Interaction with Pregnancy

Evidence regarding the effect of multiple sclerosis on pregnancy is conflicting. In one cohort study that compared 198 affected women with 1584 healthy women, the number of maternal complications was not higher in women with multiple sclerosis.⁷ However, infants delivered of women with multiple sclerosis appear to be at greater risk for meconium aspiration, even though the presence of moderate to heavy meconium is not significantly increased.⁷ This finding may reflect an intrauterine environment in patients with multiple sclerosis that is more susceptible to acute hypoxic events.⁷ A subsequent cohort study of 649 pregnancies in women with multiple sclerosis concluded that infants of these women were more likely to be small for gestational age; this outcome was also attributed to a suboptimal intrauterine environment.⁸ Moreover, this study found that mothers with multiple sclerosis were more likely to undergo induction of labor and operative delivery, possibly as a result of neuromuscular weakness and spasticity.

In a 2011 meta-analysis of reports of pregnant women with multiple sclerosis, the relapse rate was lower during pregnancy than before or after pregnancy.⁹ It is unclear whether the prevalence of cesarean deliveries, spontaneous abortions, preterm births, and LBW neonates is higher in women with multiple sclerosis than in healthy women, although the rates did not reach levels that would warrant great concern.

Data from prospective studies suggest that the rate of relapse increases during the first 3 months postpartum in comparison with the year before pregnancy.¹⁰ Relapses during this period were more likely in women who had higher relapse rates in the year before pregnancy or during pregnancy. Stress, exhaustion, infection, the loss of antenatal immunosuppression, and the postpartum decline in concentrations of reproductive hormones may account for the higher postpartum relapse rate. Treatment with immunologically active agents (e.g., interferon-beta) may result in a decreased postpartum relapse rate, but data are limited.¹⁰

Pregnancy does not negatively affect the long-term outcome of multiple sclerosis. Rather, at least one study has suggested that parturition may have a slightly favorable effect on long-term disease activity.¹¹ Data are conflicting as to whether exclusive breast-feeding is associated with a lower risk for relapse than partial or no breast-feeding.^12,13

Anesthetic Management

The anesthesiologist should assess the patient’s level of compromise, document the pattern of deficits, and give special attention to respiratory involvement. Historically, the optimal route of anesthesia in patients with multiple sclerosis has been controversial. Most anesthesia providers have considered general anesthesia to be safe, although published data are limited.^14,15 Many anesthesia providers have been reluctant to administer neuraxial anesthesia because the effect of local anesthetic drugs on the course of the disease is unclear. Some anesthesiologists have expressed concern that neuraxial anesthesia may expose demyelinated areas of the spinal cord to potentially neurotoxic effects of local anesthetic agents. Several animal studies have investigated the histologic effects of local anesthetic agents on the normal spinal cord. In one study, subarachnoid injection of small doses of a local anesthetic agent produced no histologic changes in the spinal cord or meninges.¹⁶ Injection of very large doses caused reversible inflammatory and degenerative changes, but all changes resolved within 14 days of injection.

Diagnostic lumbar puncture is not associated with a higher rate of relapse.¹⁷ Two small reports have implicated spinal anesthesia in the exacerbation of multiple sclerosis.^15,18 Bamford et al.¹⁵ described one case of relapse after the administration of spinal anesthesia in 9 patients, and Stenuit and Marchand¹⁸ identified two cases of relapse after the administration of spinal anesthesia in 19 patients. The relationship of these relapses to spinal anesthesia or other postoperative conditions (e.g., stress, infection, hyperpyrexia) known to exacerbate multiple sclerosis is unclear.

There are few published data on the use of epidural anesthesia in patients with multiple sclerosis. Warren et al.¹⁹ reported minor exacerbations after the administration of epidural anesthesia for two separate vaginal deliveries in one patient. Crawford et al.²⁰ reported one postoperative relapse in 50 nonobstetric and 7 obstetric patients who received epidural analgesia. Confavreux et al.²¹ reported a study of 269 pregnancies in 254 women with multiple sclerosis, of whom 42 received epidural analgesia. They noted that epidural analgesia did not have an adverse effect on the rate of relapse or on the progression of disability in these patients. Bader et al.²² retrospectively evaluated 32 pregnancies in women with multiple sclerosis; they observed that women who received epidural anesthesia for vaginal delivery did not have a higher incidence of relapse than those who received only local infiltration anesthesia. In a prospective study of 227 women who had multiple sclerosis for at least 1 year before conception, of whom 42 received epidural analgesia during labor, no adverse effect of epidural analgesia on the rate of relapse or the progression of disability was identified.¹⁰

Bader et al.²² observed that all of the women who experienced a relapse after epidural anesthesia had received a concentration of bupivacaine greater than 0.25%. The concentration of local anesthetic in the CSF progressively increases during prolonged administration of epidural anesthesia, and the authors suggested that the higher concentration may overwhelm the protective effect of dilution within the CSF. An alternative explanation is that women who require a higher concentration of neuraxial local anesthetic may have more stressful labor. However, these observations suggest that anesthesia providers should use a dilute solution of local anesthetic for epidural analgesia during labor, when possible.

The addition of an opioid reduces the total dose of local anesthetic required for epidural analgesia during labor. Berger and Ontell²³ reported the administration of intrathecal morphine, which was added to low-dose tetracaine for surgical anesthesia and postoperative analgesia, and observed no exacerbation of multiple sclerosis at 1 and 6 months after surgery. Leigh et al.²⁴ described the successful use of intrathecal diamorphine for postoperative analgesia in a patient with multiple sclerosis who underwent a laparotomy.

The administration of neuraxial anesthesia for cesarean delivery is controversial. Because the operation is of limited duration, multiple doses of local anesthetic are typically not needed, so a progressive increase in CSF concentration of local anesthetic over time is less likely. In light of the significant benefits of neuraxial techniques for intraoperative anesthesia and postoperative analgesia, either spinal or epidural anesthesia is the principal anesthetic technique used for cesarean delivery in patients with multiple sclerosis in many institutions, including my own.

In summary, published data do not contraindicate the use of neuraxial anesthetic techniques for labor analgesia or operative anesthesia. The patient should be aware that there is a higher incidence of relapse during the postpartum period, even without the use of neuraxial analgesia or anesthesia. In addition, when anesthetic techniques are used, the type of anesthesia selected does not appear to influence the relapse rate. Neither pregnancy nor anesthesia appears to have a negative influence on the long-term course of the disease. The willingness of anesthesiologists to use neuraxial techniques in pregnant patients with multiple sclerosis is reflected in a survey of obstetric anesthesiologists published in 2006.²⁵ The majority (91%) of respondents had seen fewer than 10 cases of multiple sclerosis in the past 10 years; 79% and 98% of anesthesiologists indicated they would perform a neuraxial anesthetic technique for labor and elective cesarean delivery, respectively.

Tension Headache

Tension or muscle contraction headaches are the most common type of headache observed during pregnancy.²⁶ The symptoms typically consist of dull, persistent pain that extends over the entire head. The onset is usually gradual, but the symptoms may persist for long periods. Although the etiology is unknown, this type of headache is believed to be associated with stress rather than hormonal changes. These headaches are more common in women, are frequently associated with anxiety, and may be a symptom of postpartum depression.²⁷

Migraine Headache

Migraine headaches are classically described as unilateral, throbbing headaches sometimes accompanied by nausea and vomiting. The duration varies from hours to days. Visual disturbances (e.g., scotomata) typically precede the onset of these headaches, and focal neurologic symptoms (e.g., aphasia, hemiplegia) may also occur. Most investigators favor neurovascular vasospasm, followed by cerebral vasodilation, as a cause of these headaches; a primary vascular disorder or a disturbance in the noradrenergic nervous system also may be involved. Patients appear to be more susceptible to symptoms when serotonin levels are low.

The 1-year period prevalence of migraine headache in the United States is 3.9% for men and 5.1% for women.³³ Prevalence is higher in middle life, between the ages of 30 and 59 years. Hormonal influences have a strong association with these headaches; estrogen withdrawal is associated with an exacerbation of symptoms.³⁴ After delivery, the reduction in hormonal concentrations coincides with an increase in migraine symptoms.³⁵ In a prospective study of 208 Japanese women,³⁶ 85% of women had headache regression during pregnancy; no patient had worsening of headache symptoms during pregnancy. More than 50% of women experienced recurrence of migraine headache in the first postpartum month; breastfeeding was protective against the recurrence of headache.

