The clinical characteristics and treatment of cerebral AVM in pregnancy

Abstract

Cerebral arteriovenous malformation (AVM) in pregnancy is a complex situation and there is no agreement on its hemorrhage risk and treatment. Although studies on bleeding risk of cerebral AVMs in pregnancy are very few and there are different results between them, pregnancy will increase the hemorrhagic risk of AVM, and ruptured cerebral AVM in pregnancy should be treated actively. After intracranial hemorrhage, cerebral angiography should be performed for pregnant women shielded correctly. Cerebral angiography could clearly demonstrate the characteristics of cerebral AVM. The results from the literature show that the radiation dose of endovascular and stereotactic radiotherapy for cerebral AVM in pregnancy is below the safety value and is safe. Unruptured AVM in pregnancy, if there is no bleeding factor, such as no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment, should be observed conservatively.

Introduction

The prevalence rate of cerebral arteriovenous malformation (AVM) is approximately 0.01–0.5% and generally presents symptoms at 20–40 years age, most commonly at 30 years old, and equally affects men and women.¹ For women, this is the age of pregnancy.² Pregnancy coexisting with cerebral AVM is a complex situation, involving preexisting, incidental findings, and hemorrhage prior to or during pregnancy; in every scenario the role of imaging and management is different. Simplifying everything to one denominator would help to sort out the problem. Therefore, this review was performed.

Clinical characteristics

Studies on bleeding risk of cerebral AVMs in pregnancy were very few and there were different results between them.^3,4 In Robinson et al.’s assessment of 24 cases of ruptured cerebral AVMs in pregnancy in 1974,⁵ they found that the bleeding risk in the same pregnancy is 27%, which is four times that of the general population. In 1990, Horton et al. studied 451 gestational age women with cerebral AVM.⁶ They found that the hemorrhagic risk of cerebral AVM during pregnancy was 3.5% (non-pregnant AVM was 3.1%), which was similar to the non-pregnant population.⁶ After the first hemorrhage of pregnant cerebral AVM, if not treated, the risk of the second bleeding increased to 6% at 1 year follow-up; this is comparable with the non-pregnant population.^3–5 One study in 2012 showed that cerebral AVM bleeding risk during pregnancy was 10.8%, hemorrhage risk for each pregnant woman was 8.1%, and an odds ratio value of cerebral AVM hemorrhage during pregnancy was 7.91.⁷ Cerebral AVM bleeding caused 28% maternal mortality, 14% fetal death rate, and could lead to miscarriage at early pregnancy.^2,8 Most cerebral AVM hemorrhages occurred between 20 weeks of pregnancy and postpartum 6 weeks, which coincided with maternal hemodynamic changes.⁹ Pregnancy increased cardiac output 30–60%; cardiac output began to increase rapidly after 3 months of pregnancy, reached the peak at sixth months, and gradually returned to normal a few weeks after childbirth. The blood volume and blood pressure also gradually increased during pregnancy, and reached a peak during late pregnancy. Cerebral AVM lost the ability to adjust blood flow because of vascular abnormalities and blood flow due to AVM vascular wall shear stress increased, causing AVM rupture and bleeding. However, in the study by Liu et al.,¹⁰ they did not find an increased risk of AVM rupture in patients aged 18–40 years, which are the prime childbearing ages in the Chinese population. The case-crossover analysis using the time of pregnancy and the puerperium as a trigger also did not reveal an increased risk of AVM rupture in patients aged 18–40 years. The annual rate of hemorrhage in these patients was similar to the rate reported by natural history studies of untreated AVM.

A pregnant women may have a preexisting unruptured or ruptured AVM, incidental unruptured AVM, or ruptured AVM during the pregnancy; in every scenario the role of imaging and management is different. Magnetic resonance imaging examination is helpful to distinguish the eclampsia, pre-eclampsia, and intracranial hemorrhage. In pregnant women with intracranial hemorrhage, 15% could present as eclampsia. For the head computed tomography (CT) examination, good shielding must be given to the pregnant uterus. After intracranial hemorrhage, cerebral angiography should be performed for pregnant women. The fetus was rarely affected by irradiation and iodine contrast agent as long as the uterus was shielded correctly. Cerebral angiography could clearly demonstrate the characteristics of cerebral AVM, such as AVM location, AVM size, feeding artery, flow rate, arteriovenous fistula, coexisting aneurysm, venous drainage, and ectasia of drainage veins. These characteristics could be used to evaluate the bleeding risk of cerebral AVM. As reported in the literature, deep location, small AVM size, arteriovenous fistula, aneurysm, and restricted venous drainage are hemorrhagic risk factors of a cerebral AVM.¹¹

