Cerebral arteriovenous malformation rupture in pregnancy

Abstract

A 30-year-old nulliparous woman at 38 5/7 weeks of gestation developed a sudden, severe headache at work and subsequent loss of consciousness. She underwent evaluation in the emergency department. CT and CT angiogram head revealed a large intraparenchymal haematoma with intraventricular extension secondary to ruptured cerebral arteriovenous malformation (cAVM). She was intubated and transferred to a tertiary care centre. The patient underwent caesarean section followed by partial embolisation of the cAVM with planned second embolisation and resection 1 week later. Due to drowsiness and headache, the planned repeat embolisation and cAVM resection were performed 3 days earlier. The patient had a full recovery. Emergency medicine physicians and obstetrician-gynaecologists should be familiar with differential diagnosis of sudden headache in pregnancy and signs of a ruptured cAVM to facilitate early diagnosis, multidisciplinary team approach and timely treatment. Early diagnosis and management of ruptured cAVM are important due to associated morbidity and mortality.

Background

Cerebral arteriovenous malformations (cAVMs) are uncommon congenital vascular lesions, occurring in approximately 0.01%–0.5% of the population.¹ The annual haemorrhage rate of cAVMs is about 2%–4% per year.^2–4 Goldberg et al found in their systematic review an average annualised haemorrhage rate of 2.2% for previously unruptured cAVM and 4.3% for cAVMs that present with haemorrhage.⁵ Overall, the risk of cAVM bleed in pregnancy is estimated to be approximately 1 in 10 000 pregnancies.⁶

Some common signs and symptoms seen in a patient with cAVM include headache, seizure, confusion, muscle weakness, aphasia, vertigo and hallucinations.⁷ In one study, headache, vomiting, limb dysfunction and altered consciousness were the main clinical manifestations in 12 patients with a cAVM bleed during pregnancy and the postpartum period.⁶ These symptoms may be mistaken for other conditions associated with pregnancy such as migraine, preeclampsia, eclampsia and cerebral venous sinus thrombosis. It is imperative that an accurate diagnosis is made so that treatment can be initiated promptly.

Case presentation

The patient was a 30-year-old nulliparous woman. Her obstetric history was positive for two prior spontaneous miscarriages. Her medical history included hypothyroidism and cholecystectomy. Her family history was insignificant and without history of hypertension, stroke or cAVMs. She had no history of drug or alcohol abuse. She was a medical professional. Her medications included daily prenatal vitamins. Her prenatal care was routine and without complication.

At 38 5/7 weeks of gestation, the patient developed a sudden and severe headache at work. She went to a dark room to see if her headache would improve. She was found unresponsive by her colleagues an hour later and was transferred to the nearest emergency department for evaluation. CT scan of the head demonstrated a right frontal intraparenchymal haematoma (IPH) with intraventricular extension (IVE). CT angiography (CTA) of the head revealed a frontal basal interhemispheric cAVM. She was intubated for airway protection and was transferred to our institution for higher level of care.

On arrival, her initial vital signs were stable: heart rate 95 bpm, blood pressure 138/94 mm Hg, respiratory rate 34 breaths/min, temperature 37.4°C, SpO₂ 100%. Neurological examination demonstrated a Glasgow Coma Scale (GCS) score of 10: she was able to open her eyes to voice, follow simple commands symmetrically and was intubated. Given the patient’s stable neurological status, an emergent neurosurgical procedure was not required and a multidisciplinary management strategy by the neurosurgery and obstetrics team was established. The plan was made to deliver the fetus via caesarean section under general anaesthesia immediately prior to cerebral angiogram and attempted endovascular embolisation of her cAVM to avoid unnecessary radiation exposure to the fetus, limit any potential increase in intracranial pressure (ICP) from delivery and expedite delivery. The patient’s condition and management plan were discussed in detail with her husband. Informed consent for surgery was obtained via her husband. The patient was admitted to the intensive care unit, and hyperosmolar therapy with serum sodium goal of 145–150 mEq/L was initiated to mitigate increased ICP. From an obstetric standpoint, the fetal heart rate remained reassuring.

Investigations

CT of the head revealed a 4.3×4.6 cm right frontal IPH with IVE (figure 1). CTA of the head revealed a frontal basal interhemispheric cAVM with a 3.5 cm nidus (figure 2A–D). After delivery and prior to partial embolisation, cerebral angiogram was performed, which demonstrated a frontal basal interhemispheric cAVM with a nidus measuring 3.5 cm (figure 3A,B). The cAVM was supplied primarily by the right anterior cerebral artery. There was a large venous varix present and venous drainage was through the superior sagittal sinus (SSS).

