CENTRAL NERVOUS SYSTEM IMAGING
DEMYELINATING OR DEGENERATIVE DISEASES
IDIOPATHIC INTRACRANIAL HYPERTENSION
MATERNAL VENTRICULAR SHUNTS
MATERNAL BRAIN DEATH
A number of neurological diseases are relatively common in women of childbearing age. In the past, some of these may have precluded pregnancy, however, few do so now. Most of those encountered during pregnancy are the same as for nonpregnant women. That said, there are a few neurological disorders that may be seen more frequently in pregnant women. Some examples are Bell palsy, specific types of strokes, and benign intracranial hypertension or pseudotumor cerebri. Neurovascular disorders are an important cause of maternal mortality and accounted for 10 percent of maternal deaths in the United States from 1998 through 2005 (Berg, 2010b).
Because many neurological disorders are chronic, they frequently precede pregnancy. Although most women with chronic neurological disease who become pregnant will have successful outcomes, some of these disorders have specific risks with which clinicians should be familiar. Conversely, some women will have new-onset neurological symptoms during pregnancy, and these frequently must be distinguished from other pregnancy complications. Psychiatric disorders may also manifest with cognitive and neuromuscular abnormalities, and they should be considered in the evaluation.
CENTRAL NERVOUS SYSTEM IMAGING
Computed tomography (CT) and magnetic resonance (MR) imaging have opened new vistas for the diagnosis, classification, and management of many neurological and psychiatric disorders. As discussed in Chapter 46 (p. 933), these cranial imaging methods can be used safely during pregnancy. CT scanning is commonly used whenever rapid diagnosis is necessary and is excellent for detecting recent hemorrhage (Smith, 2012). Because it does not use radiation, MR imaging is often preferred. It is particularly helpful to diagnose demyelinating diseases, screen for arteriovenous malformations, evaluate congenital and developmental nervous system abnormalities, identify posterior fossa lesions, and diagnose spinal cord diseases (Gjelsteen, 2008). Whenever either test is done, the woman should be positioned in a left lateral tilt with a wedge under one hip to prevent hypotension as well as to diminish aortic pulsations, which may degrade the image.
Cerebral angiography with contrast injection, usually via the femoral artery, is a valuable adjunct to the diagnosis and treatment of some cerebrovascular diseases. Fluoroscopy delivers more radiation but can be performed with abdominal shielding. Positron emission tomography (PET) and functional MRI (fMRI) have not been evaluated for use in pregnant patients (Chiapparini, 2010).
The National Health Interview Survey is provided by the Centers for Disease Control and Prevention (Pleis, 2010). In the 2009 survey, a fifth of all women aged 18 to 44 years reported a severe headache or migraine within the past 3 months, and headache was the most common neurological complaint during pregnancy. Smitherman and coworkers (2013) found that 26 percent of nonpregnant women in this age group were similarly affected. Interestingly, Aegidius and colleagues (2009) reported an overall decrease in prevalence of all headache types during pregnancy in nulliparas, especially during the third trimester. The classification of headaches by the International Headache Society (2004) is shown in Table 60-1. Primary headaches are more common in pregnant women than those with secondary causes (Digre, 2013). Migraine headaches are those most likely to be affected by the hormonal changes of pregnancy (Torelli, 2010).
TABLE 60-1. Classification of Headachea
Cluster and other trigeminal autonomic cephalgias (< 1%)
Systemic infection (63%)
Head or neck trauma (4%)
Cranial or cervical vascular disorders
Substance use or withdrawal
Disorders of homeostasis
Head and neck disorders
aPercentages in parentheses are estimated frequencies.
Data from Goadsby, 2012. Adapted from the International Headache Society, 2004.
These are most common, and characteristic features include muscle tightness and mild to moderate pain that can persist for hours in the back of the neck and head. There are no associated neurological disturbances or nausea. The pain usually responds to rest, massage, application of heat or ice, antiinflammatory medications, or mild tranquilizers.
These headaches have a 1-year prevalence in all women of approximately 15 percent, and thus they are frequently encountered during pregnancy. The term migraine describes a periodic, sometimes incapacitating neurological disorder characterized by episodic attacks of severe headache and autonomic nervous system dysfunction (Goadsby, 2012). The International Headache Society (2004) classifies three migraine types based on the presence or absence of an aura as well as chronicity:
1. Migraine without aura—was formerly termed common migraine—and is characterized by a unilateral throbbing headache, nausea and vomiting, or photophobia.
2. Migraine with aura—formerly termed classic migraine—has similar symptoms preceded by premonitory neurological phenomena such as visual scotoma or hallucinations. A third of patients have this type of migraine, which sometimes can be averted if medication is taken at the first premonitory sign.
3. Chronic migraine is defined by a migraine headache occurring at least 15 days each month for more than 3 months.
Migraines may begin in childhood, peak in adolescence, and tend to diminish in both frequency and severity with advancing years. According to Lipton and associates (2007), their annual prevalence is 17 percent in women and 6 percent in men. Another 5 percent of women have probable migraine, that is, they have all criteria but one (Silberstein, 2007). Migraines are especially common in young women and have been linked to hormone levels (Torelli, 2010).
The exact pathophysiology of migraines is uncertain, but they occur when neuronal dysfunction leads to decreased cortical blood flow, activation of vascular and meningeal nociceptors, and stimulation of trigeminal sensory neurons (Brandes, 2007; D’Andrea, 2010). A predilection for the posterior circulation has been described by Kruit and coworkers (2004). Migraines—especially those with aura in young women—are associated with increased risk for ischemic strokes as discussed on page 1191. The risk is greater in those who smoke or use combination oral contraceptives.
Migraine in Pregnancy
The prevalence of migraine headaches in the first trimester is 2 percent (Chen, 1994). Prospective as well as observational studies have shown that most migraineurs have improvement during pregnancy (Adeney, 2006; Menon, 2008; Torelli, 2010). Still, migraines—usually those with an aura—occasionally appear for the first time during pregnancy. Pregnant women with preexisting migraine symptoms may have other symptoms suggestive of a more serious disorder, and new neurological symptoms should prompt a complete evaluation (Detsky, 2006; Heaney, 2010).
Although conventional thinking has been that migraine headaches do not pose increased maternal or fetal risks, several recent studies have refuted this (Allais, 2010). For example, women with severe migraines in the first 8 weeks may be at slightly increased risk for a fetus with limb-reduction defects (Banhidy, 2006). Preeclampsia and other cardiovascular morbidities are also increased (Facchinetti, 2009; Sanchez, 2008; Schürks, 2009). In a case-control study of nearly 18.5 million pregnancy-related discharges from 2000 through 2003, Bushnell and coworkers (2009) identified an incidence of migraine discharge codes of 185 per 100,000. Associated diagnoses and increased significant risks were found for migraines and stroke—15.8-fold; myocardial infarction—4.9; heart disease—2.1; venous thromboembolism—2.4; and preeclampsia/gestational hypertension—2.3-fold.
Data are limited regarding nonpharmacological management in pregnancy such as biofeedback techniques, acupuncture, and transcranial magnetic stimulation (Airola, 2010; Dodick, 2010). Effective pharmacological interventions include nonsteroidal antiinflammatory drugs, and most migraine headaches respond to simple analgesics such as ibuprofen or acetaminophen, especially if given early. Because of patient idiosyncrasies, multitarget drug therapy is necessary in most cases for migraine relief (Gonzalez-Hernandez, 2014). Severe headaches should be treated aggressively with intravenous hydration and parenteral antiemetics and opioids. Although intravenous magnesium sulfate has gained favor in the past few years, a recent metaanalysis reported no beneficial effects (Choi, 2014). Ergotamine derivatives are potent vasoconstrictors that should be avoided in pregnancy (Briggs, 2011).
Triptans are serotonin 5-HT1B/2D-receptor agonists that effectively relieve headaches by causing intracranial vasoconstriction (Contag, 2010). They also relieve nausea and vomiting and greatly reduce the need for analgesics. They can be given orally, by injection, as a rectal suppository, or as a nasal spray. The greatest experience is with sumatriptan (Imitrex), and although not studied extensively in pregnancy, it appears to be safe (Briggs, 2011; Nezvalová-Henriksen, 2010).
For women with frequent migraine headaches, oral prophylactic therapy is warranted. Amitriptyline (Elavil), 10 to 150 mg daily; propranolol (Inderal), 20 to 80 mg three times daily; or metoprolol (Lopressor, Toprol), 50 to 100 mg twice daily, is safe in pregnancy and has been used with success (Contag, 2010; Lucas, 2009; Marcus, 2007).
This rare primary headache disorder is characterized by severe unilateral lancinating pain radiating to the face and orbit, lasting 15 to 180 minutes, and occurring with autonomic symptoms and agitation. Pregnancy does not affect symptom severity. Affected women should avoid tobacco and alcohol. Acute management includes 100-percent oxygen therapy and sumatriptan given as a 6-mg dose subcutaneously (Calhoun, 2010; Francis, 2010). If recurrent, prophylaxis is administered using a calcium-channel blocking agent.
The Centers for Disease Control and Prevention reported that the prevalence of epilepsy in adults in 2005 was 1.65 percent (Kobau, 2008). There are 1.1 million American women of childbearing age who are affected. After headaches, seizures are the next most prevalent neurological condition encountered in pregnant women, and they complicate 1 in 200 pregnancies (Brodie, 1996; Yerby, 1994). Importantly, epilepsy accounted for 13 percent of maternal deaths in the United Kingdom for the 2005 to 2007 triennium (Lewis, 2007). Seizure disorders are also associated with altered fetal development, and they can adversely affect other pregnancy outcomes. The teratogenic effects of several anticonvulsant medications are unquestioned. The American Academy of Neurology and the American Epilepsy Society have developed guidelines regarding treatment in pregnant women, which are discussed subsequently (Harden, 2009a–c).
A seizure is defined as a paroxysmal disorder of the central nervous system characterized by an abnormal neuronal discharge with or without loss of consciousness. Epilepsy encompasses different syndromes whose cardinal feature is a predisposition to recurrent unprovoked seizures. The International League Against Epilepsy Commission on Classification and Terminology recently updated its terminologies for seizures (Berg, 2010a, 2011; Shorvon, 2011). This new classification schema is under development, and for now, most adults can be said to have either focal or generalized seizures.
These originate in one localized brain area and affect a correspondingly localized area of neurological function. They are believed to result from trauma, abscess, tumor, or perinatal factors, although a specific lesion is rarely demonstrated. Focal seizures without dyscognitive features start in one region of the body and progress toward other ipsilateral areas of the body, producing tonic and then clonic movements. Simple seizures can affect sensory function or produce autonomic dysfunction or psychological changes. Cognitive function is not impaired, and recovery is rapid. Focal seizures with dyscognitive features are often preceded by an aura and followed by impaired awareness manifested by sudden behavioral arrest or motionless stare. Involuntary movements such as picking motions or lip smacking are common.
These involve both brain hemispheres and may be preceded by an aura before an abrupt loss of consciousness. There is a strong hereditary component. In generalized tonic-clonic seizures, loss of consciousness is followed by tonic contraction of the muscles and rigid posturing, and then by clonic contractions of all extremities while the muscles gradually relax. Return to consciousness is gradual, and the patient may remain confused and disoriented for several hours. Absence seizures—also called petit mal seizures—are a form of generalized epilepsy that involve a brief loss of consciousness without muscle activity and are characterized by immediate recovery of consciousness and orientation.
Causes of Seizure
Some identifiable causes of convulsive disorders in young adults include head trauma, alcohol- and other drug-induced withdrawals, cerebral infections, brain tumors, biochemical abnormalities, and arteriovenous malformations. A search for these is prudent with a new-onset seizure disorder in a pregnant woman. The diagnosis of idiopathic epilepsy is one of exclusion.
