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 S activity, increased fibrinogen, increased factors II, VII, VIII, X, and XII and von Willebrand factor, and increased activity of fibrinolytic inhibitors. (See "Maternal adaptations to pregnancy: Hematologic changes", section on 'Coagulation and fibrinolysis'.) The risk of thrombosis is increased in women with the antiphospholipid syndrome or an inherited thrombophilia, such as factor V Leiden, the prothrombin gene mutation, or a https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 15/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate deficiency of antithrombin, protein C, or protein S. (See "Inherited thrombophilias in pregnancy" and "Antiphospholipid syndrome: Obstetric implications and management in pregnancy".) Anticoagulants and antiplatelet agents have been employed to prevent stroke due to the antiphospholipid syndrome. Pregnant women with the antiphospholipid syndrome are at increased risk for maternal thrombosis and for late fetal loss, early and severe preeclampsia, growth restriction, and possibly recurrent early pregnancy loss. The management of these women is controversial and is discussed elsewhere. (See "Antiphospholipid syndrome: Obstetric implications and management in pregnancy".) The evaluation and management of the inherited thrombophilias is discussed in greater detail separately. (See "Inherited thrombophilias in pregnancy" and "Antithrombin deficiency" and "Protein C deficiency" and "Protein S deficiency" and "Factor V Leiden and activated protein C resistance" and "Prothrombin G20210A" and "Overview of homocysteine".) TTP AND HUS Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are acute syndromes with abnormalities in multiple organ systems that demonstrate microangiopathic hemolytic anemia and thrombocytopenia ( table 4). Clinical features Although some studies distinguish between TTP and HUS, the presenting features are similar in most patients: microangiopathic hemolytic anemia and thrombocytopenia without another apparent cause and, in many patients, neurologic and/or renal abnormalities. Neurologic manifestations can include coma, confusion, seizure, transient ischemic attack, stroke, posterior reversible encephalopathy syndrome (PRES), and headache. (See "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)".) Differential When developing during or after pregnancy, TTP and HUS must be distinguished from severe preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), which can be accompanied by acute thrombocytopenic disorders that are expected to resolve spontaneously within several days after delivery. The distinction between TTP, HUS, and severe preeclampsia or HELLP is important for therapeutic and prognostic reasons. However, the clinical and histologic features are so similar that establishing the correct diagnosis is often difficult; furthermore, these disorders may occur concurrently. (See "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)" and "Thrombocytopenia in pregnancy".) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 16/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Treatment For the majority of patients with suspected TTP during pregnancy, urgent plasma exchange therapy is the appropriate treatment. (See "Immune TTP: Initial treatment", section on 'Immune TTP during pregnancy'.) An exception is a woman with known hereditary TTP or a strong suspicion of hereditary TTP based on hereditary TTP in a sibling. For these individuals, plasma infusion is the appropriate treatment. (See "Hereditary thrombotic thrombocytopenic purpura (hTTP)", section on 'Management of pregnancy'.) For patients with suspected complement-mediated hemolytic uremic syndrome (HUS), which often presents in the postpartum period, the risk for end-stage kidney disease is high. It may be reasonable to initiate anticomplement therapy urgently in order to limit preventable renal damage while the diagnosis is being confirmed (or excluded). (See "Complement-mediated hemolytic uremic syndrome in children", section on 'Complement blockade (eculizumab)'.) Delivery Importantly, unlike preeclampsia and HELLP syndrome, there is no evidence that delivery alters the course of TTP or HUS. If TTP or HUS is the presumptive diagnosis, delivery should only be performed for obstetric reasons. PERIPARTUM CARDIOMYOPATHY Peripartum cardiomyopathy is characterized by the development of systolic heart failure towards the end of pregnancy or in the months following pregnancy, with left ventricular ejection fraction (LVEF) generally less than 45 percent in the absence of another identifiable cause of heart failure. Risk factors include older age, multiple gestation, African descent, and a history of preeclampsia, eclampsia, or postpartum