Cerebrovascular Disorders Complicating Pregnancy.12

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CerebrovascularDisorders ComplicatingPregnancy

Steven K. Feske, MD; Aneesh B. Singhal, MD

ABSTRACT

Purpose of Review: This article discusses the physiologic changes of pregnancy and howthey affectrisk of ischemic andhemorrhagic strokeandthen reviews epidemiology, diagnosis,and treatment of ischemic and hemorrhagic stroke in pregnancy and the puerperium.Recent Findings: This article updates our understanding of the relationship of

preeclampsia/eclampsia to the posterior reversible encephalopathy syndrome and thereversible cerebral vasoconstriction syndrome, emphasizing their shared pathogenesis. Itreviews the most recent data and offers recommendations concerning the use ofthrombolytic and other revascularization therapies for pregnancy-related strokes.Summary: Although cerebrovascular complications are uncommon occurrences duringpregnancy and the puerperium, stroke is still the most common seriously disablingcomplication of pregnancy. Therefore, stroke and other vascular issues raise questionsabout the best evaluation and management that is safe for mother and child.

Continuum (Minneap Minn) 2014;20(1):8099.

PHYSIOLOGY AND

PATHOPHYSIOLOGY OFPREGNANCY IN RELATIONTO VASCULAR DISEASEHemodynamic Changes

Pregnancy is a state of high metabolicdemand. The cardiovascular changesof pregnancy prepare the maternalcirculation to meet that demand. Es-trogen and other hormones cause anincrease in renin activity, leading toretention of sodium and water. Thissupports an increase in plasma vol-

ume beginning in the first trimesteraround 6 weeks of gestation. Somestudies suggest that this increase inplasma volume reaches a plateau inthe third trimester. Others suggest aprogressive increase until term.1 Redblood cell mass also increases, butproportionally less, resulting in a mildphysiologic hemodilutional anemia ofpregnancy. Cardiac output, stroke vol-

ume, and heart rate increase 30% to

50% as a result of the increaseddemand of the developing fetus andplacenta and maternal hypervolemia.This b eg ins as e arly as the f if thgestational week and reaches a pla-teau in the late second or third

trimester. Heart rate continues to riseuntil term. Increase in prostacyclinand redistribution of high flow in the

low-resistance uteroplacental circula-tion and breasts and kidneys causesystemic vascular resistance (SVR) to

begin to fall around the fifth gesta-tional week. This drop in SVR isaccompanied by a fall in the systolicand diastolic b lood pre ssure. I treaches a nadir in the third or latesecond trimester, about 20 to 32

weeks, after which it rises until termto levels at or slightly above the

normal nonpregnant blood pressure.There is increased venous capacitance

Address correspondence toDr Steven K. Feske, NeurologyDepartment, Brigham and

Womens Hospital, 75 FrancisStreet, Boston, MA 02115,[email protected].

Relationship Disclosure:Dr Feske has receivedroyalties from Elsevier forhis role as editor ofOfficePractice of Neurology, 2 ndEdition, and receivesresearch support from theNational Institute ofNeurological Disorders andStroke. Dr Singhal hasserved as a consultant forBiogen Idec and as a medicalexpert witness in cases ofstroke. Dr Singhals spouseholds stock or stock options

greater than 5% of thecompany or greater than$10,000 in value inBiogen Idec and VertexPharmaceuticals Incorporated.Dr Singhal has receivedresearch support from theNational Institute ofNeurological Disorders andStroke, and his institution hasreceived research supportfrom Pfizer Inc andPhotoThera, Inc, for clinicaltrial participation.

Unlabeled Use ofProducts/InvestigationalUse Disclosure:Drs Feske and Singhal report

no disclosures.* 2014, American Academyof Neurology.

80 www.ContinuumJournal.com February 2014

Review Article

Copyright American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
mailto:[email protected]:[email protected]


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and reduced blood flow (ie, relativevenous stasis), often accompanied by

orthostatic intolerance. The volumeincrease tends to increase preload.However, preload is heavily depen-dent upon position, with reducedpreload and orthostasis resulting fromthe higher venous capacitance andfrom compression on the inferior venacava in the supine position.

Vascular and ConnectiveTissue Changes

Pregnancy causes remodeling of the

heart and all blood vessels. The wallsof systemic arteries show a reductionin collagen and elastin content and aloss of distensibility. Animal modelshave shown increased contractileforce, decreased stiffness, and in-creased relaxation response in themiddle cerebral artery.2 The roles ofthe molecular promoters underlyingthese physiologic responses to preg-nancy and the full effects of theseadaptive changes are complex andpoorly understood. Their relationship

to stroke is not certain; however, onemight e xpe ct the he modynamicchanges near term combined withthese structural changes of blood

vessels to result in a state in whichmore vulnerable vascular walls experi-ence greater hemodynamic stress,possibly contributing to the risk ofhemorrhage in late pregnancy.

Changes in theCoagulation System

Both hemodynamic and biochemicalchanges make pregnancy a state ofhypercoagulability. Decreased venouscompliance results in venous stasisand congestion. Compression of theinferior vena cava, aorta, and bloodsupply of the gravid uterus can cause

vascular injury. Levels of procoagulantfactors, coagulation inhibitors, andother mediators of clot formation

and lysis are altered by pregnancyresulting in a state of incre ased

hypercoagulability in late pregnancy.Levels of procoagulant factors I, VII,

VIII, IX, X, XII, and XIII increaseduring pregnancy. There is littlechange in levels of factors II, V, and

XI. The levels of some coagulationinhibitors fall during pregnancy. Thecoagulation inhibitor antithrombin IIIfalls and is at its nadir in the thirdtrimester. Total and free levels of thecoagulation inhibitor cofactor proteinS are significantly decreased as well.

Although levels of protein C remainunchanged, almost a third of womenhave functional activated protein C resis-tance during the third trimester. Thesechanges of venous flow and the molec-ular mediators of thrombosis are greatestduring the late third trimester and earlypuerperium. Along with iron deficiencyand the acute phase responses of thetrauma and hemorrhage of delivery, theycreate the greatest hypercoagulabilityduring the early puerperium.

Preeclampsia/EclampsiaPreeclampsia is a multisystem disorderof mid- to late pregnancy traditionallycharacterized by pregnancy-inducedhypertension, edema, and proteinuria;eclampsia is the development of sei-zures in a patient with preeclampsia.Preeclampsia and eclampsia can infre-quently occur after childbirth, usually

within 48 hours (postpartum pre-eclampsia), or up to 4 to 6 weeksafter childbirth (late postpartum pre-

eclampsia).3

Postpartum preeclampsiacan manifest de novo postpartum orresult from preeclampsia, preexistingchronic hypertension, or persistentgestational hypertension (systolicblood pressure greater than 140 mmHg or diastolic blood pressure greaterthan 90 mm Hg without proteinuria).