Women with epilepsy should undergo education and counseling before pregnancy (Chap. 8, p. 158). Folic acid supplementation with 0.4 mg per day is begun at least 1 month before conception. The dose is increased to 4 mg when the woman taking antiepileptic medication becomes pregnant. These medications are assessed and adjusted with a goal of monotherapy using the least teratogenic medication. If this is not feasible, then attempts are made to reduce the number of medications used and to use them at the lowest effective dose (Dunlop, 2008). Medication withdrawal should be considered if a woman is seizure free for 2 years or more.
Epilepsy During Pregnancy
The major pregnancy-related risks to women with epilepsy are increased seizure rates with attendant mortality risks and fetal malformations. Seizure control is the main priority. Earlier studies described worsening seizure activity during pregnancy, however, this is not as common nowadays because of more effective drugs. Contemporary studies cite increased seizure activity in only 20 to 30 percent of pregnant women (Mawer, 2010; Vajda, 2008; Viinikainen, 2006). Women who are seizure free for at least 9 months before conception will likely remain so during pregnancy (Harden, 2009b).
Increased seizure frequency is often associated with decreased and thus subtherapeutic anticonvulsant serum levels, a lower seizure threshold, or both. An impressive number of pregnancy-associated alterations can result in subtherapeutic serum levels. These include nausea and vomiting, decreased gastrointestinal motility, antacid use that diminishes drug absorption, pregnancy hypervolemia offset by protein binding, induction of hepatic enzymes such as cytochrome oxidases, placental enzymes that metabolize drugs, and increased glomerular filtration that hastens drug clearance. Importantly, some women discontinue medication because of teratogenicity concerns. Finally, the seizure threshold can be affected by pregnancy-related sleep deprivation as well as hyperventilation and pain during labor.
Women with epilepsy have a small increased risk of some pregnancy complications (Borthen, 2011; Harden, 2009b). A population-based study from Iceland found that epileptic women had a twofold increased cesarean delivery rate (Olafsson, 1998). In a cohort study from Montreal, Richmond and coworkers (2004) reported an increased incidence of nonproteinuric hypertension and labor induction. From a Swedish study of 1207 epileptic women, Pilo and colleagues (2006) reported a 1.5-fold increased incidence of cesarean delivery, preeclampsia, and postpartum hemorrhage. Postpartum depression rates have also been reported to be increased in epileptic women (Turner, 2009). Finally, children of epileptic mothers have a 10-percent risk of developing a seizure disorder.
For years, it was difficult to separate effects of epilepsy versus its therapy as the primary cause of fetal malformations. As discussed in Chapter 8 (p. 158), it is now believed that untreated epilepsy is not associated with an increased fetal malformation rate (Thomas, 2008; Viinikainen, 2006). That said, the fetus of an epileptic mother who takes certain anticonvulsant medications has an indisputably increased risk for congenital malformations. Moreover, monotherapy is associated with a lower birth defect rate compared with multiagent therapy. Thus, if necessary, increasing monotherapy dosage is at least initially preferable to adding another agent (Buhimschi, 2009).
Specific drugs, when given alone, increase the malformation rate (Chap. 12, p. 246). Some of these are listed in Table 60-2. Phenytoin and phenobarbital increase the major malformation rate two- to threefold above baseline (Perucca, 2005; Thomas, 2008). A particularly potent teratogen is valproate, which has a dose-dependent effect and increases the malformation risk four- to eightfold (Eadie, 2008; Klein, 2014; Wyszynski, 2005). In general, with polytherapy, the risk increases with each drug added. At least at this time, the newer antiepileptic medications are reported to have no associations with a markedly increased risk of major birth defects (Molgaard-Nielson, 2011).
TABLE 60-2. Teratogenic Effects of Common Anticonvulsant Medications
Management in Pregnancy
The major goal is seizure prevention. To accomplish this, treatment for nausea and vomiting is provided, seizure-provoking stimuli are avoided, and medication compliance is emphasized. The fewest necessary anticonvulsants are given at the lowest dosage effective for seizure control. Although some providers routinely monitor serum drug levels during pregnancy, these concentrations may be unreliable because of altered protein binding. Free or unbound drug levels, although perhaps more accurate, are not widely available. Importantly, there is no evidence that such monitoring improves seizure control (Adab, 2006). For these reasons, drug levels may be informative if measured following seizures or if noncompliance is suspected. Some of the newer agents such as lamotrigine and oxcarbazepine may be more amenable to serum drug level monitoring (Harden, 2009a; Pennell, 2008).
For women taking anticonvulsant drugs, a targeted sonographic examination at midpregnancy is recommended by some to search for anomalies (Chap. 10, p. 197). Testing to assess fetal well-being is generally not indicated for women with uncomplicated epilepsy.
Breast Feeding and Contraception
There are limited available data regarding the safety of breast feeding with the various anticonvulsant medications. That said, no obvious deleterious effects, such as long-term cognitive issues, have been reported (Briggs, 2011; Harden, 2009c). Some of the anticonvulsant agents are associated with increased oral contraceptive failures. Thus, other more reliable methods should be considered (Chap 38, p. 696).
Abnormalities of the cerebrovascular circulation include strokes—both ischemic and hemorrhagic, as well as anatomical anomalies, such as arteriovenous malformations and aneurysms. The current endemic of obesity in this country, along with concomitant increases in heart disease, hypertension, and diabetes, has also resulted in increased stroke prevalence (Centers for Disease Control and Prevention, 2012). Women have a higher lifetime risk of stroke than men as well as higher associated mortality rates (Martínez-Sánchez, 2011; Roger, 2012). Moreover, pregnancy increases the immediate and lifetime risk of both ischemic and hemorrhagic stroke (Jamieson, 2010; Jung, 2010).
Stroke is relatively uncommon in pregnant women, but it contributes disparately to maternal mortality rates. Reported incidences of strokes in pregnancy range from 1.5 to 71 per 100,000 pregnancies (James, 2005; Kuklina, 2011; Scott, 2012). The incidence is increasing as measured by pregnancy-related hospitalizations for stroke (Callaghan, 2008; Kuklina, 2011). Importantly, most are associated with hypertensive disorders or heart disease. Almost 9 percent of the pregnancy-related mortality rate in the United States is due to cerebrovascular accidents, with a third being associated with preeclampsia (Berg, 2010b).
Most strokes in pregnancy manifest either during labor and delivery or in the puerperium. In a study of 2850 pregnancy-related strokes, approximately 10 percent developed antepartum, 40 percent intrapartum, and almost 50 percent postpartum (James, 2005). Several risk factors—unrelated and related to pregnancy—have been reported from studies that included more than 10 million pregnancies. These include older age; migraines, hypertension, obesity, and diabetes; cardiac disorders such as endocarditis, valvular prostheses, and patent foramen ovale; and smoking. Those related to pregnancy include hypertensive disorders, gestational diabetes, obstetrical hemorrhage, and cesarean delivery. By far, the most common risk factors are pregnancy-associated hypertensive disorders. As noted, one third of strokes are associated with gestational hypertension, and there is a three- to eightfold increased risk of stroke in hypertensive compared with normotensive women (Scott, 2012; Wang, 2011). Women with preeclampsia undergoing general anesthesia may be at higher risk of stroke compared with those given neuraxial anesthesia (Huang, 2010). Another risk factor for peripartum stroke is cesarean delivery, which increases the risk 1.5-fold compared with vaginal delivery (Lin, 2008).
Pregnancy-induced effects on cerebrovascular hemodynamics are unclear as related to risk for stroke. Although cerebral blood flow decreased by 20 percent from midpregnancy until term, importantly, it increased significantly with gestational hypertension (Zeeman, 2003, 2004b). Such hyperperfusion would at least intuitively be dangerous in women with certain vascular anomalies.
Acute occlusion or embolization of an intracranial blood vessel causes cerebral ischemia, which may result in death of brain tissue (Fig. 60-1). The more common associated conditions and etiologies of ischemic stroke are shown in Table 60-3. A transient ischemic attack (TIA) is caused by reversible ischemia, and symptoms usually last less than 24 hours. Patients with a stroke usually have a sudden onset of severe headache, hemiplegia or other neurological deficits, or occasionally, seizures. Focal neurological symptoms accompanied by an aura usually signify a first-episode migraine (Liberman, 2008).
FIGURE 60-1 Illustrations of a brain showing various types of strokes seen in pregnancy: (1) subcortical infarction (preeclampsia), (2) hypertensive hemorrhage, (3) aneurysm, (4) embolism or thrombosis in middle cerebral artery, (5) arteriovenous malformation, and (6) cortical vein thrombosis.
TABLE 60-3. Some Associated Disorders or Causes of Ischemic and Hemorrhagic Strokes During Pregnancy or the Puerperium
Evaluation of an ischemic stroke includes echocardiography and cranial imaging with CT, MR, or angiography. Serum lipids are measured with the caveat that their values are distorted by normal pregnancy (Appendix, p. 1291). Antiphospholipid antibodies and lupus anticoagulant are sought—these cause up to a third of ischemic strokes in otherwise healthy young women (Chap. 59, p. 1173). Also, tests for sickle-cell syndromes are completed when indicated. With a thorough evaluation, most causes can be identified, although treatment is not always available. Some of these include cardiac-associated embolism, vasculitis, or vasculopathy such as Moyamoya disease (Ishimori, 2006; Miyakoshi, 2009; Simolke, 1991).
In reproductive-age women, a significant proportion of pregnancy-related ischemic strokes are caused by gestational hypertension and preeclampsia syndrome (Jeng, 2004). As shown in Figure 60-1, areas of subcortical perivascular edema and petechial hemorrhage may progress to cerebral infarction (Aukes, 2007, 2009; Zeeman, 2004a). Although these are usually clinically manifest by an eclamptic convulsion, a few women will suffer a symptomatic stroke from a larger cortical infarction (Chap. 40, p. 742).
Other conditions with findings similar to preeclampsia include thrombotic microangiopathies (Chap. 56, p. 1116) and the reversible cerebral vasoconstriction syndrome (Chap. 40, p. 743). The latter, which is also termed postpartum angiopathy, can cause extensive cerebral edema with necrosis as well as widespread infarction with areas of hemorrhage (Katz, 2014; Ramnarayan, 2009; Singhal, 2009).
These strokes usually involve the middle cerebral artery (see Fig. 60-1). They are more common during the latter half of pregnancy or early puerperium (Lynch, 2001). The diagnosis can be made with confidence only after thrombosis and hemorrhage have been excluded. The diagnosis is more certain if an embolic source is identified. Hemorrhage may be more difficult to exclude because embolization and thrombosis are both followed by hemorrhagic infarction. Paradoxical embolism is an uncommon cause, even considering that more than a fourth of adults have a patent foramen ovale through which right-sided venous thromboemboli are deported (Kizer, 2005; Scott, 2012). Foraminal closure may not improve outcomes in these patients, however, this procedure has been performed during pregnancy (Dark, 2011; Furlan, 2012). Assorted cardioembolic causes of stroke include arrhythmias—especially atrial fibrillation, valvular lesions, mitral valve prolapse, mural thrombus, infective endocarditis, and peripartum cardiomyopathy.
Management of embolic stroke in pregnancy consists of supportive measures and antiplatelet therapy. Thrombolytic therapy and anticoagulation are controversial issues at this time (Kizer, 2005; Li, 2012).