Anesthesia methods for pregnancy with cerebral AVM are rarely reported so far. The decisions regarding treatment time, anesthesia, and analgesia for cerebral AVM in pregnancy should be made by a multidisciplinary approach to ensure its hemodynamic stability. Anesthesia should maintain the stability of the cardiovascular system during childbirth, avoiding hypotension reducing the uteroplacental blood perfusion and hypertension increasing bleeding risk of cerebral AVM.¹²

Neurosurgical treatment of cerebral AVM in pregnancy

An emergency operation is necessary for cerebral AVM bleeding in pregnancy if intracranial hematoma causes worsening of neurological symptoms or cerebral hernia. Cesarean section is indicated if the fetus is mature enough. Blood pressure should be controlled if there is no indication for emergency operation, although this might not prevent cerebral AVM bleeding because there is no history of hypertension in most cerebral AVM patients.¹³

To improve the prognosis of mother and fetus, cerebral AVM was resected in pregnancy in some case reports, but some were also resected postpartum.^5,14 If the fetus was not mature, the risk of AVM hemorrhage was high, and risk of surgical excision was low, surgical excision could be performed. If the fetus was mature and fetal distress was observed, emergency cesarean operation should be considered. Cerebral AVM operation risk should be graded according to the Spetzler–Martin classification.¹⁵ The risks of cerebral AVM excision were bleeding and of uterine and placental hypoperfusion. Preoperative intravascular embolization may reduce the risk of bleeding in surgery, but endovascular embolization likely cause ischemic or hemorrhagic complications.^16,17 If the fetus is mature, hemorrhagic AVM should be resected at early postpartum.¹⁴ Robinson et al. reported that mothers with hemorrhagic AVM were treated by neurosurgical operations, in which there were no mother deaths, 26% fetal mortality, and maternal mortality was 10% in a conservative treatment group.⁵ Sadasivan et al. assumed that AVM operation at 2 months after delivery could be performed easily because hemodynamic changes had returned to normal.¹⁸ Fukuda et al. had treated three cases of hemorrhagic AVM in pregnancy surgically.⁸ One case was an emergency excision because of consciousness disorders and the other two cases (Spetzler–Martin grades I and II) were elective operation excisions; all three cases had a good prognosis.

Endovascular embolization for cerebral AVM in pregnancy

Endovascular embolization for cerebral AVM in pregnancy should accord to their clinical manifestations and angiographic features. Radioactive diagnosis and treatment methods could be applied to cerebral AVM in pregnancy unless it is necessary. Radiation effects on maternal and fetal varied according to their development stage and irradiation dose.^19–21 During the first week (0–8 days), 100 mGy could cause embryonic fatality.¹⁹ During the period of organ development (2–8 weeks), 500 mGy will affect the normal organ development.^19,22 In the early fetal stage (8–15 weeks), the safety threshold dose is 120 mGy.²² Mid pregnancy (16–25 weeks), the safety threshold is 250 mGy.²¹ At more than 25 weeks, more than 500 mGy will lead to fetal malformations and mental retardation.²³

For hemorrhagic AVM, cerebral angiography is necessary to demonstrate the angiographic characteristics of AVM. Some reports showed that the radiation dose from cerebral angiography was safe for fetal development.²⁴ Murakami et al. reported a case of brain hemorrhage caused by AVM in a 15 weeks pregnant, 32-year-old woman.²⁴ Under the lead shielding protection, the exposure dose after head CT scanning and cerebral angiography was 0.025 mGy. The fetus was normal at the term delivery. The safety threshold of irradiation dose at 15 weeks of gestation was 120 mGy. In 2001, Piotin et al. successfully embolized two cases of ruptured aneurysm in pregnancy.²⁵ Later, Kizilkilic et al. found that even for a quite long time of embolization, the radiation level is 0.17–2.8 mGy, far below the safety threshold dose.²⁰ This dose was comparable to that of vascular plasty for acute myocardial infarction and renal hypertension. In recent years, Pumar et al. reported eight cases of ruptured aneurysm in pregnancy and concluded that endovascular embolization in the period of pregnancy for ruptured aneurysms was safe and effective.²⁶

