Headache during pregnancy is common. Usually a patient visits the neurologist to receive reassurance that no serious medical problem is apparent. Of the headaches that occur during pregnancy, benign tension headaches are seen most often (see Chapter 69). No known association exists with hormones and, specifically, no association with the hormonal changes of pregnancy. Treatment for mild headaches often includes behavioral therapy, adequate rest, moist heat, massage, exercise, avoidance of triggering factors, and use of acetaminophen. For severe headaches, the use of a tricyclic antidepressant such as amitriptyline or nortriptyline may be helpful. No evidence of embryopathy occurs with amitriptyline, and preschool children exposed in utero to tricyclic antidepressants have normal global IQs, language, and behavioral development. Fluoxetine may cause uncommon but serious fetal risks (Chambers et al., 2006; Diav-Citrin et al., 2008; Mills, 2006).

Migraine Headache

More than 80% of women with migraine clearly show improvement during pregnancy, but 15% continue to have headaches, and in 5% headaches worsen. The prognosis for women with migraine without aura is better than that for women with migraine with aura. Headaches were more likely to persist with diagnosed menstrual migraine, hyperemesis, or a “pathological pregnancy course” in a prospective study. For women anticipating pregnancy, the physician may discontinue or reduce the dose of all migraine medications to lower the risk of possible fetal damage and offer vigorous treatment with behavioral therapy, moist heat, and the judicious use of acetaminophen or opioid preparations. Migraine usually lessens during the second and third trimesters. The diagnosis of complicated migraine or de novo migraine with aura during pregnancy requires a thorough consideration of other diagnoses. Migraine may increase the risk for preeclampsia, especially for patients with prepregnancy obesity (Adeney et al., 2005) and may increase the risk for peripartum stroke (James et al., 2005). While small increased incidences of low birth weight, preterm birth, and cesarean section were noted in an Asian population (odds ratios 1.16, 1.24, and 1.16, respectively), the single large study did not control for the use of medications in this population, where the authors note equivocal clarity in the database diagnosis of migraine (Chen et al., 2010).

Before Pregnancy

Pregnancy and the anticipation of pregnancy complicate usual migraine therapy. Valproic acid causes fetal malformations. For fertile women taking prophylactic valproic acid whose migraine has been poorly responsive to other therapy, folic acid supplementation has been advised (see Epilepsy and Its Treatments). Discussion of reliable contraceptive measures and the risks for fetal malformation is essential. During pregnancy, physicians advise avoidance of valproic acid to treat headache. Topiramate is fetally toxic in animals, and the magnitude of teratogenic risk of topiramate is undetermined in humans. In older studies, approximately 50% of pregnancies were unplanned. When prescribing these medications, unintended fetal exposure during the early first trimester may occur.

During Pregnancy

During pregnancy, ergotamine and dihydroergotamine cause high rates of fetal malformation and are contraindicated. For newer drugs such as triptans, data are incomplete and their general use is inadvisable. Limited information suggests a low or no teratogenic potential (Kurth and Hernandez-Diaz, 2010). This reassuring but qualified news has emboldened some to suggest that prescription of a triptan may be acceptable in pregnant women who suffer physiologically and psychologically disabling migraine, whose headaches respond to a triptan, and in whom safer medications have failed (Von Wald and Walling 2002). Other authors offer that opioids and antiemetics, specifically prochlorperazine (oral or suppository), are drugs of choice for migraine during pregnancy (Goadsby et al., 2008). Metoclopramide, acetaminophen, and meperidine do not increase fetal risk and may be of benefit.

Rare case reports describe fetal toxicity associated with propranolol, atenolol, and other beta-blockers, but not with metoprolol. Although often safe during pregnancy, these drugs usually are discontinued or usage is reduced to the lowest effective dose. Prolonged use of atenolol to treat hypertension during pregnancy is associated with an increased risk of intrauterine growth restriction. When physician and patient are convinced that prophylactic therapy is required, the benefit of metoprolol, propranolol, or verapamil may outweigh risks. Incomplete data are available for lithium usage in humans. In animals, lithium is teratogenic. Physicians commonly advise that patients avoid lithium to treat headache during pregnancy. The use of occasional, single dose Naproxen sodium is relatively safe throughout pregnancy but safest when used during the first two trimesters. Researchers note increased risk of miscarriage for women using nonsteroidal anti-inflammatory drugs longer than one week during pregnancy and manufacturers recommend avoiding the medication after 31 to 32 weeks gestation and during breastfeeding primarily due to fetal cardiovascular risks.

