Chapter 16: Neurologic Emergencies During Pregnancy

The patient with a neurologic emergency does not present with a diagnosis but rather with one or several clinical manifestations. The nature of the presentation, sequence of events, and constellation of signs and symptoms suggest a differential diagnosis. Starting from the presentation, the physician must select diagnostic tests and procedures, and then, once a diagnosis is made initiate treatment. The differential diagnosis may be altered by pregnancy and diagnostic procedures employed may be different from those one would use in nonpregnant patients. We will consider the following presentations: headache, seizures, altered state of consciousness, and motor or sensory changes. This signs and symptoms approach was chosen because patients do not usually come to the physician with a diagnosis but with a change in their condition, appearance of symptoms, and the need for care. An exception to the signs and symptoms’ approach will be the discussion of autonomic dysreflexia at the end of the chapter.

Common Complaint in Pregnancy

Headache is a common complaint in pregnancy.¹ Patients who report having had the same problem for some time prior to pregnancy do not usually have a neurologic emergency. Chronic and recurrent headaches may be due to tension, migraine, sinusitis, pseudotumor cerebri, or in many cases be unexplained.

Migraine Headaches

Migraine headaches are relatively common in reproductive age of women and often become less frequent and severe in pregnancy (75% of women). In a minority (5%) of migraine sufferers, however, they may present for the first time or become more severe in pregnancy and must be distinguished from other more immediately dangerous conditions. Many patients who think they have migraines do not have the classical pattern of aura, headache, and nausea. Headaches which, aside from frequency, are similar to those the patient has experienced in the past can generally be considered to not represent a neurologic emergency and can be managed symptomatically. Medications used for the treatment of migraine headache are listed in Table 16-1. If headaches appear to be becoming more frequent and severe or have accompanying neurologic manifestations, then they require further evaluation.

New-Onset Headaches

The new-onset headache (Table 16-2) or the occurrence of a headache with different location, quality, or accompanying neurologic symptoms demands further evaluation. Figure 16-1 outlines an approach to the evaluation of headache in pregnancy. The sudden onset of headache requires immediate evaluation and perhaps admission to the hospital. Headache is a common feature of preeclampsia which must be considered in any patient presenting in the second half of pregnancy. Since preeclampsia consists of a constellation of clinical and laboratory abnormalities, appropriate clinical and laboratory evaluation should be able to determine if it is a likely diagnosis in a specific patient (see Chap. 5).

Sudden, Severe Headache

The differential diagnosis of sudden, severe headache in pregnancy is the same as for the nonpregnant patient with the addition of preeclampsia. It includes subarachnoid hemorrhage, intracerebral hemorrhage, cerebral venous thrombosis (CVT), meningitis, and mass lesions (tumors or abscess).

Subarachnoid Hemorrhage

Subarachnoid hemorrhage can be due to ruptured cerebral aneurysms, arteriovenous malformations (AVM), or, rarely, preeclampsia or eclampsia.² Cerebral aneurysms usually occur on the vessels of the circle of Willis or the proximal portions of the vessels arising from it. These saccular or berry aneurysms can be found in any patient but are more common in patients with Marfan syndrome or familial polycystic kidneys. Bleeds from aneurysms are more common in older patients (generally over age 30) and tend to occur in late pregnancy. In contrast, hemorrhage from an AVM tends to occur in younger patients (peak between 15 and 20 years) and are equally likely at all gestational ages. There is no way to clinically distinguish between bleeding from an AVM, a berry aneurysm, or preeclampsia. These patients all present with sudden onset of severe headache, nausea and vomiting, and meningeal signs. They may have focal neurologic deficits, altered state of consciousness, seizures, and hypertension. The condition of the patient at presentation is the most important prognostic feature (Table 16-3).

The diagnosis of possible subarachnoid hemorrhage in pregnancy starts with a high index of suspicion raised by the presentation. Clinical and laboratory evaluation for possible preeclampsia/eclampsia must be accomplished since it is the more common diagnosis and if confirmed, requires specific therapy and possible delivery as the definitive treatment. If preeclampsia is ruled out, the cornerstone of evaluation is CNS imaging with CT, MRI, or MRA. Imaging contrast dyes may be used in pregnancy to help determine the nature of the hemorrhage and its source. Cerebral angiography may also be used to pinpoint the site of bleeding. Spinal tap will serve to confirm the presence of subarachnoid blood and rule out meningitis as the cause of the headache. Simultaneously with initiating the diagnostic workup, neurologic and neurosurgical consultation should be obtained.

