Chapter 33. Nervous System & Autoimmune Disorders in Pregnancy

Cerebrovascular Disorders

Essentials of Diagnosis

• Headaches, visual disturbances, syncope, and hemiparesis are among the most common presenting findings.
• Computed tomography scan and magnetic resonance imaging can be used in pregnancy to increase the delineation of cerebrovascular involvement. Arteriography is considered definitive if surgical intervention is being considered because arteriography can more precisely localize the involved area.

Pathogenesis

The causes of cerebrovascular disease include insufficiency (arteriosclerosis, cerebral embolism, vasospasm from hypertensive disease) and disorders associated with bleeding into the cerebral cortex (arteriovenous malformation, ruptured aneurysm). The brain becomes infarcted from lack of blood flow, or intracranial bleeding results in a space-occupying lesion. The severity of such disorders can be affected by blood pressure, oxygen saturation (anemia or polycythemia), hypoglycemia, and adequacy of collateral circulation.

The overall incidence of ischemic cerebrovascular accidents in pregnancy is approximately 1 in 20,000 births, with most occurring in the last trimester or immediately postpartum. Etiologic factors for stroke include cardioembolic disorders, cerebral angiopathies, hematologic disorders, and cerebral vein thrombosis. Causes exclusive to pregnancy are eclampsia, choriocarcinoma, and amniotic fluid embolism. Although cerebral ischemic disease can occur in either the arterial or venous system, approximately 75% of occlusive cerebral disease occurs on the arterial side.

Cerebrovascular accidents involving subarachnoid hemorrhage or intraparenchymal hemorrhage similarly occur at a rate of 1 in 20,000 births. These events usually are the result of aneurysms or arteriovenous malformations. The most common aneurysm is the saccular (berry) variety, which protrudes from the major arteries in the circle of Willis, particularly at its bifurcations. Aneurysms have an increasing tendency to bleed as the pregnancy progresses, likely due to changes in hemodynamic factors. Rupture of arteriovenous malformations has been found to occur evenly throughout gestation. No consensus has been reached regarding the increased frequency of bleeding from either an aneurysm or arteriovenous malformation during pregnancy or the immediate postpartum period. Rupture of the malformation appears to be more frequent during pregnancy. Eclampsia can lead to cerebral hemorrhage when elevated blood pressures lead to vasospasm, loss of autoregulatory function, and rupture of the vessel wall.

Clinical Findings

Headaches, visual disturbances, syncope, and hemiparesis are among the most common presenting findings. The pattern of clinical signs and symptoms generally allows recognition of the area of the brain involved. Computed tomography (CT) scan and magnetic resonance imaging (MRI) can be used in pregnancy to increase the delineation of cerebrovascular involvement. Arteriography is considered definitive if surgical intervention is being considered because arteriography can more precisely localize the involved area. Because coagulopathies can also cause intracranial bleeding or may be secondary to the cerebrovascular lesion itself, a coagulation profile should be performed. Additionally, antinuclear antibody (ANA), lupus anticoagulant, factor V Leiden, homocysteine, anticardiolipin, proteins C and S, antithrombin III, and plasminogen levels should be considered with thrombotic cerebral events.

Treatment

The treatment of ischemic or hemorrhagic cerebrovascular disease is best managed supportively; however, surgery is indicated for treatment of some aneurysms and arteriovenous malformations. Anticoagulation with heparin may be required depending on the etiology of the infarction; tissue plasminogen activator is relatively contraindicated in pregnancy, but it has been used successfully according to several case reports. Normalization of blood pressure, adequate respiratory support, therapy for metabolic complications, and treatment of coagulopathies or cardiac abnormalities are crucial. Dexamethasone 10 mg intravenously initially, followed by 5 mg every 6 hours for 24 hours, may decrease cerebral edema and be of some assistance prior to surgery or in recovery. Additionally, hyperventilation, mannitol infusions, phenobarbital coma, and intracerebral pressure monitoring may be helpful with severe cerebral edema. Once the patient's condition has been stabilized, physical therapy and rehabilitation should begin as soon as possible.

Appropriate surgery for aneurysms and arteriovenous malformations should be performed with the pregnancy undisturbed unless fetal maturity allows for caesarean birth just prior to the neurosurgical procedure. On the other hand, inoperable lesions during pregnancy are managed by pregnancy conservation until fetal maturity is sufficient to allow abdominal birth. Once a lesion has been surgically corrected, vaginal delivery can be attempted depending on the practitioner's comfort level. However, the second stage of labor should be modified by regional anesthesia and forceps delivery to reduce cerebral pressures associated with the Valsalva maneuver.

Prognosis

The percentage of patients with venous occlusion who recover from the initial episode without neurologic sequelae during rehabilitation equals that of patients with arterial occlusion. Thrombosis of the superior sagittal sinus is a rare complication. Its incidence is increased in pregnancy, and it has a high mortality rate of approximately 55%.

