The Nervous System in Pregnancy

Diseases of the nervous system can affect every aspect of reproduction in women from fertility to lactation, and maternal neurologic disease and its treatment may have an impact on the offspring of that pregnancy. In addition, pregnancy may often affect neurologic conditions and the investigation and treatment of such conditions may need to be adjusted because of concern for the fetus. As well as the complex clinical problems involved in management of common neurological conditions such as epilepsy, there are the rarer problems whose management is made difficult by the widely scattered and relatively inaccessible literature.

In general, the most helpful neurologic diagnostic procedure is a careful history and physical examination by an experienced neurologist. Usually this results in a shortlist of diagnostic possibilities and limits the questions to be answered by further testing, if needed. Electroencephalography (EEG) and electromyography (EMG) can be performed without risk. Pregnancy does not alter the indications for lumbar puncture.

Pregnancy is not an absolute contraindication to any neuroradiologic procedure. However, a balance must be made between the information that can be obtained from the test and the risk to the fetus of exposure to radiation. During the first trimester high dose radiation exposure will increase the risk of miscarriage or congenital abnormality, whereas later in pregnancy exposure is associated with a very small increase in risk of childhood cancer. However, for most forms of investigations the doses used are small and well below the thresholds that are clearly associated with fetal complications. For example, the radiation dose to the uterus from a skull or cervical spine film is less that 0.001 cGy (1 mrad), from a thoracic spine series up to 0.1 cGy (0.1 rad), and from a lumbar spine series 1.5 cGy (1.5 rad), whereas there is a less than a 1% risk of congenital abnormality with radiation exposure in the first trimester of 10 cGy (10 rad). However, there remains uncertainty about the effects of lower doses, especially in the early first trimester, so the minimum exposure possible should be used wherever possible. Lumbar spine films and myelography should be avoided unless they are essential, especially during the first trimester.¹ Abdominal lead shields reduce fetal radiation exposure to small amounts during head and neck filming, including computed tomography (CT) scans. Cerebral angiography may be performed during pregnancy and transfemoral cerebral angiography has been recommended even though brief exposure to abdominal fluoroscopy during catheterization could be avoided by using a brachial artery. Iodinated contrast does cross the placenta but does not appear to be harmful to the fetus. CT scanning has supplanted radionuclide brain scans, which should be avoided during pregnancy. It appears that the strong magnetic fields of magnetic resonance imaging (MRI) do not have an effect on the fetus,² but MRI should be avoided in the first trimester unless clinically indicated.

Approximately 1 in 200 pregnancies are complicated by maternal epilepsy, and epilepsy is the most common serious neurological disease that will be encountered by an obstetrician. Many of the complex interactions between pregnancy, epilepsy, anticonvulsant metabolism, and effects on the fetus have yet to be delineated. Many clinically important questions remain to be answered.

Pregnancy has a variable effect upon the frequency of epileptic seizures. In most pregnancies there is no change, up to a quarter of women may experience a fall in the number of seizures and in up to one third of women seizure frequency will increase. It may be difficult to predict which women who have frequent seizures will have an increased seizure frequency during their pregnancy. Changes in frequency appear to be unrelated to the type of seizure, the duration of the epilepsy or the pattern of epilepsy in previous pregnancies. However, the chance of an increased seizure frequency during pregnancy appears to be related to the frequency of epileptic fits before pregnancy. Women with more than one seizure per month before pregnancy can expect worsening during pregnancy. In contrast, a woman who has been seizure free for some years before pregnancy is unlikely to convulse during pregnancy³ and in some cases may consider stopping antiepileptic medication before pregnancy. The effects on epilepsy of the enormous rises in sex steroids during pregnancy are unpredictable. Increased estrogen levels decrease the seizure threshold for both focal and generalized seizures, whereas the converse is true for progesterone. Both hormones increase during pregnancy. The net effect on the seizure threshold is unpredictable.