Postpartum

Breastfeeding reduces migraine recurrence (Sances et al., 2003). In general, the breastfeeding woman with migraine should avoid ergotamine and lithium. Cautious use of triptans and antidepressants is acceptable. One article suggests that “In the absence of a specific contraindication such as coronary or cerebrovascular disease, sumatriptan by injection is an ideal way to deal with disabling migraine in this period, even for breastfeeding women” (Goadsby et al., 2008).

When a woman presents with severe puerperal headache, physicians may derive some comfort that 34% of women with a history of migraine will develop headache during the first postpartum week, commonly between 4 and 6 days and usually benign. However, the puerperium also is the time serious illness may present with sudden severe or “thunderclap” headache (see Chapter 69). The differential diagnosis includes migraine, cerebrospinal fluid hypovolemia including postdural puncture headache, CVT, preeclampsia/eclampsia, subarachnoid hemorrhage, stroke syndromes, posterior leukoencephalopathy syndrome, postpartum cerebral angiopathy, pituitary apoplexy, Sheehan syndrome, and lymphocytic hypophysitis (Gladstone et al., 2005).

Leg Muscle Cramps

Between 5% and 30% of pregnant women experience painful leg cramps, which do not adversely affect the fetus but bother the patient. The condition resolves rapidly postpartum. Typically, cramps occur in the morning or evening during the last trimester of pregnancy. Changes in the ionic concentrations of potassium, magnesium, sodium, and calcium may be important in the pathogenesis. Magnesium lactate or magnesium citrate tablets (122 mg in the morning and 244 mg in the evening) relieve or considerably lessen symptoms in approximately 80% of patients. Placebo is similarly effective in 40%. Some physicians report successful therapy with oral calcium carbonate or gluconate, 500 mg three or four times daily. Passive stretch and massage are helpful for the acute cramp.

Myasthenia Gravis

Before Pregnancy

Fertility is unaffected by myasthenia gravis, and oral contraceptive agents do not weaken these patients. No single study offers certainty with regard to the cumulative risk pregnancy causes in the patient with known myasthenia gravis (Hoffman et al., 2007). Conditions may remain stable, improve, worsen, or both improve and worsen at different stages of pregnancy. Approximately two-thirds of patients report some worsening at some time during pregnancy or the puerperium. The puerperium and first trimester are times of greatest risk. The course of myasthenia gravis for a future pregnancy is not predictable by the course of previous pregnancies.

The effect of thymectomy on myasthenia gravis usually is delayed. The potential mother can be advised that the procedure may be helpful for a pregnancy beginning approximately 1 year after surgery. Generally in women with myasthenia who may become pregnant, the physician should use drugs other than azathioprine and cyclosporine. Mycophenolate is associated with an increased risk of congenital malformations and spontaneous abortion prompting the manufacturers to recommend a negative pregnancy test within one week before beginning therapy and use of two reliable forms of contraception four weeks before and six weeks after therapy. Mycophenolate may affect the effectiveness of hormonal contraception. Myasthenia gravis does not influence the contractile strength of the smooth muscle of the uterus, the incidence of postpartum hemorrhage, or the occurrence of toxemia.

During Pregnancy

The medical therapy of myasthenia gravis changes little with pregnancy. Anticholinesterase agents including edrophonium (Tensilon) and plasmapheresis are relatively safe. Rapid drug metabolism during pregnancy may require increasing the rate or dose of anticholinesterase drugs. Corticosteroids may increase the risk for gestational diabetes and preeclampsia. Abortion does not lessen the manifestations of myasthenia gravis. Although the use of intravenous human immunoglobulin (IVIG) appears safe during pregnancy, the number of myasthenic patients studied is small. In animals, azathioprine is teratogenic, and low levels cross the placenta. Physicians generally advise patients with myasthenia to discontinue azathioprine in preparation for pregnancy. A few women with myasthenia gravis receiving azathioprine during pregnancy have given birth to healthy children. Some researchers point to the uncommon reports of human teratogenicity and intimate that azathioprine might be safer than animal data suggest. Mycophenolate is contraindicated during pregnancy.

