Endovascular treatment for subarachnoid hemorrhage during pregnancy followed by minimum approaches for cerebral vasospasm

Abstract

Background:

Managing subarachnoid hemorrhage (SAH) during pregnancy is challenging due to its rarity, lack of definitive treatment guidelines, and significant concerns regarding both surgical and obstetric management for the pregnant mother and fetus. Treatment methods and medications must be carefully selected, considering the possibility of adverse effects and safety for both the pregnant mother and fetus. We present the case of a pregnant woman with SAH who underwent endovascular treatment (EVT) followed by minimum approaches for cerebral vasospasm prevention and treatment.

Case Description:

A 36-year-old female at 24 weeks of gestation presented with a headache without neurological deficits. Magnetic resonance imaging on admission showed SAH with diffuse clotting in the basal cistern. Digital subtraction angiography identified a small saccular aneurysm. We performed EVT, followed by minimum required prevention and treatment of cerebral vasospasm using fasudil hydrochloride, aspirin, and ozagrel sodium, as these agents seem to be associated with fewer adverse effects at 26 weeks of gestation. The patient exhibited a Glasgow outcome scale score of 5 at discharge, with no oral medications at 25 days after aneurysm rupture. The pregnancy progressed favorably, and a healthy infant was successfully delivered through a scheduled cesarean section in gestational week 37. The child showed no abnormalities at 1 year of age.

Conclusion:

We reported the case of a pregnant patient with SAH who underwent EVT, followed by the minimum required prevention and treatment for cerebral vasospasm. Clinicians should carefully select the medical approaches, including pharmacotherapies for both pregnant women with SAH and the fetus, considering radiation exposure and medication risks.

INTRODUCTION

Managing subarachnoid hemorrhage (SAH) during pregnancy is challenging due to its rarity, the absence of clear treatment guidelines, and significant concerns regarding both surgical and obstetric management for both the pregnant mother and the fetus. The incidence of SAH during pregnancy reportedly ranges between 3 and 11 cases/100,000 pregnancies.[9] The unique physiological changes associated with hemodynamic and hormonal adaptations during pregnancy may heighten vascular stress, thereby increasing the risks of aneurysm formation,growth, and rupture.[9] The infrequency of SAH during pregnancy has undoubtedly contributed to the lack of clear treatment guidelines. However, fetal mortality is estimated to be 17%, whereas maternal mortality is projected at 35% in cases of SAH during pregnancy.[9] Inappropriate perioperative management may lead to serious outcomes for both the pregnant mother and fetus. In particular, treatment methods and medications must be selected with consideration of the potential adverse effects and safety profiles for both the pregnant mother and fetus. We describe the case of a pregnant woman with SAH who experienced rupture of a small posterior communicating artery aneurysm and underwent endovascular treatment (EVT), followed by minimum prevention and treatment for cerebral vasospasm.

CASE PRESENTATION

A 36-year-old female at 24 weeks of gestation presented with a headache. She demonstrated no neurological deficits and only mild nuchal rigidity. Magnetic resonance imaging (MRI) on admission showed SAH with diffuse clotting in the basal cistern, but magnetic resonance angiography (MRA) showed no evidence of aneurysm [Figure 1a-c]. The SAH was classed as Grade II on both the modified Fisher scale and the clinical Hunt–Kosnik scale. Cerebral digital subtraction angiography (DSA) was performed to identify the aneurysm and its characteristics. During DSA, the abdomen of the patient was shielded with a radioprotective double-sided lead apron. DSA and 3D rotational angiography revealed a small saccular aneurysm <2 mm in maximum depth located on the posterior communicating artery, leading to a diagnosis of ruptured intracranial aneurysm (IA) [Figure 2a-c]. We decided to perform EVT. Intra-arterial administration of unfractionated heparin infused at 50 IU/kg at first and an additional 1000 IU at 1-h intervals during EVT. Antiplatelet therapy was withheld in consideration of the potential adverse effects on fetal development and well-being. Under general anesthesia, an 8-Fr Flowgate 90-cm balloon guiding catheter (Stryker Neurovascular, Fremont, CA, USA) was positioned at the petrous segment of the left internal carotid artery (ICA) through the right common femoral artery access. A Shoryu 4 mm × 10 mm balloon (Kaneka Medics, Kanagawa, Japan) was placed around the ruptured IA and inflated as appropriate for the situation. An Excelsior SL-10 microcatheter (Stryker Neurovascular) was gently placed in the ruptured IA. An i-ED silky soft coil 1 mm × 3 cm (Kaneka Medics, Osaka, Japan) was deployed through an SL-10 microcatheter, resulting in complete obliteration of the aneurysm [Figure 3a and b]. The total fluoroscopy time was 39.9 min, the radiation dose was 1723 mGy, and the total dose-area product (DAP), including diagnostic angiography and therapeutic endovascular interventions, was 11.9 mGym². To accelerate the removal of blood and decrease the risk of vasospasm, a lumbar drainage catheter was placed in the space of the lumbar cistern. No oral medications or intravenous infusions for the prevention of vasospasm (e.g., clazosentan or fasudil hydrochloride) were initially administered in consideration of the potential for adverse effects involving the fetus. The postoperative course was uneventful. MRA showed asymptomatic vasospasm in bilateral middle cerebral arteries 10 days after aneurysm rupture. We started to administer medications and infusions of fasudil hydrochloride, aspirin, and ozagrel sodium, as the risk posed by adverse effects appeared lower at 26 weeks of gestation. However, symptomatic vasospasm in the left ICA occurred 12 days after aneurysm rupture and was treated using percutaneous transluminal angioplasty (PTA) with a Gateway 2 mm × 12 mm balloon catheter (Stryker Neurovascular). The total fluoroscopy time was 39.5 min, the radiation dose was 1397 mGy, and the total DAP was 17.7 mGym². As soon as the vasospasm was resolved, all oral medications and infusions were discontinued. The postoperative course was good, with the patient exhibiting a Glasgow outcome scale score of 5 at discharge with no oral medications at 25 days after aneurysm rupture. The pregnancy progressed favorably, with successful delivery of a healthy infant through scheduled cesarean section at 37 weeks of gestation. The child showed no abnormalities at 1 year of age.

