Journal ofNeurology, Neurosurgery, and Psychiatry, 1978, 41, 726-729

Intracranial venous thrombosis in the first trimesterof pregnancyP. J. M. LAVIN, I. BONE, J. T. LAMB, AND L. M. SWINBURNE

From the Departments of Neurology, Pathology, and Neuroradiology, St James's University Hospitaland Chapel Allerton Hospital, Leeds

SUMMARY We describe a fatal case of intracranial venous thrombosis occurring in earlypregnancy. Such thrombosis usually occurs in late pregnancy or the puerperium but rarely duringthe first trimester of pregnancy. Computerised axial tomography suggested massive cerebralvenous infarction. Necropsy findings showed not only cerebral venous thrombosis but also ex-

tensive pelvic and iliac vein thromboses. The relationship of cerebral venous thrombosis andpregnancy is discussed and the literature reviewed.

Cerebral venous and dural sinus thrombosis areknown to occur in a variety of conditions includ-ing trauma, infection (particularly paranasalsinuses and middle ear), severe anaemia, hyper-coagulable states, dehydration, and debilitatingdiseases (Kalbag and Woolf, 1967; Gettelfingerand Kokmen, 1977).Gowers (1888) suggested an association of cere-

bral venous thrombosis, among other things, withpregnancy. In late pregnancy and in the puer-perium such an association is now well recognised,having an incidence of one in 3000 pregnancies(Huggenberg and Kesselring, 1958). Often it isfound to occur in pregnancy with obstetric com-plications (Garcin and Pestel, 1955), but it isexceedingly rare in the first trimester of pregnancy,there being only a few pathologically proven casesdescribed (Meinel, 1901; Fishman et al., 1957;Hensell, 1961; Eckerling et al., 1963; Kalbag andWoolf, 1967; Christensen et al., 1969). Diagnosisusually depends on angiography. Indeed Kalbagand Woolf (1967) state that "without it intravitam diagnosis can never be more than a guess."The case we report underwent computerised axialtomography which suggested massive cerebralvenous infarction of both hemispheres withhaemorrhage and supported the clinical diagnosisof intracranial venous thrombosis.

Address for reprint requests: Dr P. Lavin, Department of Neurology,Charing Cross Hospital, Fulham Palace Road, London W6 8RF.Accepted 22 February 1978

Case report

A 42 year old Asian housewife was admitted toan obstetric unit after a generalised tonic/clonicseizure. She was eight weeks pregnant, and hadcomplained of frontal headaches, vomiting, andinsomnia for three weeks before admission. Herrelatives gave a history of possible seizures forseveral years. She had had five uneventfulpregnancies.

Initial examination showed her to be apyrexial,drowsy with no papilloedema or focal neurologicalsigns. She was normotensive. She had five furtherseizures despite intravenous anticonvulsanttherapy. Between seizures it was noted that shewas becoming less responsive, and on the fourthday she was transferred to the NeurologicalDepartment.On arrival she was in an akinetic state, respond-

ing only to noxious stimuli. There was a paucityof movement on the left side with an extensorplantar response. The fundi were normal. Nofurther seizures occurred.

Investigations showed an ESR of 14 mm/hr;haemoglobin 15.5 gm/dl with a normal blood film;plasma urea and electrolytes normal; randomblood sugar 7.0 mmol/l. The skull and chest radio-graphs were normal. The EEG showed diffuse slowwaves alternating with low voltage rapid activity.A lumbar puncture demonstrated clear cerebro-spinal fluid with a pressure of 300 mm CSF; whitecells 3X 103/ml; protein 0.23 gm/l; no organismswere seen and the culture was negative.

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Intracranial venous thrombosis in the first trimester of pregnancy

Computerised axial tomography before andafter intravenous contrast medium (50 ml ofsodium iothalamate, 420 mg iodine/ml) showedmassively decreased absorption deeply throughoutboth cerebral hemispheres, more marked on theright, with some peripheral sparing. There waspartial involvement of the basal ganglia. Thelateral ventricles were small in size but normalin position (Fig. 1). Two small, high density areaswere seen towards the vertex (Fig. 2) suggestive ofhaemorrhage. The appearances of the CT scansuggested massive cerebral venous infarction withoedema.The patient continued to deteriorate and died

on her sixth day in hospital.