The criteria for diagnosis depend onthe definition of the clinical syndrome.

KEY POINTS

h Pregnancy results in

increased metabolic

demand, sodium and

water retention, and

decrease in systemic

vascular resistance,

leading to expansion of

plasma volume; mild

anemia; increased

stroke volume, heart

rate, and cardiac

output; and decreased

systolic and diastolic

blood pressures.

h Changes in vascular

structure and thecoagulation system,

although adaptive,

also lead to a relative

vulnerability to

hemorrhage and

ischemic stroke,

especially during the

postpartum period.

81Continuum (Minneap Minn) 2014;20(1):8099 www.ContinuumJournal.com



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Modern consensus definitions all en-dorse pregnancy-induced hypertension

beginning after the 20th week withproteinuria as preeclampsia, and gener-ally accept the inclusion of women withpregnancy-induced hypertension with-out proteinuria but with other commonmanifestations, including (1) cerebralsymptoms, (2) epigastric or right upperquadrant pain with nausea or vomiting,or (3) thrombocytopenia and abnormalliver enzymes.4 It has been claimed that,although pregnancy-induced hyperten-sion is the cornerstone of clinical

diagnosis, a significant proportion ofwomen who develop hemolysis, ele-vated liver enzymes, and low plateletcount (HELLP) syndrome or eclampticseizures do not have hypertension.5,6

Since the precise diagnosis of pre-eclampsia is currently limited by thelack of a specific biomarker, it is oftendesirable to entertain a permissivelybroad definition for use in clinicalpractice. Although much has beenlearned about preeclampsia over thelast decade, a clear understanding of

the relationship of the many underlyingrisk factors and various features ofabnormal physiology is still lacking.There is strong evidence that immunemaladaptation is central to its cause.

While abnormal placentation and pla-cental hypoperfusion play an importantrole, hypoperfusion does not seem to beprimary, because markers of preeclamp-sia are present in the first trimester,before placental hypoperfusion.7 Al-though the triggers for the abnormal

placentation are not clearly understood,there is strong evidence for dysregula-tion of angiogenic and vasoactive factors,such as vascular endothelial growthfactor (VEGF) and placental growthfactor (PlGF) and nitric oxide and,ultimately, antagonism of these factorsby binding to soluble VEGF receptor-1(also known as Fms-like tyrosine kinase1 [sFlt1]). Fundamental to many of the

relevant clinical complications of pre-eclampsia are endothelial dysfunc-

tion, absence of the normal stimulationof the renin-angiotensin system despitehypovolemia, hypersensitivity to angio-tensin II leading to increased systemic

vascular resistance and hypertension,augmentation of the normal thrombox-ane A2/prostacyclin ratio, increasedplatelet activation, and increased throm-bin formation and fibrin generation.Endothelial dysfunction contributes toincreased capillary permeability that un-derlies proteinuria, edema, and, most

important among our concerns, brainedema at relatively modest elevationsof blood pressure.

ISCHEMIC STROKE ASSOCIATEDWITH PREGNANCYEpidemiology

No long-term prospective studies ofthe incidence and types of pregnancy-associated stroke have yet been done.

Available studies handle spontaneousand therapeutic abortions and still-births differently and use different

definitions of the puerperium anddifferent methods of stroke classifica-tion. This lack of consistency of datalimits comparisons, but we can esti-mate the impact of stroke from thesestudies. Table 4-18 summarizes ninem a j or s t u di e s p u bl i s he d s i n ce1985.9Y17 From the three population-based studies, we can estimate theincidence of stroke. In these threestudies, the incidence of all types ofstroke ranges from four to seven cases

per 100,000 pregnancies. However,data from the National InpatientSample of the Healthcare Cost andUtilization Project suggest that theincidence of pregnancy-associatedstroke has risen since the 1990s. Thesedata estimate the incidence of all typesof pregnancy-associated stroke, in-cluding ischemic and hemorrhagicstrokes, subarachnoid hemorrhage,

KEY POINT

hPreeclampsia/eclampsia

is a state of

hypertension,

endothelial and

platelet dysfunction,

and enhanced

coagulability with

many pathologic

consequences.


Cerebrovascular Disorders Complicating Pregnancy



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and cerebral venous sinus thrombosis,to be 25 to 34 per 100,000 deliveries.

This analysis compares data from 1994and 1995 to data from 2006 and 2007.Between these intervals, antenatal hos-pitalizations increased by 47% (from0.15 to 0.22 per 1000 deliveries), andpostpartum hospitalizations by 83%

(from 0.12 to 0.22 per 1000 deliveries),with the increases largely explained by

concurrent hypertensive disorders orheart disease.18 In comparison, theincidence of stroke in nonpregnant

women in the 15- to 45-year age groupis 11 per 100,000.19 Kittner foundno increased risk of ischemic stroke

TABLE 4-1 Studies of Stroke in Pregnancya

Study Location MethodsTimeInterval

Number ofPregnancies

Number of Strokes

Ischemic Hemorrhagic

Feske et al,2009

Bostonhospital

Retrospective 1996Y2005 101,570 17 36

Postpartumperiod(PP) = 3 months

Liang et al,2006

Taiwanhospital

Retrospective 1992Y2004 66,781 11 21

PP = 6 weeks

Jeng et al,2004

Taiwanhospital

Retrospective 1984Y2002 Data notreported

27 22

15Y40-year-oldsPP = 6 weeks

Jaigobin et al,2000

Torontohospital

Retrospective 1980Y1997 50,711 21 13

PP = 6 weeks

Witlin et al,1997

Memphishospital

Retrospective 1985Y1995 79,301 14 6

PP = notreported

Kittner et al,1996

Maryland andWashington DC(46 hospitals)

Retrospective 1988Y1991 234,023 17 14

Population-based

PP = 6 weeks

Sharshar et al,1995

Ile de France(63 hospitals)

Retrospective 1989Y1991 348,295 15 16

Population-basedPP = 2 weeks

Awada et al,1995

Saudi Arabiahospital

Retrospective 1983Y1993 Data notreported

9 3

pp = 15 days

Wiebers et al,1985

Rochester, MNhospitals

Retrospective 1955Y1979 26,099(live births)

1 0

Population-basedPP not included

a Modified with permission from Feske SK, Semin Neurol.8 B 2007, Thieme Medical Publishers. www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126.