Obstetric Management

Pregnancy may aggravate many of the medical complications of spinal cord injury (Box 49-1).⁴⁵ The loss of both functional residual capacity and expiratory reserve volume during pregnancy may increase the likelihood of respiratory compromise associated with spinal cord injury. Pregnancy increases the risks for thromboembolic phenomena and urinary tract infection. Loss of sympathetic tone below the level of the lesion renders pregnant patients with spinal cord injury particularly prone to orthostatic hypotension, which may result in a decrease in uteroplacental perfusion. Uterine contractions can stimulate autonomic hyperreflexia, and the resultant vasoconstriction can result in fetal hypoxia and bradycardia. In pregnant women, autonomic hyperreflexia occurs most commonly during labor.

Women with a lesion above T11 may have a higher risk for preterm labor.⁴² Because these women do not experience labor pain, obstetric management includes weekly cervical examinations during the third trimester. Vaginal delivery is preferred. The use of assisted vaginal delivery may be necessary because of the parturient’s inability to push.⁴² In a study of 52 pregnancies in spinal cord–injured women, 9 of 12 patients with lesions above T5 had symptoms of autonomic hyperreflexia. The cesarean delivery rate was 47% for women with lesions above T5 and 26% for women with lesions at T5 or below.⁴⁶ Preterm delivery occurred in 19% of patients. Autonomic hyperreflexia may affect uteroplacental blood flow, necessitating careful monitoring of the fetal heart rate (FHR).

Anesthetic Management

Women with spinal cord lesions at or above T6 are at risk for autonomic hyperreflexia. This syndrome can be distinguished from other causes of intrapartum hypertension by the occurrence of cyclic hypertension (i.e., blood pressure increases during contractions and decreases between contractions). The ACOG⁴⁷ recommends continuous hemodynamic monitoring during labor for all patients at risk for autonomic hyperreflexia.

Administration of neuraxial anesthesia is the most common method for prevention or treatment of autonomic hyperreflexia during labor and delivery. Spinal anesthesia has effectively controlled blood pressure in paraplegic patients undergoing general surgical procedures.⁴⁸ Although some anesthesiologists contend that distortion of the vertebral column in paraplegic patients makes it more difficult to predict and control the level of spinal anesthesia, published data do not lend support to this argument.⁴⁸ If spinal anesthesia is chosen, insertion of an intrathecal catheter and use of a continuous technique may be appropriate; this approach may allow careful titration of the resulting neuroblockade.

Most obstetric anesthesiologists prefer the use of epidural analgesia for the prevention or treatment of autonomic hyperreflexia during labor and delivery. Consideration also should be given to providing epidural analgesia after vaginal delivery to minimize the possibility of autonomic hyperreflexia, which has been reported to occur in response to pain as late as 5 days after delivery.⁴⁹

Case reports have described the successful epidural administration of 0.25% or 0.5% bupivacaine or the administration of combined spinal-epidural (CSE) anesthesia for the mitigation of autonomic hyperreflexia.^50–52 Baraka⁵³ reported the successful use of epidural meperidine, an opioid with local anesthetic qualities, in avoiding the signs of autonomic hyperreflexia. Abouleish et al.⁵⁴ observed that epidural fentanyl alone did not effectively treat the hypertension of autonomic hyperreflexia, but the addition of 0.25% bupivacaine led to a decrease in blood pressure to baseline levels. Maehama et al.⁵⁵ described the successful use of magnesium sulfate for management of autonomic hyperreflexia during labor.

Patients with spinal cord injury often have a low baseline blood pressure and some hemodynamic instability. Placement of an intra-arterial catheter before induction of anesthesia allows the continuous assessment of blood pressure.

Positioning for neuraxial block may be difficult; the anesthesiologist should consider performing the block with the patient in a lateral position because the sitting position may cause hypotension from venous pooling in the lower body. Therapeutic doses of a local anesthetic agent should be administered cautiously with the understanding that the cephalad level of the sensory block can be fully assessed only if it is higher than the level of the spinal cord lesion. As a result, the typical epidural test dose may not identify unintentional subarachnoid injection in a patient with spinal cord injury. Neuraxial blockade can be partially assessed by evaluating segmental reflexes below the level of the lesion. For example, the anesthesiologist can lightly stroke each side of the abdomen above and below the umbilicus, looking for contraction of the abdominal muscles and deviation of the umbilicus toward the stimulus. Reflexes are absent below the level of the block. In some patients with spastic paresis at baseline, the level of anesthesia may be confirmed by the conversion of spastic paresis to flaccid paresis.⁵⁰ A decline in blood pressure may also herald the onset of neuraxial blockade. Using a nerve stimulator connected to a saline-filled, wire-reinforced epidural catheter was found to be a reliable and relatively simple method of confirming catheter placement in the epidural space.⁵⁶

Alternative means of treating autonomic hyperreflexia should be available if neuraxial anesthesia is not successful. Antihypertensive medications such as magnesium sulfate or arteriolar vasodilators may be effective, recognizing that hypotension can result in decreased uterine blood flow.⁴⁶ Careful titration of nitroprusside, noting the potential for fetal/neonatal cyanide intoxication, or beta-adrenergic receptor blockade, may also be useful. The anesthesiologist should recognize that increased vagal activity during autonomic hyperreflexia can result in electrocardiographic changes including first- and second-degree atrioventricular block and sinus arrest.⁵⁷

If cesarean delivery is necessary, epidural or spinal anesthesia can be administered. Spinal anesthesia is generally associated with a more rapid onset and a more unpredictable level of neuroblockade and can lead to significant hypotension.⁵⁸ The effect of neuraxial blockade on respiratory function may be less severe with epidural anesthesia than with spinal anesthesia.

Severe respiratory insufficiency or technical difficulties with neuraxial anesthesia may necessitate the use of general anesthesia.⁵⁹ If general anesthesia is required, a depolarizing muscle relaxant such as succinylcholine should not be given during the period of denervation injury. By a conservative definition, this period begins 24 hours after the injury and lasts for 1 year. The use of succinylcholine during this period of denervation injury may cause severe hyperkalemia⁶⁰; therefore, a nondepolarizing muscle relaxant should be used to facilitate laryngoscopy and tracheal intubation.

I. Ocular myasthenia

II. Mild generalized myasthenia; may include ocular, oropharyngeal, and respiratory involvement

III. Moderate generalized disease

IV. Severe generalized weakness

V. Defined by requirement for tracheal intubation, with or without mechanical ventilation

Medical Management

Treatment involves a thymectomy, administration of anticholinesterase medications and/or immunosuppressive agents, and plasmapheresis. A thymectomy improves the disease course in approximately 96% of patients; 46% of these patients undergo complete remission, and an additional 50% are asymptomatic or experience improvement with therapy.⁶³ In addition, a thymectomy appears to exert a favorable influence on the outcome of pregnancy.⁶⁴ One study noted decreased maternal and perinatal morbidity as well as less frequent clinical exacerbations in patients who had undergone thymectomy.⁶⁴

Anticholinesterase drugs, which inhibit the breakdown of acetylcholine, are the mainstay of therapy. Decreased muscle weakness within minutes of administering an intravenous dose of edrophonium (10 mg) confirms the diagnosis of myasthenia gravis. Physostigmine crosses the blood-brain barrier and is not used for long-term therapy. Neostigmine and pyridostigmine are quaternary ammonium compounds that do not cross the blood-brain barrier. These drugs may be administered orally or intravenously. In general, pyridostigmine is preferred because it has less severe muscarinic side effects.⁶⁵

Corticosteroids and azathioprine have been used with some success. Plasmapheresis can be especially helpful for patients in crisis. One study noted that preoperative plasmapheresis resulted in less need for mechanical ventilation and less time in the intensive care unit postoperatively.⁶⁶

Myasthenia gravis can manifest in two types of crises. A cholinergic crisis results from an excess of the muscarinic effects of anticholinesterase medications combined with a poor response to anticholinesterase therapy. Symptoms include muscle weakness, respiratory difficulty or failure, increased sweating, salivation, bronchial secretions, and miosis. In contrast, a myasthenic crisis results from a worsening of the disease; its symptoms include more severe muscle weakness, including the respiratory muscles. These two crises can be distinguished by the administration of edrophonium. The symptoms do not improve if the crisis is cholinergic. In contrast, improvement indicates a myasthenic crisis and the need for a higher dose of anticholinesterase medication.

