J t $I
Selected Neurologic Complications of Pregnancy
MARK W. FOX, M.D., Department ofNeurologic Surgery; ROGER W. HARMS, M.D., Department of Obstetrics and Gynecology; DUDLEY H. DAVIS, M.D., Department ofNeurologic Surgery
Many neurologic disorders, such as eclampsia, pseudotumor cerebri, stroke, obstetric nerve palsies, subarachnoid hemorrhage, pituitary tumors, and choriocarcinoma, can develop in the pregnant patient. Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion. Pseudotumor cerebri can be associated with serious visual complications; thus, the therapeutic goal is to prevent loss of vision. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The major causes of stroke in pregnant patients are arterial occlusion and cerebral venous thrombosis. Lumbar disk prolapse is common in pregnant patients, and lumbosacral plexus injuries can occur during labor or delivery. In addition, peripheral nerve compression or entrapment syndromes are thought to be caused by the retention of fluid during pregnancy. The incidence of subarachnoid hemorrhage during pregnancy is 1 in every 10,000 patients, a rate 5 times higher than in nonpregnant women. Because of a proliferation of prolactin-secreting cells, the pituitary gland can enlarge dramatically during pregnancy, a change that can disclose a previously unknown tumor or cause a known pituitary tumor to become symptomatic. The incidence of choriocarcinoma is 1 in 50,000 full-term pregnancies but 1 in 30 molar pregnancies. This malignant tumor has a high rate of cerebral metastatic lesions. In addition to these disorders that develop during pregnancy, the pregnant state can affect numerous preexisting neurologic conditions, including epilepsy, headaches, multiple sclerosis, myasthenia gravis, spinal cord injury, and brain tumors. We discuss advice for patients with such conditions who wish to become pregnant, recommendations for medical and surgical management, and surgical considerations for neurologic complications during pregnancy.
Numerous neurologic disorders may develop during pregnancy. In addition, pregestational neurologic disorders may influence the management of an otherwise uncomplicated obstetric case. Knowledge about neurologic disorders is important for the counseling of patients inter-
ested in childbirth and for the development of management strategies should complications arise during pregnancy. Some neurologic disorders of pregnancy are best managed medically, whereas others necessitate surgical treatment. Neurologic conditions not amenable to neurosurgical approaches include preeclampsia and Address reprint requests to Dr. D. H. Davis, Department of eclampsia, pseudotumor cerebri, stroke, and obstetric nerve palsies. Disorders potentially Neurologic Surgery, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 65:1595-1618,1990
1595
1596 NEUROLOGIC COMPLICATIONS OF PREGNANCY
Mayo Clin Proc, December 1990, Vol 65
treatable surgically include subarachnoid hem- function, hematologic dysfunction, renal ischorrhage, choriocarcinoma, and spinal disk dis- emia, or increased trophoblastic mass.' How ease. In addition to disorders that develop dur- preeclampsia gives rise to seizures or coma is ing pregnancy, many pregestational neurologic also speculative, but the final common pathway diseases are influenced by pregnancy. Examples is thought to involve loss of cerebral autoregulainclude epilepsy, headaches, multiple sclerosis, tion due to relative hypertension. Patients with myasthenia gravis, quadriplegia, and tumors of preeclampsia have a loss of the normal "refracthe central nervous system and pituitary gland. toriness" to vasoactive substances, such as angioWhat maternal and fetal risks arise with man- tensin II and catecholamines, observed during agement of such conditions? Should further pregnancy. This increased sensitivity gives rise pregnancies be recommended to women who to generalized arteriolar vasospasm, which rehave had previous neurologic complications such sults in increased peripheral vascular resistance as eclampsia during pregnancy? This review and hypertension.l-" Donaldson" believes that will discuss selected neurologic disorders of this relative hypertension overcomes the boundaries of cerebral autoregulation and results in pregnancy and management strategies. increased capillary blood flow and pressures in the brain; this situation, in turn, results in NEUROLOGIC DISORDERS THAT disruption of tight junctions of endothelial cells. DEVELOP DURING PREGNANCY Eclampsia.,..--Eclampsia is a condition charac- An extravasation of erythrocytes and plasma terized by seizures or coma (or both) in a preg- proteins follows." Vasogenic cerebral edema and nant patient with signs of preeclampsia (devel- pericapillary ring hemorrhages can result in opment of hypertension and proteinuria with or seizure foci.P-? These microscopic hemorrhages without edema after the 20th week of gestation). may form patches within the cortical gray matEclampsia has a predilection for young primipa- ter and often in both occipital lobes. The perous patients who are otherwise healthy and techial hemorrhages can also occur subcortinormotensive before pregnancy. Pregnancy- cally. A differential diagnosis of eclamptic states induced hypertension or preeclampsia develops is shown in Table 1. 1 The clinical implications of this mechanism in approximately 5% of all pregnancies in the United States, and in 2% of these patients, or for eclamptic brain lesions suggest that control 0.05 to 0.2% of all pregnancies, eclampsia may of hypertension should prevent patients with ultimately occur .1.3 preeclampsia from progressing to seizures or Preeclampsia may develop over several weeks, coma. The objective in treatment of any type of with rapid weight gain (usually in excess of 0.9 hypertension during pregnancy is to lower the kg per week) and gradual development of pro- blood pressure sufficiently to prevent complicateinuria and relative hypertension. Occasion- tions such as eclampsia or stroke, while concurally, it may have a more rapid course. If un- rently not reducing the blood pressure so low as treated, patients with preeclampsia may have to create uteroplacental hypoperfusion or marapid deterioration in hours to days with accel- ternal renal hypoperfusion. Hypertensive thererated hypertension, headaches, tremulousness, apy during pregnancy may include bed rest, visual disturbances, seizures, disseminated orally administered methyldopa, parenterally intravascular coagulation, or coma. Seizures or administered hydralazine hydrochloride, mild coma develops before delivery in 50%, during sedatives, or anticonvulsants. Diuretics can be labor in 25%, and generally within the first 24 used with caution. Medical therapy is indicated hours after birth in the other 25%. Eclampsia for diastolic blood pressures that exceed 110 mm has been diagnosed as late as 2 weeks after Hg, accelerated hypertension, or progressive preeclamptic symptorns.v" delivery, however.v' Seizures may be prevented in patients with Many causes of preeclampsia have been proposed: placental ischemia, immunologic dys- preeclampsia by the intravenous administra-
Mayo Clin Proc, December 1990, Vol 65
Table I.-Differential Diagnosis of Eclampsia Cerebrovascular accidents Cerebral venous thrombosis Cerebral arterial occlusion Cerebral arterial embolism Intracerebral hemorrhage Hypertensive disease Hypertensive encephalopathy Pheochromocytoma Space-occupying central nervous system lesions Brain tumor Brain abscess Infectious diseases Meningitis Encephalitis Metabolic diseases Hypoglycemia Hypocalcemia Water intoxication Epilepsy From Sibai and Anderson.' By permission of Futura Publishing Company, Inc.