Figure 1.

CT head of right frontal intraparenchymal haematoma with intraventricular extension.

Figure 2.

(A,B) Initial coronal and sagittal CT angiography (CTA) at the time of patient’s presentation demonstrating a large intraparenchymal haematoma with an underlying vascular lesion concerning a cerebral arteriovenous malformation (cAVM). (A) Coronal view demonstrating frontal basal interhemispheric cAVM with a nidus measuring 3.5 cm. (B) Sagittal view demonstrating superficial cortical veins draining the cAVM via the superior sagittal sinus. (C,D) Three-dimensional reconstruction of the CTA demonstrating on coronal and sagittal views that the cAVM appears to be supplied by the right anterior cerebral artery.

Figure 3.

(A,B) Preoperative right internal carotid artery (ICA) cerebral angiogram. (A) Anteriorposterior (A/P) projection demonstrating a compact cerebral arteriovenous malformation (cAVM) nidus measuring 3.5 cm in maximal diameter that is supplied by the right anterior cerebral artery. (B) Lateral projection demonstrating the superficial drainage pattern of the cAVM via the superior sagittal sinus. A venous varix is clearly seen. (C,D) Right ICA cerebral angiogram A/P and lateral projections following stage 1 microcatheter embolisation of cAVM. This reduced the nidus volume by approximately 50%–75%.

Differential diagnosis

The differential diagnosis of a pregnant patient with a sudden severe headache and loss of consciousness includes eclampsia, cerebral venous thrombosis, pituitary apoplexy, vertebral or carotid artery dissection, reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome. Abrupt onset of focal neurological symptoms is concerning for vascular aetiology.⁸

Treatment

The patient remained neurologically stable with a clear examination that could be closely followed. To prevent rise in ICP, hyperosmolar therapy was initiated. The fetus was of term age and remained stable. The patient’s stable neurological status allowed the obstetrics team to intervene. The patient underwent a successful caesarean delivery under general anaesthesia of a healthy male infant on hospital day 1. This removed the infant from any complications that could occur during neurosurgical interventions.

The patient subsequently underwent a cerebral angiogram. The angiographic architecture of the cAVM allowed for successful stage 1 microcatheter embolisation with Onyx and reduced the cAVM nidus by 50%–75% (figure 3C,D). The remainder of the nidus was to be embolised during a second stage the following week. An MRI was obtained for surgical planning (figure 4).

Figure 4.

Axial, sagittal and coronal MRI T2 sequence following embolisation of cerebral arteriovenous malformation (cAVM). Approximately 50% of the cAVM remains and is supplied by the right anterior cerebral artery. The venous drainage is via the superior sagittal sinus. There is T2 hyperintensity demonstrating oedema surrounding the intraparenchymal haematoma.

The following day, the patient was extubated. She was found to be somnolent on hospital day 4, although the patient remained with a GCS 14. Therefore, definitive treatment of the cAVM was expedited and performed on hospital day 5. The second stage of embolisation followed by a bifrontal craniotomy for evacuation of right frontal intracerebral haematoma and microsurgical resection of arteriovenous malformation (AVM) were performed successfully. Intraoperative cerebral angiogram confirmed successful removal.

Outcome and follow-up

Postoperatively, the patient returned to the neuroscience ICU for recovery. Her infant son recovered well following delivery and was discharged on day 3 of life. The patient underwent a postoperative CTA of the head, which did not demonstrate residual cAVM or any concerning acute findings (figure 5A,B). The patient underwent a CTA of the chest due to cough with low-grade fevers and to rule out hereditary haemorrhagic telangiectasia, which was normal and did not demonstrate pulmonary arteriovenous malformations. Neurological examination demonstrated that the patient had slow mentation and processing, would move extremities with good resistance and could follow simple commands with guidance. She remained stable during an uncomplicated postoperative course and was transferred to inpatient rehabilitation to receive intensive physical, occupational and speech therapy. The patient followed up in clinic with obstetrics and neurosurgery 2 months after discharge from inpatient rehabilitation. The patient demonstrated significant improvement on neurological examination and had returned to work after completing her maternity leave. At 1 year neurosurgical follow-up, the patient was neurologically intact, performing activities of daily living and working successfully at her previous job. An MRI/MR angiography (MRA) brain 1 year from resection of her cAVM demonstrated no evidence of any residual cAVM.

Figure 5.

(A,B) Coronal and sagittal CT angiography following microsurgical resection of cerebral arteriovenous malformation (cAVM). Clips are visualised adjacent to the right anterior cerebral artery where feeders to the cAVM were divided and resected. The venous drainage via the superior sagittal sinus is no longer present.