Many drugs can cause a worsening of myasthenic symptoms. These patients are extremely sensitive to drugs that potentiate muscle weakness.⁶⁷ These agents include neuromuscular blocking agents, quinidine, propranolol, aminoglycoside antibiotics, and tocolytic agents such as magnesium sulfate^68,69 and terbutaline. One case report noted worsened symptoms after the maternal administration of betamethasone.⁷⁰

Obstetric Management

The course of myasthenia gravis during pregnancy varies. In general, approximately 29% of cases improve, 41% worsen, and 30% show no change.⁷¹ Approximately 30% of patients experience a relapse postpartum. The highest chance of exacerbations occurs in the first trimester and in the acute postpartum period.⁷²

Myasthenia gravis increases the rates of pregnancy wastage, preterm labor, and maternal mortality and morbidity.^72,73 In 1991 Plauché⁷¹ estimated that maternal mortality is approximately 40 per 1000 live births and perinatal mortality is approximately 68 per 1000 births. Maternal mortality risk is inversely proportional to the duration of myasthenia gravis, with the highest risk occurring in the first year; consequently, myasthenic women are sometimes counseled to delay childbirth for the first few years after diagnosis.⁷³

The maternal physiologic changes of pregnancy, including alterations in drug absorption, increases in blood volume, and changes in renal clearance, may require adjustments in the doses of anticholinesterase drugs. However, in the presence of a myasthenic crisis, aggressive intravenous therapy is essential, even during labor. Anticholinesterase agents are quaternary ammonium compounds that undergo minimal placental transfer but have known uterotonic effects⁷³; thus, uterine activity should be monitored during the administration of these drugs. Each patient should be monitored carefully for progressive respiratory compromise secondary to diaphragmatic elevation during pregnancy. Vital capacity can be measured to monitor fatigue during labor. The treatment of the myasthenic patient with preeclampsia or preterm labor is problematic because the use of magnesium sulfate for maternal seizure prophylaxis or fetal neuroprotection may be associated with a significant increase in maternal and fetal muscle weakness.⁷²

The uterus consists of smooth muscle; therefore, myasthenia gravis should not affect the first stage of labor. However, the second stage of labor often requires the use of striated muscle and consequently an assisted (e.g., vacuum or forceps) vaginal delivery may be required.

Maternal antibodies to the acetylcholine receptor are transferred across the placenta. Neonatal myasthenia gravis occurs in approximately 16% of infants of mothers with myasthenia gravis.^64,71 Physiologic variations in the levels of alpha-fetoprotein, which can block the binding of the antibody to the acetylcholine receptor, can alter the clinical course of myasthenia during pregnancy.⁷⁴ The rapid decrease in alpha-fetoprotein concentrations in the neonate after birth may be responsible for transient symptoms of myasthenia (e.g., feeding problems, hypotonia, respiratory difficulty) within the first 4 days of life.⁷² The symptoms abate as the antibodies are metabolized, with resolution typically occurring within 2 to 4 weeks; however, anticholinesterase therapy may be required during the interim.

Anesthetic Management

Myasthenia gravis patients should undergo early antepartum consultation with an anesthesiologist. This evaluation should assess the extent of bulbar and respiratory involvement and overall baseline muscle strength. Pulmonary function testing should be performed in patients with evidence of respiratory compromise. In a study of surgical patients, the presence of bulbar symptoms, a preoperative serum level of antiacetylcholine receptor antibody greater than 100 nmol/L, and intraoperative blood loss greater than 1000 mL were risk factors for having a postoperative myasthenic crisis.⁷⁵

Patients with respiratory compromise may be more susceptible to opioid-induced respiratory depression, and consideration should be given to minimizing or avoiding opioids when possible. Neuraxial techniques are the preferred method for labor analgesia in patients with myasthenia gravis, given their association with low pain scores and high maternal satisfaction, even without the addition of opioids.⁷⁶ The use of anticholinesterase drugs may prolong the half-life of ester local anesthetic agents.

Neuraxial anesthetic techniques are preferred for cesarean delivery unless the patient has significant bulbar involvement or respiratory compromise. The use of bilevel positive airway pressure for ventilatory support in patients with moderate respiratory compromise may improve the safety of neuraxial anesthesia.⁷⁷

In the patient with severe bulbar involvement or respiratory compromise, it may be prudent to secure the airway before surgery. Sodium thiopental, ketamine, and propofol have been used successfully for the induction of general anesthesia in patients with myasthenia gravis.^73,77,78 Depolarizing muscle relaxants (e.g., succinylcholine) have an unpredictable effect in these patients, with affected and unaffected muscles being more sensitive and resistant to these agents, respectively.⁶³ However, the commonly administered dose of succinylcholine (1 to 1.5 mg/kg), which is three to five times the effective dose in 95% of normal patients, will most likely provide adequate relaxation even for resistant muscles. Anticholinesterase agents and plasmapheresis cause decreases in the activity of plasma cholinesterase and may cause delays in succinylcholine hydrolysis.

Myasthenic patients are extremely sensitive to nondepolarizing muscle relaxants. If a nondepolarizing muscle relaxant must be given, the anesthesia provider should administer a small amount of an agent with a short half-life (e.g., rocuronium, atracurium, vecuronium).⁶³ Mivacurium is metabolized via plasma pseudocholinesterase, which may be inhibited by pyridostigmine. In general, greater disease severity corresponds with enhanced sensitivity to nondepolarizing muscle relaxants, necessitating the use of clinical judgment and neuromuscular monitoring to determine the amount and timing of drug doses. Myasthenia may prevent a full-strength contraction with nerve stimulation; therefore, a control train-of-four stimulus test should be performed before paralysis for later comparison. For nondepolarizing agents, approximately 50% of the standard dose may be adequate, and a prolonged recovery should be anticipated. Small doses of neostigmine may be given cautiously for the reversal of neuromuscular blockade.

After delivery, fluid shifts and decreased maternal alpha-fetoprotein concentrations may necessitate an adjustment of anticholinesterase drug doses. Some patients who receive general anesthesia require postoperative ventilation. The following factors are predictive of an increased risk for postoperative ventilation: (1) female gender, (2) FEF_25%-75% (forced expiratory flow during the middle half of the forced vital capacity) less than 3.3 L/sec and less than 85% of that predicted, (3) FVC (forced vital capacity) less than 2.6 L/sec and less than 78% of that predicted, and (4) MEF_50% (maximal expiratory flow at 50% of expired vital capacity) less than 3.9 L/sec and less than 80% of that predicted.⁷⁹

Medical Management

A variety of antiepileptic agents are used for seizure therapy, depending on the type of seizure and clinical response (Table 49-2). A variety of adverse effects have been reported with these agents, including early-onset events (e.g., somnolence, dizziness, hypersensitivity, rash, gastrointestinal symptoms) and late-onset events (e.g., depression, leukopenia, aplastic anemia, thrombocytopenia, megaloblastic anemia, hyponatremia).⁸¹

Prognosis for medical control of seizures is good for patients with generalized seizure disorders; as many as 2% to 40% of newly diagnosed epilepsy patients become seizure-free without or with minimal antiepileptic drug therapy.⁸² Two of three newly treated epilepsy patients will eventually enter long-term remission (5 years or more without a seizure).⁸² However, about one third of patients will have an intermittent pattern (early remission with late recurrence or late remission). Finally, the standard mortality ratio for patients with epilepsy (observed number of deaths in the study compared with the general population) is consistently increased in the first several years after the diagnosis of epilepsy.

Interaction with Pregnancy

Three to five births per thousand occur in women with epilepsy.⁸³ A 2009 systematic review by the American Academy of Neurology and American Epilepsy Society concluded that there is insufficient evidence to determine whether seizure frequency changes during pregnancy.⁸⁴ Women who are free of seizures for at least 9 months to 1 year before pregnancy have a probability of 84% to 92% of remaining seizure-free during pregnancy.⁸⁴

Optimizing antiseizure therapy before pregnancy is critical. Because of the teratogenic aspects of many antiepileptic agents, some physicians consider withdrawal of these drugs after 2 years without seizures and recommend waiting at least 6 additional months after withdrawal before attempting to conceive. Substituting new antiepileptic agents after conception is not recommended.