Cerebral Artery Thrombosis
Most thrombotic strokes affect older individuals and are caused by atherosclerosis, especially of the internal carotid artery. Many are preceded by one or more transient ischemic attacks. Thrombolytic therapy with recombinant tissue plasminogen activator—rt-PA or alteplase is recommended within the first 3-hour window if there is measurable neurological deficit and if neuroimaging has excluded hemorrhage. This can be used in pregnancy. A principal risk is hemorrhagic transformation of an ischemic stroke in approximately 5 percent of treated patients (van der Worp, 2007).
Cerebral Venous Thrombosis
In a 10-center study in the United States, 7 percent of cerebral venous thromboses were associated with pregnancy (Wasay, 2008). Even so, pregnancy-associated cerebral venous thrombosis is rare in developed countries, and reported incidences range from 1 in 11,000 to 1 in 45,000 pregnancies (Lanska, 1997; Simolke, 1991). In the Nationwide Inpatient Sample of more than 8 million deliveries, James and associates (2005) observed that venous thrombosis caused only 2 percent of pregnancy-related strokes (Saposnik, 2011). There are numerous predisposing causes, and the greatest risk is in late pregnancy and the puerperium.
Thrombosis of the lateral or superior sagittal venous sinus usually occurs in the puerperium and often in association with preeclampsia, sepsis, or thrombophilia (see Fig. 60-1). It is more common in patients with inherited thrombophilias, lupus anticoagulant, or antiphospholipid antibodies (Chaps. 52, p. 1029 and 59, p. 1173). Headache is the most common presenting symptom, neurological deficits are common, and up to a third of patients have convulsions (Wasay, 2008). Diagnosis is with MR venography (Saposnik, 2011).
Management includes anticonvulsants for seizures, and although heparinization is recommended by most, its efficacy is controversial (de Freitas, 2008; Saposnik, 2011; Smith, 2012). Antimicrobials are given if there is septic thrombophlebitis, and fibrinolytic therapy is reserved for those women failing systemic anticoagulation. The prognosis for venous thrombosis in pregnancy is better than in nonpregnant subjects, and mortality rates are less than 10 percent (McCaulley, 2011). The recurrence rate is 1 to 2 percent during a subsequent pregnancy (Mehraein, 2003).
Recurrence Risk of Ischemic Stroke
Women with previous ischemic stroke have a low risk for recurrence during a subsequent pregnancy unless a specific, persistent cause is identified. Lamy and colleagues (2000) followed 37 women who had an ischemic stroke during pregnancy or the puerperium, and none of their 24 subsequent pregnancies was complicated by another stroke. In another study of 23 women who had prepregnancy strokes from a variety of causes, there were 35 subsequent pregnancies without a stroke recurrence (Coppage, 2004). Finally, in a follow-up study of 1770 nonpregnant women with antiphospholipid-related ischemic stroke, investigators reported no difference in the recurrence risk as long as preventative treatment was given with warfarin or aspirin (Levine, 2004). In another study of nonpregnant subjects, low-dose aspirin following venous thromboembolism decreased the risk of a subsequent stroke (Brighton, 2012).
Currently, there are no firm guidelines regarding prophylaxis in pregnant women with a stroke history (Helms, 2009). The American Heart Association stresses the importance of controlling risk factors such as hypertension and diabetes (Furie, 2011). Women with antiphospholipid antibody syndrome or certain cardiac conditions should be considered for prophylactic anticoagulation as discussed in Chapters 49 (p. 979) and 59 (p. 1175).
The two distinct categories of spontaneous intracranial bleeding are intracerebral and subarachnoid hemorrhage. The symptoms of a hemorrhagic stroke are similar to those of an ischemic stroke. Their differentiation is only possible with CT or MR imaging (Morgenstern, 2010).
Bleeding into the brain parenchyma most commonly is caused by spontaneous rupture of small vessels previously damaged by chronic hypertension as depicted in Figure 60-1 (Qureshi, 2001; Takebayashi, 1983). Thus, pregnancy-associated hemorrhagic strokes such as the one shown in Figure 60-2 are often associated with chronic hypertension and superimposed preeclampsia (Cunningham, 2005; Martin, 2005). Because of its location, this type of hemorrhage has much higher morbidity and mortality rates than does subarachnoid hemorrhage (Morgenstern, 2010). Chronic hypertension is uniquely associated with Charcot-Bouchard microaneurysms of the penetrating branches of the middle cerebral artery. Pressure-induced rupture causes bleeding in the putamen, thalamus, adjacent white matter, pons, and cerebellum. In the 28 women described by Martin and associates (2005), half died and most survivors had permanent disabilities. This cautions for the importance of proper management for gestational hypertension—especially systolic hypertension—to prevent cerebrovascular pathology (Chap. 40, p. 761).
FIGURE 60-2 arge intracerebral hemorrhage caused by hypertensive stroke.
In a study of 639 cases of pregnancy-related subarachnoid hemorrhage from the Nationwide Inpatient Sample, the incidence was 5.8 per 100,000 pregnancies, with half being postpartum (Bateman, 2012). These bleeds are more likely caused by an underlying cerebrovascular malformation in an otherwise normal patient (see Fig. 60-1). Ruptured saccular or “berry” aneurysms cause 80 percent of all subarachnoid hemorrhages. The remaining cases are caused by a ruptured arteriovenous malformation, coagulopathy, angiopathy, venous thrombosis, infection, drug abuse, tumors, or trauma. Such cases are uncommon, and a ruptured aneurysm or angioma or bleeding from a vascular malformation has an incidence of 1 in 75,000 pregnancies. Although this frequency is not different from that in the general population, the mortality rate during pregnancy is reported to be as high as 35 percent.
Intracranial Aneurysm. Approximately 2 to 5 percent of adults have this lesion (see Fig. 60-1). Fortunately, only a small percentage rupture—approximately 0.1 percent for aneurysms < 10 mm and 1 percent for those > 10 mm (Smith, 2008). Most aneurysms identified during pregnancy arise from the circle of Willis, and 20 percent are multiple (Stoodley, 1998). Pregnancy does not increase the risk for aneurysmal rupture. However, because of their high prevalence, they are more likely to cause subarachnoid bleeding than other causes (Hirsch, 2009; Tiel Groenestege, 2009). Aneurysms are more likely to bleed during the second half of pregnancy—only approximately 20 percent bleed during the first half (Dias, 1990).
The cardinal symptom of a subarachnoid hemorrhage from an aneurysm rupture is sudden severe headache, accompanied by visual changes, cranial nerve abnormalities, focal neurological deficits, and altered consciousness. Patients typically have signs of meningeal irritation, nausea and vomiting, tachycardia, transient hypertension, low-grade fever, leukocytosis, and proteinuria. Prompt diagnosis and treatment may prevent potentially lethal complications. The American Heart Association recommends noncontrast cranial CT imaging as the first diagnostic test, although MR imaging may be superior (Chalela, 2007; Connolly, 2012).
Treatment includes bed rest, analgesia, and sedation, with neurological monitoring and strict blood pressure control. Repair of a potentially accessible aneurysm during pregnancy depends in part on the recurrent hemorrhage risk versus surgical risks. At least in nonpregnant patients, the risk of subsequent bleeding with conservative treatment is 20 to 30 percent for the first month and then 3 percent per year. The risk of rebleeding is highest within the first 24 hours, and recurrent hemorrhage leads to death in 70 percent.
Early repair is done by surgical clipping of the aneurysm or by endovascular coil placement completed using fluoroscopic angiography yet attempting to limit radiation exposure. For women remote from term, repair without hypotensive anesthesia seems optimal. For women near term, cesarean delivery followed by aneurysm repair is a consideration, and we have successfully done this in several cases. For aneurysms repaired either before or during pregnancy, most allow vaginal delivery if remote from aneurysmal repair. A problem is what defines “remote,” and although some recommend 2 months, the time for complete healing is unknown. For women who survive subarachnoid hemorrhage, but in whom surgical repair is not done, we agree with Cartlidge (2000) and recommend against bearing down—put another way, we favor cesarean delivery.
Arteriovenous Malformations. These are congenital focal abnormal conglomerations of dilated arteries and veins with subarteriolar disorganization (see Fig. 60-1). They lack capillaries and have resultant arteriovenous shunting. Although unclear, the risk of bleeding may increase with gestational age. When arteriovenous malformations (AVMs) bleed, half do so into the subarachnoid space, whereas half are intraparenchymal with subarachnoid extension (Smith, 2008). They are uncommon and are estimated to occur in 0.01 percent of the general population. Bleeding does not appear to be more likely during pregnancy (Finnerty, 1999; Horton, 1990). AVMs are correspondingly rare during pregnancy, and in the study from Parkland Hospital, there was only one AVM in nearly 90,000 deliveries (Simolke, 1991).
Treatment of AVMs in nonpregnant patients is largely individualized. There is no consensus whether all those that are accessible should be resected. It also depends on whether the lesion is symptomatic or an incidental finding; its anatomy and size; presence of associated aneurysm, which is found in up to 60 percent; and especially, whether or not the lesion has bled. After hemorrhage, the risk of recurrent bleeding in unrepaired lesions is 6 to 20 percent within the first year, and 2 to 4 percent per year thereafter (Friedlander, 2007; Smith, 2008). The mortality rate with a bleeding AVM is 10 to 20 percent. In pregnancy, the decision to operate is usually based on neurosurgical considerations, and Friedlander (2007) recommends strong consideration for treatment if bleeding occurs. Because of the high risk of recurrent hemorrhage from an unresected or inoperable lesion, we favor cesarean delivery. An unusual case of spontaneous regression of a cerebral AVM has been described (Couldwell, 2011).
DEMYELINATING OR DEGENERATIVE DISEASES
The demyelinating diseases are neurological disorders characterized by immune-mediated focal or patchy destruction of myelin sheaths accompanied by an inflammatory response. The degenerative diseasesare multifactorial and are characterized by progressive neuronal death.
In the United States, multiple sclerosis (MS) is second only to trauma as a cause of neurological disability in middle adulthood (Hauser, 2012b). Because the disease affects women twice as often as men and usually begins in the 20s and 30s, women of reproductive age are most susceptible. The familial recurrence rate of MS is 15 percent, and the incidence in offspring is increased 15-fold.
The demyelinating characteristic of this disorder results from predominately T cell-mediated autoimmune destruction of oligodendrocytes that synthesize myelin. There is a genetic susceptibility and likely an environmental trigger such as exposure to certain bacteria and viruses, for example, Chlamydophila pneumoniae, human herpesvirus 6, or Epstein-Barr virus (Frohman, 2006; Goodin, 2009).
There are four clinical types of multiple sclerosis (Hauser, 2012b):
1. Relapsing-remitting MS accounts for initial presentation in 85 percent of affected individuals. It is characterized by unpredictable recurrent episodes of focal or multifocal neurological dysfunction usually followed by full recovery. Over time, however, relapses lead to persistent deficits.
2. Secondary progressive MS disease is relapsing-remitting disease that begins to pursue a progressive downhill course after each relapse. It is likely that all patients eventually develop this type.
3. Primary progressive MS accounts for 15 percent of cases. It is characterized by gradual progression of disability from the time of initial diagnosis.
4. Progressive-relapsing MS refers to primary progressive MS with apparent relapses.
Classic findings of MS include sensory loss, visual symptoms from optic neuritis, weakness, paresthesias, and a host of other neurological symptoms. Almost 75 percent of women with isolated optic neuritis develop multiple sclerosis within 15 years. Clinical diagnosis is confirmed by MR imaging and cerebrospinal fluid analysis. In greater than 95 percent of cases, MR imaging shows characteristic multifocal white matter plaques that represent discrete areas of demyelination such as shown in Figure 60-3. Their appearance and extent are less helpful for treatment response. Similarly, Kuhle and colleagues (2007) reported that identification of serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein are not predictive of recurrent disease activity.