tion of magnesium sulfate (although respiratory depression may occur with high serum levels). Eclamptic seizures can result in high fetal mortality. If obstetric seizures occur, they must be stopped promptly by administration of phenytoin or phenobarbital. The condition of the fetus should be monitored continuously. Magnesium sulfate should also be used to prevent recurrence of seizures.v" Once the seizures and hypertension have been controlled, preparations for delivery should be initiated. Delivery of the fetus and placenta is the definitive treatment for eclampsia occurring before birth. The risk of seizures in the patient with preeclampsia generally resolves within 24 hours after delivery, and magnesium sulfate therapy should be continued for that time. Patients should be under close surveillance during the postpartum period.' Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion.P'P Compromised uteroplacental flow may be fur-
NEUROLOGIC COMPLICATIONS OF PREGNANCY 1597
ther decreased by maternal complications. 10-12 A more complete list of maternal complications in eclampsia is shown in Table 2. 1 Analysis of the long-term prognosis in wellmanaged cases of eclampsia shows little residual maternal neurologic deficit and few growth or developmental difficulties among the involved children.l''-" Patients frequently ask about the risk for recurrence of preeclampsia. A young primigravida who has had this condition has a much more favorable prognosis (a 1 in 4 chance of recurrence if the patient is normotensive before and after pregnancy) than does an older multiparous woman with pregestational superimposed hypertension (a 7 in 10 chance of recurrenee)." The risk of recurrence is also increased by the severity of the preeclamptic episode, the presence of eclampsia, disseminated intravascular coagulation, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), parity of the patient, and new paternity.' Pseudotumor Cerebri.-Pseudotumor cerebri or benign intracranial hypertension is a disease in young women of childbearing age. The incidence of occurrence in young obese women is approximately 19 in 100,000. 14 Its frequency during pregnancy is less than would be expected for this age-group. 15,16 Pseudotumor cerebri is characterized by increased intracranial pressure (more than 200 mm of water) in the absence of structural intracranial disease. The underlying physiologic factor is thought to be decreased absorption of cerebrospinal fluid.F-" This selflimited condition generally lasts from days to months, with or without therapy. Interestingly, the disease is of shorter duration in pregnant women than in nonpregnant women. Pseudotumor has been associated with many conditions, including abnormal menses, obesity, pregnancy, menarche, steroid therapy or deficiency, oral contraceptives, tetracycline, vitamin A abuse, iron deficiency, and mild closed-head injury;" Benign intracranial hypertension usually occurs during the first half of gestation. The typical female patient is young and obese but otherwise in good health. Symptoms are those of increased intracranial pressure, including headache, visual obscurations, and nausea and
1598 NEUROLOGIC COMPLICATIONS OF PREGNANCY
Table 2.-Maternal Complications in Eclampsia Abruptio placentae Disseminated intravascular coagulopathy Intracerebral hemorrhage Pulmonary edema Aspiration pneumonia Acute renal tubular necrosis Retinal detachment Ruptured liver Transient cortical blindness From Sibai and Anderson.' By permission of Futura Publishing Company, Inc.
