Semin Neurol 2007; 27(5): 442-452
DOI: 10.1055/s-2007-991126
© Thieme Medical Publishers

Stroke in Pregnancy

Steven K. Feske1
  • 1Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
Further Information

Publication History

Publication Date:
16 October 2007 (online)

ABSTRACT

Although pregnancy-associated stroke is uncommon, the risk of stroke is greatly increased above the low baseline rate in young patients during late pregnancy and, even more so, during the puerperium. Stroke is a major contributor to the serious morbidity and mortality of pregnancy. The physiological hormonally mediated changes in circulation, vascular tissue structure, and coagulability, and the pathological state of pre-eclampsia-eclampsia contribute to this increased risk of stroke. Pregnancy-associated strokes are roughly evenly divided among hemorrhagic strokes, mainly from rupture of aneurysms and arteriovenous malformations (AVMs); ischemic strokes, mainly from late pregnancy and postpartum cerebral venous thrombosis; and strokes associated with pre-eclampsia-eclampsia, with a contribution from cardioembolism, especially in populations at risk from a high rate of underlying rheumatic valvular heart disease. Awareness of the types of stroke to expect during pregnancy will facilitate early diagnosis. This article discusses the pathogenesis of pregnancy-associated stroke, its epidemiology, and some diagnostic and therapeutic issues unique to pregnancy.

