Vascular Lesions During Pregnancy

Overview

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. 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. ^, Hypertension is a major underlying factor for the development of these conditions and subsequent stroke.

In general, the risk for stroke in a pregnant patient peaks during delivery. Specifically, the risk is greatest 2 days before delivery and 1 day after; the occurrence of stroke is also increased 6 weeks after delivery. Other studies have identified racial differences in pregnancy-related stroke, with an increased incidence in patients of Asian descent.

Evaluation

All patients suspected of having an ischemic and hemorrhagic stroke should undergo a thorough neurological examination, radiologic testing, and laboratory investigation. Because of the unique challenges presented by the pregnant patient and the fetus, close coordination among the evaluation and treatment team, including the neurosurgeon, obstetrician, neuroradiologist, neuroanesthesiologist, and, depending on the duration and state of the pregnancy, an obstetric anesthesiologist, may be helpful.

The comprehensive description of the evaluation (and treatment) of patients with ischemic and hemorrhagic stroke can be found in Part 4, “Occlusive Vascular Disease.” In the following sections, we provide focused comments on the workup of pregnant patients suspected of having a stroke. The major modifier of the workup is the potential for fetal harm.

CT is a good initial study to exclude hemorrhagic stroke and can identify some cases of ischemic and hemorrhagic stroke, depending on the region of the brain affected and the length of time since arterial occlusion. MRI has greater sensitivity and resolution than does CT for ischemic stroke. Angiography can be useful, particularly when intra-arterial thrombolytic treatment is anticipated. Helpful initial laboratory investigations include a complete blood cell count, measurement of electrolytes and erythrocyte sedimentation rate, coagulation studies, and urinalysis. When a cardiac source is suspected, a chest radiograph, ECG, and echocardiogram should be obtained. Transesophageal echocardiography is superior to transthoracic echocardiography and is safe for pregnant patients. Carotid duplex ultrasonography and MR angiography are noninvasive techniques for investigating extracranial carotid disease. According to recommendations by the American College of Obstetricians and Gynecologists Committee on Obstetric Practice regarding diagnostic imaging procedures during pregnancy and lactation, ultrasonography and MRI are not associated with fetal risk.

With a few exceptions, radiation exposure from radiography, CT, or nuclear medicine imaging techniques is at a much lower dose than the dose associated with fetal harm, and these techniques should be used in addition to ultrasonography or MRI if necessary or more readily available for the diagnosis in question.

The use of gadolinium contrast with MRI should be limited and only used if it significantly improves diagnostic performance and is expected to improve fetal or maternal outcome. However, gadolinium MRI at any time during pregnancy was associated with an increased risk for a broad set of rheumatologic, inflammatory, and infiltrative skin conditions, as well as stillbirth and neonatal death. Breastfeeding should not be interrupted after gadolinium administration.

Arterial Occlusion

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

Potential interventions for arterial occlusion in pregnant patients include antiplatelet agents and anticoagulation. Antiplatelet agents such as aspirin have the potential to cross the placental barrier. The incidence of congenital malformations was not increased among a population of 50,282 pregnant patients with variable to no exposure to aspirin in 1976. Aspirin, however, can appear highly concentrated in fetal blood and affect hemostatic mechanisms in both the mother and fetus. It is not currently recommended late in pregnancy because of bleeding complications in the mother and fetus. Lower doses of aspirin appear to be well tolerated in pregnancy. The most current American Heart Association and American Stroke Association stroke guidelines recommend consideration of tPA in patients with moderate to severe stroke if the benefits outweigh the risk for uterine bleeding (FDA category C).

Four randomized trials have demonstrated significant benefit in the cohort of patients receiving mechanical thrombectomy, and evidence now supports the ability of this technology to decrease the rate of neurological injury from stroke as well as the rate of mortality. Although pregnant patients are a small minority of those presenting with acute large-vessel occlusion, their treatment decisions cannot be significantly delayed. Two main issues with endovascular treatment of stroke are problematic in regard to the pregnant patient: iodinated contrast material and radiation exposure. The effects of radiation are highly dependent on dose and timing. When performed by an experienced technician, the expected dose to the fetus can be well below established risk thresholds during endovascular thrombectomy. Fetal radiation doses can be limited to less than 1 mGy by performing neurointerventions with lead shields, minimizing the number of views obtained, and reducing high-dose acquisition times. The fetus radiation dose below 50 mGy is considered safe and does not cause any harm. According to the Centers for Disease Control and Prevention (CDC), a radiation dose between 50 and 100 mGy is regarded inconclusive in terms of impact on the fetus. Doses above 100 mGy, especially doses above 150 mGy, are viewed as the minimum amount of dosage at which negative fetal consequences will occur, based on observation. The majority of the diagnostic studies performed during the pregnancy are below the threshold level. Iodinated contrast material crosses the placenta to the fetus. No teratogenic effects have been reported; however, the American College of Radiology recommends that it be used in pregnancy only if absolutely necessary. Pregnant patients presenting with arterial occlusions amenable to mechanical thrombectomy should be offered this treatment but should be alerted to the known and unknown risks of the various aspects of interventional procedures.

Venous Occlusion

Intracranial venous thrombosis occurs at an estimated incidence of 1 per 2500 to 1 per 10,000 deliveries and accounts for 20% to 40% of cases of ischemic stroke during pregnancy. It is more common in pregnant women than in nonpregnant women. This disorder tends to develop in multiparous women 3 days to 4 weeks after childbirth; most cases occur in the second or third postpartum week. ^{, ,} Intracranial venous thrombosis during pregnancy is less common; only 25% of cases occur during actual pregnancy, as opposed to after pregnancy. ^{, ,} Most cases are idiopathic, although many systemic conditions can predispose a person 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. ^,

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

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. Treatment options for intracranial venous thrombosis include high doses of heparin (1000 IU/h to start; activated partial thromboplastin time > 1.5 to 2 times that of control) and endovascular fibrinolysis followed by heparinization and endovascular or surgical thrombectomy. Einhaupl and colleagues found that patients receiving intravenous heparin for intracranial venous thrombosis had significantly more favorable neurological outcomes and mortality rates than did patients receiving placebo treatment. Underlying predisposing disorders, such as sinusitis, must also be treated.

The rate of mortality from intracranial venous thrombosis has been reported as 33% ; however, neurological outcomes in survivors are usually favorable. Srinivasan found that 59% of patients recovered without significant neurological disability.

Postpartum Cerebral Angiopathy

Another entity that has been described as a cause of stroke is postpartum cerebral angiopathy (PCA). PCA is a disorder of blood vessels in recently pregnant patients that can be subdivided into three categories. The cause of primary PCA is unknown. 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.

Reversible cerebral vasoconstriction syndrome (RCVS) is a postpartum angiopathy that carries significant morbidity and mortality and is characterized as the sudden onset of a severe thunderclap headache and segmental vasoconstriction of cerebral arteries documented on brain imaging. Seizures are found in up to 28% of patients. Management of this condition includes symptomatic relief, triple-H therapy (hypertension, hypervolemia, and hemodilution), and calcium channel blockers. In refractory cases with new-onset neurological deficit or worsening imaging findings, intra-arterial infusion of milrinone, verapamil, or nimodipine and balloon angioplasty have been reported with varying degrees of success.