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Cerebral Venous Thrombosis Associated WithPregnancy and Puerperium

Review of 67 Cases

Carlos Cantu, MD; Fernando Barinagarrementeria, MD

Background and Purpose: Cerebral venous thrombosis is characterized by its clinical pleomorphism andpathogenetic variability. We studied 67 patients with cerebral venous thrombosis associated withpregnancy and puerperium and compared them with 46 other cases unrelated to obstetric causes todisclose differences in their clinical presentation, neuroradiological findings, clinical course, andprognosis.Methods: In this retrospective study, we analyzed the clinical, laboratory, and neuroimaging findings of

113 patients collected consecutively at our institute. The diagnosis of cerebral venous thrombosis wasconfirmed by angiography, magnetic resonance imaging, or neuropathological study.

Results: Patients with cerebral venous thrombosis associated with pregnancy and puerperium wereyounger (average age, 26 versus 36 years), and in most, the onset of symptoms was acute (82% versus 54%;P=.003). The evolution of symptoms reached a plateau within 10 days in 70% of patients with thrombosisfrom obstetric causes, compared with only 45% in those from other causes (P=.01). Anemia was morefrequent in the obstetric group (64% versus 26%; P=.00001). There were no differences regardingneurological and neuroradiological findings. Although the initial severity of illness was similar in bothgroups, the final outcome was considered good in 80%, of patients with obstetric causes, compared with58% of patients with other causes (P=.01); mortality rates were 9% and 33%, respectively (P=.002).

Conclusions: Cerebral venous thrombosis associated with pregnancy and puerperium has a more acuteonset and a better prognosis than thrombosis due to other causes. These findings might be helpful in thediagnostic and therapeutic strategies for patients with cerebral venous thrombosis. (Stroke. 1993;24:1880-1884.)KEY WoRDs * pregnancy * puerperium * thrombosis * women

In 1828, Abercrombiel published the first clinico-pathological description of a case of puerperalcerebral venous thrombosis (CVT). Since then,

the association of CVT with pregnancy and puerperiumhas been recognized, especially in developing coun-tries.2-4 Of 113 cases of aseptic CVT seen in the past 20years at the National Institute of Neurology and Neu-rosurgery in Mexico City, 67 were diagnosed in thepuerperal period, 5 during pregnancy, and in 1 patientafter abortion. The aim of this paper is to analyze these67 cases and compare them with the remaining 46 casesof CVT, which were not related to obstetric causes, todisclose some clinical, paraclinical, or prognostic fea-tures that may be distinctive for patients with CVTassociated with pregnancy and puerperium.

Subjects and MethodsPatients with a diagnosis of aseptic CVT admitted to

our hospital were included in this study when theysatisfied any of the following criteria:

Received March 24, 1993; final revision received July 18, 1993;accepted August 3, 1993.From the Stroke Clinic, National Institute of Neurology and

Neurosurgery, Mexico City.Correspondence to Dr Carlos Cantu, Instituto Nacional de

Neurologia y Neurocirugia, Insurgentes Sur 3877, Tlalpan, Mexico14269 DF, Mexico.

1. Angiographic evidence of CVT5,6: total or partiallack of filling of at least one sinus on at least twoprojections. When the lack of filling involved only theanterior portion of the superior sagittal sinus or onlyone lateral sinus, additional signs of CVT were re-quired, such as evidence of delayed venous emptying ordevelopment of collateral circulation.

2. Evidence of CVT via neuropathological study:presence of thrombosis of venous sinuses or cerebralveins, with or without associated venous infarction.

3. Magnetic resonance imaging (MRI) evidence ofCVT7: absence of voiding on TI weighted images withisointensity or hypointensity on T2 weighted imagesduring the first few days and hyperintensity of thelumen of the sinus on T1 and T2 weighted images fromabout 1 week to 1 month after thrombosis.

Patients were excluded when (1) clinical or radiolog-ical records were incomplete, (2) radiological studieswere inconclusive, (3) there was cavernous sinus throm-bosis, or (4) CVT was associated with sepsis. Of 67patients with CVT associated with pregnancy and pu-erperium (group 1), 50 were included on the basis ofangiographic criteria, 10 by MRI criteria, and 7 byneuropathological criteria. Of the 46 cases with CVTunrelated to obstetric events (group 2), 26 were in-cluded on the basis of angiographic criteria, 11 byneuropathological criteria, and 9 by MRI criteria.The following characteristics were compared between

the two groups:

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Canti and Barinagarrementeria Cerebral Venous Thrombosis

