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REVIEW

Neurological disease in
pregnancy

premenstrual hormone changes and the combined oral contraceptive pill) and dietary factors (e.g. chocolate, cheese and wine).
Diagnosis
A careful history and neurological examination, particularly
looking for focal signs will aid diagnosis. It is important to
consider secondary causes of headache, such as pre-eclampsia,
subarachnoid haemorrhage, cerebral venous thrombosis and
meningitis, and to investigate appropriately if there are concerns.
A diagnosis of migraine is more likely if the headache is
unilateral and throbbing, and if it associated with visual
prodromal symptoms, nausea and vomiting. Migraine may also
be associated with focal signs including hemianopia and hemiplegia, although this presentation is rare (0.1% of cases), and
occurs mainly in the third trimester.
Migraine is associated with the development of gestational
hypertension or pre-eclampsia, predominantly in women whose
headache does not improve with pregnancy and has been postulated
to be an important risk factor for maternal ischaemic stroke.
Migraine has not been associated with adverse fetal effects including
miscarriage, malformations, stillbirth and low birthweight.

Muna Noori
Mandish K Dhanjal

Abstract
Neurological diseases are commonly encountered in women of childbearing age and pregnancy can pose a unique, if not challenging aspect
to their management. A number of conditions exist prior to pregnancy and
either the condition itself or its therapy may impact on the pregnancy,
labour or delivery. Conversely, pregnancy may interfere with or preclude
optimal treatment of some neurological diseases, which highlights the
importance of multidisciplinary care in such women. This review outlines
the natural history, diagnostic features and management options of
a number of common neurological conditions in pregnancy.

Keywords anti-epileptic agents; cerebrovascular disease; epilepsy;


headache; migraine; neurological disease; neuropathy; pregnancy; prepregnancy counselling

Treatment options for migraine in pregnancy


Inadequate treatment of migraine may have a serious impact on
maternal wellbeing. Effective management of migraine in pregnancy includes:
 avoidance of triggers
 treatment of acute episodes
 prevention of future attacks
Non-pharmacological measures to avoid migraine such as
adequate sleep, stress management, relaxation techniques,
biofeedback, acupuncture, and massage may be of benefit.
Among therapeutic options in an acute migraine attack, paracetamol is the first-line therapy and can be given with an antiemetic. Codeine phosphate may be of benefit if paracetamol is
ineffective. Migraleve (paracetamol, codeine  buclizine or
sumatriptan) is a useful combination drug. Non-steroidal antiinflammatory agents such as ibuprofen are effective but should
not be used in the third trimester due to the risk of premature
closure of the ductus arteriosus and oligohydramnios. Ergot
derivatives(e.g. ergotamine) cause placental ischaemia through
vasoconstriction and should be avoided in pregnancy. Many
women who experience severe migraine have been managed at
one time or another with triptans (5-HT agonists). Triptans
(sumatriptan, naritriptan), are useful in treating acute attacks but
are of limited benefit in prevention of future migraine. Triptans
bind to 5-HT receptors, causing vasoconstriction and inhibition
of neuronal inflammation. Population studies evaluating the
risks of triptan use during pregnancy have not demonstrated an
increased risk in congenital malformations. Minimal amounts of
triptans have been measured in breast milk and they are therefore considered to be safe during breastfeeding.
Frequent migraine attacks warrant prophylaxis. Low-dose
Aspirin (75 mg daily) is a first-line agent and is safe in pregnancy.
b-blockers (propranolol 10e40 mg three times a day) are effective
in 80% of cases and can be used in those without asthma if aspirin
is ineffective. Tricyclic anti-depressants (amitriptyline 25e50 mg
at night), calcium channel blockers (Verapamil 40e80 mg at
night), and cyproheptadine (2e4 mg at night) may be useful in

