The Nervous System in Pregnancy
James O. Donaldson
Table Of Contents
James O. Donaldson, MD
Diseases of the nervous system can affect every part of the childbearing process from fertility to lactation. Alternatively, pregnancy may provoke or complicate a neurologic condition. Furthermore, maternal neurologic disease may affect the offspring. Compounding this potentially complex clinical problem are the rarity of the more serious problems in anyone's practice, a widely scattered, relatively inaccessible literature, and widely divergent opinions about some subjects, notably epilepsy and anticonvulsants.1 Finally, the investigation and treatment of a neurologic condition may be inhibited appropriately or inappropriately by concern for the fetus.
The best neurologic procedure is a careful history and physical examination by an experienced neurologist. Usually this results in a short list of diagnostic possibilities and limits the questions to be answered by further testing, if needed. Electroencephalography (EEG) and electromyography (EMG) can be performed without risk. Nor does pregnancy per se alter the indications for lumbar puncture.
Pregnancy is not an absolute contraindication to any neuroradiologic procedure, although, depending on the clinical situation, umbar spine films and myelography should be avoided, especially during the first trimester.2 Abdominal lead shields reduce fetal radiation exposure during head and neck filming, including computed tomography (CT) scans, to small amounts from right-angle scatter. If cerebral angiography is indicated during pregnancy, it is usually also indicated to obtain the highest quality images. Thus, transfemoral cerebral angiography is recommended even though brief exposure to abdominal fluoroscopy during catheterization could be avoided by using a brachial artery. CT scanning has supplanted radionuclide brain scans, which should be avoided during pregnancy. The effect of the strong magnetic fields of magnetic resonance imaging (MRI) on human reproduction has not been determined, although no fetal effect was discerned after MRI of the gravid uterus.3
Approximately 0.3% to 0.5% of pregnancies are complicated by the presence of maternal epilepsy. Many of the complex interactions between pregnancy, epilepsy, anticonvulsant metabolism, and effects on the fetus have yet to be delineated. Many clinically important questions remain to be answered.
The effect of pregnancy on epilepsy was not studied before the introduction of bromide therapy in 1857. Before the use of phenobarbital (1912) and phenytoin (1938), approximately equal numbers of patients improved, remained unchanged, or worsened during pregnancy. After the use of effective anticonvulsants but before the routine monitoring of anticonvulsant blood levels, about half worsened. If the daily dosage of anticonvulsants is adjusted regularly to maintain blood levels that are determined to be therapeutic before pregnancy, less than 10% will experience more seizures during pregnancy.
Women with more than one seizure per month when not pregnant can expect worsening during pregnancy. The longer a woman has been seizure free before pregnancy the less likely it is that she will convulse during pregnancy.4 Some women convulse only while pregnant (i.e.. they have true gestational epilepsy).4 Usually these women have focal epilepsy and do not require long-term anticonvulsant therapy. Increased estrogen levels do decrease the seizure threshold for both focal and generalized seizures. The converse is true for progesterone. Both hormones increase during pregnancy. The net effect on the seizure threshold is unpredictable. Nor does a history of perimenstrual worsening of epilepsy predict the effect of pregnancy on fit frequency.
Pregnancy-induced changes in anticonvulsant metabolism is the most important manageable factor affecting the course of epilepsy.5,6 Other factors include compliance with prescribed therapy, excess weight gain due to fluid retention, mild compensated alkalosis, and, during late pregnancy, insomnia.
Usually the dosage of anticonvulsants needed to maintain a previously determined, therapeutic blood level will increase during pregnancy, especially in the second half. Often blood levels are done at monthly intervals during pregnancy, or more frequently if seizures develop. Usually dosage schedules return to the prepregnant levels within 6 weeks, often with major change within the first 2 weeks in the case of phenytoin.7
The apparent clearance of anticonvulsants, simply calculated by dividing daily dose by plasma concentration, increases during pregnancy by a factor of approximately 1.5 for phenobarbital, approximately 2 for carbamazepine, and 2 to 4 for phenytoin. The reasons differ for each drug.8,9 Although phenobarbital induces hepatic catabolism of other anticonvulsants, it is mainly excreted by the kidney. An alkaline urine promotes renal clearance of phenobarbital. The increase in a hypoxide metabolite of carbamazepine during pregnancy suggests that hepatic metabolism is the factor responsible for that drug. For phenytoin, intestinal malabsorption is the major cause and increased parahydroxylation is a secondary cause. Primidone levels decrease because both hepatic and renal clearances increase.
