CHAPTER 60: Neurological Disorders

Although several neurological diseases are relatively common in women of childbearing age, less than two pages were devoted to Diseases of the Nervous System in this textbook’s first edition. In the past, some may have precluded pregnancy, however, few do so now. Most encountered during pregnancy are the same as for nonpregnant women, however a few neurological disorders may be seen more frequently in pregnant women. 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 nearly 7 percent of maternal deaths in the United States from 2011 through 2013 (Creanga, 2017).

Many neurological disorders frequently precede pregnancy. Most women with chronic neurological disease who become pregnant will have successful outcomes, but some disorders have specific risks. Conversely, other women will have new-onset neurological symptoms during pregnancy, and these often must be distinguished from pregnancy complications. Psychiatric disorders can also manifest with cognitive and neuromuscular abnormalities and should be considered in the evaluation.

Computed tomography (CT) and magnetic resonance (MR) imaging assist in the diagnosis, classification, and management of many neurological and psychiatric disorders. As discussed in Chapter 46 (Computed Tomography), these imaging methods can be used safely during pregnancy. CT scanning is often used when rapid diagnosis is necessary and is excellent for detecting recent hemorrhage. Because it does not use radiation, MR imaging is often preferred and is particularly helpful to diagnose demyelinating diseases, arteriovenous malformations, congenital and developmental nervous system abnormalities, posterior fossa lesions, and spinal cord diseases. Whenever either test is done, the woman with advanced pregnancy should be positioned in a left lateral tilt with a wedge under one hip to prevent hypotension and 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 MR imaging (fMRI) have not been evaluated for use in pregnant patients (Chiapparini, 2010).

In one national survey in the United States in 2012, 17 percent of those aged 18 to 44 years reported a severe headache or migraine within the past 3 months (Blackwell, 2014). Burch and coworkers (2015) reported that 24 percent of nonpregnant women in this age group were similarly affected. Of pregnant women presenting with headache who received a neurological consultation, two thirds were due to primary disorders, with over 90 percent due to migraine. Of the other third due to secondary conditions, over half were due to hypertensive disorders (Robbins, 2015). Interestingly, Aegidius and associates (2009) reported a decline in the rate of all headache types during pregnancy in nulliparas, especially during the third trimester.

The classification by the International Headache Society (2013) is shown in Table 60-1. In pregnant women, primary headaches are more common than those stemming from secondary causes (Digre, 2013; Sperling, 2015). Migraine headaches are those most likely to be affected by the hormonal changes of pregnancy (Pavlovic, 2017). The incidences of severe headache causes in pregnancy are shown in Figure 60-1.

Tension-Type Headache

These are the most frequent cause of all headaches. Characteristic features include muscle tightness and mild-to-moderate pain in the back of the neck and head that can persist for hours. Neurological disturbances or nausea are typically absent. The pain usually responds to rest, massage, application of heat or ice, antiinflammatory medications, or mild tranquilizers. Hospital admission is seldom necessary.

Migraine Headache

The term migraine describes a periodic, sometimes incapacitating neurological disorder with episodic attacks of severe headache and autonomic nervous system dysfunction (Goadsby, 2015). The International Headache Society (2013) classifies three migraine types based on chronicity and on the presence or absence of an aura.

1. Migraine without aura—formerly termed common migraine—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.

These are the most common reason for admission for headache evaluation and management. 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). Specific polymorphisms have been identified that modulate the risk of migraines (Chen, 2015; Schürks, 2010). These headaches are especially common in young women and have been linked to hormone levels (Charles, 2017; Pavlovic, 2017). They are frequently encountered during pregnancy.

Sensory sensitivity with migraines is likely caused by monoaminergic sensory control systems in the brainstem and hypothalamus (Goadsby, 2015). This exact pathophysiology 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 (Kruit, 2004). Migraines—especially those with aura in young women—are associated with increased risk for ischemic strokes. 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). Most migraineurs have improvement during pregnancy (Kvisvik, 2011). 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). In these, rates of preeclampsia, gestational hypertension, preterm birth, and other cardiovascular morbidities, including ischemic stroke, were increased (Grossman, 2017; Wabnitz, 2015). Bushnell and coworkers (2009) identified an incidence of migraines during pregnancy of 185 per 100,000 deliveries. Of diagnoses associated in these gravid migraineurs, risks were significantly higher for stroke, 16-fold; myocardial infarction, fivefold; heart disease, twofold; venous thromboembolism, twofold; and preeclampsia/gestational hypertension, twofold.