Migraine and tension headache


Migraine is a common disorder in women and frequently presents during child-bearing years. It may present de novo in pregnancy and may be difficult to differentiate from tension headache
as migraine can present with or without an aura.
Migraine with and without aura may represent separate clinical entities. In a study of women who experienced migraine with
aura, 20% suffered their first episode during pregnancy, with no
predilection for a specific trimester. Frequency of migraine was
not significantly altered by pregnancy. Migraine without aura,
however, tended to improve or cease during pregnancy, particularly in later pregnancy.
Pathogenesis
Tension headache is thought to occur as a result of muscle
contraction and is often stress-related. Migraine is regarded as
a neurovascular disorder in which sensitization and activation of
trigeminal ganglia promotes inflammation of nerves supplying
meningeal blood vessels, thereby causing cerebral vasodilatation.
Triggers for migraine include stress, hormonal factors (e.g.

Muna Noori BSc MRCOG PhD is a Sub-specialty Trainee in Maternal and


Fetal Medicine at Imperial College Healthcare Trust, Queen Charlottes
and Chelsea Hospital, Du Cane Road, London, UK. Conflicts of interest:
none declared.
Mandish K Dhanjal BSc MRCP MRCOG is a Consultant Obstetrician and
Gynaecologist at Imperial College Healthcare Trust, Queen Charlottes
and Chelsea Hospital, Du Cane Road, London, UK. Conflicts of interest:
none declared.

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 Minor malformations(dysmorphic facies, hypertelorism,


hypoplastic nails, midface hypoplasia)
Associated malformations and absolute risks are summarized in
Tables 1 and 2.
Sodium valproate is the most teratogenic anti-epileptic agent and
is responsible for 2% of neural tube defects. Polytherapy, particularly regimes including valproate, increases the risk of congenital
malformation, increasing further with each additional agent. There
is likely to be a dose-dependent effect of malformations with sodium
valproate and lamotrigine so limiting the dosage of these agents
during the first trimester should be considered. The combination of
valproate and lamotrigine has also been shown to be particularly
teratogenic when compared to a combination of carbamazepine
and lamotrigine. Data regarding types of malformations and rates
with use of lamotrigine, topiramate and levetiracetam in pregnancy
are limited. There is no evidence to suggest an increased risk of fetal
malformations in women with untreated epilepsy in pregnancy.
In the last decade, an increasing number of studies have
addressed the long-term safety of AEDs on child development but
results have been conflicting. While maternal IQ has an influence
on offspring IQ, meta-analysis data have shown significantly
reduced verbal IQ in children whose mothers were treated with
sodium valproate during pregnancy. These effects were not
evident after maternal carbamazepine use.
Recent meta-analysis data have shown that epilepsy, without
the use of AEDs in pregnancy, is not associated with an increased
cognitive impairment in their offspring.

resistant cases. There are insufficient data regarding safety of


Pizotifen (Sanomigran) for prevention of migraine in pregnancy.
Treatment for tension headache
Stress relieving techniques, massage and simple analgesia work
best for alleviating tension headaches.
Postpartum headache
Migraine attacks can recur postpartum in 34e55% of cases, but
are more likely to be milder than usual attacks, and less likely to
be unilateral. Breastfeeding appears to protect women from
migraine recurrence. In one study, migraine recurred in the first
month following delivery in 43% of women who were breastfeeding and in 100% of women who were not.
Other causes of a postpartum headache must be considered, and
if persistent may require more detailed investigation with neuroimaging. If the patient received a spinal or epidural anaesthetic
during labour and delivery, a dural puncture must be ruled out.
Post-dural puncture headache
A post-dural puncture headache (PDPH) arises due to loss of
cerebrospinal fluid and reduction in cerebrospinal pressure. It
often presents in the days following delivery as a fronto-occipital,
throbbing headache which occurs abruptly on standing and
improves almost immediately on lying flat again. It may be
associated with visual symptoms, nausea and vomiting and
warrants review by an anaesthetist. An epidural blood patch is
often highly effective in relieving this form of headache.