Surgical management of both AVM and berry aneurysms can be accomplished in pregnancy but if the patient is near term, consideration of delivery prior to or simultaneously with the surgical repair should be considered. Surgery under hypotensive anesthesia or hypothermia can be well tolerated by the fetus. Continuous fetal heart rate monitoring is needed during and after surgery. Anesthetic medications generally suppress fetal heart rate variability and can make monitor interpretation more difficult. If fetal bradycardia occurs, it is desirable to raise the maternal blood pressure to improve utero-placental perfusion. Careful attention to maternal oxygenation will improve fetal condition. Almost all women known to have an AVM or berry aneurysm are delivered by cesarean section. If the lesion has been surgically treated by excision in the case of AVM or clipping in the case of aneurysm, then vaginal delivery can be safely conducted.

Cerebral Venous Thrombosis

Cerebral venous thrombosis (CVT) is uncommon. It is estimated to occur at a rate of 11.6/100,000 deliveries. Seventy-five percent of the cases occur in women. Pregnancy and oral contraceptives and the associated changes in the coagulation system are thought to be the explanation for this sex difference. Headache is the most frequent presenting symptom of CVT. The onset of headache may be gradual or acute and can even mimic subarachnoid hemorrhage. It can present similar to a migraine with an associated aura. It may be associated with signs of intracranial hypertension. It may be associated with focal neurologic signs, altered state of consciousness, or seizures. Sagittal sinus thrombosis often causes motor deficits, bilateral deficits, and seizures.

Diagnosis of CVT

MRI imaging of the brain with MR venography is the most sensitive technique for demonstrating the lesion. Overall, these studies are 90% to 100% accurate. CT of the brain may be negative in up to 30% of documented cases of CVT. CT venography is a useful alternative to MR venography if MRI is not available. There is a relatively high false-positive rate with all modalities due to normal anatomic variations in the cerebral venous sinuses. Women who are diagnosed with CVT should be evaluated for acquired and inherited thrombophilias.

Meningitis

Meningitis commonly presents with headache plus other symptoms such as fever, malaise, meningismus, and perhaps focal neurologic signs. Whether bacterial, fungal, or viral, the diagnosis must be made by spinal tap before specific treatment can be provided. In the setting of severe, sudden onset of headache, an intracranial mass lesion must be ruled out with imaging studies before a lumbar tap is performed.

Mass Lesions

Intracranial mass lesions, tumor or abscesses, can lead to headache as well as focal neurologic signs and seizures. The cornerstone of the diagnosis of mass lesions is MRI or CT imaging of the brain. As noted above, MRI exposes the fetus to no-ionizing radiation and can be safely performed at any stage of pregnancy with no adverse fetal effects. A head or neck CT exposes the uterus to about 1 mrad of radiation. If an MRI is not readily available, a CT should be performed. Neurosurgical consultation should be obtained if a mass lesion is suspected.

Rule out Eclampsia

Preexistent Seizure Disorder

When a pregnant woman presents with a seizure, the first question to ask is whether she has a seizure disorder. The second question to ask oneself is whether this represents eclampsia (Fig. 16-2). Seizure disorders occur in approximately 0.5% of the population and are the most common neurologic complication of pregnancy. There appears to be an increase in seizure frequency in pregnancy but it is unclear how much of this increase is due to increased susceptibility to seizures and how much is due to declining blood anticonvulsant drug levels.³ Both the volume of distribution and hepatic clearance of anticonvulsant drugs are increased in pregnancy.⁴ This can be especially dramatic in the case of phenytoin. The renal clearance of phenobarbital also increases in pregnancy. These physiologic changes result in falling anticonvulsant levels while the patient is maintained on a constant dose. The woman who, when not pregnant, experienced at least one convulsion per month can expect an increase in seizure frequency during pregnancy. When a pregnant woman, whose seizures have been well controlled prior to conception, presents with a recurrence of seizures, one must confirm adequate blood levels of her anticonvulsant medication.