Epileptic women who have seizures during pregnancy are often found to have subtherapeutic levels of antiepileptic drugs.^{4, 5} Plasma concentrations of antiepileptics fall with increasing gestation,^{6, 7} possibly related to impaired intestinal malabsorption, decreased plasma protein binding, reduced levels of albumin, weight gain, and increased drug clearance.⁸ However, although plasma drug levels are known to be lowest during the third trimester, the increase in seizure frequency is most commonly seen during the first trimester.⁹ Pregnancy also lowers sodium and magnesium concentrations and this change in the balance of cations may predispose to seizures. Stress and sleep deprivation may be important. In late pregnancy, insomnia can provoke seizures in women with therapeutic levels of anticonvulsants.

It is likely that decreased compliance is one of the most important causes of an increase in seizure frequency. It has been reported that more than 50% of women with an increased number of seizures during pregnancy may be noncompliant. The motivation behind this is likely to be concern about the effect of the drugs on the fetus.

Anticonvulsant metabolism

Usually the dosage of anticonvulsants needed to maintain a previously determined, therapeutic blood level will increase during pregnancy, especially in the second half. Often blood levels are done at monthly intervals during pregnancy, or more frequently if seizures develop. Usually dosage schedules return to the prepregnant levels within 6 weeks, often with major change within the first 2 weeks in the case of phenytoin.¹⁰

The apparent clearance of anticonvulsants increases during pregnancy by a factor of approximately 1.5 for phenobarbital, approximately 2 for carbamazepine, and 2–4 for phenytoin. The reasons differ for each drug.^{11, 12} The increase in clearance of lamotrigine clearance seems to be greater than with other anticonvulsants and is associated with an increase in seizure frequency^{13, 14}so adjusting lamotrigine dosage based on levels seems appropriate with this treatment. Although phenobarbital induces hepatic catabolism of other anticonvulsants, it is mainly excreted by the kidney. Alkaline urine promotes renal clearance of phenobarbital. The increase in a hypoxide metabolite of carbamazepine during pregnancy suggests that hepatic metabolism is the factor responsible for that drug. For phenytoin, intestinal malabsorption is the major cause and increased parahydroxylation is a secondary cause.

Teratogenicity

It is difficult to evaluate the teratogenicity of antiepileptic drugs (AEDs) because of the large number of individual drugs used, differing doses, and multidrug regimens. However, it is clear that in utero exposure to AEDs is associated with increased risk of congenital malformation. For example, a recent Finnish population study compared the risk of major malformation in women with known epilepsy and demonstrated that major congenital malformations were more common among women on AEDs (4.6%) than among untreated patients (2.8%), OR 1.7 (95% CI 1.05–2.81).¹⁵

Most studies demonstrate that the risk of harelip, cleft palate, and congenital heart disease, mainly septal defects, is increased two to fourfold among the offspring of epileptic mothers who were treated during pregnancy with anticonvulsant drugs. The risk of fetal malformation is certainly greater with polytherapy, particularly so in combinations involving valproate.

It is difficult to be precise about the estimation of increased congenital abnormality risk with an individual AED as there are few or no controlled data and the effect of potential confounders such as type of epilepsy, seizure frequency, family history of birth defects, socioeconomic factors, nutrition, and exposure to additional teratogens are difficult to determine.¹⁶ The development of AED registries which attempt to enrol women at the start of pregnancy aims to clarify these issues.^{17, 18, 19, 20, 21} Two messages have emerged to date from registry data; that the rate of malformation with lamotrigine appears to be similar to, or less than, older AEDs, and that valproate as a single agent is associated with the highest rate of malformations, and that this relationship is dose-dependent. Information concerning other newer AEDs, e.g., topiramate, levetiracetam, and gabapentin remains limited at present.

Neurocognitive effects

Recently there has been increasing concern about the effect of AEDs on cognitive development, and several studies have suggested that adverse effects on IQ and behavior are greatest with valproate.^{22, 23, 24, 25, 26, 27}

Management of pregnancy

Women should be strongly advised to have preconceptual counseling with the aim of optimizing seizure control, AED medication, and starting folic acid 5 mg/day at least a month before conception to reduce the risk of neural tube defects.

Arrangements should be made for high definition ultrasound scanning by suitably experienced personnel at 11–13 and 18–23 weeks' gestation. Serial AED levels may be performed every 4 weeks, and is especially indicated in those women in whom seizure control is poor or those taking lamotrigine. Antenatal care should be provided by a multidisciplinary team comprising an obstetrician and a neurologist, and labor should occur in a setting where seizures can be controlled and delivery expedited as needed.