REFERENCES

  • 1 Bogousslavsky J. Stroke in young adults. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM Stroke: Pathophysiology, Diagnosis, and Management. 2nd ed. New York; Churchill Livingstone 1992
  • 2 Hart R G, Miller V T. Cerebral infarction in young adults: a practical approach.  Stroke. 1983;  14 110-114
  • 3 Mackey M, Meyer M C, Stirewalt W S, Starcher B C, McLaughlin M K. Composition and mechanics of mesenteric resistance arteries from pregnant rats.  Am J Physiol. 1992;  263 R2-R8
  • 4 Hull A D, Long D M, Longo L D, Pearce W J. Pregnancy-induced changes in ovine cerebral arteries.  Am J Physiol. 1992;  262 R137-R143
  • 5 Wickstrom K, Edelstam G, Lowbeer C, Hansson L O, Seigbahn A. Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy.  Scand J Clin Lab Invest. 2004;  64 31-40
  • 6 Clark P, Brennand J, Conkie J A, McCall F, Greer I A, Walker I D. Activated protein C sensitivity, protein C, protein S, and coagulation in normal pregnancy.  Thromb Haemost. 1998;  79 1166-1170
  • 7 Vodnik T, Ignjatovic S, Majkic-Singh N. Changes in the plasma levels of protein C system parameters in pregnancy.  Scand J Clin Lab Invest. 2003;  63 481-488
  • 8 Veltkamp R, Kupsch A, Polasek J, Yousry T A, Pfister H W. Late onset postpartum eclampsia without pre-eclampsia prodromi: clinical and neuroradiological presentation in two patients.  J Neurol Neurosurg Psychiatry. 2000;  69 824-827
  • 9 Qureshi A I, Frankel M R, Ottenlips J R, Stern B J. Cerebral hemodynamics in preeclampsia and eclampsia.  Arch Neurol. 1996;  53 1226-1231
  • 10 Zunker P, Hohenstein C, Deuschl G. Pathophysiology of pre-eclampsia/eclampsia syndrome.  J Neurol. 2001;  248 437-438
  • 11 Roberts J M, Cooper D W. Pathogenesis and genetics of pre-eclampsia.  Lancet. 2001;  357 53-56
  • 12 Trommer B L, Homer D, Mikhael M A. Cerebral vasospasm and eclampsia.  Stroke. 1988;  19 326-329
  • 13 Will A D, Lewis K L, Hinshaw Jr D B et al.. Cerebral vasoconstriction in toxemia.  Neurology. 1987;  37 1555-1557
  • 14 McCrae K R, Samuels P, Schreiber A D. Pregnancy-associated thrombocytopenia: pathogenesis and management.  Blood. 1992;  80 2697-2714
  • 15 Zeeman G G, Fleckenstein J L, Twickler D M, Cunningham F G. Cerebral infarction in eclampsia.  Am J Obstet Gynecol. 2004;  190 714-720
  • 16 Schaefer P W, Buonanno F S, Gonzalez R G, Schwamm L H. Diffusion-weighted imaging discriminates between cytotoxic and vasogenic edema in a patient with eclampsia.  Stroke. 1997;  28 1082-1085
  • 17 Lewis L K, Hinshaw D B, Will A D, Hasso A N, Thompson J R. CT and angiographic correlation of severe neurological disease in toxemia of pregnancy.  Neuroradiology. 1988;  30 59-64
  • 18 Raps E C, Galetta S L, Broderick M, Atlas S W. Delayed peripartum vasculopathy: cerebral eclampsia revisited.  Ann Neurol. 1993;  33 222-225
  • 19 Singhal A B. Postpartum angiopathy with reversible posterior leukoencephalopathy.  Arch Neurol. 2004;  61 411-416
  • 20 Weinstein L. Syndrome of hemolysis, elevated liver enzymes, and low platelet count: a severe consequence of hypertension in pregnancy.  Am J Obstet Gynecol. 1982;  142 159-167
  • 21 Kittner S J, Stern B J, Feeser B R et al.. Pregnancy and the risk of stroke.  N Engl J Med. 1996;  335 768-774
  • 22 Dias M S, Sekhar L N. Intracranial hemorrhage from aneurysms and arteriovenous malformations during pregnancy and the puerperium.  Neurosurgery. 1990;  27 855-865
  • 23 Wiebers D O, Whisnant J P. The incidence of stroke among pregnant women in Rochester, Minn, 1955 through 1979.  JAMA. 1985;  254 3055-3057
  • 24 Awada A, al Rajeh S, Duarte R, Russell N. Stroke and pregnancy.  Int J Gynaecol Obstet. 1995;  48 157-161
  • 25 Sharshar T, Lamy C, Mas J L. for the Stroke in Pregnancy Study Group . Incidence and causes of stroke associated with pregnancy and puerperium: a study in public hospitals of Ile de France.  Stroke. 1995;  26 930-936
  • 26 Witlin A G, Friedman S A, Egerman R S, Frangieh A Y, Sibai B M. Cerebrovascular disorders complicating pregnancy-beyond eclampsia.  Am J Obstet Gynecol. 1997;  176 1139-1145
  • 27 Jaigobin C, Silver F L. Stroke and pregnancy.  Stroke. 2000;  31 2948-2951
  • 28 Jeng J S, Tang S C, Yip P K. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women.  Cerebrovasc Dis. 2004;  18 290-295
  • 29 Liang C C, Chang S D, Lai S L, Hsieh C C, Chueh H Y, Lee T H. Stroke complicating pregnancy and the puerperium.  Eur J Neurol. 2006;  13 1256-1260
  • 30 James A H, Bushnell C D, Jamison M G, Myers E R. Incidence and risk factors for stroke in pregnancy and the puerperium.  Obstet Gynecol. 2005;  106 509-516
  • 31 Ferro J M, Canhao P, Stam J, Bousser M G, Barinagarrementeria F. for the ISCVT Investigators . Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).  Stroke. 2004;  35 664-670
  • 32 American College of Radiology Committee on Drugs and Contrast Media .Manual on Contrast Media. 5th ed. Reston, VA; American College of Radiology 2004
