Stroke in Pregnancy

Christina Mijalski Sells, MD, MPH; Steven K. Feske, MD


Semin Neurol. 2017;37(6):669-678. 

In This Article

Some Specific Causes of Pregnancy-related Strokes


Preeclampsia–eclampsia has been strongly correlated with stroke risk. Its contribution to stroke is complex and includes its relationship to hypertension, endothelial, and platelet dysfunction, thrombophilia and two related syndromes: posterior reversible encephalopathy syndrome (PRES) and the reversible cerebral vasoconstriction syndrome (RCVS). In addition to hypertension, other known risk factors for preeclampsia and eclampsia have also been described well as independent risk factors for stroke, including diabetes, myocardial infarction, and prior stroke. In addition, preeclampsia–eclampsia is itself a risk factor for pregnancy-associated strokes, both ischemic and hemorrhagic. The incidence of preeclampsia–eclampsia in the United States is ~3 to 8%.[15,16] Preeclampsia is diagnosed in the setting of new-onset hypertension and proteinuria or evidence of end-organ damage after the 20th week of pregnancy. Eclampsia has been traditionally defined as preeclampsia with generalized tonic clonic seizures. Many clinicians now favor the extension of the definition of eclampsia to include the major types of cerebral involvement that often leads to seizures, even if seizures do not occur.[21,22] There is strong evidence supporting the continuum of postpartum angiopathy with RCVS and PRES, suggesting that these entities share basic pathophysiologic features with eclampsia.[23] Considered in this inclusive way, the eclamptic state includes PRES and RCVS and their often overlapping co-occurrence.[23] Following this formulation, we typically interpret PRES and RCVS in late pregnancy and the puerperium as manifestations of eclampsia, even in women who fail to fulfill that diagnosis by traditional criteria.

Women with preeclampsia–eclampsia are at a significantly increased risk of stroke during pregnancy and throughout the first year postpartum. The risk of both hemorrhagic and ischemic stroke is dramatically increased in the setting of preeclampsia–eclampsia. In a study by Tang et al, the risk of ischemic stroke was highest during the 3 months antepartum (RR 40.86) compared with 12 months postpartum (RR 4.35), while hemorrhagic stroke was more likely to occur later in the postpartum period (RR 19.9) compared with the 3 months antepartum (RR 10.68).[24] This study also made the important observation that women with preeclampsia–eclampsia appear to be at continued risk of ischemic and hemorrhagic stroke through the first year postpartum. Bellamy et al performed a systematic review and meta-analysis of women with preeclampsia and cardiovascular events that showed an increased risk of vascular disease for several years afterward, as well as increased mortality. Specifically, this study found that preeclampsia significantly increased future risk of hypertension, ischemic heart disease, stroke, and venous thromboembolism, suggesting that those affected may warrant a prolonged period of additional surveillance and monitoring.[25]


Changes to the cerebral vasculature during pregnancy and the postpartum period have many causes, including hormonal and hemodynamic influences. Endothelial dysfunction has been described in several studies as an underlying feature of eclamptic pregnancies, affecting the sensitivity to biochemical mediators of vascular tone, specifically affecting vasoconstriction,[26] which may lead to deleterious hemodynamic effects.[16,27,28,29]

Hypertension is a common risk factor for stroke across all populations, but during pregnancy and the puerperium is a unifying feature of several related pathophysiologic processes. The presence of hypertension is a major diagnostic criterion of preeclampsia–eclampsia. The cerebral edema of PRES results from a combination of (1) increased hydrostatic pressure as a result of hypertension and (2) impaired integrity of the blood–brain barrier as a result of endothelial dysfunction. It the setting of both of these consequences of preeclampsia–eclampsia, there is failure of autoregulation of the cerebral vasculature, resulting in vasodilation and an increase in cerebral blood flow, which exacerbates cerebral edema and may lead to cerebral hemorrhage and infarction. While PRES can affect any part of the brain, it most typically affects the posterior circulation territories, probably due to the relatively poor adrenergic innervation in the posterior compared with the anterior.[26]