Pre-pregnancy management
Pre-pregnancy counselling should be routine practise in women
with epilepsy. Prior to pregnancy, seizures should be well-controlled
on the least number of AEDs and with the lowest possible dose. A
recent meta-analysis has shown that freedom from seizures for
9 months prior to pregnancy is associated with a high likelihood
(84e92%) of remaining seizure-free during pregnancy. Women
who have been seizure-free for 2 years prior to pregnancy, may
consider discontinuation of their anti-epileptic medication, although
this should be an informed decision, particularly as return of seizure
activity could risk loss of their driving licence. Women with juvenile
myoclonic epilepsy should not discontinue their medication.
Women treated with sodium valproate should be counselled
regarding reducing their dose or switching to an alternative AED.
If this is not deemed appropriate, divided doses or a slow release
preparation (EpilimChrono) are preferable, as peak plasma
concentrations are lower and the risk of neural tube defects is
reduced.

Epilepsy
Epilepsy, which occurs in 0.5e1% of women, is the most
common neurological disease to complicate pregnancy and is
one of the leading causes of indirect maternal deaths in the UK.
Classification
Epilepsy is classified according to the clinical type of seizures,
electroencephalographic (EEG) appearances, and whether they
are partial or generalized. The most common forms are:
 tonic-clonic (grand-mal)
 absence (petit mal)
 temporal lobe seizures (complex partial seizures)
 myoclonic seizures
The majority of cases of epilepsy are idiopathic although a family
history exists in up to 30% of patients. Secondary epilepsy may
occur in subjects who have had previous neurosurgery, an
intracranial mass lesion or antiphospholipid syndrome.
Furthermore, while most women with epilepsy are diagnosed
prior to pregnancy, some may have their first fit in pregnancy.
The differential diagnosis for a seizure in pregnancy includes
eclampsia, intracranial mass lesion, cerebral thrombosis, stroke,
metabolic (hypoglycaemia) and electrolyte imbalances (hyponatraemia, hypocalcaemia).

Malformations associated with anti-epileptic drugs


Phenytoin
Carbamazepine
Sodium Valproate
Phenobarbitone
Lamotrigine

Anti-epileptic drugs
Anti-epileptic drugs (AEDs) cross the placenta and are teratogenic. The major malformations seen include:
 Neural tube defects
 Orofacial clefts
 Congenital heart defects

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Topiramate

Cleft palate
Posterior cleft palate; neural tube defects
Neural tube defects; facial clefts, hypospadias
Cardiac malformations; orofacial clefts
Neural tube defects; facial clefts;
hypospadias e limited data
Orofacial clefts; hypospadias e limited data

Table 1

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Intrapartum management
Epilepsy is not a contraindication to vaginal delivery and
Caesarean section should be performed for obstetric indications or
in the event of recurrent generalized seizures in labour. Seizure
recurrence is higher during labour and in the first 24 h after
delivery. When in labour, women should be offered an early
epidural as pain and anxiety can trigger seizures. Anti-epileptic
drugs should be continued throughout labour in suppository form
if necessary. In the event of a seizure, women should be managed
with facial oxygen, intravenous lorazepam or rectal diazepam.

Absolute risks of congenital malformations arising from


anti-epileptic drug monotherapy
Carbamazepine
Lamotrigine
Phenytoin
Sodium valproate

900
647
82
715

2.2
3.2
3.7
6.2

(1.4e3.4)
(2.1e4.9)
(1.3e10.2)
(4.6e8.8)

Table 2

Postpartum care
Sleep deprivation lowers seizure threshold so women often
require additional supervision and support postpartum. They
should be advised about ways of minimizing risk to herself and
the baby, such as not to bathe their babies unaccompanied and to
change nappies on the floor rather than on a changing table.
The neonate should be given 1 mg of intramuscular vitamin K to
prevent haemorrhagic disease of the newborn. Women should be
encouraged to breastfeed as in most cases, AEDs cross into breast
milk in minimal amounts(3e5% of maternal levels). Lamotrigine
and phenobarbitone cross in larger amounts (30e50%) so women
treated with these agents should be advised to breastfeed prior to
taking their AEDs to minimize neonatal exposure.

