Stroke

Stroke is defined by the World Health Organization as a “neurological deficit of cerebrovascular cause that persists beyond 24 hours or is interrupted by death within 24 hours.” Estimates of the incidence of cerebral infarction in pregnant women vary widely and range from 0.004% to 0.2% of all deliveries.⁴ The risk for stroke in a pregnant patient is 13 times higher than in an age-matched nonpregnant patient and can be attributed to a variety of causes. The most common causes of stroke in pregnancy are arterial occlusion, venous thrombosis, and preeclampsia/eclampsia.^9,¹⁰ Hypertension is a major underlying factor for the development of these conditions and subsequent stroke.¹⁰

Arterial embolism or thrombosis accounts for 60% to 80% of cases of ischemic stroke during pregnancy.¹¹ Stroke secondary to arterial occlusion tends to occur during the second and third trimesters of pregnancy and during the first week after delivery.¹¹ This gestational pattern corresponds to appearance of the hypercoagulable state in the latter stages of pregnancy and the puerperium.

All patients suspected of having an ischemic stroke should undergo a thorough radiologic and laboratory investigation. Computed tomography (CT) is a good initial study to exclude hemorrhagic stroke and can identify some cases of ischemic stroke, depending on the region of the brain affected and the length of time since arterial occlusion. Magnetic resonance imaging (MRI) has greater sensitivity and resolution than CT. Angiography can be useful, particularly when intra-arterial thrombolytic treatment is anticipated. Helpful initial laboratory investigations include a complete blood count, electrolytes, erythrocyte sedimentation rate, coagulation studies, and urinalysis. When a cardiac source is suspected, a chest radiograph, electrocardiogram, and echocardiogram should be obtained. Transesophageal echocardiography is superior to transthoracic echocardiography and is safe for pregnant patients.¹² Carotid duplex ultrasound and magnetic resonance angiography are noninvasive techniques for investigating extracranial carotid disease.

Potential interventions for arterial occlusion in pregnant women include antiplatelet agents and anticoagulation. Appropriate medical care, including intravenous hydration, antibiotics, and treatment of seizure disorders, is important when indicated.

Intracranial venous thrombosis occurs at an estimated incidence of 1 in 2500 to 1 in 10,000 deliveries ¹³ and accounts for 20% to 40% of cases of ischemic stroke during pregnancy.¹¹ It is more common in pregnant women than in nonpregnant women.¹⁴ This disorder tends to develop in multiparous women 3 days to 4 weeks after childbirth, with most cases occurring in the second or third postpartum week.^11,^13,¹⁵^–¹⁸ Intracranial venous thrombosis during pregnancy is less common, with just a quarter of cases occurring during actual pregnancy as opposed to after pregnancy.^13,^14,¹⁹^–²¹ Most cases are idiopathic,²¹ although many systemic conditions can predispose to intracranial venous thrombosis. Venous sinus thrombosis is thought to arise as a result of the hypercoagulable state of pregnancy, in addition to alterations in cerebral vessel walls.^22,²³

More than 70% of cases involve occlusion of multiple venous sinuses or cerebral veins.²⁴ Cortical veins are involved more commonly than deep cerebral and cerebellar veins.²¹ Headache is the most common initial symptom.²⁵ Other common clinical findings are nausea and vomiting, seizures, focal neurological deficits, fever, and altered mental status.²¹

The diagnosis of intracranial venous thrombosis is based on clinical findings and radiologic studies. Imaging modalities such as CT, MRI, and angiography are useful. Investigation of possible predisposing factors with tests such as coagulation studies is important. When the diagnosis is confirmed, management begins with adequate hydration and treatment of elevated intracranial pressure, hydrocephalus, and seizures.²¹ Treatment options for intracranial venous thrombosis include high doses of heparin (1000 IU/hr to start; activated partial thromboplastin time >1.5 to 2 times control) and endovascular fibrinolysis followed by heparinization and surgical thrombectomy.²¹ Einhaupl and colleagues found that patients receiving intravenous heparin for intracranial venous thrombosis had significantly better neurological outcomes and mortality rates than did patients receiving placebo treatment.²⁶ Underlying predisposing disorders, such as sinusitis, must also be treated.²¹

Mortality rates of 33% for intracranial venous thrombosis have been reported ¹⁵; however, neurological outcomes in survivors are usually good.²¹ Srinivasan found that 59% of patients recovered without significant neurological disability.¹⁵

Another entity that has been described as a cause of stroke is postpartum cerebral angiopathy (PCA).²⁷ PCA is a disorder of blood vessels in recently pregnant patients that can be subdivided into three categories. Primary PCA occurs without a known etiology. Secondary PCA results from medications, particularly ergot derivatives. Tertiary PCA occurs in the setting of eclampsia. Angiography in patients with PCA reveals irregular narrowing of affected blood vessels.

