Stroke in Pregnancy

Christina Mijalski Sells, MD, MPH; Steven K. Feske, MD

Disclosures

Semin Neurol. 2017;37(6):669-678. 

In This Article

Management of Stroke Associated With Pregnancy

Intravenous thrombolysis and endovascular clot extraction are the best therapies for acute ischemic stroke in eligible patients; however, neither of these therapies has been studied well in pregnant women because they are routinely excluded from trials as a vulnerable population.[39] Tissue plasminogen activator (tPA) is the intravenous agent most commonly used for thrombolytic therapy in acute stroke. It is a very large molecule, and there is no evidence from animal models that it crosses the placenta.[17] However, there are safety concerns for maternal and placental hemorrhage that may complicate pregnancy.[40] Intravenous tPA has not been studied in controlled trials including pregnant women, and concern remains for teratogenicity if given in the first trimester. Leonhardt et al retrospectively analyzed 28 cases of intravenous tPA used for various indications to treat women during pregnancy. Indications for its use included stroke (10/28), cardiac valve thrombosis (7/28), pulmonary embolism (7/28), deep venous thrombosis (3/28), and myocardial infarction (1/28). Complications of thrombolysis for the specified indications did not exceed what was expected for non-pregnant patients. Two of the 28 patients died; however, both were patients with severe underlying disorders. It is difficult to analyze fetal survival, because women will sometimes choose to terminate pregnancies in the setting of critical illness. In this case series, 6 of 26 fetuses died, and 3 of these were due to elective termination. None of the surviving fetuses had any teratogenic defects identifiable at birth, which is encouraging for the safety of treatment in this population.[41]

Another series published by Murugappan et al evaluated the use of intravenous tPA in eight women for the indication of acute ischemic stroke during pregnancy. Of these eight women, seven recovered, while one died as a result of arterial dissection from angiography. One patient had an intrauterine hematoma, one patient an asymptomatic ICH, one an intravenous catheter-associated hemorrhage, and one a buttocks hematoma. There was one spontaneous abortion and one case of fetal demise. There were three elective medical terminations of pregnancy and two healthy deliveries. It is difficult to generalize concerning drug toxicities from these data given the small number of patients and the strong influence of the disease states, yet, the data suggest that it is reasonably safe to give intravenous (IV) tPA in pregnant women who otherwise qualify. Each case of ischemic stroke in pregnancy should be considered carefully, following a team-based approach to decision-making, involving neurologists, obstetricians, and family in the risk versus benefit considerations whenever possible.[42]

Table 2 summarizes 10 cases in which IV tPA was used for the treatment of stroke in the setting of pregnancy. It includes both maternal and fetal outcomes. While the number of cases is small, only one maternal and a subsequent fetal death occurred in the setting of a procedural complication. Of those patents treated medically who did not elect to pursue medical termination of pregnancy, no maternal or fetal complications were reported.

Case reports have suggested favorable efficacy and relative safety of intra-arterial administration of tPA during pregnancy.[43] Endovascular therapy is now most commonly limited to mechanical clot extraction; however, intra-arterial administration of tPA may also be helpful in some cases. Limited data suggest that this may be a safe and feasible approach to thrombectomy in pregnant patients.

Although limited, the available data strongly suggest that tPA, both intravenous and intra-arterial, and endovascular clot retraction are relatively safe during pregnancy. Multiple governing organizations recommend that treatment of an individual patient should not be delayed or compromised due to pregnancy.[40–43]

Vascular malformations should be closely followed up and managed with the goal of decreasing morbidity and mortality. Dias et al studied the benefits of surgical treatment of women with ruptured aneurysmal SAH and ruptured AVMs during pregnancy. These data demonstrate a clear benefit for properly selected women and their fetuses after aneurysmal SAH. There was also a trend in favor of benefit for both women and fetuses after AVM rupture; however, the numbers of these events were small, and the differences did not reach statistical significance.[38] Only cases of ICH occurring in the antepartum period were included. For aneurysmal SAH, 55 patients were treated surgically, and 51 were managed medically. Of those cases, the maternal mortality was significantly greater among those without surgical management (63%) compared with those who underwent surgical intervention (11%). A similar benefit was realized for fetal mortality, with a rate of 27% in the non-surgical group and only 5% in those who underwent surgical management. Although surgical selection was subject to bias, this difference was held up to statistical correction for clinical grade at presentation. For ruptured AVM, 13 patients were treated surgically, and 22 were managed medically. The mortality rates after AVM rupture were as follows: women without surgery 32%, with surgery 23%, and fetuses of mothers without 23%, and with surgery 0%.[38] Although such data do not give us clear direction for surgical care after AVM rupture, recognizing the limits of the population studied, it is widely felt that after rupture of AVMs as well as aneurysms, women and fetuses benefit from surgical intervention based on neurosurgical principles. (These issues are discussed in more detail in the paper by Drs. Can and Du Neurosurgical Issues in Pregnancy in this issue.)

Preeclampsia should be managed with close monitoring of hemodynamic status, aggressive control of hypertension, magnesium sulfate, and early delivery for definitive treatment whenever it is feasible. The Magnesium Sulfate for Prevention of Eclampsia (MAGPIE) trial randomized preeclamptic women with severe features and those without to magnesium sulfate or placebo, respectively, and evaluated them for progression to eclampsia. This study found that women randomized to magnesium sulfate had a 58% lower rate of eclampsia compared with the placebo group, and there were no significant adverse maternal or fetal events attributable to magnesium sulfate.[44] Lucas et al studied the benefit of magnesium sulfate in severely preeclamptic women compared with that of phenytoin and found magnesium sulfate to be the superior agent for the prevention of eclamptic convulsions. Magnesium sulfate has also been shown to be superior to diazepam and phenytoin for prevention of recurrent seizures in randomized control trials of women with established eclampsia. This same benefit did not translate to a decrease in mortality; however, women given magnesium sulfate were significantly less likely to endure additional medical complications as were their babies.[45] These studies support the use of magnesium sulfate over other anticonvulsants in both the treatment and prevention of eclampsia.[46] Based on these trials, magnesium sulfate is now the standard of care both to prevent progression to eclampsia in women with preeclampsia and to prevent recurrent seizures in women who have already had an eclamptic seizure.

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