Regional anesthesia is preferred for cesarean section. When the patient is taking anticholinesterase agents, metabolism of procaine is slowed and poorly predictable; in these patients, lidocaine is favored for local anesthesia. Neuromuscular blocking agents such as curariform drugs must be avoided because they may have a greatly prolonged effect in patients with myasthenia gravis. The use of magnesium sulfate as a tocolytic agent or a treatment for preeclampsia may precipitate a myasthenic crisis and is contraindicated.

Postpartum

Breastfeeding poses no significant difficulty, despite evidence that the antiacetylcholine receptor antibodies do pass to the baby in breast milk. Cyclosporine and azathioprine are secreted in breast milk; in general they should be avoided because of their risk for immunosuppression and tumorigenic potential. When medically necessary, the small but uncertain tumorigenic potential of azathioprine must be weighed against the known benefits of breast milk.

Corticosteroids also are secreted into breast milk but in small amounts. Large doses of anticholinesterase drugs taken by the mother may lead to gastrointestinal upset in the breastfed newborn.

Pregnancy Outcome

A retrospective Norwegian study reported an increased risk for premature rupture of amniotic membranes and double the rate of cesarean section among myasthenic women (Hoff et al., 2003). A smaller retrospective Taiwanese study found statistically insignificant increased risk of cesarean section, infants small for gestational age, low birthweight, and no difference for preterm delivery (Wen et al., 2009). Premature labor may be more common in women with myasthenia gravis but varies considerably among multiple studies.

Perinatal mortality increases to 6% to 8% for infants of women with myasthenia gravis, which is approximately five times that of the normal population. Approximately 2% of these are stillborn. Transient neonatal myasthenia affects 10% to 20% of infants born to women with myasthenia gravis. Most infants who develop transient myasthenia gravis do so within the first day, but weakness may begin up to 4 days after delivery and usually resolves within 3 to 6 weeks. Neonates require careful observation for at least 4 days. An imperfect correlation exists between maternal levels of antiacetylcholine receptor antibodies and the likelihood that the neonate will develop transient myasthenia gravis. Intrauterine exposure to receptor antibodies rarely may result in arthrogryposis, which has a high likelihood of recurrence in future pregnancy. The role of intragestational plasmapheresis and immunosuppression to prevent this condition in subsequent pregnancies is unknown (Polizzi et al., 2000).

Disorders of Muscle

Myotonic Dystrophy

Pregnancy is uncommon in women who have advanced myotonic dystrophy, probably because of progressive ovarian failure. Before the development of advanced disease, there is no significant reduction in fertility. For women who are able to conceive, pregnancy can be hazardous for both mother and fetus. Myotonic weakness often worsens during the second half of pregnancy. Congestive heart failure is reported. Ineffective uterine contractions, premature labor, and breech presentation often complicate labor. Tocolysis may result in aggravation of myotonia. Oxytocin can stimulate the myotonic uterus to produce increased contractions. Myotonic dystrophy complicates obstetric anesthesia, and regional anesthesia is preferred. Patients with myotonic dystrophy are unduly sensitive to respiratory suppression with pentobarbital. After delivery, hypotonic uterine dysfunction results in an increased risk for retained placenta and postpartum hemorrhage.

Half of children born to women with myotonic dystrophy inherit the disorder. Anticipation due to an increased number of triplet repeats (see Chapter 40) is responsible for the syndrome of congenital myotonic dystrophy in the neonate (see Chapter 79). Many neonates are hypotonic, and reported rates of morbidity are high. Fetal myotonic dystrophy may affect fetal swallowing, causing polyhydramnios. Prenatal diagnostic testing with amniocentesis or chorionic villus biopsy is available.

