Neurologic emergency in pregnancy is one that typically presents in a similar manifestation to the nonpregnant patient. The presentation, constellation of findings, and timing of symptoms help develop the differential diagnosis; however, the pregnant state increases the differential diagnosis with pregnancy specific and pregnancy related diseases. Pregnancy physiology and concern for the fetus can additionally make the evaluation and treatment more complex because of changing maternal physiology, as well as need to care for the maternal-fetal dyad.

In this chapter, we will consider the following presentations: headache, seizures, altered state of consciousness, and motor or sensory changes. These signs and symptoms are common in pregnancy, and the differential wide. The focus will be on acute, life-threatening events as opposed to the management of known chronic neurological conditions. Using this approach will provide a more “real life” approach—one of evaluating the pregnant women with a complaint and moving forward to a diagnosis.

As a general guiding principle, the pregnant women with neurologic emergency should receive the same imaging, care, medications, evaluation, including contrast studies, thrombolytics, and surgery as needed to improve the maternal neurologic outcome regardless of stage of pregnancy. Care should not be delayed to the mother for fetal evaluation or delivery, but often fetal evaluation including monitoring and ultrasound can be accomplished simultaneously and provide valuable clinical information to aid in decision making. Consultation and coordination of care with neurology, neurosurgery, anesthesia, neonatology, and maternal-fetal medicine (MFM) are needed to allow the best outcomes for the maternal-fetal dyad—and should be accomplished as rapidly as possible. However, as the common adage so eloquently says—“time is brain”—and immediate and aggressive care for the woman with an acute neurologic event should be prioritized to optimize the maternal neurologic outcome.

Neuroimaging and Evaluation in Pregnancy

If an intracranial process is suspected, the patient should undergo emergent central nervous system (CNS) imaging with either computerized tomography (CT) or magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) as needed. CT has the advantage of being rapidly and readily available, and being highly sensitive for subarachnoid blood, large masses, and early stroke evaluation. The fetal radiation exposure during cerebral CT imaging with shielding is minimal (~10 mrads). The American College of Obstetricians and Gynecologists (ACOG) guidelines are clear that if CT is the better or more readily available test than it should not be withheld from a pregnant patient.¹ MRI has the advantage of being magnetic based, and therefore having no radiation exposure—but has limited availability and may be lead to delay in diagnosis over CT imaging. If necessary, CT contrast dyes and cerebral angiography may be safely used in pregnancy. The use of MRI contrast (gadolinium) is controversial in pregnancy due to fetal concerns. However, the utilization of gadolinium contrast may be justified depending on the diagnosis in questions and if the benefits outweigh the risks of exposure.^1,2 There is evidence that gadolinium does cross the placenta, is cleared by the fetal kidneys that therefore has the potential to concentrate in the amniotic fluid. However, a large study of first trimester exposure to date did not show an increased risk for congenital anomalies or stillbirth with exposure in the first trimester, but did show an increased risk for rheumatologic/inflammatory conditions, stillbirth, and neonatal death with exposures in any trimester, suggesting that later exposures may be risker.³ These data were controlled for severity score—as women receiving MRI examinations in pregnancy are inherently an at risk population (having underlying disease that requires evaluation), but did not address the risks of “nonexposure” to imaging—such as the fetal risks of poor outcomes were mother to be compromised by failure to evaluate a serious condition. Therefore, gadolinium may still be utilized in pregnancy, if necessary after discussion with the patient and family. After evaluation for elevated intracranial pressure (ICP), my MRI or CT, spinal tap can be safely utilized in pregnancy to evaluate for subarachnoid blood and to rule out meningitis. Simultaneously with initiating the diagnostic workup, neurologic and neurosurgical consultation should be obtained when a neurologic condition is suspected.

Pregnancy is a unique physiologic state with multiple hormonal and physical changes—some of which increase the risk of neurologic disease manifestation. Maternal blood volumes are markedly increased, and there is an increase in angiogenic factors such as vascular endothelial growth factor, basic fibroblast growth factor (VEGF, bFGF), placental growth factor, estrogen, and progesterone—all of which promote the vascular proliferation and expansion, and perfusion of the placental.^4,5 Additionally, the placenta and fetus act as neuroendocrine organs—secreting a many of the hormones and peptides typically produced by the hypothalamus, pituitary, or their downstream endocrine organs, the adrenal glands and ovaries.⁶ Progesterone, one of the primary pregnancy hormones has a complex relationship with the brain and nervous system—promoting neurogenic repair, remyelination, as well as attenuating the inflammatory CNS responses in traumatic brain injury. Although exogenous progesterone has failed to produce clinical benefits for those with neurologic injury, there are currently phase III clinical trials underway utilizing progesterone for refractory epilepsy.^7,8 The pregnant state appears to be neurogenically complex in ways that we are only being to appreciate. Although acute brain injury and care is similar to the nonpregnant patient, as these complex hormonal interplays become better characterized, it is possible that their effects on recovery and care will be also become further delineated.

