathioprene and plasmapharesis: crises
ELBOHOTY3/24/20 177
177
Antepartum care
• Joint care with a neurologist
• Continue anticholinesterase medications, e.g. pyridostigmine.
Increased doses may be required as pregnancy advances – it may
be appropriate to reduce the dosage interval rather than increasing
each dose. In large doses anticholinergics can result in paradoxical
weakness and respiratory failure
• Any infection should be promptly diagnosed and treated
• Anaesthetic assessment – many drugs should be avoided in MG.
Women with MG are more resistant to depolarising neuromuscular
blocking agents, e.g. suxamethonium and are more sensitive to
non-depolarising muscle relaxants. Narcotics can cause muscle
fatigue
• Magnesium sulfate should be avoided as it may precipitate a crisis
• Corticosteroids, immunosupressants and plasmapheresis may be
required for disease control and can be used in pregnancy.
ELBOHOTY3/24/20 178
178

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90
Intrapartum care
• Administer anticholinesterase medications
parenterally to ensure adequate absorption
• Aim for vaginal delivery but may require
instrumental delivery to avoid exhaustion in
second stage
• Caesarean section should be performed for
obstetric reasons only.
ELBOHOTY3/24/20 179
179
Breast feeding
• Acetylcholinesterase receptor antibodies pass
to the neonate in breast milk and may
potentiate neonatal MG
• Maternal anticholinesterase drugs in breast
milk may cause gastrointestinal upset in the
newborn
• Breast feeding may be inadvisable in the
presence of high maternal antibody titres
and/or high doses of anticholinesterases.
ELBOHOTY3/24/20 180
180

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91
Bell's palsy
• Typically presents in the third trimester or
early puerperium.
• Differential diagnosis includes meningitis, SAH
and SOL.
• Associated with raised BP and PET.
• Usually resolves completely.
• Steroids are not usually indicated
ELBOHOTY3/24/20 181
181
182

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Pregnancy and spinal cord injury
183
184

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93
185
Antenatal problems
186

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Autonomic dysreflexia
• A spinal cord injury at the level of T6 or above results in loss
of supraspinal control of the greater splanchnic sympathetic
outflow.
• AD results from disconnection of the sympathetic nervous
system from supraspinal regulation, disabling the negative
feedback loop.
• A noxious stimulus below the level of the SCI will result in an
uncontrolled sympathetic outflow below the level of the
lesion.
• This causes a rise in blood pressure, activating the vagus
nerve via baroreceptors, (that have ‘reset to fire’ at a lower
blood pressure since the SCI) causing bradycardia.
• AD is a medical emergency and can be fatal.
• Treatment is by removing the noxious stimuli, or medical
management in the absence of an identifiable trigger.3/24/20 ELBOHOTY 187
187
• Delayed or suboptimal management can lead to
maternal intracranial bleeding, death and fetal
bradycardia or heart rate irregularities due to
paroxysmal hypertensive episodes.
• This is in contrast to pregnancy-induced hypertension,
usually (but not always) presenting as a gradual and
sustained rise in blood pressure.
• An early sign of AD, rising blood pressure in a
tetraplegic, is frequently missed. This is because of a
low basal blood pressure; an individual’s baroreceptors
are reset to fire at a lower level than in those without
SCI. For example, a blood pressure of 120/80 mmHg in
a tetraplegic may be a sign of AD and would require
immediate sublingual nifedipine if the cause for AD is
not identified or removed.
188

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Autonomic dysreflexia Symptoms
189
190

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Spasticity
• Spasticity is a ‘symptom of upper motor neurone disorder,
resulting from intact spinal reflexes persisting below the level of
the injury’.
• Spasms protect bone by reducing osteoporosis in limbs although
at times may cause injury by throwing a person off their
wheelchair.
• a 12% incidence of worsening of spasticity in pregnancy.
• Treatment of spasms in pregnancy is with baclofen (ideally via an
intrathecal pump).
• Oral baclofen has been associated with neonatal withdrawal
symptoms – from irritability and poor feeding to seizures. This
effect has not been reported with the use of intrathecal baclofen.
• Local practice is to use oxybutinin for the control of bladder
spasms in pregnancy, discontinuing oral baclofen if possible.
191
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Anesthetic review
193
• Unless there is an obstetric contraindication, a vaginal
delivery is recommended. Multidisciplinary care of women
• with SCI, involving obstetricians, midwives and obstetric
anaesthetists with experience in caring for women with
spinal cord injury, together with support from the spinal
team and physiotherapy is essential for optimal care. If a
psychiatric referral is needed, this too should be to a unit
with experience in managing women with SCI.
• When cared for at a centre with expertise in managing
women with SCI, a safer pregnancy and delivery can be
expected.
• Alternatively, the local unit should work in collaboration with
the nearest spinal injuries centre.
194