vomiting. Physical findings include papilledema, enlarged blind spots, and palsies ofthe abducent nerve. Studies of the cerebrospinal fluid show an increased opening pressure and occasionally a low protein level. Computed tomographic scans of the head are generally normal except for small ventricles in some patients. The differential diagnosis includes venous sinus thrombosis, hypertensive encephalopathy, or space-occupying lesions.lv''? As its name implies, benign intracranial hypertension is generally a benign process, and therapy is symptomatic. The spontaneous remission rate is high. Medical management includes the use of analgesics. Diuretics or acetazolamide is useful in the nongravid patient, and both can be used with caution during pregnancy. Although more invasive, one or several spinal taps may temporarily or permanently relieve increased pressures. Some investigators believe that high-dose oral prednisone therapy (considered safe during pregnancy) for 2 to 4 weeks is helpful.l" Just as in patients with eclampsia, delivery ofthe fetus often relieves the symptoms of increased intracranial pressure by reducing maternal intravascular volume. 16 Pseudotumor cerebri can be associated with serious visual complications. Up to 50% of patients have transient visual obscurations or even temporary blindness. With persistently increased intracranial pressures, severe deficits in visual acuity, including permanent blindness, may occur in 5 to 10% of patients. Therefore, the therapeutic goal is to prevent visual loss. 16,18,21,22 Progressive loss of visual acuity due to pseudotumor cerebri that is resistant to medical
Mayo Cltn Proc, December 1990, Vol 65
therapy is an indication for neurosurgical or ophthalmologic intervention. In recent years, lumboperitoneal shunting has been the treatment of choice for medically refractory loss of vision in patients with pseudotumor cerebri. 23-25 A needle is passed into the subarachnoid space percutaneously; a catheter is then threaded through the needle, and its distal end is passed subcutaneously around the flank to the abdomen. The distal end is then placed into the peritoneum through a small incision. Selman and associates'" and James and Tibbs'" reported that this procedure is safe and can prevent or improve deteriorating vision in most patients. Shunt malfunction occurred in 14% of patients. Decompression of the optic nerve sheath for the relief of papilledema and visual deterioration in pseudotumor cerebri has been shown to be effective at centers trained in this technique. 18 ,2 7 Ophthalmologists make small slits in the optic nerve sheath to allow egress of the cerebrospinal fluid into the orbit; thus, the optic nerve is decompressed. Improved vision has been noted in more than two-thirds of the patients. Unilateral decompression often relieved papilledema in both eyes. 25 ,26 ,28-30 Complications of this technique have included disturbances in ocular motility, irregular pupils, and tonic pupils. Vision was worse in 10% of patients.F-" The authors concluded that this technique is useful and safe for treatment of progressive loss of vision in patients with pseudotumor cerebri. The risk of neurologic visual loss during pregnancy does not differ from that during the nonpregnant state, although current evidence suggests that pregnant women with pseudotumor cerebri may have an increased risk for spontaneous abortion. In four articles that discussed 11 patients with pseudotumor cerebri who had 3 miscarriages during their current pregnancies as well as 4 miscarriages in 9 previous pregnancies unassociated with pseudotumor cerebri.sv"? a cause-and-effect relationship was not evident. Perhaps these women have an increased risk of spontaneous abortion for other reasons. 18 In summary, for pregnant patients with pseudotumor cerebri without major visual field defi-
Mayo Clin Proc, December 1990, Vol 65
NEUROLOGIC COMPLICATIONS OF PREGNANCY 1599
cits, analgesics, diuretics, or spinal taps may be used. Ifvisual acuity decreases, orallyadministered corticosteroids may be considered. If vision continues to deteriorate, lumboperitoneal shunting or decompression of the optic nerve sheath should be considered versus early delivery if the fetus is mature. 18 Stroke.-Cerebrovascular ischemic events or strokes are well-recognized neurologic complications of pregnancy. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The overall risk is 1 stroke in every 3,000 pregnancies.:" In a review of the incidence of stroke among female patients 15 to 45 years old, 23 of 65 patients (35%) had a stroke during pregnancy or in the early postpartum period.P" Although atherosclerosis accounts for most strokes in. older patients, it is incriminated in only about 25% of strokes in pregnant patients. 40 ,4 1 The causes of stroke in pregnant patients include arterial occlusion (in 60 to 80%) and cerebral venous thrombosis (in 20 to 40%). Arterial occlusions are most common during the second and third trimesters, whereas venous occlusions are most common in the first postpartum month." Arterial occlusive disease may result from valvular heart disease, cardiomyopathy ofpregnancy, patent foramen ovale with systemic venous thromboembolism, vasculitis, subarachnoid hemorrhage with associated vasospasm, or underlying hematologic disorders. Less common causes include amniotic fluid embolism, air or fat embolism, or metastatic choriocarcinoma.Pr" A more complete listing of causes of stroke in the pregnant patient is shown in Table 3. 4 2 Venous occlusive disease also may give rise to stroke during pregnancy or, more commonly, in the postpartum period.v'" In most cases, the cause is not found. Underlying hematologic disorders such as polycythemia vera, cancer, sickle cell anemia, or dehydration may predispose to this condition.v-v This disease generally manifests with symptoms that result from superior sagittal sinus thrombosis, with or without extension into cortical veins. The thrombosis
Table 3.-Potential Risk Factors and Causes of Stroke in Pregnancy and the Puerperium. Vasculopathy Aneurysm Arteriovenous malformation Venous thrombosis Atherosclerosis Vasculitides Systemic lupus erythematosus Polyarteritis nodosa Syphilis Takayasu's disease Fibromuscular dysplasia Arterial dissection Spontaneous Traumatic Carotid cavernous sinus fistula Moyamoya disease Transient emboligenic aortoarteritis Embolism Paradoxical embolus Peripartum cardiomyopathy Nonbacterial thrombotic endocarditis Fat or air embolism Mitral valve prolapse Valvular heart disease Infective endocarditis Marantic endocarditis Libman-Sacks endocarditis Atrial fibrillation Sick sinus syndrome Left atrial myxoma Cardiomyopathy Hematologic conditions Hemoglobin SS and SC disease Thrombotic thrombocytopenic purpura Paroxysmal nocturnal hemoglobinuria Increase in factor VIII Lupus anticoagulant Miscellaneous Migraine Alcohol intoxication Drug abuse Metastatic trophoblastic carcinoma Eclampsia From Stem.P By permission of Futura Publishing Company, Inc.