A variety of causes have been proposed for the increase in seizure frequency observed in some pregnant women (Table 49-3). Higher estrogen concentrations in pregnancy lower the seizure threshold.⁸⁵ Greater sodium and water retention, alkalosis secondary to hyperventilation, sleep deprivation, and increased stress and anxiety also have been suggested as mechanisms.⁸⁶ In addition, anticonvulsant drug levels can decrease during pregnancy, often despite the administration of a larger dose⁸⁷; this may be partially explained by the decreased plasma protein binding and greater drug clearance observed during pregnancy.⁸⁸ The American Academy of Neurology and American Epilepsy Society concluded that monitoring of lamotrigine, carbamazepine, and phenytoin levels should be considered during pregnancy. Monitoring of levetiracetam and oxcarbazepine (and its active metabolite, monohydroxy derivative) may be considered, and monitoring of other antiepileptic agents should not be discouraged despite limited data regarding their pharmacokinetic behavior during pregnancy.⁸⁹

Maternal seizures can have devastating consequences. Hypoxia and acidosis that occur during a generalized seizure can result in fetal compromise or intrauterine fetal death. During the past three decades, the overall risk for obstetric complications in epileptic women has declined. Although some studies have suggested an increased risk for hypertension in pregnancy (including preeclampsia), bleeding, and preterm birth, a systematic review concluded that evidence is inconclusive.⁸⁴ However, women with epilepsy may have a moderately increased risk for cesarean delivery.⁸⁴

Fetuses and neonates of women with epilepsy are approximately twice as likely to have adverse pregnancy outcomes, including intrauterine fetal death, cesarean delivery, 1-minute Apgar score less than 7, neonatal and perinatal death, LBW, and abnormal development.⁹⁰ Antiepilepsy drugs taken in the first trimester of pregnancy are associated with an increased risk for major congenital malformations.^83,90,91 Data are insufficient to judge whether in utero exposure to antiepileptic agents in general increases the risk for cognitive impairment in the offspring of women with epilepsy, although there is some evidence that the risk may be increased for specific drugs.^83,91 Specifically, in utero exposure to valproate has been associated with maladaptive childhood behavior and autism.⁹¹

The risk for congenital malformations in women with epilepsy receiving antiepileptic drug monotherapy is 4% to 6%^90,91 Malformations have been associated with all currently used therapeutic modalities; those most often observed are cleft lip and palate and cardiac, neural tube, and urogenital defects (hypospadias).⁹¹

Certain drugs have been associated with a higher relative risk for congenital defects than others. Data from prospective studies indicate that valproate in particular is associated with significantly higher rates of major malformations.^83,91 Animal studies suggest that newer agents (e.g., lamotrigine, gabapentin, felbamate, topiramate, tiagabine, levetiracetam, pregabalin) have less terato­genic effect in animals, but adequate human studies have not been performed.⁹¹ Lamotrigine may be less teratogenic in humans than other antiepileptic agents, although neonates with orofacial clefts have been reported in association with its use.⁹² Collaborative international registries are collecting more information regarding the dose-dependent effects of antiepileptic agents during pregnancy, particularly information regarding the newer drugs.⁹³ Several studies suggest that maternal folic acid supplementation before conception may decrease the risk for major congenital abnormalities in the offspring of women with epilepsy on antiepileptic therapy.⁸⁹

Tomson and Battino⁹¹ reviewed data from the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) and made the following suggestions: (1) before conception select the most appropriate agent for the woman’s type of epilepsy, (2) select the drug with the lowest teratogenic potential, (3) aim for monotherapy with the lowest effective dose, (4) whenever possible avoid valproate, and (5) if possible avoid valproate at doses of 700 mg/d and higher.

Neonates of mothers undergoing long-term antiepileptic therapy may be at risk for deficiencies in vitamin K–dependent clotting factors or other coagulation defects, despite the absence of clinically evident maternal coagulation abnormalities.⁸⁹ Enzyme-inducing antiepileptic agents (e.g., phenytoin, phenobarbital, carbamazepine) can cross the placenta and may increase the rate of oxidative degradation of vitamin K in the fetus. Affected infants are at risk for neonatal hemorrhage and respond to vitamin K (1 mg) given intramuscularly at birth. The administration of prenatal vitamin K to epileptic women with long-term exposure to these particular antiepileptic agents has not been conclusively shown to reduce the risk for neonatal hemorrhage.⁸⁹

Anesthetic Management

There are significant interactions between antiepileptic drugs and anesthetic agents.⁹⁴ Carbamazepine, pheny­toin, phenobarbital, and primidone are potent inducers of the cytochrome P450 enzymes in hepatic metabolism (see Table 49-2), which may result in decreased plasma concentrations of many medications, including beta-adrenergic receptor antagonists and calcium entry–blocking agents.⁸¹

Serum levels of antiepileptic drugs should be checked if therapeutic levels are known (see Table 49-2). Drug doses should not be missed during the peripartum period. If the patient experiences a seizure during labor, airway protection and support of ventilation are essential. Small doses of a benzodiazepine, propofol, or sodium thiopental arrest most seizures. Fetal bradycardia may necessitate immediate delivery.

Oral antiepileptic therapies should be continued whenever possible throughout the peripartum period. Unfortunately many of the agents are not available in parenteral forms. If oral agents cannot be taken, conversion to a parenteral agent such as phenytoin may be required. In general, antiepileptic agents have sedating properties and some are known to induce liver enzymes; this feature could potentially lead to more rapid breakdown of anesthetic agents that are metabolized by the liver.

The presence of epilepsy is not a contraindication to the administration of neuraxial analgesia or anesthesia. In a retrospective review of 100 epileptic obstetric patients, 19 received general anesthesia, 48 received spinal anesthesia, 21 received epidural or caudal anesthesia, and 12 received pudendal nerve block.⁹⁵ Of the 5 women who had a postpartum seizure, 4 had received spinal anesthesia and 1 had received general anesthesia with enflurane. No seizures occurred in patients who received epidural or caudal anesthesia. Although antiepileptic drugs have been associated with adverse effects on the coagulation system, Manohar et al.⁹⁶ observed no abnormal clotting parameters or platelet counts preoperatively in a series of patients with epilepsy undergoing surgery.

If general anesthesia is necessary, it seems prudent to avoid drugs such as ketamine and meperidine, which may lower the seizure threshold.^86,97 Sevoflurane has stronger epileptogenic properties than isoflurane, but co-administration of nitrous oxide and hyperventilation both counteract this effect.⁹⁸ Low doses of propofol also have been shown to cause activation of the electrocorticogram in epileptic patients, but at higher doses burst suppression was induced.⁹⁹ The highest incidence of seizure activity with induction of anesthesia is believed to occur with etomidate, followed by thiopental, methohexital, and propofol. Ketamine may also facilitate seizures at low dosages, but at high doses each of these induc­tion agents acts as an anticonvulsant.⁹⁴ Induction of general anesthesia can be performed with propofol or sodium thiopental and succinylcholine, and anesthesia may be maintained with a mixture of oxygen, nitrous oxide, and isoflurane. One study noted that some patients who receive phenytoin are resistant to vecuronium but not to atracurium.¹⁰⁰

Obstetric Management

In patients with myotonic dystrophy, symptoms of weakness and myotonia usually remain unchanged during pregnancy; however, in a minority of women, symptoms worsen during pregnancy but generally resolve after delivery.¹⁰⁶ Antepartum evaluation should include pulmonary function testing, to assess the severity of restrictive lung disease due to muscle wasting, and an electrocardiogram, which may reveal conduction abnormalities.

There may be a higher risk for preterm labor in patients with myotonic dystrophy. Other complications of pregnancy include polyhydramnios (secondary to reduced fetal swallowing) and an increased risk for placenta previa.¹⁰⁷ Magnesium sulfate has been reported to cause respiratory compromise.¹⁰⁸ Poor uterine contractions may result in prolonged labor, uterine atony, and an increased risk for postpartum hemorrhage.^109,110 Muscle weakness may result in a prolonged second stage of labor and a higher incidence of operative delivery.¹⁰⁷ The neonate also may have respiratory distress if affected by congenital myotonic dystrophy.

There are reports of patients with myotonia congenita who experience temporary worsening of symptoms during pregnancy.¹¹¹ Obstetric problems have not been described, most likely because this disease involves skeletal muscle only; uterine smooth muscle is not affected in these patients.