If the cerebral hemorrhagic disorder is operable, the prognosis is favorable, with few long-term neurologic deficits. In inoperable lesions or when severe maternal cerebral hemorrhage has occurred, the prognosis—although unfavorable—is better for those with aneurysms than for those with arteriovenous fistulas. If a neurosurgical procedure is performed during pregnancy, the fetus usually is not adversely affected, despite the induced hypotension that is often necessary. The prognosis for the mother and fetus is the same as that in a normal gestation once the condition has been corrected.

Cerebral Neoplasms

Essentials of Diagnosis

• The clinical manifestations are generally characterized by a slow progression of neurologic signs with evidence of increased intracranial pressure and headache.
• CT or MRI of the brain reveals a mass lesion within the skull.

Pathogenesis

Cerebral neoplasms occur primarily at the extremes of life; thus, primary cancer or even metastatic tumors are uncommon during the childbearing years. Although brain tumors are not specifically related to gestation, meningiomas, angiomas, and neurofibromas are thought to grow more rapidly with pregnancy. Of the primary neoplasms (half of all brain tumors), gliomas are the most common (50%), with meningiomas and pituitary adenomas accounting for 35%. Of the metastatic cerebral tumors, lung and breast tumors account for 50%. Choriocarcinoma commonly metastasizes to the cerebrum.

Clinical Findings

Symptoms & Signs

The clinical manifestations, although dependent on the type and location of the tumor, are generally characterized by a slow progression of neurologic signs with evidence of increased intracranial pressure. One of the most frequent signs is headache, which must be differentiated from that occurring in tension and in vascular or inflammatory conditions. Pain that is not relieved by analgesics or muscle relaxants (as a tension headache would be), the absence of a history of migraine headaches, and the lack of signs of infection or meningeal inflammation all point to increased intracranial pressure as a possible cause of the headache. Tumors in the pituitary gland or occipital region may be associated with visual deficits. Other presenting signs and symptoms include nausea, vomiting, double vision, vertigo, seizures, and altered mental status.

Imaging Studies

CT scan and MRI are of greatest assistance in revealing space-occupying lesions. MRI is generally preferred during pregnancy, although fetal radiation exposure from CT of the brain is minimal.

Laboratory Findings

If the cerebrospinal fluid glucose and protein levels are normal, inflammation or infection of the central nervous system is unlikely. Similarly, an increase in the cerebrospinal fluid human chorionic gonadotropin (hCG) titer raises the suspicion of metastatic choriocarcinoma. Pleocytosis may be present with cerebral neoplasia, but usually it is lymphocytic or monocytic, without an increase in the number of polymorphonucleocytes. Finally, failure to find blood or xanthochromic fluid in the cerebrospinal fluid helps in differentiating a neoplasm from a hemorrhagic lesion, unless the tumor has undergone hemorrhagic necrosis.

Treatment

The treatment of cerebral neoplasms during pregnancy depends on the type of tumor, its location, and the stage of gestation. Anticonvulsants should be used only if seizures have occurred. Steroids can be used to decrease intracranial pressure causing focal neurologic signs or headaches. Deterioration of the patient's status in early pregnancy should prompt a discussion about the risks of continuing the pregnancy. Nevertheless, most such pregnancies can be carried through successfully. During the second trimester, treatment with surgery, chemotherapy, or directed radiation can be started and the pregnancy allowed to continue. Later in gestation, maternal treatment can be delayed until delivery. Pituitary adenomas can be treated with bromocriptine if visual problems or disabling headaches occur.

Prognosis

Brain tumors usually do not affect pregnancy or the fetus unless the neoplasm leads to early delivery or maternal death. When diagnosed in the second or third trimester, the outcome for the fetus is excellent, even though therapy may be initiated during the course of the pregnancy.

Migraine Headache

Essentials of Diagnosis

• Headache attacks that last 4–72 hours in duration.
• Headaches may be associated with nausea or vomiting, photophobia, or phonophobia.
• Headaches may also be accompanied by focal neurologic symptoms (“aura”).

Chronic migraine headaches decrease during pregnancy in 50–80% of affected patients. Women with classic migraine (migraine with aura) may experience their initial onset during pregnancy.

Clinical Findings

Most often, the patient has a history of migraine headaches, which usually are described as “pounding” and may settle in the eyes, the temporal region, or occiput. The pain can be unilateral or bilateral. Frequently, migraines are associated with gastrointestinal complaints (eg, nausea, vomiting, and diarrhea) or with systemic symptoms (eg, vertigo or syncope). Light sensitivity (photophobia) and noise sensitivity (sonophobia) often accompany the pain. An aura may or may not precede the headache. Aura is characterized by focal neurologic symptoms, most commonly visual changes, that are fully reversible. Sleep often aborts the attack.