Headache is a common complaint in pregnancy.⁹ For patients with history of similar headaches outside of pregnancy, these not typically related a neurologic emergency. Chronic and recurrent headaches may be due to tension, migraine, sinusitis, pseudotumor cerebri, or in many cases be unexplained. However, a headache that is markedly different in character or manifestation, and/or is accompanied by focus neurologic symptoms should NOT be dismissed due to a prior history of headaches.

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 with 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 generally do not represent a neurologic emergency and can be managed symptomatically. Some medications used for the treatment of migraine headache are listed in Table 16-1. If headaches are becoming more frequent or severe, or have accompanying neurologic manifestations, they require further evaluation.

New-Onset Headaches

The new-onset, sudden, and/or severe headache (Table 16-2) or a headache with different location, quality, or accompanying neurologic symptoms should be under further evaluation (Fig. 16-1). 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 Chapter 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 (SAH), intracerebral hemorrhage (ICH), cerebral venous thrombosis (CVT), meningitis, and mass lesions (tumors or abscess).

Subarachnoid Hemorrhage

SAH can occur due to a wide variety of conditions, and it is responsible for 5% to 12% of maternal deaths in pregnancy.^10,11 Possible etiologies include ruptured cerebral aneurysms, cavernous malformations, arteriovenous malformations (AVM), or preeclampsia or eclampsia.¹² There is no way to clinically distinguish between intracranial bleeding due to 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 or may not have focal neurologic deficits, altered state of consciousness, seizures, and hypertension. The condition of the patient at presentation is the most important prognostic feature and is scored I to V (Table 16-3). For pregnant women with intracerebral hemorrhage—the traditional data suggest that 77% are due to aneurysmal rupture, and 23% due to AVM, with the remainder due to preeclampsia, vasculitis, and cavernous angioma.¹³ However, other data suggest that uncontrolled hypertension in preeclampsia is the more common reason for intracerebral hemorrhage.¹⁴ This significant risk of intracranial hemorrhage in preeclampsia appears to be primarily related to systolic hypertension.¹⁴ California data on maternal death suggests that majority of preeclampsia/eclampsia related deaths are due to delayed responses to vital signs, as well as poor provider knowledge of managing hypertensive disease, and inadequate control of blood pressure.¹⁵ Assuring that the team is appropriately knowledgeable and adequately controlling systolic blood pressure for these patients should therefore be a key goal of care.

The diagnosis of possible SAH in pregnancy starts with a high index of suspicion raised by the presentation and imaging with CT, MRI, or MRA. Clinical and laboratory evaluation for possible preeclampsia/eclampsia must be accomplished since this is the more common diagnosis and if confirmed, requires specific therapy and delivery for definitive treatment. However, SAH can occur with preeclampsia, especially for those with severe hypertension, seizure, and/or low platelet manifestations; therefore, the diagnosis of preeclampsia does not rule out the possibility of concurrent intracranial hemorrhage. If SAH is suspected than emergent imaging should be done and CT contrast dyes and cerebral angiography can both be safely utilized if needed. Spinal tap can be utilized to confirm the presence of subarachnoid blood and rule out meningitis as the cause of the headache once elevations in ICP by CT have been ruled out. Simultaneously with initiating the diagnostic workup, neurologic and neurosurgical consultation should be obtained.

Cerebral Aneurysms

Cerebral aneurysms usually occur on the vessels of the circle of Willis or the proximal portions of the vessels arising from it, with up to 2% of women of child bearing age having a known diagnosis of cerebral aneurysms.¹⁶ Saccular or berry aneurysms can be found in any patient but are more common in patients with Marfan, Ehlers-Danlos, or familial polycystic kidneys. Bleeds from aneurysms are more common in patients over 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. However, rupture is a rare event occurring in far less than 1% of pregnancies (1-10/10,000).¹⁷ Among those that do experience rupture in pregnancy, the majority of these events occur antepartum (more than 90%), with the majority occurring in the third trimester (80% of events). The 2015 American Heart Association guidelines discuss best practice on the management of unruptured aneurysms outside of pregnancy based on the best evidence for risk of rupture, and can be helpful to guide discussion.¹⁸ Aneurysmal rupture risks are highest with lesions more than 6 mm, with more than 91% of those experiencing rupture having lesions over that size. Those between 3 and 6 mm have a 62% rupture rate, and therefore treatment before pregnancy may be warranted for women with lesions in this size range.¹⁹