hypertension. Symptoms are similar to those in other forms of heart failure due to cardiomyopathy; left ventricular thrombus with systemic or pulmonary thromboembolism can result. Women with peripartum cardiomyopathy may be at risk for cardioembolic stroke due to the hypercoagulable state of pregnancy and poor cardiac function. (See "Peripartum cardiomyopathy: Etiology, clinical manifestations, and diagnosis".) The treatment of peripartum cardiomyopathy, including anticoagulation for patients with intracardiac thrombus or systemic embolism, is discussed elsewhere. (See "Peripartum cardiomyopathy: Treatment and prognosis".) AMNIOTIC FLUID EMBOLISM https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 17/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Amniotic fluid embolism is a rare, often catastrophic condition that typically occurs during labor or within 30 minutes postpartum. It is caused by a breach in maternal-fetal interface with entry of amniotic fluid (which contains fetal cells and other antigenic material) into the maternal systemic circulation, which leads to abnormal activation of humoral and immunological processes and release of vasoactive and procoagulant substances. Patients classically develop cardiorespiratory compromise or sudden hypoxia and hypotension, often with noncardiogenic pulmonary edema and hemorrhage due to disseminated intravascular coagulopathy. Neurologic manifestations may include ischemic stroke, seizure, and altered mental status. Persistent neurological impairment has been reported in 6 to 61 percent of survivors [71]. Clinical aspects of amniotic fluid embolism, including management, are reviewed in detail separately. (See "Amniotic fluid embolism".) GESTATIONAL TROPHOBLASTIC DISEASE Gestational trophoblastic disease comprises a heterogeneous group of related lesions arising from abnormal proliferation of trophoblast of the placenta. The maternal lesions arise from fetal, not maternal, tissue. Metastases from gestational trophoblastic neoplasia can involve the brain; patients may be asymptomatic initially, but as the disease progresses, patients develop neurologic signs and symptoms due to increased intracranial pressure or hemorrhage. (See "Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk stratification".) UNIQUE MANAGEMENT ISSUES Anticoagulation during pregnancy Definitive recommendations for anticoagulant therapy for stroke during pregnancy are difficult because of a lack of applicable studies. In theory, anticoagulation can be given to prevent recurrent thrombosis in hypercoagulable states and to treat cerebral venous thrombosis. (See 'Cerebral venous thrombosis' above.) While there are no randomized controlled trials or epidemiologic studies to guide the duration of anticoagulant therapy, many patients will require anticoagulation throughout the pregnancy and the postpartum period, after which re-evaluation of the need for treatment can take place. We typically reinitiate unfractionated heparin or low molecular weight heparin (LMWH) 4 to 6 hours after vaginal delivery or 6 to 12 hours after Cesarean delivery, unless there was significant intraoperative or postpartum bleeding. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 18/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate The 2012 American College of Chest Physician (ACCP) guidelines recommend LMWH instead of unfractionated heparin for the prevention and treatment of venous thromboembolism during pregnancy and recommend LMWH instead of vitamin K antagonist treatment antenatally [72]. The ACCP guidelines further suggest that anticoagulant therapy be continued for at least six weeks postpartum, and for a minimum total duration of three months for pregnant women with acute venous thromboembolism. The ACCP guidelines recommend discontinuation of LMWH or unfractionated heparin at least 24 hours before induction of labor, cesarean delivery, or expected time of neuraxial anesthesia [72]. Other approaches to the management of anticoagulation and neuraxial analgesia are reviewed separately. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Neuraxial analgesia and the anticoagulated patient'.) Concerns related to the different types of anticoagulants can be summarized as follows: Warfarin is potentially teratogenic when given between the sixth and ninth weeks of gestation. In addition, when given in the second and third trimesters, warfarin can lead to central nervous system abnormalities that are thought to be due to repeated cerebral microhemorrhages. Heparin does not cross the placenta and therefore is not teratogenic and does not anticoagulate the fetus. Concerns with heparin therapy include the relative difficulty of maintaining a stable therapeutic response, the inconvenience of parenteral administration, and