The diagnosis of migraine headaches usually is made clinically by the characteristics of the pain, associated symptoms, event triggers (see below), and absence of neurologic signs. Tension and caffeine withdrawal headaches typically are associated with bandlike pressure pain. If vertigo is associated with migraine headaches, it is important to rule out Ménière's disease (labyrinthitis). In the latter, vertigo is accompanied by tinnitus, a fluctuating sensorineural hearing loss, and nystagmus. If vertigo is associated with ataxia of gait, it is almost always central in origin, in which case head trauma, brain tumors, seizure disorders, and multiple sclerosis must be excluded. Syncope (fainting) may occur with migraine or vascular headaches and is common during pregnancy. However, when syncope occurs with migraine headache, it usually is associated with vertigo. Rarely, ocular nerve palsy develops in association with migraine headaches; the third cranial nerve is the most commonly involved, and the palsy usually disappears with abatement of the migraine. It is important to visualize the optic disk to ensure that cerebrospinal fluid pressure is not increased. In cases where the disk borders are not sharp, pseudotumor cerebri or an intracranial mass lesion should be considered first.

Treatment

Treatment of migraine headaches initially includes identification of any trigger that precipitates attacks, followed by avoidance of those triggers. Common triggers for some migraine patients include missing meals, stress, aged cheeses, sausage or other nitrates, chocolate, citrus fruit, wine and other sulfites, monosodium glutamate, strong odors, lights or glare, and inadequate sleep. When this environmental manipulation fails to control migraines, drug therapy is indicated. Migraine therapy is either abortive or prophylactic depending on the frequency and severity of attacks. Preferred abortive medications during pregnancy include acetaminophen, acetaminophen and codeine or other narcotics, and magnesium. The following are more effective migraine abortive medications but are not preferred during pregnancy: butalbital, isometheptene, caffeine, aspirin, naproxen, ibuprofen, and triptan drugs (eg, sumatriptan). The nonsteroidal anti-inflammatory drugs should not be used for prolonged periods and should be avoided in the third trimester because of possible oligohydramnios or premature closure of the ductus arteriosus. Prophylactic medications should be instituted if abortive therapy is only partially effective and if disabling migraines are occurring more than once per week. Options include beta mimetic blockers, low-dose tricyclic antidepressants, calcium channel blockers, magnesium, riboflavin, and topiramate. Valproic acid or divalproate should be avoided in pregnancy.

Prognosis

Migraine headaches usually have no deleterious long-term effect on mother or fetus, and treatment of acute exacerbation usually is successful.

Epilepsy & Seizure Disorders

Essentials of Diagnosis

• Epilepsy is defined as 2 or more unprovoked seizures.
• Seizures associated with epilepsy can be generalized convulsive (tonic-clonic or grand mal), complex partial (loss of awareness or staring with mild motor movements), focal motor or sensory (jacksonian with no loss of awareness), absence or petit mal (brief eye blinking with no postictal confusion), myoclonic jerks, or auras of déjà vu, fear, or abnormal odors.

The onset of epilepsy is not increased during pregnancy. More than 95% of patients who have seizures during pregnancy have a history of epilepsy or have been receiving anticonvulsant therapy. Patients whose seizures are adequately controlled are not likely to experience a deterioration of their condition during pregnancy. On the other hand, patients who have experienced frequent and uncontrolled seizures before pregnancy likely will experience the same pattern, particularly during early pregnancy.

Clinical Findings

A detailed history from the patient and observers helps to distinguish true seizures from other forms of loss of consciousness, such as syncopal episodes, hysteric attacks, or hyperventilation. These problems do not commonly involve a postictal confusional state, nor do they usually involve loss of bladder or bowel control or tongue biting. Non–central nervous system causes, such as hypoxia, hypoglycemia, hypocalcemia, and hyponatremia, also must be excluded. Finally, seizures may result from drug withdrawal, medications, or exposure to toxic substances; thus, appropriate physical examination and screening for toxic substances are important in patients suffering an apparent first seizure during pregnancy.

Detailed neurologic workup is required in patients whose first seizure occurs during pregnancy. Electroencephalogram (EEG), CT scan with shielding or MRI, and lumbar puncture are useful for detailing the cause of the seizure and are not contraindicated during pregnancy. In established epilepsy, EEG is useful to confirm the type of epilepsy and therefore provide the appropriate drug therapy.

Treatment

Treatment of epilepsy should consist of the medication that has been most beneficial for the patient and at the lowest possible dose to maintain seizure control with some caveats. Some antiepileptic agents are more likely to cause birth defects than are others, and attempts to change medications should be made prior to conception.

During pregnancy, anticonvulsant levels change as a result of decreased protein binding, increased plasma volume, and alterations in the absorption and excretion of drugs. In addition, lamotrigine, phenytoin, phenobarbital, and carbamazepine have an increased plasma clearance that probably is related to high hepatic metabolism. These factors most often lead to low antiseizure plasma levels. Noncompliance, morning sickness, and hyperemesis gravidarum are other reasons for low drug levels. Therefore, blood level measurements of antiseizure medications are used to monitor and maintain a therapeutic range. Levels should be checked at least each trimester and prior to delivery. More frequent monitoring may be needed. Because of decreased protein binding, serum-free drug levels rather than routine serum levels will be more accurate. Breakthrough seizures can result from poor sleep in the third trimester because the patient cannot obtain a comfortable sleeping position. For patients with refractory seizures while taking medication, an attempt should be made to maximize the dosage and the level of 1 medication before switching or adding another agent.