Management

Data are limited regarding nonpharmacological management in pregnancy such as biofeedback techniques, acupuncture, and transcranial magnetic stimulation (Airola, 2010; Dodick, 2010). Effective medications include nonsteroidal antiinflammatory drugs (NSAIDs), and most migraine headaches respond to simple analgesics such as ibuprofen, acetaminophen, or Midrin, especially if given early.

Severe migraines are vexing for the patient and her caregivers. Multitargeted drug therapy is necessary in most cases for migraine relief (Gonzalez-Hernandez, 2014). Headaches are treated aggressively with intravenous hydration and parenteral antiemetics and opioids for immediate pain relief. Although a 2-g infusion of magnesium sulfate has gained favor in the past few years, a metaanalysis reported no benefits (Choi, 2014). Ergotamine derivatives are potent vasoconstrictors and are avoided in pregnancy because of their uterotonic effects (Briggs, 2015).

Triptans are serotonin 5-HT_1B/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. Triptans can be given as an oral tablet, injection, rectal suppository, or intranasal spray. They are best used in combination with NSAIDs (Goadsby, 2015). The greatest experience is with sumatriptan (Imitrex), and although not studied extensively in pregnancy, it appears to be safe (Briggs, 2015; Nezvalová-Henriksen, 2010). However, in one follow-up study at 36 months of children exposed to triptans in pregnancy, Wood and colleagues (2016) found neurodevelopment differences, including emotionality and activity problems.

Some women will benefit from peripheral nerve blocks, and Govindappagari and coworkers (2014) described their experiences with 13 pregnant women. For women with frequent migraine headaches, oral prophylactic therapy is warranted. Amitriptyline (Elavil), 10 to 175 mg daily; propranolol (Inderal), 40 to 120 mg daily; or metoprolol (Lopressor, Toprol), 25 to 100 mg daily, have been used with success (Contag, 2010; Goadsby, 2015; Lucas, 2009).

Cluster Headache

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 (VanderPluym, 2016). 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—thus over 1 million American women of childbearing age are affected (Kobau, 2008). After headaches, seizures are the next most prevalent neurological condition encountered in pregnancy, and they complicate 1 in 200 births (Brodie, 1996; Yerby, 1994). Importantly, epilepsy accounted for 5 percent of maternal deaths in the United Kingdom for the 2011 to 2013 triennium (Knight, 2015).

Pathophysiology

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. 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.

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 the following definitions (Fisher, 2014).

Focal 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.

Generalized Seizures

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.

Preconceptional Counseling

Women with epilepsy ideally are counseled before pregnancy and relevant points are presented also in Chapter 8 (Epilepsy). 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 (Patel, 2016). 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 fetal malformations and increased seizure rates. Seizure control is the main priority to avoid its attendant morbidity and mortality risks. Early studies described worsening seizure activity during pregnancy, however, this is less so now because of more effective drugs. Contemporary studies cite higher rates of seizure activity in only 20 to 30 percent of pregnant women (Mawer, 2010; Vajda, 2008). Women who are seizure free for at least 9 months before conception will likely remain so during pregnancy (Harden, 2009b).

Greater 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, slower 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 and by hyperventilation and pain during labor.

Pregnancy Complications

Women with epilepsy have a small increased risk of pregnancy complications that include spontaneous abortion, hemorrhage, hypertensive disorders, preterm birth, fetal-growth restriction, and cesarean delivery (Harden, 2009b; Viale, 2015). Importantly, MacDonald (2015) also reports a tenfold higher maternal death rate, and, as mentioned earlier, epilepsy accounted for 5 percent of maternal deaths in the United Kingdom. Postpartum depression rates are also reportedly higher in epileptic women (Turner, 2009). Finally, children of epileptic mothers have a 10-percent risk of developing a seizure disorder.

Embryofetal Malformations

For years, it was difficult to separate effects of epilepsy from those of its therapy as the primary cause of fetal malformations. As discussed in Chapter 8 (Epilepsy), it is now believed that untreated epilepsy is not associated with an elevated fetal malformation rate (Thomas, 2008). That said, the fetus of an epileptic mother who takes certain anticonvulsant medications has an indisputably greater 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, Antiepileptic Medications). 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). Valproate is a particularly potent teratogen, which has a dose-dependent effect and raises the malformation risk four- to eightfold (Eadie, 2008; Klein, 2014; Wyszynski, 2005). Valproate is also associated with lower cognitive performance (Kasradze, 2017). In general, with polytherapy, the risk rises with each drug added. A metaanalysis of 31 studies found lamotrigine and levetiracetam to carry the lowest risk of malformations (Weston, 2016).