It is generally agreed that trimethadione and its congeners are teratogens for humans. Beyond that the teratogenicity of anticonvulsant drugs is controversial and the literature on the subject, all accumulated since 1963, is a morass. Basically, the risk of fetal malformation due to the presence of maternal epilepsy severe enough to warrant treatment cannot be separated from the risk due to the treatment per se. The incidence of all malformations varies widely from study to study; the incidence in prospective studies may double the rate in retrospective studies. Most studies do not consider other factors, including blood levels of anticonvulsants, maternal age, maternal diabetes, family history, and ethnic origin.
Most studies agree that the risk of harelip, cleft palate, and congenital heart disease, mainly septal defects, is increased twofold to fourfold among the offspring of epileptic mothers who were treated during pregnancy with anticonvulsant drugs.10,11,12 These defects originate around the time a woman misses her second menstrual period and suspects she may be pregnant. The risk of fetal malformation may increase with polytherapy, but then again it may increase owing to the severity of the maternal epilepsy. Even though the risk is higher, the incidence of these defects is still below 20 in 1000 births and does not justify either discouraging an epileptic woman who needs treatment from becoming pregnant or stopping an effective drug regimen.
Phenytoin has been implicated as a cause of orofacial clefts in humans because it is proven to be so in rodents. The development of stubby distal digits and hypoplastic nails and a broad or depressed nasal bridge has also been attributed to anticonvulsants, primarily phenytoin. However, what is referred to by American pediatricians as the fetal hydantoin syndrome is not held to be specific for any anticonvulsant by many others, certainly including European neurologists.
Phenobarbital taken regularly during the first trimester and at other times during pregnancy by nonepileptic women is not associated with an increased incidence of fetal malformations.10 However, it is associated with a higher malformation rate, at approximately the same rate as phenytoin, if the mother is epileptic. Carbamazepine is not a teratogen for rodents, and some reports suggest that the fetal malformations rate may be lower among those whose mothers took other anticonvulsants.13
Ethosuximide is the preferred treatment of fertile young women with classic, three-per-second spike-and-wave petit mal because the alternative effective drug, valproic acid, is associated with a 1% chance of spina bifida and other neural tube defects among infants exposed in utero.14 The data on ethosuximide are sparse, but its track record is much longer. Neural tube defects may be detected in utero by ultrasonography and by determination of α-fetoprotein in amniotic fluid early enough to allow proper counseling concerning induced abortions.15
Management of Pregnancy
Bleeding appears to be the only significantly increased complication during pregnancy, labor, and delivery, based on a case-control study of 3826 deliveries of epileptic women in Norway from 1967 to 1978.16 It is unclear whether or not the risk of toxemia is increased. Dietary supplementation with folic acid is recommended because long-term administration of phenobarbital, phenytoin, and primidone is associated with a macrocytic anemia, which in turn can be associated with third-trimester bleeding.1
Infants exposed in utero to phenobarbital, phenytoin, and primidone may have at birth a coagulopathy due to decreased vitamin K-dependent clotting factors.1,6,17 One study indicates this may be prevented by maternal supplementation with vitamin K1, 20 mg/day orally, for 2 weeks before delivery.18 Infants at risk should be given phytonadione, 1 mg intramuscularly, soon after birth. If bleeding occurs, fresh plasma transfusions will be needed.
Because newborns do not drink much milk, the dose of anticonvulsant drugs a neonate ingests from breast milk is small even if either neonatal drug metabolism is slow (e.g., phenytoin) or the concentration in milk is a high percentage of the serum concentration (e.g., 70% for primidone).9 In some cases, poor suckling and somnolence have been attributed to phenobarbital and primidone in breast milk owing to slow excretion and high maternal blood level. If the concentration of these anticonvulsants in the infant's blood is elevated, early weaning may be considered. In other cases, neonates have experienced a withdrawal syndrome from phenobarbital and primidone characterized by hyperactivity and feeding difficulty while being breast-fed.19
Cerebrovascular disease during pregnancy is a major cause of maternal mortality and morbidity. Often the condition is unusual in some aspect. Clinical judgment of each patient is important because in many instances firm recommendations cannot be made from our current knowledge of the pathogenesis and natural history of the condition.