In patients with status epilepticus, control of seizures is mandatory for the safety of the patient and fetus. Lorazepam 2 mg intravenous (IV) push followed by 2 mg IV every minute up to 0.1 mg/kg is first-line treatment. If seizures continue, phenytoin 20 mg/kg slow IV push at a rate of 50 mg/min or fosphenytoin 20 phenytoin equivalents/kg IV at 150 phenytoin equivalents/min can be given intravenously. General anesthesia can be considered if seizures persist. In these cases, cerebral edema almost invariably is present and may be reduced with dexamethasone, mannitol, or hyperventilation. Many cases of status epilepticus in pregnancy are the result of inadequate treatment with antiepileptic drugs, abrupt withdrawal of phenobarbital or benzodiazepines, noncompliance, or failure to monitor serum levels.

Antiepileptic drugs and seizures can negatively affect a fetus. Seizures can cause maternal and fetal injury, spontaneous abortion, premature labor, and fetal bradycardia. All antiepileptic drugs cross the placenta, equilibrate rapidly in cord blood, and may have teratogenic effects. The risk of anomalies among infants exposed to anticonvulsants is approximately 2-fold greater than in the general population. The previous thinking that women with seizure disorders had an increased risk of fetal malformations even without exposure to anticonvulsant medication has been disproved. The most common defects fall into 2 categories: major and minor malformations. Major malformations include orofacial clefts, neural tube defects, and congenital heart disease. Minor malformations consist of craniofacial anomalies (eg, low-set ears, widely spaced eyes), short neck, and hypoplastic fingernails. The fetal hydantoin syndrome (associated with phenytoin) was the first described association between antiepileptic drugs and birth defects. It affects 3–5% of exposed offspring. It is characterized by mental retardation, small for gestational age size, craniofacial anomalies, and limb defects. A milder phenytoin-associated syndrome may be present at a greater frequency (8–15%) but is detectable only by careful assessment during the first 3 years of life. Use of trimethadione in pregnancy has been abandoned given the high rate of anomalies (up to 30%) associated with intrauterine trimethadione exposure.

The teratogenic potential of specific antiepileptic agents has been the subject of much debate. Prospective pregnancy registries have been established around the world to clarify the risks. The older anticonvulsants—ethosuximide, carbamazepine, phenobarbital, valproic acid, primidone, and phenytoin—are all pregnancy category D because of known increased risk of birth defects in exposed fetuses. Neural tube defects are most common with carbamazepine (0.5–1%) and valproic acid (1–2%). The North American AED (antiepileptic drug) Pregnancy Registry has determined that the overall major malformation rate with exposure to valproic acid is 10.7%. Other pregnancy registries and studies have found the teratogenic potential of valproic acid increases with doses higher than 1000 mg/d or levels higher than 70 μg/mL. Besides neural tube defects, hypospadia, polydactyly, and kidney and heart malformation have been associated with valproic acid, so its use during pregnancy should be avoided if possible. Phenobarbital, previously believed to be safe during pregnancy, has a malformation rate of 6.5%, which is slightly higher than the approximately 3% rate of other antiepileptic drugs such as carbamazepine, phenytoin, and lamotrigine. Less human data on the newer antiepileptic drugs are available, with the exception of lamotrigine and oxcarbazepine. All newer antiepileptic drugs are category C, but more data are needed before they can be deemed safe.

Treatment with 2 or more antiseizure medications approximately doubles the risk for malformations.

Women with existing seizure disorders who are contemplating pregnancy should be tested to determine whether they still require anticonvulsant therapy—particularly if anticonvulsants were started during childhood or if the patient has been seizure-free for 2–5 years. If a pregnant woman requires seizure medication, she should be informed of the likelihood of fetal anomalies associated with each drug, and a discussion regarding the risks and benefits of attempting to switch to a different or safer drug, if available, should ensue. The patient should be counseled regarding folic acid supplementation (4 mg/d) starting at least 3 months preconceptionally to possibly reduce the chance of neural tube defects.

If the patient is taking an antiseizure medication metabolized by the P450 liver enzyme system, she should take vitamin K 10 mg/d from week 36 until delivery to prevent hemorrhage in her baby. This is in addition to the intramuscular vitamin K the infant will receive after delivery.

Antiepileptic drugs pass into the breast milk to varying degrees, depending on protein-binding characteristics. The benefits of breast milk usually outweigh the small risk from the medication to the infant. If a breastfed infant is too sedated and not feeding well, presumably from the medication in the breast milk, breastfeeding should be suspended and supplanted with formula.