FIGURE 60-3 Magnetic resonance cranial images from a woman with multiple sclerosis. A. T2-weighted axial image shows bright signal abnormalities in white matter, typical for multiple sclerosis. B.Sagittal T2-FLAIR image shows hyperintense areas within the corpus callosum that are representative of demyelination in multiple sclerosis. (From Hauser, 2012b, with permission.)
Effects of Pregnancy on MS
The PRegnancy In Multiple Sclerosis—PRIMS—study is a European prospective multicenter study in which 254 pregnancies were described (Vukusic, 2006). A principal finding was a confirmed 70-percent reduction in relapse risk during pregnancy, but with a significantly increased relapse rate postpartum. This may be related to increased pregnancy-induced numbers of T-helper lymphocytes with an increased T2/T1 ratio (Airas, 2008). In a metaanalysis of women with more than 1200 pregnancies complicated by multiple sclerosis, their relapse rate was 0.4 per year before pregnancy; 0.26 per year during pregnancy; and this increased to 0.7 per year after delivery (Finkelsztejn, 2011). Factors associated with postpartum relapse include a high relapse rate before pregnancy, relapses during pregnancy, and a high MS disability score (Portaccio, 2014; Vukusic, 2006). Breast feeding has no apparent effect on postpartum relapses (Airas, 2010; Portaccio, 2011).
Effects of MS on Pregnancy
There are usually no adverse effects on pregnancy outcome with uncomplicated disease. Some women may become fatigued more easily, those with bladder dysfunction are predisposed to urinary infection, and women with spinal lesions at or above T6 are at risk for autonomic dysreflexia. Dahl and coworkers (2006) described 449 such pregnancies, and they reported a higher labor induction rate and longer second-stage labor. The increased induction rate as well as elective operations contributed to the overall increased cesarean delivery rate. They also reported outcomes in 649 affected women and described a lower mean birthweight but similar perinatal mortality rate compared with that of controls (Dahl, 2005). Other studies have corroborated that MS does not significantly affect obstetrical and neonatal outcomes (Finkelsztejn, 2011).
Management During Pregnancy and the Puerperium
Goals are to arrest acute or initial attacks, employ disease-modifying agents, and provide symptomatic relief. Some treatments may need to be modified during pregnancy. Acute or initial attacks are treated with high-dose intravenous methylprednisolone—500 to 1000 mg daily for 3 to 5 days, followed by oral prednisone for 2 weeks. Plasma exchange may be considered. Symptomatic relief can be provided by analgesics; carbamazepine, phenytoin, or amitriptyline for neurogenic pain; baclofen (Lioresal, Kemstro) for spasticity; α2-adrenergic blockade for bladder neck relaxation; and cholinergic and anticholinergic drugs to stimulate or inhibit bladder contractions.
Several disease-modifying therapies can be used for relapsing multiple sclerosis or exacerbations. Examples include interferons β1a (Rebif) and β1b (Betaseron) and glatiramer acetate (Copaxone), which have been shown to decrease relapse rates by a third (Rudick, 2011). Data concerning safety in pregnancy are limited but overall reassuring (Amato, 2010; Salminen, 2010). Clinical trials with natalizumab (Tysabri), an alpha 4 integrin antagonist—especially when combined with interferon β1a—significantly reduced MS clinical relapse rates (Polman, 2006; Rudick, 2006). In a review of 35 pregnancies, early pregnancy drug exposure did not worsen outcomes (Hellwig, 2011). Because of limited data, however, women are currently advised to stop the drug 3 months before conception. Fingolimad (Gilenya) is a new oral medication, and pregnancy safety data are unavailable (Briggs, 2011).
Prevention of relapses postpartum is afforded by treatment with intravenous immune globulin (IVIG) given in a dose of 0.4 g/kg daily for 5 days during weeks 1, 6, and 12 (Argyriou, 2008). The Prevention of Postpartum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPART’MUS) trial is a multicenter randomized controlled trial currently enrolling patients (Vukusic, 2009).
This adult-onset neurodegenerative disease results from an autosomal dominant expanded CAG trinucleotide repeat within the Huntington gene on chromosome 4. It is characterized by a combination of choreoathetotic movements, progressive dementia, and psychiatric manifestations. Because the mean age of onset is 40 years, Huntington disease rarely complicates pregnancy. Prenatal diagnosis is discussed in Chapter 14 (p. 297). However, prenatal screening is controversial because this usually is a late-onset adult disease. Thus, extensive pretest counseling is imperative (Novak, 2010).
This autoimmune-mediated neuromuscular disorder affects approximately 1 in 7500 persons. It is more common in women, and its incidence peaks in their 20s and 30s. The etiology is unknown, but genetic factors likely play a role. Most patients demonstrate antibodies to the acetylcholine receptor, although 10 to 20 percent are seronegative. The latter often have antibodies to muscle-specific tyrosine kinase (MuSK) that regulates assembly of the acetylcholine receptor subunits at the neuromuscular junction (Cavalcante, 2011; Pal, 2011).
Cardinal features of MG are weakness and easy fatigability of facial, oropharyngeal, extraocular, and limb muscles. Deep tendon reflexes are preserved. Cranial muscles are involved early and disparately, and diplopia and ptosis are common. Facial muscle weakness causes difficulty in smiling, chewing, and speaking. In 85 percent of patients, the weakness becomes generalized. Other autoimmune diseases may coexist, and hypothyroidism should be excluded. The clinical course is marked by exacerbations and remissions, especially when it first becomes clinically apparent. Remissions are not always complete and are seldom permanent. Systemic diseases, concurrent infections, and even emotional upset may precipitate exacerbations, of which there are three types:
1. Myasthenic crises—characterized by severe muscle weakness, inability to swallow, and respiratory muscle paralysis.
2. Refractory crises—characterized by the same symptoms but unresponsive to the usual therapy.
3. Cholinergic crises—excessive cholinergic medication leads to nausea, vomiting, muscle weakness, abdominal pain, and diarrhea.
All three of these can be life threatening, but a refractory crisis is a medical emergency. Those with bulbar myasthenia are at particular risk because they may be unable to swallow or even ask for help.
Myasthenia is manageable but not curable. Thymectomy is generally recommended for long-term benefits in the 75 percent of patients who have thymic hyperplasia or a thymoma seen with CT or MR imaging (Drachman, 2012; Nam, 2011). Anticholinesterase medications such as pyridostigmine (Mestinon), an analogue of neostigmine, improve symptoms by impeding acetylcholine degradation. They seldom produce normal muscle function. Ironically, overdose is manifest by increased weakness—the cholinergic crisis—that may be difficult to differentiate from myasthenic symptoms. Most of those refractory to anticholinesterase therapy respond to immunosuppressive therapy with glucocorticoids, azathioprine, methotrexate, cyclosporine, and mycophenolate mofetil. Tacrolimus, an immunosuppressant used in organ transplantation, and rituximab, a chimeric monoclonal antibody, are currently being evaluated (Ibrahim, 2010; Maddison, 2011; Yoshikawa, 2011). Cyclophosphamide is reserved for severe, generalized refractory cases. When short-term, rapid clinical improvement is needed—such as for a surgical procedure or a myasthenic crisis—high-dose immunoglobulin G or plasma exchange is usually effective (Barth, 2011; Cortese, 2011; Mandawat, 2010).
Myasthenia and Pregnancy
Because the greatest period of risk is within the first year following diagnosis, it seems reasonable to postpone pregnancy until there is sustained improvement. Antepartum management of myasthenia includes close observation with liberal rest and prompt treatment of infections (Heaney, 2010; Kalidindi, 2007). Women in remission who become pregnant while taking corticosteroids or azathioprine should continue these. Thymectomy has been successfully performed during pregnancy in refractory cases (Ip, 1986). Acute onset of myasthenia or its exacerbation demands prompt hospitalization and supportive care. Plasmapheresis and high-dose immunoglobulin therapy should be used for emergency situations (Drachman, 2012).
Although pregnancy does not appear to affect the overall course of MG, fatigue common to most pregnancies may be exacerbated, and the expanding uterus may compromise respiration. During pregnancy, maternal hypotension or hypovolemia are avoided. The clinical course of MG during pregnancy is unpredictable, and frequent hospitalizations are the norm. Up to a third of women have worsening MG during pregnancy, with exacerbations occurring equally in all three trimesters (Djelmis, 2002; Podciechowski, 2005).
Myasthenia gravis has no significant adverse effects on pregnancy outcomes (Wen, 2009). Preeclampsia is a concern because magnesium sulfate may precipitate a severe myasthenic crisis (Hamaoui, 2009; Heaney, 2010). Although phenytoin use is also problematic in this regard, its adverse effects are less troublesome, and thus many choose it for neuroprophylaxis in MG patients with severe preeclampsia. Because smooth muscle is unaffected, most women have normal labor. Oxytocin is given for the usual indications, and cesarean delivery reserved for obstetrical indications. Because narcotics may cause respiratory depression, close observation and respiratory support are essential during labor and delivery. Curariform drugs should be avoided—examples include magnesium sulfate discussed above, muscle relaxants used with general anesthesia, and aminoglycosides. Neuraxial analgesia is accomplished with amide-type local agents. Regional analgesia is preferred unless there is significant bulbar involvement or respiratory compromise (Almeida, 2010; Blichfeldt-Lauridsen, 2012). During second-stage labor, some women may have impaired voluntary expulsive efforts that may warrant operative vaginal delivery.
As discussed above, 80 percent of mothers with myasthenia gravis have anti-acetylcholine-receptor IgG antibodies. These and anti-MuSK antibodies are transported transplacentally, and the fetus can be affected to cause hydramnios (Heaney, 2010). Similarly, 10 to 20 percent of neonates manifest MG symptoms (Murray, 2010; Niks, 2008). Transient symptoms usually include a feeble cry, poor suckling, and respiratory distress. Symptoms usually respond to cholinesterase inhibitors and resolve within a few weeks.
Peripheral neuropathy is a general term used to describe disorders of peripheral nerve(s) of any cause. Because neuropathy can result from a variety of sources, its discovery should prompt a search for an etiology. Polyneuropathiescan be either axonal or demyelinating as well as acute, subacute, or chronic (Chaudhry, 2008). They are often associated with systemic diseases such as diabetes, with drug or environmental toxin exposure, or with genetic diseases.
Mononeuropathies are relatively common in pregnancy, and they signify focal involvement of a single nerve trunk and imply local causation such as trauma, compression, or entrapment. Traumatic pudendal, obturator, femoral, and common fibular mononeuropathies are usually caused by childbirth and are discussed in Chapter 36 (p. 676).
In 75 percent of cases, this acute demyelinating polyradiculoneuropathy has clinical or serological evidence for an acute infection. Commonly associated are infection with Campylobacter jejuni, cytomegalovirus, and Epstein-Barr virus; surgical procedures; and immunizations (Haber, 2009; Hauser, 2012a). Guillain-Barré syndrome (GBS) is thought to be immune-mediated from antibodies formed against nonself antigens. Demyelination causes sensory and motor conduction blockade, and recovery occurs with remyelination in most cases.
Clinical features include areflexic paralysis—usually ascending—with or without sensory disturbances. Autonomic dysfunction is common. The full syndrome develops over 1 to 3 weeks. Management is supportive, but in the worsening phase, patients should be hospitalized because at least a third will need ventilatory assistance. Intravenous high-dose immunoglobulin (IVIG) or plasmapheresis is beneficial if begun within 1 to 2 weeks of motor symptoms, however, neither decreases mortality rates (Cortese, 2011; Gwathmey, 2011; Hughes, 2011). Although most patients recover fully within several months to a year, up to 20 percent are severely disabled, and 5 percent die, despite treatment (Yuki, 2012). Some manifest as chronic inflammatory demyelinating polyneuropathy, and our experiences indicate that it may be relatively common in these young women.