may give rise to hemorrhagic infarctions, increased intracranial pressure, or seizure foci."? Seizures occur in 80% of patients, focal motor or sensory changes occur in 60%, and the mental status is altered in 50%.47 Papilledema and meningismus are usually evident on physical examination." The assessment of the pregnant patient with transient ischemic attacks or stroke parallels
1600 NEUROLOGIC COMPLICATIONS OF PREGNANCY
the approach in nonpregnant patients, including use of computed tomographic scanning of the head, noninvasive neurovascular studies, cardiac echocardiography, and workup for underlying hematologic disorders. Angiography should be performed if indicated. Similarly, management should proceed with the same indications as in the nonpregnant patient. Generally, the optimal management of cerebrovascular disease during pregnancy is based on a precise knowledge ofthe underlying pathophysiologic process. 38,42 Anticoagulant management during pregnancy has been controversial because of the increased incidence of maternal and fetal hemorrhage, fetal wastage, and teratogenicity.38,48-54 Warfarin is known to cross the placenta and increase hemorrhagic complications; it also is a wellknown teratogen if it is taken at conception or during the first trimester. Heparin does not cross the placenta, but hemorrhagic complications are still observed in the mother. Additionally, long-term use of heparin can lead to osteopenia and thrombocytopenia, and heparin must be given intravenously or subcutaneously. At the Mayo Clinic, warfarin is uncommonly used during pregnancy. Women in need of anticoagulant therapy are maintained on subcutaneously administered heparin throughout pregnancy, and heparin therapy is discontinued when labor begins. Generally, 4 hours elapse before an epidural catheter is placed. Vaginal or cesarean delivery is performed with the usual indications. Intravenous or subcutaneous administration of heparin is resumed 6 hours after vaginal delivery or 24 hours after cesarean delivery. The decision for long-term oral or parenteral anticoagulant therapy during the postpartum period is made on an individual basis; issues such as the maternal disease process, neurologic stability, and the desire for breast-feeding should be considered. (Warfarin is secreted in breast milk [Ney J: Personal communication].) Obstetric Nerve Palsies.-Plexopathies or radiculopathies can develop in pregnant patients just as in the nonpregnant state. In addition, pregnant patients are particularly predisposed to certain peripheral neuropathies.
Mayo elin Proc, December 1990, Vol 65
At the root level, pregnancy is thought to predispose patients to disk prolapse. Although cervical disk disease is rare during pregnancy, lumbar disk prolapse is common. In a review of 179 female patients of childbearing age who had been pregnant one or more times, O'Connell'" found that 39% had symptoms of disk prolapse during pregnancy. These women had surgically proven disk disease. Intuitively, the postural and mechanical stresses of pregnancy would seem to contribute to this problem. During pregnancy, prolapsed disks are generally managed by symptomatic medical therapy. Postponing surgical treatment until after delivery is usually recommended, unless protrusion of the disk occurs early in pregnancy and causes intractable pain or a severe neurologic deficit. Inadvertent lumbosacral plexus injuries that occur during labor or delivery are often confused with a prolapsed disk. Patients with fetal-pelvic disproportion or primiparous patients with large babies that necessitate difficult midforceps delivery are at greatest risk for development of these injuries. The fetal head or obstetric forceps can cause compression or stretching of the anterior division of the lumbosacral trunk (L-4 or L-5) against the pelvic brim. The upper sacral roots are also endangered at this level. The upper lumbar plexus and the femoral nerve are protected by the psoas muscle and are distant from the true pelvis. These patients will often complain of buttock or leg pain, which intensifies with uterine contraction. Numbness, tingling, or weakness can also occur during delivery or in the postpartum period. A footdrop or weakness of the tibialis anterior muscle (L-4 and L-5 roots) is the most common finding; weakness of the gastrocnemius and soleus muscles (S-1 and S-2 roots) occurs less frequently. Return of normal sensory function is usually complete within 4 weeks; motor function recovers more slowly (within 1 to 4 months in most cases).56,57 Malpositioning ofthe patient in the lithotomy position may cause compression of the peroneal nerve at the fibular head, resulting in a footdrop, or may cause a femoral neuropathy. Strong flexion of the thighs on the abdomen with abduction and outward rotation produces pressure on
Mayo Clin Proc, December 1990, Vol 65
the femoral nerve by Poupart's ligament or by the iliopsoas muscle. Direct compression of the nerve or its blood supply may cause iliopsoas and quadriceps weakness (but spare the tibialis anterior muscle) with associated sensory loss over the anterior aspect of the thigh. Tight application of foot straps can also result in damage to the small cutaneous branches of the foot. With these conditions, the prognosis for recovery is good. Finally, peripheral nerve disorders, especially peripheral nerve compression or entrapment syndromes, commonly occur in pregnant patients. The most common compression-entrapment syndromes experienced during pregnancy are carpal tunnel syndrome and the lateral femoral cutaneous nerve syndrome (meralgia paresthetica). Voitk and associates'" reviewed questionnaires sent to 1,000 consecutive postpartum patients and found that 25% had had symptoms of carpal tunnel compression during pregnancy, three-fourths of whom had bilateral symptoms. This syndrome has been thought to be attributable to the retention of fluid during pregnancy. Treatment includes restricting the intake of salt, splinting, and use of diuretics and analgesics. Surgical treatment is rarely indicated because the disease resolves spontaneously with delivery in most cases. Massey'" stated that symptoms may persist for as long as 12 weeks or may resolve within several days after delivery. Tobin'" found that only 85% of carpal tunnel symptoms resolve completely. Carpal tunnel release is the definitive therapy for refractory patients with severe symptoms, and surgical treatment will prevent recurrence during subsequent pregnancies, which commonly occurs.F' Of the cranial nerves, the only well-documented palsy with an increased incidence during pregnancy is a facial or Bell's palsy. The onset is usually sudden and is most common during the third trimester. Bell's palsy is 3 times more common in pregnant patients than in nonpregnant women of the same age. Its presence does not affect the course of the pregnancy. The prognosis for recovery is satisfactory if the initial paralysis is partial. The cause of this
NEUROLOGIC COMPLICATIONS OF PREGNANCY 1601
disorder and its relationship to pregnancy are unknown.F'
Selected Neurologic Complications of Pregnancy
MARK W. FOX, M.D., Department ofNeurologic Surgery; ROGER W. HARMS, M.D., Department of Obstetrics and Gynecology; DUDLEY H. DAVIS, M.D., Department ofNeurologic Surgery
Many neurologic disorders, such as eclampsia, pseudotumor cerebri, stroke, obstetric nerve palsies, subarachnoid hemorrhage, pituitary tumors, and choriocarcinoma, can develop in the pregnant patient. Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion. Pseudotumor cerebri can be associated with serious visual complications; thus, the therapeutic goal is to prevent loss of vision. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The major causes of stroke in pregnant patients are arterial occlusion and cerebral venous thrombosis. Lumbar disk prolapse is common in pregnant patients, and lumbosacral plexus injuries can occur during labor or delivery. In addition, peripheral nerve compression or entrapment syndromes are thought to be caused by the retention of fluid during pregnancy. The incidence of subarachnoid hemorrhage during pregnancy is 1 in every 10,000 patients, a rate 5 times higher than in nonpregnant women. Because of a proliferation of prolactin-secreting cells, the pituitary gland can enlarge dramatically during pregnancy, a change that can disclose a previously unknown tumor or cause a known pituitary tumor to become symptomatic. The incidence of choriocarcinoma is 1 in 50,000 full-term pregnancies but 1 in 30 molar pregnancies. This malignant tumor has a high rate of cerebral metastatic lesions. In addition to these disorders that develop during pregnancy, the pregnant state can affect numerous preexisting neurologic conditions, including epilepsy, headaches, multiple sclerosis, myasthenia gravis, spinal cord injury, and brain tumors. We discuss advice for patients with such conditions who wish to become pregnant, recommendations for medical and surgical management, and surgical considerations for neurologic complications during pregnancy.