Management in Pregnancy

The American Academy of Neurology and the American Epilepsy Society have guidelines regarding treatment in pregnant women (Harden, 2009a–c). 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, 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 most informative if measured following seizures or if noncompliance is suspected.

For women taking anticonvulsant drugs, a targeted sonographic examination at midpregnancy is recommended by some to search for anomalies. Testing to assess fetal well-being is generally not indicated for women with uncomplicated epilepsy.

For women desiring to breastfeed, data regarding the safety of the various anticonvulsant medications are limited. That said, no obvious deleterious effects, such as long-term cognitive issues, have been reported (Briggs, 2015; Harden, 2009c). Of birth control methods, oral contraceptive pill failure rates are higher with some of the anticonvulsant agents, especially lamotrigine. Thus, other more reliable methods should be considered (Chap. 38, Introduction).

Abnormalities of the cerebrovascular circulation include strokes—both ischemic and hemorrhagic, as well as anatomical anomalies, such as arteriovenous malformations and aneurysms. Cerebral ischemia is caused by reduction in blood flow that lasts longer than several seconds. Early, neurological symptoms may manifest. After a few minutes, however, infarction often follows. Hemorrhagic stroke is caused by bleeding directly into or around the brain. It produces symptoms by its mass effect, by toxic effects of blood, or by increasing intracranial pressure. Of strokes in pregnant women, roughly half are ischemic and the other half hemorrhagic (Zofkie, 2018).

The current obesity endemic in this country, along with concomitant increases in rates of heart disease, hypertension, and diabetes, has increased the prevalence of strokes (Centers for Disease Control and Prevention, 2012). Women have higher lifetime risk of stroke than men and greater 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, occurring in 10 to 40 per 100,000 births, but it contributes disparately to maternal mortality rates (Leffert, 2016; Miller, 2016; Yoshida, 2017). The incidence is rising as measured by pregnancy-related hospitalizations for stroke (Callaghan, 2008; Kuklina, 2011). Importantly, most are associated with hypertensive disorders or heart disease. Of the pregnancy-related mortality rate in the United States, 6.6 percent is due to cerebrovascular accidents, and 7.4 percent is associated with preeclampsia (Creanga, 2017). Of maternal deaths after 42 days postpartum, 9.8 percent were attributable to cerebrovascular accidents.

Risk Factors

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). In contrast, Leffert (2016) reports a timing of 45 percent antepartum, 3 percent intrapartum, and 53 percent postpartum in 145 women. Several risk factors—unrelated and related to pregnancy—have been reported from studies that included more than 10 million pregnancies. These include 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. A third of strokes are associated with gestational hypertension, and hypertensive women compared with normotensive counterparts have a three- to eightfold greater risk of stroke (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 raises the risk 1.5-fold compared with vaginal delivery (Lin, 2008).

Pregnancy-induced effects on cerebrovascular hemodynamics include enhanced autoregulation that maintains blood flow despite changes in systemic blood pressure (van Teen, 2016). Although cerebral blood flow decreases by 20 percent from midpregnancy until term, it increases significantly with gestational hypertension (Zeeman, 2003, 2004b). Such hyperperfusion at least intuitively would be dangerous for women with certain vascular anomalies.

Ischemic Stroke

Acute occlusion or embolization of an intracranial blood vessel causes cerebral ischemia, which may result in death of brain tissue (Fig. 60-2). 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. Approximately 10 percent of these patients have a stroke by 1 year (Amarenco, 2016). Patients with a stroke usually have a sudden onset of severe headache, hemiplegia or other neurological deficits, or occasionally seizures. In contrast, focal neurological symptoms accompanied by an aura usually signify a first-episode migraine (Liberman, 2008).

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, Serum and Blood Constituents). Tests to detect antiphospholipid antibodies and lupus anticoagulant are performed. These underlie up to a third of ischemic strokes in otherwise healthy young women (Chap. 59, Antiphospholipid Syndrome). Also, sickle-cell syndromes are evaluated when indicated (Buonanno, 2016).