Guillain-Barré syndrome is not more common in pregnancy, although inconclusive data suggest rates are increased in the puerperium (Cheng, 1998). Its clinical course in pregnancy is the same as for nonpregnant individuals, and after an insidious onset, paresis and paralysis most often continue to ascend to cause ventilatory weakness. Hurley and colleagues (1991) reported that a third of pregnant women required ventilatory support, with a mortality rate of 13 percent. The acute syndrome is treated with either high-dose IVIG or plasmapheresis (Chan, 2004; Yuki, 2012).
This disfiguring palsy is usually a mononeuropathic acute facial paralysis that is relatively common in reproductive-aged women (Fig. 60-4). It has a female predominance, and pregnant women are at a fourfold risk compared with nonpregnant women (Cohen, 2000; Heaney, 2010). The disease is characterized by facial nerve inflammation and often is associated with reactivation of herpes virus or herpes zoster virus.
FIGURE 60-4 Bell facial nerve palsy developing on the day of delivery after a cesarean for dichorionic twins. This woman was treated with prednisone and antiviral medication, and the palsy had almost resolved 3 weeks postpartum.
Bell palsy usually has an abrupt and painful onset with maximum weakness by 48 hours. In some cases, hyperacusis and loss of taste accompany paralysis (Beal, 2012). Management includes supportive care with facial muscle massage and eye protection against corneal lacerations from drying. There is general consensus that prednisone, 1 mg per kg given orally daily for 5 days, will result in improved outcomes and a shortened recovery period (Salinas, 2010; Sullivan, 2007). It is controversial if addition of an antiviral medication will improve these outcomes (de Almeida, 2009; Lockhart, 2009; Quant, 2009).
It is unclear if pregnancy alters the prognosis for spontaneous facial palsy recovery. Gillman and colleagues (2002) found that only half of pregnant women recovered to a satisfactory level after 1 year—this compared with approximately 80 percent of nonpregnant women and men. Some prognostic markers for incomplete recovery are bilateral palsy, recurrence in a subsequent pregnancy, greater percentage of nerve function loss, and a faster rate of loss (Cohen, 2000; Gilden, 2004). Corticosteroid therapy given early in the course of the disease significantly improves outcomes. Other than a fivefold increased rate for gestational hypertension or preeclampsia, women with Bell palsy do not have increased adverse pregnancy outcomes (Katz, 2011; Shmorgun, 2002).
Carpal Tunnel Syndrome
This syndrome results from compression of the median nerve and is the most frequent mononeuropathy in pregnancy (Padua, 2010). Symptoms include burning, numbness, or tingling along the inner half of one or both hands. Also, wrist pain and numbness extend into the forearm and sometimes into the shoulder (Katz, 2002). Symptoms are bilateral in 80 percent of pregnant women, and 10 percent have evidence for severe denervation (Seror, 1998). Differential diagnosis includes cervical radiculopathy of C6–C7 and de Quervain tendonitis, which is caused by swelling of the conjoined tendons and their sheaths near the distal radius. Nerve conduction studies may be helpful (Alfonso, 2010).
The reported incidence is 7 to 43 percent and varies greatly because the range of symptoms is marked (Finsen, 2006; Padua, 2010). Symptomatic treatment with a splint applied to the slightly flexed wrist during sleep relieves pressure and usually provides relief. Although symptoms typically are self-limited, occasionally surgical decompression and corticosteroid injections are necessary (Keith, 2009; Shi, 2011). Symptoms may persist in more than half of patients at one year and in a third at 3 years (Padua, 2010).
According to the National Spinal Cord Injury Statistical Center (2012), there are approximately 12,000 spinal cord injuries each year. At least half affect reproductive-age individuals, with a male-to-female predominance of 4 to 1. The severity of cord injury determines the short- and long-term prognosis as well as that for pregnancy. Incomplete neurological lesions are associated with at least some sensory and/or motor function below the level of injury, whereas there is none with complete cord transection. Many women develop sexual function alteration and transient hypothalamic pituitary hypogonadism, however, pregnancy is not uncommon if menstruation resumes (Bughi, 2008).
Women with spinal cord injury have an increased frequency of pregnancy complications that include preterm and low-birthweight infants. Most have asymptomatic bacteriuria with sporadic symptomatic urinary infections. Bowel dysfunction causes constipation in more than half, and anemia and pressure-necrosis skin lesions are also common. There are two serious and life-threatening complications with spinal cord injuries:
1. If the cord is transected above T10, the cough reflex is impaired, respiratory function may be compromised, and pneumonitis from covert aspiration can be serious. Pulmonary function tests are considered, and some women may need ventilatory support in late pregnancy or in labor.
2. Women with lesions above T5–T6 are at risk for autonomic dysreflexia. With this, stimuli from structures innervated below the level of the spinal lesion results in massive disordered sympathetic stimulation. Abrupt catecholamine release can cause vasoconstriction with severe hypertension and symptoms that include throbbing headaches, facial flushing, sweating, bradycardia, tachycardia, arrhythmias, and respiratory distress. Dysreflexia can be precipitated by a variety of stimuli, such as urethral catheterization; bladder distention from retention; rectal or cervical distention with digital examinations; uterine contractions and cervical dilatation; or any other pelvic structure manipulation (American College of Obstetricians and Gynecologists, 2005; Krassioukov, 2009). In one report, 12 of 15 women at risk for autonomic dysreflexia suffered at least one episode during pregnancy (Westgren, 1993).
Because uterine contractions are not affected by spinal cord lesions, labor is usually easy—even precipitous, and comparatively painless. If the lesion is below T12, uterine contractions are felt normally. For lesions above T12, the risk of out-of-hospital delivery is substantial and can be minimized by teaching women to palpate for uterine contractions. This is especially important because up to 20 percent of women deliver preterm (Westgren, 1993). Some recommend tocodynamometry and weekly cervical examinations beginning at 28 to 30 weeks. Another reasonable option that we frequently employ at Parkland Hospital is elective hospitalization after 36 to 37 weeks (Hughes, 1991).
Spinal or epidural analgesia extending to T10 prevents autonomic dysreflexia and should be instituted at the start of labor. If there are severe symptoms before epidural placement, steps are taken to abolish the provoking stimulus. A parenteral antihypertensive agent such as hydralazine or labetalol is given. Labor and vaginal delivery with epidural or spinal analgesia are preferable and will minimize autonomic dysreflexia (Kuczkowski, 2006). Operative vaginal delivery is frequently necessary.
IDIOPATHIC INTRACRANIAL HYPERTENSION
Also known as pseudotumor cerebri or benign intracranial hypertension, this disorder is characterized by increased intracranial pressure without hydrocephalus. The cause is unknown, but it may be the result of either overproduction or underabsorption of cerebrospinal fluid. Symptoms include headache in at least 90 percent of cases, visual disturbances such as loss of a visual field or central visual acuity in 70 percent, and commonly occurring papilledema that may be sight-threatening (Evans, 2000; Heaney, 2010). Other complaints are stiff neck, back pain, pulsatile tinnitus, cranial nerve palsies such as facial palsy, ataxia, or paresthesias. The syndrome is commonly found in young women and is prevalent in those who are obese, who recently gained weight, or both (Fraser, 2011). Along with symptoms, other criteria for diagnosis include elevated intracranial pressure > 250 mm H2O, normal cerebrospinal fluid (CSF) composition, normal cranial CT or MR imaging findings, and no evidence for systemic disease (International Headache Society, 2005).
Idiopathic intracranial hypertension is usually self-limited. Visual defects can be prevented by lowering the cerebrospinal fluid pressure. Drugs given to lower pressure include acetazolamide (Diamox) to reduce fluid production, furosemide (Lasix), or topiramate (Topamax). Corticosteroids are now rarely used. Surgical intervention is occasionally necessary and is accomplished by either lumboperitoneal shunting of spinal fluid or optic nerve sheath fenestration.
Effects of Pregnancy
It is controversial if pregnancy is a risk factor for idiopathic intracranial hypertension. Certainly, symptoms may first appear in pregnancy, and women previously diagnosed may become symptomatic. These usually develop by midpregnancy, tend to be self-limited, and usually resolve postpartum.
There is general agreement that pregnancy does not alter management. Some recommend serial visual field testing to prevent permanent vision loss. In a report of 16 pregnant women, visual field loss developed in four, and it became permanent in one (Huna-Baron, 2002). Visual field loss is often coincident with the development of papilledema, for which acetazolamide is given. Lee and associates (2005) reported successful treatment of 12 pregnant women. Although outmoded for treatment of nonpregnant individuals, repeated lumbar punctures are generally successful in providing temporary relief throughout pregnancy. In some pregnant women, surgical therapy becomes necessary, and we and others have had promising results with optic nerve sheath fenestration (Thambisetty, 2007).
Pregnancy complications are likely due to associated obesity and not to intracranial hypertension. In a review of 54 pregnancies, there were no excessive adverse perinatal outcomes (Katz, 1989). The route of delivery depends on obstetrical indications, and conduction analgesia is safe (Aly, 2007; Karmaniolou, 2011).
MATERNAL VENTRICULAR SHUNTS
Pregnancies in women with previously placed ventricular shunts for obstructive hydrocephalus usually have satisfactory outcomes (Landwehr, 1994). Shunts may be ventriculoperitoneal, ventriculoatrial, or ventriculopleural. Partial obstruction of a shunt is common, especially late in pregnancy (Schiza, 2012). In one report of 17 such pregnancies, neurological complications were reported in 13 (Wisoff, 1991). Findings included headaches in 60 percent, nausea and vomiting in 35 percent, lethargy in 30 percent, and ataxia or gaze paresis, each in 20 percent. Most symptoms respond to conservative management. However, if CT scanning during symptom evaluation discloses acute hydrocephaly, then the shunt is tapped or pumped several times daily. In some cases, surgical revision is necessary and may be emergently required (Murakami, 2010).
Another shunting procedure involves placement of an endoscopic third ventriculostomy for hydrocephalus in children or adults (de Ribaupierre, 2007). One report described successful results in five pregnant women who underwent successful ventriculostomy placement (Riffaud, 2006). In a review, reproductive function and miscarriage rates were found to significantly worsen in these women (Bedaiwy, 2008).
Vaginal delivery is preferred in women with shunts, and unless there is a meningomyelocele, conduction analgesia is permitted. Antimicrobial prophylaxis is indicated if the peritoneal cavity is entered for cesarean delivery or tubal sterilization.
MATERNAL BRAIN DEATH
Brain death is rare in obstetrics. Life-support systems and parenteral alimentation for up to 15 weeks have been described while awaiting delivery (Hussein, 2006; Powner, 2003; Souza, 2006). Some women were treated with aggressive tocolysis and antimicrobial therapy. Chiossi and coworkers (2006) reviewed outcomes in 17 women with persistent vegetative state who were given various levels of support. At least five died after delivery, and most of the remainder continued to be in the vegetative state. There are no published reports of neurological recovery with a diagnosis of brain death using the uniform Determination of Death Act definition (Wijdicks, 2010). The ethical, financial, and legal implications, both civil and criminal, that arise from attempting or not attempting such care are profound (Farragher, 2005; Feldman, 2000). In some women, perimortem cesarean delivery is performed as discussed in Chapter 47 (p. 956).
