Stroke in Pregnancy: A Focused Update

Abstract

Ischemic stroke (IS) and hemorrhagic stroke (HS) can be devastating complications during pregnancy and the puerperium that are thought to occur in approximately 30 in 100,000 pregnancies. In high-risk groups, such as women with preeclampsia, the incidence of both stroke subtypes, combined, is up to 6-fold higher than in pregnant women without these disorders. IS or HS may present in young women with atypical symptoms including headache, seizure, extremity weakness, dizziness, nausea, behavioral changes, and visual symptoms. Obstetric anesthesiologists who recognize these signs and symptoms of pregnancy-related stroke are well positioned to facilitate timely care. Acute stroke of any type is an emergency that should prompt immediate coordination of care between obstetric anesthesiologists, stroke neurologists, high-risk obstetricians, nurses, and neonatologists. Historically, guidelines have not addressed the unique situation of maternal stroke, and pregnant women have been excluded from the large stroke trials. More recently, several publications and professional societies have highlighted that pregnant women suspected of having IS or HS should be evaluated for the same therapies as nonpregnant women. Vaginal delivery is generally preferred unless there are obstetric indications for cesarean delivery. Neuraxial analgesia and anesthesia are frequently safer than general anesthesia for cesarean delivery in the patient with a recent stroke. Potential exceptions include therapeutic anticoagulation or intracranial hypertension with risk of herniation. General anesthesia may be appropriate when cesarean delivery will be combined with intracranial neurosurgery.

Ischemic stroke (IS) and hemorrhagic stroke (HS) are rare, yet highly morbid complications during pregnancy and the puerperium. The incidence of maternal strokes was recently estimated to be approximately 30 in 100,000 pregnancies including all subtypes.¹ In high-risk groups, such as women with preeclampsia and other hypertensive disorders of pregnancy, the incidence of maternal HS and IS combined is up to 6-fold higher than in pregnant women without these disorders.^2–5 In addition to maternal mortality, pregnancy-related stroke can lead to disability affecting a woman’s ability to care for herself and her children and to be productive personally and professionally. In this focused update, we review the available data on the epidemiology, pathophysiology, risk factors, and treatment of maternal stroke and discuss the role of the obstetric anesthesiologist in the identification and peripartum management of this potentially catastrophic event.

STROKE DEFINITIONS AND SUBTYPES

“Stroke” is defined broadly by the American Heart Association/American Stroke Association (AHA/ASA) to include IS due to central nervous system arterial or venous infarction or HS including nontraumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH).⁶ Cerebral venous thrombosis (CVT) can result in venous infarction and/or hemorrhage (ICH and/or SAH) due to venous congestion. The heterogeneity of stroke diagnoses can be confusing, and acute management differs depending on the specific stroke mechanism. Unless otherwise specified, we will use stroke to indicate the inclusive AHA/ASA definition (IS and HS); however, we will discuss the pathophysiology and management of each stroke subtype separately.

EPIDEMIOLOGY OF MATERNAL STROKE

Stroke accounted for 7.4% of maternal deaths in the United States from 2011 to 2014.⁷ The incidence of pregnancy-related stroke in the United States and Canada is increasing; recent population-based Canadian data suggest a 60% increase from 2003 to 2004, to 2015 to 2016.^8,9 Stroke-related maternal mortality may be underestimated because hypertensive disorders of pregnancy accounted for another 6.8% of US maternal deaths⁷ and 40%–70% of maternal mortality in women with preeclampsia is due to stroke. Pregnant and newly postpartum women are at risk for all stroke subtypes including IS, HS, and CVT. HS is the most common type of pregnancy-related stroke. Although stroke may occur throughout pregnancy, the highest risk epochs are in the third trimester and in the early postpartum period (within the first 6 weeks postpartum).¹⁰

General Risk Factors for Stroke

Risk factors for maternal stroke of all types include older age (although most pregnancy-related strokes occur in women under the age of 35 years old),¹¹ African American race, heart disease, thrombophilias, rheumatological disorders, and sickle cell disease. Pregnancy-specific risk factors include hypertensive disorders of pregnancy via endothelial dysfunction and impaired cerebral autoregulation, gestational diabetes, severe postpartum hemorrhage, and cesarean delivery.^{2–4,9,12–16} A population-based study found that having traditional stroke risk factors (eg, congenital heart disease, atrial fibrillation, or coagulation defects) substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations from adjusted odds ratio (aOR) 2.7 (95% confidence interval [CI], 1.8–3.9) for congenital coagulation defects to aOR 13.1 (95% CI, 9.1–18.9) for congenital heart disease.³ A subsequent study using the New York State Department of Health inpatient database highlighted preeclamptic women with infections, chronic hypertension, coagulopathies, or underlying pro-thrombotic conditions as particularly high-risk groups.¹³

Ischemic Stroke in Pregnancy and Postpartum

Risk Factors and Etiologies.