Numerous neurologic disorders may develop during pregnancy. In addition, pregestational neurologic disorders may influence the management of an otherwise uncomplicated obstetric case. Knowledge about neurologic disorders is important for the counseling of patients inter-
ested in childbirth and for the development of management strategies should complications arise during pregnancy. Some neurologic disorders of pregnancy are best managed medically, whereas others necessitate surgical treatment. Neurologic conditions not amenable to neurosurgical approaches include preeclampsia and Address reprint requests to Dr. D. H. Davis, Department of eclampsia, pseudotumor cerebri, stroke, and obstetric nerve palsies. Disorders potentially Neurologic Surgery, Mayo Clinic, Rochester, MN 55905. Mayo Clin Proc 65:1595-1618,1990
1595
1596 NEUROLOGIC COMPLICATIONS OF PREGNANCY
Mayo Clin Proc, December 1990, Vol 65
treatable surgically include subarachnoid hem- function, hematologic dysfunction, renal ischorrhage, choriocarcinoma, and spinal disk dis- emia, or increased trophoblastic mass.' How ease. In addition to disorders that develop dur- preeclampsia gives rise to seizures or coma is ing pregnancy, many pregestational neurologic also speculative, but the final common pathway diseases are influenced by pregnancy. Examples is thought to involve loss of cerebral autoregulainclude epilepsy, headaches, multiple sclerosis, tion due to relative hypertension. Patients with myasthenia gravis, quadriplegia, and tumors of preeclampsia have a loss of the normal "refracthe central nervous system and pituitary gland. toriness" to vasoactive substances, such as angioWhat maternal and fetal risks arise with man- tensin II and catecholamines, observed during agement of such conditions? Should further pregnancy. This increased sensitivity gives rise pregnancies be recommended to women who to generalized arteriolar vasospasm, which rehave had previous neurologic complications such sults in increased peripheral vascular resistance as eclampsia during pregnancy? This review and hypertension.l-" Donaldson" believes that will discuss selected neurologic disorders of this relative hypertension overcomes the boundaries of cerebral autoregulation and results in pregnancy and management strategies. increased capillary blood flow and pressures in the brain; this situation, in turn, results in NEUROLOGIC DISORDERS THAT disruption of tight junctions of endothelial cells. DEVELOP DURING PREGNANCY Eclampsia.,..--Eclampsia is a condition charac- An extravasation of erythrocytes and plasma terized by seizures or coma (or both) in a preg- proteins follows." Vasogenic cerebral edema and nant patient with signs of preeclampsia (devel- pericapillary ring hemorrhages can result in opment of hypertension and proteinuria with or seizure foci.P-? These microscopic hemorrhages without edema after the 20th week of gestation). may form patches within the cortical gray matEclampsia has a predilection for young primipa- ter and often in both occipital lobes. The perous patients who are otherwise healthy and techial hemorrhages can also occur subcortinormotensive before pregnancy. Pregnancy- cally. A differential diagnosis of eclamptic states induced hypertension or preeclampsia develops is shown in Table 1. 1 The clinical implications of this mechanism in approximately 5% of all pregnancies in the United States, and in 2% of these patients, or for eclamptic brain lesions suggest that control 0.05 to 0.2% of all pregnancies, eclampsia may of hypertension should prevent patients with ultimately occur .1.3 preeclampsia from progressing to seizures or Preeclampsia may develop over several weeks, coma. The objective in treatment of any type of with rapid weight gain (usually in excess of 0.9 hypertension during pregnancy is to lower the kg per week) and gradual development of pro- blood pressure sufficiently to prevent complicateinuria and relative hypertension. Occasion- tions such as eclampsia or stroke, while concurally, it may have a more rapid course. If un- rently not reducing the blood pressure so low as treated, patients with preeclampsia may have to create uteroplacental hypoperfusion or marapid deterioration in hours to days with accel- ternal renal hypoperfusion. Hypertensive thererated hypertension, headaches, tremulousness, apy during pregnancy may include bed rest, visual disturbances, seizures, disseminated orally administered methyldopa, parenterally intravascular coagulation, or coma. Seizures or administered hydralazine hydrochloride, mild coma develops before delivery in 50%, during sedatives, or anticonvulsants. Diuretics can be labor in 25%, and generally within the first 24 used with caution. Medical therapy is indicated hours after birth in the other 25%. Eclampsia for diastolic blood pressures that exceed 110 mm has been diagnosed as late as 2 weeks after Hg, accelerated hypertension, or progressive preeclamptic symptorns.v" delivery, however.v' Seizures may be prevented in patients with Many causes of preeclampsia have been proposed: placental ischemia, immunologic dys- preeclampsia by the intravenous administra-
Mayo Clin Proc, December 1990, Vol 65
Table I.-Differential Diagnosis of Eclampsia Cerebrovascular accidents Cerebral venous thrombosis Cerebral arterial occlusion Cerebral arterial embolism Intracerebral hemorrhage Hypertensive disease Hypertensive encephalopathy Pheochromocytoma Space-occupying central nervous system lesions Brain tumor Brain abscess Infectious diseases Meningitis Encephalitis Metabolic diseases Hypoglycemia Hypocalcemia Water intoxication Epilepsy From Sibai and Anderson.' By permission of Futura Publishing Company, Inc.