Dashti et al. reported a case of cerebellar hemorrhage (AVM Spetzler–Martin grade IV) at 20 weeks of pregnancy and two fetuses.²⁷ The AVM was treated by ONYX embolization and fetal exposure radiation dose was very low (1.9 × 10⁻³⁰ mGy). They suggested that the EVAL in ONYX was an inert chemical and it was not clear that whether the clinical dose of organic solvent DMSO was teratogenic. Salvati et al. reported two cases of ruptured AVM in pregnancy.²⁸ One case was a 23-year-old woman, 19 weeks pregnant, in which cerebral angiography showed an intraventricular AVM supplied by a callosomarginal artery and drained by a single deep vein with drainage vein ectasia. This AVM was treated by n-butyl cyanoacrylate (NBCA) embolization under general anesthesia. The infant was healthy at full-term cesarean birth. The second case was a 30-year-old woman, 26 weeks pregnant, with a right central sulcus region AVM. Cerebral angiography showed no coexisting aneurysm and smooth venous drainage. This AVM was conservative observed and NBCA embolization was performed 15 days after cesarean section. They suggested that the AVM should be treated aggressively if the AVM had definite weak point and its bleeding risk was high; the AVM should be treated conservatively if there is no risk of bleeding and treatment could be performed postpartum.

Stereotactic radiosurgery for cerebral AVM in pregnancy

The radiation dose of stereotactic radiotherapy in the treatment of pregnant cerebral AVM is below the safety threshold. Nagayama et al. reported a case of basal ganglia of an AVM patient,²³ 24 weeks pregnant, treated with linear accelerator radiosurgery. The intracranial target dose was 20 Gy, under lead shielding protection, and the abdominal area dose is 14.05 mGy (13.64–14.34 mGy). Cesarean section was performed at 36 weeks and normal development was observed at 7 years follow-up. A case of brain melanoma, 25 weeks pregnancy, was treated with stereotactic radiation by Yu et al.²⁹ The target dose was 25 Gy, fetal exposure dose was 1.5–3.1 mGy. Radiation safety threshold at 16–25 weeks was 250 mGy and 500 mGy after 25 weeks. Therefore, the fetus was safe and developed normally at 14 months follow-up. These results showed that the radiation dose of endovascular and stereotactic radiotherapy treatment for cerebral AVM in pregnancy was below the safety value and was safe. However, unless it is necessary, non-radiation diagnosis and treatment means should be chosen.

Obstetrical treatment

There is no evidence suggesting that vaginal delivery will increase the cerebral AVM bleeding risk and cesarean section can prevent the hemorrhage of AVM. In 2013, Kalani et al.,³⁰ who studied 64 cases of gestational cerebral cavernous malformation, found that the risk of bleeding during the period of pregnancy was 3%, the risk did not increase, and concluded that cerebral cavernous malformation was not contraindication of pregnant and vaginal delivery. In 36 cases of hemorrhagic AVM reported by Dias and Sekhar,² only two cases occurred during childbirth. Cesarean section was selected in some cases, but there is still a lack of studies about the delivery mode and AVM bleeding risk.^2,3,6,12,31 Although AVM rupture in the childbirth process does not seem to increase, cesarean section can control the maternal blood pressure and avoid brief and intense hemodynamic changes of intracranial vascular pressure, which could lead to an increase of the stress that the vessel wall will bear. If the AVM has been completely removed, the method of delivery should accord with the obstetric indications.

Conclusion

Case reports and studies on cerebral AVM treatment during pregnancy are rare. The treatment strategy has depended on the risk of cerebral AVM treatment and its bleeding risk in pregnancy. In this situation, treatment of cerebral AVM in pregnancy should be based on neurosurgical indications instead of obstetric indications, but ectopic pregnancy should be based on obstetric indications. There is no best treatment for symptomatic cerebral AVM in gestation and postpartum angiography and treatment could reduce the X-ray contrast and complications on fetal effect. The hemorrhagic risk of AVM will increase during pregnancy, so ruptured cerebral AVM in pregnancy should be treated actively. An unruptured AVM in pregnancy, if there are no bleeding factors, such as no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment, should be observed conservatively. In most cases, risk–benefit analysis results do not support AVM treatment during the gestation period. Hemorrhagic cerebral AVM in pregnancy could be treated immediately after delivery due to rebleeding risk in puerperal. Unruptured AVM presenting epilepsy should be treated following obstetric indications and should be treated as for non-pregnant women after birth. For an intracranial hemorrhage occurring in pregnancy, whether treated or not, attention should be paid to adverse effects of drugs commonly used in neurosurgery on the fetus.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.