Infants exposed in utero to enzyme inducing AEDs may have a coagulopathy at birth due to decreased vitamin K-dependent clotting factors and this may be prevented by maternal supplementation with vitamin K₁, 10–20 mg/day orally, for 2 weeks before delivery.²⁸ Infants at risk should be given phytonadione, 1 mg intramuscularly, soon after birth. 

Breastfeeding

Breastfeeding is appropriate in most women taking AEDs. Although AEDs pass to the baby in breast milk, neonatal AED plasma levels are substantially less than the levels seen in the fetus as a result of placental transfer. Breastfeeding may prevent AED withdrawal in the early neonatal period, which is characterized by hyperactivity and feeding difficulty while being breastfed.²⁹ In contrast, a that baby appears sleepy may be being affected by AEDs within the breast milk and the mother should be encouraged to feed before and some time after taking her AEDs, depending on the medication.  

Cerebrovascular disease during pregnancy is a major cause of maternal mortality and morbidity. Individualized care of each patient is important because in many instances firm recommendations cannot be made from our current knowledge of the pathogenesis and natural history of the condition.

Eclamptic hypertensive encephalopathy

Central nervous system lesions account for at least 30% of eclamptic deaths. The typical gross neuropathologic findings are patches of petechiae in the cortical ribbon of gray matter and compacted small hemorrhages in the subcortex, the corona radiata, the caudate nucleus, the thalamus, and the pons.²² The patches of petechiae and the subcortical “hematomas” are located in border zones between major arterial territories, and particularly in the distribution of the posterior cerebral arteries. Large, deep hematomas also occur. The classic microscopic lesion is a ring hemorrhage about a precapillary or capillary occluded by fibrinoid material. Seizures, visual disturbance including flashing lights and cortical blindness, progressive stupor, and coma are easily explained by these lesions.

CT scans can show larger hemorrhages but may not detect the cortical petechiae. Arcuate hypodense bands denoting edema may occur in or adjacent to the basal ganglia and thalamus.¹⁴ The EEG of eclamptic women has generalized delta and theta activity, especially in posterior regions, on which may be superimposed epileptiform activity. Cerebrospinal fluid (CSF) pressure may be normal or elevated; CSF protein concentration may be normal or up to 150 mg/dl.

Although preeclamptic toxemia is unique to pregnant women, the cerebral lesions are not, being similar to the manifestations of hypertensive encephalopathy in usually previously normotensive patients. The blood pressure at the time of eclamptic seizure varies; one half of Sheehan's series convulsed with systolic pressure between 160 and 195 mmHg, and the rest were divided above and below that range.²² In physiological terms the patient's blood pressure has exceeded that patient's upper limit of the autoregulation of cerebral blood flow.^{3, 24} The upper limit is directly dependent on that person's usual blood pressure. Beyond the upper limit, precapillary arteriolar constriction no longer limits the perfusion pressure exerted on the capillary bed, with resultant rupture of capillary walls, exudation of plasma proteins, and diapedesis of erythrocytes. Thus, a ring hemorrhage is formed. The earliest breakthroughs occur in the border zones and act as safety valves to protect the rest of the brain unless even higher blood pressures are generated.

Aside from termination of pregnancy, the treatment of eclamptic hypertensive encephalopathy should decrease blood pressure and arrest seizures.³ Intravenous hydralazine, labetalol, and nitric oxide may be used to treat severe hypertension.

In North America and the UK, parenteral magnesium sulfate is the standard treatment of severe preeclampsia and eclampsia, and is both antihypertensive³⁰ and effective in preventing convulsions.³¹ The mechanism by which MgSO₄ acts in the treatment and prevention of preeclampsia remains uncertain, but may include cerebrovascular effects to prevent vasospasm, direct action on neural conduction, or effects on the general cardiovascular system.

Spontaneous subarachnoid hemorrhage complicates only 1 or 2 in 10,000 pregnancies but accounts for almost 10% of maternal deaths. The main cause of subarachnoid hemorrhage in women under 25 years of age is an arteriovenous malformation. Older women are more likely to have a ruptured berry aneurysm.^{3, 29, 32, 33} At all ages approximately one third of spontaneous subarachnoid hemorrhages are due to other causes, including bleeding disorders, vasculitis, subacute bacterial endocarditis, sickle cell anemia, and metastatic choriocarcinoma. No cause for bleeding will be found in approximately 5% of pregnant women so afflicted.