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during pregnancy (relative risk 0.7) buta large relative increase during the

6-week postpartum period (relativerisk 8.7). Figure 4-1 shows a similarpreponderance of events in the post-partum period in the authors study. Thehigher proportions of strokes in theother studies are probably due to referralbias, since these represent series fromsingle large referral hospitals. Despite itslow overall incidence, stroke contributesa major proportion of the long-termdisability resulting from pregnancy.

Mechanisms

Although differences and limitationsin methods of case assessment com-promise interpretations, the ischemicstrokes can be broken down by typesto assess the mechanisms and con-tributing causes of pregnancy-relatedstrokes (Table 4-28). Here, the au-thors have classified venous sinus throm-bosis with ischemic-thrombotic stroke,although many will have components ofhemorrhage. When mechanisms of ische-mic stroke are identified, the major ones

are cardioembolism and venous sinusthrombosis. Preeclampsia/eclampsia ap-pears to be a major contributor to stroke

risk. In studies in which preeclampsia/eclampsia is reported, it is present in

11% to 47% of cases of stroke. Thecontribution of preeclampsia/eclampsiato the cause of strokes is presumed tobe complex and related to the various

vasculopathic and prothrombotic ef-fects discussed above. Other well-established causes of stroke in youngpatients, such as arterial dissectionand moyamoya syndrome, can presentduring pregnancy and should be consid-ered (Case 4-1). Other pregnancy-specific causes, such as peripartum

cardiomyopathy, choriocarcinoma,and embolization of amniotic fluidor air, are very rare and should beconsidered based on the clinical pre-sentations. Amniotic fluid embolismshould be considered when evidence ofdiffuse or multifocal brain ischemia ispresent and accompanied by features ofpulmonary embolism.

Evaluation

Stroke is suspected clinically based on

the sudden onset of a neurologicdeficit suggestive of a focal lesionand without an alternative cause.

KEY POINTS

hThe risk of ischemic

stroke is increased

during the postpartum

period.

hAlthough

pregnancy-associated

ischemic stroke is rare, it

is a major contributor to

long-term disability

resulting from

pregnancy.

hCardioembolism,

preeclampsia/eclampsia,

and cerebral venous

sinus thrombosis

account for most

pregnancy-related

ischemic stroke.

FIGURE 4-1 Timing of events during pregnancy and the puerperium. Each dot representsthe time during pregnancy (in weeks) or the puerperium (in days) of a singleevent as color-coded.

Reprinted with permission from Feske SK, et al, International Stroke Conference.17





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Properly timed neuroimaging will con-firm the great majority of ischemicstrokes. Concerns arise when planningneuroimaging during pregnancy.These are discussed in detail in thearticle Neuroradiology in Women ofChildbearing Age by Drs Riley Boveand Joshua Klein in this issue of

. In general, with prop-er precautions, CT and MRI should beused as with nonpregnant patients toidentify areas of infarction and to

investigate the cerebral vasculature.Cerebral vessel imaging with magneticresonance (MR) angiography, CTangiography, or transfemoral catheterangiography is indicated to assessfor cerebral arterial dissection, revers-ible cerebral vasoconstriction syn-drome, moyamoya disease, or otherarteriopathies. Cardiac ultrasound shouldbe performed in patients with embolic

infarctions, and should include agitatedsaline injection (bubble study) to investi-gate for a right-to-left shunt from a patentforamen ovale, the presence of whichmay suggest paradoxical embolism and

warrant further testing for lower extrem-ity or pelvic deep vein thrombus.22 As

with any patient with stroke, blood testssuch as lipid panel, hemoglobin A1C,erythrocyte sedimentation rate, C-reactive protein, and others should beroutinely performed, with additional tests

such as hemoglobin electrophoresis forsickle cell disease or antiphospholipidantibody panel performed on a case bycase basis. Genetic testing for throm-bophilia (prothrombin G20210A muta-t i on , f ac to r V L ei d en m u ta ti o n,methylenetetrahydrofolate reductasemutation) can be performed duringpregnancy, but testing for other hyper-coagulable states (protein C, protein S,

TABLE 4-2 Causes of Ischemic Strokes in Pregnancy (% of All Ischemic Strokes)a,b,c

Study Cardioembolism

Preeclampsia/EclampsiaAngiopathy

Venous SinusThrombosis Unknown Other

Feske et al,2009

35 30 39 I 22

Liang et al,2006

36 18 27 I I

Jeng et al,2004

44 I 22 22 I

Jaigobin et al,2000

20 20 40 20 15

Witlin et al,1997

I I 64 I I

Kittner et al,1996

I 38d 6 38 19

Sharshar et al,1995

I 54d I 27 20

Awada et al,1995

33 11 I 44 11

a Modified with permission from Feske SK, Semin Neurol.8 B 2007, Thieme Medical Publishers. www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126.

b Totals of the rows may exceed 100% because multiple contributing causes may be counted.c Ellipses indicate that data was not reported.d These authors reported preeclampsia/eclampsia-associated and CNS angiopathy separately (see text).


http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126http://www.thieme-connect.com/DOI/DOI?10.1055/s-2007-991126


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and antithrombin III deficiency) shouldbe performed at least 6 weeks afterdelivery when physiologic changes dueto pregnancy will have normalized.

Therapies and Outcomes

IV recombinant tissue plasminogenactivator (tPA) is a US Food and Drug

Administration (FDA)Yapprove dthrombolytic drug that remains theonly proven efficacious therapy foracute ischemic stroke.23,24 Many largestroke centers offer intra-arterial throm-

bolysis as a salvage therapy in severe

stroke cases. Intra-arterial thromboly-

sis typically involves mechanical clot

Case 4-1

A 20-year-old woman developed right hemichorea during the secondtrimester of her first pregnancy. Brain imaging showed subcortical infarctionspredominantly in the left hemisphere and severe stenosis of the right and leftmiddle cerebral arteries (Figure 4-2). No headache or fever or segmental arterialnarrowing or other evidence of cerebral arteritis or infection was present.Hemoglobin electrophoresis was normal, ruling out sickle cell anemia.

Comment. This patient was diagnosed with moyamoya disease,an idiopathic noninflammatory cerebral arteriopathy. The choreiformmovements resolved after a short course of steroids. The patient declinedthe option of surgical intervention with the encephaloduroarteriosynangiosisprocedure, which has been shown to reduce the risk for future stroke.20,21

She was treated with aspirin 325 mg/d for stroke prevention. She went on tohave three vaginal deliveries without further neurologic symptoms such asheadache, chorea, or weakness. Follow-up brain imaging studies showed noevidence for new stroke.