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Anesthesia
• In patients with a history of AD, a prophylactic
epidural is recommended early in labour.
• Epidurals and spinal analgesia are useful because
opioid analgesia and local analgesia that are used to
block the efferent and afferent nerves, help to
attenuate potential triggers for autonomic
dysreflexia.
195
During CS
Lower segment caesarean section with a suprapubic
catheter in situ
The skin incision is made 2 cm above the suprapubic
catheter insertion. The catheter is recommended to
be changed 24 hours before surgery. Non-absorbable
sutures are used for closing the rectus sheath and
skin to reduce the risk of wound dehiscence in
denervated tissue. Skin is usually sutured using
interrupted non absorbable suture material.
196

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99
• A 26-year-old obese white women at 34 weeks of gestation presented to triage
with history of waking up with headache that has been gradually worsening. The
headache is associated with nausea, one episode of vomiting, intermittent tingling
in her left arm and blurring of vision in left eye. She has past history of headaches;
however, it has not been as intense as it is now.
• Body mass index = 40
• Blood pressure = 130/80 mmHg
• Pulse rate = 78 per minute
• Respiratory rate = 13 per minute
• Temperature = 37.2 °C
• There is no neurological deficit and neck stiffness, normal fundoscopy and no pedal
edema.
• Haematology: WBC = 9.0 x10
9
/l, Hb = 134 g/l, platelets = 325, ESR = 5
• Biochemistry: CRP = 2, liver function tests and U&Es are within normal limits
• Urinalysis: protein negative, glucose negative, pus cells positive, WBC negative,
nitrite negative
• What would be the most likely cause of her headache?
• Sub-arachnoid haemorrhage.
Space occupying lesion.
Pre-eclampsia.
Migraine.
Benign intracranial hypertension.
ELBOHOTY3/24/20 197
197
• The answer is migraine. The patient has
migraine which is one of the most common
cause headache in pregnancy. All her
observations, examination findings along with
blood and urinalysis are within normal limit.
This makes the other diagnoses
unlikely
ELBOHOTY3/24/20 198
198

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100
• A 25-year-old obese women was rushed into A&E following a seizure affecting the left side of her
body. She was 3 days postnatal and had a history of gradual onset of headache for 2 days with
photophobia. On further examination she was unable to move the left side of her body, had
difficulty in speaking and slight disorientation.
• On examination:
• BMI = 42
• BP = 140/90
• HR = 100
• saturations = 98% air
• temperature = 38.6°C
• chest = clear
• CVS = normal heart sounds
• CNS = left upper and lower limb decrease in power, weak reflexes and variable sensory loss.
• Urine dipstick = blood +++ and leucocytes +
• What is the most likely diagnosis?
• Status epilepticus
Subarachnoid hemorrhage
Migraine
Eclampsia
Cerebral vein thrombosis
ELBOHOTY3/24/20 199
199
• The correct answer is cerebral vein
thrombosis. Risk factors for CVT include
obesity, thrombophilia, dehydration, infection.
This woman presents with seizures, a
decreased level of consciousness and focal
neurological deficit depending on the area
involved. Diagnosis is made by CT venography
or MRI venography. Treatment includes
hydration, anticonvulsant and antcoagulation.
ELBOHOTY3/24/20 200
200

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101
stroke in pregnancy
• It is defined as a neurological deficit attributed to
acute focal injury of the central nervous system by a
vascular cause, including cerebral infarction,
cerebral vein thrombosis (CVT), intracranial
haemorrhage (ICH) and subarachnoid
haemorrhage.
• Pregnancy-related strokes occurring in 30 in 100000
pregnancies; strokes are three times more common
among pregnant than among nonpregnant
individuals aged 15–44 years.
201
• In pregnancy, ischaemia, haemorrhage and venous
thrombosis have a similar contribution to aetiolog
• Most of strokes (90%) occur peripartum or in the 6
weeks following delivery
• A case fatality rate ranging from 8.8% to 20.0%.
• Fatality in haemorrhagic stroke of pregnancy is 13.9%,
compared with 3.4% in ischaemic stroke in pregnancy.
Likewise, residual disability is higher in haemorrhagic
stroke (50%) compared with ischaemic stroke (33%)
events in pregnancy, with ICH being the single greatest
cause of death
•
202

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The independent risk factors for stroke
• maternal age >35 years (odds ratio [OR] 2.3),
• migraine (OR 8.5)
• gestational diabetes (OR 26.8)
• pre-eclampsia or eclampsia (OR 7.7)
• pre- existing hypertension (OR 8.5),
203
Symptoms
• Stroke is a clinical syndrome characterised by
rapidly developing symptoms, with signs of focal
cerebral loss of function and no cause other than
that of a vascular origin. The symptoms and signs
relate to the affected area of the brain
• 40% of patients presenting with typical stroke
symptoms and signs. It is often associated with a
headache; drowsiness or confusion can also occur
with deep vein occlusion of the thalamus
204

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103
205
• Subarachnoid haemorrhage is not uncommonly
associated with hypertension as a consequence of
the bleed, rather than being caused by
hypertension itself.
• Severe intracranial bleeds can also be associated
with a relative bradycardia.
206