Discussion

The natural history of cAVMs during pregnancy is largely unknown.^{2 6 8} Blood flow through the middle cerebral artery has been shown to decrease during pregnancy, though early on in pregnancy, blood flow may be increased throughout most of the brain.^{9 10} Progesterone and oestrogen have been speculated to act as vasoactive mediators during pregnancy and perhaps contribute to any vasodilatory effect seen during this time.^{9 10} It has been speculated that some other vasomediators may have a pronounced effect on cerebral blood flow early on in pregnancy.¹⁰

Impact of pregnancy on cAVM rupture is controversial due to inconsistency among rates reported in the literature.⁴ Factors such as increasing age, initial haemorrhagic cAVM presentation, deep brain location, presence of associated aneurysms, deep venous drainage, small nidus size and high feeding artery pressure have been determined to be independent predictors of cAVM haemorrhage.^{7 11} Specifically, prior haemorrhage and deep cAVM location have been identified most consistently as a risk factor for future haemorrhage.⁵ With respect to pregnancy, Liu et al report no change in risk of haemorrhage during pregnancy (3.1%) in a retrospective review of 979 women diagnosed with a cAVM.¹² Zhu et al found in their single-centre case series a haemorrhage risk of 5.59% during pregnancy and puerperium and a 2.52% risk in the non-pregnant period.⁴ Looking specifically at the North American population, Porras et al and Gross et al found an increased cAVM haemorrhage risk in pregnancy: 5.7% versus 1.3% and 8.1% versus 1.1%, respectively.^{4 13 14} cAVMs are typically identified by CT/CTA head or MRI brain as these studies are more readily available and are non-invasive in comparison with catheter-based cerebral angiogram. In the setting of concern for spontaneous intracerebral haemorrhage, the American Heart Association/American Stroke Association recommend rapid non-contrast CT or MRI.¹⁵ CT is very sensitive for identifying acute haemorrhage.¹⁵ CT/CTA head can be safely performed in pregnancy with lead shielding of the abdomen and pelvis.¹⁶ Shielded fetal radiation exposure is less than 0.005 mGy.^{16 17} Fetal exposure with CTA or cerebral angiogram is less than 0.025 mGy.¹⁸ The adverse effects on the fetus from iodine-based contrast studies appear to be low.¹⁹ MRI safety in pregnancy is well established. MRI is as sensitive as CT for detection of acute haemorrhage and is more sensitive for detecting chronic haemorrhage.²⁰ MRA is highly sensitive and specific for detection of intracranial vascular malformations.²¹ However, in comparison with CT/CTA, the time, proximity to the ED, patient tolerance, clinical status and MRI availability may preclude emergent MRI.²² Intra-arterial digital subtraction angiography is considered the ‘standard’ for diagnosing arteriovenous malformations, dural arteriovenous fistulae and aneurysms and is required to plan appropriate treatment strategies, which include surgical resection, endovascular embolisation, radiation, observation or a combination of these modalities.²¹

The exact threshold for the decision to operate on a pregnant woman with a known cAVM is debatable; however, in the setting of a haemorrhage from a ruptured cAVM, there is an increased urgency to remove a cAVM due to the risk of rebleeding and increased ICP from the surrounding haematoma.^{23 24} Overall, the maternal management of patients with cAVM haemorrhage should be based on neurological indications rather than obstetrical indications.²⁵

Once the decision is made to intervene, the major treatment options include microsurgery, radiosurgery and endovascular embolisation techniques.1 2 26 27 Grading systems for cAVMs have been proposed to stratify morbidity and mortality of microsurgical resection of these lesions. The Spetzler-Martin grading scale provides a preliminary assessment of surgical risk based on nidus size, pattern of venous drainage and neurological eloquence of adjacent brain.²⁸ The points are added to give a Spetzler-Martin grade of I to VI. The authors of the original study found that major postoperative deficits were found in 0% of grades I and II patients, 4% of grade III patients, 7% of grade IV patients and 12% of grade V patients. These deficits included prolonged hemiparesis, persistent dense aphasia and persistent homonymous hemianopsia. Based on these results, grades I to III cAVMs have been traditionally considered amenable for safe microsurgical resections and grades IV and V unsafe for microsurgical resection.