Fetal Malformations Associated With Seizure Disorder

Infants of epileptic women have a higher incidence of birth defects than the general population. This risk is present for those women not on medication as well as those on anticonvulsants. The magnitude of the risk increases with the severity of the maternal condition and the number of drugs required to control the seizures. A variety of malformations have been associated with maternal anticonvulsant use. Dysmorphic facial features are seen with a variety of agents. Distal digital hypoplasia occurs in 15% to 30% of infants exposed to phenytoin and carbamazepine.⁵ Neural tube defects appear in 1% to 2% of infants exposed to valproic acid in the first trimester.⁶ It is unclear whether the anomalies seen with anticonvulsant therapy are due to direct embryo toxic effect of the drug or relative folate deficiency or antagonism. Dietary supplementation with folic acid in doses of 0.5 to 1 mg/d starting prior to conception seems reasonable but direct proof of efficacy is lacking. Table 16-6 lists the usual doses, therapeutic blood levels, and side effects of commonly used anticonvulsants.

Use of anticonvulsants in the third trimester may contribute to bleeding problems in the fetus and newborn. While the mothers’ clotting system appears to be unaffected by anticonvulsants, about one-half of exposed newborns will have a deficiency of vitamin K–dependent clotting factors. Maternal vitamin K supplementation with 20 mg/d for 2 weeks prior to delivery results in normal clotting parameters in the newborn. In case of preterm labor, a single 10-mg intramuscular dose to the mother should be adequate. Since most infants receive 1 mg of vitamin K intramuscularly at birth, clinical hemorrhagic disease of the newborn is quite rare even in patients on anticonvulsants.

New Onset of Seizures

The new onset of seizures, especially in the third trimester or postpartum, should be considered to be due to eclampsia until proven otherwise. The initial treatment should be magnesium sulfate as outlined in Chap. 5. Earlier in pregnancy or with eclampsia ruled out, the initial therapy can be with phenytoin. If the patient is in status epilepticus, this can be accomplished with an intravenous loading dose of 18 to 20 mg/kg given at a maximum rate of 50 mg/min. Transient hypotension and heart block can occur with rapid intravenous infusion of phenytoin. The patient should be on a cardiac monitor during this therapy. For the patient not in status, oral treatment is appropriate and safer.

Status epilepticus is a life-threatening emergency and treatment must be initiated immediately to preserve both maternal and fetal well-being. Prolonged seizure activity can lead to lactic acidosis, cardiovascular instability, and irreversible brain injury. Initial steps in therapy are to establish an airway and venous access. The Epilepsy Foundation of America has published a timetable for the treatment of status epilepticus (Table 16-4).⁷

Differential Diagnosis

Once the acute seizure is controlled the patient must be evaluated for etiology. Potential causes include trauma, infection, metabolic disorders, space-occupying lesions, central nervous system bleeding, and drug use. Neurologic consultation should be obtained as soon as the workup is started (see Fig. 16-2 and Table 16-5).

The pregnant woman with a seizure disorder may be on one or several of the commonly used anticonvulsants. While none have been shown to be completely safe for the fetus, uncontrolled seizures are unequivocally dangerous to both the mother and fetus. Table 16-6 lists the doses, therapeutic blood levels, and side effects of the commonly used drugs.

When a patient presents with altered state of consciousness, it is often accompanied or preceded by seizure, headache, or focal neurologic signs. When it occurs without these other features, one must consider drug exposure or a catastrophic intracerebral event such as massive hemorrhage or stroke. In these latter conditions, the onset of the event may not have been witnessed and only the fully developed situation is observed. The evaluation of patients with altered consciousness is similar to that of new onset of seizures. Often the patient has had a seizure which was not witnessed and she is found in the postictal state. Because of its serious consequences and relatively high prevalence, eclampsia must be considered in any patient with altered consciousness. Preeclampsia is a predisposing factor for both ischemic and hemorrhagic stroke. Once eclampsia is eliminated and a thorough neurologic examination is completed, the cornerstone of evaluation is brain imaging by MRI or CT. Figure 16-3 outlines the initial steps in evaluation and management of this emergency.

Thrombotic Stroke

Thrombotic stroke is relatively rare in the reproductive age group. The overall incidence is 1 per 20,000 live births.⁸ About half of the pregnancy-associated events occur in the immediate postpartum period. The other half occurs predominantly in the late second and third trimester. Certain conditions predispose to it including preeclampsia, hypertension, diabetes, hyperlipidemias, smoking, collagen vascular disease, and some thrombophilias. During the first 24 hours, attention should be paid to maintaining normal blood sugar and adequate arterial pressure to ensure cerebral perfusion. Bed rest assists in cerebral perfusion by avoiding orthostatic changes in blood pressure. Heparin appears to have little role in the acute phase, but in certain circumstances, it is useful in preventing recurrence. Intracranial hypertension may develop and must be controlled with dexamethasone and osmotic diuresis with mannitol. In the absence of vascular instability, maternal stroke poses little threat to the fetus. If associated with an acquired thrombophilia such as lupus anticoagulant or anticardiolipin antibody, that condition may pose an independent threat to fetal well-being. The role of thrombolytic therapy in pregnancy is uncertain. There are no randomized trials or large observational studies in pregnant patients.