Arteriovenous Malformations

AVM has a general population prevalence of 18/100,000, with annual rupture risk of 2% to 4%.^20,21 AVM is most common cause of SAH in the pregnant patient, with up to 25% of SAH in pregnancy due to AVM.¹⁰ Given this, women with known AVM should likely undergo treatment prior to planning pregnancy.²² AVMs tend to rupture earlier in pregnancy than aneurysms, with a peak of 20 to 24 weeks, and then secondary peak postpartum.²³ Maternal mortality is high at 30% to 40%.²⁴

Ruptured Arteriovenous Malformations and Cerebral Aneurysm Management

The goal for acute treatment for pregnant women with SAH are the same as for any patient, including airway management, blood pressure reduction (systolic BP <140), management of cerebral edema, and seizure control. The patient should be positioned to allow lateral uterine displacement to improve perfusion with hypotension. Continuous fetal heart rate monitoring should only be utilized if there is concern for maternal hemodynamic instability, the fetal gestational age is viable and the hospital has neonatal facilities, the family preference is for fetal intervention, and interventions can safely be performed on the mother. Otherwise, intermittent fetal assessment is likely reasonable.²⁵ Careful attention to maternal oxygenation will improve fetal condition.

Supportive care maybe possible for some women, but often surgery is necessary in those with acute clinical deterioration.^22,26 Surgical management of both AVM and berry aneurysms can be accomplished in pregnancy but if the patient is near term with an unstable condition or SAH, consideration of delivery prior to or simultaneously with the surgical repair should be considered. A combined neurosurgical and MFM approach is necessary to assure predelivery care and planning for the best outcome for mom and baby. Surgery under hypotensive anesthesia is not recommended due to fetal perfusion concerns, but both hyperventilation and hypothermia have been utilized, although data is limited.^27,28 Hypothermia does not appear to improve outcomes however.²⁷ Mannitol for cerebral edema has very limited data, but appears to be safe. There are concerns for fluid shift and electrolyte imbalance in the fetus, and mannitol does appear to decrease uterine volumes at least in the short term.^28-30 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 uteroplacental perfusion. For ruptured cerebral aneurysms, endovascular treatment appears to have a lower complication rate than surgical clipping (9% vs 23%), although the approach is dependent on the specific patient and aneurysm characteristics.¹⁹ Women with ruptured AVMs during pregnancy are often delivered by cesarean section, although data on this are minimal, with the idea to decrease the risk of recurrent bleeding during the second stage with Valsalva and for blood pressure control. However, likely passive descent with operative delivery is a reasonable approach for some women as well to minimize risk. For stable, unruptured aneurysms the data suggest that vaginal delivery is safe for most women.¹⁶ Additionally, if the lesion (either AVM or aneurysm) has been surgically treated by excision or clipping, then vaginal delivery is reasonable.

Cerebral Venous Thrombosis

CVT is uncommon, accounting for less than 1% of strokes. However, 75% of these occur in women (3× the rate for men) likely due to the hormonal exposures of contraception and pregnancy, with a rate in pregnancy of 11.6/100,000 deliveries, and the majority occurring third trimester and during the postpartum period.^31,32 There are many predisposing risk factors including infection, cancer, thyroid disease, prothrombotic conditions, dehydration (hyperemesis), and autoimmune disease.³³

Headache is the most frequent presenting symptom of CVT—but the onset varies from gradual to acute and can even mimic SAH. It can also present similarly to a migraine with an associated aura. There may be associated with signs of intracranial hypertension, focal neurologic signs, altered state of consciousness, or seizures. The superior sagittal (62%) and transverse sinuses (45%) are the most commonly involved. Sagittal sinus thrombosis often causes motor deficits, bilateral deficits, and seizures. The deep venous sinuses are only rarely (11%) involved, but the mortality in these patients is 3 times higher than other locations.³⁴

Diagnosis of CVT

MRI imaging of the brain with MR venography is the most sensitive technique (90-100% accuracy) for demonstrating the lesion. CT of the brain may be negative in up to 30% of documented cases of CVT, but is still often utilized as a first test in women with new, severe headache where SAH is of high concern due to the rapidly available nature of this test, and the ability to evaluate for SAH. 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 thrombophilia.