TABLE 1. Clinical Profile and Evolution of Cerebral Venous Thrombosis

Group 1 (n=67) Group 2 (n=46)

n % n % P

Onset

Acute 55 82.1 25 54.3 .003

Insidious 12 17.9 21 45.7

Evolution

Progressive 48 71.6 24 52.2 .03

Nonprogressive 19 28.4 22 47.8

Time elapsed between onset andstabilization of symptoms

<10 days 47 70.1 21 45.7 .01

>10 days 20 29.9 25 54.3

Time elapsed between onset anddiagnosis<1 week 38 56.7 10 21.7 .0002

1-3 weeks 25 37.3 16 34.8

>3 weeks 4 6.0 20 43.5

1. Clinical: mode of onset, classified as "acute"(symptoms appeared suddenly or developed in less than48 hours) or "insidious" (gradual development of symp-toms over several days or weeks); presenting symptoms;clinical course, classified as "progressive" (developmentof additional symptoms and/or worsening of the pre-senting symptoms) or "nonprogressive" (presentingsymptoms remained stable or tended to subside withoutdevelopment of additional symptoms); neurologicalsigns and symptoms; time elapsed between the onsetand stabilization of symptoms; and time elapsed be-tween onset and diagnosis.

2. Hematologic: anemia (hemoglobin <12 g%), leu-kocytosis (white blood count >10 000/mm3), thrombo-cytosis (platelet count >450 000/mm3), erythrocyte sed-imentation rate (ESR) (normal 0 to 20 mm/h), andpolycythemia (hematocrit >60%).

3. Cerebrospinal fluid (CSF) data: opening pressure(normal pressure <200 mm water), total protein (nor-mal value 15 to 45 mg/dL), and cell count (normal value<5 cells/mm3).

4. Neuroimaging: evidence of CVT and associatedparenchymal lesions detected by computerized tomogra-phy (CT) and MRI. Abnormalities considered as directsigns of CVT on CT scan included the cord sign, thedense triangle, and the empty delta sign. Hemorrhagicinfarction was defined as patchy areas of high attenuationwith indistinct margins and a speckled or mottled appear-ance, whether separate or coalescent, within a venousinfarction. Intracerebral hemorrhage was defined as ahomogeneous region of high attenuation.

5. Sites of thrombosis within the cerebral venoussystem.

6. Clinical evaluation at the time of discharge fromhospital: classified as "good outcome" when patientsrecovered fully or had partial functional recovery withonly mild sequelae and "poor outcome" when sequelaewere serious or the patient died.

Treatment for both groups was mainly conservative.Only five patients with puerperal CVT received antico-agulation therapy, and their data were excluded fromthe final outcome evaluation tables because it is wellknown that anticoagulation in the early stages of CVTmodifies its natural history.8'9

Differences between groups were tested for statisticalsignificance using multivariate analysis with 2x 2 contin-gency tables, x2 test, and Fisher's exact test.

ResultsThe mean age of group 1 patients was 26 years (range,

16 to 44 years) and of group 2, 36 years (range, 15 to 77years). Thirteen male patients were included in group 2.

Regarding puerperal patients, 21 cases of CVT(34.4%) occurred during the first week after delivery (9within the first 48 hours) and 36 (59%) during weeks 2and 3 postpartum. Pregnant patients were affected inany trimester (1 in the first, 2 in the second, and 2 in thethird trimester). In group 1, there were 43 multiparas(64.1%), 36 women (53.7%) from low or rural socialstratum, and 21 women (31.3%) whose delivery wasconducted at home by midwives and who did not haveproper prenatal care. Three patients had a history ofvenous thrombosis outside the central nervous systemduring previous pregnancies (two instances of pelvicvenous thrombosis and 1 case of pulmonary embolism).

Patients from group 2 had the following predisposingfactors for CVT: use of oral contraceptives (7 patients),thrombocytosis in 4 patients, secondary polycythemia in3 cases, circulating lupus anticoagulant in 2, and proteinS deficiency in 2. In addition, an arteriovenous malfor-mation was present in 2 patients and metastatic carci-noma in 1. In the remaining 25 cases, no predisposingfactors were found.

