Hailey Bossio, MD
Kent Hospital, Warwick, RI

INTRODUCTION

The incidence of stroke is common – someone in the United States has a stroke every 40 seconds. In the management of stroke, expediency is key. Like the majority of hospitals, Kent Hospital has a stroke protocol in place, but this does not include an approach to stroke in the pregnant patient. Should the protocol be any different?

CASE

A 37-year-old female who is 8 weeks pregnant was brought in by ambulance to our community emergency department at 8:15AM with slurred speech, right-sided facial droop, and right-sided arm and leg weakness. We had report from EMS that the patient was a Los Angeles Motor Scale (LAMS) of 5. The patient had been walking to the bathroom at 6:30AM that morning when she experienced sudden-onset right-sided weakness and fell to the floor. The patient’s last known normal was 6:30AM. Emergency medical services (EMS) was notified by the patient’s mother, who calls the patient every morning and was surprised to hear her 3-year-old granddaughter answer the phone.

The patient was 8 weeks pregnant by last menstrual period and had a confirmed intrauterine pregnancy (IUP) by ultrasound. The patient had a past medical history notable for a complicated premature delivery of a fetus with trisomy 21 who expired at 6-weeks-old and a miscarriage 6 months prior to this pregnancy.

Her vital signs on arrival were temperature of 36.6 degrees, heart rate 86 beats per minute and regular, respiratory rate 16 breaths per minute, blood pressure 100/66 mmHg, and oxygen saturation 100% on room air. The patient was assessed immediately upon arrival, had dysarthria, right upper and lower facial weakness, right-sided upper and lower extremity weakness. Initial National Institute of Health Stroke Scale (NIHSS) was 7. Patient’s fingerstick blood glucose was 86 mg/dL, other labs were within the limits of normal.

A code stroke was called and the patient was rushed to have a computed tomography scan (CT) of her head without contrast and a CT for large vessel occlusion (CT ELVO) which includes a CT angiogram CTA of the head and neck. We contacted our region’s comprehensive stroke center due to the patient’s symptoms suggestive of a possible large vessel occlusion. As our patient was undergoing her CT scan, an interventional neurologist at the comprehensive stroke center was reviewing the images. CT head without contrast had no evidence of intracranial hemorrhage. The patient was found to have a possible M2 branch occlusion on CTA per the interventional neurologist and he advised us to transfer the patient immediately to his center 15 minutes away for evaluation and potential mechanical thrombectomy.

Our patient returned from CT scan and had a mild but noticeable improvement in her neurological deficits. She was transferred to the comprehensive stroke center and on arrival had drastic improvement in her neurological exam. The interventional neurology team decided against mechanical thrombectomy and IV thrombolytic therapy due to the patient’s rapidly improving symptoms. The patient was started on low molecular weight heparin. Patient was discharged home with complete resolution of her neurological deficits and a viable IUP.

CASE DISCUSSION

The pregnant patient is at an increased risk of stroke due to venous stasis, hypercoagulability in pregnancy, and pregnancy-related diseases including HELLP syndrome, eclampsia, and pre-eclampsia. Patients are at an even greater risk of stroke during the postpartum period. Management of stroke in the pregnant patient is complicated by concern for both the mother and the developing fetus, but the health of the mother should take precedent. The approach to such a patient should be multi-disciplinary including specialists from emergency medicine, obstetrics and gynecology, maternal-fetal medicine, neurology, and interventional radiology. American guidelines are scarce due to current evidence existing primarily in the form of case reports. The Heart and Stroke Foundation of Canada is the only group to have published consensus statements on acute management of stroke in pregnancy and prevention of recurrent stroke in pregnancy.

DIAGNOSIS

What would be your differential diagnosis for this patient?

• Ischemic stroke
• Hemorrhagic stroke
• Eclampsia
• Pre-eclampsia
• HELLP
• Cerebral venous thrombosis (CVT)
• Hypoglycemia
• Complex migraines
• Carotid dissection
• Postpartum angiopathy

What would you do first in this patient?

• IV, O2, monitor, fingerstick blood glucose
• Vitals are extremely important to look for hypertension, which would increase your concern for eclampsia/pre-eclampsia.