Anesthetic Management

Patients with myotonic disorders may be especially sensitive to the respiratory depressant effects of opioid analgesic and general anesthetic agents.¹¹² Sedative-hypnotic agents should be used with caution; in some cases, opioids or sedatives may precipitate apnea. Thus, neuraxial anesthesia is preferred for labor and vaginal or cesarean delivery. Both spinal and epidural anesthesia have been used successfully in patients with myotonic dystrophy.^113–115 Although the clinical characteristics of myotonic dystrophy DM2 are generally more benign than DM1, anesthesiologists should be aware that both may be associated with dysphagia, cardiomyopathy, and cardiac conduction abnormalities.¹¹⁶

The prolonged contractions witnessed in patients with myotonia are due to an intrinsic muscle disorder that is not relieved by spinal or epidural anesthesia; however, infiltration with a local anesthetic agent may partially release contractions. Cold external temperatures and shivering are known triggers of myotonia, so the patient should be kept warm. Some anesthesiologists recommend the cautious administration of intrathecal or epidural opioids for their anti-shivering effect.¹¹³ Patients with myotonic dystrophy have a high incidence of pulmonary complications after general anesthesia.¹¹⁷

If general anesthesia is required, it is prudent to limit the use of opioids and carefully titrate muscle relaxants to mitigate the risk for postoperative pulmonary complications.¹¹⁸ Depolarizing agents such as succinylcholine should be avoided because fasciculations may trigger myotonia,¹¹⁹ thereby making ventilation and tracheal intubation difficult. By contrast, patients with myotonic dystrophy appear to have a normal response to nondepolarizing muscle relaxants. Regardless, careful neuromuscular monitoring is essential, particularly in those with significant baseline muscle weakness. Patients receiving quinine may require a smaller dose of a nondepolarizing muscle relaxant. In a review of dystrophic myotonias and their possible association with malignant hyperthermia, Parness et al.¹²⁰ concluded that susceptibility to malignant hyperthermia in this group of patients is similar to that of the general population. Patients with central core disease should be assumed to be susceptible to malignant hyperthermia.¹⁰⁴

Obstetric Management

The classification of the muscular dystrophies is defined by DNA and dystrophin analysis. The presentations of these dystrophinopathies are variable, and the overall management is guided by the presence and severity of symptoms. If significant weakness is present, pulmonary function testing should be obtained to assess the extent of restrictive disease. An antepartum electrocardiogram and echocardiogram should also be considered. Pregnant women with muscular dystrophies may have an increased incidence of operative delivery; the presence of severe pelvic wasting may necessitate an instrumental vaginal or cesarean delivery.^122,123 In a series of pregnant women with fascioscapulohumeral dystrophy, increased rates of LBW infants and operative deliveries were observed; the disorder worsened in 24% of these pregnancies and generally did not resolve after delivery.¹²² A larger study of the course of pregnancy in women with hereditary neuromuscular disorders reported a high rate (27%) of abnormal fetal presentation in women with limb-girdle muscular dystrophy, especially in chair-bound patients.¹⁰⁶ About half of patients with limb-girdle muscular dystrophy reported a deterioration of symptoms during and after pregnancy.

Anesthetic Management

Limb-girdle muscular dystrophy is associated with various cardiac abnormalities, including cardiomyopathies and conduction abnormalities. Reduced lung function and respiratory compromise can be exacerbated by the physiologic changes of pregnancy; one report of a parturient with limb-girdle muscular dystrophy noted the requirement of noninvasive positive-pressure ventilation during the third trimester of pregnancy for progression of severe restrictive pulmonary disease.¹²⁴ Neuraxial techniques are preferred for labor analgesia and cesarean delivery anesthesia. Severe disease may result in both airway abnormalities and spinal deformities, which may complicate the administration of either general or neuraxial anesthesia. Severe kyphoscoliosis during pregnancy can prevent adaptive hyperventilation and gradually result in respiratory insufficiency.¹²⁵

Whereas most females are asymptomatic carriers of the abnormal gene for muscular dystrophies, approximately 2.5% of female carriers have symptoms of the disease—although usually in milder forms than those witnessed in men.¹²⁶ There are reported cases of muscular dystrophy associated with “malignant hyperthermia.” In a systematic review, Gurnaney et al.¹²⁷ summarized reported cases of patients with muscular dystrophy who developed hyperthermia, tachycardia, rhabdomyolysis, and hyperkalemia after exposure to succinylcholine and/or volatile anesthetic agents. However, none of these patients had other classic signs of malignant hyperthermia or evidence of hypermetabolism. The mechanism for this response is not well understood but may be related to the ability of these agents to exacerbate instability and permeability of dystrophin-deficient muscle membranes.¹²⁷ Although the authors concluded that muscular dystrophy patients are unlikely to be at increased risk for malignant hyperthermia, they recommended that volatile anesthetic agents be used cautiously because of the risk for severe rhabdomyolysis. Succinylcholine may lead to hyperkalemia because of up-regulation of extrajunctional acetylcholine receptors or as a result of rhabdomyolysis. Thus, succinylcholine should not be administered to patients with known muscular dystrophy. In general, these patients have a normal response to nondepolarizing muscle relaxants, but careful neuromuscular monitoring is needed, especially in patients with severe muscle wasting.

Neurofibromatosis

Neurofibromatosis occurs as a result of excessive proliferation of neural crest elements such as Schwann cells, melanocytes, and fibroblasts. Clinical manifestations include hyperpigmented lesions (café-au-lait spots) accompanied by a variety of cutaneous and subcutaneous tumors. This disorder is now believed to exist in two distinct forms with gene abnormalities on two different chromosomes. Neurofibromatosis type 1, the “classic” form, has an incidence of approximately 1 in 3000. The severity and progression of the disease are variable, with the neurologic symptoms depending on the location of the tumors. Intracranial tumors and paraspinal neurofibromas are a cause of concern and may require surgical excision. The risk for pheochromocytoma is greater in these patients.¹²⁹ Neurofibromatosis type 2 is a less common, more recently discovered, form of the disease with fewer cutaneous lesions. Acoustic neuromas as well as other cranial or spinal neurofibromas, meningiomas, and gliomas may be present.

Tuberous Sclerosis

Tuberous sclerosis is a phakomatosis characterized by epilepsy, mental retardation, and adenoma sebaceum.¹³⁶ The brain shows abnormal growth of glial cells in hamartomas called tubers. Hamartomatous tumors can occur in multiple organs, including the heart, kidneys, liver, and lungs. The inheritance pattern is autosomal dominant with a variable expression, and the disease is slowly progressive.

Cutaneous Angiomatosis with Central Nervous System Abnormalities

One group of phakomatoses consists of disorders in which a cutaneous vascular anomaly is accompanied by CNS abnormalities (see Box 49-2).¹⁴⁰ There are few reports of pregnancy in patients with these disorders. Patients may have neurologic problems related to hemangiomas of the CNS. Cesarean delivery with epidural anesthesia has been reported in a patient with spinal hemangiomas.¹⁴¹ The presence of widespread varicosities in these disorders may result in a chronically low ventricular preload; if a significant increase in preload occurs during the peripartum period, cardiac overload and peripartum cardiomyopathy may occur.¹⁴²

Obstetric Management

The incidence of this syndrome appears to be lower in pregnant women than in nonpregnant women. Using data from several nationwide registries, Jiang et al.¹⁴⁵ found that the age-adjusted relative risk of Guillain-Barré syndrome appears to be decreased during pregnancy but increases in the first 3 postpartum months. In severe cases, the risk for preterm labor is increased and neurologic deterioration may occur after delivery.¹⁴⁶ Termination of pregnancy does not appear to improve the course of the disease, but induction of labor may be indicated if autonomic dysfunction occurs. Instrumental vaginal delivery may be necessary.¹⁴⁶

Anesthetic Management

Anesthetic management depends on patient status at the time of delivery; epidural, spinal, and CSE techniques have been described in patients with Guillain-Barré syndrome.^147–149 However, some anesthesiologists have expressed concern regarding the use of neuraxial techniques in these patients, citing the theoretical potential for neurologic changes as a result of anesthetic toxicity or immunologic modulation. Steiner et al.¹⁵⁰ implicated epidural anesthesia as a trigger of Guillain-Barré syndrome in four patients; Wiertlewski et al.¹⁴⁸ reported the immediate worsening of neurologic status after delivery in a pregnant patient with Guillain-Barré syndrome who had received epidural anesthesia. These reports did not establish a causal relationship between the disease and neuraxial anesthesia techniques, nor did they properly acknowledge the increased frequency of Guillain-Barré syndrome in the postpartum period.