tion of magnesium sulfate (although respiratory depression may occur with high serum levels). Eclamptic seizures can result in high fetal mortality. If obstetric seizures occur, they must be stopped promptly by administration of phenytoin or phenobarbital. The condition of the fetus should be monitored continuously. Magnesium sulfate should also be used to prevent recurrence of seizures.v" Once the seizures and hypertension have been controlled, preparations for delivery should be initiated. Delivery of the fetus and placenta is the definitive treatment for eclampsia occurring before birth. The risk of seizures in the patient with preeclampsia generally resolves within 24 hours after delivery, and magnesium sulfate therapy should be continued for that time. Patients should be under close surveillance during the postpartum period.' Maternal mortality from eclampsia, which ranges from 0 to 14%, can be due to intracerebral hemorrhage, pulmonary edema, disseminated intravascular coagulation, abruptio placentae, or failure of the liver or kidneys. Associated fetal mortality ranges from 10 to 28% and is directly related to decreased placental perfusion.P'P Compromised uteroplacental flow may be fur-
NEUROLOGIC COMPLICATIONS OF PREGNANCY 1597
ther decreased by maternal complications. 10-12 A more complete list of maternal complications in eclampsia is shown in Table 2. 1 Analysis of the long-term prognosis in wellmanaged cases of eclampsia shows little residual maternal neurologic deficit and few growth or developmental difficulties among the involved children.l''-" Patients frequently ask about the risk for recurrence of preeclampsia. A young primigravida who has had this condition has a much more favorable prognosis (a 1 in 4 chance of recurrence if the patient is normotensive before and after pregnancy) than does an older multiparous woman with pregestational superimposed hypertension (a 7 in 10 chance of recurrenee)." The risk of recurrence is also increased by the severity of the preeclamptic episode, the presence of eclampsia, disseminated intravascular coagulation, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count), parity of the patient, and new paternity.' Pseudotumor Cerebri.-Pseudotumor cerebri or benign intracranial hypertension is a disease in young women of childbearing age. The incidence of occurrence in young obese women is approximately 19 in 100,000. 14 Its frequency during pregnancy is less than would be expected for this age-group. 15,16 Pseudotumor cerebri is characterized by increased intracranial pressure (more than 200 mm of water) in the absence of structural intracranial disease. The underlying physiologic factor is thought to be decreased absorption of cerebrospinal fluid.F-" This selflimited condition generally lasts from days to months, with or without therapy. Interestingly, the disease is of shorter duration in pregnant women than in nonpregnant women. Pseudotumor has been associated with many conditions, including abnormal menses, obesity, pregnancy, menarche, steroid therapy or deficiency, oral contraceptives, tetracycline, vitamin A abuse, iron deficiency, and mild closed-head injury;" Benign intracranial hypertension usually occurs during the first half of gestation. The typical female patient is young and obese but otherwise in good health. Symptoms are those of increased intracranial pressure, including headache, visual obscurations, and nausea and
1598 NEUROLOGIC COMPLICATIONS OF PREGNANCY
Table 2.-Maternal Complications in Eclampsia Abruptio placentae Disseminated intravascular coagulopathy Intracerebral hemorrhage Pulmonary edema Aspiration pneumonia Acute renal tubular necrosis Retinal detachment Ruptured liver Transient cortical blindness From Sibai and Anderson.' By permission of Futura Publishing Company, Inc.