Clinical, laboratory, and neuroradiological findingsare displayed in Tables 1 through 5. Results of the finalclinical evaluation are shown in Table 6. Several differ-ences were relevant: (1) Patients of group 1 had an

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1882 Stroke Vol 24, No 12 December 1993

TABLE 2. Presenting Symptoms in 113 Patients WithCerebral Venous Thrombosis

Group 1 Group 2(n=67) (n=46)

n % n %

Headache 49 73.1 28 60.8

Seizures

Generalized 1 1.4 5 10.8

Focal 7 8.9 2 4.3

Focal signsMotor 1 1.5 5 10.9

Sensitive 6 9.0 4 8.7

Disorders ofconsciousness 3 4.5 2 4.3

acute onset more often (P=.003); (2) although thecourse of illness was progressive in more patients ofgroup 1 (P=.03), symptoms tended to become stable orbegan to subside in a shorter interval (P=.01); (3)diagnosis was established within a week of onset in ahigher proportion of patients of group 1 (P=.0002); (4)concomitant extraneurological thrombosis was morefrequent in group 1 (22.3% versus 6.5%; P=.01); (5)anemia was more often present in group 1 (P=.00001)and was usually related to an inadequate supply of ironduring pregnancy with or without blood loss duringdelivery and puerperium (hypochromic, 26/43, 60.5%;normochromic, 17/43, 39.5%); (6) although the severityof illness was similar in both groups, with comparableneurological and neuroradiological findings, CVT asso-ciated with pregnancy and puerperium had a much

TABLE 3. Neurological Findings in CVT

Group 1 Group 2(n=67) (n=46)

Findings n % n %

Headache 59 88.0 32 69.5

Focal signs 53 79.1 35 76.0

Motor 52 77.6 33 71.7

Sensitive 25 37.3 13 28.2

Aphasia 17 25.3 10 21.7

Disorders of consciousness 42 62.6 27 58.6

Somnolence 24 35.8 9 19.5

Stupor/coma 16 23.9 15 32.6

Confusion 2 2.9 3 6.5

Seizures 40 59.7 29 63.0Generalized 18 26.9 16 34.8Focal 22 32.8 13 28.2Bilateral pyramidal signs 28 41.7 18 39.1Papilledema 27 40.2 24 52.1Nuchal rigidity 22 32.8 12 26.0Isolated intracranialhypertension 5 7.4 8 17.3

TABLE 4. Hematologic and Cerebrospinal FluidFindings in Cerebral Venous Thrombosis

Group 1 Group 2(n=67) (n=46)

n % n %Hematologic

Anemia* 43 64.1 12 26.0

Leukocytosis 24 35.8 20 43.4

Increased erythrocytesedimentation ratet 26/47 55.3 12/41 29.2

Thrombocytosis 2 2.9 6 13.0

Cerebrospinal fluid

Normal 13/46 28.2 6/27 22.2

Increased openingpressure 19/46 41.3 15/27 55.5

Abnormal cytologicalexam 29/46 43.4 11/27 20.7

Hemorrhagic 11/46 23.9 9/27 33.3

*P=.00001, tP=.01.

better outcome (P=.01) and(P=.002).

a lower mortality rate

There were no differences between groups regardingsites of thrombosis within the cerebral venous system(Table 7).

DiscussionA wide variety of well-known conditions may cause or

predispose to CVT, and their relative importance mayvary in different areas of the world.9-14 In the presentstudy. 60% of cases were associated with pregnancy andpuerperium (ratio group 1/group 2, 1.5). This complica-tion is also common in India, with a prevalence of4.5/1000 obstetric admissions.2.15 In accordance with anobstetric CVT series,16 symptoms of CVT appeared inthe first 3 weeks after delivery in the majority of casesand, as in the Indian series, women who had homedeliveries and poor prenatal care were more oftenaffected. CVT should be suspected in any woman whodevelops neurological symptoms in the immediate post-partum period, since nearly 15% of our cases occurredin the first 2 days after a normal childbirth. CVToccurred 13 times more often during puerperium thanduring pregnancy. Although in the Indian population,multiparas are more often affected than primiparas, in aproportion of 4: 1,17 in our population this differencewas not so striking (1.8:1).

In this study, we found a high frequency (70%) ofparenchymal lesions (venous infarcts and intracerebralhemorrhages) that manifested as focal neurological signs,epileptic seizures, disorders of consciousness, intracranialhypertension, nuchal rigidity, and hemorrhagic CSF.These findings also explain the high mortality rate in ourwhole series (18.5%). This is in contrast with reports fromother countries18-20 and illustrates the great clinical andneuroradiological pleomorphism of this condition world-wide. Our series is characterized by a low frequency ofisolated intracranial hypertension and absence of Behcet'sdisease as a cause of CVT. Even when we consider thesevariations, there seem to be important differences be-

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Cantu and Barinagarrementeria Cerebral Venous Thrombosis 1883

TABLE 5. Neuroradiological Findings

Computed Tomographic Scan Magnetic Resonance Imaging

Group 1 Group 2 Group 1 Group 2(n=59) (n=36) (n=19) (n=20)