Arteriovenous malformations are prone to bleed in the mid-trimester and during delivery. The risk of berry aneurysms rupturing increases during pregnancy, but rarely does initial bleeding occur intrapartum. Rebleeding occurs during the Valsalva maneuver accompanying hard labor.

Unless the woman is in active labor, she should be evaluated and treated as if nonpregnant. CT scans and four-vessel cerebral angiography will be needed to define the lesions. Controlled hypotension can be used safely during pregnancy.³³ If the responsible aneurysm or arteriovenous malformation can be surgically cured with clipping or coiling, pregnancy and delivery can proceed with risk of rebleeding. If multiple aneurysms exist, obliteration of unruptured aneurysms can wait until several months postpartum, with the possible exception of aneurysms more than 10 mm in diameter. If curative surgery is not performed, women with arteriovenous malformations and most women with aneurysms, certainly primiparous women, are often delivered by cesarean section at 38 weeks' gestation.²⁹ If a multiparous woman who has bled during early pregnancy can avoid bearing down perhaps with the administration of regional anesthesia, vaginal delivery is an option.³²

Ischemic stroke

The incidence of ischemic arterial vascular events (stroke plus transient ischemic attacks) during pregnancy is approximately equal to the incidence of subarachnoid hemorrhage, but death is rare unless the stroke is symptomatic of systemic disease. It remains uncertain whether pregnancy plays an important role in the etiology of ischemic strokes during pregnancy and the puerperium, and it is unclear whether the risk is increased by pregnancy. Some have reported that pregnancy increases the risk of ischemic stroke at least by a factor of 3 or 4.³⁴ Any pregnant woman who develops ischaemic stroke during pregnancy needs extensive evaluation to identify the cause (see Table 1).

Approximately 30% of pregnancy-related arterial occlusions occur in each of the second and third trimesters.^{34, 35} Approximately one quarter of pregnancy-associated strokes occur in the first postpartum week. Thirty-five per cent are occlusions of the middle cerebral artery, which, in the absence of demonstrable atheromatous disease, may be emboli from or through the heart. The internal carotid artery is occluded in 20%. Vertebrobasilar stroke is rare in both nonpregnant and pregnant young women, although 25–40% of strokes associated with oral contraceptives are in the posterior circulation.³⁶

Probably only one quarter of pregnancy-associated strokes are arteriosclerotic, although the presence of an atheromatous lesion has not been confirmed in all cases.³⁷ Usually those patients can be identified by the coexistence of diabetes mellitus, hyperlipidemia, and chronic hypertension. Many pregnancy-associated strokes and most fatal ischemic strokes of pregnancy are symptomatic of other conditions, including atrial fibrillation, peripartum cardiomyopathy, subacute bacterial endocarditis, arteritis, sickle hemoglobinopathy, thrombotic thrombocytopenic purpura, and metastatic choriocarcinoma.^{37, 38, 39, 40}

Indications for anticoagulation in pregnancy include peripartum cardiomyopathy, deep vein thrombosis, and the hypercoagulable state associated with thrombophilias, and atrial fibrillation. Heparin or heparin-like compounds (e.g., low molecular weight heparin) are the preferred anticoagulant during pregnancy. They are large molecules which do not pass through the placenta. Thus, heparin neither predisposes the fetus to hemorrhage nor causes congenital abnormalities. Bleeding complications with heparin are not increased during pregnancy.⁴¹ Warfarin crosses the placenta and should be avoided during the first trimester owing to its teratogenicity. It is to be avoided late in pregnancy owing to the risk of placental and fetal bleeding. Some physicians use warfarin in the second and third trimesters up to the last month before expected delivery. Others advocate subcutaneous heparin throughout pregnancy.