If general anesthesia is necessary in a patient with Guillain-Barré syndrome, succinylcholine most likely should be avoided because of the risk for hyperkalemia in patients with acute muscle wasting. Careful titration of nondepolarizing muscle relaxants is also necessary.

The parturient with a history of remote Guillain-Barré syndrome may have persistent diminished respiratory reserve, even in the absence of obvious residual disability.¹⁵¹ Pulmonary evaluation should be considered before the administration of anesthesia. Approximately 5% of patients experience a relapse, with a small number of cases progressing to a chronic disorder.

Obstetric Management

Currently, polio is a cause for concern only in countries with ineffective vaccination programs. Although the poliovirus vaccine has been available since the 1950s, the last phase of poliomyelitis eradication has been difficult; as of 2011, transmission of the disease continues in countries such as such as Nigeria, India, Pakistan, and Afghanistan.¹⁵⁵ The oral form of the vaccination does not appear to have harmful effects on fetal development and can be used if vaccination is required during pregnancy.¹⁵⁶ In the past, a history of poliomyelitis was believed to affect labor and delivery only if residual deficits resulted in pelvic asymmetry or an inability to push effectively¹⁵⁷; however, more recent data suggest a higher incidence of preeclampsia, maternal renal dysfunction, LBW infants, perinatal death, and cesarean delivery in poliomyelitis survivors.¹⁵⁸ Some of these adverse outcomes may be related to chronic pulmonary issues or mechanical obstruction during labor.

Anesthetic Management

A complete preanesthetic evaluation should be performed for the presence of respiratory impairment, sleep apnea, swallowing difficulties, and other neurologic and motor deficits in all parturients with a history of poliomyelitis.¹⁵² Some anesthesiologists have feared that administration of neuraxial anesthesia in patients with a history of poliomyelitis might cause reactivation of the virus or postpoliomyelitis and muscular atrophy. However, there is no evidence that neuraxial analgesia or anesthesia worsens symptoms in these patients. Crawford et al.¹⁴⁷ reported the successful use of epidural analgesia with no adverse complications in patients with a history of poliomyelitis. Rezende et al.¹⁵⁹ reported a series of 123 patients with a history of poliomyelitis undergoing 162 surgical procedures and observed postoperatively for 22 months; neuraxial blockade was used in 64% of cases, with no patients exhibiting worsening of neurologic symptoms. Anesthetic considerations in these patients should include assessment for pulmonary restrictive disease as well as anatomic issues that may make neuraxial techniques difficult.^160,161 A study from India reported that about one third of pregnancies complicated by kyphoscoliosis occurred in patients with a history of poliomyelitis in infancy.¹⁶¹ Radiographic imaging has been successfully used to guide spinal needle placement in these patients.

Suneel et al.¹⁶² reported a patient with a history of poliomyelitis who developed muscle weakness after general anesthesia that responded to additional neostigmine, suggesting that these patients may have a low threshold for the effects of neuromuscular blocking agents. For the patient with poliomyelitis in whom general anesthesia is needed, some anesthesiologists have suggested the use of a decreased dose of a short-acting nondepolarizing muscle relaxant in lieu of succinylcholine, which may provoke severe acute hyperkalemia.¹⁶³

Obstetric Management

The incidence of primary brain tumors first manifesting in pregnancy does not appear to be greater than that in aged-matched, nonpregnant women.¹⁶⁵ Approximately 9% of patients with choriocarcinoma have brain metastases at the time of diagnosis.¹⁶⁶ In one epidemiologic study, patients with primary brain tumors had a higher incidence of spontaneous abortion, possibly because of hormonal factors.¹⁶⁷ A 2012 study using a retrospective cohort from the National Inpatient Sample reported an increased rate of maternal mortality, cesarean delivery, and preterm labor in patients with malignant brain tumors, and an increased rate of preterm labor and cesarean delivery in patients with benign brain tumors.¹⁶⁸ Pregnancy complications were significantly more likely to occur in patients having a neurosurgical procedure during their admission.

Although pregnancy does not affect the incidence of brain tumors, some of these lesions appear to grow faster during pregnancy. Visual field defects from pituitary adenomas worsen as a result of tumor enlargement during pregnancy, and symptoms have been observed to improve during the postpartum period.¹⁶⁹ Edema and the increased blood volume may account for some of these symptoms. Pregnancy-induced hormonal changes also may play a role because estrogen and progesterone receptors are present in meningiomas and some gliomas.¹⁷⁰

Diagnosis during pregnancy requires intracranial imaging. In general, MRI is preferred because it avoids the use of ionizing radiation. MRI may require the use of gadolinium-based contrast agents. Gadolinium has the advantage compared with other contrast agents of not containing iodine, and studies demonstrating adverse fetal effects are lacking in humans. However, gadolinium appears rapidly in the fetal bladder and amniotic fluid, from where it may be swallowed by the fetus and absorbed from the gastrointestinal tract. Its fetal half-life is unknown. The American College of Radiology has stated that the “decision to administer a gadolinium-based MR contrast agent to pregnant patients should be accompanied by a well-documented and thoughtful risk-benefit analysis.”¹⁷¹

Management during pregnancy depends on the nature of the tumor. Surgery for benign tumors (e.g., meningiomas) with mild symptoms can often be delayed until after delivery. Women with more aggressive, malignant tumors or with tumors causing seizures or severe visual impairment may require urgent surgery during pregnancy to avoid acute neurologic deterioration. Delivery also may be recommended as soon as reasonable fetal survival can be expected, sometimes by cesarean delivery immediately before neurosurgery. For women with pregnancies far from fetal viability, radiation therapy or stereotactic radiosurgery can be considered. Cranial radiation therapy is generally administered as a first therapeutic procedure to reduce the size of the mass in cases of aggressive neoplasm. However, radiation therapy, and particularly systemic chemotherapy, can pose significant hazards to the fetus, especially when administered during the first trimester.¹⁶⁵ Some women may opt for surgery after an elective abortion.

In the normal parturient, CSF pressure may increase significantly with painful uterine contractions.¹⁷² In patients with an intracranial mass lesion, this situation could result in an increased risk for herniation. The location and size of the tumor should be assessed in the individual patient so that an appropriate delivery plan can be developed with multidisciplinary input. In general, either a pain-free second stage (with instrumental vaginal delivery to avoid pushing) or cesarean delivery may be appropriate.¹⁷³

Anesthetic Management

The optimal anesthetic technique for labor analgesia and cesarean delivery anesthesia in the patient with an intracranial tumor is controversial. Epidural analgesia prevents the increase in ICP that can result with pushing during the second stage of labor.¹⁷⁴ Several published reports have described the successful use of labor epidural analgesia in women with intracranial neoplasms^174,175; in addition, the use of spinal anesthesia for an emergency cesarean delivery in a patient with a glioblastoma has been described.¹⁷⁶ However, in pregnant women with increased ICP, an unintentional dural puncture associated with an attempted epidural catheter placement can result in a fatal brain herniation.¹⁷⁷ As a consequence, many anesthesiologists favor general anesthesia for cesarean delivery in the patient with a brain neoplasm¹⁷⁸; however, potential disadvantages of general anesthesia include (1) the loss of verbal and motor responses that facilitate neurologic assessment and (2) the risks of increased ICP with tracheal intubation and extubation.

Wang and Paech¹⁷⁹ have reviewed specific elements in the anesthetic management of the pregnant patient undergoing neurosurgery, many of which are also relevant to the patient with an intracranial tumor undergoing cesarean delivery. The induction of general anesthesia may consist of the administration of an induction dose of propofol or sodium thiopental and either a depolarizing or a rapid-acting nondepolarizing neuromuscular blocking agent. Some anesthesiologists avoid succinylcholine because it may cause a transient increase in ICP, but others consider this effect to be clinically insignificant.¹⁷⁹ A combination of a volatile halogenated agent (sevoflurane or isoflurane), nitrous oxide, and an opioid is commonly used for maintenance of anesthesia. The FHR should be monitored during intracranial surgery when possible.