With a thorough evaluation, most causes of embolism 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). Outcomes of embolic strokes were reported to be favorable and similar to those of nonpregnant women (Leffert, 2016). Thrombolysis for ischemic stroke during pregnancy has been reported (Tversky, 2016).

Preeclampsia Syndrome

In reproductive-age women, a significant proportion of pregnancy-related ischemic strokes are caused by gestational hypertension and preeclampsia (Jeng, 2004; Miller, 2016). As shown in Figure 60-2, 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, Eclampsia).

Other conditions with findings similar to preeclampsia include thrombotic microangiopathies (Chap. 56, Thrombotic Microangiopathies) and the reversible cerebral vasoconstriction syndrome (Chap. 40, Long-Term Consequences). The latter, also termed postpartum angiopathy, can cause extensive cerebral edema with necrosis and widespread infarction with areas of hemorrhage (Edlow, 2013; Katz, 2014; Miller, 2016).

Cerebral Embolism

These strokes usually involve the middle cerebral artery (see Fig. 60-2). The diagnosis can be made with confidence only after thrombosis and hemorrhage have been excluded and 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 (Scott, 2012). Foraminal closure may not improve outcomes in these patients, however, this procedure has been performed during pregnancy (Dark, 2011). 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 in pregnancy are controversial issues (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 TIAs. Thrombolytic therapy with a recombinant tissue plasminogen activator (rt-PA) is recommended. Alteplase is one of these and given within the first 3-hour window if there is measurable neurological deficit and if neuroimaging has excluded hemorrhage. This recombinant enzyme can be used in pregnancy. A principal risk is hemorrhagic transformation of an ischemic stroke in 3 to 5 percent of treated patients (Smith, 2015; van der Worp, 2007).

Cerebral Venous Thrombosis

In one study in the United States, 7 percent of cerebral venous thromboses were associated with pregnancy (Wasay, 2008). But, in the Nationwide Inpatient Sample of more than 8 million deliveries, James and associates (2005) reported that venous thrombosis caused only 2 percent of pregnancy-related strokes (Saposnik, 2011). There are numerous predisposing causes, and for gravidas, late pregnancy and the puerperium are times of greatest risk.

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. 60-2). It is more common in patients with inherited thrombophilias or antiphospholipid antibodies (Chaps. 52, Inherited Thrombophilias and 59, Antiphospholipid Syndrome). Headache is the most frequent presenting symptom, neurological deficits are common, and up to a third of patients have convulsions (Wasay, 2008). The diagnosis is made using MR venography (Saposnik, 2011).

Management includes anticonvulsants for seizures, and although heparinization is recommended by most, its efficacy is controversial (Saposnik, 2011; Smith, 2015). Antimicrobials are given if there is septic thrombophlebitis, and fibrinolytic therapy is reserved for those women failing systemic anticoagulation. The acute prognosis for venous thrombosis in pregnant women is better than in nonpregnant subjects, and mortality rates are less than 10 percent (McCaulley, 2011).

In women with a prior cerebral venous thrombosis, one systematic review found only one recurrence in 217 pregnancies and five noncerebral venous thrombotic events in 186 pregnancies (Aguiar de Sousa, 2016). In a study of 52 women on prophylactic anticoagulation with prior cerebral venous thrombosis, there were no cases of recurrent thrombosis or bleeding, however 24 percent had late obstetrical complications (Martinelli, 2016).

Recurrence Risk of Ischemic Stroke

Women with prior ischemic stroke have a low risk for recurrence during a subsequent pregnancy unless a specific, persistent cause is identified. During a 5-year follow-up of 373 women with arterial ischemic strokes, there were 187 pregnancies in 125 women. Thirteen women had a recurrent ischemic stroke, and of these, only two were associated with pregnancy. The authors concluded that the risk of stroke recurrence is low and a previous ischemic stroke is not a contraindication to pregnancy (Lamy, 2000). In one 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).

Currently, no firm guidelines define 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 syndrome or certain cardiac conditions should be considered for prophylactic anticoagulation as discussed in Chapter 49 (Surgically Corrected Heart Disease) and 52 (Acquired Thrombophilias).

Hemorrhagic Stroke

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, and their differentiation is only possible with CT or MR imaging (Morgenstern, 2010; Smith, 2015).

Intracerebral Hemorrhage

Bleeding into the brain parenchyma most often is caused by spontaneous rupture of small vessels previously damaged by chronic hypertension (see Fig. 60-2). Thus, pregnancy-associated hemorrhagic strokes such as the one shown in Figure 60-3 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 (Smith, 2015). Pressure-induced rupture causes bleeding into 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, Management Considerations).