The early investigations of stroke in pregnancy reported a poor outcome. However, these studies may have been influenced by small numbers of patients and selection bias.⁴² A more recent study reported no maternal deaths due to stroke in pregnancy. However, half of the women included were left with some residual neurological deficit. The fetal mortality was 12%.⁴³ 

Abrupt hypotension can selectively infarct the watersheds between the territories of major cerebral arteries. Acute blood loss during delivery may infarct the pituitary gland (Sheehan's syndrome), the optic chiasm, and cerebral border zones.⁴⁴ Other causes of abrupt hypotension during delivery include amniotic fluid embolism, air embolism, and spinal anesthesia.

Cerebral venous thrombosis

There is a clear association between cerebral venous thrombosis and pregnancy and the puerperium.⁴⁵ Women 3–4 weeks' postpartum may develop an aseptic thrombosis of cerebral veins and sinuses.^{35, 46, 47} Of all cerebral venous thrombosis 80% occurs in the 2nd or 3rd week postpartum. Many cases historically called “late postpartum eclampsia” proved to be cerebral venous thromboses.²² For unknown reasons the incidence of this disorder in India is ten times greater than in North America and Europe, where the incidence is estimated to be 1 in 10,000 deliveries.³⁵ Age and parity are indeterminant factors. Labor and delivery are usually uncomplicated. Risk factors include dehydration and infection. Trauma to the endothelium during labour, hypercoagulation, and blood stasis have all been hypothesized as possible causes of cerebral venous thrombosis.⁴⁸

The usual clinical presentation is an increasingly severe headache preceding focal or generalized seizures, which are followed by stupor, paralysis, and aphasia. The clinical diagnosis is confirmed by CT, MRI or angiography. Digital subtraction angiography is usually sufficient and is more sensitive that either CT or MRI. Although the use of anticoagulation is controversial it is considered by most as the first line treatment of cerebral venous thrombosis, even if hemorrhagic transformation is seen on CT.⁴⁸

Multiple sclerosis is characterized by patchy demyelination in the central nervous system. The neurological symptoms and signs depend upon the sites of the demyelination. The natural history of multiple sclerosis is an unpredictable series of relapses that may meld into a chronically progressive course. Thus, counseling the patient and her husband is very difficult. Although most young women with an episodic course and little disability can expect to rear their children with acceptable limitations, the threat of serious disability is always present.

Most women with uncomplicated multiple sclerosis can be reassured that their disease will have little effect on a pregnancy and vice versa.^{32, 33} The relapse rate is lower during pregnancy, although it is higher postpartum. Relapses which occur during pregnancy are usually mild and associated with little or no residual neurological deficit.³⁴  The risk of relapse in the 6 months' postpartum is estimated to be 2–3 times higher than the non-pregnant risk.³⁵ Overall, taking the antenatal period and puerperium together, there does not appear to be any long-term effect on disability related to pregnancy. Women with neurogenic bladders require special attention to prevent infection and minimize bladder dysfunction. Multiple sclerosis is not known to have any effect on the rate of obstetric complications.

Although the evidence concerning the use of epidural and spinal anesthesia in pregnant women with multiple sclerosis is conflicting taken as a whole the data suggest that both can probably be used safely and have no convincing effect on subsequent relapse rates.

Help with childcare may be needed after delivery, especially if there is a relapse. A multidisciplinary approach involving pediatricians, social workers, and occupational therapists is often needed. 

Chorea gravidarum is any chorea or hemichorea acquired during pregnancy. In the era before penicillin it was a feared, relatively common condition almost synonymous with acute rheumatic fever or rheumatic heart disease, usually with a history of Syndenham's chorea. Now it is rare and approximately 50% of cases of chorea gravidarum are idiopathic.³⁶ In those cases where a cause is found it is most commonly associated with autoimmune and rheumatic diseases.

Chorea gravidarum usually begins in the first half of pregnancy and for 70% lasts until childbirth; thereafter, it dramatically disappears.³⁸ Women typically present with sudden onset of chorea during an otherwise uneventful pregnancy. Women who experience chorea during one pregnancy have a 25% risk of chorea during subsequent pregnancies and this is most lilkely if antiphospholipid syndrome is the underlying cause.