Adab N: Therapeutic monitoring of antiepileptic drugs during pregnancy and in the postpartum period: is it useful? CNS Drugs 20:791, 2006
Adeney KL, Williams MA: Migraine headaches and preeclampsia: an epidemiologic review. Headache 46:794, 2006
Aegidius K, Anker-Zwart J, Hagen K, et al: The effect of pregnancy and parity on headache prevalence: the head-HUNT study. Headache 49:851, 2009
Airas L, Jalkanen A, Alanen A, et al: Breast-feeding, postpartum and prepregnancy disease activity in multiple sclerosis. Neurology 75:474, 2010
Airas L, Saraste M, Rinta S, et al: Immunoregulatory factors in multiple sclerosis patients during and after pregnancy: relevance of natural killer cells. Clin Exp Immunol 151:235, 2008
Airola G, Allais G, Castagnoli I, et al: Non-pharmacological management of migraine during pregnancy. Neurol Sci 31(1):S63, 2010
Alfonso C, Jann S, Massa R, et al: Diagnosis, treatment and follow-up of the carpal tunnel syndrome: a review. Neurol Sci 31:243, 2010
Allais G, Castagnoli Gabellari I, Borgogno P, et al: The risks of women with migraine during pregnancy. Neurol Sci 31(Suppl 1):S59, 2010
Almeida C, Coutinho E, Moreira D, et al: Myasthenia gravis and pregnancy: anaesthetic management—a series of cases. Eur J Anaesthesiol 27:985, 2010
Aly EE, Lawther BK: Anaesthetic management of uncontrolled idiopathic intracranial hypertension during labour and delivery using an intrathecal catheter. Anaesthesia 62:178, 2007
Amato MP, Portaccio E, Ghezzi A, et al: Pregnancy and fetal outcomes after interferon-beta exposure in multiple sclerosis. Neurology 75:1794, 2010
American College of Obstetricians and Gynecologists: Obstetric management of patients with spinal cord injuries. Committee Opinion No. 275, September 2002, Reaffirmed 2005
Argyriou AA, Makris N: Multiple sclerosis and reproductive risks in women. Reprod Sci 15(8):755, 2008
Aukes AM, de Groot JC, Aarnoudse JG, et al: Brain lesions several years after eclampsia. Am J Obstet Gynecol 200(5):504.e1, 2009
Aukes AM, Wessel I, Dubois AM, et al: Self-reported cognitive functioning in formerly eclamptic women. Am J Obstet Gynecol 197:365.e1, 2007
Banhidy F, Acs N, Horvath-Puho E, et al: Maternal severe migraine and risk of congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol 76:592, 2006
Barth D, Nouri M, Ng E, et al: Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology 76:2017, 2011
Bateman BT, Olbrecht VA, Berman MF, et al: Peripartum subarachnoid hemorrhage. Anesthesiology 116:242, 2012
Beal MF, Hauser SL: Trigeminal neuralgia, Bell’s palsy, and other cranial nerve disorders. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 18th ed. McGraw-Hill, New York, 2012, p 3362
Bedaiwy MA, Fathalla MM, Shaaban OM, et al: Reproductive implications of endoscopic third ventriculostomy for the treatment of hydrocephalus. Eur J Obstet Gynecol Reprod Biol 140(1):55, 2008
Berg AT, Berkovic SF, Brodie MJ, et al: Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia 51:676, 2010a
Berg AT, Scheffer IE: New concepts in classification of the epilepsies: entering the 21st century. Epilepsia 52(6):1058, 2011
Berg CJ, Callaghan WM, Syverson C: Pregnancy-related mortality in the United States, 1998 to 2005. Obstet Gynecol 116:1302, 2010b
Blichfeldt-Lauridsen L, Hansen BD: Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand 56(1):17, 2012
Borthen I, Eide MG, Daltveit AK, et al: Obstetric outcome in women with epilepsy: a hospital-based, retrospective study. BJOG 118(8):956, 2011
Brandes JL, Kudrow D, Stark SR, et al: Sumatriptan-naproxen for acute treatment of migraine. JAMA 297:1443, 2007
Briggs GG, Freeman RK, Yaffe SJ: Drugs in Pregnancy and Lactation, 9th ed. Philadelphia, Lippincott Williams & Wilkins, 2011
Brighton TA, Eikelboom JW, Mann K, et al: Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 367:1979, 2012
Brodie MJ, Dichter MA: Antiepileptic drugs. N Engl J Med 334:168, 1996
Bughi S, Shaw SJ, Mahmood G, et al: Amenorrhea, pregnancy, and pregnancy outcomes in women following spinal cord injury: a retrospective cross-sectional study. Endocr Pract 14(4):437, 2008
Buhimschi CS, Weiner CP: Medication in pregnancy and lactation: part 1. Teratology. Obstet Gynecol 113:166, 2009
Bushnell CD, Jamison M, James AH: Migraines during pregnancy linked to stroke and vascular diseases: US population based case-control study. BMJ 338:b664, 2009
Calhoun AH, Peterlin BL: Treatment of cluster headache in pregnancy and lactation. Curr Pain Headache Rep 14:164, 2010
Callaghan WM, MacKay AP, Berg CJ: Identification of severe maternal morbidity during delivery hospitalizations, United States, 1991–2003. Am J Obstet Gynecol 199:133.e1, 2008
Cartlidge NEF: Neurologic disorders. In Barron WM, Lindheimer MD (eds): Medical Disorders During Pregnancy, 3rd ed. St. Louis, Mosby, 2000, p 516
Cavalcante P, Le Panse R, Berrih-Aknin S, et al: The thymus in myasthenia gravis: site of “innate autoimmunity”? Muscle Nerve 44(4):467, 2011
Centers for Disease Control and Prevention: Prevalence of stroke–United States, 2006–2010, MMWR 61:379, 2012
Chalela JA, Kidwell CS, Nentwich LM, et al: Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet 369:293, 2007
Chan LY, Tsui MH, Leung TN: Guillain-Barré syndrome in pregnancy. Acta Obstet Gynecol Scand 83:319, 2004
Chaudhry V: Peripheral neuropathy. In Fauci AS, Braunwald E, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill, New York, 2008, p 2651
Chen TC, Leviton A: Headache recurrence in pregnant women with migraine. Headache 34:107, 1994
Cheng Q, Jiang GX, Fredrikson S, et al: Increased incidence of Guillain-Barré syndrome postpartum. Epidemiology 9:601, 1998
Chiapparini L, Ferraro S, Grazzi L: Neuroimaging in chronic migraine. Neurol Sci 31(Suppl 1):S19, 2010
Chiossi G, Novic K, Celebrezze JU, et al: Successful neonatal outcome in 2 cases of maternal persistent vegetative state treated in a labor and delivery suite. Am J Obstet Gynecol 195:316, 2006
Choi H, Parman N: The use of intravenous magnesium sulphate for acute migraine: meta-analysis of randomized controlled trials. Eur J Emerg Med 21:2, 2014
Cohen Y, Lavie O, Granoxsky-Grisaru S, et al: Bell palsy complicating pregnancy: a review. Obstet Gynecol Surv 55:184, 2000
Connolly ES JR, Rabinstein AA, Carhuapoma JR: Guidelines for the management of aneurismal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:1711, 2012
Contag SA, Bushnell C: Contemporary management of migraine disorders in pregnancy. Curr Opin Obstet Gynecol 22:437, 2010
Coppage KH, Hinton AC, Moldenhauer J, et al: Maternal and perinatal outcome in women with a history of stroke. Am J Obstet Gynecol 190:1331, 2004
Cortese I, Chaudhry V, So YT, et al: Evidence-based guideline update: plasmapheresis in neurologic disorders. Neurology 76:294, 2011
Couldwell SM, Kraus KL, Couldwell WT: Regression of cerebral arteriovenous malformation in the puerperium. Acta Neurochir 153:359, 2011
Cunningham FG: Severe preeclampsia and eclampsia: systolic hypertension is also important. Obstet Gynecol 105:237, 2005
D’Andrea G, Leon A: Pathogenesis of migraine: from neurotransmitters to neuromodulators and beyond. Neurol Sci 31(Supp 1):S1, 2010
Dahl J, Myhr KM, Daltveit AK, et al: Planned vaginal births in women with multiple sclerosis: delivery and birth outcome. Acta Neurol Scand Suppl 183:51, 2006
Dahl J, Myhr KM, Daltveit AK, et al: Pregnancy, delivery, and birth outcome in women with multiple sclerosis. Neurology 65:1961, 2005
Dark L, Loiselle A, Hatton R, et al: Stroke during pregnancy: therapeutic options and role of percutaneous device closure. Heart Lung Circ 20:538, 2011
De Almeida JR, Khabori MA, Guyatt GH, et al: Combined corticosteroid and antiviral treatment for Bell palsy. JAMA 302(9):985, 2009
De Freitas GR, Bogousslavsky J: Risk factors of cerebral vein and sinus thrombosis. Front Neurol Neurosci 23:23, 2008
De Ribaupierre S, Rilliet B, Vernet O, et al: Third ventriculostomy vs ventriculoperitoneal shunt in pediatric obstructive hydrocephalus: results from a Swiss series and literature review. Childs Nerv Syst 23:527, 2007
Detsky ME, McDonald DR, Baerlocher MO: Does this patient with headache have a migraine or need neuroimaging? JAMA 296(10):1274, 2006
Dias MS, Sekhar LN: Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Neurosurgery 27:855, 1990
Digre KB: Headaches during pregnancy. Clin Obstet Gynecol 56:317, 2013
Djelmis J, Sostarko M, Mayer D, et al: Myasthenia gravis in pregnancy: report on 69 cases. Eur J Obstet Gynecol Reprod Biol 104:21, 2002
Dodick DW, Schembri CT, Helmuth M, et al: Transcranial magnetic stimulation for migraine: a safety review. Headache 50:1153, 2010
Drachman DB: Myasthenia gravis and other diseases of the neuromuscular junction. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 18th ed. McGraw-Hill, New York, 2012, p 3480
Dunlop AL, Jack BW, Bottalico JN, et al: The clinical content of preconception care: women with chronic medical conditions. Am J Obstet Gynecol 199(6B):S310, 2008
Eadie MJ: Antiepileptic drugs as human teratogens. Expert Opin Drug Saf 7:195, 2008
Evans RW, Friedman DI: Expert opinion: the management of pseudotumor cerebri during pregnancy. Headache 40:495, 2000
Facchinetti F, Allais G, Nappi RE: Migraine is a risk factor for hypertensive disorders in pregnancy: a prospective cohort study. Cephalagia 29(3):286, 2009
Farragher RA, Laffey JG: Maternal brain death and somatic support. Neurocrit Care 3:99, 2005
Feldman DM, Borgida AF, Rodis JF, et al: Irreversible maternal brain injury during pregnancy: a case report and review of the literature. Obstet Gynecol Surv 55:708, 2000
Finkelsztejn A, Brooks JBB, Paschoal FM Jr, et al: What can we really tell women with multiple sclerosis regarding pregnancy? A systemic review and meta-analysis of the literature. BJOG 118:790, 2011
Finnerty JJ, Chisholm CA, Chapple H, et al: Cerebral arteriovenous malformation in pregnancy: presentation and neurologic, obstetric, and ethical significance. Am J Obstet Gynecol 181:296, 1999
Finsen V, Zeitlmann H: Carpal tunnel syndrome during pregnancy. Scand J Plast Reconstr Hand Surg 40:41, 2006
Francis GJ, Becker WJ, Pringsheim TM: Acute and preventive pharmacologic treatment of cluster headache. Neurology 75:463, 2010
Fraser C, Plant GT: The syndrome of pseudotumour cerebri and idiopathic intracranial hypertension. Curr Opin Neurol 24:12, 2011
Friedlander RM: Arteriovenous malformations of the brain. N Engl J Med 356(26):2704, 2007
