Outcome of a Late Preterm Infant With Prenatally Diagnosed Vein of Galen Malformation

A 31-year-old Gravida 4, Para 3 woman was referred to our fetal health center because of a concerning prenatal ultrasonogram that showed a posterior fossa abnormality. Fetal magnetic resonance imaging (MRI) obtained at 36 weeks’ gestation showed aneurysmal dilatation of the median prominent cephalic vein, which drained into the straight sinus with a moderately dilated transverse sinus, and no fetal hydrops (Figure 1). Fetal echocardiography at 36.5 weeks’ gestation revealed cardiomegaly, a dilated superior vena cava, and reversal of flow in the aortic isthmus and arch; all these findings were thought to be attributed to steal in the low-resistance vein of Galen malformation (VGM). Most importantly, the combined cardiac output was calculated to be 719 (normal: 400–600), which was suggestive of high output cardiac failure. Neurosurgery met with the family and discussed that given the change in cardiac status, they recommended to proceed with delivery and start with initial medical management after birth with endovascular management later if the infant is stable. Cardiology also met with the family and recommended urgent delivery. As a result, delivery was induced at 36 6/7 weeks’ gestation.The female infant was born by vaginal delivery and emerged with a spontaneous cry but had cyanosis and tachypnea that was treated with 2-L humidified high-flow nasal cannula with fraction of inspired oxygen (FIO2) of 0.3. Her Apgar score was 6 and 9 at 1 and 5 minutes after birth, respectively. The infant’s birth weight was 4.2 kg (80th percentile), length was 50 cm (58th percentile), and head circumference was 35.5 cm (54th percentile). Umbilical lines were placed in the delivery room, and the infant was transferred to the neonatal intensive care unit for further management. A chest radiograph was obtained that showed appropriate lung expansion with mild cardiomegaly (Figure 2). The infant remained on supplemental oxygen and started on total parenteral nutrition. A postnatal echocardiogram showed a mildly hypoplastic aortic arch with a wide bidirectional patent ductus arteriosus, a mildly dilated right ventricle with normal systolic function, and normal left ventricular size and systolic function. Postnatal brain MRI performed 1 day after birth revealed a large void in the region of the porencephalic vein (Figure 3A), and MR angiography noted multiple arterial feeders (Figure 3B, blue arrows) from the posterior cerebral and choroidal arteries and venous drainage into the transverse sinus.Two days after birth, the infant transitioned to room air and started on oral feedings. She had a short, self-limited supraventricular tachycardia event 2 days after birth, which was secondary to a deep umbilical venous catheter; this arrhythmia did not recur after the removal of the central line. The infant continued in room air but had intermittent tachypnea. At 4 days of age, her tachypnea persisted and she was started on a low-flow nasal cannula at 0.1 L with an FiO2 of 1.0. Follow-up echocardiography at 5 days of age showed pulmonary hypertension and a moderately dilated right ventricle with qualitatively low-normal systolic function. Two days later, her echocardiography showed that her left ventricular ejection fraction had decreased from 60% to 45%; she continued to have a moderately dilated right ventricle with mildly diminished systolic function and suprasystemic right ventricular pressures. With worsening pulmonary hypertension and heart function, her feedings were discontinued and her respiratory support was increased to 0.5-L nasal cannula. She was treated with daily diuretics and low-dose milrinone because of progressively worsening left ventricular dilation and a lower left ventricular ejection fraction leading to renal and hepatic insufficiency. A peripheral arterial line was placed for continuous blood pressure monitoring. The cardiac failure biomarker N-terminal pro-B-Type natriuretic peptide (NT-Pro-BNP) level was elevated at 30 000 pg/mL at 7 days of age.The infant was urgently transferred to another facility for neurosurgical intervention due to worsening high-output heart failure. She underwent endovascular glue embolization of 3 large feeding pedicles of the VGM at 14 days of age. Endovascular embolization was done with n-butyl cyanoacrylate using a right femoral artery approach in the operating room by neurosurgery. There was rapid improvement after the procedure with normalization of hepatic and renal function and resolution of cardiac failure. She was weaned to room air and reached full oral feedings on postoperative day 6. The infant was discharged home at 26 days of age in room air with full oral feedings. She passed her hearing screen prior to discharge home.Follow-up at 2 months of age showed normal biventricular function with mild left ventricular dilatation. She was