In an effort to further refine patient selection for microsurgical resection of cAVMs, Lawton et al proposed a supplementary grading scale to the original Spetzler-Martin scale.²⁹ Lawton et al performed a prospective analysis to test the association of specific variables with change in the modified Rankin Scale.²⁹ This study demonstrated that patient age in years (<20, 20–40, >40), non-hemorrhagic presentation and diffuseness of nidus were significant factors in addition to those in the original grading scale. The age cut-offs were intended to capture paediatric patients and to separate adults with and without significant comorbidities. Haemorrhagic presentation and less diffuse nidus both have more distinct planes between AVM and normal brain and facilitate surgical resection. The supplementary grading scale assigns points in a fashion analogous to the original scale.

Our patient would be assigned points as follows: 2 for nidus size of 3.5 cm, 0 for superficial venous drainage to SSS, 0 for non-eloquent location, 2 for age of 30 years, 0 for ruptured presentation and 0 for compact nidus. Based on these points, our patient’s cAVM is a Spetzler-Martin grade II of V, supplementary grade II of V and combined grade IV of X. Our patient was a low grade according to both individual scales and would have an 85% chance of improved or at the least unchanged neurological outcome.²⁹ Therefore, in our patient’s case, the supplementary grade further strengthens the recommendation for microsurgical resection as suggested by the patient’s cAVM Spetzler-Martin grade.

Potential complications of such interventions include risk of intraoperative bleeding, which can compromise uteroplacental perfusion, fetal exposure to contrast media and radiation risk. Endovascular surgery and stereotactic radiosurgery expose patients and fetuses to varying degrees of radiation. Fetal radiation impact depends on the gestational age and dose with lead shielding. A fetal dose of 10–20 mGy may increase the risk of leukaemia to 1 in 2000 children compared with 1 in 3000 for the general population between the gestational ages of 8 and 15 weeks.³⁰ The risk of fetal anomalies, growth restriction and miscarriage are not increased with radiation doses <50 mGy.³¹ Marshman et al measured and extrapolated absorbed fetal doses ranging from 0.17 to 2.8 mGy assuming screening durations of 0–30 s for the femoral region and 15–45 min to the head.³¹ Dashti et al extrapolated radiation doses of 1.9×10^–30 mGy to twin fetuses primarily from scatter from cranial focus.³² Delivery with subsequent endovascular embolisation was chosen in our case to decrease radiation exposure to the term fetus and decrease potential comorbidities of surgery. These risks should be considered in the preoperative evaluation without withholding necessary treatment or limiting treatment options that could potentially decrease mortality risk of the mother and ultimately fetus.

The treatment options and recommendations will differ depending on gestational age at presentation and the acuity of the cAVM. An emergency surgery is necessary for cAVM haemorrhage in pregnancy if the intracranial haematoma causes worsening neurological symptoms or evidence of cerebral herniation.³³ Due to risk of re-bleed, ruptured cAVMs are recommended to be treated prior to or during pregnancy.³⁴ Delivery route is dependent on gestational age at diagnosis and presentation. Vaginal delivery may not increase risk of haemorrhage in cAVMs in pregnancy.³⁴ Caesarean delivery has been preferred due to better control of maternal blood pressure and avoidance of haemodynamic changes of intracranial vascular pressure. There are reports of vaginal delivery without adverse outcomes.³⁴

In conclusion, we report a case of a 30-year-old woman of term pregnancy found to have a ruptured cAVM on presentation with headache and altered mental status. The complexity of the patient and fetus’ condition required an interdisciplinary approach. We demonstrate that good long-term outcome can be achieved in such a medical conundrum with a well-formulated, interdisciplinary, timely and multimodality management strategy.

Patient’s perspective.

I remember waking up that morning with a severe migraine. I thought it was a migraine. I drove to work like usual and recall being there a little that morning. From that point until approximately 3 weeks later, I have no memory of anything that took place. Once I regained my memory, I had been transferred to in-patient rehabilitation. I remember my energy level being very low as I began daily physical, occupational and speech therapy. As the next several months went by, I slowly began regaining energy and strength while I was trying to return to normal life at home, except with a newborn.

Learning points.

• Headache is a common complaint of pregnant women. Headaches associated with altered mental status, seizures, changes in vision, neck stiffness, sudden and severe onset, awakens from sleep, unrelieved by pain medication and preceded by fever, head trauma, exertion, substance abuse or Valsalva manoeuvre require prompt evaluation.

• Timely recognition of signs and symptoms of a ruptured cerebral arteriovenous malformation (cAVM) in pregnancy is crucial for optimal outcomes of mother and child.

• Obstetric and perioperative treatment of a cAVM haemorrhage should be managed by a multidisciplinary team including obstetrics, neurosurgery, neurology and anaesthesia.

• Cerebral angiography and endovascular embolisation with lead shielding for ruptured cAVM are reasonable in pregnancy when necessary.