Eclamptic Hypertensive Encephalopathy
Central nervous system lesions account for at least 30% of eclamptic deaths. The typical gross neuropathologic findings are patches of petechiae in the cortical ribbon of gray matter and compacted small hemorrhages in the subcortex, the corona radiata, the caudate nucleus, the thalamus, and the pons.20 The patches of petechiae and the subcortical “hematomas” are located in border zones between major arterial territories, and particularly in the distribution of the posterior cerebral arteries. Large, deep hematomas also occur. The classic microscopic lesion is a ring hemorrhage about a precapillary or capillary occluded by fibrinoid material. Seizures, cortical blindness, progressive stupor, and coma are easily explained by these lesions.
CT scans can show larger hemorrhages but may not detect the cortical petechiae. Arcuate hypodense bands denoting edema may occur in or adjacent to the basal ganglia and thalamus.12 The EEG of eclamptic women has generalized delta and theta activity, especially in posterior regions, on which may be superimposed epileptiform activity. Cerebrospinal fluid (CSF) pressure may be normal or elevated; CSF protein concentration may be normal or up to 150 mg/dl. Grossly bloody CSF is an ominous sign.
Although toxemia is unique to pregnant women, the cerebral lesions are not, being the manifestations of hypertensive encephalopathy in usually previously normotensive patients. The blood pressure at the time of eclamptic seizure varies; one half of Sheehan's series convulsed with systolic pressure between 160 and 195 mm Hg, and the rest were divided above and below that range.20 In physiological terms the patient's blood pressure has exceeded that patient's upper limit of the autoregulation of cerebral blood flow.1,22 The upper limit is directly dependent on that person's usual blood pressure. Beyond the upper limit, precapillary arteriolar constriction no longer limits the perfusion pressure exerted on the capillary bed, with resultant rupture of capillary walls, exudation of plasma proteins, and diapedesis of erythrocytes. Thus, a ring hemorrhage is formed. The earliest breakthroughs occur in the border zones and act as safety valves to protect the rest of the brain unless even higher blood pressures are generated.
Short of the termination of pregnancy, the treatment of eclamptic hypertensive encephalopathy should decrease blood pressure and arrest seizures.1 The best antihypertensive drug will also be the best prophylactic anticonvulsant medicine. Hydralazine, nitroprusside, and diazoxide lower peripheral resistance with little effect on cerebral vessels. Diazepam, 5 mg to 10 mg intravenously, can control individual seizures without affecting fetal pH, PaCO2, and PaO2. Hypercarbia, which lowers the upper limit of autoregulation and increases cerebral blood flow, must be avoided.
In North America, parenteral magnesium has been a standard treatment of severe preeclampsia and eclampsia, although it is effective against neither hypertensions nor convulsions.23,24 Even among its advocates, there is no agreement on “therapeutic” blood levels. The EEG of normal subjects and of eclamptic women has not been altered by high blood levels of magnesium, 15 and up to 9.2 mEg/liter, respectively.25 Cases of floppy babies due to hypermagnesemia are well documented, although the obstetric and pediatric communities diverge regarding its incidence among offspring of eclamptic women to whom magnesium sulfate was administered.26 The use of magnesium sulfate remains empirical and controversial.
Spontaneous subarachnoid hemorrhage complicates only 1 or 2 in 10,000 pregnancies but accounts for almost 10% of maternal deaths. The main cause of subarachnoid hemorrhage in women under 25 years of age is an arteriovenous malformation. Older women are more likely to have a ruptured berry aneurysm.1,27,28,29 At all ages approximately one third of spontaneous subarachnoid hemorrhages are due to other causes, including bleeding disorders, vasculitis, subacute bacterial endocarditis, sickle cell anemia, and metastatic choriocarcinoma. No cause for bleeding will be found in approximately 5% of pregnant women so afflicted.