Antenatal management
The consequences of uncontrolled epilepsy for mother and baby
must be balanced against the risks of teratogenesis and childhood
neurocognitive development that are associated with use of
AEDs. Although short periods of hypoxia occurring during
seizures are not known to be harmful for the developing fetus,
more prolonged or recurrent episodes of hypoxia may be
harmful.
While women with uncontrolled epilepsy prior to pregnancy
are more likely to experience an increase in seizure frequency
during pregnancy, other causes for poor control include:
 a lack of drug compliance (due to concerns regarding
teratogenesis)
 decreased drug levels as a result of vomiting in early
pregnancy
 lower circulating free drug levels (carbamazepine and
lamotrigine)
 decreased gastrointestinal absorption
 lack of sleep
The option of discontinuing AEDs warrants very careful consideration as in doing so, seizure activity may resume or increase.
Some women choose to discontinue their AEDs when they become
pregnant due to concerns about teratogenesis. It may be appropriate to counsel restarting AEDs in women with regular seizures,
especially after the first trimester when the risk of teratogenesis
has passed. However, long-term neurocognitive effects of sodium
valproate are likely to be associated with exposure throughout
pregnancy, particularly in the third trimester.
Women on AEDs should commence folic acid (5 mg daily)
pre-conception and to continue this throughout pregnancy.
Those on carbamazepine, valproate or lamotrigine, which exhibit
little protein binding, may need to increase their doses with
advancing pregnancy as free drug levels tend to fall. This fall is
most marked with lamotrigine. A baseline serum AED level may
be useful in establishing compliance and for adjusting future
doses, particularly in women who have regular seizures. Vitamin
K (10e20 mg daily) should be prescribed from 36 weeks gestation, to women taking enzyme-inducing AEDs (phenytoin, carbamazepine, phenobarbitone, and primidone), to increase
vitamin K-dependent clotting factors in the baby and reduced the
incidence of haemorrhagic disease of the newborn.
Women should be offered first trimester ultrasound screening
and a detailed anomaly scan, including fetal echocardiography to
detect fetal malformations. The womans family members need
to be aware of how to place her in the recovery position in the
event of a seizure and the woman should be advised to either
shower, or to bathe in shallow water.

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Multiple sclerosis
Multiple sclerosis (MS) is a chronic inflammatory condition affecting
the central nervous system. Onset is typically in the second or third
decade of life and it is twice as prevalent in females as males. Multiple
sclerosis tends to run a relapsing and remitting course and most
commonly presents with optic neuritis, diplopia, sensory impairment
or motor weakness of the limbs. Disease progression is extremely
variable with complete resolution between relapses in some cases,
and progressive neurological deterioration in others. Multiple sclerosis is unlikely to present for the first time during pregnancy.
Pathogenesis
The pathogenesis of MS is incompletely understood but involves
a maladaptive humoural and cell-mediated (predominantly T
helper cell type I) response to an antigen that has yet to be
characterized. The autoimmune inflammatory cascade that
ensues results in CNS conduction block, demyelination, and
axonal damage which may be reversible or persistent. Areas of
demyelination within the spinal cord and brain can be demonstrated using Magnetic Resonance Imaging (MRI).
Pregnancy and MS
The prospective PRIMS (Pregnancy in Multiple Sclerosis) study
reported a reduction in MS relapse during pregnancy, particularly
in the third trimester (70% reduction), and a compensatory
increase in relapse rates in the first 3 months postpartum (40%
relapse rate), with a subsequent decline in relapse rates to prepregnancy levels by 10 months postpartum. Pregnancy and
breastfeeding do not appear to have an adverse effect on future
disease course or MS progression, and MS does not appear to
have an effect on pregnancy outcome and is not a contraindication to vaginal delivery or epidural anaesthesia.
Women with advanced MS may experience deterioration in their
mobility and worsening spasticity as pregnancy advances, due to

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increasing weight and an altered centre of gravity. Patients should


be warned against falls and may require additional physiotherapy
during pregnancy. As pregnancy is a prothrombotic state, thromboprophylaxis with compression stockings, aspirin or low molecular weight heparin should be considered in immobile patients.
Patients with a pre-existing neurogenic bladder are at
increased risk of recurrent urinary tract infections, which require
prompt treatment with antibiotics, or more frequent self-catheterizations to minimize infections.