Available data suggest that myotonic dystrophy type 2 (see Chapter 79) is more benign than type 1 and may not result in problems with general anesthesia or increase problems of delivery for the pregnant woman. Type 2 may not increase the risk for polyhydramnios or stillbirth or result in congenital myotonic dystrophy (Day et al., 2003). Another study noted that about 21% in their series first presented with myotonic weakness during pregnancy, which worsened during subsequent pregnancies (Rudnik-Schöneborn et al., 2006). Some 17% of patients miscarried, half experienced preterm labor, and 27% delivered preterm.

Facioscapulohumeral Dystrophy

Information gathered in a study with self-selected and possible recall bias provides insight that the second stage of labor may be adversely affected by skeletal muscle weakness for many, and associated with worsened irreversible weakness in 24% of patients with this dominantly inherited disorder. In order of frequency, complaints included worsening of generalized weakness, frequent falling, difficulty carrying the infant owing to worsening of shoulder weakness, worsening or new-onset pain, and difficulty carrying the infant owing to worsening of leg weakness. Despite the worsening, 90% of women reported they would choose pregnancy again. Outcomes of pregnancy were good, with a statistically higher frequency of low birth weight (16.4%), the incidence of operative delivery (23.8%), and forceps delivery was more than doubled (19%) (Ciafaloni et al., 2006).

Inflammatory Myopathy

Pregnancy worsens or activates polymyositis and dermatomyositis. Manifestations of collagen vascular disease commonly associated with myositis may complicate pregnancy. More than half of fetuses die, but surviving infants thrive. Immunosuppressive treatment is advisable for gravid women. In small studies, decreased activity of myositis correlates with a more favorable outcome for the fetus (Silva et al., 2003; Váncsa et al., 2007).

Neuropathy

Bell Palsy

Facial nerve palsy occurs three to four times more commonly during pregnancy and the puerperium, usually occurring at about 35 weeks’ gestation (Shmorgun et al., 2002). However, reanalysis of these data suggests that this conclusion may be inaccurate, and the frequency of Bell palsy may be about the same in women of childbearing age (Vrabec et al., 2007). A retrospective chart review found the prognosis for recovery of facial nerve function to be worse when facial palsy occurs during pregnancy (Gillman et al., 2002) but not usually when the severity of the facial palsy is mild. Researchers find increased frequency of toxemia and hypertension in patients with gestational facial palsy and recommend careful and continued monitoring of the affected woman for these conditions. Herpes simplex virus type 1 is the cause of most facial palsies, and varicella-zoster far less often. Pharmacological therapy of Bell palsy during pregnancy remains controversial. When begun within 3 days of onset of facial weakness, prednisone 1 mg/kg for 5 days, tapering rapidly over a total 10-day course, may be effective in improving the prognosis in nongravid adults and is considered safest when not used during the first trimester (Vrabec et al., 2007). The routine use of antiviral drugs simultaneously has not been proven unequivocally effective in nongravid adults in the absence of a varicella-zoster syndrome (Ramsay Hunt syndrome or zoster sine herpete), including a meta-analysis (Browning, 2010; Quant et al., 2009). This combination of drugs has not been tested adequately during pregnancy. Individually, the drugs pose low risk. Patching of the eye and lubricating eye drops may help prevent corneal irritation (see Chapter 70).

Carpal Tunnel Syndrome

Approximately one in five pregnant women reports nocturnal hand paresthesias, primarily during the last trimester, often associated with peripheral edema. Excessive weight gain and fluid retention increase the occurrence of these complaints. Symptoms usually resolve spontaneously within weeks after parturition. During pregnancy, conservative therapy is indicated. Splinting of the wrist in the neutral position is helpful. Additionally, some physicians inject corticosteroids into the carpal tunnel. When hand muscles supplied by the median nerve weaken, the treatment of choice is surgical decompression using fiberoptic techniques.