Mothers with frequent seizures must be counseled on seizure and infant safety. Sponge baths instead of tub baths and use of a strap on the changing table will decrease potential injury to an infant in case of a maternal seizure.

Multiple Sclerosis

Essentials of Diagnosis

• Multiple sclerosis is a clinical diagnosis made on the basis of 2 or more clinically distinct episodes of central nervous system dysfunction.
• The diagnosis may be supported by findings on laboratory or imaging studies such as MRI.

Pathogenesis

Multiple sclerosis is an autoimmune demyelinating process in the white matter of the central nervous system. It affects women twice as often as men and usually has its onset between the ages of 20 and 40 years. People in the Northern Hemisphere are more commonly affected. The cause is not known, but possible etiologies include environmental, viral, and genetic.

Clinical Findings

The 2 patterns of disease are relapsing remitting and primary progressive. Findings include weakness in the extremities, sensory loss, difficulty with coordination, and visual problems. Increased reflexes, spasticity, and bladder control problems develop over time. Myasthenia gravis should be ruled out with an anticholinesterase (neostigmine) challenge and acetylcholine receptor antibody testing. Guillain-Barré syndrome should be ruled out if the patient has a history of recent viral infection.

Laboratory tests and imaging should be performed to rule out other possible etiologies. Serum should be checked for vitamin B12, Lyme and HTLV-1 (human T-cell lymphotropic virus type 1) titers, erythrocyte sedimentation rate (ESR), ANA, and rheumatoid factor. An MRI would reveal lesions (plaques) in the white matter of the brain and spinal cord. Active plaques would enhance with contrast materials. An elevated level of immunoglobulin (Ig) G in the cerebrospinal fluid is virtually diagnostic.

Treatment

Treatment options include interferon beta-1a, interferon beta-1b, and glatiramer. These medications decrease relapse rates, decrease disease activity as measured by serial MRI, and decrease disease progression. The interferon beta-1b and -1a multiple sclerosis trials showed an increased rate of spontaneous abortions of exposed fetuses. Although the increased rate did not reach statistical significance, there is good reason for caution. In patients planning to become pregnant, interferon treatment should be switched to glatiramer until conception and then discontinued once pregnancy is established. Symptomatic treatment of spasticity, pain, fatigue, and bowel and bladder dysfunction will be required as well. IV immunoglobulin (IVIG) has been used in the postpartum period to decrease the risk of exacerbation with some success. Short courses of corticosteroids may be helpful if the patient has optic neuritis or other disabling relapse.

Prognosis

The disease is characterized by exacerbations and remissions, with 70% of patients experiencing slow progression over a number of years. Pregnancy does not appear to exert any deleterious effect on multiple sclerosis and may improve the rate of exacerbation. The risk of exacerbations is increased in the first 3 months postpartum. Family planning should be discussed because of the progressive nature of the disease. If so desired, families should be completed or started as soon as possible.

Myasthenia Gravis

Essentials of Diagnosis

• Myasthenia gravis is an autoimmune disorder characterized by antibodies to acetylcholine receptors at the neuromuscular junction.
• It is characterized by muscle weakness, particularly with repetitive movement.

Myasthenia gravis is a chronic disorder of the neuromuscular junction of striate muscles as result of acetylcholine receptor dysfunction. Antibodies to acetylcholine receptors usually are present. It occurs more commonly in females than in males, and its peak occurrence is in the third decade of life. It is characterized by abnormal voluntary muscle function with muscle weakness after repeated effort. Although some cases of myasthenia gravis appear to be hereditary, most adult cases appear to be acquired.

Clinical Findings

The most common symptom is easily fatigued small muscles, most frequently the ocular muscles, which results in double vision. Weakness usually increases as the muscles are used repeatedly. Patients who may not have noticeable symptoms in the morning may be easily diagnosed in the afternoon. Difficulties with swallowing and speech are not uncommon, and the facial muscles are almost always affected.

The diagnosis can be confirmed by administering edrophonium (Tensilon; a total of 10 mg, consisting of 2 mg followed by 8 mg 45 seconds later) to assess improvement in muscular weakness. A radioimmunoassay for the acetylcholine receptor antibody can be performed. Repetitive nerve stimulation would show a decrement >15% in a person with the condition.

One-third of patients with myasthenia gravis experience exacerbation during pregnancy, one-third do not experience a change in disease, and one-third experience remission during pregnancy. The disease does not affect uterine activity because the uterus consists of smooth muscle. The length of labor is not affected. However, an assisted second stage might be considered because of maternal fatigue. Exacerbations are most common during the postpartum period. Placental transfer of acetylcholine receptor antibodies can occur, so the fetus should be monitored at frequent intervals during pregnancy with fetal kick counts and ultrasound. A rare finding in neonates is arthrogryposis multiplex congenita, congenital contractures secondary to lack of movement in utero. Antibodies may affect the fetal diaphragm and lead to pulmonary hypoplasia and polyhydramnios. From 12–15% of newborns will be affected with transient myasthenia gravis. The mean duration of neonatal symptoms is 3 weeks.