Subarachnoid Hemorrhage

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 occurring postpartum (Bateman, 2012). A remarkably similar incidence was reported in Japanese women (Yoshida, 2017). These bleeds are more likely caused by an underlying cerebrovascular malformation in an otherwise normal patient (see Fig. 60-2). 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 (Yoshida, 2017).

Intracranial Aneurysm. 

Approximately 1 to 2 percent of adults have this lesion (Lawton, 2017). Fortunately, only a small percentage rupture. The rate approximates 0.1 percent for aneurysms <10 mm and 1 percent for those >10 mm (Smith, 2015). Most aneurysms identified during pregnancy arise from the circle of Willis, and in 20 percent of case, there are multiple lesions. Pregnancy does not raise the risk for aneurysmal rupture. However, because of their high prevalence, they are more likely to cause subarachnoid bleeding than other etiologies (Hirsch, 2009; Tiel Groenestege, 2009). A systematic review of 44 women with 50 aneurysms in pregnancy reported that 72 percent ruptured during pregnancy, and 78 percent of these did so during the third trimester (Barbarite, 2016). This proclivity for rupture late in pregnancy was also reported by Yoshida and colleagues (2017).

The cardinal symptom of a subarachnoid hemorrhage from an aneurysm rupture is sudden severe headache that is 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 (Connolly, 2012; Smith, 2015).

Treatment of subarachnoid hemorrhage 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 risk of recurrent hemorrhage versus the 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 after the sentinel hemorrhage is done by surgical clipping of the aneurysm. Also, an endovascular coil can be placed using fluoroscopic angiography, while attempting to limit fetal radiation exposure. Barbarite and colleagues (2016) report lower complication rates with coil embolization than clipping. For unruptured aneurysms, surgical management resulted in a third fewer complications than no treatment. For gravidas 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 labor ensues remote from aneurysmal repair. Problems arise in defining “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. 60-2). They lack capillaries and have resultant arteriovenous shunting. Although unclear, the risk of bleeding may rise with gestational age. When arteriovenous malformations (AVMs) bleed, half do so into the subarachnoid space, whereas half are intraparenchymal with subarachnoid extension (Smith, 2015). They are uncommon and are estimated to occur in 0.01 percent of the general population. Of 65 identified cases of AVM in pregnancy, 83 percent ruptured during pregnancy or postpartum, and more than 80 percent of these ruptured in the second or third trimester. Hemorrhage upon presentation is associated with poor maternal outcome (Lu, 2016).

Bleeding does not appear to be more likely during pregnancy. Although these malformations are correspondingly rare during pregnancy, AVM bleeding accounted for 17 percent of hemorrhagic strokes in one study (Yoshida, 2017). At Parkland Hospital in a 33-year period during which there were about 466,000 births, 57 women had a CVA, and five of these strokes were due to a bleeding AVM (Simolkie, 1991; Zofkie, 2018).

Treatment of AVMs in nonpregnant patients is largely individualized. No consensus guides whether all accessible lesions should be resected. Factors include AVM symptoms; its anatomy and size; presence of an associated aneurysm, which is found in up to 60 percent of cases; and especially, prior AVM bleeding. 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, 2015). 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.

The demyelinating diseases are neurological disorders characterized by immune-mediated focal or patchy destruction of myelin sheaths accompanied by an inflammatory response. The degenerative diseases are multifactorial and are characterized by progressive neuronal death.

Multiple Sclerosis

In the United States, multiple sclerosis (MS) is second only to trauma as a cause of neurological disability in middle adulthood (Hauser, 2015b). The disease affects women twice as often as men, and it usually begins in the 20s and 30s. The familial recurrence rate of MS is 15 percent, and the incidence in offspring is increased 15-fold. Studying California deliveries, Fong and colleagues (2018) reported that 0.03 percent of deliveries were complicated by MS between 2001 and 2009.

The demyelinating characteristic of this disorder results predominately from 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. Of these, Chlamydophila pneumoniae, human herpesvirus 6, or Epstein-Barr virus are implicated (Frohman, 2006; Goodin, 2009).

There are four clinical types of MS:

1. Relapsing-remitting MS accounts for initial presentation in 85 percent of affected individuals. With it, unpredictable recurrent episodes of focal or multifocal neurological dysfunction usually are 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. All patients likely develop this type eventually.