Arteriovenous malformations are prone to bleed in the mid-trimester and during delivery. The risk of berry aneurysms rupturing increases during pregnancy, but rarely does initial bleeding occur intrapartum. Rebleeding occurs during the Valsalva maneuver accompanying hard labor.
Unless the woman is in active labor, she should be evaluated and treated as if nonpregnant. CT scans and four-vessel cerebral angiography will be needed to define the lesions. Hypothermia and controlled hypotension can be used safely during pregnancy.29 If the responsible aneurysm or arteriovenous malformation can be surgically cured, pregnancy and delivery can proceed with risk of rebleeding. If multiple aneurysms exist, obliteration of unruptured aneurysms can wait until several months post partum, with the possible exception of aneurysms more than 10 mm in diameter. If curative surgery is not done, women with arteriovenous malformations and most women with aneuryms, certainly primiparous women, are delivered by cesarean section at 38 weeks' gestation.27 If a multiparous woman with a proven pelvis who bled during early pregnancy can avoid bearing down by panting and the administration of regional anesthesia, vaginal delivery is an option.28
The incidence of ischemic arterial vascular events (stroke plus transient ischemic attacks) during pregnancy is approximately equal to the incidence of subarachnoid hemorrhage, but death is rare unless the stroke is symptomatic of systemic disease. Pregnancy increases the risk of ischemic stroke at least by a factor of 3 or 4.30 Most pregnancy-associated ischemic strokes occur in women younger than 30 years because most pregnancies occur before that age. The risk of cerebral ischemia increases with age for pregnant and nonpregnant women.
Approximately 30% of pregnancy-related arterial occlusions occur in each of the second and third trimesters.30,31 Fully one quarter of pregnancy-associated strokes occur in the first post-partum week. Thirty-five percent are occlusions of the middle cerebral artery, which, in the absence of demonstrable atheromatous disease, may be emboli from or through the heart. The internal carotid artery is occluded in 20%. Vertebrobasilar stroke is rare in both nonpregnant and pregnant young women, although 25% to 40% of strokes associated with oral contraceptives are in the posterior circulation.32
Probably only one quarter of pregnancy-associated strokes are arteriosclerotic. Usually those patients can be identified by the coexistence of diabetes mellitus, hyperlipidemia, and chronic hypertension. No cause was found in at least another quarter, but many series were accumulated before the availability of echocardiography, which is required to detect mitral valve prolapse and other intracardiac disorders. The incidence of mitral valve prolapse in patients with pregnancy-associated ischemic events is unknown. Many pregnancy-associated strokes and most fatal ischemic strokes of pregnancy are symptomatic of other conditions, including atrial fibrillation, peripartum cardiomyopathy, subacute bacterial endocarditis, arteritis, sickle hemoglobinopathy, thrombotic thrombocytopenic purpura, and metastatic choriocarcinoma.33,34
Paradoxical cerebral embolism is an often-overlooked diagnosis that can especially follow uterine manipulation and cesarean section.35 Pulmonary emboli may force right atrial pressures to exceed left atrial pressures, thereby opening an anatomically patent but usually functionally closed foramen ovule. Clots may then cross to the left side of the heart and be pumped to cerebral, renal, and peripheral arteries.
The presence of the “lupus anticoagulant” signifies a hypercoagulable state associated with multiple cerebral ischemic events and a high risk of first-trimester miscarriages and second- and third-trimester fetal deaths, thought to be caused by placental vascular thrombosis and placental infarction.36 The lupus anticoagulant has not been associated with abnormal bleeding or subarachnoid hemorrhage. The best therapeutic strategy is an unsettled issue. Corticosteroid therapy is usually combined with either anticoagulation or low-dose aspirin.
Indications for anticoagulation in pregnancy include peripartum cardiomyopathy, deep vein thrombosis and the hypercoagulable state associated with a circulating lupus anticoagulant, and atrial fibrillation. I recommend anticoagulation for unexplained multiple transient ischemic attacks during pregnancy but not for a single episode. Heparin is the preferred anticoagulant during pregnancy.37 It is a large molecule, which does not pass through the placenta. Thus, heparin neither predisposes the fetus to hemorrhage nor causes congenital abnormalities. Warfarin does cross the placenta. It must be avoided during the first trimester owing to its teratogenicity. It is to be avoided late in pregnancy owing to the risk of fetal wastage. Some physicians switch anticoagulants back and forth, using warfarin in the second and third trimesters up to the last month before expected delivery. Others advocate subcutaneous heparin throughout pregnancy.