Arterial IS (AIS) is defined as an episode of acute neurological dysfunction attributable to focal infarction of the brain, spinal cord, or retina, in a defined arterial distribution.⁶ While AIS may be confirmed via radiological or pathological evidence, AIS can be diagnosed clinically based on the presence of neurological symptoms consistent with a vascular ischemic event persisting ≥24 hours without alternative explanation. Neurological signs and symptoms of AIS depend on the vascular distribution of the infarction (Table 1). Like myocardial infarction, AIS may present with atypical symptoms in young women including headache, dizziness, nausea, behavioral changes, and visual symptoms.^17–19

Table 1.

Common Arterial Ischemic Stroke Syndromes

Artery	Possible Symptoms/Signs
Anterior circulation (carotid system)
ICA	Contralateral hemiplegia; ipsilateral forced gaze deviation; global aphasia (left ICA), or severe hemineglect (right ICA)
Left middle cerebral	Aphasia (may be receptive, expressive, or both); right face/arm weakness/clumsiness/numbness; left gaze preference
Right middle cerebral	Left hemineglect; left face/arm weakness/numbness; right gaze preference; agitated delirium; anosognosia (lack of awareness of deficit)
Anterior cerebral	Contralateral leg weakness; apathy or abulia (particularly if bilateral); may mimic spinal cord compression if bilateral
Ophthalmic	Monocular blindness (amaurosis fugax)
Posterior circulation (vertebrobasilar system)
Anterior spinal	Bilateral weakness and numbness below level of lesion, sparing face
Vertebral and/or posterior inferior cerebellar artery	Vertigo; nausea; hiccups; headache; nystagmus; ataxic gait; hoarse voice/dysphagia; ipsilateral facial and contralateral limb/trunk numbness; Horner syndrome; tongue weakness/dysarthria
Anterior inferior cerebellar artery	Ataxia; contralateral weakness/numbness; acute unilateral hearing loss
Superior cerebellar	Ataxic gait; vertigo; nausea; nystagmus; headache; dysarthria
Midbasilar or basilar penetrators	Quadriplegia with preserved consciousness, vertical eye movements, and blinking (“locked-in syndrome”)
Top of the basilar	Loss of consciousness; posturing (may resemble seizure); cortical blindness
Posterior cerebral	Headache; contralateral visual field deficit; difficulty reading; amnesia; somnolence (if thalamic involvement); disconjugate gaze (if midbrain involvement); contralateral weakness/clumsiness

Symptoms may vary from patient to patient.

Abbreviation: ICA, internal carotid artery.

While AIS in older adults is often due to atrial fibrillation, large vessel atherosclerosis, or cerebral small vessel disease, maternal AIS is less commonly associated with traditional vascular risk factors.^2,4,20 Instead, in addition to the general pregnancy-related stroke risk factors listed above, unusual mechanisms such as carotid or vertebral artery dissection, paradoxical cardioembolism due to patent foramen ovale, and reversible cerebral vasoconstriction syndrome (RCVS) cause AIS in this population.

Pregnancy constitutes a physiological “stress test” challenging the maternal cardiovascular system. Cardiac remodeling, including left atrial dilation and left ventricular mass increase of up to 35%,²¹ may contribute to an increased risk of AIS due to cardioembolism. Preexisting heart disease was shown to confer a greatly increased odds (OR, 13.2; 95% CI, 10.2–17.0) of maternal stroke in 1 study.⁴ Pregnancy-associated cardiac dysfunction may be more severe in women with preeclampsia than in those without,^22,23 and preeclampsia increases the risk of peripartum cardiomyopathy.²⁴ Peripartum cardiomyopathy, occurring in approximately 1 in 3000 live births, is associated with major adverse cerebrovascular events, including cardioembolic stroke.²⁵

In the setting of increased preload and hypercoagulability, pregnant and postpartum women with a patent foramen ovale are also more vulnerable to AIS due to paradoxical embolism to the cerebral circulation. Amniotic fluid embolism can rarely cause AIS in patients with a patent foramen ovale or pulmonary shunt.²⁶ A recent systematic review found a strong association between active migraine, particularly migraine with aura, during pregnancy and increased IS risk (OR, 7.9–30.7).²⁷ This finding may be confounded by misclassification between migraine and severe preeclampsia in administrative data. The high rate of patent foramen ovale in migraineurs²⁸ may partially explain the increased risk of pregnancy-associated AIS in this population.²⁹

Timing of Stroke.