Necropsy findings

BRAIN AND MENINGESThe dura mater was tense and the brain evenlyswollen with flattened convolutions. There wereareas of haemorrhagic infarction in the medialportions of both parietal lobes which extendedto the surface over the vertex, but spared the greymatter on either side of the central sulcus (Fig. 3).That on the right was more extensive, impingingon the medial surface and extending anteriorly

Fig. 1 CT scan showing massively decreasedabsorption in both cerebral hemispheres, more

marked on the right, with small lateral ventricles.

Fig. 2 CT scan showing two high density areastowards the vertex, suggestive of haemorrhage.

and posteriorly to the anterior end of the occipitallobe (Fig. 4). On the left side there was a crescenticarea of haemorrhage 40X 10 mm on the deep sur-face of the infarct. Petechial haemorrhages in thesoftened cerebral tissue surrounded the main areasof dense infarction. The dural veins and bothlateral and sigmoid sinuses contained soft ante-mortem thrombus. The smaller veins containedclot of the agonal type. There was slight, cere-bellar coning with trivial tentorial notching. Theinternal carotid arteries, the circle of Willis, andthe cavernous sinuses were normal.

OTHER FINDINGSThe pelvic veins contained antemortem thrombuswhich extended to the common iliac veins, mainlydown the left side, even to the femoral and theposterior tibial veins, and which was firmlyadherent in places.There were one or two thrombi in the peripheral

branches of the right main pulmonary artery butno infarction.The uterus contained an 18 mm embryo with no

visible abnormality. The placenta was partiallyseparated.

There was a large nodular goitre.

Discussion

Cerebral venous thrombosis is a well-recognisedcomplication of late pregnancy or the puerperium(Kalbag and Woolf, 1967) and has been the subjectof an extensive review (Carroll et al., 1966). It

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P. J. M. Lavin, I. Bone, J. T. Lamb, and L. M. Swinburne

Fig. 4 Brain sectioned in horizontal plane, showinghaemorrhagic infarction of both cerebral hemispheres,more marked on the right.

Fig. 3 Coronal section of brainA showing extensive areas of

haemorrhagic infarction in bothcerebral hemispheres.

may take the form of superior sagittal sinusthrombosis or be more advanced, with involve-ment of the cortical veins and haemorrhagic in-farction of the cerebral hemispheres. The clinicalpicture depends on the extent of thrombosis. Inpregnancy, Carroll et al. (1966) found that 34%of cases presented with headache, presumed to bedue to raised intracranial pressure, while 30% pre-sented with seizures. The prognosis is variablewith a mortality rate of between 33% (Fishmanet al., 1957) and 56% (Huggenberg and Kesselring,1958). Treatment is symptomatic; the role of anti-coagulants and fibrinolytic therapy remains doubt-ful in view of the almost constant pathologicalfinding of haemorrhagic infarction, as in ourpatient.

In pregnancy it seems likely that a coagulopathyis contributory to the development of cerebralvenous thrombosis, there being an increase inplatelet number and adhesiveness as well as ofclotting factors VII, IX, and fibrinogen and alsoa decrease in fibrinolysis (Gillman et al., 1959;Pechet and Alexander, 1961; Amias, 1970; Gettel-finger and Kokmen, 1977). Another importantcontributory factor may be the predisposition ofthe cortical venous system to thrombotic episodes,by virtue of its lack of valves, low pressure, fibrousseptae, and transient changes in pressure duringpregnancy (Amias, 1970). Embolism of pelvic

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Intracranial venous thrombosis in the first trimester of pregnancy

thrombi via the paravertebral venous plexus tothe cerebral veins as suggested by Batson (1940)has been proposed in this situation by Kalbag andWoolf (1967).Whatever the mechanism, the rarity of cerebral