RCVS is a related vasculopathy typically presenting with thunderclap headache and focal neurological deficits.[30] Generalized seizures may also occur. The pathophysiology is poorly understood; however, like PRES, its manifestations, most importantly pathological vasoconstriction, are a consequence of impaired endothelium and dysregulated vascular tone. Many patients will have no abnormalities on brain imaging at the time of presentation, but a majority (81%) develop lesions during the clinical course. The shared pathophysiologies of RCVS and PRES are evidenced by their shared risk profiles and by their frequent co-occurrence. The most common pathological consequences of RCVS are ischemic infarction (39%), SAH (34%), ICH (20%), and cerebral edema (38%).[31] Yet, the prognosis of RCVS is usually favorable, with ~90% experiencing a good outcome.[31]

Cerebral Venous Thrombosis

CVT may result from multiple factors, including hypercoagulable states, as found in pregnancy and the puerperium, oral contraceptive pills (OCPs), infection, malignancy, and direct injury to the venous system in the head or neck.[20,32,33] Pregnancy or the use of OCPs in patients with an underlying genetic susceptibility, such as factor V Leiden or factor II G20210A mutations or hyperhomocysteinemia, compounds the risk of CVT.[20]

Ferro et al identified 624 patients from 21 countries between 1998 and 2001 with a diagnosis of CVT and found that the majority were female (74.5%) and Caucasian (79.2%), with a median age of 37. Of these cases, 6.3% occurred during pregnancy and another 13.8% during the puerperium. Cerebral infarction was identified in 46.5% of cases, and "any parenchymal lesion," presumably mostly edema and hemorrhage, was identified in 62.9% of cases. Thirty-nine percent of these venous infarctions had associated hemorrhage on computed tomography (CT) or magnetic resonance imaging (MRI).[33]

In the general population and during pregnancy, CVT is a rare diagnosis, but it is one of the most common cerebrovascular complications in pregnancy, affecting 11.6 per 100,000 deliveries.[12] Lanska and Kryscio found that hypertension, cesarean delivery, and infection were all significantly associated with CVT.[12] Studies have demonstrated a wide range of incidence of CVT-attributable pregnancy-related stroke, from 6 to 64%.[6,17] CVT is most likely to occur in the third trimester and, especially, the puerperium. Seventy-three percent occurred during the puerperium in one Taiwanese study.[7] In the general population, CVT is approximately three times more common in women than in men.[33] CVT most commonly presents with headache and other signs of increased intracranial pressure, focal neurologic deficits, or seizures.

Peripartum Cardiomyopathy

Peripartum cardiomyopathy is a rare complication of pregnancy usually occurring in the late third trimester or the early postpartum period. It has been estimated to affect one in 4,000 pregnancies. Presenting symptoms commonly include edema, dyspnea, cough, and fatigue; many of which are common in late pregnancy and can delay diagnosis. The pathophysiology of peripartum cardiomyopathy is poorly understood and likely multifactorial. Pathologic alterations of angiogenic and hormonal factors have been identified in animal models.[34] Though uncommon, it is an important severe complication of pregnancy, with mortality reaching as high as 9%.[35] It confers an increased risk of stroke as a result of decreased left ventricular ejection fraction, chamber dilation, and atrial fibrillation, all predisposing to cardioembolism.

Vascular Malformations

Aneurysms and AVMs are important causes of ICH during pregnancy and the puerperium. The overall prevalence of AVMs in the general population is ~0.1%, while aneurysms are much more common, occurring in ~10% of patients.[36] Among patients with ICH during pregnancy or the puerperium, these numbers are significantly higher. Data on the relative frequency of the various vascular malformations are conflicting. Several studies have found that, except preeclampsia–eclampsia, AVMs were the most common cause of ICH during pregnancy and the puerperium, followed by intracerebral aneurysms, then cavernous malformations.[2,4,6,7,17,37] In another study, investigators found that 77% of pregnancy-associated hemorrhages with a defined vascular lesion were due to aneurysms, while only 23% were attributed to AVM.[38]

Dias and Sekhar analyzed a series of 154 cases of ICH with identified vascular lesions that occurred during pregnancy or the puerperium. An overwhelming majority of patients in this series experienced ICH in the antepartum (92%) versus the postpartum (8%) period. Mortality from hemorrhage of AVMs and aneurysms is high, and such hemorrhages are responsible for 5 to 12% of all maternal deaths. Maternal mortality in patients with aneurysmal ICH is ~35% in one study, which also reflects the proportion of those affected in the general population.[38] Fetal mortality is also very high, occurring in 17% of cases associated with aneurysms in the same study. Mortality rates were similar in cases where AVMs were identified; maternal mortality was 28% and fetal mortality 14%.