AIS can occur at any time during pregnancy or the puerperium.^2,30–32 It is most commonly seen in the third trimester or the early postpartum period.

Cerebral Venous Thrombosis in Pregnancy and Postpartum

Risk Factors and Timing.

CVT occurs when a clot arises in the dural sinuses or cerebral cortical veins. While CVT does not always lead to stroke, CVT can result in venous infarction and/or hemorrhage due to venous congestion and breakdown of the blood–brain barrier. The puerperium is one of the more common precipitants of CVT likely due to hypercoagulability, venous stasis, and endothelial damage.^33,34 CVT associated with inadvertent dural puncture during epidural catheter placement has also been reported.³⁵ Cesarean delivery, preeclampsia, and infections all increase the risk of puerperal CVT.³⁶ As the venous clot propagates, venous congestion, cerebral edema, increased intracranial pressure (ICP), infarction, and hemorrhage may develop. Unlike the classic sudden onset “thunderclap” headache of SAH, the onset of CVT symptoms is often insidious. Patients may only present for medical attention when the headache becomes intolerable, neurologic symptoms develop, or catastrophic bleeding occurs.

Emerging evidence implicates bacterial, fungal, viral, and some parasitic infections and inflammation as IS and CVT risk factors and “triggers” in vulnerable patients including obstetric patients.^4,13,37–41 A recent study using state-based administrative data (2007–2011) revealed that infection on admission increased the risk of stroke: aOR, 2.56 (CI, 1.25–5.24) for genitourinary infections and aOR, 10.4 (CI, 2.15–20.0) for sepsis.⁴²

Hemorrhagic Stroke In Pregnancy And Postpartum

Risk Factors and Etiologies.

Over 50% of pregnancy-related strokes are hemorrhagic and are often associated with high morbidity and mortality.^43,44 Although HS may result from vascular malformation rupture (eg, arteriovenous malformations [AVMs], cavernous malformations, cerebral aneurysms, or moyamoya-related vasculopathy), this mechanism is less likely in pregnant than in nonpregnant women.^45–47 Other risk factors for HS include hypertensive disorders of pregnancy, congenital or acquired coagulopathy, or CVT with associated hemorrhage. SAH can be a rare complication associated with dural puncture in obstetric patients.⁴⁸ While HS, particularly ICH, may present with focal neurological deficits, affected patients often present with more generalized symptoms such as severe headache, altered mental status, loss of consciousness, or seizure. Classically, SAH presents with a thunderclap headache, often described by the patient as the “worst headache of my life.”

Hypertensive Disorders of Pregnancy.

Preeclampsia and severe hypertension have been repeatedly associated with HS in pregnancy.^12,49,50 In 1 case series of patients with severe preeclampsia or eclampsia and stroke, 25 of 27 had HS and 2 of 27 had IS. Twenty-four (24) of these women were under active medical care at the time of their event, and each had prestroke systolic hypertension (systolic blood pressure [SBP] >155 mm Hg).⁵⁰ Based on their observations, the authors recommended antihypertensive treatment in preeclamptic and eclamptic women with SBP ≥150–160 mm Hg. In a retrospective review of UK maternal stroke-related deaths for a 30-year period (1979–2008), substandard management of dangerously high blood pressure was also implicated as a preventable cause.⁴⁹

RCVS and Posterior Reversible Encephalopathy Syndrome.

Preeclampsia and eclampsia are highly associated with RCVS, a transient vasospastic vasculopathy first described by Call et al⁵¹ in postpartum women.⁵² RCVS typically presents with recurrent, sudden onset, severe thunderclap headaches.^53–55 In severe cases, segmental vasoconstriction of the large cerebral arteries may lead to IS due to vasospasm. Cortical SAH or ICH is also often seen, possibly due to associated blood–brain barrier dysfunction.⁴⁶ In addition, preeclampsia and eclampsia have overlapping features with posterior reversible encephalopathy syndrome (PRES),^56,57 including vasogenic edema and blood-brain barrier dysfunction which can cause seizures and ICH. PRES often predominantly affects the parietal and occipital lobes, causing severe headache, confusion, and visual symptoms, like severe preeclampsia. In case series, 92%–98% of women with eclampsia had radiographic evidence of PRES on magnetic resonance imaging (MRI).^58,59 Despite their “reversible” monikers, RCVS and PRES can cause irreversible damage and are important causes of both IS and HS in peripartum women.

Brain AVMs.