3. Primary progressive MS accounts for 15 percent of cases. With it, disability gradually progresses 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 MS 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 (Fig. 60-4). Their appearance and extent are less helpful for predicting treatment response. Similarly, identification of serum antibodies against myelin oligodendrocyte glycoprotein and myelin basic protein is not predictive of recurrent disease activity (Kuhle, 2007).

Effects of Pregnancy

The PRegnancy In Multiple Sclerosis—PRIMS—study was a European prospective multicenter study in which 254 pregnancies were described (Vukusic, 2006). Relapse risk was reduced 70 percent during pregnancy, but with a significantly greater relapse rate postpartum. This may be related to higher pregnancy-induced numbers of T-helper lymphocytes and an increased T2/T1 ratio (Airas, 2008). In a metaanalysis of women with more than 1200 pregnancies complicated by MS, 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). Bove and associates (2014) reached similar conclusions after a systematic review. 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). Breastfeeding has no apparent effect on postpartum relapses (Hellwig, 2015; Portaccio, 2011).

Effects of Multiple Sclerosis on Pregnancy

With uncomplicated disease, there are usually no adverse effects on pregnancy outcome (Bove, 2014). 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. In one study of 449 pregnancies in affected women, the labor induction rate was higher, and second-stage labor was longer (Dahl, 2006). The greater induction rate and elective operations contributed to the overall higher cesarean delivery rate. In an analysis of 649 affected women, the mean birthweight was lower but the perinatal mortality rate was similar compared with that of controls (Dahl, 2005). Other studies have corroborated that MS does not significantly affect obstetrical and neonatal outcomes (Finkelsztejn, 2011; Fong, 2018).

Management in Pregnancy

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 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 MS or for exacerbations. Examples include interferons β1a (Rebif), β1b (Betaseron), and glatiramer acetate (Copaxone), which lower relapse rates by a third (Rudick, 2011). Data concerning safety in pregnancy are limited but overall reassuring (Amato, 2010; Salminen, 2010). In clinical trials, natalizumab (Tysabri), an α₄-integrin antagonist, especially when combined with interferon β1a, significantly reduced MS clinical relapse rates (Polman, 2006; Rudick, 2006). In a review of 35 pregnancies, first-trimester drug exposure did not worsen outcomes (Hellwig, 2011). If these drugs are used in pregnancy, the neonate should be monitored for thrombocytopenia and anemia (Alroughani, 2016).

Fetal exposure in 89 pregnancies to fingolimod (Gilenya), another immune-modulating drug, was associated with six fetal malformations and nine spontaneous losses. Because of this and associated animal teratogenicity, its use in pregnancy is not recommended. Due to its prolonged persistence, contraception is recommended for 2 months after drug cessation (Alroughani, 2016; Karlsson, 2014).

Prevention of relapses postpartum is afforded by treatment with intravenous immunoglobulin (IVIG), given in a dose of 0.4 g/kg daily for 5 days during weeks 1, 6, and 12 (Argyriou, 2008).

Huntington Disease

This adult-onset neurodegenerative disease stems from an autosomal dominant expanded CAG trinucleotide repeat within the Huntington gene on chromosome 4. It is characterized by 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 (Carrier Screening for Genetic Disorders). Prenatal screening is controversial, and because this usually is a late-onset adult disease, extensive counseling is important (Schulman, 2015).

Myasthenia Gravis

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 (Drachman, 2015). The latter often have antibodies to muscle-specific tyrosine kinase (MuSK), which regulates assembly of the acetylcholine receptor subunits at the neuromuscular junction (Pal, 2011).

Cardinal features of myasthenia 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.

Management

Myasthenia is manageable but not curable. Oral pyridostigmine is the first-line treatment. Thymectomy is recommended but postponed until after pregnancy (Sanders, 2016). Anticholinesterase medications improve symptoms by impeding acetylcholine degradation but seldom produce normal muscle function. Ironically, overdose is manifest by increased weakness—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, or cyclosporine in pregnancy. When short-term, rapid clinical improvement is needed—such as for a surgical procedure or a myasthenic crisis—high-dose IVIG or plasma exchange is usually effective (Barth, 2011; Cortese, 2011; Sanders, 2016).

Myasthenia and Pregnancy

Because the greatest period of risk is within the first year following diagnosis, postponing pregnancy until there is sustained improvement is reasonable. 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 IVIG are options for emergency situations (Drachman, 2015).