the complications of heparin-induced thrombocytopenia and bone demineralization, which can lead to fractures in patients treated for more than six months. LMWH does not cross the placenta. Compared with unfractionated heparin, LMWH has the advantages of producing a more predictable anticoagulant response to fixed doses administered once or twice daily and is less likely to produce thrombocytopenia or possibly bone demineralization. Issues related to anticoagulation in pregnant women are discussed in detail elsewhere. (See "Use of anticoagulants during pregnancy and postpartum".) Stroke remote from term When stroke occurs in a pregnant woman who is <24 weeks of gestation, the stroke should be managed as dictated by the patient's clinical condition. Every effort should be made to protect the salvageable brain tissue, prevent medical complications (eg, aspiration), control maternal physiologic factors that may worsen the stroke, such as blood pressure, and facilitate long-term physical rehabilitation. Pregnancy termination is an option if thrombolytic therapy is being considered. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 19/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate As mentioned earlier, some women with ischemic stroke or cerebral venous thrombosis will require anticoagulation throughout the pregnancy. (See 'Anticoagulation during pregnancy' above.) Stroke near term For women who have a stroke between 24 and 32 weeks gestation, antenatal glucocorticoids can be administered to accelerate fetal lung maturation. A multidisciplinary approach in consultation with neurology, neurosurgery, anesthesia, neonatology, and perinatology should take place to stabilize the mother and assess fetal status. As long as maternal and fetal well-being are not deteriorating, plans can be made to continue the pregnancy with a scheduled controlled delivery between 34 to 39 weeks gestation to optimize fetal outcome. For pregnant women diagnosed with ischemic stroke or cerebral venous sinus thrombosis, anticoagulation with unfractionated heparin, LMWH, or antiplatelet therapy with aspirin should be considered in consultation with neurologists throughout the remainder of the pregnancy. (See 'Anticoagulation during pregnancy' above.) After 36 weeks of pregnancy, LMWH can be changed over to unfractionated heparin until a scheduled labor induction at 39 weeks can take place, and LMWH can resume in the postpartum period. Aspirin should be stopped within one week of a planned delivery (ie, induction of labor or cesarean delivery). Breastfeeding A small fraction of iodinated or gadolinium contrast agents is secreted in maternal milk. Based upon these data, women who require neurovascular imaging should discontinue breastfeeding for 24 hours after receiving intravenous contrast media and discard milk expressed during that interval before resuming normal breastfeeding. There are no contraindications to breastfeeding while being treated with unfractionated heparin or LMWH. Similarly, nursing mothers can safely take warfarin because there is no convincing evidence that warfarin exerts an anticoagulant effect on the breast-fed infant. FUTURE PREGNANCY Counseling When counseling women with a prior history of stroke, it is important to obtain a detailed history of the etiology of and the circumstances surrounding the stroke to determine the stroke type (ischemic/thrombotic or hemorrhagic) and underlying mechanism. This classification will help to guide management for the impending pregnancy. Consultation with a neurologist, hematologist, or neurosurgeon may also be indicated prior to attempting conception to optimize pregnancy outcomes. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 20/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Risk of recurrent stroke For most women with prior stroke during pregnancy, the recurrence rate during a subsequent pregnancy and postpartum period is low ( 1 percent), particularly if any causative vascular lesions have been repaired [73-76]. However, data are sparse, and the risk in future pregnancies varies depending upon the cause of the initial stroke. Ischemic stroke The risk of recurrent ischemic stroke is low. This was illustrated in a review of 441 women with a history of ischemic stroke (373 with arterial ischemic stroke and 68 with cerebral venous thrombosis); during a mean follow-up of five years, there were 13 recurrent arterial ischemic strokes and no recurrences of cerebral venous thrombosis [74]. The overall risk of recurrence was 1 percent at one year and 2.3 percent at five years. The risk of recurrence during pregnancy or the puerperium was 1.8 percent (not significantly different from outside pregnancy), but the relative risk of recurrence was significantly higher during the postpartum