The literature is sparse and contradictory regarding whether the risk of AVM rupture is increased during pregnancy. One study showed an annual 5.7% versus 1.3% hemorrhage rate in pregnant versus nonpregnant women.⁶⁰ However, several other studies have shown no substantial increased hemorrhage risk in pregnant versus nonpregnant women.^44,61–63

Although some experts recommend elective treatment of unruptured AVMs before pregnancy,⁶⁴ the risks of treating unruptured AVMs may outweigh the benefits. The only randomized trial of medical versus interventional treatment of unruptured cerebral AVMs was stopped due to evidence of superiority of medical management,⁶⁵ and long-term outcomes continue to support this approach.⁶⁶ Treatment of ruptured AVMs in a pregnant woman should be guided by neurosurgical considerations, as they would be in nonpregnant patients.

Cerebral Cavernous Malformations and Unruptured Cerebral Aneurysms.

Cerebral cavernous malformations do not appear to have an increased risk of rupture (3%/year) in pregnant versus nonpregnant women.^67,68 Similarly, recent population-based studies do not support an increased risk of bleeding from unruptured cerebral aneurysms during pregnancy (1.4%) or delivery (0.05%), so prophylactic intervention is typically not indicated for asymptomatic, unruptured aneurysms.^69,70 One of the studies showed a 70% cesarean delivery rate, although a detailed review of the delivery decision-making process was not included. When aneurysm rupture does occur, prompt neurosurgical intervention with clipping or coiling of the culprit aneurysm is associated with improved maternal and fetal outcomes.⁷¹

Moyamoya Vasculopathy.

Moyamoya syndrome is a progressive stenotic vasculopathy of the terminal internal carotid arteries, leading to formation of fragile collateral vessels. The syndrome is named for the “puff of smoke” appearance of these collaterals, which are prone to rupture. Moyamoya can cause both HS, due to vessel rupture, as well as IS, due to “border zone” infarction in territories hypoperfused by severely stenotic terminal carotid arteries. There are few high-quality data regarding the risk of stroke in pregnant women with moyamoya syndrome. Some case series suggest an increased IS and HS risk, but there is no clear protective effect of surgical revascularization before pregnancy.^72,73

Timing of Stroke.

The timing of HS in pregnancy tends to be more varied than that of IS, with elevated risk extending from the second half of pregnancy through the early postpartum periods.³⁰ There is some disagreement in the literature as to the highest risk time for pregnancy-related ICH.^2,44,74 HS due to rupture of vascular lesions such as AVMs and aneurysms is more often seen in the late second and third trimesters, whereas hypertensive and RCVS-related hemorrhages are most often seen postpartum.^46,71

ACUTE STROKE MANAGEMENT IN PREGNANCY AND POSTPARTUM

Arterial Ischemic Stroke

AIS in pregnancy is a neurological emergency, and well-established protocols should be in place to guide initial triage and management. Historically, guidelines have not addressed the unique situation of maternal stroke, and pregnant women have been excluded from the large IS trials. Several publications and professional societies, such as Heart & Stroke of Canada, have since highlighted that pregnant women suspected of having AIS should be evaluated for the same therapies as nonpregnant women.^75–77 A “code stroke” rapid response protocol should be immediately initiated with initial neurological assessment by the treating physician in conjunction with a neurologist in-person or via telemedicine. The “last known well” time should be established as the time of stroke onset. Emergent brain imaging (ideally within 20 minutes of arrival to the emergency department⁷⁵) should be obtained either with computed tomography (CT) or MRI, if available immediately; neither of these imaging technologies is contraindicated during pregnancy.^78,79 If symptoms suggest a large cerebral vessel occlusion, CT or magnetic resonance (MR) angiography should be performed for confirmation. Iodinated CT contrast may be used if a large vessel occlusion is suspected, with minimal fetal risk. Gadolinium contrast should ideally be avoided during pregnancy and is not needed for acute stroke diagnosis.