Figure 1:

(a) Magnetic resonance imaging on admission shows subarachnoid hemorrhage with diffuse clotting in the basal cistern. (b) Magnetic resonance angiography (MRA) shows no evidence of an aneurysm. (c) MRA shows no evidence of an aneurysm.

Figure 2:

(a) Cerebral digital subtraction angiography (DSA) and 3D rotational angiography of a small saccular aneurysm about 1.60 mm in maximum depth located on the left posterior communicating artery. (b) Cerebral DSA and 3D rotational angiography showed a small saccular aneurysm about 1.60 mm in maximum depth, located on the left posterior communicating artery. (c) Cerebral DSA and 3D rotational angiography showed a small saccular aneurysm about 1.60 mm in maximum depth located on the left posterior communicating artery.

Figure 3:

(a) Balloon-assisted coil embolization is performed. (b) 3D rotational angiography shows complete obliteration of the small saccular aneurysm located on the left posterior communicating artery.

DISCUSSION

Cardiac output is significantly increased 60% by the end of the second trimester of pregnancy, whereas blood volume and blood pressure gradually rise, peaking during the final trimester. [5] These unique physiological changes increase the risks of aneurysm formation, growth, and rupture.[8] Cerebrovascular disease, chronic headaches, advanced maternal age, obesity, chronic hypertension, pregnancy-related hypertension, and hypercoagulability represent significant additional risk factors.[5]

Treatment approach

The choice between clipping and coil embolization for the treatment of ruptured aneurysms is highly contentious, particularly during pregnancy. In addition, rebleeding resulting from an untreated ruptured aneurysm occurs in approximately 33–50% of cases. Further, the mortality rate associated with such incidents is 50–68%.[13] This highlights the critical need for prompt and effective interventions to mitigate the potentially catastrophic outcomes. A previous study demonstrated that patients suffering from ruptured aneurysms accounted for 73% (1115/1537) of all patients with pregnant IA. The majority of patients did not receive treatment for the aneurysm (77%; 781/1013). On the other hand, among those who were treated, surgical clipping (15%; 149/1013), coil embolization (8%; 82/1013), and wrapping (0.1%; 1/1013) were used.[8] That study also recommended coil embolization as the first-line therapy for aneurysms in pregnant patients due to the low complication rate and reduced risks.[8] In the present case, we decided to perform EVT with balloon-assisted coil embolization.

Risk of medications

Ethical considerations largely prevent the inclusion of pregnant women in the majority of premarketing clinical trials.[7] During pregnancy, even when teratogenicity is a potential problem, the adverse results of not administering pharmacotherapies can impact not only the pregnant woman but also the fetus. Simply discontinuing or reducing the dose of a medication due to concerns about adverse effects on the fetus may thus endanger both the pregnant mother and fetus. Moreover, when considering the effects of medication use on the fetus, identifying the specific stage of pregnancy in which the medication is to be administered is important. In each stage, the benefits and risks of the medications to be administered need to be evaluated by referring to guidelines or data from the United States Food and Drug Administration (FDA) and the World Health Organization, as well as specialized texts summarizing research findings on each medication, and the package inserts of the medication. In our case, according to the package inserts, we selected medications and treatments. Prasugrel and clopidogrel should be administered only when the benefits of administration exceed the risks of no administration. On the other hand, aspirin is contraindicated within 12 weeks of expected delivery, and cilostazol is contraindicated for administration during certain or all trimesters of pregnancy, as indicated in the package inserts. Regarding intravenous infusions to prevent vasospasm, clazosentan is also contraindicated for administration during certain or all trimesters of pregnancy due to the potential teratogenic and embryotoxic effects, whereas fasudil hydrochloride and ozagrel sodium should be administered only when the benefits of administration exceed the risks of no administration, as indicated in the package inserts. In the present case, we administered fasudil hydrochloride, aspirin, and ozagrel sodium, as these agents seemed to present the least risk of adverse effects at 26 weeks of gestation.