vomiting. Physical findings include papilledema, enlarged blind spots, and palsies ofthe abducent nerve. Studies of the cerebrospinal fluid show an increased opening pressure and occasionally a low protein level. Computed tomographic scans of the head are generally normal except for small ventricles in some patients. The differential diagnosis includes venous sinus thrombosis, hypertensive encephalopathy, or space-occupying lesions.lv''? As its name implies, benign intracranial hypertension is generally a benign process, and therapy is symptomatic. The spontaneous remission rate is high. Medical management includes the use of analgesics. Diuretics or acetazolamide is useful in the nongravid patient, and both can be used with caution during pregnancy. Although more invasive, one or several spinal taps may temporarily or permanently relieve increased pressures. Some investigators believe that high-dose oral prednisone therapy (considered safe during pregnancy) for 2 to 4 weeks is helpful.l" Just as in patients with eclampsia, delivery ofthe fetus often relieves the symptoms of increased intracranial pressure by reducing maternal intravascular volume. 16 Pseudotumor cerebri can be associated with serious visual complications. Up to 50% of patients have transient visual obscurations or even temporary blindness. With persistently increased intracranial pressures, severe deficits in visual acuity, including permanent blindness, may occur in 5 to 10% of patients. Therefore, the therapeutic goal is to prevent visual loss. 16,18,21,22 Progressive loss of visual acuity due to pseudotumor cerebri that is resistant to medical
Mayo Cltn Proc, December 1990, Vol 65
therapy is an indication for neurosurgical or ophthalmologic intervention. In recent years, lumboperitoneal shunting has been the treatment of choice for medically refractory loss of vision in patients with pseudotumor cerebri. 23-25 A needle is passed into the subarachnoid space percutaneously; a catheter is then threaded through the needle, and its distal end is passed subcutaneously around the flank to the abdomen. The distal end is then placed into the peritoneum through a small incision. Selman and associates'" and James and Tibbs'" reported that this procedure is safe and can prevent or improve deteriorating vision in most patients. Shunt malfunction occurred in 14% of patients. Decompression of the optic nerve sheath for the relief of papilledema and visual deterioration in pseudotumor cerebri has been shown to be effective at centers trained in this technique. 18 ,2 7 Ophthalmologists make small slits in the optic nerve sheath to allow egress of the cerebrospinal fluid into the orbit; thus, the optic nerve is decompressed. Improved vision has been noted in more than two-thirds of the patients. Unilateral decompression often relieved papilledema in both eyes. 25 ,26 ,28-30 Complications of this technique have included disturbances in ocular motility, irregular pupils, and tonic pupils. Vision was worse in 10% of patients.F-" The authors concluded that this technique is useful and safe for treatment of progressive loss of vision in patients with pseudotumor cerebri. The risk of neurologic visual loss during pregnancy does not differ from that during the nonpregnant state, although current evidence suggests that pregnant women with pseudotumor cerebri may have an increased risk for spontaneous abortion. In four articles that discussed 11 patients with pseudotumor cerebri who had 3 miscarriages during their current pregnancies as well as 4 miscarriages in 9 previous pregnancies unassociated with pseudotumor cerebri.sv"? a cause-and-effect relationship was not evident. Perhaps these women have an increased risk of spontaneous abortion for other reasons. 18 In summary, for pregnant patients with pseudotumor cerebri without major visual field defi-
Mayo Clin Proc, December 1990, Vol 65
NEUROLOGIC COMPLICATIONS OF PREGNANCY 1599
cits, analgesics, diuretics, or spinal taps may be used. Ifvisual acuity decreases, orallyadministered corticosteroids may be considered. If vision continues to deteriorate, lumboperitoneal shunting or decompression of the optic nerve sheath should be considered versus early delivery if the fetus is mature. 18 Stroke.-Cerebrovascular ischemic events or strokes are well-recognized neurologic complications of pregnancy. The risk of stroke in the pregnant patient is 13 times the risk in the nonpregnant patient of the same age. The overall risk is 1 stroke in every 3,000 pregnancies.:" In a review of the incidence of stroke among female patients 15 to 45 years old, 23 of 65 patients (35%) had a stroke during pregnancy or in the early postpartum period.P" Although atherosclerosis accounts for most strokes in. older patients, it is incriminated in only about 25% of strokes in pregnant patients. 40 ,4 1 The causes of stroke in pregnant patients include arterial occlusion (in 60 to 80%) and cerebral venous thrombosis (in 20 to 40%). Arterial occlusions are most common during the second and third trimesters, whereas venous occlusions are most common in the first postpartum month." Arterial occlusive disease may result from valvular heart disease, cardiomyopathy ofpregnancy, patent foramen ovale with systemic venous thromboembolism, vasculitis, subarachnoid hemorrhage with associated vasospasm, or underlying hematologic disorders. Less common causes include amniotic fluid embolism, air or fat embolism, or metastatic choriocarcinoma.Pr" A more complete listing of causes of stroke in the pregnant patient is shown in Table 3. 4 2 Venous occlusive disease also may give rise to stroke during pregnancy or, more commonly, in the postpartum period.v'" In most cases, the cause is not found. Underlying hematologic disorders such as polycythemia vera, cancer, sickle cell anemia, or dehydration may predispose to this condition.v-v This disease generally manifests with symptoms that result from superior sagittal sinus thrombosis, with or without extension into cortical veins. The thrombosis
Table 3.-Potential Risk Factors and Causes of Stroke in Pregnancy and the Puerperium. Vasculopathy Aneurysm Arteriovenous malformation Venous thrombosis Atherosclerosis Vasculitides Systemic lupus erythematosus Polyarteritis nodosa Syphilis Takayasu's disease Fibromuscular dysplasia Arterial dissection Spontaneous Traumatic Carotid cavernous sinus fistula Moyamoya disease Transient emboligenic aortoarteritis Embolism Paradoxical embolus Peripartum cardiomyopathy Nonbacterial thrombotic endocarditis Fat or air embolism Mitral valve prolapse Valvular heart disease Infective endocarditis Marantic endocarditis Libman-Sacks endocarditis Atrial fibrillation Sick sinus syndrome Left atrial myxoma Cardiomyopathy Hematologic conditions Hemoglobin SS and SC disease Thrombotic thrombocytopenic purpura Paroxysmal nocturnal hemoglobinuria Increase in factor VIII Lupus anticoagulant Miscellaneous Migraine Alcohol intoxication Drug abuse Metastatic trophoblastic carcinoma Eclampsia From Stem.P By permission of Futura Publishing Company, Inc.