Possible causes should be sought and treated. Treatment of the chorea in mild cases consists of rest and sedation. In severe cases, dopamine blockade with haloperidol or a phenothiazine will be needed to prevent hyperthermia and rhabdomyolysis.³⁹

Myasthenia gravis is an acquired autoimmune disease of motor end-plates of striated muscle in which pathogenic autoantibodies against  acetlycholine receptors at the neuromuscular junction induce failure of neuromuscular transmission. It is clinically characterized by fluctuating fatigability of eyelids, extraocular muscles, facial and oropharyngeal muscles, and limbs muscles. Young women with the disease often possess the HLA-A8 human leukocyte antigen. Myasthenia gravis is associated with other autoimmune diseases such as SLE and rheumatoid arthritis. Thyroid disease is found in 1 in 7 women.

Because a fluctuating course is typical of myasthenia gravis, it is not unexpected that the effect of pregnancy on myasthenia gravis varies from pregnancy to pregnancy and is unrelated to the severity of maternal disease. Abortion does not induce a remission. Because up to a third of women have an exacerbation, often severe, within a few weeks' postpartum, careful monitoring and adequate treatment for first few weeks after delivery are recommended.

Pregnancy alters the treatment of myasthenia gravis in few patients.⁴⁹ Corticosteroids and anticholinesterase therapy may be used in dosages as if the patient were not pregnant. Pyridostigmine and other quaternary ammonium compounds do not cross the placenta, and negligible amounts are excreted in milk. Thymectomy and plasmapheresis can be performed if necessary. Azathioprine may be used during pregnancy. It does not appear to be associated with a clear increased risk of congenital abnormality and breastfeeding appears to be safe.⁵⁰

Myasthenia gravis does not affect uterine contractions because the myometrium is unaffected, but striated muscle will become weak during prolonged pushing so instrumental vaginal delivery may be needed. Magnesium sulfate used in the treatment of eclampsia may cause an exacerbation.

Approximately 10–20% of babies of women with generalized myasthenia gravis will develop neonatal myasthenia, a self-limited condition usually lasting about 3 weeks. Symptoms may present at birth or up to 4 days thereafter. There is no relationship between any clinical factor in the mother's condition and the development of neonatal myasthenia. Although maternal acetylcholine-receptor antibody titer is related to the risk of neonatal myasthenia there have been reports of neonatal myasthenia in women without elevated antibodies. Anticholinesterase drugs and ventilatory support should be used until the weakness subsides. Plasmapheresis can quickly reverse the condition in severe cases.⁵¹

Brain tumors of all types may coexist with pregnancy, but the overall incidence is not increased compared with age-matched nonpregnant women. The growth and vascularity of tumors in some cases is accelerated during pregnancy.^{44, 46} The stimulation of estrogen and progesterone receptors in meningiomas and neurofibromas, may be a reason why tumors may become symptomatic in pregnancy⁴⁷ but other factors such as immunologic tolerance and alterations in tissue fluid distribution may be important.  Most tumors become symptomatic during the second half of pregnancy. Approximately one third of these women die while pregnant or during childbirth. All tumors appear to undergo remission postpartum, at least temporarily. Some small acoustic neuromas and meningiomas may recur years later or during subsequent pregnancies.

The management of each case must be individualized and decided only after thorough study. The possibility of an abscess or a metastatic tumor, especially a choriocarcinoma, should not be overlooked. Patients whose tumors are associated with a high mortality rate (i.e., malignant gliomas and almost all infratentorial tumors except some acoustic neuromas) are usually operated on before delivery. More benign tumors are approached several weeks' postpartum, when a drier surgical field and a reduction in tumor size can be expected. In women with an elevated intracranial pressure or large space occupying lesions delivery is usually by cesarean section to avoid the increase in CSF pressure associated with pushing, which may lead to brain herniation. Vaginal delivery can be considered for some women with small lesions, e.g., pituitary tumors, if the Valsalva maneuver, which increases CSF pressure, can be avoided by instrumental delivery.

Interruption of an early pregnancy has been recommended on both therapeutic and elective bases for women with malignant gliomas, certainly those with uncontrollable seizures. Increased intracranial pressure and visual failure are reasons for premature termination of pregnancy in the last 2 months of gestation. In almost all cases it is inadvisable for a woman known to have a brain tumor to become pregnant.