Risk factors for stroke during pregnancy


Migraine
Haematological
Sickle cell disease, thrombophilia,
Cardiovascular
Hypertension, mitral valve disease, infective endocarditis,
peripartum cardiomyopathy, paradoxical embolus, aortic dissection
Endocrine
Diabetes, electrolyte disturbances
Antiphospholipid syndrome
Vasculitis
Systemic lupus erythematosus (SLE), TTP
Black ethnicity
Age >35 years
Pregnancy-related
Pre-eclampsia, eclampsia, multiple pregnancy, multiparity,
Caesarean section
Lifestyle
Smoking, alcohol and substance abuse

Treatment
Relapses of MS can be managed with rehabilitation but severe,
acute relapses may warrant treatment with high dose corticosteroids during pregnancy and breastfeeding. Agents that reduce
relapses such as b-interferon and Glatiramer are usually discontinued during pregnancy due to a paucity of safety data. The
mainstay of MS relapse prevention is b-interferon. Recent case
series of women with first trimester exposure to either b-interferon
or Glatiramer did not demonstrate an increased miscarriage rate or
congenital malformation rate compared to women who were not
treated with these agents. Treatment with b-interferon was
however associated with lower birthweight. As data are limited,
use of either b-interferon or Glatiramer should be restricted to
more complicated cases, where benefits outweigh potential risks.
Additional drugs that are occasionally used warrant consideration. Azathioprine is safe in pregnancy, but methotrexate is
associated with miscarriage and malformations and should be
avoided. Drugs used to relieve spasticity (baclofen), paroxysmal
pain or dysaesthesiae (carbamazepine and gabapentin) may also
be used. Depression is sometimes encountered in MS sufferers so
anti-depressants may be required during pregnancy.

Table 3

Subarachnoid haemorrhage
Subarachnoid haemorrhage (SAH) occurs in two per 10,000
pregnancies which is a two to three fold increase from nonpregnant rates. In the puerperium, rates of SAH are up to 20-fold
higher. Presenting signs and symptoms include:
 Headache, which is often sudden-onset and occipital
 Vomiting
 Altered consciousness or sudden collapse
 Neck stiffness
 Papilloedema
 Focal neurological signs
Subarachnoid haemorrhage may occur due to rupture of an
arterial (Berry) aneurysm or an arterio-venous malformation
(AVM). Pregnancy-related ruptured aneurysms have been shown
to occur antenatally in 90% of cases (most commonly in late
pregnancy), in the puerperium in 8% of women, and during
labour in the remaining 2% of cases.

Stroke
Stroke in pregnancy occurs in 34.2 per 100,000 deliveries, and
contributes to more than 12% of maternal deaths. Pre-eclampsia
and eclampsia are associated with 25e45% of pregnancy-related
stroke, including haemorrhagic and non-haemorrhagic causes.
Most pregnancy-related strokes occur in the third trimester or
postpartum and this is especially true of venous thrombosis. The
common causes of stroke out with pregnancy, including hypertension, and diabetes and smoking are less common in pregnancy so rarer causes need to be considered. Risk factors are
outlined in Table 3.

Investigation
Investigation of stroke in pregnancy should proceed as in the
non-pregnant state, but pregnancy-specific causes require special
consideration. Magnetic resonance imaging (MRI) or computed
tomography (CT) can confirm ischaemic stroke and differentiate
haemorrhage from infarction. Lumbar puncture, echocardiography and carotid artery Dopplers may also help to establish an
underlying cause. CT angiography may also be useful and should
not be withheld in pregnancy.