Abrupt hypotension can selectively infarct the watersheds between the territories of major cerebral arteries. Acute blood loss during delivery may infarct the pituitary gland (Sheehan's syndrome), the optic chiasm, and cerebral border zones.38 Other causes of abrupt hypotension during delivery include amniotic fluid embolism, air embolism, and spinal anesthesia.
Cerebral Venous Thrombosis
Women 3 days to 4 weeks post partum may develop an aseptic thrombosis of cerebral veins and sinuses.31,39,40 Most cases historically called “late postpartum eclampsia” proved to be cerebral venous thromboses.20 For unknown reasons the incidence of this disorder in India is ten times greater than in North America and Europe, where the incidence is estimated to be 1 in 10,000 deliveries.31 Age and parity are indeterminant factors. Labor and delivery are usually uncomplicated. Cerebral phlebothrombosis may coexist with phlebitis in the pelvis and legs.
The usual clinical presentation is an increasingly severe headache preceding focal or generalized seizures, which are followed by stupor, paralysis, and aphasia. The clinical diagnosis is confirmed by angiography. Digital subtraction angiography is an excellent method of studying the venous system. The prognosis is good if the patient lives. CT scans are useful to detect hemorrhagic infarction, which is both a poor prognostic finding and a relative indication to heparin anticoagulant therapy. Anticoagulation in the early puerperium also carries the risk of profuse uterine bleeding.
The natural history of multiple sclerosis is an unpredictable series of relapses that may meld into a chronically progressive course. Thus, counseling the patient and her husband is very difficult. Although most young women with an episodic course and little disability can expect to rear their children with acceptable limitations, the threat of serious disability always lurks. Both parents must make mature, personal decisions.
Most women with uncomplicated multiple sclerosis can be reassured that their disease will have little effect on a pregnancy and vice versa.41,42 In fact, the relapse rate is lower during pregnancy, although it is higher post partum. Interrupting a pregnancy during a relapse will not induce a remission. Women with neurogenic bladders require special attention to prevent infection and minimize bladder dysfunction. Spinal anesthesia during labor is not recommended.
Chorea gravidarum is any chorea or hemichorea acquired during pregnancy. In the era before penicillin it was a feared, relatively common condition almost synonymous with acute rheumatic fever or rheumatic heart disease, usually with a history of Syndenham's chorea. Now it is rare and just as likely to be a manifestation of systemic lupus erythematosus.
Chorea gravidarum usually begins in the first half of pregnancy and for 70% lasts until childbirth; thereafter, it dramatically disappears.43 Women who experience chorea during one pregnancy may or may not have chorea during subsequent pregnancies. The mechanism for the recrudescence of chorea during pregnancy is unknown, although estrogen-induced stimulation of postsynaptic dopamine receptor sensitivity is one leading proposal. Treatment of mild cases consists in rest and sedation. In severe cases, dopamine blockade with haloperidol or a phenothiazine will be needed to prevent hyperthermia and rhabdomyolysis.44
Myasthenia gravis is an autoimmune disease of motor end-plates of striated muscle that is clinically characterized by fluctuating fatigability of eyelids, extraocular muscles, facial and oropharyngeal muscles, and limbs muscles. Young women with the disease often possess the HLA-A8 human leukocyte antigen. Because a fluctuating course is typical of myasthenia gravis, it is not unexpected that the effect of pregnancy on myasthenia gravis varies from pregnancy to pregnancy and is unrelated to the severity of maternal disease. Abortion does not induce a remission. Because almost one half weaken within a few weeks post partum, follow-up visits every 2 weeks for 6 weeks after delivery are recommended. I recommend that women with generalized myasthenia gravis have a thymectomy and allow a year thereafter for their disease to become stable before becoming pregnant. This is arbitrary advice because the relapse rates during pregnancy before and after thymectomy have not been determined. Women with malignant thymomas should be considered for therapeutic abortion because four of five have developed extrathoracic metastases.