Embolic Stroke

Embolic stroke usually occurs in the setting of known valvular heart disease, cardiomyopathy, or arrhythmia. For these reasons, cardiac evaluation is essential to the evaluation of maternal stroke. Once the diagnosis of embolic stroke is confirmed, the management is similar to thrombotic stroke with the exception of anticoagulation. As with thrombosis, heparin does little to improve the acute condition but is useful to prevent recurrence. In many cases, anticoagulation should be delayed for 7 to 10 days to avoid converting an infarct to a hemorrhagic infarct.

Hemorrhagic Stroke

Hemorrhagic stroke is usually due to either aneurismal bleeding or bleeding from an arteriovenous malformation. Aneurismal bleeding is usually subarachnoid and comes from aneurysms on or near the circle of Willis. Bleeding from an arteriovenous malformation can be either subarachnoid or parenchymal. Subarachnoid bleeding is discussed earlier under the heading “Headache". Management of intracranial bleeding during pregnancy is similar to management in the nonpregnant patient.

Focal neurologic signs can be caused by several of the conditions discussed earlier including migraine syndrome, stroke, and cerebral venous thrombosis. Appropriate diagnostic tests and management is as described earlier.

Guillain-Barré Syndrome

This presents as progressive, usually symmetric muscle weakness and absence of reflexes. It seems to be provoked by a recent infection and is thought to be an auto-antibody-mediated disease. It usually starts in the lower extremities and progresses upward but may start in the upper extremities or in the face. The disease generally progresses over a course of 4 weeks and then begins to resolve. Severe respiratory muscle involvement requiring ventilator support occurs in 10% to 30% of cases.⁹ Autonomic dysreflexia occurs in 70% of cases (see later).¹⁰ Pain in the back and extremities are reported in two-thirds of cases. With resolution of the syndrome, recovery of motor function may or may not be complete. Diagnosis is confirmed by electromyography and nerve conduction studies showing demyelinating polyneuropathy. Lumbar puncture shows elevated cerebrospinal fluid (CSF) protein but a normal white blood count (WBC) count.

The cornerstone of management of Guillain-Barré syndrome is supportive care. Up to 30 percent of patients will develop respiratory failure and need mechanical ventilation. With the high incidence of autonomic dysreflexia, admission to the intensive care unit is suggested for all patients showing rapid progression. Randomized controlled studies have shown that plasmapheresis and intravenous immunoglobulin (IVIG) have both been shown to hasten the recovery in Guillain-Barré syndrome. They appear to be similarly efficacious. IVIG is better tolerated and is recommended in pregnancy as it avoids the risk of hypotension and electrolyte disturbance which are associated with plasmapheresis.

This is a potentially life-threatening complication of a chronic spinal cord injury at or above T6. It is a result of sympathetic hyperactivity below the level of the lesion because this area is deprived of control by higher CNS regions.¹¹ This results in hypertension, headache, nasal congestion, facial erythema, sweating, piloerection, bradycardia, tachycardia, or arrhythmia, and perhaps loss of consciousness. Fetal hypoxia may develop due to uterine vasoconstriction. The event can be triggered by a variety of mild or noxious stimuli below the level of the spinal cord injury. The occurrence of autonomic dysreflexia is estimated to be between 20% and 75% of the patients with spinal cord injury above T6.

Triggers in Pregnancy, Labor, and Delivery

Eighty-five percent of patients who are prone to autonomic dysreflexia will develop it in labor.¹² It can be precipitated by vaginal examination, bladder distention, fecal impaction, or uterine contractions. Safe conduct of labor in these patients entails recognition of the risk and appropriate management of labor. Anesthetic consultation in advance of labor is important. Epidural anesthetic extending to T10 should be used to prevent the problem even though the patient will not perceive pain.¹³ If the patient presents with the problem before anesthetic has be instituted, sitting the patient up may help to ameliorate the hypertension by pooling blood in the lower extremities. Antihypertensive treatment with intravenous labetalol or oral nifedipine can be used to reduce blood pressure. An indwelling urinary catheter or frequent bladder catheterization to prevent distention is important.