Treatment

Treatment with anticholinesterases (eg, neostigmine) is the same as in the nonpregnant state, although dosages must be administered more frequently during pregnancy. Other treatment options include thymectomy, steroids, plasma exchange, and IVIG. During labor, anticholinesterases should be administered parenterally rather than orally. Parenteral and regional anesthesia is not contraindicated in labor. Curare-like agents (eg, aminoglycoside antibiotics) and magnesium sulfate, as well as the older general anesthetics such as ether and chloroform, should be avoided. Women taking anticholinesterase drugs are advised not to breastfeed.

Spinal Cord Disorders

Spinal cord lesions that are caused by trauma, tumor, infection, or vascular disorders usually do not prevent conception. Diagnosis and therapy should be performed without regard to pregnancy. In general, pregnancy coexisting with trauma to the spinal cord from any cause, even paraplegia, proceeds unremarkably with the exception of an increased frequency of urinary tract infections and sepsis from pressure necrosis of the skin. Fetal growth usually is unimpeded even though initial maternal weight is frequently <100 lb because of muscular wasting. Generally labor proceeds without evidence of fetopelvic disproportion. Women whose paraplegia is related to anterior horn cell damage or to cord lesions below the tenth thoracic level have appropriate perception of labor contractions and may require analgesia or anesthesia. In most patients, rapid, painless labors are the rule, with the only abnormality being a prolonged second stage because of decreased muscular effort. Paraplegic patients may develop autonomic hyperreflexia during labor due to loss of central regulation of the sympathetic nervous system below the level of the lesion. This is best managed with an epidural, continuous monitoring of the cardiac rhythm and blood pressures, antihypertensives, and an assisted second stage.

Disorders of Cranial Nerves

Palsies of the facial nerve due to inflammation are called Bell's palsy. Although patients may complain of paresthesia over the area of paralysis, this is strictly a motor disorder involving paralysis of the muscles of facial expression on 1 side that are innervated by the facial nerve. Given that approximately one-fifth of cases of Bell's palsy occur during pregnancy or shortly thereafter, it has been suggested that pregnancy increases the frequency of this disorder, although viral infections also have been causally related. Treatment with corticosteroids (prednisone 40–60 mg/d) and acyclovir is helpful if given within 1 week of onset. However, Bell's palsy usually is self-limited. Because the patient is unable to blink or close her eye on the affected side, corneal damage will occur if frequent eye drops and nighttime closure of the eye with patches and lubrication are not instituted. Rarely is surgical decompression of the nerve indicated.

Guillain-Barré Syndrome

Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy often related to an upper respiratory or gastrointestinal infection or recent immunization. Rapid onset of weakness occurs, most frequently in an ascending pattern involving the extremities first, then respiratory muscles and face. Hospitalization is required, and supportive treatment aimed at preventing respiratory failure is mandatory. If the vital respiratory capacity falls to 800 mL or below, tracheostomy should be performed. Plasmapheresis or IVIG is the treatment of choice to shorten the course of illness. Most patients progress normally through pregnancy and deliver at term, so abortion is not mandated. On the other hand, if respiratory paralysis occurs near term, caesarean delivery may be indicated to improve ventilation.

Peripheral Neuropathies

Carpal tunnel syndrome is a neuropathic disorder related to median nerve compression by swelling of the tissue in the synovial sheaths at the wrist. Symptoms usually are limited to paresthesia over the thumb, index, and middle fingers and the medial portion of the ring finger. Most commonly, symptoms are noted at night and usually are best treated conservatively with elevation of the affected wrist and splinting. The syndrome usually abates postpartum. Surgery and corticosteroids are rarely indicated.

Compression of the femoral or obturator nerve can occur from retraction at the time of caesarean delivery or hysterectomy, but it is most commonly related to pressure of the fetus just before and during vaginal delivery.

Femoral nerve palsy results in weakness of the iliopsoas and quadriceps muscles and sensory loss over the anterior thigh. Obturator nerve palsy is characterized by adduction weakness of the thigh and minimal sensory loss over the medial aspect of the affected limb. Peroneal neuropathy reveals footdrop and weakness on dorsiflexion of the foot, occasionally with paresthesia in the foot and second toes. This disorder usually appears 1–2 days postpartum and may be related to prolonged episiotomy repair and to pressure on the nerve from knee stirrups. Women at risk include small women with relatively large babies, those who have had midforceps rotations, and those who have had prolonged labor, especially with abnormally large infants (owing to compression of the L4–5 lumbosacral nerve trunk). The prognosis is excellent with conservative therapy, but occasionally a short leg brace is necessary.

Brachialgia or the thoracic outlet syndrome occurs when the brachial plexus and subclavian artery are compressed by the clavicle and first rib. Occurrence in pregnancy is increased because of the greater weight of the breasts and abdomen. The pain is referred to the lateral aspect of the hand and forearm, although motor symptoms are rare. Blanching of the fingers and exacerbation of symptoms when the hands are elevated are diagnostic. The syndrome usually is self-limited; posture instruction and strengthening of shoulder suspension muscles are helpful. Surgical removal of the rib is very occasionally necessary (as in the nonpregnant patient).