venous thrombosis in early pregnancy is remark-able. There are only eight necropsy proven casesdescribed in the literature, occurring during thefirst trimester of pregnancy (Meinel, 1901; Fish-man et al., 1957; Hensell, 1961; Eckerling et al.,1963; Kalbag and Woolf, 1967; Christensen et al.,1969). These show an age range of 20 to 42 years.Only two were known to be multiparous (Ecker-ling et al., 1963; Kalbag and Woolf, 1967). Exten-sive cortical venous thrombosis with haemorrhagicinfarction was found in all but two cases (Fishmanet al., 1957; Christensen et al., 1969). In threecases there was a complication of pregnancy(Meinel, 1901; Fishman et al., 1957; Kalbag andWoolf, 1967). In none of the eight cases wasthrombosis of the systemic veins reported. Thepresence of thrombosis in the pelvic and iliacveins in our patient would support the mechanismsof either a generalised coagulopathy or embolismvia the paravertebral venous plexus. The role ofthe placental separation is unknown but it couldhave contributed to or caused the generalisedcoagulopathy, or, in fact, have been the result ofa seizure. However, the development of symptomsearly in pregnancy, probably as early as two weeksgestation in our patient, must raise the questionof a hormonal role in the mechanism of acoagulopathy such as probably occurs with theoestrogen containing contraceptive pill (Inmanet al., 1970).Kalbag and Woolf (1967) found their patient to

have thrombosis in an advanced state of organisa-tion and suggested that the process might havecommenced in a previous pregnancy.Antemortem diagnosis in the past has depended

on the angiographic appearances of delay or defectin venous filling and persistence of the venousphase. Computerised axial tomography with theappearances of bilateral cerebral venous infarctiontaken in conjunction with the clinical picturemakes possible the diagnosis, intra vitam, of thisdisorder. However, in the early stages or milderform, cerebral angiography remains desirable.

We wish to thank Dr Simon Currie for his per-mission to report the case.

References

Amias, A. G. (1970). Cerebral vascular disease inpregnancy. Journal of Obstetrics of the BritishCommonwealth, 77, 312-325.

Batson, D. V. (1940). Function of the vertebral veins.Annals of Surgery, 112, 138-149.

Carroll, J. D., Leak, D., and Lee, H. A. (1966). Cere-bral thrombophlebitis in pregnancy and thepuerperium. Quarterly Journal of Medicine, 35,347-368.

Christensen, E., Gormsen, J., and Rosenklint, A.(1969). Thrombosis in the superior sagittal sinusduring pregnancy. Ugeskrift for Laeger, 131, 869-873.

Eckerling, B., Goldman, J. A., and Gans, B. (1963).Intracranial sinus thrombosis: a rare complicationof pregnancy (3 cases). Obstetrics and Gynaecology,21, 368-371.

Fishman, R. A., Cowen, D., and Silbermann, M.(1957). Intracranial venous thrombosis during thefirst trimester of pregnancy. Neurology (Minne-apolis), 7, 217-220.

Garcin, R., and Pestel, M. (1955). Thrombo-phlebitescerebrales. XXXe Congres France de Medecine,Algiers. Pp. 503-533. Association des Medicins deLangue Francaise: Paris.

Gettelfinger, D. M., and Kokmen, 0. (1977).Superior sagittal sinus thrombosis. Archives ofNeurology (Chicago), 34, 2-6.

Gillman, T., Naidoo, S. S., and Hathorn, M. (1959).Plasma fibrinogen activity in pregnancy. Lancet,2, 70-71.

Gowers, W. R. (1888). On thrombosis in the cerebralsinuses and veins. In A Manual Of Diseases of theNervous System. Vol. 2, p. 416. Churchill: London.

Hensell, V. (1961). Traumatische Hirnsinus-undVenenthrombosen. A cta Neurochirurgica, Supple-ment 7, 362-366.

Huggenberg, H. R., and Kesselring, F. (1958). Postpartum cerebral complications. Gynaecologia, 146,312-317.

Inman, W. H. W., Vessey, M. P., Westerholm, B.,and Engelund, A. (1970). Thromboembolic diseaseand the steroidal content of oral contraceptives. Areport to the Committee on Safety of Drugs. BritishMedical Journal, 2, 203-209.

Kalbag, R. M., and Woolf, A. L. (1967). CerebralVenous Thrombosis. Oxford University Press:London.

Meinel, A. (1901). Ueber das Vorkommen des autoch-thonen Sinus Thrombose bei Chlorose (Inauguraldissertation, Munich). Quoted by Kalbag and Woolf(1967).

Pechet, L., and Alexander, B. (1961). Increased clot-ting factors in pregnancy. New England Journal ofMedicine, 265, 1093-1097.

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