period (risk ratio 9.7, 95% CI 1.2-78.9). The outcome of the 187 subsequent pregnancies was similar to that expected from the general population. The authors concluded that a previous ischemic stroke is not a contraindication to a subsequent pregnancy. Hypercoagulable states Few studies have examined recurrence after pregnancy-related stroke associated with hypercoagulable states. One report evaluated 12 women with a previous cerebrovascular event (infarction, transient ischemic attack, or amaurosis fugax) in the setting of thrombophilia [77]. In 15 subsequent pregnancies, there were four thromboembolic events, including two amaurosis fugax, one transient ischemic attack, and one cerebral infarction. None of the patients had persistent neurologic deficits. CVT There are insufficient data to assess the risk of recurrent cerebral venous sinus thrombosis (CVT), and the role of antithrombotic prophylaxis during subsequent pregnancies is unproven in women with a history of CVT. There is no consensus regarding this issue. Many experts believe that antithrombotic prophylaxis during pregnancy is probably unnecessary unless a prothrombotic condition or a previous thromboembolism (ie, a previous CVT or deep venous thrombosis before the index CVT) has been identified. However, other experts would prefer to treat with intravenous heparin or subcutaneous low molecular weight heparin starting during the late third trimester and continuing for up to eight weeks postpartum. (See "Cerebral venous thrombosis: Treatment and prognosis", section on 'Subsequent pregnancy'.) Untreated AVMs Untreated brain arteriovenous malformations (AVMs) are prone to rebleeding whether or not the patient becomes pregnant. In one study, the annual rate of recurrent hemorrhage in women with a brain AVM was estimated to be 31 percent in the first year following an initial hemorrhage and 6 percent in subsequent years [78]. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 21/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Therefore, brain AVMs should be definitively treated by surgical excision or endovascular embolization in women before reattempting pregnancy, if possible. (See "Vascular malformations of the central nervous system" and "Brain arteriovenous malformations", section on 'Acute management issues'.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Anticoagulation in pregnancy".) SUMMARY AND RECOMMENDATIONS Incidence Pregnant or recently pregnant women have a higher incidence of stroke (incidence 30 per 100,000 pregnancies) compared with their nonpregnant counterparts. 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 stroke. (See 'Epidemiology' above.) Evaluation All patients with suspected acute stroke require an urgent evaluation. An imaging study of the brain is an essential component of the evaluation. A head computed tomography (CT) scan is both informative and readily available. However, brain magnetic resonance imaging (MRI) is more sensitive than CT for the detection of early infarction, small infarcts, cerebral venous thrombosis, and structural lesions (eg, cavernous malformations). Etiologies The most common causes of hemorrhagic stroke in pregnancy are preeclampsia/eclampsia, arteriovenous malformations, and aneurysms. The most common causes of ischemic stroke are cerebral venous sinus thrombosis, preeclampsia/eclampsia, and cardiogenic embolism. The main causes of stroke and stroke-like episodes in pregnancy are listed in the table ( table 1). (See 'Stroke subtypes' above.) Acute ischemic stroke For eligible patients with acute ischemic stroke, intravenous alteplase administration may be considered in pregnancy when the anticipated benefits outweigh the anticipated increased risks of uterine bleeding. Eligible patients should be treated as quickly as possible within the appropriate 3- or 4.5-hour time window from time last known well. Mechanical thrombectomy is indicated for selected patients with acute https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 22/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 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. Cerebral venous thrombosis The treatment of symptomatic cerebral venous thrombosis, with or without hemorrhagic venous infarction, is anticoagulation therapy with intravenous heparin or subcutaneous low molecular weight heparin. Intracranial hemorrhage Subarachnoid and/or intracerebral hemorrhage due to aneurysmal rupture or bleeding from a vascular malformation can be managed by surgical (ie, clipping) or endovascular (eg, embolization) treatment of the causative lesion. (See 'Intracranial hemorrhage' above.) Preeclampsia/eclampsia/HELLP Preeclampsia/eclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelets) are among the most common causes of both