Chapter 81 Neurological Problems of Pregnancy
Neurological Complications of Contraception
An international task force on combined oral contraceptives (COCs) (usually ethinylestradiol and levonorgestrel) and migraine cautiously suggested that women who suffer migraine and smoke tobacco should stop smoking before beginning COCs to reduce their risk of ischemic stroke. The task force identified COCs as potentially increasing the risk for ischemic stroke in women who have migraine with aura (Bousser et al., 2000). Consistent with this approach, other investigators reasonably suggest that the cautious use of COCs for a woman with migraine without aura who has a history of a stroke risk factor does not itself contraindicate the use of COCs.
Anticonvulsants do not affect the efficacy of medroxyprogesterone. Medroxyprogesterone may be the contraceptive pharmaceutical of choice in women with seizure disorders (Kaunitz, 2000). Based on theoretical considerations, some investigators recommend administering medroxyprogesterone injections every 10 weeks rather than every 12 weeks for women taking anticonvulsants that induce hepatic microsomal enzymes (Crawford, 2002).
Unwanted pregnancies with levonorgestrel use have occurred in women taking phenytoin and in women taking carbamazepine. Some researchers advise against the use of levonorgestrel in patients taking liver enzyme–inducing drugs of any kind, including enzyme-inducing anticonvulsants. Usual dose COCs, progesterone-only pills, medroxyprogesterone injections, and levonorgestrel implants have no known interactions and can be used in patients receiving valproic acid, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide, ethosuximide, and benzodiazepines. Failure of COCs with oxcarbazepine is reported in incomplete studies. A World Health Organization Working Group recommended against use of COCs, transdermal patch, vaginal ring, and progesterone-only pills for women taking phenytoin, caramazepine, barbiturates, primidone, topiramate, or oxcarbazepine due to reduced contraceptive effect (Gaffield et al., 2011).
In a careful study of small numbers of women, COCs lowered levels of lamotrigine by about 33%. This same study demonstrated that the lamotrigine levels of women in mid-luteal menstrual phase and not taking COCs dropped by about 31% (Herzog et al., 2009). Other studies report that when women take COCs, lamotrigine levels may decrease by half and some patients may suffer an increase in seizures. This effect is not seen when additional anticonvulsants are used with lamotrigine. Manufacturers of lamotrigine recommend that physicians increase that medication when patients taking lamotrigine monotherapy are placed on COCs.
Estrogen-containing oral contraceptive agents may worsen chronic inflammatory demyelinating polyneuropathy (CIDP) and moyamoya disease, unmask systemic lupus erythematosus (SLE), worsen migraine, and produce chorea in patients with antiphospholipid antibody syndrome. Based on recent studies, some physicians advise that an individually tailored contraceptive approach may include the recommendation of COCs in antiphospholipid antibody–negative patients with inactive or moderately active stable SLE (Bermas, 2005). The heightened risk for cerebral venous thrombosis (CVT) in women taking oral contraceptive agents increases with prothrombin or factor V gene mutations.
Ethical Considerations
When a diagnosis of maternal death by neurological criteria is confirmed, a decision whether to continue medical interventions for the sake of a viable or marginally viable fetus is required. No consensus as to the conditions under which such medical intervention must be offered are established. Physicians sometimes turn to the ethically appropriate surrogate(s), sometimes one for the mother and one for the fetus, to discuss the foreseeable possible futures and ask the surrogate to make a decision with regard to offered medical therapies. A model written by the Council on Ethical Affairs of the California Medical Association, with variable applicability outside of the State of California, can be obtained online (CMA, 2009). In some states, the physician helps select surrogates. In others, a statute-driven “hierarchy” exists. Some states prohibit an appropriate surrogate from permitting the termination of pregnancy for an incapacitated patient but not when the patient is dead. Advising pregnant women to execute advance directives for medical care seems an unlikely and incomplete solution.
Imaging
Computed tomography (CT) scanning employs ionizing radiation with known risks of teratogenesis, mutagenesis, and carcinogenesis. In general, physicians avoid ionizing radiation during pregnancy, particularly between 8 and 15 weeks, the gestational period most sensitive to ionizing radiation. However, the risk is not as high as perceived by some medical professionals, and several authors urge an approach balanced to the diagnostic needs of the woman and fetus. Researchers estimate the average woman receives background radiation less than 0.1 rad over 9 months. Risks of fetal malformation demonstrably increase with radiation doses above 15 rads. Induced miscarriages and major congenital malformations occur at negligibly increased risk with doses to the fetus under 5 rads. Estimated radiation dosage from a typical CT scan of the brain is less than 0.050 rads when employing precautionary lead shielding. Lumbar spine CT delivers some 3.5 rads. Acting on anxiety attributed by some to physician advice, women have opted for pregnancy termination after receiving low-dose diagnostic radiation during early gestation (Ratnapalan et al., 2008). Iodinated contrast media used for radiological procedures has the potential to depress fetal thyroid production. Most states mandate routine newborn thyroid screening; this is especially important in infants receiving iodinated contrast agents in utero.
Magnetic resonance imaging (MRI) can be used selectively to scan the brain and the venous and arterial circulations and is useful during pregnancy. No study or clinical observation has detailed harmful effects to mother or child, but detailed longitudinal studies on children exposed in utero to MRI are lacking. Despite the observations by the American College of Obstetricians and Gynecologists and the American College of Radiology (ACOG, 2004; American College of Radiology Committee on Drugs and Contrast Media, 2004; Kanal et al., 2007) that there is no known adverse effect of MRI on the fetus, only two human studies on this point exist, neither of which was of a design adequate to detect adverse effects that may be significant (International Commission on Non-Ionizing Radiation Protection, 2004). Restriction of maternal brain MRI, especially during the first trimester, is prudent.
Fortunately, most MRI studies relevant to neurological disease do not require the use of gadolinium. However, definitive studies detailing the safety of gadolinium-based magnetic resonance contrast agents during pregnancy and lactation are lacking. Gadolinium crosses the placenta, finds its way into amniotic fluid, and is swallowed by the fetus. Fetal developmental delay occurs in animals receiving high doses of gadolinium. No reports of mutagenic and teratogenic effects in humans appear in reviews of available literature. A small prospective study of 26 women who received gadolinium inadvertently during the periconceptional period and first trimester yielded a single child with a minor congenital anomaly (De Santis, 2007). Some authorities recommend that a woman abstain from breastfeeding for 24 hours after receiving iodinated contrast agents including gadolinium (Tang et al., 2004). Others, citing the tiny amount of contrast entering breast milk and the minute amount absorbed from the baby’s gut suggest that the potential risks are insufficient to warrant a recommendation to interrupt breastfeeding (Chen et al., 2008; Webb et al., 2005).
Headache
Tension Headache
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.
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).
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.
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
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.
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).
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.
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.
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.
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).
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.