Herniation of intervertebral disks occurs more commonly in the lumbar than the cervical region. There are both motor and sensory findings along the distribution of the sciatic nerve. It is limited to 1 extremity and must be differentiated from more serious disorders such as spinal cord tumors and hemorrhage. Diagnosis usually can be made by physical examination and history. MRI of the spine is the best diagnostic modality if needed. Conservative management with bedrest and physical therapy is helpful. The process should cause no problems during pregnancy or vaginal delivery unless the patient has cervical disk disease. In that event, caesarean delivery is advised to prevent herniation and paralysis. Surgical correction should be avoided during pregnancy if possible.

Rheumatoid Arthritis

Essentials of Diagnosis

• Inflammatory arthritis involving 3 or more joints
• The presence of certain biomarkers on serum testing such as rheumatoid factor, elevated C-reactive protein, or elevated ESR
• Most patients with rheumatoid arthritis in pregnancy diagnosed prior to pregnancy

Pathogenesis

Rheumatoid arthritis is a chronic autoimmune disease characterized by symmetric inflammatory synovitis. The prevalence in North America is 0.5–3.8%, and it occurs 3 times more frequently in women.

Clinical Findings

Symptoms of rheumatoid arthritis are insidious, with a prodrome of fatigue, weakness, generalized joint stiffness, and myalgias preceding the appearance of joint swelling. The diagnosis can be made when the patient is found to have inflammatory arthritis involving 3 or more joints; the patient has abnormal biomarkers such as rheumatoid factor, elevated C-reactive protein, or elevated ESR, the duration of symptoms is more than 6 weeks; and other diseases have been excluded. Laboratory findings are mild leukocytosis, elevated ESR (which may not always reflect the activity of the disease), and a positive rheumatoid factor (in the majority of patients).

Treatment

Treatment consists of rest, anti-inflammatory drugs, splints, physical therapy, a well-balanced diet, and adequate movement of all joints. Cyclooxygenase (COX)-1 and COX-2 inhibitors should be avoided in pregnancy. If they are used, therapy should be limited to short courses prior to 32 weeks' gestation to avoid premature closure of the ductus arteriosus, and the amniotic fluid index should be followed for oligohydramnios. Low-dose oral corticosteroid therapy, hydroxychloroquine, or sulfasalazine can be substituted safely for COX inhibitors. Tumor necrosis factor (TNF)-α inhibitors, penicillamine, gold, and methotrexate should be avoided. Methotrexate should be stopped 1–3 months prior to conception, and patients on leflunomide should wait to conceive until serum concentrations are undetectable. Symptoms improve during pregnancy in approximately 75% of women. However, many patients relapse within 6 months postpartum. The activity of the disease during pregnancy is best followed by assessment of duration of morning stiffness and the number of joints involved. Levels of Ro/SS-A and La/SS-B antibodies should be obtained to determine the fetal risk for complete heart block. In cases of severe postpartum exacerbation, early termination of breastfeeding may be necessary in order to allow the full range of pharmacologic therapy, including TNF-α inhibitors.

Prognosis

The course is variable and unpredictable, with spontaneous remissions and exacerbations.

Systemic Lupus Erythematosus

Essentials of Diagnosis

• Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a wide spectrum of disease manifestations.
• The diagnosis can be made when 4 of the following criteria are present: malar rash, discoid rash, photosensitivity, oral ulcers, serositis, renal disorders, neurologic disorders, hematologic disorders (hemolytic anemia, leukopenia, thrombocytopenia), immunologic disorders (anti-DNA, anti-Sm, false-positive Venereal Disease Research Laboratory [VDRL] test), or an abnormal ANA titer.
• As with other autoimmune diseases in pregnancy, the diagnosis of SLE is usually made prior to pregnancy.

Pathogenesis

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect many different organ systems. It is of interest to obstetricians because it affects women more commonly than men (10:1), and the women it affects tend to be of reproductive age. The cause of SLE is unknown, and the clinical course is variable. Common serologic markers of SLE are present 5 years before the diagnosis is made in up to 50% of women. Complications of pregnancy characteristic of SLE may precede the clinical diagnosis by many years as well.

Clinical Findings

The diagnosis can be made when 4 of the following criteria are present: malar rash, discoid rash, photosensitivity, oral ulcers, serositis, renal disorders, neurologic disorders, hematologic disorders (hemolytic anemia, leukopenia, thrombocytopenia), immunologic disorders (anti-DNA, anti-Sm, false-positive Venereal Disease Research Laboratory [VDRL] test), or an abnormal ANA titer.