Low Back Pain

Low back pain is ubiquitous in the nongravid female population and increases during pregnancy. In retrospective questionnaires, researchers find more than half the pregnant population recall pain during their pregnancy and half of those women remembered radiation of the back pain to the extremeties (Fast et al., 1987). As many as three-quarters of pregnant women report low back pain at some time in their pregnancy in prospective studies (Pennick and Young, 2008). A careful, prospective study estimated the prevalence of “true” sciatica, radiation of the pain in a dermatomal distribution to be less than 1% (Ostgaard et al., 1991). Investigators blame this torment and its propensity to increase after the fifth month of pregnancy on increasing lumbar lordosis, direct pressure from the enlarging uterus, postural stress, and hormonally-induced ligamentous laxity. In one Swedish study, nearly all women experiencing back pain during pregnancy serious enough to provoke loss of work suffered recurrence of back pain in a subsequent pregnancy and low back pain recurred commonly in the nongravid state (Brynhildsen et al., 1998). MRI and electromyography (EMG) can be helpful rarely. Risks of EMG are negligible. Authorities advise avoiding muscles that bring the EMG needle too close to the developing fetus. Risks of MRI are known incompletely (see Imaging, earlier). An extensive review of the literature concluded that interventions for the treatment of the low back pain of pregnancy are biased enough that unequivocal therapeutic direction cannot be indicated. The efficacy and risk of techniques to prevent low back pain are unknown. Studies of specifically tailored strengthening exercise, sitting pelvic tilt exercise programs and water gymnastics all reported beneficial effects. The effect of physiotherapy is small but may be of some benefit as may be acupuncture. Studies on acupuncture claim better results than for physiotherapy (Pennick et al., 2008).

When minor neurological deficits accompany a syndrome suggesting compressive disc disease, authorities recommend a conservative approach based on limited case series (Laban et al., 1995). Surgical management for compressive disc disease has been successfully employed and is suggested during pregnancy to treat severe or progressive neurological deficits and in the presence of a cauda equina syndrome (Brown and Levi, 2001; Laban et al., 1995).

We lack studies or consensus agreement on the preferred mode of delivery for patients with herniated and symptomatic lumbosacral disc disease. Laban et al., (1995) describes patients who underwent cesarean section successfully to avoid the theoretical increases of epidural venous pressure during the valsalva maneuver associated with pregnancy. This author suggests that a reflex response of skeletal muscle to pain during pregnancy may be responsible for elevated venous pressure, and that regional block anesthesia may be as effective with vaginal delivery.

Meralgia Paresthetica

The expanding abdominal wall and the increased lordosis of pregnancy stretch the lateral femoral cutaneous nerve to the thigh as it penetrates the tensor fascia lata or at the inguinal ligament. This unilateral or bilateral affliction of late pregnancy resolves within 3 months postpartum. The condition may be exacerbated during the hip flexion and increased intra-abdominal pressure of delivery and when retractors are applied for cesarean section.

Acute Polyradiculoneuropathy (Guillain-Barré Syndrome)

Pregnancy does not affect the incidence or course of acute polyradiculoneuropathy, but some investigators believe the pregnant patient may be more vulnerable to complications (Chan et al., 2004). Usually, infants of a mother without complications are born healthy. Only one case of neonatal acute polyradiculopathy resulting from maternal disease is reported. Some investigators recommend fluid loading before plasmapheresis to prevent hypotension. Others suggest avoidance of tocolytics in the presence of autonomic instability. IVIG has been used safely during pregnancy, but the number of patients who received this therapy and were studied remains small. Uterine contractions are unaffected by the disease. Cesarean section is only for obstetric indications. Severe hyperkalemia caused presumably by succinylcholine anesthesia resulting in reversible cardiac arrest has been described in a pregnant woman 3 weeks after complete recovery from acute polyradiculopathy (Feldman J.M., 1990). This case and additional related reports have prompted some authors to suggest that the combination of pregnancy and acute polyradiculopathy should lead to the cautious use or avoidance of depolarizing neuromuscular blocking agents.

Chronic Inflammatory Demyelinating Polyneuropathy

CIDP is three times more likely to relapse during the last trimester and puerperium than in the absence of pregnancy. Infants are unaffected. Corticosteroids, plasmapheresis, and IVIG treat exacerbations during pregnancy. Oral contraceptives can worsen CIDP.