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Imaging
• All patients with suspected AIS should have
brain imaging on arrival to hospital. In most
cases, non-contrast computed tomography
(CT) will provide the necessary information to
make decisions about acute intravenous
thrombolysis.
• ICH is a contraindication to thrombolysis, with
management directed towards haemostasis
and correction of coagulopathy with surgical
intervention if appropriate.3/24/20 ELBOHOTY 207
207
• CT angiogram should be performed for all potential
candidates for mechanical thrombectomy to
evaluate for large vessel occlusion
208

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105
MRI
• Other investigations include magnetic resonance
imaging (MRI) of the brain, which may further
distinguish between stroke subtypes and vascular
imaging, either with carotid Doppler or magnetic
resonance angiogram.
• Magnetic resonance angiogram of extracranial and
intracranial vessels may be particularly helpful for
further evaluation of posterior circulation strokes if
CT angiography is unavailable
209
Investigations for underlying causes of
stroke in a young woman
210

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106
Intravenous thrombolysis
• Irrespective of age or stroke severity and
despite a risk of haemorrhagic transformation
of 2–6% in the first few days after treatment,
recombinant tissue plasminogen activator (rt-
PA) significantly improves the overall odds of
good stroke outcome when administered
within 4.5 hours of stroke onset.
211
212

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107
213
• Antenatal patients should be observed for vaginal or
intra-abdominal bleeding, pain and further
neurological signs. Ultrasound can be useful to
observe for retroplacental haematoma formation and
to assess fetal wellbeing.
• The safety and efficacy of thrombolysis in the early
postpartum period (<14 days after delivery) are not
well established.
• A history of major surgery within the preceding
2weeks is a relative contraindication for systemic
thrombolytic therapy. This curtails its use after a
caesarean section or a difficult vaginal delivery.
• Levels of thrombolytic agents in milk are highest in
colostrum and decrease rapidly during the first week.
No information is available, however, on its safety
during breastfeeding.
214

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Mechanical thrombectomy
• Up to 6 hours
• All eligible patients with a large vessel
occlusion on CT angiogram should be
considered for clot retrieval and urgently
referred to a neurointerventional centre.
215
Management of intracerebral
haemorrhage
• Immediate treatment is directed towards haemostasis, correction of
coagulopathy and hyper/hypoglycaemia, blood pressure control and
venous thromboembolism prophylaxis.
• Coagulopathy and thrombocytopenia should be corrected.
• Patients on warfarin with a prolonged international normalised ratio for
prothrombin time should have their warfarin withheld and receive
intravenous vitamin K and prothombin complex.
• Aggressive blood pressure control with an aim to lower systolic blood
pressure to 140 mmHg is safe unless contraindicated and can be effective
in improving functional outcome.
• All patients with ICH should have intermittent pneumatic compression
from the day of admission.
• Antiepileptic medications should be used to treat patients with clinical
seizures or with electroencephalogram changes.
• Surgical decompression (with or without external ventricular drain
insertion) should be considered in patients with cerebellar haemorrhage
with deteriorating neurological function, or in patients with brainstem
compression and/or hydrocephalus from ventricular obstruction3/24/20 ELBOHOTY 216
216

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Management of cerebral venous
thrombosis
• The treatment of CVT is predominantly
anticoagulation with either low molecular
weight heparin (LMWH)
217
Management of pre-
eclampsia/eclampsia and posterior
reversible encephalopathy syndrome
• Magnesium sulphate treatment has been shown to
increase seizure threshold and decrease
neuroinflammation without affecting blood–brain-
barrier permeability
• The treatment of PRES is directed towards
optimising blood pressure control, removal or
treatment of suspected causative factors and, in the
case of pre-eclampsia and eclampsia, delivery of the
fetus. In most cases, PRES resolves spontenously
within days to weeks.
218

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Secondary prevention strategies
• Recurrent strokes account for 25–30% of all strokes.
• Blood pressure management is one of the key elements of secondary
prevention.
• Gradual, sustained lowering of blood pressure is recommended for all
stroke patients – but care is needed, particularly in patients with
carotid or vertebrobasilar occlusive disease.
• Administration of aspirin is recommended in AIS within 24–48 hours
of onset. For patients receiving thrombolysis, aspirin is delayed until
24 hours later, when ICH is excluded. In patients presenting with
minor stroke or transient ischaemic attacks, treatment with dual
antiplatelet therapy (aspirin and clopidogrel), begun within 24 hours
and continued for 21 days, can be beneficial for early secondary
stroke prevention but this combination can lead to major
haemorrhage so risk benefit should be strictly applied.
219
Medications and safety during the
pregnancy
• The safety of aspirin in pregnancy is well
documented
• clopidogrel should not be withheld because of
pregnancy but should be stopped 7–10 days before
a scheduled surgery or delivery.
• statin use: no clear relationship between congenital
anomalies
220

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Mode of delivery
• In most cases, an early epidural was planned to
reduce fluctuation in maternal blood pressure, as
well as a shortened second stage with an elective
operative vaginal delivery to prevent prolonged
Valsalva and increased intracranial pressure
• it remains unclear as to which is the safest mode
of delivery in women with ruptured aneurysms,
untreated or partially treated arteriovenous
malformations and very recent neurosurgery
221
222

Neurological diseases in pregnancy

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