Once cerebral hemorrhage has been ruled out by neuroimaging, thrombolytic treatment can be considered while weighing the maternal and fetal risks and benefits. In general, recombinant tissue plasminogen activator (alteplase) is effective therapy for AIS for selected patients when given in the first 4.5 hours after symptom onset or last known well time^80,81 and is the current standard of care unless medically contraindicated.⁷⁵ Tenecteplase may be equally effective for selected patients and may come into wider use in the future due to its ease of administration as a single bolus.^82,83

There are no human studies exploring the fetal risks of these thrombolytic agents. Alteplase and tenecteplase are large molecules that do not cross the placenta and are not teratogenic at stroke treatment doses in animal studies.⁸⁴ Case reports cite a few examples of placental hemorrhage (not morbid) or early pregnancy loss, which may be more related to the underlying maternal condition than to the therapy.^85,86 There are also limited data to guide assessment of maternal risks. Recent lumbar dural puncture is not an absolute contraindication to thrombolysis, although the allowable needle gauge is not specified.⁷⁵ Cesarean delivery within the past 48 hours was associated with bleeding requiring transfusions after thrombolysis, but no deaths were reported in the limited available data.⁸⁷ Despite the absence of randomized controlled trials, case reports and registry data about pregnant women treated with intravenous (IV) thrombolysis report similarly good maternal and fetal outcomes to nonpregnant women (Supplemental Digital Content, Table 1, http://links.lww.com/AA/C810).^88–90

For patients with AIS due to large vessel cerebral occlusions, mechanical thrombectomy is now the standard of care in most patients within 6 hours of symptom onset⁹¹ and in selected patients up to 24 hours from last known well time.^92,93 Pregnant or postpartum patients with large vessel occlusions should be transferred emergently to a thrombectomy-capable stroke center. Advanced imaging techniques such as perfusion-weighted CT or MRI can help to identify patients who may be appropriate candidates for mechanical thrombectomy outside of the standard 6-hour time window (Supplemental Digital Content, Table 2, http://links.lww.com/AA/C810).

Overall, current expert opinion favors treating pregnant women with moderate to severe AIS, after weighing the relative maternal and fetal risks and benefits in consultation with a multidisciplinary team including a neurologist with expertise in AIS treatment, a high-risk obstetrician, and the patient or her health care proxy if she is unable to consent.^75,76

Management of Hypertension.

The management of hypertension is complicated by different definitions of and recommended treatment for mild and moderate disease. Blood pressure thresholds for treatment of hypertension for primary cardiovascular disease prevention vary in the general population from BP = 130–139/80–89 mm Hg to BP ≥140/90 depending on the patient’s underlying risk factors.⁹⁴ Obstetric guidelines have differed on whether or not to treat maternal blood pressure in this range, in part due to concern for negatively impacting the fetus.⁹⁵ A recent trial investigated fetal outcome in women with chronic or gestational hypertension who were randomized to either a “less tight” target DBP = 100 mm Hg or “tight” target DBP = 85 mm Hg.⁹⁶ There was no significant difference in the fetal outcomes between groups. A recent Cochrane Review (49 trials, 4723 women) reported that the use of antihypertensive agents to treat mild and moderate hypertension in pregnant women (defined as SBP = 140–169 mm Hg or DBP = 90–109 mm Hg, or both) reduced the risk of ≥1 severe hypertensive events by 50%.⁹⁷ However, there were insufficient data to comment on the impact of specific outcomes such as stroke. Recently, the International Society for the Study of Hypertension in Pregnancy (ISSHP) recommended more active management of mild to moderate hypertension (defined as BP ;≥135–140/85–90 mm Hg) in pregnant women, suggesting a target BP = 110–140/85 mm Hg.⁹⁸

Severe hypertension in pregnant women (sustained BP ≥160/110 mm Hg) should be treated with the mixed nonselective β-blocking and α-1-receptor blocking agent labetalol as the first-line therapy according to American College of Obstetrics and Gynecology (ACOG), due to its efficacy and lack of serious side effects.^99,100 Hydralazine is an alternative first-line agent. Despite a recent meta-analysis suggesting that oral nifedipine may be a viable alternative therapy in pregnant women,¹⁰¹ it is not among the agents recommended in the 2018 AHA Guidelines for acute management of hypertension in AIS patients before IV alteplase.⁷⁵ IV labetalol, hydralazine, and nicardipine are recommended in both settings.

In the setting of AIS, management of hypertension is complicated by the loss of normal cerebral autoregulation, causing cerebral perfusion to become pressure passive.¹⁰² This can result in a “pressure-dependent examination,” wherein the patient may have neurological deficits at a lower blood pressure that resolve at higher blood pressures. Thus, AIS patients without renal or myocardial injury may be allowed “permissive hypertension” although the evidence is mixed on the efficacy of this approach.^103–108

Hemorrhagic Stroke

Initial HS management for both acute ICH and SAH includes blood pressure reduction (to SBP ≤160 mm Hg), reversal of anticoagulation, and identification of the etiology, with source control if feasible. Repeat CT should be obtained within 6 hours (or sooner, if neurological examination deteriorates) to assess for hematoma expansion. CT or conventional angiography can identify vascular lesions amenable to endovascular or neurosurgical intervention.¹⁰⁹ Early life-threatening complications of HS include hematoma expansion, hydrocephalus, increased ICP, and brain herniation, highlighting the need for specialized neurocritical care. Aneurysm clipping and coiling, AVM embolization, and resection have each been successfully performed in pregnant women.^110,111

