7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Cerebrovascular disorders complicating pregnancy : Susan Hickenbottom, MD, MS, Men-Jean Lee, MD : Jos Biller, MD, FACP, FAAN, FAHA, Charles J Lockwood, MD, MHCM : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 14, 2022. INTRODUCTION Cerebrovascular disease during pregnancy can be distilled into two major categories: thrombosis/ischemia (including arterial and venous infarction) and hemorrhage (including intracerebral and subarachnoid hemorrhage). Normal physiologic changes associated with pregnancy, combined with pathophysiologic processes unique to pregnancy, predispose women to develop stroke during pregnancy and the puerperium. This topic review will focus on the relationship between pregnancy and cerebrovascular disorders. Other neurologic disorders complicating pregnancy are discussed separately. (See "Neurologic disorders complicating pregnancy".) EPIDEMIOLOGY Incidence Pregnant or recently pregnant women develop stroke (incidence 30 per 100,000 pregnancies) more frequently than their nonpregnant counterparts (annual incidence, 10.7 per 100,000 women of reproductive age) [1]. Data from a population-based registry in Finland suggest that the incidence of stroke during pregnancy or puerperium has increased over time; in the study, the incidence rose by more than two-fold from the initial five-year period (1987 to 1991) compared with the last five-year period (2012 to 2016) [2]. Highest risk periods The third trimester of pregnancy and the postpartum period are associated with a marked increase in the relative risk and a small increase in the absolute risk of ischemic stroke and intracerebral hemorrhage; the highest risk is during the puerperium [3-8]. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 1/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Approximately 10 percent of strokes occur in the antepartum period, 40 percent occur proximate to delivery, and 50 percent occur postpartum and after discharge [3]. Although data are inconsistent, the incidence of stroke during the antenatal period alone, excluding stroke during the puerperium, may be similar to the incidence in nonpregnant women of childbearing age [9]. The increased relative risk of stroke in the postpartum period was illustrated in a review of female hospital discharges from central Maryland and Washington, DC for the years 1988 and 1991 that determined the magnitude of the effect of pregnancy (including spontaneous and induced abortions) on stroke risk [4]. For cerebral infarction, the relative risk was 0.7 during pregnancy (a nonsignificant difference) but increased to 8.7 in the postpartum period (within six weeks of a live birth or stillbirth). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy but increased to 28.3 in the postpartum period. For both types of stroke, which occurred with equal frequency, the excess risk during the postpartum period was 8.1 strokes per 100,000 pregnancies. Similar findings were reported in a large study from France [5] and in an analysis from the Nationwide Inpatient Sample of all pregnancy-related discharges in the United States from 2000 to 2001 [3]. Major risk factors and mechanisms Important physiologic and pathophysiologic alterations are associated with an increased risk for ischemic and hemorrhagic strokes during pregnancy. These include changes in cardiovascular hemodynamics, coagulation factors, and hemoconcentration, accompanied by endothelial dysfunction, inflammation, and impaired cerebrovascular tone [10]. A number of complications of pregnancy can present as either a stroke or a stroke-like event, including the following: Preeclampsia/eclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) (see 'Preeclampsia, eclampsia, and HELLP' below) Reversible cerebral vasoconstriction syndrome/postpartum cerebral angiopathy (see 'RCVS/postpartum angiopathy' below) Cerebral venous thrombosis (see 'Cerebral venous thrombosis' below) Hypercoagulable state (see 'Hypercoagulable state' below) Peripartum cardiomyopathy (see 'Peripartum cardiomyopathy' below) Amniotic fluid embolism (see "Amniotic fluid embolism") Gestational trophoblastic disease (see 'Gestational trophoblastic disease' below) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 2/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Other risk factors for stroke related to pregnancy include cesarean delivery, gestational hypertension [7], and peripartum infection [3,11,12]. The risk factors for stroke in pregnancy also include the risk factors for nonpregnant patients, such as hypertension, smoking, antiphospholipid antibody syndrome, inherited thrombophilia, arterial disease, certain