Frohman EM, Racke MK, Raine CS: Multiple sclerosis—the plaque and its pathogenesis. N Engl J Med 354:942, 2006
Furie KL, Kasner SE, Adams RJ, et al: Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:227, 2011
Furlan AJ, Reisman M, Massaro J, et al: Closure or medical therapy for cryptogenic stroke with patient foramen ovale. N Engl J Med 366:991, 2012
Gilden DH: Bell’s palsy. N Engl J Med 351:1323, 2004
Gillman GS, Schaitkin BM, May M, et al: Bell’s palsy in pregnancy: a study of recovery outcomes. Otolaryngol Head Neck Surg 126:26, 2002
Gjelsteen AC, Ching BH, Meyermann MW: CT, MRI, PET, PET/CT, and ultrasound in the evaluation of obstetric and gynecologic patients. Surg Clin North Am 88:361, 2008
Goadsby PJ, Raskin NH: Headache. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 18th ed. McGraw-Hill, New York, 2012, p 112
Gonzalez-Hernandez A, Condes-Lara M: The multitarget drug approach in migraine treatment: the new challenge to conquer. Headache 64:197, 2014
Goodin DS: The causal cascade to multiple sclerosis: a model for MS pathogenesis. PLoS One 4(2):e4565, 2009
Gwathmey K, Balogun RA, Burns T: Neurologic indications for therapeutic plasma exchange: an update. J Clin Apheresis 26:261, 2011
Haber P, Sejvar J, Mikaeloff Y, et al: Vaccines and Guillain-Barré syndrome. Drug Saf 32(4):309, 2009
Hamaoui A, Mercado R: Association of preeclampsia and myasthenia: a case report. J Reprod Med 54(9):587, 2009
Harden CL, Hopp J, Ting TY, et al: Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency. Neurology 73(2):126, 2009a
Harden CL, Meador KJ, Pennell PB, et al: Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes. Neurology 73(2):133, 2009b
Harden CL, Pennell PB, Koppel BS, et al: Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding. Neurology 73(2):142, 2009c
Hauser SL, Amato AA: Guillain-Barré and other immune-mediated neuropathies. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 18th ed. McGraw-Hill, New York, 2012a, p 3474
Hauser SL, Goodin DS: Multiple Sclerosis and other demyelinating diseases. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 18th ed. McGraw-Hill, New York, 2012b, p 3395
Heaney DC, Williams DJ, O’Brien PO: Neurology. In Powrie R, Greene M, Camann W (eds): de Swiet’s Medical Disorders in Obstetric Practice, 5th ed. Wiley-Blackwell, Oxford, 2010, p 371
Hellwig K, Haghikia A, Gold R. Pregnancy and natalizumab: results of an observational study in 35 accidental pregnancies during natalizumab treatment. Mult Scler 17:958, 2011
Helms AK, Drogan O, Kittner SJ: First trimester stroke prophylaxis in pregnant women with a history of stroke. Stroke 40(4):1158, 2009
Hirsch KG, Froehler MT, Huang J, et al: Occurrence of perimesencephalic subarachnoid hemorrhage during pregnancy. Neurocrit Care 10(3):339, 2009
Holmes LB, Baldwin EJ, Smith CR, et al: Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 70(22 Pt 2):2152, 2008
Horton JC, Chambers WA, Lyons SL, et al: Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations. Neurosurgery 27(6):867, 1990
Huang CJ, Fan YC, Tsai PS: Differential impacts of modes of anaesthesia on the risk of stroke among preeclamptic women who undergo Caesarean delivery: a population-based study. BJA 105(6):818, 2010
Hughes RA, Pritchard J, Hadden RD: Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain-Barré syndrome. Cochrane Database Syst Rev 3:CD008630, 2011
Hughes SJ, Short DJ, Usherwood MM, et al: Management of the pregnant women with spinal cord injuries. Br J Obstet Gynaecol 98:513, 1991
Huna-Baron R, Kupersmith MJ: Idiopathic intracranial hypertension in pregnancy. J Neurol 249(8):1078, 2002
Hunt S, Russell A, Smithson WH, et al: Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 71(4):272, 2008
Hurley TJ, Brunson AD, Archer RL, et al: Landry Guillain-Barré Strohl syndrome in pregnancy: report of three cases treated with plasmapheresis. Obstet Gynecol 78:482, 1991
Hussein IY, Govenden V, Grant JM, et al: Prolongation of pregnancy in a woman who sustained brain death at 26 weeks of gestation. BJOG 113:120, 2006
Ibrahim H, Dimachkie MM, Shaibani A: A review: the use of rituximab in neuromuscular diseases. J Clin Neuromusc Dis 12:91, 2010
International Headache Society: The International Classification of Headache Disorders, 2nd ed. Cephalalgia 24:1, 2004
International Headache Society: The International Classification of Headache Disorders, 2nd ed.—revision of criteria for 8.2 Medication-overuse headache. Cephalalgia 25:460, 2005
Ip MSM, So SY, Lam WK, et al: Thymectomy in myasthenia gravis during pregnancy. Postgrad Med J 62:473, 1986
Ishimori ML, Cohen SN, Hallegue DS, et al: Ischemic stroke in a postpartum patient: understanding the epidemiology, pathogenesis, and outcome of Moyamoya disease. Semin Arthritis Rheum 35:250, 2006
James AH, Bushnell CD, Jamison MG, et al: Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 106:509, 2005
Jamieson DG, Skliut M: Stroke in women: what is different? Curr Atheroscler Rep 12:236, 2010
Jeng JS, Tang SC, Yip PK: Stroke in women of reproductive age: comparison between stroke related and unrelated to pregnancy. J Neurol Sci 221:25, 2004
Jung SY, Bae HJ, Park BJ, et al: Parity and risk of hemorrhagic strokes. Neurology 74:1424, 2010
Kalidindi M, Ganpot S, Tahmesebi F, et al: Myasthenia gravis and pregnancy. J Obstet Gynaecol 27:30, 2007
Karmaniolou I, Petropoulos G, Theodoraki K: Management of idiopathic intracranial hypertension in parturients: anesthetic considerations. Can J Anesth 58:650, 2011
Katz A, Sergienko R, Dior U, et al: Bell’s palsy during pregnancy: is it associated with adverse perinatal outcome? Laryngoscope 121:1395, 2011
Katz BS, Fugate JE, Ameriso SF, et al: Clinical worsening in reversible vascoconstriction syndrome. JAMA Neurol 71:68, 2014
Katz JN, Simmons BP: Carpal tunnel syndrome. N Engl J Med 346: 1807, 2002
Katz VL, Peterson R, Cefalo RC: Pseudotumor cerebri and pregnancy. Am J Perinatol 6:442, 1989
Keith MW, Masear V, Amadio PC, et al: Treatment of carpal tunnel syndrome. J Am Acad Orthop Surg 17:397, 2009
Kizer JR, Devereux RB: Patient foramen ovale in young adults with unexplained stroke. N Engl J Med 353:2361, 2005
Klein P, Mathews GC: Antiepileptic drugs and neurocognitive development. Neurology January 8, 2014 [Epub ahead of print]
Kobau R, Zahran H, Thurman DJ, et al: Epilepsy surveillance among adults—19 states, behavioral risk factor surveillance system, 2005. MMWR 57:1, 2008
Krassioukov A, Warburton DE, Teasell R, et al: A systematic review of the management of autonomic dysreflexia after spinal cord injury. Arch Phys Med Rehabil 90:682, 2009
Kruit MC, van Buchem MA, Hofman PA, et al: Migraine as a risk factor for subclinical brain lesions. JAMA 291:427, 2004
Kuczkowski KM: Labor analgesia for the parturient with spinal cord injury: what does an obstetrician need to know? Arch Gynecol Obstet 274:108, 2006
Kuhle J, Pohl C, Mehling M, et al: Lack of association between antimyelin antibodies and progression to multiple sclerosis. N Engl J Med 356:371, 2007
Kuklina EV, Tong X, Bansil P, et al: Trends in pregnancy hospitalizations that included a stroke in the United States from 1994 to 2007. Stroke 42:2564, 2011
Lamy C, Hamon JB, Coste J, et al: Ischemic stroke in young women. Neurology 55:269, 2000
Landwehr JB, Isada NB, Pryde PG, et al: Maternal neurosurgical shunts and pregnancy outcome. Obstet Gynecol 83:134, 1994
Lanska DJ, Kryscio RJ: Peripartum stroke and intracranial venous thrombosis in the National Hospital Discharge Survey. Obstet Gynecol 89:413, 1997
Lee AG, Pless M, Falardeau J, et al: The use of acetazolamide in idiopathic intracranial hypertension during pregnancy. Am J Ophthalmol 139:855, 2005
Levine SR, Brey RL, Tilley BC, et al: Antiphospholipid antibodies and subsequent thrombo-occlusive events in patients with ischemic stroke. JAMA 291:576, 2004
Lewis G: Saving mothers’ lives: reviewing maternal deaths to make motherhood safer—2003–2005. Confidential Enquiries into Maternal and Child Health, London, 2007
Li Y, Margraf J, Kluck B, et al: Thrombolytic therapy for ischemic stroke secondary to paradoxical embolism in pregnancy. Neurologist 18:44, 2012
Liberman A, Karussis D, Ben-Hur T, et al: Natural course and pathogenesis of transient focal neurologic symptoms during pregnancy. Arch Neurol 65:218, 2008
Lin SY, Hu CJ, Lin HC: Increased risk of stroke in patients who undergo cesarean section delivery: a nationwide population-based study. Am J Obstet Gynecol 198:391.e1, 2008
Lipton RB, Bigal ME, Diamond M, et al: Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68:343, 2007
Lockhart P, Daly F, Pitkethly M, et al: Antiviral treatment for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 4:CD001869, 2009
Lucas S. Medication use in the treatment of migraine during pregnancy and lactation. Curr Pain Headache Rep 13:392, 2009
Lynch JK, Nelson KB: Epidemiology of perinatal stroke. Curr Opin Pediatr 13:499, 2001
Maddison P, McConville J, Farrugia ME, et al: The use of rituximab in myasthenia gravis and Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry 82(6):671, 2011
Mandawat A, Kaminski HJ, Cutter G, et al: Comparative analysis of therapeutic options used for myasthenia gravis. Ann Neurol 68:797, 2010
Marcus DA: Headache in pregnancy. Curr Treat Options Neurol 9:23, 2007
Martin JN Jr, Thigpen BD, Moore RC, et al: Stroke and severe preeclampsia and eclampsia: a paradigm shift focusing on systolic blood pressure. Obstet Gynecol 105:246, 2005
Martínez-Sánchez P, Fuentes B, Fernández-Domínguez J, et al: Young women have poorer outcomes than men after stroke. Cerebrovasc Dis 31:455, 2011
Mawer G, Briggs M, Baker GA, et al: Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study. Seizure 19(2):112, 2010
McCaulley JA, Pates JA: Postpartum cerebral venous thrombosis. Obstet Gynecol 118:423, 2011
Mehraein S, Ortwein H, Busch M, et al: Risk of recurrence of cerebral venous and sinus thrombosis during subsequent pregnancy and puerperium. J Neurol Neurosurg Psychiatry 74:814, 2003
Menon R, Bushnell CD: Headache and pregnancy. Neurologist 14:108, 2008
Miyakoshi K, Matsuoka M, Yasutomi D, et al: Moyamoya-disease-related ischemic stroke in the postpartum period. J Obstet Gynaecol Res 35(5):974, 2009
Molgaard-Nielsen D, Hviid A: Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 305(19):1996, 2011
Morgenstern LB, Hemphill III JC, Anderson C, et al: Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 41:2108, 2010