Hydrocephalus due to obstruction of the cerebral ventricular drainage system can develop rapidly in patients with ICH or SAH. Signs of high ICP include severe headache, hyperreflexia, nausea, vomiting, blurred or double vision, and decreased level of consciousness. Management of high ICP includes elevation of the head of the bed, judicious use of analgesic and anxiolytic medications to minimize pain and agitation, maintenance of normothermia, and hyperosmolar therapy. Mannitol has been associated with a decrease in amniotic fluid volume without deleterious fetal effects¹¹² and may be given during pregnancy. As mannitol (1 g/kg) and hypertonic saline (30 mL bolus of 23.4% NaCl) are typically used only in life-threatening situations with impending brain herniation, potential fetal risks would likely be outweighed by the maternal therapeutic benefits. Cerebral venous congestion should be minimized; specifically, central venous catheters should be placed in the subclavian or femoral veins rather than in the internal jugular position and the patient’s head should be kept midline. Hyperventilation may be used as a temporizing measure pending emergent surgery,¹¹³ but should not be continued due to risk of cerebral and placental ischemia from vasoconstriction. In the absence of specific hyperventilation targets in pregnancy, it may be reasonable to aim for a partial pressure of arterial carbon dioxide (Paco₂) less than the baseline mean of 25–30 mm Hg at term and greater than a Paco₂ of 20 mm Hg which has experimentally been associated with fetal compromise.¹¹⁴ Management of severely increased ICP may require placement of an external ventricular drain and/or emergent decompressive craniectomy and clot evacuation. After 24 weeks of pregnancy, women should be positioned with left uterine displacement intraoperatively to minimize compression of the inferior vena cava.

Seizures should be aggressively controlled in women with ICH or SAH. Electroencephalography should be performed for at least 24 hours if the woman is comatose following HS, as seizures may be subclinical.¹¹⁵ In addition to hydrocephalus, cerebral edema, and increased ICP, SAH may be complicated by delayed cerebral ischemia due to vasospasm.¹¹⁶ Nimodipine, which is commonly given as part of post-SAH protocols, is safe during pregnancy.¹¹⁷

Cerebral Venous Thrombosis

The recommended treatment for CVT is therapeutic anticoagulation. Both unfractionated and low–molecular weight heparin are safe to use during pregnancy.¹¹⁸ For CVT with concomitant ICH, anticoagulation should still be given, as there does not seem to be increased bleeding risk.^33,34,119 Endovascular thromborhexis (mechanical disruption) and thrombectomy (extraction) of the clot may be utilized in severe cases.¹²⁰ While the puerperal state is often the provoking factor, women with pregnancy-related CVT should be evaluated for an underlying thrombophilia.

INTRAPARTUM CARE OF THE PARTURIENT WITH STROKE

The intrapartum care of a woman with pregnancy-related stroke is governed by the same basic principles as is the care of pregnant women with other comorbidities. In general, neurological emergencies should be prioritized and treated according to neurological principles. Of paramount importance is coordinated, interdisciplinary planning between the neurological experts, high-risk obstetricians, obstetric anesthesiologists, neonatologists, and nurses. Depending on the illness acuity and severity, these conversations may need to take place urgently. Recent data found an increased risk of additional cardiovascular and cerebrovascular events in nonpregnant IS patients who undergo elective, noncardiac surgery up to 9 months after their stroke.¹²¹ Comparable data to predict the risk of obstetric surgery or vaginal delivery for pregnant women with recent stroke is lacking. If there are no obstetric indications for cesarean delivery, then it may be prudent to proceed with a vaginal delivery if not contraindicated.

THE ROLE OF THE OBSTETRIC ANESTHESIOLOGIST

Stroke Recognition

Obstetric anesthesiologists are ideally suited to recognize the key signs and symptoms of pregnancy-related stroke, given their role as labor floor intensivists. Early warning systems should alert the obstetric anesthesiologist when pregnant or newly postpartum women present with seizure, extremity weakness, or postpartum headache. Addressing a few specific considerations can help to identify patients at risk and to plan appropriate care (Table 2). First, stroke must be considered early in the differential diagnosis, as “time is brain.” Although postpartum headache occurs in up to 40% of women,¹²² severe headache that is different from her usual migraine and is associated with other neurological findings (eg, facial drooping, aphasia, arm or leg weakness, Table 1) should prompt an immediate “code stroke.” Bilateral neck pain commonly accompanies postdural puncture headache, but severe unilateral neck pain can represent a more ominous carotid or vertebral artery dissection, potentially leading to stroke. A severe positional headache, worse when the patient is supine and improved when she is upright, the reverse of postdural puncture headache symptoms, can be a sign of increased ICP. These and other atypical, severe headaches warrant additional expert guidance on diagnosis as they can signal stroke etiologies such as CVT, even in the setting of a known dural puncture.¹²³ Pregnancy-related stroke can also present with seizure, which may or may not be related to preeclampsia.