FIGURE 4-2 Brain imaging of a 20-year-old primigravida with right hemichorea. Note the

subcortical infarctions predominantly in the left hemisphere (A, fluid-attenuatedinversion recovery [FLAIR] MRI) and severe stenosis of the right and left middlecerebral arteries (B, head magnetic resonance [MR] angiogram,three-dimensional time-of-flight image).





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retrieval using FDA-approved devices.Recent phase III clinical trials showing

no benefit of intra-arterial over IVt h r o m b o l y s i s2 5 w i l l p r o m p t areassessment of the role of catheter-based therapies, but evidence existsthat improved outcomes dependon early recanalization of occludedarteries, and FDA-approved devices

will continue to find use as researchproceeds on this issue. Because preg-nant women were excluded from allof these trials, there has been nocontrolled study of the use of such

agents in pregnancy. Although thereare case reports of successful IV andintra-arterial thrombolytic use inpregnant women,26Y31 questions forcl inicians re main: S hould thesetherapies be applied in pregnant

wo me n su ff er in g ac ut e is ch em icstrokes? Are they safe and effectivefor the mother? Are they safe for thefetus?

IV tPA has a very short serum half-life of less than 5 minutes. However, itbinds to newly formed fibrin clots,

where its lytic effect lasts for manyhours. It is a large molecule that doesnot cross the placenta in animals, andso it should not be expected to placethe fetus at risk of teratogenicity. Thepotential risks of real concern arematernal hemorrhage, placental hem-orrhage and abruption, fetal loss, andpreterm delivery. Although there aretheoretical reasons to question com-parisons to its use in nonpregnantpatients, mainly that pregnancy is a

state of relative hypercoagulabilitycharacterized by decreased intrinsictPA and increased plasminogen activa-tor inhibitor, the ultimate effects ofthese changes on the clinical efficacyof tPA are speculative and unlikely tobe answered by clinical trials. There-fore, more empirical clinical data mustbe used to estimate the risk. Theauthors have found reports in the

literature of six women who havereceived IV tPA for stroke while preg-

nant, although many more have beentreated as this has become acceptedpractice.26Y31 Of the six women whoreceived IV tPA, three suffered nohemorrhagic complications, one hadminor hemorrhagic transformation ofthe cerebral infarct, and one had anintrauterine hematoma. Of these sixcases, no fetal complications occurredin three, and in two cases the preg-nancy was terminated allowing nofurther analysis. The sixth patient and

fetus died as a result not of a directeffect of the systemic tPA, but fromarterial dissection complicating angio-plasty. Of five women treated withintra-arterial thrombolysis for acutearterial occlusion (three tPA, two uro-kinase), none had serious complica-tions from the procedure; two hadhemorrhagic transformation of thestroke with good neurologic out-comes, and one had a minor buttockhematoma.26,29,32 Four of the f ive

women delivered healthy babies; one

preg nancy, in w hich the strokeresulted from bacterial endocarditis,ended in spontaneous abortion. Itshould be noted that urokinase, un-like tPA, does cross the placenta.Minor hemorrhagic transformation iscommon after thrombolysis in gener-al, and it does not appear to worsenoutcomes. In fact, it has been associ-ated with better outcomes, possiblybecause it is a marker of early recan-alization. To summarize, of these 11

women who rece ived IV or intra-a r t er i a l t h r om b ol y s is a n d w e rereported in the literature, 10 had nomajor complications from thromboly-sis, and the patient who died had amajor complicating illness; of the 11reported fetal outcomes, seven weredelivered without complications, two

were terminated therapeutically, onepatient with bacterial endocarditis had




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a spontaneous abortion, and one fetusdied along with the mother.

With such limited and uncontrolleddata, it is not possible to draw firmconclusions; however, it is reasonableto judge that pregnancy does notappear to present a decisive addedrisk to thrombolytic therapy. There-fore, thrombolysis should be consid-ered for all potentially disablingstrokes during pregnancy, and itshould not be excluded based on thefact of pregnancy alone. As in allpatients, the details of the case should

be carefully weighed, and patients orproxy decision makers should be wellinformed of risks. Obstetric consulta-tion should be sought from the outsetfor careful monitoring and decisionmaking. Care in facilities with experi-ence both in advanced stroke care andhigh-risk obstetrics is optimal, and thecause and mechanism of the strokeshould be carefully determined tothe extent possible before therapy isprescribed. For example, women withstroke as a result of amniotic fluid

embolism would not benefit fromtPA. Additionally, given the known riskof cerebral hemorrhage from hyper-tensive encephalopathy in the settingof preeclampsia/eclampsia, patients

who have strokes complicating pre-eclampsia or eclampsia should notreceive tPA.

PREECLAMPSIA/ECLAMPSIA,HYPERTENSIVE ENCEPHALOPATHY,AND POSTPARTUM CEREBRAL

ANGIOPATHY

Overview

Preeclampsia/eclampsia contributes tocerebrovascular events in two major

ways. First, as noted above, preeclampsia/eclampsia causes many pathophysio-logic changes in blood vessels andthe thrombotic system and in this wayaccounts for a large proportion of is-

chemic strokes in pregnancy. Second,one direct consequence of preeclampsia/

eclampsia is the posterior reversibleencephalopathy syndrome (PRES), aform of the syndrome of hypertensiveencephalopathy characterized by re-

versible brain edema, often associatedwith elevated blood pressure, seizures,brain hemorrhage, and ischemicstrokes.

Preeclampsia/Eclampsiaand Posterior ReversibleEncephalopathy Syndrome

Pathophysiologic mechanisms. Thepathophysiology of preeclampsia/eclampsia is discussed briefly above.The features of preeclampsia/eclampsiadirectly relevant to PRES and probablyalso to eclamptic seizures are (1) anabnormal increase in vascular tone and(2) dysfunction of endothelial cells.Patients with preeclampsia/eclampsiahave heightened sensitivity to media-tors of vasoconstriction, such as angio-tensin II. This resultant increase in

vascular tone is responsible for system-

ic hypertension and for the vasomotorinstability that underlies vasospasm.Endothelial dysfunction is in part re-sponsible for the instability of vasculartone, and it also results in increased

vascular permeability that underlies thedevelopment of edema and protein-uria that characterize preeclampsia/eclampsia. The syndrome commonlycalled PRES results from the develop-ment of cerebral edema. Fluid crossesfrom the intravascular to the interstitial

space as a result both of an increase incapillary filtration pressure caused byhypertension and of loss of integrityof the blood-brain barrier causedby endothelial dysfunction. Animalmodels of the blood-brain barriersresponse to severe acute hypertensionhave shown both increased pinocytosisand flow across impaired endothelialgap junctions.33

KEY POINT

hAlthough data on the

use of thrombolytic

therapies during

pregnancy are scarce,

limited experience

suggests that these

agents can be given

with safety comparable

to that in nonpregnant

patients.