ischemic infarction and hemorrhagic stroke in pregnancy. Management goals are to stabilize the mother, prevent recurrent convulsions, treat severe hypertension to reduce or prevent cerebral edema and hemorrhage, and initiate prompt delivery. (See 'Preeclampsia, eclampsia, and HELLP' above.) RCVS/postpartum angiopathy Postpartum angiopathy is one type of a group of reversible cerebral vasoconstriction syndromes (RCVS) characterized by thunderclap headache and diffuse, segmental, reversible cerebral vasospasm. Some patients develop neurologic symptoms (eg, visual disturbance, hemiplegia, dysarthria, aphasia, ataxia, seizure, and encephalopathy). With severe cases, intraparenchymal hemorrhage, subarachnoid hemorrhage, or ischemic stroke may result. No therapeutic intervention has been proven effective. The syndrome is usually self-limiting. (See 'RCVS/postpartum angiopathy' above.) Other causes Several other causes of stroke and cerebrovascular events during pregnancy and postpartum are reviewed above: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (see 'TTP and HUS' above) Peripartum cardiomyopathy (see 'Peripartum cardiomyopathy' above) Amniotic fluid embolism (see 'Amniotic fluid embolism' above) Gestational trophoblastic disease (see 'Gestational trophoblastic disease' above) Recurrence risk The risk of recurrent stroke in future pregnancy is probably low, but data are sparse. (See 'Risk of recurrent stroke' above.) https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 23/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Swartz RH, Cayley ML, Foley N, et al. The incidence of pregnancy-related stroke: A systematic review and meta-analysis. Int J Stroke 2017; 12:687. 2. Karjalainen L, Tikkanen M, Rantanen K, et al. Stroke in Pregnancy and Puerperium: Validated Incidence Trends With Risk Factor Analysis in Finland 1987-2016. Neurology 2021; 96:e2564. 3. James AH, Bushnell CD, Jamison MG, Myers ER. Incidence and risk factors for stroke in pregnancy and the puerperium. Obstet Gynecol 2005; 106:509. 4. Kittner SJ, Stern BJ, Feeser BR, et al. Pregnancy and the risk of stroke. N Engl J Med 1996; 335:768. 5. Sharshar T, Lamy C, Mas JL. Incidence and causes of strokes associated with pregnancy and puerperium. A study in public hospitals of Ile de France. Stroke in Pregnancy Study Group. Stroke 1995; 26:930. 6. Bateman BT, Schumacher HC, Bushnell CD, et al. Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome. Neurology 2006; 67:424. 7. Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke 2000; 31:1274. 8. Kamel H, Navi BB, Sriram N, et al. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014; 370:1307. 9. Scott CA, Bewley S, Rudd A, et al. Incidence, risk factors, management, and outcomes of stroke in pregnancy. Obstet Gynecol 2012; 120:318. 10. Feske SK, Singhal AB. Cerebrovascular disorders complicating pregnancy. Continuum (Minneap Minn) 2014; 20:80. 11. Miller EC, Gallo M, Kulick ER, et al. Infections and Risk of Peripartum Stroke During Delivery Admissions. Stroke 2018; 49:1129. 12. Miller EC, Wen T, Elkind MSV, et al. Infection During Delivery Hospitalization and Risk of Readmission for Postpartum Stroke. Stroke 2019; 50:2685. 13. Wabnitz A, Bushnell C. Migraine, cardiovascular disease, and stroke during pregnancy: systematic review of the literature. Cephalalgia 2015; 35:132. 14. Skeith L, Carrier M, Robinson SE, et al. Risk of venous thromboembolism in pregnant women with essential thrombocythemia: a systematic review and meta-analysis. Blood 2017; 129:934. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 24/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 15. Camargo EC, Feske SK, Singhal AB. Stroke in Pregnancy: An Update. Neurol Clin 2019; 37:131. 16. Camargo EC, Singhal AB. Stroke in Pregnancy: A Multidisciplinary Approach. Obstet Gynecol Clin North Am 2021; 48:75. 17. Hung SK, Lee MS, Lin HY, et al. Impact of Hypertensive Disorders of Pregnancy on the Risk of Stroke Stratified by Subtypes and Follow-Up Time. Stroke 2022; 53:338. 18. Mas JL, Lamy C. Stroke in pregnancy and the puerperium. J Neurol 1998; 245:305. 19. Cauldwell M, Rudd A, Nelson-Piercy C. Management of stroke and pregnancy. Eur Stroke J 2018; 3:227. 20. Kupferminc MJ, Yair D, Bornstein NM, et al. Transient focal neurological deficits during pregnancy in carriers of inherited thrombophilia. Stroke 2000; 31:892. 21. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. 22. De Keyser J, Gdovinov Z, Uyttenboogaart M, et al. Intravenous alteplase for stroke: beyond the guidelines and in particular clinical situations. Stroke 2007; 38:2612. 23. Selim MH, Molina CA. The use of tissue plasminogen-activator in pregnancy: a taboo treatment or a time to think out of the box. Stroke 2013; 44:868. 24. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 25. Activase (alteplase) prescribing information. https://www.accessdata.fda.gov/drugsatfda_do cs/label/2018/103172s5259lbl.pdf (Accessed on October 25, 2021). 26. Murugappan A, Coplin WM, Al-Sadat AN, et al. Thrombolytic therapy of acute ischemic stroke during pregnancy. Neurology 2006; 66:768. 27. Leonhardt G, Gaul C, Nietsch HH, et al. Thrombolytic therapy in pregnancy. J Thromb Thrombolysis 2006; 21:271. 28. Leffert LR, Clancy CR, Bateman BT, et al. Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period. Am J Obstet Gynecol 2016; 214:723.e1. 29. Dicpinigaitis AJ, Sursal T, Morse CA, et al. Endovascular Thrombectomy for Treatment of Acute Ischemic Stroke During Pregnancy and the Early Postpartum Period. Stroke 2021; 52:3796. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 25/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 30. Lansberg MG, O'Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e601S. 31. Sibai BM, Caritis SN, Thom E, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 1993; 329:1213. 32. Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet drugs for prevention of pre- eclampsia and its consequences: systematic review. BMJ 2001; 322:329. 33. Jeng JS, Tang SC, Yip PK. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women. Cerebrovasc Dis 2004; 18:290. 34. Silvis SM, Lindgren E, Hiltunen S, et al. Postpartum Period Is a Risk Factor for Cerebral Venous Thrombosis. Stroke 2019; 50:501. 35. Cantu-Brito C, Arauz A, Aburto Y, et al. Cerebrovascular complications during pregnancy and postpartum: clinical and prognosis observations in 240 Hispanic women. Eur J Neurol 2011; 18:819. 36. Skidmore FM, Williams LS, Fradkin KD, et al. Presentation, etiology, and outcome of stroke in pregnancy and puerperium. J Stroke Cerebrovasc Dis 2001; 10:1. 37. Witlin AG, Friedman SA, Egerman RS, et al. Cerebrovascular disorders complicating pregnancy beyond eclampsia. Am J Obstet Gynecol 1997; 176:1139. 38. Liang CC, Chang SD, Lai SL, et al. Stroke complicating pregnancy and the puerperium. Eur J Neurol 2006; 13:1256. 39. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42:1158. 40. Bushnell C, McCullough LD, Awad IA, et al. Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45:1545. 41. Miller EC, Leffert L. Stroke in Pregnancy: A Focused Update. Anesth Analg 2020; 130:1085. 42. Marshman LA, Aspoas AR, Rai MS, Chawda SJ. The implications of ISAT and ISUIA for the management of cerebral aneurysms during pregnancy. Neurosurg Rev 2007; 30:177. 43. Fox MW, Harms RW, Davis DH. Selected neurologic complications of pregnancy. Mayo Clin Proc 1990; 65:1595. https://www.uptodate.com/contents/cerebrovascular-disorders-complicating-pregnancy/print 26/41 7/5/23, 12:04 PM Cerebrovascular disorders complicating pregnancy - UpToDate 44. Salonen Ros H, Lichtenstein P, Bellocco R, et al. Increased risks of circulatory diseases in late pregnancy and puerperium. Epidemiology 2001; 12:456. 45. Tiel Groenestege AT, Rinkel GJ, van der Bom JG, et al. The risk of aneurysmal subarachnoid hemorrhage during pregnancy, delivery, and the puerperium in the Utrecht population: case-crossover study and standardized incidence ratio estimation. Stroke 2009; 40:1148. 46. Horton JC, Chambers WA, Lyons SL, et al. Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations. Neurosurgery 1990; 27:867. 47. Liu XJ, Wang S, Zhao YL, et al. Risk of cerebral arteriovenous malformation rupture during pregnancy and puerperium. Neurology 2014; 82:1798. 48. Gross BA, Du R. Hemorrhage from arteriovenous malformations during pregnancy. Neurosurgery 2012; 71:349. 49. Porras JL, Yang W, Philadelphia E, et al. Hemorrhage Risk of Brain Arteriovenous Malformations During Pregnancy and Puerperium in a North American Cohort. Stroke 2017; 48:1507. 50. Dias MS, Sekhar LN. Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium. Neurosurgery 1990; 27:855. 51. POOL JL. TREATMENT OF INTRACRANIAL ANEURYSMS DURING PREGNANCY. JAMA 1965; 192:209. 52. Qaiser R, Black P. Neurosurgery in pregnancy. Semin Neurol 2007; 27:476. 53. Tarnaris A, Haliasos N, Watkins LD. Endovascular treatment of ruptured intracranial aneurysms during pregnancy: is this the best way forward? Case report and review of the literature. Clin Neurol Neurosurg 2012; 114:703. 54. Pumar JM, Pardo MI, Carreira JM, et al. Endovascular treatment of an acutely ruptured intracranial aneurysm in pregnancy: report of eight cases. Emerg Radiol 2010; 17:205. 55. Meyers PM, Halbach VV, Malek AM, et al. Endovascular treatment of cerebral artery aneurysms during pregnancy: report of three cases. AJNR Am J Neuroradiol 2000; 21:1306. 56. Piotin M, de Souza Filho CB, Kothimbakam R, Moret J. Endovascular treatment of acutely ruptured intracranial aneurysms in pregnancy. Am J Obstet Gynecol 2001; 185:1261.