Ischaemic stroke
Most pregnancy-related ischaemic strokes occur in the distribution of the carotid and middle cerebral arteries, and predominantly occur postpartum.
Haemorrhagic stroke
Haemorrhagic stroke is rare in women of child-bearing age
outside pregnancy but is as common as ischaemic stroke during
pregnancy. It accounts for two to four maternal deaths annually
in the United Kingdom.
Haemorrhage occurring in pre-eclampsia and eclampsia is
thought to occur secondary to cerebral vasospasm, loss of cerebral autoregulation and breakthrough of the vessel wall. Rupture
of vascular malformations may also contribute to maternal stroke
rates and may occur in any trimester.

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Management
Management of ischaemic stroke includes anti-platelet therapy
(Aspirin 75 mg daily), which should be continued postpartum.
Some patients require anticoagulation with unfractionated or low
molecular weight heparin. Warfarin crosses the placenta and is
teratogenic, so its use requires careful consideration. Thrombolysis for stroke is generally contraindicated in pregnancy and

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the puerperium due to the increased risks of haemorrhage but


data are limited.
Management of haemorrhagic stroke is similar to non-pregnant women and often involves neurosurgical intervention,
including clipping or endovascular treatment. These interventions have been performed in all trimesters of pregnancy and are
associated with low fetal and maternal mortality rates. With
regards to delivery, epidural is contraindicated only if the intracranial pressure is elevated and Caesarean section should be
performed for obstetric indications.

edrophonium chloride, a short-acting anticholinesterase, which


transientlyimproves symptoms. Electromyography is an alternative investigation. Anticholinesterase antibodies are present in
90% of patients with MG.
Myasthenia gravis and pregnancy
During pregnancy, the course of the disease is unpredictable and
MG may remain stable, improve or worsen, although women who
have undergone thymectomy have lower relapse rates during
pregnancy. Postpartum exacerbations occur in 30% of women.
Myasthenia gravis can be managed during pregnancy with
relatively safe and effective therapies. Caesarean section is recommended for obstetric reasons only. Epidural anaesthesia is
advised to reduce physical and emotional stress of labour. Longacting anticholinesterase drugs (pyridostigmine) are the mainstay of treatment and higher or more frequent doses may be
required with advancing gestation. When MG symptoms are not
satisfactorily controlled, corticosteroids, azathioprine and in
some cases cyclosporin A have be used; thymectomy is rarely
recommended in pregnancy. Life-threatening conditions such as
respiratory insufficiency may occur during pregnancy so close
monitoring by a multidisciplinary team is necessary.

Cerebral venous thrombosis


Cerebral sinus thrombosis (CVT) in pregnancy and the puerperium accounts for 5e30% of all cases in Western European and
North American populations (up to 60% in India), and is associated with mortality rates of 4e36%. Patients most commonly
present within 3 weeks of delivery with signs of raised intracranial pressure including:
 headache
 seizures
 vomiting
 photophobia
 focal signs
Maternal pyrexia and a leukocytosis may also be evident.
The hypercoagulable state of pregnancy and the puerperium is
the most likely underlying cause for CVT, although underlying
thrombophilias may also contribute to its pathogenesis. Dehydration and maternal sepsis are often associated with CVT in
pregnancy.
Diagnosis is made using CT, MRI or venous angiography.
Other differential diagnoses including eclampsia and subarachnoid haemorrhage must be considered and investigated as
deemed appropriate.
Management of CVT during pregnancy should include rehydration, anticoagulation and anti-convulsants (if associated with
seizures). There is controversy surrounding optimal anticoagulation
although outcome is regarded as better with heparin use. Full anticoagulation with intravenous unfractionated heparin or subcutaneous low molecular weight heparin is safe 24 h after delivery and
warfarin may be commenced a week later. Both heparin and
warfarin are safe in breastfeeding. A thrombophilia screen should be
performed 4 weeks after anticoagulation has been discontinued and
no earlier than 6 weeks postpartum (after which time the low protein
S levels of pregnancy have returned to pre-pregnancy values).