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Postpartum CerebralAngiopathy

Postpartum angiopathy is one of severalconditions included in the spectrum ofthe reversible cerebral vasoconstrictionsyndromes (RCVS).34 Postpartum an-giopathy is characterized by severeheadaches and reversible narrowing ofintracerebral arteries, often com-plicated by seizures, reversible brainedema, lobar hemorrhage, convexity(nonaneurysmal) subarachnoid hemor-rhage, and ischemic strokes. In thepast, patients with this syndrome were

often misinterpreted as having inflam-matory cerebral vasculitis because thelatter can also manifest with headache,stroke, and cerebral angiographic ab-normalities; however, postpartumangiopathy is a noninflammatory, vaso-constrictive condition. Approximatelyone-third of patients with postpartumangiopathy are noted to have revers-ible cerebral edema and clinical fea-tures (headaches, seizures) which are

very similar to patients with PRES, andmore than half the patients with PRESshow evidence of cerebral artery nar-rowing on vascular imaging.35 Hence,postpartum angiopathy and PRES areconsidered overlapping conditions.36

Case 4-2 illustrates this overlap in asingle patient. The pathophysiologicmechanisms whereby preeclampsia/eclampsia is related to PRES are prob-ably also applicable to postpartumangiopathy.

Evaluation

The syndromes mentioned aboveVvariously called eclampsia, hyperten-sive encephalopathy, PRES, RCVS, andpostpartum angiopathyVcan then beconsidered as various presentations ofa similar fundamental underlying path-ophysiology. This clinical lumping isnot meant to oversimplify the com-plex pathophysiology of preeclampsia/eclampsia, nor to make the claim that

our understanding of this disorder iswell developed. For example, there

may be important pathophysiologicdifferences in classic preeclampsia/eclampsia and postpartum syndromesthat lack proteinuria or even hyper-tension.4 Nonetheless, it has beenrecognized in recent years that thebasic preeclampsia/eclampsia patho-physiology may account for these latepre gnancy and postpartum syn-dromes when they do not fit thetraditional definition of preeclampsia/eclampsia with proteinuria and when

they develop up to many weeks afterdelivery.4,38

Eclamptic hypertensive encepha-lopathy (ie, PRES) typically presents

with headache, visual symptoms refer-able to the occipital lobes, and sei-zures. Eclamptic RCVS presents withthunderclap headache, seizures, andfocal neurologic deficits. Imaging typ-ically shows posterior white and oftengray matter change consistent with

vasogenic cerebral edema (hypodenseon CT and hyperinte nse on T2-

weighted MRI), the findings typical ofPRES, or segmental narrowing anddilation of large and medium-sizedcerebral arteries, the findings typicalof RCVS. Both or either of theseimaging patterns may be seen, andthese imaging findings have limitedsensitivity, so imaging may be un-revealing in otherwise clinically con-

vincing cases. Although most lesionsare limited to edema and are there-fore reversible, hemorrhages and focal

ischemic strokes may also occur.

Therapies and Outcomes

The goals of therapy are to controlelevated blood pressure, control sei-zures, and minimize vasospasm and riskof secondary infarct and hemorrhage.Because the authors interpret thesesyndromes in association with preg-nancy as manifestation of eclampsia,

KEY POINTS

h Preeclampsia/eclampsia

can lead to several

cerebrovascular

syndromes, including

posterior reversible

encephalopathy

syndrome, reversible

cerebral vasoconstriction

syndrome, and ischemic

and hemorrhagic

strokes.

h The major CNS

complications of

preeclampsia/eclampsia

are a form of

hypertensiveencephalopathy.

They should be treated

aggressively with

rapid control of blood

pressure and IV

magnesium sulfate.




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Case 4-2

A 36-year-old woman developed severe headaches associated with new-onset hypertension 10 daysafter delivery of twins by cesarean delivery. The initial brain MRI and CT examinations were normal.Headaches persisted despite antihypertensive medications. A seizure and an episode of aphasia andhemiparesis occurred. Repeat MRI on day 18 (Figure 4-3A37) showed hyperintense regions in bothparietalYoccipital lobes with elevated diffusionVfindings consistent with vasogenic edema. Theseclinical-imaging features are consistent with the posterior reversible encephalopathy syndrome (PRES).Magnetic resonance (MR) angiography of the circle of Willis showed multifocal stenoses in the

FIGURE 4-3 Brain imaging of a 36-year-old woman with severe headaches associated with postpartum hypertension.A, fluid-attenuated inversion recovery (FLAIR) image shows hyperintense regions in both parietal and occipitallobes (arrows) with elevated diffusion (not shown), findings that are consistent with vasogenic edema.

B, Magnetic resonance (MR) angiography of the circle of Willis shows multifocal stenoses in the proximal anterior, middle, andposterior cerebral arteries. This finding is consistent with postpartum angiopathy. Cand D show hyperintense lesions (arrows)on FLAIR and diffusion-weighted images, respectively, from MRI performed 1 day later, a finding consistent with ischemicstroke.E, a follow-up MR angiogram shows worsening of the multifocal cerebral arterial stenosis. F, FLAIR shows bilateralcerebral infarction with edema and hemorrhage.

Reprintedwithpermission from Singhal AB etal, N Engl J Med.37 Copyright B2009, Massachusetts Medical Society.www.nejm.org/doi/full/10.1056/NEJMcpc0809063.