Although pregnancy does not appear to affect the overall course of myasthenia, fatigue common to most pregnancies may be exacerbated, and the expanding uterus may compromise respiration. Maternal hypotension or hypovolemia are ideally avoided as they can trigger crises. The clinical course of myasthenia during pregnancy is unpredictable, and frequent hospitalizations are the norm. Up to a third of women have worsening myasthenia during pregnancy, and exacerbations occur equally in all three trimesters (Djelmis, 2002; Podciechowski, 2005). In women with stable disease, most will remain stable throughout pregnancy but likely worsen in the first few months postpartum (Sanders, 2016).

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. Thus, many choose it for neuroprophylaxis in women with severe preeclampsia.

Because smooth muscle is unaffected, most women have normal labor. Oxytocin is given for the usual indications, and cesarean delivery is reserved for obstetrical indications. Narcotics may cause respiratory depression, and close observation and respiratory support are essential during labor and delivery. Curariform drugs are 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.

Neonatal Effects

As discussed above, 80 percent of mothers with myasthenia gravis have anti-acetylcholine-receptor immunoglobulin G (IgG) antibodies. These and anti-MuSK antibodies cross transplacentally, and the fetus can be affected. Poor fetal swallowing may yield hydramnios (Heaney, 2010). Similarly, 10 to 20 percent of neonates manifest myasthenia symptoms (Jovandaric, 2016). Transient symptoms usually include a feeble cry, poor suckling, and respiratory distress. Symptoms usually respond to cholinesterase inhibitors and resolve within a few weeks as maternal IgG antibodies clear.

Peripheral neuropathy is a general term used to describe disorders of peripheral nerve(s) from various sources. Polyneuropathies can be axonal or demyelinating as well as acute, subacute, or chronic (Amato, 2015). These are often associated with systemic diseases such as diabetes, with drug or environmental toxin exposure, or with genetic disease.

Mononeuropathies are relatively common in pregnancy and signify focal involvement of a single nerve trunk. These 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 (Pain, Mood, and Cognition).

Guillain-Barré Syndrome

In 75 percent of cases, this acute demyelinating polyradiculoneuropathy has clinical or serological evidence for an acute infection. Commonly associated are infections with Campylobacter jejuni, cytomegalovirus, Zika virus, and Epstein-Barr virus; surgical procedures; and immunizations (Haber, 2009; Hauser, 2015a; Pacheco, 2016). Guillain-Barré syndrome is thought to be immune-mediated from antibodies formed against nonself antigens. Demyelination causes sensory and motor conduction blockade, and remyelination yields recovery 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. Some manifest as chronic inflammatory demyelinating polyneuropathy, and our experiences indicate that this may be relatively common in these young women.

Guillain-Barré syndrome is not more common in pregnancy, and its clinical course mirrors that for nonpregnant individuals. After an insidious onset, paresis and paralysis most often continue to ascend to cause ventilatory weakness. Management is supportive and incorporates venous thromboembolism prophylaxis, pressure ulcer prevention, and enteral nutrition. In the worsening phase, patients are hospitalized, and a fourth requires ventilatory assistance. IVIG or plasmapheresis is beneficial if begun within 1 to 2 weeks of motor symptoms, however, neither decreases mortality rates (Cortese, 2011; Gwathmey, 2011; Pritchard, 2016). Up to 10 percent of patients deteriorate after initial improvement on therapy, and retreatment with 2 g/kg IVIG over 5 days is recommended. Although most patients recover fully within several months to a year, the mortality rate is 5 percent, mainly due to pulmonary complications and arrhythmias (Hauser, 2015a; Pacheco, 2016).

Bell Palsy

This disfiguring palsy is usually a mononeuropathic acute facial paralysis that is relatively common in reproductive-aged women (Fig. 60-5). It has a female predominance, and pregnant women carry 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 simplex virus or herpes zoster virus.

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, 2015). Management includes supportive care with facial muscle massage and eye protection against corneal lacerations from drying. There is general consensus that prednisone, 1 mg/kg given orally daily for 5 days, will improve outcomes and shorten the recovery period (Salinas, 2016; Sullivan, 2007). It is controversial whether addition of an antiviral medication will add benefits (de Almeida, 2009; Gagyor, 2015; Quant, 2009).