Fetal and neonatal effects


Neonatal myasthenia affects 20% of offspring, due to transplacental passage of IgG antibodies. Most affected neonates
present within in the first few days of life with difficulties in
feeding, hypotonia and respiratory distress. Symptoms are transient and gradually resolve within 6e8 weeks as maternal antibodies are cleared from the neonatal circulation. Arthrogryposis
multiplex congenital is a more severe form of neonatal MG which
occurs in the fetus due to poor movement resulting in multiple
joint contractures and can be fatal.
Myasthenia gravis is associated with a higher rate of preterm
delivery and growth restriction compared with healthy controls.
It is exacerbated by several drugs which should be avoided.
These include aminoglycosides, b-blockers, b-adrenergics, and
magnesium sulphate which impair or block neuromuscular
transmission. Caution must be exercised with some anaesthetic
agents, although epidural anaesthesia and analgesia can be safely
administered.

Myotonic dystrophy
Myotonic dystrophy (MD) is a rare degenerative neuromuscular
and neuroendocrine disease. Pregnancy is uncommon in all but
milder cases. The most common form is myotonic dystrophy
type I which is inherited in an autosomal dominant pattern. The
affected gene is located on chromosome 19, making the condition
amenable to prenatal diagnosis.
Myotonic dystrophy is characterized by progressive muscular
dystrophy, muscle weakness and myotonia, and eventually
cataracts, cognitive impairment, cardiac conduction defects,
dysphagia, and respiratory compromise may become evident.
In pregnancy, MD can worsen, particularly in the third
trimester when a diagnosis is often made in those previously
undiagnosed. Symptoms improve postnatally. Myotonic
dystrophy is associated with pregnancy loss throughout pregnancy, preterm delivery and placenta praevia. Dysfunctional
labour is more common, probably as a result of abnormal

Myasthenia gravis
Myasthenia gravis (MG) is a chronic, autoimmune disorder of
neuromuscular transmission, characterized by varying degrees of
weakness and easy fatigability of skeletal muscles. It is twice as
prevalent in women as men, with onset in the second or third decade
of life, and is diagnosed in approximately one in 20,000 pregnancies.
It presents with diplopia, ptosis, dysphagia, and in severe
cases, respiratory muscle weakness. Patients with MG have
a thymoma in 10e50% of cases and approximately 10% have
concurrent thyroid disease.
MG is caused by IgG antibodies against the nicotinic acetylcholine receptors on the motor endplate, which cause blockade
of neuromuscular signalling and consequent skeletal muscle
weakness and fatigue. Diagnosis can be made by administering

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myometrial contractility, and postpartum haemorrhage is


frequent, which can be managed with uterotonics. Congenital
MD occurs in a proportion of pregnancies and is characterized by
generalized hypotonia of the neonate, arthrogryposis, talipes,
and neurodevelopmental problems.
Other neuromuscular disorders such as spinal muscular
atrophy, facioscapulohumeral dystrophy, and limb-girdle
muscular dystrophies are rare, but are usually unaffected by
pregnancy although gestational weight gain may impair mobility.
Caesarean section is indicated for obstetric indications.

nerve (L4-5). Differential diagnoses include epidural-related


complications such as an abscess or haematoma.
Meralgia paraesthetica
Numbness or pain in the distribution of the lateral cutaneous
nerve of the thigh may arise in pregnancy due to nerve
compression at the lateral aspect of the inguinal ligament. It
resolves spontaneously following delivery.

Cerebral tumours
Primary tumours of the central nervous system and metastatic
cancer may present during pregnancy with signs and symptoms
including headache, nausea and vomiting, and visual symptoms
that are often unremitting. Neurological deficit may also be
a feature. Meningiomas and pituitary tumours are more common
among women and tumour size and may be influenced by the
vascular and hormonal changes that accompany pregnancy. Neuroimaging will aid diagnosis and guide further investigations. A