types of heart disease, hyperlipidemia, paradoxical emboli, arterial dissection, substance abuse, age over 35 years, migraine with aura, and being from a Black population [3,13]. Women with essential thrombocythemia (primary thrombocytosis) are also at increased risk for thromboembolic events during pregnancy [14]. Risk factors and causes of cerebral venous thrombosis and intracranial hemorrhage in pregnancy are reviewed in greater detail below. (See 'Epidemiology of CVT' below and 'Causes of intracranial hemorrhage' below.) Stroke subtypes All types of stroke can be seen in pregnancy and the puerperium ( table 1). The major causes in this setting are the following [15-17]: Hemorrhagic stroke from hypertensive disorders of pregnancy (preeclampsia/eclampsia, HELLP), reversible cerebral vasoconstriction syndrome (RCVS), arteriovenous malformations, and aneurysms Ischemic stroke from cerebral venous sinus thrombosis, preeclampsia/eclampsia, and cardiogenic embolism OVERVIEW OF DIAGNOSTIC EVALUATION The diagnostic evaluation and treatment of stroke in pregnant women is similar to that in nonpregnant individuals [18]. (See "Initial assessment and management of acute stroke".) Rapid evaluation In pregnant patients, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and cerebral venous thrombosis have clinical features similar to those occurring in nonpregnant patients. All patients with suspected acute stroke require an urgent evaluation; important aspects include: Assessing vital signs and ensuring stabilization of airway, breathing, and circulation. Checking serum glucose with finger stick or rapid point of care test. Low serum glucose (<60 mg/dL [3.3 mmol/L]) should be corrected rapidly. It is reasonable to treat https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 3/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate hyperglycemia if the glucose level is >180 mg/dL (>10 mmol/L) with a goal of keeping serum glucose levels within a range of 140 to 180 mg/dL (7.8 to 10 mmol/L). Obtaining a rapid but accurate history (including the time last known well) and examination to help distinguish stroke mimics and other disorders in the differential diagnosis ( table 2) of acute stroke. Obtaining urgent brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI), neurovascular imaging with CT angiography (CTA) or magnetic resonance angiography (MRA) and other important laboratory studies including cardiac monitoring. Managing volume depletion and electrolyte disturbances. Assessing swallowing and preventing aspiration. Neuroimaging An imaging study of the brain is an essential component of the evaluation, regardless of cause. CT versus MRI Noncontrast head CT is often the first diagnostic study in patients with suspected stroke. The main advantages of CT are widespread access and speed of acquisition. However, MRI is safe during all trimesters of pregnancy (see "Diagnostic imaging in pregnant and lactating patients", section on 'Magnetic resonance imaging'). In addition, MRI is more sensitive than CT for the detection of early infarction, small infarcts, cerebral venous thrombosis, and structural lesions (eg, cavernous malformations) [19]. (See "Neuroimaging of acute stroke", section on 'CT or MRI for initial imaging?'.) The neuroradiographic abnormalities of reversible posterior leukoencephalopathy syndrome are often apparent on head CT but are best depicted by MRI using fluid- attenuated inversion recovery (FLAIR) sequences. (See "Reversible posterior leukoencephalopathy syndrome", section on 'Neuroimaging'.) Note that a small subarachnoid hemorrhage (SAH) can be missed by both CT and MRI, especially as the time from SAH onset to imaging study increases. Lumbar puncture may be needed to make the diagnosis of SAH in such patients. This issue is discussed in detail elsewhere. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Evaluation and diagnosis'.) Use of contrast agents Iodine and gadolinium-based contrast agents are avoided in pregnancy, if possible. (See "Diagnostic imaging in pregnant and lactating patients".) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 4/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Radiation exposure Radiation exposure to the fetus with head CT, cerebral angiography, and chest radiography is approximately 50, 10, and 1 milliradians, respectively. These levels are considered safe, as there is no evidence of an increased risk of fetal anomalies, intellectual disability, growth restriction, or pregnancy loss from ionizing radiation at doses less than 5000 milliradians. The abdomen should be shielded from radiation. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Fetal risks'.) Cardiac studies Cardiac monitoring and echocardiography should be obtained in patients with embolic infarctions. Echocardiography should include a bubble contrast study with agitated saline to look for evidence of a right-to-left shunt via a patent foramen ovale as a pathway for paradoxical embolism from a venous source [10]. Laboratory studies The laboratory evaluation includes a complete blood count, metabolic profile, lipid panel, and toxicology screen [10]. Additional studies may be useful in select patients. Sickle cell disease Testing for sickle cell disease is warranted if there is suspicion for the diagnosis. Despite newborn screening, some adults with sickle cell disease may be undiagnosed. The diagnosis of sickle cell disease is reviewed in detail elsewhere. (See "Diagnosis of sickle cell disorders".) Hypercoagulable testing We obtain a laboratory evaluation for an inherited or acquired thrombophilia for women presenting with a cryptogenic ischemic stroke or transient ischemic attack during pregnancy. Molecular genetic testing for inherited thrombophilias (antithrombin deficiency, prothrombin G20210A, factor V Leiden, protein S deficiency, protein C deficiency) can be done anytime. For patients who are pregnant or were recently pregnant, nonmolecular laboratory testing (eg, activated protein C resistance ratio, functional assay for protein C, free protein S antigen assay, antithrombin-heparin cofactor assay) ideally should be delayed until three months or more following delivery. Details are reviewed separately. (See "Inherited thrombophilias in pregnancy".) Evaluation for the antiphospholipid syndrome includes antibody testing for antiphospholipid antibodies, as reviewed in detail elsewhere. (See "Diagnosis of antiphospholipid syndrome".) Although data are limited, the potential value of this approach was illustrated in a report of 12 previously healthy women who had a first transient ischemic neurologic event during pregnancy https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 5/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate [20]. Ten (83 percent) had an inherited thrombophilia, much higher than the 17 percent rate seen in 24 controls. (See 'Hypercoagulable state' below.) ACUTE ISCHEMIC STROKE In pregnant patients, ischemic stroke has clinical features similar to those occurring in nonpregnant patients. Evaluation The evaluation and treatment of acute ischemic stroke in pregnancy is mostly guided by the same principles as in the general population. These are discussed separately. (See "Initial assessment and management of acute stroke" and "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack" and "Initial evaluation and management of transient ischemic attack and minor ischemic stroke".) Acute reperfusion therapy Intravenous thrombolysis and endovascular mechanical thrombectomy are effective reperfusion therapies for acute ischemic stroke. The immediate goal of reperfusion therapy is to restore blood flow to the regions of brain that are ischemic but not yet infarcted. (See "Approach to reperfusion therapy for acute ischemic stroke".) Intravenous thrombolysis Intravenous thrombolytic therapy with alteplase is indicated for patients with acute ischemic stroke who meet eligibility criteria outlined in the table ( table 3), provided that treatment is initiated within 4.5 hours of clearly defined symptom onset. We agree with the 2019 American Heart Association/American Stroke Association guidelines, which state that intravenous alteplase administration may be considered in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding [21]. Eligible patients should be treated as quickly as possible within the appropriate 3- or 4.5-hour time limit after careful discussion of the potential risks and benefit [22-24]. (See "Intravenous thrombolytic therapy for acute ischemic stroke: Therapeutic use".) The prescribing label for alteplase does not list pregnancy as a contraindication but states that the risk of therapy may be increased in pregnancy [25]. Potential risks include the maternal hemorrhage with thrombolysis, possibly resulting in premature labor, placental abruption, and/or fetal demise [10,26]. Hemorrhage during parturition or cesarean delivery is a particular risk with thrombolytic therapy if the patient goes into labor or operative delivery is required [26]. Based on its molecular weight, alteplase is not expected to cross the placenta; it is unknown if alteplase is present in breast milk. There are no data regarding teratogenicity in humans, but no such risk was found in animal studies [27]. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 6/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Mechanical thrombectomy Mechanical thrombectomy is indicated for selected patients with acute ischemic stroke caused by an intracranial large artery occlusion in the proximal anterior circulation who can be treated within 24 hours of the time last known to be well. (See "Mechanical thrombectomy for acute ischemic stroke".) Endovascular treatment options, particularly mechanical thrombectomy, may be preferred over intravenous thrombolytic therapy for women considered to have a high risk of hemorrhage, such as those with placenta previa or a history of obstetric hemorrhage [28]. These interventions should be attempted only at centers with appropriate expertise. (See "Approach to reperfusion therapy for acute ischemic stroke" and "Mechanical thrombectomy for acute ischemic stroke".) Efficacy and safety in pregnancy The efficacy and safety of reperfusion therapies for acute ischemic stroke in pregnancy are not firmly established, as pregnant women were excluded from the randomized controlled trials testing intravenous thrombolysis and mechanical thrombectomy. However, observational data suggest these therapies are reasonably safe and effective [28,29]. One report evaluating stroke registry data found that the use of acute reperfusion therapy in pregnant or postpartum women was associated with outcomes that were similar to those in nonpregnant women [28]. The study included 338 pregnant or postpartum women and over 24,000 nonpregnant women ages 18 to 44 years with ischemic stroke. Acute reperfusion therapy was defined as intravenous tissue plasminogen activator (tPA), catheter-based thrombolysis or thrombectomy, or any combination of these interventions. Rates of acute stroke reperfusion therapy were similar in pregnant or postpartum women compared with nonpregnant women (11.8 versus 10.5 percent), although treatment with intravenous tPA monotherapy was less frequent in pregnant or postpartum women compared with nonpregnant women (4.4 versus 7.9 percent). Among those treated with acute reperfusion therapy, there was no difference between pregnant or postpartum women and nonpregnant women for rates of in-hospital death (2.1 versus 2.7 percent), discharge to home (75 versus 73 percent), or independent ambulation at home (74 versus 71 percent). There was a higher rate of symptomatic intracranial hemorrhage in pregnant or postpartum women (7.5 percent) compared with nonpregnant women (2.6 percent); the difference did not achieve statistical significance, although it was limited by small numbers of patients. Another analysis of female patients with acute ischemic stroke from the National Inpatient Sample identified 180 pregnant or postpartum women treated with mechanical thrombectomy [29]. Compared with over 48,000 nonpregnant female patients treated with https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 7/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate mechanical thrombectomy, pregnant and postpartum patients had lower rates of both intracranial hemorrhage (11 versus 24 percent) and poor functional outcome (50 versus 72 percent). Blood pressure control Treatment of hypertension for patients with acute ischemic stroke is reviewed separately. (See "Initial assessment and management of acute stroke", section on 'Blood pressure management'.) Patients with ischemic stroke attributed to preeclampsia or eclampsia require treatment of severe hypertension and prompt delivery. (See 'Preeclampsia, eclampsia, and HELLP' below.) Acute antiplatelet therapy Early aspirin therapy is recommended for patients with acute ischemic stroke who are not receiving full-dose anticoagulation. This recommendation is in accord with national guidelines [21,30]. Aspirin should be given as soon as possible within 48 hours of stroke onset, except that aspirin should be withheld for 24 hours following intravenous thrombolytic therapy. Aspirin may also be used in combination with subcutaneous heparin for deep vein thrombosis prophylaxis. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack", section on 'Efficacy of aspirin'.) We do not routinely use clopidogrel or any regimen of dual antiplatelet therapy (DAPT) to treat ischemic stroke or transient ischemic attack (TIA) during pregnancy, given the risk of bleeding in pregnancy. However, the short-term use of DAPT (eg, aspirin with clopidogrel) during pregnancy for the treatment of minor ischemic stroke or high-risk TIA may be considered using shared decision-making and based upon individual patient circumstances and risk factors. Secondary prevention An antiplatelet agent for secondary prevention is recommended for patients with a history of noncardioembolic stroke or TIA of atherothrombotic, lacunar (small vessel occlusive type), or cryptogenic type. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) Aspirin, clopidogrel, and the combination of aspirin-extended-release dipyridamole are all acceptable options for preventing recurrent noncardioembolic ischemic stroke after pregnancy. An aspirin dose of 60 to 81 mg/day is considered safe in pregnancy [31,32]. Clopidogrel and the combination of aspirin-extended-release dipyridamole have not been evaluated in large numbers of patients or over prolonged periods of time. Ischemic stroke associated with a hypercoagulable state Rare cases of ischemic stroke in pregnancy may be associated with a documented hypercoagulable state; management is reviewed separately. (See 'Hypercoagulable state' below and "Inherited thrombophilias in https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 8/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate pregnancy" and "Antiphospholipid syndrome: Obstetric implications and management in pregnancy".) CEREBRAL VENOUS THROMBOSIS Epidemiology of CVT Cerebral venous thrombosis (CVT), also known as cerebral venous sinus thrombosis, is rare in the general population but occurs more commonly in association with pregnancy [33,34]. It presents most often in the third trimester of pregnancy and the puerperium. In hospital discharge data from the United States covering 2850 pregnancies that included a diagnosis of stroke for the years 2000 and 2001, CVT was the cause of 2 percent of pregnancy-related stroke [3]. Smaller retrospective studies have reported that CVT accounts for 3 to 57 percent of pregnancy-related stroke [4,33,35-38]. Some cases have been linked to inherited and acquired thrombophilias [33,36]. Other risk factors include cesarean delivery, hypertension, and infection. (See "Inherited thrombophilias in pregnancy".) Clinical manifestations Clinical manifestations of CVT consist of headache, vomiting, focal or generalized seizure, confusion, blurred vision, focal neurologic deficits, and/or altered consciousness. The headache frequently precedes other symptoms, is diffuse, and is often severe. The severity of symptoms correlates with the degree of thrombosis and the vessel involved. Isolated intracranial hypertension syndrome (ie, headache associated with papilledema or visual obscurations) accounts for a significant proportion of CVT cases. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis", section on 'Clinical aspects'.) Diagnosis Urgent neuroimaging is necessary as the first step in the diagnostic evaluation of suspected CVT. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis", section on 'Diagnosis'.) Anticoagulation The mainstay for the treatment of symptomatic CVT, with or without hemorrhagic venous infarction, is anticoagulation therapy with intravenous heparin or subcutaneous low molecular weight heparin. For women with CVT during pregnancy, guidelines from the American Heart Association/American Stroke Association conclude that low molecular weight heparin in full anticoagulant doses should be continued throughout pregnancy, and low molecular weight heparin or a vitamin K antagonist with a target international normalized ratio (INR) of 2 to 3 should be continued for at least six weeks postpartum for a total minimum duration of therapy of six months [39,40]. Symptomatic management issues include control of seizures and intracranial hypertension. (See "Cerebral venous thrombosis: Treatment and prognosis".) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 9/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate INTRACRANIAL HEMORRHAGE Causes of intracranial hemorrhage Subarachnoid and/or intracerebral hemorrhage during pregnancy or the postpartum period may be caused by hypertensive disorders of pregnancy (preeclampsia, eclampsia, and HELLP [hemolysis, elevated liver enzymes, and low platelets]), reversible cerebral vasoconstriction syndrome (RCVS), and bleeding from a vascular malformation [16,41]. Hemodynamic, angiogenic, and endocrine changes associated with pregnancy may affect the growth and rupture of aneurysms in the gravid patient [42]. Data are conflicting regarding the occurrence of aneurysmal subarachnoid hemorrhage (SAH) during pregnancy, delivery, and the postpartum period. Some studies have reported an increased risk [43,44], while others concluded that aneurysmal rupture is not more frequent [45]. Most data suggest that the risk of hemorrhage from a cerebral arteriovenous malformation is not increased during pregnancy, but the issue is controversial, and no definitive data exist [46- 49]. One of the better studies was a retrospective analysis of 451 women with a brain