Initial Labs: BMP, CBC, PT/INR, AST, ALT, Bilirubin, Serum hCG.

*None of these labs should hinder you from getting the patient to the CT scanner, including serum hCG.

Diagnostic Workup

CT Head without contrast +/- CTA of the head and neck for severe disabling strokes where the symptoms are concerning for a large-vessel occlusion.1 It is essential to advocate for a CTA if the patient may be a candidate for mechanical thrombectomy. Magnetic resonance imaging (MRI) can also be considered a first-line imaging modality in pregnant patients, but timely completion of the study is often a limiting factor. A European review recommends MRI without gadolinium as the preferred imaging modality for stroke in pregnancy as it has a greater sensitivity for detecting small infarcts, CVT, and cavernomas.(2) Gadolinium should particularly be avoided in the first trimester due to its teratogenic effects. The time-of-flight series (non-contrast MR angiography or venography) would provide us with the most information but multiple societies agree that CT imaging should not be withheld if MRI cannot be performed in a timely fashion.(1,2) Each center is aware of their capabilities, and their stroke protocol should reflect that with a goal door-to-needle time of 60 minutes.

But what about the risk of radiation and contrast?  

Exposure to a cumulative dose of less than 5 rads during pregnancy has not been shown to affect the outcome of a pregnancy compared to control populations. (3) One CT scan of the head is equal to <0.050 rads; therefore, it is of negligible risk to the developing fetus.(3) CTA exposes the fetus to <0.050 rads, but it does requires the use of IV contrast. (3) Contrast does cross the placenta but in such small amounts that no teratogenic effects have been reported to date. (1)

A great article to reference when discussing the risks of radiation can be viewed here. (3)

TREATMENT

1. Thrombolytics for Treatment of Ischemic Stroke in Pregnancy

• IV Alteplase: 0.9 mg/kg
• 10% bolus over 1-2 minutes, 90% infusion over 1 hour

American Stroke Association: consider Alteplase in pregnancy when the anticipated benefits of treating moderate to severe stroke outweigh the risks of uterine bleeding [Class 2b; Level of evidence C].(4)

Canadian Stroke in Pregnancy Guidelines: consider Alteplase IV in a pregnant patient with disabling ischemic stroke who meets existing criteria for thrombolysis, in consult with a stroke specialist. (1)

Despite these guidelines, according to the American Heart Association/American Stroke Association (AHA/ASA) Get with the Guidelines database, we give IV tPA less frequently in pregnant/postpartum women compared to non-pregnant women, 4.4% vs. 7.9%, respectively.(5)

Areas of debate

• • Maternal intracranial hemorrhage
    • AHA/ASA database → higher rate of spontaneous intracranial hemorrhage in pregnant and postpartum women compared to non-pregnant women → NOT statistically significant.(5)
    • No difference in rate of in-hospital death, discharge to home, or independent ambulation at home. (5)
  • Fetal hemorrhage
    • Alteplase is a large molecule and does not cross the placenta, therefore unexpected to cause fetal hemorrhage.
  • Placental abruption
    • No reports of placental abruption in case studies – 1 case of intra-uterine hematoma which required surgical drainage and was followed by medical termination of the pregnancy. (5)
    • Patients are at risk of placental abruption with or without alteplase and close monitoring is recommended. (1)
  • Early postpartum period → maternal postpartum hemorrhage
    • Akazawa et al. collected data on 13 cases of systemic thrombolytic therapy given in the early post-partum period (< 48 hours after delivery) for different indications (primarily pulmonary embolism and one case of ischemic stroke).(6) Twelve of the thirteen cases required significant blood transfusions due to bleeding, 5/13 cases (38%) required laparotomy to control bleeding, and 2/13 resulted in hysterectomy. All laparotomies occurred in patients whose mode of delivery was a caesarean section. (6)

2. Mechanical Thrombectomy

In theory, mechanical thrombectomy is a safe option for the pregnant patient, but it has only been reportedly performed in four case reports. (7,8) All women in these cases were in their third trimester and had a high NIHSS score, except for one case in which the patient was transferred to the center intubated and the NIHSS couldn’t be assessed. Three women had a good neurological outcome with a modified rankin score (mRS) of 0-1 and the woman intubated without a calculated NIHSS had an mRS of 2. There were no maternal complications reported (ie. sICH, placental abruption). Fetal mortality was 0% with three healthy babies delivered and the fourth pregnancy still ongoing. These studies advocate for mechanical thrombectomy to be considered first-line treatment for proximal large-vessel thromboembolic occlusions.