Morrow J, Russell A, Guthrie E, et al: Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry77(2):193, 2006
Murakami M, Morine M, Iwasa T, et al: Management of maternal hydrocephalus requires replacement of ventriculoperitoneal shunt with ventriculoatrial shunt: a case report. Arch Gynecol Obstet 282:339, 2010
Murray EL, Kedar S, Vedanarayanan VV: Transmission of maternal muscle-specific tyrosine kinase (MuSK) to offspring: report of two cases. J Clin Neuromusc Dis 12:76, 2010
Nam TS, Lee SH, Kim BC, et al: Clinical characteristics and predictive factors of myasthenic crisis after thymectomy. J Clin Neurosci 18(9):1185, 2011
National Spinal Cord Injury Statistical Center: Spinal cord injury facts and figures at a glance. 2012. Available at: https://www.nscisc.uab.edu. Accessed February 9, 2012
Nezvalová-Henriksen K, Spigset O, Nordeng H: Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes: results from the Norwegian Mother and Child Cohort Study. Headache 50:563, 2010
Niks EH, Verrips A, Semmekrot BA, et al: A transient neonatal myasthenic syndrome with anti-MuSK antibodies. Neurol 70(14):1215, 2008
Novak MJ, Tabrizi SJ: Huntington’s disease. BMJ 340:c3109, 2010
Olafsson E, Hallgrimsson JT, Hauser WA, et al: Pregnancies of women with epilepsy: a population-based study in Iceland. Epilepsia 39:887, 1998
Padua L, Di Pasquale A, Pazzaglia C, et al: Systematic review of pregnancy-related carpal tunnel syndrome. Muscle Nerve 42:697, 2010
Pal J, Rozsa C, Komoly S, et al: Clinical and biological heterogeneity of autoimmune myasthenia gravis. J Neuroimmunol 231:43, 2011
Pennell PB, Peng L, Newport DJ, et al: Lamotrigine in pregnancy. Clearance, therapeutic drug monitoring, and seizure frequency. Neurology 70(22 pt 2):2130, 2008
Perucca E: Birth defects after prenatal exposure to antiepileptic drugs. Lancet Neurol 4:781, 2005
Pilo C, Wide K, Winbladh B: Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs. Acta Obstet Gynecol 85:643, 2006
Pleis JR, Ward BW, Lucas JW: Summary health statistics for U.S. adults: National Health Interview Survey, 2009. Vital Health Stat 10(249):1, 2010
Podciechowski L, Brocka-Nitecka U, Dabrowska K, et al: Pregnancy complicated by myasthenia gravis—twelve years experience. Neuro Endocrinol Lett 26:603, 2005
Polman CH, O’Connor PW, Havrdova E, et al: A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354:899, 2006
Portaccio E, Ghezzi A, Hakiki B, et al: Breastfeeding is not related to postpartum relapses in multiple sclerosis. Neurology 77:145, 2011
Portaccio E, Ghezzi A, Hakiki B, et al: Postpartum relapses increase the disability progression in multiple sclerosis: the role of disease modifying drugs. J Neurol Neurosurg Psychiatry January 8, 2014 [Epub ahead of print]
Powner DJ, Bernstein IM: Extended somatic support in pregnant women after brain death. Crit Care Med 31:1241, 2003
Quant EC, Jeste SS, Muni RH, et al: The benefits of steroids versus steroids plus antivirals for treatment of Bell’s palsy: a meta-analysis. BMJ 339:b3354, 2009
Qureshi AI, Tuhrim S, Broderick JP, et al: Spontaneous intracerebral hemorrhage. N Engl J Med 344:1450, 2001
Ramnarayan R, Sriganesh J: Postpartum cerebral angiopathy mimicking hypertensive putaminal hematoma: a case report. Hypertens Pregnancy 28(1)34, 2009
Richmond JR, Krishnamoorthy P, Andermann E, et al: Epilepsy and pregnancy: an obstetric perspective. Am J Obstet Gynecol 190:371, 2004
Riffaud L, Ferre JC, Carsin-Nicol B, et al: Endoscopic third ventriculostomy for the treatment of obstructive hydrocephalus during pregnancy. Obstet Gynecol 108:801, 2006
Roger VL, Go AS, Lloyd-Jones DM, et al: Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation 125:e2, 2012
Rudick RA, Goelz SE: Beta-interferon for multiple sclerosis. Exp Cell Res 317:1301, 2011
Rudick RA, Stuart WH, Calabresi PA, et al: Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 354:911, 2006
Salinas RA, Alvarez G, Daly F, et al: Corticosteroids for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev. 3:CD001942, 2010
Salminen HJ, Leggett H, Boggild M: Glatiramer acetate exposure in pregnancy: preliminary safety and birth outcomes. J Neurol 257:2020, 2010
Sanchez SE, Qui C, Williams MA, et al: Headaches and migraines are associated with an increased risk of preeclampsia in Peruvian women. Am J Hypertens 21(3):360, 2008
Saposnik G, Barinagarrementeria F, Brown RD, et al: Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:1158, 2011
Schiza S, Starnatakis E, Panagopoulou A, et al: Management of pregnancy and delivery of a patient with malfunctioning ventriculoperitoneal shunt. J Obstet Gynaecol 32(1):6, 2012
Schürks M, Rist PM, Bigal ME, et al: Migraines and cardiovascular disease: systemic review and meta analyses. BMJ 339:b3914, 2009
Scott CA, Bewley S, Rudd A: Incidence, risk factors, management, and outcomes of stroke in pregnancy. Obstet Gynecol 120:318, 2012
Seror P: Pregnancy-related carpal tunnel syndrome. J Hand Surg Br 23:98, 1998
Shi Q, MacDermid JC: Is surgical intervention more effective than non-surgical treatment for carpal tunnel syndrome? A systemic review. J Orthop Surg 6:17, 2011
Shorvon SD: The etiologic classification of epilepsy. Epilepsia 52(6):1052, 2011
Shmorgun D, Chan WS, Ray JG: Association between Bell’s palsy in pregnancy and pre-eclampsia. QJM 95:359, 2002
Silberstein S, Loder E, Diamond S, et al: Probable migraine in the United States: results of the American Migraine Prevalence and Prevention (AMPP) Study. Cephalalgia 27(3):220, 2007
Simolke GA, Cox SM, Cunningham FG: Cerebrovascular accident complicating pregnancy and the puerperium. Obstet Gynecol 78:37, 1991
Singhal AB, Kimberly WT, Schaefer PW, et al: Case 8—2009—a 36-year-old woman with headache, hypertension, and seizure 2 weeks postpartum. N Engl J Med 360(11):1126, 2009
Smith WS, English JD, Johnston C: Cerebrovascular diseases. In Fauci AS, Braunwald E, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill, New York, 2008, p 2513
Smith WS, English JD, Johnston C: Cerebrovascular diseases. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison’s Principles of Internal Medicine, 18th ed. McGraw-Hill, New York, 2012, p 3270
Smitherman TA, Burch R, Sheikh H, et al: The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache 53(3):427, 2013
Souza JP, Oliveira-Neto A, Surita FG, et al: The prolongation of somatic support in a pregnant woman with brain-death: a case report. Reprod Health 27:3, 2006
Stoodley MA, Macdonald RL, Weir BK: Pregnancy and intracranial aneurysms. Neurosurg Clin North Am 9:549, 1998
Sullivan FM, Swan IR, Donnan PT, et al: Early treatment with prednisolone or acyclovir in Bell’s palsy. N Engl J Med 357:1598, 2007
Takebayashi S, Kaneko M: Electron microscopic studies of ruptured arteries in hypertensive intracerebral hemorrhage. Stroke 14:28, 1983
Thambisetty M, Lavin PJ, Newman NJ, et al: Fulminant idiopathic intracranial hypertension. Neurology 68:229, 2007
Thomas SV, Ajaykumar B, Sindhu K, et al: Cardiac malformations are increased in infants of mothers with epilepsy. Pediatr Cardiol 29:604, 2008
Tiel Groenestege AT, Rinkel GJ, van der Bom JG, et al: The risk of aneurysmal subarachnoid hemorrhage during pregnancy, delivery, and the puerperium in the Utrecht population: case-crossover study and standardized incidence ratio estimation. Stroke 40(4):1148, 2009
Torelli P, Allais G, Manzoni GC: Clinical review of headache in pregnancy. Neurol Sci 31(Suppl 1):S55, 2010
Turner K, Piazzini A, Franza A, et al: Epilepsy and postpartum depression. Epilepsia 50(1):24, 2009
U.S. Food and Drug Administration: FDA drug safety communication: risk of oral clefts in children born to mothers taking Topamax (topiramate). 2011. Available at: http://www.fda.gov/drugs/drugsafety/ucm245085.htm. Accessed January 11, 2014
Vajda FJ, Hitchcock A, Graham J, et al: Seizure control in antiepileptic drug-treated pregnancy. Epilepsia 49(1):172, 2008
van der Worp HB, van Gijn J: Acute ischemic stroke. N Engl J Med 357(6):572, 2007
Viinikainen K, Heinonen S, Eriksson K, et al: Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy. Epilepsia 47:186, 2006
Vukusic S, Confavreux C: Pregnancy and multiple sclerosis: the children of PRIMS. Clin Neurol Neurosurg 108:266, 2006
Vukusic S, Ionescu I, El-Etr M: The prevention of post-partum relapses with progestin and estradiol in multiple sclerosis (POPART’MUS) trial: rational, objectives and state of advancement. J Neurol Sci 286(1):114, 2009
Wang IK, Chang SN, Liao CC, et al: Hypertensive disorders in pregnancy and preterm delivery and subsequent stroke in Asian women: a retrospective cohort study. Stroke 42:716, 2011
Wasay M, Bakshi R, Bobustuc G, et al: Cerebral venous thrombosis: analysis of a multicenter cohort from the United States. J Stroke Cerebrovasc Dis 17:49, 2008
Wen JC, Liu TC, Chen YH, et al: No increased risk of adverse pregnancy outcomes for women with myasthenia gravis: a nationwide population-based study. Eur J Neurol 16:889, 2009
Westgren N, Hultling C, Levi R, et al: Pregnancy and delivery in women with a trauma spinal cord injury in Sweden, 1980–1991. Obstet Gynecol 81:926, 1993
Wijdicks EFM, Varelas PN, Gronseth GS, et al: Evidence-based guideline update: determining brain death in adults. Neurology 74:1911, 2010
Wisoff JH, Kratzert KJ, Handwerker SM, et al: Pregnancy in patients with cerebrospinal fluid shunts: report of a series and review of the literature. Neurosurgery 29:827, 1991
Wyszynski DF, Nambisan M, Surve T, et al: Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology 64:961, 2005
Yager PH, Singhal AB, Nogueira RG: Case 31-2012: an 18-year-old-man with blurred vision, dysarthria, and ataxia. N Engl J Med 367:1450, 2012
Yerby MS: Pregnancy, teratogenesis, and epilepsy. Neurol Clin 12:749, 1994
Yoshikawa H, Kiuchi T, Salda T, et al: Randomised, double-blind, placebo-controlled study of tacrolimus in myasthenia gravis. J Neurol Neurosurg Psychiatry 82(9):970, 2011
Yuki N, Hartung HP: Guillain-Barré syndrome. N Engl J Med 366:2294, 2012
Zeeman GG, Fleckenstein JL, Twickler DM, et al: Cerebral infarction in eclampsia. Am J Obstet Gynecol 190:714, 2004a
Zeeman GG, Hatab M, Twickler DM: Increased cerebral blood flow in preeclampsia with magnetic resonance imaging. Am J Obstet Gynecol 191:1425, 2004b
Zeeman GG, Hatab M, Twickler DM: Maternal cerebral blood flow changes in pregnancy. Am J Obstet Gynecol 189:968, 2003