Findings n % n % n % n %

Normal 5 8.4 4 11.1 0 0 0 0

Signs of cerebral venous thrombosis 19 32.2* 13 36.1* 17 89.4 19 95

Parenchymal lesions

Nonhemorrhagic venous infarct 16 27.1 7 19.4 3 15.7 2 10

Hemorrhagic venous infarct 21 35.5 12 33.3 10 52.6 11 55

Intracerebral hemorrhage 6 10.1 5 13.8 2 10.5 4 20

Unilateral lesion 25 42.3 15 41.6 8 42.1 12 60

Bilateral lesions 18 30.5 9 25 7 36.8 5 25

*Delta sign, dense triangle, or empty delta sign.

tween CVT associated with pregnancy and puerperiumand that with nonobstetric causes. The clinical picture ofthe former featured a disease with sudden or acute onset,with a progressive course that tends to become stable orbegin to subside in a short time (5 to 10 days). Innonobstetric cases, the onset was insidious in about halfthe patients; the course could be progressive or not andtended to be stable after 10 days in >50% of patients.These findings suggest that, in obstetric cases, the patho-physiological process leading to venous occlusion developsfaster but is usually self-limited and resolves itself in a

shorter time. Further evidence for this is the shorterperiod between onset of symptoms and diagnosis in ob-stetric patients; however, it should be born in mind thatpuerperium represents an important clue for suspectingCVT.Another important difference was the high frequency

of anemia in obstetric patients, probably reflecting a

poor diet during pregnancy and/or blood loss duringdelivery. The high prevalence of anemia has beenrecognized in most obstetric series of CVT23 and de-serves further study to clarify its role in the pathogen-esis of this entity.

Traditionally, the most frequently postulated mecha-nism involved in CVT in obstetric patients is a hyper-coagulable state2122 associated with dehydration andanemia. However, other factors may play an important

TABLE 6. Final Outcome in 108 Cases of CerebralVenous Thrombosis

Group 1 Group 2(n=62)* (n =46)

n % n % P

Good outcome .01

Total recovery 31 50.0 24 52.1

Mild sequelae 19 30.6 3 6.5

Poor outcome

Severe sequelae 6 9.7 4 8.7

Death 6 9.7 15 32.6 .002

*Five patients who had good outcome received anticoagula-tion and were excluded from statistical analysis.

role, such as protein S deficiency, which is commonduring pregnancy and puerperium.23 25 Deficiency ofprotein S has been reported in previous cases of CVT inobstetric patients.11,26.27 The higher prevalence of extra-neural thrombosis in CVT associated with pregnancyand puerperium may represent the systemic repercus-sion of a hypercoagulable state.Although the disease was of similar severity in both

groups, the outcome was more favorable in obstetricpatients. Possibly, CVT in obstetric subjects is a morebenign entity than the one affecting other types ofpatients because of a more limited and transient occlu-sion, with rapid sinovenous recanalization by spontane-ous thrombolysis or development of collaterals.

TABLE 7. Site of Venous Occlusion in 113 Patients WithCerebral Venous Thrombosis

Group 1 Group 2(n=67) (n=46)

n % n %

SSS 60 89.5 45 97.8

22 32.8* 11 23.9*

LS 23 34.3 20 43.4

1 1.4* 1 2.1*DVS 17 25.3 10 21.7

4 7.4* 0 ...

CCV 13 19.4 14 30.4

SSS+LS 16 23.8 15 32.6

SSS+CCV 9 13.4 8 17.3

SSS+DVS 6 8.9 5 10.8

SSS+LS+DVS 4 5.9 2 4.3

SSS+CCV+DVS 2 2.9 2 4.3

SSS+CCV+LS 1 1.4 1 2.1

SSS+CCV+LS+DVS 0 ... 1 2.1

CCV+LS 1 1.4 0 ...

SSS indicates superior sagittal sinus; LS, lateral sinus; DVS,deep venous system; and CCV, cortical cerebral veins.

*Isolated venous occlusion involvement.

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1884 Stroke Vol 24, No 12 December 1993

Prognosis and treatment are the most controversialissues of cerebral venous thrombosis. Prognosis is quitevariable. The outcome can range from total recovery todeath. Since the introduction of MRI, an increasingnumber of patients with a benign course of CVT havebeen diagnosed.28'29 Conversely, the benefit of anticoag-ulation now appears well established.89 It would be ofparamount importance to be able to identify the benigncases that will recover completely whatever the treat-ment and the severe cases that would justify the risk ofanticoagulation. Based on the experience acquired atour institution, we do not recommend anticoagulationin patients without the factors associated with a badprognosis.30

AcknowledgmentWe are grateful to Dr Carlos Marquez for his assistance.

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C Cantú and F Barinagarrementeriacases.

Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 1993 American Heart Association, Inc. All rights reserved.

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