  • 33 Mevissen M, Buntenkotter S, Loscher W. Effects of static and time-varying (50 Hz) magnetic fields on reproduction and fetal development in rats.  Teratology. 1994;  50 229-237
  • 34 Beers G J. Biological effects of weak electromagnetic fields from 0 Hz to 200 Hz: a survey of the literature with special emphasis on possible magnetic resonance effects.  Magn Reson Imaging. 1989;  7 309-331
  • 35 Schwartz J L, Crooks L E. NMR imaging produces no observable mutations or cytotoxicity in mammalian cells.  AJR Am J Roentgenol. 1982;  139 583-585
  • 36 Kanal E, Borgstede J P, Barkovich A J et al.. American College of Radiology White Paper on MR Safety: 2004 update and revisions.  AJR Am J Roentgenol. 2004;  182 1111-1114
  • 37 Morisetti A, Tirone P, Luzzani F, de Haën C. Toxicologic safety assessment of iomeprol, a new x-ray contrast agent.  Eur J Radiol. 1994;  18(suppl 1) 21-31
  • 38 Ralston W H, Robbins M S, James P. Reproductive, developmental, and genetic toxicity of ioversol.  Invest Radiol. 1989;  24(suppl 1) S16-S22
  • 39 Bona G, Zaffaroni M, Defilippi C et al.. Effects of iopamidol on neonatal thyroid function.  Eur J Radiol. 1992;  14 22-25
  • 40 Kanal E, Borgstede J P, Barkovich A J et al.. American College of Radiology white paper on MR safety.  AJR Am J Roentgenol. 2002;  178 1335-1347
  • 41 Kubik-Huch R A, Gottstein-Aalame N M, Frenzel T et al.. Excretion of gadopentetate dimeglumine into human breast milk during lactation.  Radiology. 2000;  216 555-558
  • 42 Mutzel W, Speck U. Pharmacokinetics and biotransformation of iohexol in the rat and the dog.  Acta Radiol Suppl. 1980;  362 87-92
  • 43 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group . Tissue plasminogen activator for acute ischemic stroke.  N Engl J Med. 1995;  333 1581-1587
  • 44 del Zoppo G J, Higashida R T, Furlan A J, Pessin M S, Rowley H A, Gent M. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke.  Stroke. 1998;  29 4-11
  • 45 Furlan A, Higashida R, Wechsler L et al.. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II Study: a randomized controlled trial.  JAMA. 1999;  282 2003-2011
  • 46 Smith W S, Sung G, Starkman S. for the MERCI Trial Investigators . Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial.  Stroke. 2005;  36 1432-1440
  • 47 Ahearn G S, Hadjiliadis D, Govert J A, Tapson V F. Massive pulmonary embolism during pregnancy successfully treated with recombinant tissue plasminogen activator: a case report and review of treatment options.  Arch Intern Med. 2002;  162 1221-1227
  • 48 Bechtel J J, Mountford M C, Ellinwood W E. Massive pulmonary embolism in pregnancy treated with catheter fragmentation and local thrombolysis.  Obstet Gynecol. 2005;  106 1158-1160
  • 49 Dapprich M, Boessenecker W. Fibrinolysis with alteplase in a pregnant woman with stroke.  Cerebrovasc Dis. 2002;  13 290
  • 50 Johnson D M, Kramer D C, Cohen E, Rochon M, Rosner M, Weinberger J. Thrombolytic therapy for acute stroke in late pregnancy with intra-arterial recombinant tissue plasminogen activator.  Stroke. 2005;  36 e53-e55
  • 51 Nassar A H, Abdallah M E, Moukarbel G V, Usta I M. Sequential use of thrombotic agents for thrombosed mitral valve prosthesis during pregnancy.  J Perinat Med. 2003;  31 257-260
  • 52 Patel R K, Fasan O, Arya R. Thrombolysis in pregnancy.  Thromb Haemost. 2003;  90 1216-1217
  • 53 Song J Y, Valentino L. A pregnant patient with renal vein thrombosis successfully treated with low-dose thrombolytic therapy: a case report.  Am J Obstet Gynecol. 2005;  192 2073-2075
  • 54 Trukhacheva E, Scharff M, Gardner M, Lakkis N. Massive pulmonary embolism in pregnancy treated with tissue plasminogen activator.  Obstet Gynecol. 2005;  106 1156-1158
  • 55 Turrentine M A. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy.  Obstet Gynecol Surv. 1995;  50 534-541
  • 56 Usta I M, Abdallah M E, El-Hajj M, Nassar A H. Massive subchorionic hematomas following thrombolytic therapy in pregnancy.  Obstet Gynecol. 2004;  103 1079-1082
  • 57 Murugappan A, Coplin W M, Al-Sadat A N et al.. Thrombolytic therapy of acute ischemic stroke during pregnancy.  Neurology. 2006;  66 768-770
  • 58 Weatherby S J, Edwards N C, West R, Heafield M T. Good outcome in early pregnancy following direct thrombolysis for cerebral venous sinus thrombosis.  J Neurol. 2003;  250 1372-1373
  • 59 Lecander I, Nilsson M, Astedt B. Depression of plasminogen activator activity during pregnancy by the placental inhibitor PAI2.  Fibrinolysis. 1988;  2 165-167
  • 60 Einhäupl K M, Villringer A, Meister W et al.. Heparin treatment in sinus venous thrombosis.  Lancet. 1991;  338 597-600
  • 61 Bousser M G. Cerebral venous thrombosis: diagnosis and management.  J Neurol. 2000;  247 252-258