Choriocarcinoma

Patients with choriocarcinoma usually present with vaginal bleeding and an enlarged uterus in the months following a molar pregnancy or a miscarriage. However, 15% of cases follow or accompany a normal pregnancy.⁵² Some cases present as single or multiple “strokes”, intracranial hemorrhage, or solitary mass lesions with or without jacksonian seizures. The chest film usually shows metastases in these instances but may not in 5%. Aggressive treatment with irradiation and chemotherapy has resulted in regression of cerebral metastases.

Pituitary adenomas

In the past most women with pituitary adenomas were infertile owing to hyperprolactinemia, but modern intervention with bromocriptine or cabergoline and transsphenoidal pituitary surgery has meant that this tumor is often encountered in pregnancy.^{53, 54} Pregnancy-induced growth of prolactinomas may produce headache, visual disturbances, diabetes insipidus, and deficits of other pituitary hormones. Women with microadenomas with diameters less than 10 mm are usually treated with bromocriptine or cabergoline, and those with macroadenomas are usually treated with transsphenoidal surgery and administration of bromocriptine. Microadenomas are less likely (1–5%) to have symptomatic enlargement during pregnancy than macroadenomas (15–35%). The visual fields of women with microadenomas are usually followed during pregnancy with bedside techniques. Pregnant women with macroadenomas must have careful visual-field determination by perimetry on a monthly basis or by serial MRI scans. MRI imaging of the tumor is essential if the woman becomes symptomatic.

If prolactinomas become symptomatic during pregnancy, bromocriptine or cabergoline may be reinstituted. If this is not successful, surgery and, if the fetus is mature enough, delivery of pregnancy are options. Surgery would become necessary if despite medical treatment there is extension of visual-field deficits into nasal sectors or significant visual acuity deterioration.⁵⁵

The most common headache during pregnancy is the muscle contraction/tension headache producing band-like and exploding persistent pain usually accompanied by tender cervical and shoulder muscles. These headaches may be aggravated by pregnancy-induced postural changes and new or anticipated situational problems and anxiety. They may be a marker of antenatal or postpartum depression. Most are symptomatically treated with common analgesics and muscle massage. Severe, recurrent muscle contraction headaches may prompt psychiatric counseling and prophylactic therapy with a tricyclic antidepressant.

Migraine

Classic migraine is a severe, throbbing, often unilateral headache associated with nausea and vomiting that follows a 20–30-minute prodromal stage of scintillating scotomata. These headaches are often aggravated by menstruation and oral contraceptives, and relieved during pregnancy for most women.⁵⁶ Acute migraines during pregnancy are usually treated with analgesics and phenothiazine antiemetics. Propranolol, 40–160 mg daily in divided doses, is effective prophylaxis for frequently recurrent migraine and has been shown to be effective during pregnancy,⁵⁷ although fetal intrauterine growth restriction has been reported.⁵⁸ Ergot compounds are absolutely contraindicated during pregnancy because of a high risk of fetal abnormalities and uterotonic and vasoconstrictive effects. Although sumatriptan is not currently used for the treatment of migraine in pregnancy it does not appear to be associated with a marked increase in teratogenic risk, so women who have inadvertently taken it during early pregnancy may be reassured.⁵⁹

Pseudotumor cerebri

Headache due to pseudotumor cerebri is usually a retro-orbital pain that may be altered by coughing and changing position. Pregnancy-associated pseudotumor cerebri usually begins in the third to fifth month of pregnancy, but may start in any trimester, and lasts about 2 months, but it may persist until the puerperium.⁶⁰ Women with pseudotumor who become pregnant usually worsen. Obesity is characteristic.

Examination may be normal except for papilledema, although diminished visual acuity and abducens nerve palsy also occur. CT scanning rules out a mass lesion and hydrocephalus. Lumbar CSF pressure is elevated, and commonly CSF protein concentration is less than 20 mg/dl.

Treatment is indicated for women who develop progressive symptoms and may be a short course of prednisolone or CSF drainage. In some cases serial CSF drainage or lumboperitoneal shunting must be considered to prevent blindness.

Bell's palsy

Bell's palsy, or idiopathic palsy of the seventh cranial nerve, is seven times more prevalent than expected during the third trimester of pregnancy.⁶¹ The reason for this is unknown. It is an isolated phenomenon. Close to delivery the prognosis is excellent for a spontaneous recovery. Supportive therapy with artificial tears and patching of the lid is advised to prevent corneal abrasion. Earlier in pregnancy a short course of high-dose corticosteroids or acyclovir may be indicated for complete facial weakness.