To preserve cerebral and uteroplacental perfusion, hemodynamic stability should be maintained through appropriate fluid administration, avoidance of aortocaval compression, the prophylactic or early use of vasopressor drugs, and intra-arterial blood pressure monitoring instituted before induction of anesthesia.¹⁷⁹ In general, blood pressure should be kept close to baseline measurements; in the setting of an emergency neurosurgical procedure in a patient with increased ICP, a drop in blood pressure may compromise cerebral perfusion. Fluid management for intracranial surgery should involve administration of isonatremic, isotonic, and glucose-free intravenous solutions to reduce the risk for cerebral edema and hyperglycemia.¹⁷⁹ Mannitol administered to a pregnant woman slowly accumulates in the fetus, leading to fetal hyperosmolality and the subsequent physiologic changes of reduced fetal lung fluid production, decreased fetal urine production, and increased fetal plasma sodium concentrations^180,181; however, mannitol in doses of 0.25 to 0.5 mg/kg has been reported in individual cases and appears to be associated with good maternal and fetal outcomes.¹⁷⁹ Furosemide is an alternative diuretic that also should be administered cautiously.

There may be some conflict between maternal and fetal interests in the patient with increased ICP. Moderate mechanical hyperventilation may be used to reduce the increased ICP that occurs in nonpregnant patients with a brain tumor or brain injury. Minute ventilation increases during normal pregnancy, resulting in a maternal PaCO₂ of 28 to 32 mm Hg; additional hyperventilation and hypocapnia may cause uterine artery vasoconstriction and a leftward shift in the maternal oxyhemoglobin dissociation curve (see Chapter 2). For pregnant women with an acute increase in ICP, Wang and Paech¹⁷⁹ have suggested a target PaCO₂ range of 25 to 30 mm Hg; however, data are currently insufficient to support evidence-based recommendations specific to pregnant women undergoing intracranial surgery. In pregnant patients with increased ICP, we recommend maintenance of maternal PaCO₂ in the middle or at the lower end of the normal range for pregnancy. Management should be individualized according to the clinical setting.

When the decision is made to perform a cesarean delivery and brain tumor resection sequentially during a single anesthetic, hypertension should be avoided to prevent deleterious effects from tumor expansion. To avoid this complication during induction, some authors have used a combination of a high dose of fentanyl, thiopental, or propofol with succinylcholine.

A recent report of a patient with an unresected astroglioma undergoing cesarean delivery describes the postoperative use of transversus abdominis plane block to provide analgesia and reduce opioid requirements, thus reducing the risk for postoperative respiratory depression and potential exacerbation of ICP.¹⁸² In cases for which it is considered optimal to initially perform neurosurgery and then allow completion of the pregnancy, neuraxial techniques may be considered for delivery. The patient should be assessed to determine if ICP is elevated because this may preclude the use of a neuraxial technique. After neurosurgery, a reduction in ICP from a CSF leak may cause intracranial hypotension and may make confirmation of correct spinal needle placement by identification of CSF difficult.¹⁷⁹

Interaction with Pregnancy

Symptoms of idiopathic intracranial hypertension worsen during pregnancy in 50% of cases and typically improve after delivery.¹⁸⁴ However, in the presence of severe maternal symptoms, the placement of an intracranial shunt can result in clinical improvement and normal perinatal outcomes.¹⁸⁵ Overall, this disorder does not seem to adversely affect maternal and perinatal outcomes.¹⁸⁶

Anesthetic Management

Deliberate lumbar puncture represents a common form of treatment for idiopathic intracranial hypertension. Cerebellar tonsillar herniation does not occur because of the uniform, global increase in ICP. Paruchuri et al.¹⁸⁷ noted that there are only two published cases of cerebellar tonsillar herniation after diagnostic lumbar puncture in patients with this disorder. Both patients had severe headache, neck pain exacerbated by movement, and focal neurologic deficits. In the absence of these signs and symptoms, the anesthesia provider can provide neuraxial analgesia or anesthesia.¹⁸⁸

Some anesthesiologists recommend the administration of general anesthesia for cesarean delivery in patients with lumboperitoneal shunt. They contend that local anesthetic agents that reach the subarachnoid space may escape into the peritoneum, making it difficult to achieve adequate anesthesia. Moreover, the performance of neuraxial anesthesia may result in trauma to the shunt catheter. Bédard et al.¹⁸⁹ reported the successful administration of epidural anesthesia in a preeclamptic patient with a lumboperitoneal shunt that had been placed for the treatment of idiopathic intracranial hypertension. Preoperative radiographic examination may help the anesthesia provider avoid needle placement near the catheter, although such imaging was not used in this published case. Provision of neuraxial anesthesia with an intrathecal catheter has been performed for both vaginal and cesarean delivery in parturients with idiopathic intracranial hypertension and a lumboperitoneal shunt; in one case, the intrathecal catheter provided both labor analgesia and temporary control of ICP.^190,191 Questions regarding the functional status of an in situ subarachnoid shunt or the possible (very rare) use of the shunt for the administration of spinal anesthesia should be discussed with neurologic or neurosurgical consultants.¹⁹²

Obstetric Management

Obstetric management depends on the presence of other medical and neurologic conditions. In general, although maternal shunt dependency carries a relatively high risk for complications for some patients, proper management can lead to normal pregnancy and delivery.¹⁹⁴ Neurologic complications may occur in as many as 76% of pregnant women with preexisting shunts, including severe headache, shunt obstruction, and increased ICP.¹⁹⁵ Most symptoms resolve postpartum.

Most pregnant women with intracranial shunt catheters can undergo labor and vaginal delivery; elective cesarean delivery is recommended only in the presence of severe neurologic symptoms or instability.

Anesthetic Management

Anesthetic management of the patient with hydrocephalus may depend on the location of the shunt. There has been concern that some of the local anesthetic agent entering the CSF may escape into the atrium or peritoneum, resulting in inadequate analgesia. However, both epidural and spinal anesthesia have been used in patients with lumboperitoneal, ventriculoatrial, and ventriculoperitoneal shunts (as discussed earlier).^189–191 The anesthetic technique chosen for an urgent sequential ventriculoperitoneal shunt revision and cesarean delivery must balance the needs of the maternal neurologic condition and the pregnancy.

Because of the risk for shunt infection, some physicians recommend preoperative use of a prophylactic antibiotic regimen similar to that used to prevent bacterial endocarditis.¹⁹⁶

Obstetric Management

If the lesion has been treated surgically, the patient requires no special care during labor and delivery. For an untreated aneurysm or arteriovenous malformation, the hemodynamic stress occurring during labor and delivery should be minimized. Current data do not demonstrate a definite advantage of cesarean delivery over assisted vaginal delivery.²⁰⁴ The decision about the method of delivery should be based on the individual patient and her pregnancy history. For labor and vaginal delivery, neuraxial analgesia and low outlet forceps or vacuum assistance may be used to shorten the second stage of labor and attenuate fluctuations in blood pressure.

Anesthetic Management

If the parturient has undergone surgical repair of either an aneurysm or arteriovenous malformation, anesthetic management need not differ from that for other obstetric patients. Hypertension should be avoided in the parturient with an untreated lesion. If vaginal delivery is planned, epidural or CSE analgesia should be considered. For cesarean delivery, either epidural or spinal anesthesia can be used. Some anesthesiologists contend that epidural anesthesia or sequential CSE anesthesia (e.g., initial use of a lower intrathecal drug dose, followed by block augmentation with epidural injection of local anesthetic) provides greater hemodynamic stability and is thus preferred for cesarean delivery. Interdisciplinary planning is important.^196,205

In some cases, the neurosurgeon may ligate or excise the vascular lesion during pregnancy, before delivery. The anesthesiologist should consider the general principles of anesthetic management for pregnant women undergoing nonobstetric surgery (see Chapter 17) as well as the special considerations for pregnant women undergoing neurosurgery (as discussed earlier).¹⁷⁹ The risks for hypertension and intracranial bleeding, as well as the risk for aspiration should be considered during induction of anesthesia. It is critical to maintain stable blood pressure during induction of anesthesia, laryngoscopy, tracheal intubation, and extubation. The patient should receive adequate sedation before and after arrival in the operating room. Placement of an intra-arterial catheter is mandatory. The anesthesiologist may attenuate the hypertensive response to laryngoscopy and tracheal intubation by intravenous administration of esmolol, labetalol, lidocaine, nitroglycerin, nitroprusside, and/or an opioid (e.g., remifentanil). Succinylcholine can be used for tracheal intubation. Regardless of the choice of muscle relaxant, it is critical that laryngoscopy and tracheal intubation not be performed until the patient is anesthetized adequately.