arteriovenous malformation [46]. The hemorrhage rate in pregnant women in this population was not significantly different compared with the rate for nonpregnant women (3.5 versus 3.1 percent per person-year). In a study that examined a 10-year representative sample of the entire United States obstetrical population, involving nearly seven million deliveries, 423 women had pregnancy-related intracerebral hemorrhage [6]. Independent risk factors for intracerebral hemorrhage in this population were advanced maternal age, preexisting and gestational hypertension, preeclampsia/eclampsia, preexisting hypertension superimposed on preeclampsia/eclampsia, coagulopathy, tobacco abuse, and being from a Black population. One retrospective study reported 154 women with intracranial hemorrhage during pregnancy or the puerperium who had an identified vascular lesion [50]. The cause of the hemorrhage was cerebral aneurysm or arteriovenous malformation in 77 and 23 percent, respectively. Aneurysm rupture during pregnancy occurred most frequently in the third trimester (55 percent) and less so in the second trimester (31 percent), first trimester (6 percent), or postpartum period (8 percent). One old retrospective study found that among 37 pregnant women in good condition after SAH from a verified intracranial aneurysm, recurrent bleeding during the same pregnancy from surgically untreated aneurysms occurred in 13 (35 percent) [51]. The overall incidence of rebleeding after initial SAH in the modern era is uncertain. Limited data from older literature https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 10/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate suggest that the maternal case fatality rate of aneurysmal SAH is approximately 50 percent [50], which is similar to that of the general population (see "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Complications'). The fetal case fatality rate is approximately 17 percent [50]. Management by cause of hemorrhage Preeclampsia/eclampsia/HELLP Retrospective data suggest that severe preeclampsia/eclampsia/HELLP (hemolysis, elevated liver enzymes, and low platelets) is the cause of 14 to 55 percent of hemorrhagic strokes in pregnancy. In such cases, management goals are to stabilize the mother, prevent recurrent convulsions, treat severe hypertension to reduce or prevent cerebral edema and hemorrhage, and initiate delivery of the fetus. (See 'Preeclampsia, eclampsia, and HELLP' below.) Vascular malformations Intracerebral aneurysms and arteriovenous malformations (AVMs) can be managed by surgical (ie, clipping) or endovascular (eg, embolization) treatment of the causative lesion [52]. Treatment In general, ruptured intracranial aneurysms in pregnant women are treated as they would be in patients who are not pregnant. Endovascular coiling is preferred to surgical clipping for appropriately shaped aneurysms. Several reports have described successful endovascular coiling of intracranial aneurysms associated with term or near-term births [53-56]. However, aneurysms with broad necks, a low neck-to- fundus ratio, distal segment lesions, and a number of giant aneurysms are not amenable to endovascular therapy. Stable, unruptured asymptomatic aneurysms can usually be observed without intervention during pregnancy, whereas symptomatic or enlarging unruptured aneurysms can be treated [57,58]. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Unruptured intracranial aneurysms".) Symptomatic AVMs in pregnant women are treated as they would be in patients who are not pregnant. There are a few case reports of successful embolization of hemorrhagic AVMs during pregnancy via the endovascular approach, followed by surgical resection of the AVM [59,60]. Computed tomography (CT) angiography with shielding of the abdomen during pregnancy can be performed prior to the embolization procedure to delineate any prenidal or intranidal aneurysms that might be the source of the bleed. (See "Brain arteriovenous malformations" and "Vascular malformations of the central nervous system".) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 11/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Labor and delivery Women who have had the cause of their cerebral hemorrhage treated (eg, clipping or embolization of a cerebral aneurysm or AVM) may undergo labor and delivery. However, there is controversy regarding management of labor and delivery with ruptured aneurysms or AVMs that have not been definitively treated. The two major alternatives are (1) prophylactic cesarean delivery and (2) regional anesthesia with instrumental delivery to eliminate cerebral hemodynamic fluctuations associated with pain and the Valsalva maneuver. There are no data from large series or randomized trials, but it appears that maternal and fetal mortality rates are the same with both methods. As a result, cesarean delivery should be reserved for the usual obstetrical indications [50]. Aneurysm rupture has occurred during elective cesarean birth; thus, it is not completely protective. Therefore, regardless of the mode of delivery, it is important to control hypertension and minimize fluctuations in blood pressure. Some experts believe that selected patients who are stable after intracranial hemorrhage can be managed supportively until the pregnancy is taken to term [52]. The lesion can then be treated by surgical or endovascular means after delivery. However, emergency surgery is indicated if there is neurologic deterioration caused by recurrent bleeding. RCVS The evaluation and management of RCVS/postpartum angiopathy is reviewed below. (See 'RCVS/postpartum angiopathy' below.) PREECLAMPSIA, ECLAMPSIA, AND HELLP The syndromes of severe preeclampsia, eclampsia, and HELLP (hemolysis, elevated liver enzymes, and low platelets) are among the most common causes of both ischemic and hemorrhagic stroke in pregnancy [4,5,35,61,62]. However, the most frequent cerebrovascular disturbance associated with preeclampsia and eclampsia is posterior reversible encephalopathy syndrome (PRES), which is also known as reversible posterior leukoencephalopathy syndrome. The presumed mechanism is impairment of cerebrovascular autoregulation. (See "Reversible posterior leukoencephalopathy syndrome".) Preeclampsia, eclampsia, and HELLP syndrome are discussed in detail elsewhere. (See "Preeclampsia: Clinical features and diagnosis" and "Eclampsia" and "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 12/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Manifestations Neurologic manifestations of the reversible encephalopathy associated with severe preeclampsia, eclampsia, and HELLP syndrome may include headache, blurred vision, scotomata, cortical blindness, and/or generalized tonic-clonic seizures. Untreated cases may progress to coma. Neuroimaging often shows vasogenic edema in subcortical white matter, predominantly in the parietal and occipital lobes. (See "Preeclampsia: Clinical features and diagnosis" and "Eclampsia" and "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)".) The available data regarding ischemic and hemorrhagic stroke associated with severe preeclampsia/eclampsia/HELLP are limited to retrospective studies. In a report from Mexico of 240 women with pregnancy-related cerebrovascular complications, preeclampsia/eclampsia was commonly associated with both ischemic stroke of arterial origin (36 percent) and intracerebral hemorrhage (55 percent) but less frequently with cerebral venous thrombosis (10 percent) [35]. In a review from Maryland of 31 pregnancy-related strokes, 17 patients had cerebral infarction and 14 had intracerebral hemorrhage [4]. Severe preeclampsia/eclampsia accounted for 24 percent of infarctions and 14 percent of hemorrhages. In a study from France of 31 pregnancy-related strokes, eclampsia accounted for 47 percent of infarctions and 44 percent of hemorrhages [5]. The clinical characteristics of patients with stroke in association with severe preeclampsia/eclampsia/HELLP were illustrated in a review of 28 such patients with a mean age of 30 years (range 14 to 42 years) who were otherwise free of risk factors for stroke [61]. Seven of the patients were ascertained from hospital medical records, while the other 21 were derived from forensic sources. In the 27 patients who had intracranial imaging, the type of stroke was hemorrhagic-arterial in 25 (93 percent) and thrombotic-arterial in 2 (7 percent). There were more strokes in the postpartum than antepartum period (57 versus 43 percent). Since most of the cases reported were derived from forensic sources, these findings may not be representative of the risks to the overall population of pregnant women with severe preeclampsia/eclampsia/HELLP [61]. Management The goals of management of severe preeclampsia and eclampsia and HELLP are to stabilize the mother, prevent recurrent convulsions, treat severe hypertension promptly to reduce or prevent cerebral edema and hemorrhage, and initiate prompt delivery. Indications for antihypertensive therapy and drug choices are discussed in detail separately. (See "Treatment of hypertension in pregnant and postpartum patients".) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 13/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Magnesium sulfate is the drug of choice for seizure prophylaxis. Platelet transfusion is indicated in HELLP syndrome if there is significant maternal bleeding or if the platelet count is <20,000 cells/microL. (See "Preeclampsia: Antepartum management and timing of delivery" and "Eclampsia", section on 'Management' and "HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets)", section on 'Management of patients presenting before delivery'.) RCVS/POSTPARTUM ANGIOPATHY Postpartum angiopathy is one member of a group of reversible cerebral vasoconstriction syndromes (RCVS) with similar clinical and radiologic features that are characterized by thunderclap headache and diffuse, segmental, reversible cerebral vasospasm [63]. Other entities encompassed by RCVS include idiopathic thunderclap headache with vasospasm, benign angiopathy of the central nervous system, migrainous vasospasm, Call-Fleming syndrome, and drug-induced cerebral vasoconstriction. (See "Reversible cerebral vasoconstriction syndrome".) The available retrospective studies are inconsistent regarding the frequency of pregnancy complications (eg, eclampsia or gestational diabetes) preceding RCVS [64,65]. However, the clinical, laboratory, and neuroimaging features of RCVS/postpartum angiopathy and eclampsia are not strictly separated, suggesting these entities may represent different clinical expressions of the same underlying pregnancy-related disorder [66,67]. In one retrospective series that reported 18 patients with postpartum angiopathy from three tertiary care centers, pregnancy was complicated by preeclampsia or eclampsia in 7 (39 percent) [65]. It is important to determine if any drugs capable of causing vascular spasm have been used. Some reports suggest that sympathomimetic drugs may increase the risk of postpartum angiopathy [64]. Clinical features Headache remains the only symptom in many patients with RCVS; others develop focal deficits neurologic findings that can include visual disturbance, hemiplegia, dysarthria, aphasia, numbness, ataxia, seizure, and encephalopathy, often in combination [65]. Vasogenic brain edema, intraparenchymal hemorrhage, subarachnoid hemorrhage, ischemic stroke ( image 1), and even death have been reported [65,68]. Blood pressure may be normal or elevated. Imaging and laboratory studies Smooth narrowing of multiple segments of intracranial arteries is seen on cerebral angiography and can be seen on magnetic resonance angiography or computed tomographic angiography ( image 2), although these noninvasive studies may not be able to adequately image smaller arterioles that are https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 14/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate typically involved. In addition, cerebral angiography may be normal early in the clinical course [65]. The angiographic changes are reversible but may persist for days to months. Laboratory testing is usually normal. Cerebrospinal fluid findings are typically without abnormalities, but minor abnormalities can result from ischemic or hemorrhagic strokes. Differential diagnosis The differential diagnosis of postpartum angiopathy and RCVS includes primary angiitis of the central nervous system (PACNS). Findings that favor PACNS rather than postpartum angiopathy associated with pregnancy include an insidious onset of dull headache, stepwise progression of symptoms, spinal fluid abnormalities, and more distal intracranial blood vessels affected on angiography. (See "Primary angiitis of the central nervous system in adults".) Treatment of postpartum angiopathy As with all central nervous system vasculopathy syndromes, there is no proof that any therapeutic intervention is effective for postpartum angiopathy. The syndrome is usually self-limiting. Some patients have received glucocorticoids (especially those with findings that suggest primary angiitis of the central nervous system), calcium channel blockers, and/or magnesium [65]. Progressive deterioration is usually a relatively early finding (within the first few weeks) and may be due to increasing brain edema. Prognosis The prognosis of postpartum angiopathy was thought to be good, but in one of the largest series (n = 18), a complete recovery was achieved by nine patients (50 percent), while a fulminant course followed by death affected four patients (22 percent) [65]. There is no evidence of a high risk of recurrence in future pregnancies [69], although at least one recurrent case has been reported [70], or of an increased risk of eclampsia/preeclampsia in future pregnancies. HYPERCOAGULABLE STATE Pregnancy is a hypercoagulable state that is due, in part, to the progressive increase in resistance to activated protein C in the second and third trimesters, as well as decreased protein