Pregnancy alters the treatment of myasthenia gravis in only a few patients.45 Corticosteroids and anticholinesterase therapy are used as if the patient were not pregnant. Pyridostigmine and other quaternary ammonium compounds do not cross the placenta, and negligible amounts are excreted in milk. Thymectomy and plasmapheresis can be performed if necessary. Azathioprine should not be used during pregnancy or by myasthenic women who may become pregnant.
Myasthenia gravis does not cause uterine inertia because the myometrium is unaffected. Lidocaine and other aminoacylamide local anesthetics are recommended because neostigmine and pyridostigmine inhibit the hydrolysis of the procaine family. Magnesium sulfate, given for eclampsia, and magnesium-containing enemas can precipitate a myasthenic crisis.
Approximately one in eight babies of women with generalized myasthenia gravis will develop neonatal myasthenia, a self-limited condition usually lasting about 3 weeks.46 Symptoms may present at birth or up to 4 days thereafter. There is no relationship between any factor in the mother's condition and the development of neonatal myasthenia except probably the antiacetylcholine-receptor antibody titer. Twenty percent of affected infants do not require anticholinesterase drugs. Exchange transfusions can quickly reverse the condition.
Brain tumors of all types may coexist with pregnancy. Each profoundly affects the other. The growth and vascularity of tumors is accelerated during pregnancy.1,47 Probably one factor is the stimulation of estrogen receptors in meningiomas, neurofibromas, and other tumors.48 Most tumors become symptomatic during the second half of pregnancy. Approximately one third of these women die while pregnant or during childbirth. All tumors appear to undergo remission post partum, at least temporarily. Some small acoustic neuromas and meningiomas may recur years later or during subsequent pregnancies.
The management of each case must be individualized and decided only after thorough study. The possibility of an abscess or a metastatic tumor, especially a choriocarcinoma, should not be overlooked. Patients whose tumors are associated with a high mortality rate (i.e., malignant gliomas and almost all infratentorial tumors except some acoustic neuromas) are usually operated on before delivery. More benign tumors are approached several weeks post partum, when a drier surgical field and a reduction in tumor size can be expected. Childbirth is usually by cesarean section for primiparous women. Vaginal delivery can be considered for women with pituitary tumors and for some multiparous women, provided the Valsalva maneuver, which increases CSF pressure, can be avoided.
Interruption of an early pregnancy has been recommended on both therapeutic and elective bases for women with malignant gliomas, certainly those with uncontrollable seizures. Increased intracranial pressure and visual failure are reasons for premature termination of pregnancy in the last 2 months of gestation. In almost all cases it is inadvisable for a woman known to have a brain tumor to become pregnant.
Patients with choriocarcinoma usually present with vaginal bleeding and an enlarged uterus in the months following a molar pregnancy or a miscarriage. However, 15% of cases follow or accompany a normal pregnancy.49 Some cases present as single or multiple “strokes,” intracranial hemorrhage, or solitary mass lesions with or without jacksonian seizures. The chest film usually shows metastases in these instances but may not in 5%. Aggressive treatment with irradiation and chemotherapy has resulted in regression of cerebral metastases.
Most women with pituitary adenomas were infertile owing to hyperprolactinemia until modern intervention with bromocriptine and transsphenoidal pituitary surgery.50,51 Pregnancy-induced growth of prolactinomas may produce headache, visual disturbances, diabetes insipidus, and deficits of other pituitary hormones. Women with microadenomas with diameters less than 10 mm are usually treated with bromocriptine, and those with macroadenomas are usually treated with transsphenoidal surgery and administration of bromocriptine. Microadenomas are less likely (1%–5%) to have symptomatic enlargement during pregnancy than macroadenomas (15%–35%). The visual fields of women with microadenomas are usually followed during pregnancy with bedside techniques. Pregnant women with macroadenomas must have careful visual-field determination by perimetry on a monthly basis. Repeated imaging of the tumor is reserved for those who become symptomatic.
If prolactinomas become symptomatic during pregnancy, bromocriptine may be reinstituted. If this is not successful, surgery and, if the fetus is mature enough, termination of pregnancy are options. Therapeutic decisions are forced by extension of visual-field deficits into nasal sectors and by visual acuity decreasing to less than 20/50.