The anesthesiologist may maintain anesthesia with nitrous oxide and modest doses of isoflurane and an opioid. Aggressive maternal hyperventilation may result in decreased uterine blood flow.¹⁹⁶ However, the anesthesiologist may use modest hyperventilation (e.g., PaCO₂ of 28 to 30 mm Hg) as needed to reduce maternal ICP. The anesthesiologist should maintain left uterine displacement in patients beyond 20 weeks’ gestation. Intraoperative FHR monitoring allows assessment of the fetal response to maternal general anesthesia and hyperventilation. At many institutions, including my own, intraoperative FHR monitoring is used beginning at 24 weeks’ gestation, which corresponds to the onset of extrauterine neonatal viability. Typically, an obstetric nurse monitors the FHR tracing during surgery and requests obstetric consultation if needed. An adverse change in the FHR tracing should prompt the anesthesiologist to ensure adequate maternal oxygenation, ventilation, and perfusion.

Use of deliberate hypotension may compromise uteroplacental perfusion, although its safe use has been reported during neurovascular intracranial surgery in pregnant women. There is no consensus regarding an acceptable or safe level of hypotension, or the ideal method for achieving hypotension, in these patients. The prolonged administration of large doses of nitroprusside may result in fetal cyanide toxicity, although short-term administration appears safe. Intraoperative FHR monitoring allows assessment of the fetal response to deliberate hypotension. Endovascular treatment with general anesthesia avoids the need for craniotomy and deliberate hypotension.

In some cases, the obstetrician and neurosurgeon may perform a combined procedure (e.g., a cesarean delivery followed by ligation or excision of the neurovascular lesion). Principles of anesthetic management are similar to those described earlier for intracranial neurovascular surgery during pregnancy.

Rarely, anesthesiologists may provide care for pregnant women who are receiving extended somatic support after brain death. Powner and Bernstein²⁰⁶ reviewed 11 reports of 10 cases of brain death during pregnancy, in which somatic support was provided until successful delivery. Intracranial hemorrhage was the cause of maternal brain death in 6 of the 10 patients. The longest period of support was 107 days, from 15 to 32 weeks’ gestation. All 10 infants survived. The authors concluded that preservation of uteroplacental blood flow is the most important priority during extended somatic support, but they acknowledged that this goal is difficult to achieve because of hemodynamic instability, the high prevalence of infection, and other adverse consequences (e.g., diabetes insipidus) associated with brain death.

Obstetric and Anesthetic Management

Cerebral vein thrombosis rarely occurs before delivery, although such an occurrence may prompt an urgent delivery if associated with maternal neurologic instability and fetal deterioration. Maternal anticoagulation contraindicates the administration of neuraxial anesthesia. The anesthesia provider should avoid systemic hypotension, which may reduce cerebral perfusion pressure and blood flow to injured areas already subjected to marginal perfusion. If the patient has an asymmetric cerebral hematoma, dural puncture may precipitate herniation of the brainstem. Thus, it seems preferable to administer general anesthesia for cesarean delivery, with special attention to the treatment of increased ICP. Cerebral venous thrombosis is a rare, but reported, complication after spinal and epidural anesthesia, presumably due to intracranial hypotension.²¹⁰

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis involves progressive degeneration of anterior horn cells with progressive atrophic weakness and hyperreflexia. Patients typically succumb to respiratory failure within 6 years of diagnosis.

This disease is seen more often in patients older than 50 years, but there are several reports of this disorder in pregnant women.^211,212 Physicians should assess and frequently monitor the patient’s respiratory compromise throughout the peripartum period. Epidural analgesia and anesthesia have been used in these patients without evidence of worsened neurologic function postoperatively.^213,214 Patients with amyotrophic lateral sclerosis may be sensitive to the effects of nondepolarizing muscle relaxants.²¹⁵ The physiologic changes during late stages of pregnancy may worsen marginal respiratory status in these patients, and early cesarean delivery may be warranted.²¹⁶

Spinal Muscular Atrophy

Like amyotrophic lateral sclerosis, primary spinal muscular atrophy involves degeneration of anterior horn cells. However, affected patients tend to be younger, and this disorder progresses more slowly. Some types are hereditary. Spinal muscular atrophy mainly involves the spinal cord, without involvement of the corticospinal tract. Marked kyphoscoliosis combined with truncal and limb weakness, especially involving the proximal musculature, can occur and result in significant ventilatory limitations.

Spinal muscular atrophy may be associated with an increased incidence of preterm labor.²¹⁷ One series noted that pregnancy was associated with an exacerbation of muscle weakness in 8 of 12 patients.²¹⁷ Epidural and spinal analgesia and anesthesia have been used successfully in patients with this disorder.^218,219 In children with this rare disorder, both general and regional anesthesia have been successfully used; special attention should be paid to postoperative respiratory function.²²⁰

Peroneal Muscular Atrophy

Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, includes several inherited peripheral motor and sensory neuropathies; it is one of the most common inherited neuromuscular diseases.²²¹ It involves a progressive sensory and motor degeneration of peripheral nerves and roots. The peroneal nerve is affected early. The disorder progresses to involve all the nerves and muscles of the legs and finally the hands. Paresthesias are typically present. Restrictive pulmonary impairment, phrenic nerve dysfunction, diaphragmatic dysfunction, thoracic cage abnormalities, and sleep apnea have been described in association with peroneal muscular atrophy. Vocal cord dysfunction, possibly due to laryngeal nerve involvement, can also be present. Assessment of peripartum respiratory function is essential. Approximately 30% of patients with this disorder report deterioration in overall function during pregnancy, with approximately 20% indicating persistent postpartum deficits.¹⁰⁶

A review of 108 deliveries found that women with this disorder have higher rates of abnormal fetal presentation, emergency operative delivery, and postpartum bleeding.²²² Both neuraxial and general anesthesia have been used for delivery.²²³ Careful titration of muscle relaxants is essential if general anesthesia is employed.

Bell’s Palsy

Bell’s palsy is a syndrome of acute-onset paralysis of the facial nerve; it tends to present during the third trimester and the first few postpartum weeks. The incidence during pregnancy is approximately 3.3 times higher than that in nonpregnant women, which in turn is 2 to 4 times higher than that in men.²²⁴ Some studies have suggested an association with preeclampsia, which may be based on increased interstitial edema.²²⁵ Interestingly, Maloney²²⁶ proposed that the smile of the famed portrait “The Mona Lisa” was the result of Leonardo da Vinci’s anatomically precise rendering of a new mother affected by Bell’s palsy during her pregnancy.

One study noted that pregnant patients whose symptoms progressed to complete facial paralysis within 10 days of onset were less likely to experience satisfactory recovery than a comparison group of nonpregnant patients.²²⁷ Patients may benefit from a short course of prednisone.²²⁸

Dorsey and Camann²²⁹ retrospectively reviewed 36 cases of Bell’s palsy associated with pregnancy; 25 women experienced symptoms during the third trimester, and the remaining 11 had symptoms during the first week postpartum. Of the 36 women, 27 received spinal or epidural analgesia or anesthesia. There were no differences in incidence or progression of the Bell’s palsy or maternal and fetal outcomes in relation to the type of anesthesia given; therefore, neuraxial analgesia or anesthesia does not appear to be contraindicated in patients with Bell’s palsy.

Carpal Tunnel Syndrome

Carpal tunnel syndrome is common during pregnancy; in a systematic review, the reported incidence ranged from 0.8% to 70%.²³⁰ The disorder results from compression of the median nerve in the flexor retinaculum at the wrist. Patients typically report paresthesias and weakness in the median nerve distribution, with symptoms worse in the morning on awakening from sleep. Symptoms have been reported to persist in approximately 50% and 30% of patients after 1 year and 3 years, respectively.²³⁰ Patients may be treated with splinting of the wrists, although in severe cases, surgery may be required. In many cases, symptoms resolve spontaneously within the first 2 months postpartum and appear to correlate with losing the weight gained during pregnancy.²³¹

Meralgia Paresthetica

Meralgia paresthetica involves sensory loss and paresthesias in the lateral thigh stemming from compression of the lateral femoral cutaneous nerve. Obesity and the exaggerated lordosis of pregnancy can stretch the nerve. Symptoms of meralgia paresthetica typically resolve within 3 months of delivery. This peripheral nerve palsy and other neurologic deficits are discussed more fully in Chapter 32.