Differential Diagnosis

The differential diagnosis includes rheumatoid arthritis, drug-induced SLE syndromes, polyarteritis, chronic active hepatitis, and, late in pregnancy, preeclampsia. Common symptoms at presentation in pregnancy are malaise, fever, myalgias, and weight loss.

Complications

Considerable controversy exists about the effects of pregnancy on SLE and vice versa. Most patients who become pregnant while their SLE is not active for at least 6 months seem to have few problems except for a 2- to 3-fold increased risk of superimposed preeclampsia and fetal growth restriction; the risk of a lupus flare is 20%. Women with active SLE are at very high risk for superimposed preeclampsia (60–80%), fetal growth restriction, preterm birth, and lupus flare (50–80%). Women with preexisting renal disease frequently have some deterioration in renal function, but it is irreversible in only 10% of cases.

Treatment

Management during pregnancy includes a careful history, physical examination, and laboratory evaluation. A history of prior spontaneous abortions or fetal losses should be elicited. The history should note the manifestations of SLE in the past; determination of the severity of disease activity is important in anticipating pregnancy complications. Although the fertility rate of patients with SLE is normal, patients have a higher percentage of total fetal losses. This may be associated with the presence of antiphospholipid antibodies. Physical examination should focus on signs of active disease. Laboratory evaluation should include a complete blood count, serum chemistries, and liver function tests. ANA (if the diagnosis is not previously confirmed), double-stranded DNA, urine protein, C3, C4, and CH50 tests should be obtained. Subsequent changes in these values may herald a flare of lupus nephritis. The results of the SS-A, lupus anticoagulant, anticardiolipin antibody, and anti-β2 glycoprotein 1 tests should be known. The presence of SS-A is associated with neonatal lupus, manifested by cutaneous lesions or congenital heart block. Anticardiolipin antibody and lupus anticoagulant anti-β2 glycoprotein 1 tests are associated with antiphospholipid antibody syndrome (APS), which predisposes patients to thromboembolic events, fetal death, fetal growth restriction, and preeclampsia. Prophylactic treatment with daily baby aspirin and heparin is recommended when APS is diagnosed. Diagnostic criteria require a clinical event (as listed earlier) plus a positive lupus anticoagulant result, moderate- to high-titer anticardiolipin antibody (>40 IgG phospholipid units or IgM phospholipid units or >99th percentile for the testing laboratory), or anti-β2 glycoprotein 1 antibodies (IgG or IgM >99th percentile for the testing laboratory). These tests should be positive on 2 occasions 12 weeks apart. Most fetal loss in SLE appears to be due to concomitant APS, which occurs in approximately 30% of patients.

Distinguishing between superimposed preeclampsia in the third trimester and an SLE flare often is difficult. In fact, it is not possible to say with certainty that preeclampsia is not present, but careful consideration can suggest whether an SLE flare is a contributing factor. In a pregnancy remote from term, aggressive empiric therapy of presumed SLE may allow significant prolongation of pregnancy.

Serial ultrasounds for fetal growth and antenatal testing starting at 32–34 weeks should be instituted to ensure fetal well-being. Delivery is often recommended at 39 weeks' gestation. Uterine artery Doppler at midgestation can be used to predict early-onset preeclampsia and fetal growth restriction.

The mainstay of treatment of SLE in pregnancy consists of corticosteroids, hydroxychloroquine, and azathioprine. Corticosteroids appear to be weak teratogens, resulting in 1 extra facial cleft for every 1000 first-trimester exposures. Thereafter, there is a risk of premature rupture of membranes and preterm birth, but usually after 34 weeks' gestation. Corticosteroids also increase the risk for gestational diabetes and maternal hypertension. Medications used to treat SLE that should be avoided during conception and pregnancy include mycophenolate mofetil, cyclophosphamide, methotrexate, and warfarin. Little information on the use of newer agents (eg, rituximab, abatacept) is available. The chance of successful pregnancy outcome for women with SLE has improved dramatically over the years with better understanding of the natural history of the disease and medical therapy in pregnancy.

Scleroderma (Systemic Sclerosis)

Essentials of Diagnosis

• Scleroderma, or systemic sclerosis, is a rare condition that is uncommonly seen in pregnancy.
• It is a systemic disorder characterized by the presence of thickened, hardened skin, circulatory abnormalities, and often involvement of multiple organ systems.

Clinical Findings

Pregnancy in patients with scleroderma is rare because the disorder occurs most frequently in patients beyond reproductive age. Symptoms include malaise, fatigue, arthralgias, Raynaud's phenomenon, and myalgias. The course of the disease appears to improve or remain unchanged during pregnancy. One study did show an increase in preterm births. Pregnancy progresses normally in otherwise stable disease. When scleroderma-related renal disease and/or hypertension are present, pregnancy is at increased risk of being complicated by preeclampsia or malignant hypertension.

Treatment

Treatment options for women with systemic sclerosis in pregnancy include anti-inflammatory and immunosuppressive drugs such as prednisone, hydroxychloroquine, and nonsteroidal anti-inflammatory drugs.