The most common headache during pregnancy is the muscle contraction/tension headache producing bandlike and exploding persistent pain usually accompanied by tender cervical and shoulder muscles. These headaches may be aggravated by pregnancy-induced postural changes and new or anticipated situational problems and anxiety. They may be a harbinger of severe postpartum depressions. Most are symptomatically treated with common analgesics and muscle massage. Severe, recurrent muscle contraction headaches may prompt psychiatric counseling and prophylactic therapy with a tricyclic antidepressant. The regular use of benzodiazepine tranquilizers cannot be recommended for pregnant or lactating women because these drugs are poorly metabolized by the fetus and neonate.
Classic migraine is a severe, throbbing, often unilateral headache associated with nausea and vomiting that follows a 20- to 30-minute prodromal stage of scintillating scotomata. These headaches are often aggravated by menstruation and oral contraceptives and relieved during pregnancy for most women.52 Acute migraines during pregnancy are usually treated with analgesics and phenothiazine antiemetic. Propranolol, 40 mg to 160 mg daily in divided doses, is effective prophylaxis for frequently recurrent migraine and has been shown acceptably safe during pregnancy.53 Ergot compounds are avoided during pregnancy and lactation.
Headache due to pseudotumor cerebri is usually a retro-orbital pain that may be altered by coughing and changing position. Pregnancy-associated pseudotumor cerebri usually begins in the third to fifth month of pregnancy and lasts about 2 months, but it may persist until the puerperium.54 Women with pseudotumor who become pregnant usually worsen. Obesity is characteristic.
Examination may be normal except for papilledema, although diminished visual acuity and abducens nerve palsy also occur. CT scanning rules out a mass lesion and hydrocephalus. Lumbar CSF pressure is elevated, and commonly CSF protein concentration is less than 20 mg/dl.
Treatment usually consists in repeated CSF drainage and preventing excessive weight gain. Corticosteroids are usually added if visual fields become restricted or visual acuity diminishes. In some cases lumboperitoneal shunting must be considered to prevent blindness.
Bell's palsy, or idiopathic palsy of the seventh cranial nerve, is seven times more prevalent than expected during the third trimester of pregnancy.55 The reason is unknown. It is an isolated phenomenon. Close to delivery the prognosis is excellent for a spontaneous recovery. Earlier in pregnancy a short course of high-dose corticosteroids is indicated for complete facial weakness.
Carpal Tunnel Syndrome
Nocturnal acroparesthesias are a common complaint during pregnancy and are often misdiagnosed as the carpal tunnel syndrome, which is much less common but does occur with increased frequency during the second and third trimesters.56,57 The diagnosis may be confirmed by measurement of motor and sensory median nerve conduction parameters. Because this syndrome spontaneously regresses within a few weeks after childbirth, conservative therapy, with nocturnal splinting with the wrist in mid-position or slightly flexed, is recommended. Only if weakness exists is division of the transcarpal ligament indicated during pregnancy.
Meralgia paresthetica is a nagging stinging pain along the middle third of the lateral thigh that some pregnant women develop, usually around the 30th week of gestation. Obesity and an exaggerated lumbar lordosis stretch the purely sensory lateral femoral cutaneous nerve, probably trapping it against the inguinal ligament. Symptoms resolve spontaneously within 3 months after childbirth.58
The Guillain-Barré syndrome is an idiopathic inflammatory demyelinating polyneuritis of rapid onset in which weakness is more prominent than sensory loss. Areflexia is the rule. The classic laboratory finding is an elevated CSF protein concentration with a normal CSF leukocyte count. Plasmapheresis has been therapeutic if the procedures can be started within days after the onset of neuropathic symptoms. Otherwise treatment consists in preventing complications.
The concurrence of Guillain-Barré syndrome and pregnancy is a coincidence.59 The disease may occur and the patient begin to recover at any time during pregnancy. Labor and delivery are normal. Uterine contractions are unaffected. These apprehensive women require constant reassurance that they will recover and that their infants will not be affected.