Management of CVT

For all patients with CVT, admission for evaluation and anticoagulation are necessary, even in the setting of intracranial hemorrhage, as this can be secondary to the thrombosis and elevated venous pressure.³³ Low-molecular weight heparin is the first line anticoagulant therapy in pregnancy, and should be continued throughout the remainder of the pregnancy and at least 6 weeks postpartum (for a minimum total duration of 3-6 months of treatment unless a significant thrombophilia is identified).³³ A heparin drip can be utilized acutely for those with bleeding or where surgery may be needed due to the shorter half-life and easier ability to reverse. Transition to heparin therapy for delivery to allow for regional anesthesia may be accomplished with input from neurology, anesthesia, and obs/gyn physicians. Although the risk of seizures is high with this diagnosis, prophylactic antiepileptic therapy is not typically recommended.³³ All women with this diagnosis should avoid estrogen-containing contraception, but progesterone only contraception, including pills, implants, and intrauterine devices (IUDs) are generally considered safe for those with prior thrombosis diagnosis. The Centers for Disease Control and Prevention (CDC) medical eligibility for contraception guideline contains detailed information by diagnosis and method for providers discussing contraceptive options with women with neurologic disease.³⁵

Meningitis

Meningitis is inflammation of the meninges, or the membranes surrounding the brain and spinal cord and commonly presents with headache plus other symptoms such as fever, malaise, meningismus, photophobia, drowsiness, nausea/vomiting, neck stiffness, and perhaps focal neurologic signs. Overall, the most common cause of meningitis in both the population and pregnant women is herpes simplex virus (HSV), but there is a long list of viruses, fungi, and bacteria that can cause meningitis.³⁶ Viral meningitis has an incidence of 7.9/100,000 adults each year, with the most common viral ideologies being Enterovirus and HSV, while bacterial meningitis affects 2.6-6/100,000 adults, with the most common causes being Streptococcus pneumoniae, Neisseria meningitides, Haemophilus influenza type, and Listeria monocytogenes (to which pregnant women are particularly susceptible).³⁷ Bacterial meningitis in pregnancy has a high mortality rate (28%) as well as fetal loss rate (38%) and, therefore, a high degree of clinical suspicion is necessary for this diagnosis.³⁸

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. Empiric therapy for meningitis in pregnancy should include coverage for both HSV (acyclovir) as well as Listeria (a third- or fourth-generation cephalosporin, vancomycin, and ampicillin), all of which are safe in pregnancy at any stage. Dexamethasone is typically also recommended for adults with bacterial meningitis.³⁹ For viral meningitis, depending on the virus involved, there is the potential for fetal transmission, and further counseling, discussion and testing for fetal transmission and potential effects on fetal growth and development may be needed.

Mass Lesions

Intracranial mass lesions, tumor, or abscesses, can be another ideology of headache as well as other focal neurologic signs and seizures. Women of child-bearing age have an incidence of brain tumor of approximately 12/100,000, making it a rare new diagnosis in pregnancy. However, the volume expansion of pregnancy can unmask lesions in the third trimester due to fluid shifts.⁴⁰ Headaches with persistent nausea and vomiting are common symptoms of brain tumors due to increased ICP. These headaches are typically worse with position change, cough, Valsalva, and overnight (all signs of atypical headache associated with increased ICP). Brain tumors are NOT typically associated with hypertension or proteinuria, common findings for women with preeclampsia related headaches.

The cornerstone of the diagnosis of mass lesions is MRI or CT imaging of the brain. As noted above, MRI exposes the fetus to nonionizing radiation and can be safely performed at any stage of pregnancy with no known 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. However, MRI with contrast may be needed depending on the type and location of the tumor. Neurosurgical consultation should be obtained, if a mass lesion is suspected. Timing, treatment options, and evaluation will need to be individualized based on the type of mass, the findings, the patient’s symptoms, and stage of pregnancy. A full discussion with obstetrical team, MFM, and neurosurgery will be necessary for these complex patients. Patients with brain tumors are at high risk for seizures, although there is no evidence to support prophylactic antiepileptic therapy. Corticosteroids are typically given to reduce ICP acutely (and are considered safe in pregnancy). Women with brain tumors in pregnancy are at especially high risk for thrombosis (a leading cause of maternal mortality worldwide) especially if neurosurgery is required, and therefore should typically be anticoagulated with low-molecular weight heparin in the perioperative and postpartum period.⁴¹ Delivery planning will depend on the stage of the tumor, ICP at the time of delivery, and associated symptoms of elevated ICP. Regional anesthesia may or may not be possible depending on ICP as well, and anesthesia consultation as part of delivery planning is necessary.