Continued on page 91



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treatment with IV magnesium sulfatealong with other therapies directed atb lo od p re s su re a nd s e iz u re s i srecommended. Several studies haveshown the superiority of magnesiumsulfate over commonly used anticon-

vulsants for prevention and treatmentof eclamptic seizures.39Y41 The authorsgive a loading dose of 4 g to 6 g ofmagnesium sulfate over 20 to 30minutes followed by continuous infu-sion at 2 g per hour with an additional2 g bolus if seizures occur during thistherapy. Patients should be monitoredc l os e ly a n d m a gn e si u m s u lf a testopped if deep tendon reflexes arelost, if respirations are depressed, or ifurine output falls below 100 mL in 4

hours. Calcium gluconate 1 g slow IVpush can be given to reverse severetoxicity. In addition, patients witheclamptic syndromes should be treatedurgently with IV antihypertensiveagents and with additional antiepilepticagents if needed for seizure control.Most women with preeclampsia/ eclampsia are volume contracted and

will benefit from volume replacement

and maintenance. Although many prac-titioners have used calcium channelblockers and glucocorticoids in thesepatients, this use is not supported byclinical data. No evidence has proventhat calcium channel blockers are more

effective than other antihypertensiveagents. In a study of 139 patients withRCVS, of which 12 were postpartum,corticosteroids were associated with atrend toward poorer outcomes.34 Thisseries is weighted toward the RCVSpresentation, so it is not representativeof eclampsia in general. A third of thepatients in this series presented withseizures, and a third suffered ischemicstrokes. Ninety percent had good out-comes (Modified Rankin Scale 0 to

3).34

Most patients with pregnancy-associated PRES and RCVS have a self-limited clinical course with benignoutcome and resolution of brain and

vascular imaging abnormalities withindays to weeks; however, 5% to 12%can have a fulminant course with prog-ressive vasoconstriction, brain edema,and strokes, culminating in persistentsevere neurologic deficits or death.37,42

proximal anterior, middle, and posterior cerebral arteries. This finding is consistent withpostpartum angiopathy. MRI performed on postpartum day 19 showed hyperintense lesions on FLAIRand diffusion-weighted images, a finding consistent with ischemic stroke. Despite multiple attempts todilate the cerebral arteries with intracerebral vasodilator injections, the patient showed clinical andangiographic progression over the course of 1 week. A follow-up MR angiogram showed worsening ofthe multifocal cerebral arterial stenosis, and FLAIR showed bilateral cerebral infarction with edema andhemorrhage. The patient eventually died. On autopsy, the cerebral arteries were normal, with noevidence of inflammation.

Comment. This is a classic example of postpartum eclampsia with postpartum angiopathy andfeatures of posterior reversible encephalopathy and reversible cerebral vasoconstriction syndromes,illustrating that these causes of postnatal ischemic and hemorrhagic stroke are interrelatedconditions. These syndromes are difficult to predict or prevent. Considering these as manifestationsof preeclampsia/eclampsia, the authors treat with magnesium sulfate, based on the clinical trialsdiscussed in the text. It is also important to control blood pressure when elevated, as with other formsof hypertensive encephalopathy. No treatment has proven efficacy for the cerebral artery narrowingof postpartum angiopathy. Calcium channel blockers are a reasonable, if untested, choice. While90% of patients have a self-limited course and recover within days to weeks, some patients(as in this example) may have a progressive course and even a fatal outcome.

Continued from page 90




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CEREBRAL VENOUS SINUSTHROMBOSIS

Epidemiology

This review includes the cases ofcerebral venous thrombosis amongthose of arterial ischemic infarctionabove in discussing the rate of ische-mic stroke in pregnancy because it isoften not clearly distinguished fromarterial stroke in large series of preg-nancy and stroke. However, cerebral

venous sinus thrombosis is a disordervery different from arterial occlusion

with different pathophysiology, ther-apy, and outcomes. Cerebral venousthrombosis accounts for 6% to 64% ofall pregnancy-associated strokes inlarge reported series and 17% in theauthors series.16 Venous thrombosismay present with imaging findings ofthrombus within a cerebral vein or

venous sinus without parenchymalchanges or with evidence of cerebraledema, apparent ischemic stroke, orhemorrhage, and as a result, thisdisorder is classified differently by

different authors.

Mechanisms

Thrombosis in the venous circulation,including the cerebral venous sinusesand veins, is presumed to be theoutcome of the underlying hyper-coagulable state of pregnancy, promotedb y the various pathophysiologicchanges of pregnancy described above.These effects reach their peak duringthe early postpartum period, the time

when most cases of cerebral venousthrombosis present. Figure 4-1 showsthe time during pregnancy of thediagnosis of cerebral venous thrombo-sis in the authors patients.17 In addi-tion to the known alterations inplatelet function and prothromboticand antithrombotic proteins, iron defi-ciency anemia and the adaptive re-sponse to the acute trauma and

hemorrhage of labor and delivery maycontribute to the propensity for abnor-

mal thrombosis. This timing of risk iscomparable to lower extremity deep

venous thrombosis in pregnancy.43

Although often called venous infarc-tion, with large collecting sinusthrombosis, the brain lesions typicallybegin as areas of brain edema withoutinfarction as a result of impaired venousdrainage and increased venous pres-sures. Ultimately, stasis of flow maycause these lesions to progress to in-clude areas of infarction and hemor-

rhage. In addition, hemorrhage mayextend to other compartments, includ-ing the subarachnoid, subdural, andintraventricular spaces. Because the pri-mary process is edema, much of the

visualized lesion (hypodensity on CT orhyperintensity on T2-weighted MR) isreversible with treatment, and outcomesare typically very good, much better thanfor comparable-sized arterial strokes.

Evaluation

Women with cerebral venous throm-

bosis may present with headaches,focal neurologic deficits, depressedlevel of consciousness, or seizures,and the pregnant state should greatlyheighten the index of suspicion forthis diagnosis. Cerebral venous sinusthrombosis can b e de te cte d onnoncontrast CT as hyperdensity inthe region of thrombosis or as paren-chymal hypodensity from edema orinfarction or hyperdensity from hem-orrhage. Contrast CT may show a

filling defect within the thrombosedsinus surrounded by the enhancingdura of the sinus wall (empty deltasign). Contrast CT venography mayshow the thrombosis as a filling defectin the region of the affected sinus. OnMRI, venous sinus thrombosis can beseen directly as thrombus with signalcharacteristics appropriate to thetime since onset (T1-isodense and

KEY POINT

hCerebral venous

thrombosis, especially

postpartum, is one

of the most common

cerebrovascular

complications of

pregnancy.





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T2-hypodense when acute, with T1turning hyperintense followed by T2

turning hyperintense so that thethrombus is bright on both T1- andT2-weighted images when in the latesubacute phase). Since cerebral venousthrombosis may have been present forsome time before symptoms lead todiagnosis, it is common to see later-phase characteristics upon initial diag-nosis. MR venography can also showthe thrombosis as a filling defect. Thiscan be done without contrast, an advan-tage during pregnancy and nursing. As

with arterial stroke, with proper pre-cautions, it is possible to obtain goodimaging confirmation safely duringpregnancy. Cerebral cortical vein throm-bosis without venous sinus thrombosiscan be more difficult to confirm but iscommonly visible as an expanded tubu-lar vein on the cortical surface, often

with T2-weighted signal hyperintensityin the adjacent parenchyma.