Canadian Stroke in Pregnancy Guidelines: pregnancy is not a contraindication to angiography and endovascular thrombectomy. For patients with large vessel occlusions eligible for and with rapid access to endovascular thrombectomy, proceeding directly to without administering intravenous alteplase could be considered. (1)

Most of our evidence is derived from case reports, thrombolytic use for indications other than ischemic stroke, and a retrospective review of the Get with the Guidelines AHA/ASA database, which is a voluntary observational database rather than a clinical outcomes database.

CASE CONCLUSION

Our patient had evidence of a suspected large-vessel occlusion. In her case, it was appropriate to order a CTA of the head and neck as she was a potential candidate for mechanical thrombectomy. We would not have been able to perform an MRI + MR angiography/venography at our institution in a timely fashion. Our patient’s CT head without contrast showed no evidence of intracranial hemorrhage so we knew that she was not having a massive hemorrhagic stroke. The CTA identified a possible M2 lesion. It was a crucial step to consult with our area’s comprehensive stroke center upon patient arrival to facilitate her rapid transfer.

The recommendation from the interventional neurology team not to administer tPA prior to transfer could be debated; the decision was justified by her short transfer time of 15 minutes and the fact that tPA administration would have delayed the transfer. Our patient was evaluated and out the door to our comprehensive stroke center in 48 minutes. She should receive a full hypercoagulable workup as case reports suggest that women with ischemic stroke or transient ischemic attacks are more likely to have an inherited thrombophilia.9 Her work-up should also include an echocardiogram. Pregnant patients including our patient should be initiated on low dose aspirin 81 mg and must continue to take it throughout the pregnancy.

REFERENCES

1. Stroke C, Practices B, Committees QA. CANADIAN STROKE BEST PRACTICE Stroke in Pregnancy. 2018;(July).
2. M. C, A. R, C. N-P. Management of stroke and pregnancy. Eur Stroke J. 2018;3(3):227-236. doi:10.1177/2396987318769547 LK  – http://resolver.ebscohost.com/openurl?sid=EMBASE&issn=23969881&id=doi:10.1177%2F2396987318769547&atitle=Management+of+stroke+and+pregnancy&stitle=Eur.+Stroke+J.&title=European+Stroke+Journal&volume=3&issue=3&spage=227&epage=236&aulast=Cauldwell&aufirst=Matthew&auinit=M.&aufull=Cauldwell+M.&coden=&isbn=&pages=227-236&date=2018&auinit1=M&auinitm=
3. Ratnapalan S, Bentur Y, Koren G. Doctor, will that x-ray harm my unborn child? CMAJ. 2008. doi:10.1503/cmaj.080247
4. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Vol 49.; 2018. doi:10.1161/STR.0000000000000158
5. Leffert LR, Clancy CR, Bateman BT, et al. Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period. Am J Obstet Gynecol. 2016. doi:10.1016/j.ajog.2015.12.016
6. Akazawa M, Nishida M. Thrombolysis with intravenous recombinant tissue plasminogen activator during early postpartum period: a review of the literature. Acta Obstet Gynecol Scand. 2017. doi:10.1111/aogs.13116
7. Aaron S, Shyamkumar N, Alexander S, et al. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system. Ann Indian Acad Neurol. 2016. doi:10.4103/0972-2327.173302
8. Bhogal P, Aguilar M, AlMatter M, Karck U, Bäzner H, Henkes H. Mechanical Thrombectomy in Pregnancy: Report of 2 Cases and Review of the Literature. Interv Neurol. 2017. doi:10.1159/000453461
9. Kupferminc MJ, Yair D, Bornstein NM, Lessing JB, Eldor A. Transient focal neurological deficits during pregnancy in carriers of inherited thrombophilia. Stroke. 2000. doi:10.1161/01.STR.31.4.892