may give rise to hemorrhagic infarctions, increased intracranial pressure, or seizure foci."? Seizures occur in 80% of patients, focal motor or sensory changes occur in 60%, and the mental status is altered in 50%.47 Papilledema and meningismus are usually evident on physical examination." The assessment of the pregnant patient with transient ischemic attacks or stroke parallels
1600 NEUROLOGIC COMPLICATIONS OF PREGNANCY
the approach in nonpregnant patients, including use of computed tomographic scanning of the head, noninvasive neurovascular studies, cardiac echocardiography, and workup for underlying hematologic disorders. Angiography should be performed if indicated. Similarly, management should proceed with the same indications as in the nonpregnant patient. Generally, the optimal management of cerebrovascular disease during pregnancy is based on a precise knowledge ofthe underlying pathophysiologic process. 38,42 Anticoagulant management during pregnancy has been controversial because of the increased incidence of maternal and fetal hemorrhage, fetal wastage, and teratogenicity.38,48-54 Warfarin is known to cross the placenta and increase hemorrhagic complications; it also is a wellknown teratogen if it is taken at conception or during the first trimester. Heparin does not cross the placenta, but hemorrhagic complications are still observed in the mother. Additionally, long-term use of heparin can lead to osteopenia and thrombocytopenia, and heparin must be given intravenously or subcutaneously. At the Mayo Clinic, warfarin is uncommonly used during pregnancy. Women in need of anticoagulant therapy are maintained on subcutaneously administered heparin throughout pregnancy, and heparin therapy is discontinued when labor begins. Generally, 4 hours elapse before an epidural catheter is placed. Vaginal or cesarean delivery is performed with the usual indications. Intravenous or subcutaneous administration of heparin is resumed 6 hours after vaginal delivery or 24 hours after cesarean delivery. The decision for long-term oral or parenteral anticoagulant therapy during the postpartum period is made on an individual basis; issues such as the maternal disease process, neurologic stability, and the desire for breast-feeding should be considered. (Warfarin is secreted in breast milk [Ney J: Personal communication].) Obstetric Nerve Palsies.-Plexopathies or radiculopathies can develop in pregnant patients just as in the nonpregnant state. In addition, pregnant patients are particularly predisposed to certain peripheral neuropathies.
Mayo elin Proc, December 1990, Vol 65
At the root level, pregnancy is thought to predispose patients to disk prolapse. Although cervical disk disease is rare during pregnancy, lumbar disk prolapse is common. In a review of 179 female patients of childbearing age who had been pregnant one or more times, O'Connell'" found that 39% had symptoms of disk prolapse during pregnancy. These women had surgically proven disk disease. Intuitively, the postural and mechanical stresses of pregnancy would seem to contribute to this problem. During pregnancy, prolapsed disks are generally managed by symptomatic medical therapy. Postponing surgical treatment until after delivery is usually recommended, unless protrusion of the disk occurs early in pregnancy and causes intractable pain or a severe neurologic deficit. Inadvertent lumbosacral plexus injuries that occur during labor or delivery are often confused with a prolapsed disk. Patients with fetal-pelvic disproportion or primiparous patients with large babies that necessitate difficult midforceps delivery are at greatest risk for development of these injuries. The fetal head or obstetric forceps can cause compression or stretching of the anterior division of the lumbosacral trunk (L-4 or L-5) against the pelvic brim. The upper sacral roots are also endangered at this level. The upper lumbar plexus and the femoral nerve are protected by the psoas muscle and are distant from the true pelvis. These patients will often complain of buttock or leg pain, which intensifies with uterine contraction. Numbness, tingling, or weakness can also occur during delivery or in the postpartum period. A footdrop or weakness of the tibialis anterior muscle (L-4 and L-5 roots) is the most common finding; weakness of the gastrocnemius and soleus muscles (S-1 and S-2 roots) occurs less frequently. Return of normal sensory function is usually complete within 4 weeks; motor function recovers more slowly (within 1 to 4 months in most cases).56,57 Malpositioning ofthe patient in the lithotomy position may cause compression of the peroneal nerve at the fibular head, resulting in a footdrop, or may cause a femoral neuropathy. Strong flexion of the thighs on the abdomen with abduction and outward rotation produces pressure on
Mayo Clin Proc, December 1990, Vol 65
the femoral nerve by Poupart's ligament or by the iliopsoas muscle. Direct compression of the nerve or its blood supply may cause iliopsoas and quadriceps weakness (but spare the tibialis anterior muscle) with associated sensory loss over the anterior aspect of the thigh. Tight application of foot straps can also result in damage to the small cutaneous branches of the foot. With these conditions, the prognosis for recovery is good. Finally, peripheral nerve disorders, especially peripheral nerve compression or entrapment syndromes, commonly occur in pregnant patients. The most common compression-entrapment syndromes experienced during pregnancy are carpal tunnel syndrome and the lateral femoral cutaneous nerve syndrome (meralgia paresthetica). Voitk and associates'" reviewed questionnaires sent to 1,000 consecutive postpartum patients and found that 25% had had symptoms of carpal tunnel compression during pregnancy, three-fourths of whom had bilateral symptoms. This syndrome has been thought to be attributable to the retention of fluid during pregnancy. Treatment includes restricting the intake of salt, splinting, and use of diuretics and analgesics. Surgical treatment is rarely indicated because the disease resolves spontaneously with delivery in most cases. Massey'" stated that symptoms may persist for as long as 12 weeks or may resolve within several days after delivery. Tobin'" found that only 85% of carpal tunnel symptoms resolve completely. Carpal tunnel release is the definitive therapy for refractory patients with severe symptoms, and surgical treatment will prevent recurrence during subsequent pregnancies, which commonly occurs.F' Of the cranial nerves, the only well-documented palsy with an increased incidence during pregnancy is a facial or Bell's palsy. The onset is usually sudden and is most common during the third trimester. Bell's palsy is 3 times more common in pregnant patients than in nonpregnant women of the same age. Its presence does not affect the course of the pregnancy. The prognosis for recovery is satisfactory if the initial paralysis is partial. The cause of this
NEUROLOGIC COMPLICATIONS OF PREGNANCY 1601
disorder and its relationship to pregnancy are unknown.F'