Table 2.

Key Considerations for Diagnosis and Anesthetic Care of Peripartum Stroke

Stroke Recognition

Is her headache atypical for (benign) tension, migraine or postdural puncture etiology?

Is there severe unilateral neck pain, worse pain when supine, or associated focal neurologic findings?

Have you considered stroke EARLY in the diagnosis? (“Time is Brain”)

Have you initiated a “code stroke” rapid response protocol?

Anesthetic Planning

Is she a candidate for neuraxial anesthesia?

What is her coagulation status (considering thrombolytic, other anticoagulant, and antiplatelet therapies)?

Is she at increased risk for brain herniation with a dural puncture (via spinal or attempted epidural anesthesia)?

Concerning features include brain imaging evidence of mass effect, ventricular obstruction, signs or symptoms of increased intracranial pressure

If general anesthesia is needed for cesarean delivery and/or neurosurgical intervention

Does she have a relative contraindication to succinylcholine?

Would she benefit from a total intravenous anesthetic?

Does she need transient hyperventilation, and/or hyperosmolar therapy to decrease ICP?

Abbreviation: ICP, intracranial pressure.

Anesthetic Planning

For anesthetic planning, the same basic principles with some additional considerations apply for women with and without pregnancy-related stroke. Neuraxial techniques provide optimal labor pain management and cesarean delivery anesthesia and are therefore the techniques of choice unless specifically contraindicated. Some clinical scenarios may lend themselves to vaginal delivery without Valsalva (eg, in moyamoya vasculopathy) facilitated by epidural analgesia. Critical to assessing the feasibility of neuraxial techniques is knowing (a) the woman’s coagulation status; and (b) the impact of the stroke and any related lesions have had on her intracranial anatomy and physiology. In women with altered mental status or inability to cooperate, neuraxial anesthesia likely is not feasible.

Many pregnant women with prior stroke, risk factors for stroke, or recent stroke may be receiving anticoagulants or antiplatelet therapy. In these cases, the Society for Obstetric Anesthesia and Perinatology (SOAP) and American Society for Regional Anesthesia and Pain Medicine (ASRA) guidelines for neuraxial anesthesia for women on anticoagulants may be consulted.^124,125 Two additional key issues should be addressed in consultation with a neurological expert. First, intracranial mass effect that predisposes the patient to brain herniation in the setting of dural puncture (intentional or unintentional) should be excluded. If the stroke-associated intracranial hemorrhage, edema, or other tissue damage do not cause significant intracranial mass effect, hydrocephalus with obstruction to cerebrospinal fluid (CSF) flow, or increased ICP, then it is often safe to proceed with a neuraxial anesthesia if feasible.¹²⁶ Second, the risk of disrupting an intracranial vascular lesion should be considered. Typically, neuraxial anesthetics do not disrupt unruptured intracranial vascular lesions in the absence of extreme blood pressure changes. However, there may be ideal blood pressure ranges that decrease the hemorrhage risk for fragile vascular lesions such as moyamoya vasculopathy or help maintain adequate cerebral perfusion in AIS.

If general anesthesia is needed, it is equally important to understand the degree to which ICP or other stroke sequelae need to be accommodated.^126,127 Succinylcholine, commonly used for rapid sequence induction, causes a small increase in ICP, but is unclear the degree to which this finding is clinically significant.^128,129 In addition, some women with a dense paresis or restricted ambulation poststroke may be at risk for proliferation of extrajunctional cholinergic receptors leading to critical hyperkalemia with succinylcholine use.¹³⁰ This vulnerability typically occurs at least 24 hours after the neurologic injury. Alternative strategies to facilitate endotracheal intubation include rocuronium (1.2 mg/kg) or high-dose remifentanil (4–6 μg/kg rapid bolus).^126,131 With high-dose remifentanil, a generous dose of ephedrine (15–20 mg) is recommended to prevent hypotension and bradycardia in women without underlying hypertension. Women on antiseizure medications including magnesium sulfate (MgSO₄) can experience prolonged neuromuscular blockade from nondepolarizing agents.¹³²

