Neurological disease in pregnancy

Published on 09/03/2015 by admin

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Chapter 52 Neurological disease in pregnancy

Michael Flynn

Epilepsy and pregnancy

Incidence. Epilepsy occurs in 0.5%–1% of the population. Over 90% of women with epilepsy have a normal pregnancy.

Effects of epilepsy on pregnancy

• reports of fetal bradycardia after generalised seizure
• increased risk of childhood epilepsy of 3%–4% if one parent has epilepsy
• increased association with pre-eclampsia, preterm delivery, low birthweight, higher perinatal mortality and congenital malformations due to the epilepsy and the anticonvulsant drugs; fetal effects include cerebral palsy, seizures and mental retardation

Effect of pregnancy on epilepsy

• About 50% remain stable, with improvement in seizure frequency in 25% and deterioration in 25% of women.
• The deterioration is attributed to hormonal and metabolic changes and diminished compliance with drug therapy.
• In about 70% of patients, serum levels of anticonvulsants fall in early pregnancy and return to prepregnancy levels by 4 weeks postpartum; so if seizure activity increases, it is often in the first two trimesters.
• If epilepsy presents for the first time in pregnancy, rigorous investigation is required to exclude other neurological abnormalities.

Pharmacokinetics of anticonvulsants in pregnancy

• Drug absorption may be lowered with vomiting in early pregnancy.
• Volume of distribution is increased due to raised plasma volume and total body water, and results in a reduced steady state of plasma levels.
• Increased fat stores will lower lipid-soluble drug excretion.
• Phenytoin and valproate are highly protein-bound. With the reduction of albumin in pregnancy, there is a lower percentage of bound drug. Therefore, unbound levels in plasma remain constant, but total plasma levels are reduced.
• The glomerular filtration rate rises, raising the clearance of renally excreted drugs.
• Hepatic hydroxylation of phenytoin is increased, and this causes a reduction in free drug.
• Non-compliance due to maternal fears of teratogenicity often reduces plasma levels of drug.

Teratogenicity of anticonvulsants

• In a woman with epilepsy treated with a single anticonvulsant, the fetus has a risk of congenital malformation of 7%, compared with 3% in non-epileptics. There may be a higher incidence with polypharmacy.
• The defects include orofacial clefts, cardiovascular anomalies, neural tube defects (which are commonly primary myelomeningocele and anencephaly, and especially if valproate is taken in the first trimester), microcephaly and digital hypoplasia.
• Epilepsy pregnancy registries indicate valproate at doses >1100 mg/day confer significant risk compared to other doses and other drugs.

Other maternal effects of anticonvulsants

• reduced folate levels
• increased vitamin D metabolism with phenytoin and phenobarbitone, and risk of hypocalcaemia

Fetal/neonatal effects of anticonvulsants

• reduced fetal thyroxine as phenytoin competes for thyroxine-binding sites
• increased risk of haemorrhagic phenomenon of the newborn (mostly internal bleeding, secondary to decreased levels of vitamin K-dependent clotting factors as a result of drug-induced liver enzyme induction)
• increased drowsiness, jitteriness, irritability and poor suckling in the neonate

Anticonvulsants and breastfeeding

• Although all anticonvulsants except valproate cross the placental barrier, breastfeeding is not contraindicated.
• Neonatal serum levels are 40%–80% of maternal levels, and drowsiness may be a problem.

Anticonvulsants and contraception

• There is an increased risk of pregnancy and contraception failure secondary to hepatic enzymatic induction from anticonvulsants (carbamazepine, phenytoin, phenobarbitone, primidone, oxcarbazepine and topiramate >200 mg/day). There is no interference for gabapentin, lamotrogine, valproate and levetiracetam.
• The higher dose oestrogen (50 μg ethinyloestradiol) pill is required.

Management of epilepsy in pregnancy

Before conception

• If seizure-free for 2 years, consider withdrawing therapy. When possible, this should be 6 months prior to pregnancy.
• Aim for monotherapy or at least lowest possible dose.
• With the exception of valproate, there is no agreement as to which anticonvulsant drug should be used. It is appropriate to avoid valproate, especially at doses >1100 mg, if epilepsy is controlled by other medications.