Generally, the risk for stroke in a pregnant patient is at its peak during delivery.²⁸ Specifically, the risk is greatest 2 days before delivery and 1 day after; there has also been found to be an increased occurrence of stroke 6 weeks after delivery.²⁹ Other studies have identified racial differences in pregnancy-related stroke, with an increased incidence in patients of Asian descent.³⁰

Aneurysmal Subarachnoid Hemorrhage

Epidemiology

Generally speaking, intracranial hemorrhage can be either intracerebral (ICH) or subarachnoid (SAH). SAH accounts for approximately half the cases of intracranial hemorrhage in pregnant patients.¹⁶ The majority of SAH is from aneurysms, although a small proportion can be secondary to AVMs (discussed later).³¹ Other reported causes of SAH during pregnancy include mycotic aneurysms,³² postpartum angiopathy,³³ and unidentifiable causes.³⁴

The incidence of spontaneous SAH during pregnancy ranges from 0.01% to 0.05% of all pregnancies.^6,^8,³⁵ This equates to 1 per 10,000, which is five times higher than in nonpregnant patients.⁹ Dias and Sekhar found the mean age for pregnant patients with aneurysmal hemorrhage to be 29.4 years and the mean gestational age to be 30.5 weeks.⁸ SAH accounts for approximately 5% of maternal mortality, a figure that has stayed consistent over time, and it is at least the third most common nonobstetric cause of maternal death.³⁶^–³⁹ In some regions, SAH is the leading cause of nonobstetric maternal death.⁴⁰ The overall mortality rate is 35%, which is comparable to that in the nonpregnant population.⁸

Certain periods of pregnancy confer an increased risk for aneurysmal rupture. The second and third trimesters of pregnancy are associated with an elevated risk for rupture because of the increase in cardiac output that takes place after the first trimester.^41,⁴² This risk peaks at 30 to 34 weeks’ gestation.⁸ Aneurysmal rupture is also more common during the actual time of labor and delivery, presumably because of the hypertensive nature of childbirth.³⁷

The menstrual and reproductive characteristics of the patient likewise play a role in the risk for aneurysmal rupture. SAH has been found to affect primiparous women more than multiparous women,⁴² but also the other way around.⁴³ Okamoto and coworkers found that nulligravidity conferred a fourfold increased risk for aneurysmal SAH.⁴⁴ In that same study, patients with earlier menarche (defined as onset before the age of 13 years) had a threefold increased risk. In a Taiwanese cohort, older age at first pregnancy and earlier pregnancies were risk factors.⁴⁵ Contrarily, another study found that older age at first pregnancy was protective.⁴⁶

Further research is needed to understand the endocrinology underlying aneurysms and pregnancy inasmuch as clinical studies have been inconclusive. Some studies have found increased parity to confer a long-term protective effect on the risk for SAH,⁴⁷ whereas other data have shown an increased risk for hemorrhage with increasing parity.⁴⁸ In addition, the use of hormone replacement therapy has been found to be protective against SAH.⁴⁶

Management

Management of SAH is complicated by the fact that two patients are involved, not just one. When aneurysmal SAH has been diagnosed, treatment begins with medical stabilization of the patient. Placement of an arterial catheter permits continuous monitoring of blood pressure and treatment of hypertension and hypotension. Maternal hypotension should be avoided because the fetus is passively dependent on maternal blood pressure for adequate perfusion and is vulnerable to maternal hypotension. As in nonpregnant patients with SAH, seizure prophylaxis and treatment with nimodipine in anticipation of vasospasm are important. Continuous fetal heart rate monitoring is essential. Adequate analgesia, sedation, and antiemesis should be provided.

The risk for recurrent bleeding during the remainder of pregnancy in patients with an untreated aneurysm is 33% to 50%,^49,⁵⁰ with a maternal mortality rate of 50% to 68%.^49,^51,⁵² In an analysis of 118 pregnant patients with aneurysmal SAH, Dias and Sekhar found that surgical treatment of a ruptured aneurysm was associated with significantly lower maternal and fetal mortality rates than was conservative treatment.⁸ Thus, management of aneurysmal SAH in pregnant patients should be the same as in patients who are not pregnant^23,^42,^53,⁵⁴ (i.e., the ruptured aneurysm should be treated). Unruptured aneurysms should be treated if they are symptomatic or enlarging.⁵⁴ Afterward, the pregnancy can be allowed to progress to term. Such an approach of treatment of the aneurysm followed by delivery of the child has been found to result in good outcomes for both patients.⁵⁵ In more complicated cases, however, it has been argued that treatment of the aneurysm should follow delivery of the child via cesarean section.⁵⁶