growing appropriately with a weight of 5.5 kg (80th percentile), height of 57 cm (40th percentile), and head circumference of 39 cm (60th percentile). She had normal developmental milestones. Follow-up brain MRI at 3 months of age showed that the lesion was smaller than at birth and there was no hydrocephalus. The neurosurgery team made a tentative plan for further embolization at 6 months of age.Unfortunately, she was readmitted to the pediatric floor in our hospital at 4 months of age due to progressive hydrocephalus requiring a third ventriculostomy. A gastrostomy tube was placed, and she was discharged home without any further readmissions. Her recent echocardiogram at 8 months of age shows normal function, and her brain MRI remains stable with no hydrocephalus. At her most recent visit to the follow-up clinic at 8 months of age, she is doing well in room air with gastrostomy tube feedings. She is growing well with a weight of 9.5 kg (87th percentile), length of 74 cm (92nd percentile), and head circumference of 44 cm (68th percentile) at 8 months of age (Figure 4). Developmentally, at 8 months of age she was reaching and grabbing for her gastrostomy-tube extension tubing and teething on crackers and her pacifier, and she was able to bring these items to her mouth. She was lifting her feet and toes to her mouth, laughing, giggling, spitting, and blowing bubbles, but not yet babbling. She is sitting well with forward propping but dislikes tummy time. She can roll from her stomach to her back and can roll from her back to side. She can scoot on her back to travel. She has increased tone in her right leg but uses all 4 extremities. She has passed a follow-up hearing screen and receives occupational, speech, and physical therapy through early intervention services once a week.VGM is a congenital malformation involving the arteriovenous system of the embryonic choroid plexus and is quite rare.1 Although the incidence of VGM is less than 1 in 25 000 live births,2 it constitutes 30% of pediatric vascular anomalies3 and 1% of all pediatric congenital anomalies.The arterial supply to the choroidal plexus comes from the internal carotid artery and venous drainage in utero is through the median prosencephalic vein (MprosV) of Markowski.2 By 11 weeks of gestation, the arterial network of the cortex matures and the choroidal arteries lose their control in central vascularization.4,5 Paired internal cerebral veins then develop and drain into the choroid plexus, which terminates in the posterior portion of MProsV of Markowski and begins to involute by 10 to 11 weeks of gestation. After involution, the remaining caudal portion of the MprosV joins the internal cerebral veins to form the VGM.6,7 Once the VGM develops, it results in arteriovenous shunts between the choroidal circulation and MProsV of Markoswki. The arterial feeders for the VGM include the choroidal arteries and anterior cerebral arteries in addition to a small contribution from circumferential arteries, mesencephalic vessels, and some ependymal vessels of the posterior circle of Willis. Because of these shunts, the MProsV of Markowski remains patent and keeps enlarging resulting in the formation of VGM.8,9In VGM, the vein of Galen dilates because the high flow into the fistula does not allow a normal dural sinus to form. There is persistence of fetal sinuses such as the falcine sinus that connects the MprosV to the superior sagittal sinus. Other variations include persistence of the hypoplastic or absent straight sinuses.The 2 most common classifications of VGM are Lasjaunias8 and Yasargil.10 Lasjaunias described primary or true VGM and a secondary type where a deep arteriovenous malformation drains into the vein of Galen. The primary type is further subdivided into the mural and choroidal type. The mural type has multiple direct arterial connections into the MProsV of Markowski, whereas the choroidal type has many choroidal feeders from a nidal network that drains into MProsV of Markowski. The mural type is associated with absence or stenosis of dural sinuses and stenosis at the level of jugular foramen; affected patients present with hydrocephalus later during infancy. The choroidal type has more severe shunts and affected patients present earlier in the neonatal period with high output cardiac failure because of multiple high-flow fistulas with less outflow obstruction.Yasargil proposed 4 types based on arterial feeders10: Type I consists of 1 or more direct fistulous connections between the vein of Galen and the pericallosal/posterior cerebral arteries.Type II consists of a thalamoperforator network between the arterial feeders and the vein of Galen.Type III consists of multiple fistulas from different vessels with characteristics of type I and II malformations.Type IV consists of arteriovenous malformations that drain into the vein of Galen leading to a secondary aneurysmal venous dilatation.In