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 they provide different results, pregnancy will increase the hemorrhagic risk of AVM and ruptured cerebral AVM in pregnancy should be actively treated. After intracranial hemorrhage, cerebral angiography should be performed for pregnant women shielded correctly. Cerebral angiography could clearly demonstrate the characteristics of cerebral AVM. Results from the literature show that the radiation dose of endovascular and stereotactic radiotherapy for cerebral AVM in pregnancy was below the safety value and was safe. For an unruptured AVM in pregnancy, if there are no bleeding factors, e.g. no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment, then it should be observed conservatively.

Introduction

Cerebral arteriovenous malformation (AVM) has a prevalence rate of approximately 0.01–0.5% and generally presents symptoms at 20–40 years of age, most commonly at about 30 years old. It equally affects both men and women,¹ but for women this is the age when pregnancy is most likely.² Pregnancy coexisting cerebral AVM is a complex situation, with preexisting, incidental findings and hemorrhage prior to or during pregnancy, but 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 carried out to address this problem.

Clinical characteristics

Studies on bleeding risk of cerebral AVMs in pregnancy are very few and have provided different results.^3,4 Robinson et al. provided an assessment of cerebral AVM in 24 cases of ruptured cerebral AVMs in pregnancy in 1974.⁵ They found that bleeding risk in the same pregnancy is 27%, which is four times higher than that of the general population.⁵ In 1990, Horton et al.,⁶ who studied 451 gestational age women with cerebral AVM, 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. 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 the odds ratio value of cerebral AVM hemorrhage during pregnancy is 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 hemorrhage occurred between 20 weeks of pregnancy and postpartum 6 weeks, which coincided with maternal hemodynamic changes.⁹ Pregnancy increased cardiac output by 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, reaching the peak during late pregnancy. Those with 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, Liu et al. did not find an increased risk of AVM rupture in patients aged 18 to 40 years,¹⁰ which are the prime childbearing ages in the Chinese population. A 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 to 40 years. The annual rate of hemorrhage in these patients was similar to the rate reported by natural history studies of untreated AVM.

Those pregnant may have a preexisting unruptured or ruptured AVM, an incidental unruptured AVM, or ruptured AVM during the pregnancy, so 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 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 is rarely affected by irradiation and iodine contrast agent as long as the uterus is shielded correctly. Cerebral angiography could clearly demonstrated 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 have to date rarely been reported. The decisions concerning treatment time, anesthesia, and analgesia for cerebral AVM in pregnancy should be made using a multidisciplinary approach to ensure its hemodynamic stability. Anesthesia should maintain the stability of the cardiovascular system during childbirth, avoiding hypotension, which reduces the uteroplacental blood perfusion, and hypertension, which increases the bleeding risk of cerebral AVM.¹²

Neurosurgical treatment of cerebral AVM in pregnancy

Emergency operation is necessary for cerebral AVM bleeding in pregnancy if intracranial hematoma causes worsening 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, the 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, an 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 are uterine and placental bleeding and hypoperfusion. Preoperative intravascular embolization may reduce the risk of bleeding in surgery, but endovascular embolization is likely to cause ischemic or hemorrhagic complications.^16,17 If the fetus is mature, a hemorrhagic AVM should be resected at an early stage postpartum.¹⁴ Robinson et al. reported that when mothers with hemorrhagic AVM were treated by neurosurgical operation, there were no deaths among the mothers, fetal mortality was 26%, 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 grade I and II) were elective operation excision; all three cases had a good prognosis.

Endovascular embolization for cerebral AVM in pregnancy

Endovascular embolization for cerebral AVM in pregnancy should accord with their clinical manifestations and angiographic features. Radioactive diagnosis and treatment methods should not be applied to cerebral AVM in pregnancy unless they are necessary. Radiation effects on maternal and fetal recipients vary according to their development stage and irradiation dose.^19–21 In the first week (0–8 days), 100 mGy could prove fatal for an embryo.¹⁹ During the period of organ development (2–8 weeks), 500 mGy will affect 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 the AVM. Some reports have shown 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 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 for even 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. Recently, Pumar et al. reported eight cases of ruptured aneurysm in pregnancy and concluded that endovascular embolization was safe and effective in the period of pregnancy for ruptured aneurysms.²⁶

Dashti et al. reported a case of cerebellar hemorrhage (AVM Spetzler–Martin IV) at 20 weeks of pregnancy with two fetuses.²⁷ The AVM was treated by Onyx embolization and fetal exposure radiation dose was very low (1.9 × 10⁻³⁰mGy). They suggested that the ethylene–vinyl alcohol copolymer in Onyx is an inert chemical and it was not clear whether the clinical dose of organic solvent dimethyl sulfoxide 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 whom 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, 24 weeks pregnant, treated with linear accelerator radiosurgery.²³ The intracranial target dose was 20 Gy, under lead shielding protection, and the abdominal area dose was 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 and fetal exposure dose was 1.5–3.1 mGy. The radiation safety threshold at 16–25 weeks was 250 mGy and was 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 study about delivery mode and AVM bleeding risk.^2,3,6,12,31 Although AVM rupture in the childbirth process does not seem more likely, 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 in the stress on the vessel wall. If the AVM has been completely removed, the method of delivery should accord to the obstetric indications.

Conclusion

Case reports and studies on cerebral AVM treatment during pregnancy are seldom. The treatment strategy depends 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 of fetal effects. The hemorrhagic risk of AVM will increase during pregnancy, so ruptured cerebral AVM in pregnancy should be treated actively. An unruptured AVM in pregnancy should be observed conservatively, provided there are no bleeding factors such as no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment. 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 the rebleeding risk in puerperal. Unruptured AVM presenting with epilepsy should be treated according to obstetric indications and should be treated as non-pregnant women after birth. If intracranial hemorrhage occurs in pregnancy, whether treated or not, attention should be paid to adverse effects of drugs commonly used in neurosurgery on the fetus.