Pregnancy

• Adopt a combined approach with the obstetrician and neurologist.
• Continue current anticonvulsant therapy and folate. Do not change therapy in established pregnancy solely to decrease teratogenicity.
• Plasma levels of free anticonvulsant drugs should be monitored where available.
• At 18 weeks gestation, a detailed fetal morphology ultrasound scan is required to assess for neural tube defects and orofacial clefts.
• Vitamin K 20 mg/day orally in the last 2–3 weeks of pregnancy may help reduce the risk of haemorrhagic disease of the newborn.
• Intramuscular vitamin K injection for the neonate is indicated.

Delivery

• Seizures during labour and delivery should be treated with intravenous benzodiazepines. Magnesium sulfate is not first-choice management, but may be used if eclampsia is suspected.

Postpartum

• Return to prepregnancy medication dose.
• Advise on the importance of sleep and rest.

Cerebral and spinal tumours

Prolactinoma

• Hyperprolactinaemia stimulates an increase in dopamine secretion, thereby inhibiting the release of gonadotrophin-releasing hormone (GnRH). Most women will be infertile unless treated.
• During normal pregnancy, the pituitary increases in size by 50%–70% secondary to lactotroph hyperplasia, and prolactin levels rise. Pituitary tumours are also likely to expand in pregnancy.

Management

• Institute combined obstetrician/neurologist management.
• Review regularly to assess growth of prolactinoma.
• Microadenoma causing hyperprolactinaemia: bromocriptine or cabergoline is withdrawn after pregnancy is confirmed and reinstated after delivery without significant risk of disease progression.
• Macroadenoma: the risk of expansion in pregnancy is <10%. It is recommended that pregnancy only be attempted when the tumour has shrunk to at least the confines of the sella turcica.
• Combined management during pregnancy with endocrinologists and neurosurgeons is indicated. The common complaints of tumour expansion are visual field defects and headaches. There is no evidence of teratogenesis with bromocriptine. Surgical management in pregnancy may be required.
• In symptomatic women, induction of labour at 38 weeks is indicated with elective use of forceps.

Neurofibroma

An acoustic neuroma can expand in pregnancy, as can cutaneous neurofibromatosis. This condition is associated with hypertension.

Neuropathies

Carpal tunnel syndrome

This is a common condition in pregnancy due to fluid retention, and resolves mostly in the postpartum period. It is often symptomatic at night, and management is initially with splints and physiotherapy. If these bring no improvement, then orthopaedic review and hydrocortisone injections or surgery may be indicated.

Bell’s palsy

This is more common in pregnancy, especially in the last trimester with increasing oedema. Management is with corticosteroids, optimally within 1 day of onset. It is probably associated with increased risk of eclampsia.

Paraplegia

Antenatal care involves an increased incidence of urinary tract infections and constipation.

Management in labour

• Management is dependent on the level of spinal cord lesion.
• If the spinal cord is divided above T10, labour will be painless.
• If the division is above T5–T6, there is a risk of autonomic hyperreflexia. This is an autonomic and somatic hyperreflexia in response to intense sensory stimulation. In labour, uterine contractions can overstimulate the splanchnic sympathetic bed and release catecholamines, which results in hypertension, arrhythmia, headache, facial flushing and sweating. This response can be prevented by epidural and spinal anaesthesia to the level of the umbilicus (T10).

Multiple sclerosis in pregnancy

Effects of pregnancy on multiple sclerosis

• Pregnancy is generally considered to provide a stabilising effect on multiple sclerosis. This is thought to be due to the altered immune state in pregnancy.
• Relapses are common in the first 3–6 months postpartum.
• There is no significant effect on fertility or fetal wastage.
• When combining both the protective effect of pregnancy and postpartum risk period, there seems no change to multiple sclerosis relapse rate or long-term disability from pregnancy.

Management

• General measures include rest, counselling, preventing urinary tract infections and treating anaemia.
• Epidural anaesthesia has no effect on the disease.
• No contraindications exist to breastfeeding.
• Acute exacerbations of the disease are treated with glucorticoids.

Further reading

EURAP Study Group. Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology. 2006;66:354-360.

Vukusic S., Hutchinson M., Hours M., et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004;127:1353-1360.

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