the primary type described by Lasjaunias and Yasagil’s types I to III, the MprosV of Markowskii is the pathological vessel, hence representing a true VGM. The dilation of vein of Galen in the secondary type in the Lasjuanias classification and type IV in the Yasagil classification are a result of arteriovenous malformations.The presentation of an infant with VGM varies depending on the age of the patient. In utero, the low-resistance placental circulation competes with the VGM for blood flow and thus limits the blood flow through the VGM. However, soon after birth, the low resistance in the VGM steals almost 80% of the cardiac output to the cerebral circulation resulting in increased venous return and right ventricular dilatation. The presence of right-to-left shunts through the foramen ovale and ductus arteriosus decrease coronary blood flow leading to myocardial ischemia.2 Diastolic flow reversal in the descending aorta can lead to hepatic and renal insufficiency.11 Most neonates present with high output cardiac failure. Other presentations in neonates include pulmonary hypertension, seizures, and multiorgan failure. The most common cardiac manifestations include symptoms of congestive heart failure like tachypnea, cyanosis, and tachycardia, which worsens within the first few days after birth.Neurological manifestations like hydrocephalus and macrocrania usually appear late during infancy. Communicating hydrocephalus usually results from decreased absorption of cerebrospinal fluid because of increased pressure in the venous sinuses.4 Other manifestations include cerebral atrophy, irreversible brain damage, progressive developmental decline, and seizures.4 Hydrocephalus is a secondary phenomenon and can significantly improve after embolization. Older infants may present with a headache or intracranial hemorrhage.A VGM is visible by routine prenatal ultrasonography starting at 11 to 13 weeks of gestation. Antepartum diagnosis has improved in recent years from 11% in 199412 to 73% in 2019.10 Routine prenatal ultrasonogram screening can detect the majority of VGMs with fetal MRI being used for more detailed evaluation. Prenatal ultrasonogram can demonstrate a dilated venous sac posterior to the third ventricle. This sac is differentiated from other cysts because of the pulsatile flow within the venous sac on color Doppler.13 Cardiac abnormalities due to the VGM such as signs of right heart failure and cerebral malformations like ventriculomegaly can also be appreciated by prenatal imaging. Postnatal investigations include MRI with MR venography/MR angiography and computed tomography angiography, which provided information about the arterial feeders and size of the malformation. Postnatal laboratory testing includes assessment of liver and renal function to assess for hepatic and or renal ischemia. Cardiac function can be determined by NT-Pro-BNP levels as well as echocardiography.Management of patients with a VGM is challenging. Historically, the treatment of VGM was surgical but surgical results have been associated with high mortality and morbidity.9 Recent emphasis has been placed on the preservation of normal brain development without creating any new neurological deficits, which is best achieved by minimally invasive techniques such as endovascular intervention. Following intrauterine diagnosis, the goal is to continue the pregnancy until as close to term gestational age as possible because embolization in infants weighing less than 2500 g carries risk of major cerebral hemorrhage.14 However, if the fetal MRI demonstrates pseudo feeders of the middle cerebral artery or loss of white-gray matter differentiation, delivery may need to be earlier so that an emergency embolization can be performed (ideally, when the infant weighs more than 2000 g).15 Delivery of the infant in a tertiary referral center is recommended because of the risk of cardiac decompensation in the hours following birth14 with the potential need for access to emergency embolization.Management of infants with a VGM depends on the patient’s age and severity of presentation and is divided into medical, endovascular, and surgical approaches. A team approach that includes but is not limited to neurology, neurosurgery, interventional radiology, cardiology, and neonatology is recommended given the complexity of these patients. The main aim of medical management in VGM is to stabilize cardiac and other systemic complications so endovascular intervention can be performed16 at approximately 5 to 6 months of age. The associated increased venous flow combined with high-output cardiac failure can lead to renal and/or hepatic insufficiency and myocardial ischemia and prevent closure of the ductus arteriosus. Treatment options include the use of diuretics and pulmonary vasodilators to decrease the flow to the VGM. If there is a need for escalating medical management such as using multiple