Charcot-Marie-Tooth Disease Type 1

Small studies indicate that Charcot-Marie-Tooth disease type 1 worsens in approximately half of affected women during pregnancy. The magnitude of the effect of pregnancy on this disease remains unclear. Risk is less when weakness begins in adult life. After delivery, this deterioration improves in a third of patients and becomes persistently progressive in two-thirds of patients, although studies vary in their observations (Swan et al., 2007). A retrospective Norwegian study found that affected women were twice as likely as the general population to have fetal-presentation anomalies, experience postpartum hemorrhage, and undergo cesarean section—commonly on an emergency basis. Forceps delivery occurred three times as often (Hoff et al., 2005). Epidural anesthesia for labor is safe.

Gestational Polyneuropathy

Distal symmetrical neuropathy affects malnourished women. Presumably, thiamine and possibly other nutrients are deficient. The acute presentation of symmetrical neuropathy and Wernicke encephalopathy (see later discussion) in the third and fourth months may be due to the thiamine deficiency associated with hyperemesis gravidarum.

Maternal Brachial Plexus Neuropathy

Hereditary brachial plexus neuropathy is an autosomal dominant disorder characterized by periodic attacks of asymmetrical pain, weakness, atrophy, and sensory alteration of the shoulder girdle and upper limbs attributed to involvement of proximal upper-limb nerves or the brachial plexus. Symptoms are indistinguishable from those of Parsonage-Turner syndrome (see Chapter 29). Attacks may begin as early as 3 hours postpartum despite cesarean section, may recur for weeks following parturition, and may follow subsequent pregnancies. Intravenous methylprednisolone may reduce the pain but seems not to influence the course of the disease (Klein et al., 2002).

Maternal Obstetric Palsy

Peripheral nerves are occasionally compressed by the fetal head, the application of forceps, and improperly positioned leg holders. Craniopelvic disproportion, dystocia, prolonged labor, and primigravida status contribute to these injuries. Unilateral lumbosacral (L4, L5, and rarely S1) plexus injury is most common. The fetal brow strikes the nerves as they cross the posterior brim of the true pelvis. The associated sensory deficit usually involves more widespread sensory loss than that due to peroneal neuropathy. Peroneal nerve injuries often are caused when the nerve is compressed between a leg holder and the fibular head. Less common obstetric palsies include those of the femoral and obturator nerves.

Most maternal obstetric palsies are neurapraxic and resolve within 6 weeks. In future pregnancies, women with recurrent craniopelvic disproportion, dystocia, or axonal degeneration with their initial neuropathy are candidates for cesarean delivery. Otherwise, a cautious trial of labor may be prudent.

Movement Disorders

Restless Legs

Unpleasant paresthesias (described as creeping, crawling, aching, or fidgetiness) localized deep within both legs affect 10% to 27% of pregnant women. Usually they begin 30 minutes after the patient lies down and occur mainly in the last trimester. An irresistible desire to move the legs accompanies the discomfort. Symptoms resolve sharply during the first month postpartum, after which time about 5% of women remain affected. A study found lower average hemoglobin and mean corpuscular volume than in healthy subjects (Manconi et al., 2004). This same study describes gestational worsening in about 60% of patients reporting restless legs syndrome (RLS) before pregnancy, but improvement during pregnancy in some 12% of preexisting RLS. Approximately 80% of patients complaining of restless legs experience periodic movements of sleep (see Chapter 68). These stereotyped flexion movements of the legs during non–rapid eye movement sleep may awaken the patient, leading to sleep loss and excessive daytime somnolence. Caffeine ingestion, uremia, alcohol use, iron deficiency, hypothyroidism, vitamin deficiency, rheumatoid arthritis, peripheral neuropathy, and medications are important, if only occasional, associated factors. The importance of iron and folic acid supplementation remains unclear. Folic acid may be of benefit in treating restless legs during pregnancy. Anecdotal reports suggest a benefit from vitamin E, vitamin C, and magnesium supplements. Electric vibrators, stretching, walking, decreased activity, and massage also may be helpful. The use of dopaminergic agonists and levodopa to treat periodic limb movements of sleep during pregnancy has not undergone systematic study. Anecdotal reports indicate success and safety with levodopa. When a physician decides to offer either of these therapies, careful disclosure of the potential for known and also unforeseen risks to the fetus may allow the patient to make an informed decision.