Therapy

The best available data support, if

weakly, the use of anticoagulation totreat cerebral venous thrombosis, in-cluding in those patients with hemor-rhagic lesions. Meta-analysis and theauthors experience treating manysuch patients are consistent with thisrecommendation from the litera-ture.44,45 A randomized, controlledtrial by Einhaupl was small but seemedto show a clear benefit.46 In fact, it wassmall because it was terminated earlydue to the evidence of benefit in favor

of heparin anticoagulation after only20 patients had been enrolled. A largerDutch study of low-molecular-weightheparin was negative but showed atrend in favor of early anticoagula-tion.46 This study was limited by thefact that patients in both groupsreceived warfarin anticoagulation afterthe first 3 weeks of the study treat-ment, possibly accounting to some

degree for the small difference be-tween groups. Cerebral hemorrhage

occurs in nearly half of patients withcerebral venous thrombosis, so thequestion of the safety of anticoagula-tion in this subset is important. In theEinhaupl study, three of 10 patientstreated with heparin had experiencedhemorrhage before treatment. Noneof these patients had expansion oftheir hemorrhage or new hemor-rhage, and all recovered fully. Thisstudy also included a retrospectivereview of 102 patients with cerebral

venous thrombosis. Among these pa-tients, 27 of 43 with hemorrhagereceived full-dose heparin, while 13received no heparin after hemor-rhages were found. Those who re-ceived heparin had lower mortality(15% versus 56%). In the Dutch studyas well, no worsening occurred inthose receiving anticoagulation de-spite the presence of hemorrhage.The authors recommend full heparinanticoagulation during the acutephase of cerebral venous thrombosis

whether hemorrhage is present ornot, and then a period of approxi-mately 3 to 6 months of ambulatoryanticoagulation. This extended periodof anticoagulation is typically accom-plished with warfarin postpartum.During pregnancy, when warfarin iscontraindicated, low-molecular-weighth ep ar in i s g iv en a nd t he n h el dduring the period of labor and deliv-ery (Case 4-3).

HEMORRHAGIC STROKE ANDVASCULAR MALFORMATIONSEpidemiology

Hemorrhagic, like ischemic, stroke isuncommon during pregnancy and thepuerperium. The proportion rangesfrom five to 35 per 100,000 in thereported series (see Table 4-1), andestimating the incidence from thethree population-based series, it

KEY POINT

h Patients with cerebral

venous sinus

thrombosis benefit

from anticoagulation.




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range s f rom 0 to 6 per 1 00 ,0 00 .However, despite the low absoluterisk, pregnancy increases the risk forhemorrhagic much more than forischemic stroke. This risk increase issubstantial during pregnancy (relativerisk 2.5) and very great during theearly postpartum period (relative risk

28.5).9 Despite its rarity, because of thesevere implications of cerebral hemor-rhage, hemorrhagic stroke is also animportant cause of pregnancy-relatedmortality. The major established causesof pregnancy-related cerebral hemor-rhage are preeclampsia/eclampsia, fol-lowed by arteriovenous malformations

KEY POINT

hPregnancy increases the

risk of hemorrhagic

stroke. This increased

risk is greatest in the

postpartum period.

Case 4-3

A 40-year-old woman developed progressively worsening headaches and nausea in the first trimesterof her third pregnancy. She had a medical history of depression and chronic hypertension; twoprevious pregnancies had been uneventful. Her blood pressure was 120/78 mm Hg. The neurologicand systemic examination findings were unremarkable. On brain imaging (Figure 4-4), MRI showedhyperintense signal in the region of the right transverse sinus, and magnetic resonance (MR)venogram showed absence of flow-related signal within the right transverse sinus and decreasedflow-related signal within the right sigmoid sinus and internal jugular veinVresults consistent withcerebral venous sinus thrombosis. Laboratory tests showed an elevated D-dimer and a low protein Slevel. She was treated with low-molecular-weight heparin, and the headaches resolved within 5 days.A follow-up MR venogram performed after 2 weeks showed complete recanalization of the venoussinuses. She went on to have an uncomplicated vaginal delivery. Follow-up blood tests showed normalD-dimer and protein S levels. Six weeks after delivery, low-molecular-weight heparin was discontinued,and she began treatment with aspirin.

Comment.This case illustrates the association between pregnancy and cerebral venous sinus thrombosis.Several mechanisms, including low levels of protein S as documented in this patient, contribute to atransient hypercoagulable state during pregnancy. MR venography was preferred over CT venography toavoid radiation risks during pregnancy. This patient was treated with low-molecular-weight heparin and

not warfarin because warfarin is teratogenic and can cause bleeding in the fetus.

FIGURE 4-4 Brain imaging of a 40-year-old pregnant woman with progressively worsening headaches and nausea. MRIrevealed hyperintense signal in the region of the right transverse sinus (A, fluid-attenuated inversion recovery[FLAIR] image), and magnetic resonance (MR) venogram (B) showed absence of flow-related signal within

the right transverse sinus and decreased flow-related signal within the right sigmoid sinus and internal jugular vein. Theseimaging results are consistent with cerebral venous sinus thrombosis. A follow-up MR venogram performed after 2 weeks oftreatment with low-molecular-weight heparin showed complete recanalization of the venous sinuses ( C).





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and aneurysms. Preeclampsia/eclampsiaprobably contributes even a larger por-tion than is apparent from the series

reported inTable 4-3, since it is likelythat cases that present in late pregnancyor the puerperium without proteinuriaare often diagnosed and classified as ofunknown cause. Other potential causes,such as disseminated intravascular co-agulation, have not been reported com-monly in these series.

The physiologic changes of pregnancyreviewed above include expansion ofblood volume, increased stroke volumeand cardiac output, rise of blood pres-

sure from its nadir in the late second orearly third trimester to near or slightlyabove normal as term approaches, andremodeling of vascular tissue with lossof collagen and elastin content and lossof distensibility. One might expectthese changes to underlie an increasedrisk of hemorrhage near term. Thestrain and trauma of labor might beexpected to add to the increased risk.