If ICP is greatly increased, then the techniques described in the treatment of HS can be used acutely in the operating room: head elevation if feasible, a brief period of mild-moderate hyperventilation (eg, 20 mm Hg < Paco₂ < the baseline mean of 25–30 mm Hg as described above), and/or hyperosmolar therapy (eg, mannitol). A total IV anesthesia technique with propofol (100–150 μ/kg/min) and remifentanil (0.1–0.2 μ/kg/min) infusions may facilitate ICP stability when compared with a volatile agent and nitrous oxide–based technique.¹³³ Remifentanil or IV lidocaine can also be used as adjuncts to facilitate a smooth intubation or extubation without coughing.¹²⁷ Multimodal analgesic therapy with scheduled nonsteroidal anti-inflammatory agents and acetaminophen has an opioid-sparing effect for postoperative analgesia.^134,135 In the absence of neuraxial opioids, transverse abdominis plane blocks, catheters, or quadratus lumborum blocks can add significant additional postoperative analgesia, if not contraindicated by anticoagulants or other antiplatelet agents.^136,137

Stroke Sequelae

A small fraction of general AIS patients may develop central pain syndrome. This stroke sequela, usually seen after thalamic stroke, can manifest typically 1–3 months poststroke as neuropathic pain in a variety of distributions (shoulder, head, extremity) corresponding to the territory of the initial insult.^75,138 Potential therapies include pregabalins, antiseizure medications, and antidepressants. Although central pain syndrome has not yet been reported in a pregnant IS patient, one could envision associated challenges to placing standard monitors and sterile barriers in the affected areas and to overall pain management. These women would likely benefit from neuraxial analgesia or anesthesia for labor or cesarean delivery.

Rarely, women may experience transient reemergence of stroke-related deficits or poststroke recrudescence (PSR) when exposed to triggers such as hypotension, insomnia/stress, or benzodiazepine use.¹³⁹ In 1 investigation, mild PSR symptoms occurred abruptly and transiently, on average 4 days poststroke, without evidence of new radiologic findings. Another report described a woman in sickle cell crisis treated with high-dose hydromorphone who manifested PSR from a stroke 30 years prior.¹⁴⁰

POSTPARTUM CARE AND FUTURE PREGNANCIES

Few studies document the risk of recurrent strokes in pregnant women with pregnancy-related strokes. One study found the recurrent AIS risk during pregnancy or puerperium to be 1% within 1 year and 2.3% within 5 years, with the greatest risk during the 6 weeks postpartum.¹⁴¹ The pooled incidence of recurrent CVT in future pregnancies is approximately 8 of 1000 pregnancies, and women with previous CVT may benefit from low–molecular weight heparin thromboprophylaxis.^142,143 There is a paucity of data on the recurrence risk of HS.

Women with pregnancy-related stroke should be referred to a vascular neurologist for follow-up. Secondary stroke prevention depends on the stroke etiology and will in most cases include antiplatelet or anticoagulant therapy. Women with hypertensive disorders of pregnancy are particularly vulnerable to future cerebrovascular and cardiovascular morbidity and mortality and should have close follow-up.¹⁴⁴ Modifiable risk factors such as obesity, hypertension, physical inactivity, tobacco use, poor diet, or substance use disorders should all be addressed during this period. Despite the risks, women with prior stroke have successfully delivered healthy babies during the index and future pregnancies should not routinely be discouraged from pursuing desired pregnancies.^145,146

BREASTFEEDING

A recent study of 300,000 Chinese women revealed that breastfeeding for at least 6 months was associated with a reduced risk of both cardiovascular disease and stroke in later life.¹⁴⁷ The risk was inversely proportional to the length of time breastfeeding. Breastfeeding as secondary stroke prevention was not examined, and adjustments were not made for preexisting risk factors. Warfarin, unfractionated heparin, and low–molecular weight heparin can be used as needed in breastfeeding women for secondary prevention of stroke and transient ischemic attack.¹⁴⁸ The National Institutes of Health website Lactmed (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm) can be referenced for information on the compatibility of specific medications with breastfeeding.

SUMMARY

Stroke is a key cause of severe maternal morbidity and mortality. Early identification of stroke is critical, and women with pregnancy-related stroke require complex interdisciplinary care. Obstetric anesthesiologists should be familiar with the signs and symptoms of stroke and the initial management, short-term complications, and long-term sequelae. Coordinated care between obstetric anesthesiologists, neurologists, and obstetricians is needed in the peripartum period, with the goal to minimize complications and long-term disability.