It is unclear if pregnancy alters the prognosis for spontaneous facial palsy recovery. Gillman and associates (2002) found that only half of pregnant women recovered to a satisfactory level after 1 year, 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). Other than a fivefold greater rate for gestational hypertension or preeclampsia, women with Bell palsy do not have increased adverse pregnancy outcomes rates (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. Others are wrist pain and numbness extending into the forearm and sometimes into the shoulder (Katz, 2002). Symptoms are bilateral in 80 percent of gravidas, and 10 percent have evidence for severe denervation (Seror, 1998). Differential diagnosis includes cervical radiculopathy of C₆–C₇ and de Quervain tendonitis. The latter is caused by swelling of the conjoined tendons and their sheaths near the distal radius. Nerve conduction studies may be helpful for clarification (Alfonso, 2010).

In pregnancy, the reported incidence of carpal tunnel syndrome is 7 to 43 percent and varies greatly because the range of symptoms is marked (Meems, 2015; Padua, 2010). Symptomatic treatment with a splint applied to a slightly flexed wrist during sleep lightens 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 1 year and in a third at 3 years (Padua, 2010).

According to the National Spinal Cord Injury Statistical Center (2017), there are approximately 17,000 new spinal cord injuries each year. The average age is 42 years, and males account for 80 percent of new cases. Cord injury severity determines the short- and long-term prognosis as well as that for pregnancy. For women, many have altered sexual function and transient hypothalamic pituitary hypogonadism. That said, pregnancy is not uncommon if menstruation resumes (Bughi, 2008). In a review of nearly 2000 women in the National Spinal Cord Injury Database, 2 percent reported pregnancy in the prior 12 months (Iezzoni, 2015).

Gravidas with spinal cord injury have an increased frequency of pregnancy complications that include preterm and low-birthweight neonates. Recent observations in nonpregnant women note that the vaginal microbiota is altered in these women (Pires, 2016). Perhaps related, 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.

Two serious and life-threatening events can complicate spinal cord injuries. First, 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 to assess this risk, and some women may need ventilatory support in late pregnancy or in labor.

Second, 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 lead to 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 various stimuli. These include urethral catheterization, bladder distention from urinary retention, rectal or cervical stretch during digital examinations, uterine contractions and cervical dilation, or any manipulation of other pelvic structures (American College of Obstetricians and Gynecologists, 2016; 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’ gestation (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 is preferable and will minimize autonomic dysreflexia (Kuczkowski, 2006). Operative vaginal delivery is frequently necessary.

Also known as pseudotumor cerebri, this disorder is typified by increased intracranial pressure without hydrocephalus. The cause is unknown, but it may result from overproduction or under absorption of cerebrospinal fluid (CSF). 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, and cranial nerve palsies.

The syndrome is often 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 >25 cm H₂O, normal CSF composition, normal cranial CT or MR imaging findings, papilledema, and no evidence for systemic disease. If papilledema is not present, other criteria are required (Friedman, 2013).

Idiopathic intracranial hypertension is usually self-limited. Visual defects can be prevented by lowering the CSF pressure, and agents include acetazolamide to reduce fluid production, furosemide, or topiramate. 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.

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. Symptoms usually develop by midpregnancy, tend to be self-limited, and usually resolve postpartum.

Pregnancy does not alter management. Some recommend serial visual field testing to forestall 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, rates of adverse perinatal outcomes were not elevated (Katz, 1989). The route of delivery depends on obstetrical indications, and conduction analgesia is safe (Aly, 2007; Karmaniolou, 2011).

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 indicated (Murakami, 2010).

Another shunting procedure is placement of an endoscopic third ventriculostomy for hydrocephalus (de Ribaupierre, 2007). With this, a small hole is created in the floor of the third ventricle to allow CSF to flow directly into lower cisterns. One report described successful results in five pregnant women who underwent endoscopic ventriculostomy (Riffaud, 2006). In a review, however, 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.

Brain death is rare in obstetrics. Life-support systems and parenteral alimentation for up to 15 weeks while awaiting delivery have been described (Hussein, 2006; Powner, 2003; Souza, 2006). Some women were treated with aggressive tocolysis and antimicrobial therapy. In one review of 17 women with persistent vegetative state who were given various levels of support, five women died after delivery, and most of the others remained in their vegetative state (Chiossi, 2006).

With a diagnosis of brain death using the uniform Determination of Death Act definition, there are no published reports of neurological recovery (Wijdicks, 2010). Few institutional brain-death policies address pregnancy (Lewis, 2016). 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 (Cardiopulmonary Resuscitation).