  • 62 de Bruijn S F, Stam J. for the Cerebral Venous Sinus Thrombosis Study Group . Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight-heparin for cerebral sinus thrombosis.  Stroke. 1999;  30 484-488
  • 63 Einhäupl K, Bousser M G, de Bruijn S F et al.. EFNS guideline on the treatment of cerebral venous and sinus thrombosis.  Eur J Neurol. 2006;  13 553-559
  • 64 Stam J, de Bruijn S FTM, DeVeber G. Anticoagulation for cerebral sinus thrombosis.  Cochrane Database Syst Rev. 2002;  (4) CD002005
  • 65 Rai R, Cohen H, Dave M et al.. Randomized controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriages associated with phospholipid antibodies (or antiphospholipid antibodies).  BMJ. 1997;  314 253-257
  • 66 Kutteh W H. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone.  Am J Obstet Gynecol. 1996;  174 1584-1589
  • 67 Bates S M, Greer I A, Hirsh J, Ginsberg J S. Use of antithrombotic agents during pregnancy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126(suppl 3) 627S-644S
  • 68 Flessa H C, Klapstrom A B, Glueck M J et al.. Placental transport of heparin.  Am J Obstet Gynecol. 1965;  93 570-573
  • 69 Forestier F, Daffos F, Rainaut M et al.. Low molecular weight heparin (CY 216) does not cross the placenta during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound.  Thromb Res. 1984;  34 557-560
  • 70 Forestier F, Daffos F, Rainaut M et al.. Low molecular weight heparin (CY 216) does not cross the placenta during the third trimester of pregnancy [abstract].  Thromb Haemost. 1987;  57 234
  • 71 Ginsberg J S, Greer I, Hirsh J. Use of antithrombotic agents during pregnancy.  Chest. 2001;  119 122S-131S
  • 72 CLASP: a randomized trial of low-dose aspirin for the prevention and treatment of preeclampsia among 9364 pregnant women.  Lancet. 1994;  343 619-629
  • 73 ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women. ECPPA Collaborative Group.  Br J Obstet Gynaecol. 1996;  103 39-47
  • 74 Benigni A, Gregorini G, Frusca T et al.. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension.  N Engl J Med. 1989;  321 357-362
  • 75 Brown C EL, Gant N F, Cox K, Spitz B, Rosenfeld C R, Magness R R. Low-dose aspirin: II. Relationship of angiotensin II pressor responses, circulating eicosanoids, and pregnancy outcome.  Am J Obstet Gynecol. 1990;  163 1853-1861
  • 76 Hauth J C, Goldenberg R L, Parker Jr C R et al.. Low-dose aspirin therapy to prevent preeclampsia.  Am J Obstet Gynecol. 1993;  168 1083-1093
  • 77 Schiff E, Peleg E, Goldenberg M et al.. The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies.  N Engl J Med. 1989;  321 351-356
  • 78 Wallenburg H CS, Dekker G A, Makovitz J W, Rotmans P. Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae.  Lancet. 1986;  1 1-3
  • 79 Wang K C, Chen C P, Yang Y C, Wang K G, Hung F Y, Su T H. Stroke complicating pregnancy and the puerperium.  Zhonghua Yi Xue Za Zhi (Taipei). 1999;  62 13-19
  • 80 Lamy C, Hamon J B, Coste J, Mas J L. Ischemic stroke in young women: risk of recurrence during subsequent pregnancies. French Study Group on Stroke in Pregnancy.  Neurology. 2000;  55 269-274
  • 81 Wiebers D O. Subarachnoid hemorrhage in pregnancy.  Semin Neurol. 1988;  8 226-229
  • 82 Daane T A, Tandy R W. Rupture of congenital intracranial aneurysms in pregnancy.  Obstet Gynecol. 1960;  15 305-314
  • 83 Pool J L. Treatment of intracranial aneurysms during pregnancy.  JAMA. 1965;  192 209-214
  • 84 Schwartz J. Pregnancy complicated by subarachnoid hemorrhage.  Am J Obstet Gynecol. 1951;  62 539-547
  • 85 Botterell E H, Cannell D E. Subarachnoid hemorrhage and pregnancy.  Am J Obstet Gynecol. 1956;  72 844-855
  • 86 Robinson J L, Hall C J, Sedzimir C B. Subarachnoid hemorrhage in pregnancy.  J Neurosurg. 1972;  36 27-33
  • 87 Parkinson D, Bachers G. Arteriovenous malformations: summary of 100 consecutive supratentorial cases.  J Neurosurg. 1980;  53 285-299
  • 88 Itoyama Y, Uemura S, Ushio Y et al.. Natural course of unoperated intracranial arteriovenous malformations: study of 50 cases.  J Neurosurg. 1989;  71 805-809
  • 89 Horton J C, Chambers W A, Lyons S L et al.. Pregnancy and the risk of hemorrhage from cerebral arteriovenous malformations.  Neurosurgery. 1990;  27 867-872
  • 90 Weir B, Macdonald R L. Management of intracranial aneurysms and arteriovenous malformations during pregnancy. In: Wilkins RH, Rengachary SS Neurosurgery. New York; McGraw-Hill 1996: 2421-2427
  • 91 Mast H, Young W L, Koennecke H C et al.. Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation.  Lancet. 1997;  350 1065-1068
  • 92 Sawin P. Spontaneous subarachnoid hemorrhage in pregnancy and the puerperium. In: Loftus C Neurological Aspects of Pregnancy. Park Ridge, IL; American Association of Neurological Surgeons 1996: 85-99

Steven K FeskeM.D. 

Department of Neurology, Brigham and Women's Hospital

75 Francis Street, Boston, MA 02115

Email: skfeske@bics.bwh.harvard.edu