Peripheral neuropathies
Bells palsy
Bells palsy, a mononeuritis of the facial nerve, occurs 10 times
more commonly during pregnancy, with an incidence of 45 per
100,000 pregnancies.
It presents most commonly in the third trimester and puerperium as a unilateral lower motor neurone lesion of the VIIth
cranial nerve, with weakness of the facial muscles on the affected
side. It can be associated with loss of taste sensation on the
anterior two-thirds of the tongue or earache.
Most cases arising outside pregnancy are due to reactivation
of latent herpes virus, but in pregnancy, facial nerve oedema may
cause nerve compression as it passes through the petrous
temporal bone. Ramsay Hunt syndrome (herpes zoster of the
geniculate ganglion) should be excluded in women presenting
with Bells palsy, in which herpetic vesicles may be visualized in
the external auditory meatus or soft palate. In very rare
circumstances, Bells palsy may be bilateral although
GuillaineBarre syndrome, sarcoidosis and Lyme disease should
be excluded.
Bells palsy resolves spontaneously in most cases but may
take several months. If the patient presents within 72 h of onset,
a 1-week course of prednisolone (40 mg daily) may improve
symptoms and shorten recovery time, although treatment is
unlikely to alter long-term prognosis. Steroids should be avoided
in Ramsay Hunt syndrome and acyclovir must be commenced
instead. Eye care and physiotherapy should be considered.

FURTHER READING
Allais G, Gabellari IC, Borgogno P, de Lorenzo C, Benedetto C. The risks of
women with migraine during pregnancy. Neurol Sci 2010; 31: S59e61.
Banach R, Boskovic R, Einarson T, Koren G. Long-term developmental
outcome of children of women with epilepsy, unexposed or exposed
prenatally to antiepileptic drugs: a meta-analysis of cohort studies.
Drug Saf 2010; 33: 73e9.
Contag SA, Mertz HL, Bushnell CD. Migraine during pregnancy: is it more
than a headache? Nat Rev Neurol 2009; 5: 449e56.
EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology 2006;
66: 354e60.
Jaigobin C, Silver FL. Stroke and pregnancy. Stroke 2000; 31: 2948e51.
Lockhart EM, Baysinger CL. Intracranial venous thrombosis in the parturient. Anesthesiology 2007; 107: 652e8.
Morrow J, Russel A, Guthrie E, et al. Malformation risks of antiepileptic
drugs in pregnancy: a prospective study from the UK Epilepsy and
Pregnancy Register. J Neurol Neurosurg Psychiatry 2006; 77: 193e8.
Vukusic S, Hutchinson M, Hours M, et al. The pregnancy in multiple
sclerosis group: pregnancy and multiple sclerosis (the PRIMS study):
clinical predictors of post-partum relapse. Brain 2004; 127: 1353e60.

Carpel tunnel syndrome


Carpal tunnel syndrome affects 2e3% of women during pregnancy and arises due to median nerve compression at the flexor
retinaculum. It presents in later pregnancy with paraesthesia and
numbness of the thumb and lateral two and a half fingers, and
can sometimes be painful. In severe cases, motor loss of the
median nerve occurs, resulting in wasting of the thenar
eminence. Symptoms can be reproduced by percussing the carpal
tunnel (Tinels sign) or through sustained flexion of the wrist
(Phalens sign). Carpal tunnel syndrome improves following
pregnancy but wrist splints and physiotherapy may offer
symptom relief during pregnancy.

Practice points
C

Lumbosacral plexopathies
Nerves arising from the lumbosacral plexus may become
damaged during delivery, particularly following a long second
stage, due to fetal head compression. The commonest presentation is of foot drop due to compression of the sciatic nerve
(L4-S3), the lumbosacral trunk (L4-5) or the common peroneal

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163

Neurological disease is commonly encountered in pregnancy


and effective management requires taking a detailed history,
a physical examination and planning appropriate investigations. Computed tomography (CT) imaging and contrast
studies should not be withheld in pregnancy.
Pre-pregnancy counselling allows evaluation of the existing
neurological condition, optimization of its treatment prior to
pregnancy, and discussion of potential effects of neurological
disease or its therapies on the developing fetus, as well as
effects of pregnancy on the condition itself.
A multidisciplinary team approach is central to planning
antenatal, intrapartum, and postnatal care.

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