The risk of aneurysmal ruptureappears to increase severalfold, rising

with gestational age until it peaks at 30

to 34 weeks.48 Dias and Sakhar48

reported the mortality of pregnancy-associated aneurysmal subarachnoidhemorrhage to be 35%, with a fetalmortality of 17%. If a ruptured aneu-rysm is left unsecured surgically, ratesof recurrent hemorrhage and maternaland fetal mortality are very high. Thismortality may be greatly reduced byearly surgery. In one study, subarach-noid hemorrhage without early sur-gery resulted in a maternal mortality

of 63% and fetal mortality of 27%;these mortalities were lowered to 11%and 5%, respectively, by early sur-gery.48 With evidence that early sur-gery, open or endovascular, to secureruptured aneurysms leads to bettermaternal and fetal outcomes, it is rec-ommended that therapy for womenafter aneurysmal rupture proceed as itdoes for all patients as dictated by

KEY POINTS

hThe major causes of

pregnancy-associated

hemorrhage are

preeclampsia/eclampsia

and cerebral vascular

malformations, such

as aneurysms and

arteriovenous

malformations.

hAneurysmal subarachnoid

hemorrhage during

pregnancy confers a

high risk of death to

both mother and baby.

hWomen withsubarachnoid

hemorrhage should beseen by a neurosurgeon

and undergo vascular

imaging to look for

aneurysm, arteriovenous

malformation, or other

vascular lesions.

TABLE 4-3 Causes of Hemorrhagic Strokes in Pregnancy (% of All Hemorrhagic Strokes)a,b

StudyCerebralAneurysm

ArteriovenousMalformation

CavernousMalformation

Preeclampsia/Eclampsia Unknown Other

Feskeet al, 2009

14 14 3 42 22 11

Lianget al, 2006

10 19 I 24 24 24

Jeng et al,2004

14 23 I 32 I I

Jaigobinet al, 2000

23 38 I I 23 15

Witlinet al, 1997

50c I I 50 I

Kittneret al, 1996

I 23 I 15 31 31

Sharsharet al, 1995

13 13 13 44 19 I

Awadaet al, 1995

I I I I 100 I

a Totals of the rows may exceed 100% because multiple contributing causes may be counted.b Ellipses indicate that data was not reported.c This value combines both cerebral aneurysm and arteriovenous malformation.




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neurosurgical principles. Therefore, ifaneurysmal subarachnoid hemorrhage

occurs during pregnancy, the patientshould proceed to surgery immediately,if feasible. Endovascular coiling maybe an alternative with proper shieldingto minimize fetal radiation exposure.49

If urgent obstetric issues (such as ac-tive labor, eclampsia, or fetal distress)prevent immediate surgery, then the

woman should undergo urgent cesar-ean delivery followed by surgical con-trol of the aneurysm. Because of thesevere morbidity and high mortality

rate of subarachnoid hemorrhage andthe increased risk of rupture nearterm, it is recommended that un-ruptured aneurysms at significant riskof rupture be secured before preg-nancy, whenever possible. With thehigh rate of screening by MR angiogra-phy for headaches and other commondisorders, it is not uncommon to findsmall, asymptomatic, unruptured aneu-rysms. In general, the risk of rupturedepends on size and morphology. Therisk is low for small, uncomplicated

aneurysms. Systematically evaluatedclinical experience that would dictatethe best policy for management of suchaneurysms is lacking; however, it isoften considered prudent to deliversuch women by cesarean delivery orby vaginal methods that interrupt thesecond stage of labor. No clear datahave been published to argue against

vaginal delivery for women who havesurgically secured aneurysms, and mostsuch women can be delivered vaginally

with close monitoring.Data are conflicting concerning the

influence of pregnancy on arteriove-nous malformations (AVMs). Hemor-rhage is the most common presentingmanifestation of AVM, and AVMs thatpresent with hemorrhage are morelikely to bleed again than those dis-covered as a result of seizures or focalneurologic deficits. For many years,

practitioners followed the analysis ofRobinson and colleagues, which

suggested that pregnancy increasedthe rate of hemorrhage of AVMs.50 Alater influential analysis found a back-ground annual rate of hemorrhage of3.5% in women with AVM and no priorhemorrhage and 5.8% in those withprior hemorrhage, with no increaseconferred by pregnancy.51 However,an analysis of the risk of rupture perday found a severalfold increase in riskon the day of delivery.52,53 Also,although overall hemorrhage rates

appear to be comparable to nonpreg-nant women, evidence suggests thatwhen an AVM bleeds during pregnancy,the rebleeding rate is higher than innonpregnant women. In one study of27 women with intracerebral hemor-rhage due to AVM during pregnancy

who were not treated with immediateresection, seven had recurrent hemor-rhage during or immediately afterpregnancy. This 26% rate of recurrenthemorrhage in the first year is signifi-cantly higher than the roughly 6%

rate in nonpregnant women. Well-controlled data on which to base ther-apeutic decisions concerning AVMsdiscovered during pregnancy are lack-ing; however, based on the aboveconsiderations, expert recommenda-tions are that (1) if a woman withknown AVM anticipates pregnancy, the

AVM should be treated before preg-nancy; (2) if an AVM is discoveredduring pregnancy and has not bledduring the pregnancy, conservative

observation is usually recommended,with plans to proceed to definitivetreatment after delivery; (3) if an AVMbleeds during pregnancy, considerationshould be given to treatment during thepregnancy, taking into account thegrade of the lesion and the expectedtiming of benefit in lowering risk(immediate for low-grade lesions ame-nable to complete surgical excision or

KEY POINT

hAneurysmal

subarachnoid

hemorrhage should

be treated with early

surgery or endovascular

techniques to secure the

ruptured aneurysm and

minimize the risk of

recurrent hemorrhage.





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embolization but delayed by up to 1 to3 years for higher-grade lesions requir-

ing radiosurgery and combination ther-apies).54 Although no study has shownan advantage to cesarean delivery,based on the suggestion of higherrates of hemorrhage on the day ofdelivery, many obstetricians will favorthis approach to minimize risk.

CONCLUSION

Ischemic and hemorrhagic strokes areuncommon but serious complicationsof late pregnancy and the puerperium,

and when they occur, they confera major risk of long-term disabilityor death. Knowledge of the risksof pregnancy-associated stroke andthe neurologic manifestations of preeclampsia/eclampsia will supportand encourage early diagnosis andoptimal management decisions. Withproper precautions to minimize risk tothe fetus, women can generally undergodiagnostic evaluations and be treated

with aggressive measures appropriate tothe severity of the condition.

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embolization.




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