Fetal radiation exposure

Imaging studies such as computed tomography (CT) or MRI/MRA are necessary for definitive diagnosis of SAH. Exposure to ionizing radiation is to be avoided when possible in the treatment of pregnant women, particularly in relation to the fetus, depending on the gestational age. The effects of radiation on the fetus vary with the dose and stage of development and can be classified into four categories: pregnancy loss, malformation, growth retardation, and carcinogenesis. Exposure during early pregnancy (<2 weeks) is most often associated with pregnancy loss. Exposure during organogenesis (2–8 weeks) can cause malformations and growth retardation, and exposure during brain development (more than 8 weeks) can cause mental disorders.[4,6] Since some conditions are life-threatening for both the pregnant mother and fetus, clinicians must consider these concerns. To avoid exposure to ionizing radiation, MRI and MRA, which are considered safe from the first trimester, are better for diagnosing SAH and visualizing ruptured aneurysms.[10]In the present case, we diagnosed SAH from MRI/MRA to avoid exposure of the fetus to ionizing radiation. However, the site of aneurysm rupture could not be diagnosed from MRI/MRA, and DSA was therefore performed to visualize the ruptured aneurysm. DSA exposes both the pregnant woman and fetus to ionizing radiation. However, exposure to ionizing radiation can be reduced by shielding the lower abdomen with a double-sided lead apron and by selecting the transradial approach.[4] As EVT is increasingly regarded as a treatment option for pregnant women, fetal radiation protection is crucial for diagnosis, treatment strategy planning, and the procedure itself.[3] In our case, DSA and EVT were performed with the abdomen shielded using the radioprotective double-sided lead apron through the right femoral artery for use with a balloon guiding catheter. Moreover, the total fluoro time was 79.4 min and total DAP was 29.6 mGym². In a previous study, the mean and maximum radiation doses to the lower abdomen were 0.05 mGy and 0.07 mGy, respectively, when the maximum dose near the external occipital protuberance during fluoroscopy and imaging was approximately 800 mGy. Both doses were significantly lower than 1 in 10,000.[12] Namely, in our case, the ionizing radiation dose received by the fetus from EVT, coil embolization, and PTA was estimated to be <0.3 mGy, reflecting a level of exposure that is considered safe and unlikely to cause any significant harm to fetal development.[2]

Contrast agent

The FDA categorizes iodinated contrast agents as pregnancy category B drugs, indicating safety for pregnant women and lactating mothers, with the exception of diatrizoate meglumine and sodium, which are classified as category C drugs.[9] Iodinated contrast agents can be classified by osmolarity, ionicity, and benzene ring count. Nonionic contrast agents, with lower osmolality, cause fewer adverse reactions than ionic agents. Nonionic contrast agents have thus mostly been used in recent X-ray studies. Ionic contrast agents can cause significant adverse effects during pregnancy, whereas nonionic iodine agents do not affect fetal thyroid-stimulating hormone and free thyroxine (T4) levels due to the transient presence in fetal blood.[14] Although iopamidol and iopromide are nonionic, low-osmolarity agents that can pass through the placenta, these agents are considered safe in terms of teratogenic and mutagenic effects.[9] In the present case, we performed DSA and EVT with iopamidol. While the safety of this agent is well established, some clinical studies on humans have raised concerns about its use in pregnant patients.[9]

Aneurysmal rupture complicating pregnancy has been associated with a maternal mortality rate of 13–35% and a fetal mortality rate of 10–25%.[1,11] Although no studies have been conducted to guide the optimal management of SAH during pregnancy, prompt treatment of a ruptured aneurysm at an appropriate time and continuation of the pregnancy will result in favorable outcomes for both the pregnant woman and fetus until the third trimester.[1] However, treatment before the third trimester requires careful selection of medical approaches, including pharmacotherapies, for both the pregnant mother and fetus, considering concerns about radiation exposure and medication risks. In addition, we must strive to minimize risks for both the pregnant woman and the fetus.

CONCLUSION

We have reported the case of a pregnant woman with SAH at 24 weeks of gestation who underwent EVT, followed by minimum required prevention and treatment for cerebral vasospasm. Clinicians should thoughtfully select medical approaches, including pharmacotherapies, for pregnant patients, considering concerns about radiation exposure and medication risks.

Ethical approval:

Institutional review board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.