Carpal tunnel syndrome

Nocturnal acroparesthesias are a common complaint during pregnancy and are often misdiagnosed as the carpal tunnel syndrome, which is much less common but does occur with increased frequency during the second and third trimesters.^{62, 63} The diagnosis may be confirmed by measurement of motor and sensory median nerve conduction parameters. Because this syndrome spontaneously regresses within a few weeks after childbirth in around 95% of women, conservative therapy with nocturnal splinting with the wrist in mid-position or slightly flexed is recommended. Only if weakness exists is division of the transcarpal ligament indicated during pregnancy.

Meralgia paresthetica

Meralgia paresthetica is a nagging stinging pain along the middle third of the lateral thigh that some pregnant women develop, usually around the 30th week of gestation. Obesity and an exaggerated lumbar lordosis stretch the purely sensory lateral femoral cutaneous nerve, trapping it against the inguinal ligament. Symptoms resolve spontaneously within 3 months after childbirth.⁶⁴

Guillain-Barré syndrome

The Guillain-Barré syndrome is an idiopathic inflammatory demyelinating polyneuritis of rapid onset in which weakness is more prominent than sensory loss. Areflexia is the rule. The classic laboratory finding is an elevated CSF protein concentration with a normal CSF leukocyte count. Plasmapheresis or intravenous immunoglobulins are therapeutic if the procedures can be started within days after the onset of neuropathic symptoms. Otherwise treatment consists in preventing complications.

The concurrence of Guillain-Barré syndrome and pregnancy is a coincidence.⁶⁵ The disease may occur and the patient begin to recover at any time during pregnancy. Labor and delivery are normal. Uterine contractions are unaffected. These apprehensive women require constant reassurance that they will recover and that their infants will not be affected.

Intrapartum lumbosacral plexopathy

Intrapelvic entrapment neuropathies may affect the lumbosacral trunk, the femoral nerve, the obturator nerve, and, rarely, the lateral femoral cutaneous nerve and nerves destined for the sciatic nerve.^{66, 67, 68} Cephalopelvic disproportion dystocia and primiparity are common factors. The femoral nerve may be compressed by self-retaining retractors. The incidence of these neuropathies has decreased with modern obstetric practices.

The most common syndrome is postpartum footdrop caused by compression of the lumbosacral trunk composed of fourth and fifth lumbar nerves as it crosses the pelvic brim by the fetal brow. It is unilateral and contralateral to the side on which the vertex presents (i.e., right occiput anterior is equivalent to left brow position). In contrast, unilateral and bilateral femoral and obturator neuropathies can be caused by the fetal head exerting pressure down in the pelvis on one or both sides. Footdrop may also be caused by the pressure of leg holders on the common peroneal nerve as it passes the fibular head.

In most instances the prognosis is excellent, with full recovery expected within 6–8 weeks, because the lesion was neuropractic (i.e., only the myelin sheath was distorted). Recovery will be slow and perhaps incomplete if axons were crushed.

Exaggeration of the lumbar lordotic curve during the second and third trimesters stresses articulations and produces backache. Obesity, wearing high-heeled shoes, and preexisting structural conditions such as spondylolisthesis, sacralization of the fifth lumbar vertebra, and previous back surgery worsen the pain. The back pain may be localized to the back and sacroiliac joints, or it may radiate into the thigh but not below the knee. The neurologic examination will be normal. Treatment consists of heat, massage, simple analgesics, and exercises to strengthen the back and increase its flexibility.

The pain of herniation of a lumbar intervertebral disk is of sudden onset, is exacerbated by coughing, and radiates to the ankle. Weakness of the extensor hallucis longus (L5) and a diminished ankle jerk (S1) may be present. Unless impairment of sphincter function dictates urgent myelography and surgery, the treatment is strict bed rest for 2 weeks. Surgery is indicated if pain is refractory to conservative treament after 6 weeks, if there is loss of bladder control or limb paralysis. Lumbar laminectomy may be performed during pregnancy,⁶⁹ although correct positioning of the patient may be challenging.

This chapter is based on the original contribution by Dr James O. Donaldson whose writing in this field I have always admired.