inotropes in the immediate neonatal period, it is usually associated with poor outcomes.Endovascular treatment is the preferred modality as primary surgery is associated with high mortality. The endovascular treatment aims to maintain hemodynamic balance and attain a physiologic rather than anatomic cure. This leads to favorable neurologic and developmental outcomes.17 Complete VGM exclusion produces a sudden reversal of blood flow with consequent venous infarction and ischemia;18 hence, a stepwise approach is preferred. The first treatment is delayed, preferably until 4 to 6 months of age, provided that the infant is stable. Endovascular embolization can be done using the transarterial or transvenous route. The transvenous approach is associated with a higher morbidity because of risk of hemorrhage, venous infarction, and consumptive coagulopathy.4,17 Hence, the transvenous approach is used only when the transarterial approach is not possible. If treatment is required within the first few days after birth, the umbilical artery can be used for access. Otherwise, the femoral artery or vein is preferred.In the United States, there are 2 liquid embolic agents available: n-butyl cyanoacrylate (Trufill, Codman Neurovascular) and ethylene vinyl alcohol copolymer (onyx, Micro therapeutics).1,19 N-butyl cyanoacrylate is preferred for its reliability and safety.14 Endovascular embolization can also be done using detachable microcoils.Intraoperative risks during embolization include rapid fluid shifts and is important to maintain cardiac output with good oxygenation and ventilation. Other surgical risks include air embolism and glue migration. Surgery usually plays an adjunctive role in the treatment of hydrocephalus. Diversion of the increased cerebrospinal fluid can be done by shunting or ventriculostomy. Surgery also plays a part in the evacuation of intracranial hematomas. If the embolization attempts fail, surgery remains a last-resort intervention.A common tool used for prognostication is the Bicetre score,1 which is a 21-point score based on the function of the cardiac, cerebral, respiratory, hepatic, and renal systems. Each system gets a score of 0 to 3 depending on the function. When the Bicetre score is less than 8, it indicates a grave prognosis and no treatment is considered. When the score is between 8 and 12, the recommendation is urgent embolization. A score between 12 and 21 suggests that the infant is stable and allows for postponement of the endovascular treatment to age 5 months.A newer classification proposed by Mortazavi et al considers the arterial feeders, clinical symptoms of heart failure, and age (<5 months vs ≥5 months) with a score of 0 or 1 for each factor with a total of up to 3.20 The proposed treatment recommendation would be endovascular (no urgency) for patients with 0 to 1 points, endovascular (urgency, multiple stages) for patients with 2 points, and endovascular or palliative approach for patients with 3 points.VGM associated with antenatal cardiac failure carries an 80% mortality risk,12 and those with severe antenatal cerebral damage may have irreversible multiorgan failure. The volume of malformation recently has been a prognostic item of interest. With the advent of endovascular embolization, the prognosis for neonatal VGM has improved although neonatal mortality is higher than mortality in infants and children. Emerging therapies include transuterine ultrasonogram-guides and fetal embolization of the VGM, which eliminates postnatal pathophysiology. Targeted gene therapy is still under investigation.VGM is a congenital vascular malformation that has improved prognosis with prompt management. It is often diagnosed during routine prenatal ultrasonography and requires multidisciplinary delivery and postnatal management at a tertiary-level hospital.Most affected neonates present with high-output cardiac failure. Other presentations in neonates include pulmonary hypertension, seizures, and multiorgan failure. Neurological manifestations like cerebral atrophy and irreversible brain damage with hydrocephalus may be seen as a secondary phenomenon.Postnatal investigations include cranial ultrasonogram, MRI, MR angiography, MR venography, and computed angiography.Management in the acute phase is the stabilization of an infant with diuretics, inotropes, and pulmonary vasodilators until endovascular intervention can be performed at approximately 5 to 6 months of age. A stepwise endovascular management with embolization restores hemodynamic balance and is the treatment modality of choice for infants.Emerging therapies include transuterine ultrasonogram-guided fetal embolization, thus eliminating postnatal pathophysiology.American Board of Pediatrics Neonatal-Perinatal Content SpecificationRecognize issues pertaining to the physiology of the nervous systemUnderstand neurologic examination and developmental evaluation regarding VGM.