Gestational polyneuropathy is symmetrical dying-back axonal neuropathy similar to alcoholic polyneuropathy deficiency and perhaps other nutritional factors. In early pregnancy it may follow hyperemesis gravidarum and be associated with Wernicke's encephalopathy.60 Otherwise it is an insidiously progressive subacute condition. Symptomatic beriberi may recur with successive pregnancies. Treatment consists in large doses of thiamine and other vitamins and an adequate diet. Parenteral thiamine is recommended for a week.
Intrapartum Lumbosacral Plexopathy
Intrapelvic entrapment neuropathies may affect the lumbosacral trunk, the femoral nerve, the obturator nerve, and, rarely, the lateral femoral cutaneous nerve and nerves destined for the sciatic nerve.61,62,63 Cephalopelvic disproportion dystocia and primiparity are common factors. The incidence of these neuropathies has decreased with modern obstetric practices. Also the fernoral nerve may be compressed by self-retaining retractors.
The most common syndrome is postpartum footdrop caused by compression of the lumbosacral trunk composed of fourth and fifth lumbar nerves as it crosses the pelvic brim by the fetal brow. It is unilateral and contralateral to the side on which the vertex presents (i.e., right occiput anterior is equivalent to left brow position). In contrast, unilateral and bilateral fernoral and obturator neuropathies can be caused by the fetal head exerting pressure down in the pelvis on one or both sides. Footdrop may also be caused by the pressure of leg holders on the common peroneal nerve as it passes the fibular head.
In most instances the prognosis is excellent, with full recovery expected within 6 to 8 weeks, because the lesion was neuropractic, (i.e., only the myelin sheath was distorted). Recovery will be slow and perhaps incomplete if axons were crushed. Women who had axonal degeneration probably thereafter should be delivered by cesarean section. Women who had neuropraxis with full recovery may have a trial of labor but should have a cesarean section should dystocia develop.
Exaggeration of the lumbar lordotic curve during the second and third trimesters stresses articulations and produces backache. Obesity, wearing high-heeled shoes, and preexisting structural conditions such as spondylolisthesis, sacralization of the fifth lumbar vertebra, and previous back surgery worsen the pain. The back pain may be localized to the back and sacroiliac joints, or it may radiate into the thigh but not below the knee. The neurologic examination will be normal. Treatment consists in bed rest, heat, massage, simple analgesics, and exercises to strengthen the back and increase its flexibility. Regular swimming is excellent.
The pain of herniation of a lumbar intervertebral disk is of sudden onset, is exacerbated by coughing, and radiates to the ankle. Weakness of the extensor hallucis longus (L5) and a diminished ankle jerk (S1) may be present. Unless impairment of sphincter function dictates urgent myelography and surgery, the treatment is strict bed rest for 2 weeks. Lack of improvement at that time is justification for myelography and surgery if needed. Lumbar laminectomy has been performed during pregnancy without causing special problems.64
11. Nakane Y, Okuma T, Takahashi R et al: Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: A report of a collaborative study group in Japan. Epilepsia 21: 663, 1980
12. Janz D: On major malformations and minor anomalies in the offspring of parents with epilepsy: A review of the literature. In Janz D, Dam M, Richens A et al (eds): Epilepsey, Pregnancy and the Child, p 211. New York, Raven Press, 1982
16. Egenaes J: Outcome of pregnancy in women with epilepsy-Norway, 1967–1978: Complications during pregnancy and delivery. In Janz D, Dam M, Richens A et al (eds): Epilepsy, Pregnancy and the Child, p 81. New York, Raven Press, 1982
25. Sibai BM, Spinnato JA, Watson DL et al: Effect of magnesium sulfate on electroencephalographic findings in preeclampsia-eclampsia. Obstet Gynecol 64: 261, 1984
44. Donaldson JO: Control of chorea gravidarum with haloperidol. Obstet Gynecol 59: 381, 1982
48. Cahill DW, Bashirelahi N, Solomon LW et al: Estrogen and progesterone acceptors in meningiomas. J Neurosurg 60: 985, 1984
51. Konopka P, Raymond JP, Merceron RE et al: Continuous administration of bromocriptine in the prevention of neurological complications in pregnant women with prolactinomas. Am J Obstet Gynecol 146: 935, 1983