Vein of Galen Malformations: Epidemiology, Clinical Presentations, Management

The vein of Galen aneurysmal malformation is a congenital vascular malformation that comprises 30% of the pediatric vascular and 1% of all pediatric congenital anomalies. Treatment is dependent on the timing of presentation and clinical manifestations. With the development of endovascular techniques, treatment paradigms have changed and clinical outcomes have significantly improved. In this article, the developmental embryology, clinical features and pathophysiology, diagnostic workup, and management strategies are reviewed.

The vein of Galen aneurysmal malformation (VGAM) is a congenital vascular malformation that comprises 30% of the pediatric vascular and 1% of all pediatric congenital anomalies. Abnormal development causes shunting of arterial blood into the median prosencephalic vein (MProsV) of Markowski, which is the ectatic vessel. Although this vein is a precursor of the vein of Galen, it is a separate entity, making the term vein of Galen malformation a misnomer. The rare nature of these lesions, along with differences in their evolution, presentation, angioarchitecture, and effects on systemic physiology, makes their management a formidable challenge.

Historical overview

The first published description of a presumed VGAM was in 1895 by Steinheil. However, this was an arteriovenous malformation (AVM) that drained into the vein of Galen and not a true VGAM. At the time, there was no distinction between a VGAM and an AVM that drained into the vein of Galen. In 1949, Boldrey and Miller treated 2 patients with “arteriovenous fistula of the cerebral vein of Galen” with carotid artery ligation. Of these 2 patients, the second patient likely represented a true VGAM. In 1955, Silverman and colleagues described 2 neonates who had died of cardiac failure without a primary cardiovascular disorder and were also found to have an AVM involving the vein of Galen. They were the first to suggest that a cerebral AVM could be the cause of cardiac failure. In 1964, Gold and colleagues were the first to classify patients with a VGAM into 3 different groups based on their presenting features. It was the first correlation between age of presentation, hemodynamic manifestations, and angioarchitecture of the lesion.

Treatment of VGAMs was initially surgical, but surgical results were associated with a high morbidity and mortality. In 1982, Hoffman and colleagues reported a series of 29 patients with VGAM. Of 29 patients, 16 were managed operatively, making it the largest reported surgical series at the time. They reported 56% mortality in patients treated with surgery. Based on their results and reported literature, they concluded that only surgical occlusion of the fistulous tracts, rather than resection of the lesion, was necessary. This differed from surgical management of other AVMs in which resection of the nidus was the operative goal.

With advances in imaging, microcatheters, and angiographic techniques, it has become possible to better define the angiographic anatomy of the VGAM. The ability to superselectively occlude vessels using coils and liquid embolic agents (in particular, n -butyl cyanoacrylate [ n -BCA]; Trufill, Codman Neurovascular, NJ, USA), has made it technically feasible to perform an endovascular approach to previously inaccessible, deep-seated lesions. In addition, selective vessel occlusion could be performed with improved mortality and morbidity compared with open surgical techniques. Lasjaunias and colleagues pioneered treatment of this condition and classified vein of Galen malformations in detail. In 1989, his group reported on the results of 36 patients treated via the transfemoral route with no morbidity and a 13% mortality. Thus, endovascular treatment became the primary treatment option for patients with a VGAM.

Anatomy and embryology of the vein of Galen

In normal neurovascular development, the choroid plexus becomes responsible for fluid circulation within the neural tube after closure of the anterior and posterior neuropores between gestational weeks 6 and 10. At this stage, the telencephalon is supplied by multiple choroidal arteries that arise from the choroid plexus. Concurrently, the MProsV of Markowski develops on the roof of the diencephalon and is responsible for the venous drainage. Between gestational weeks 10 and 11, the arterial network of the cortex matures and the choroidal arteries lose their central role in cerebral vascularization. Paired internal cerebral veins develop and drain the choroid plexus. The internal cerebral veins terminate in the posterior portion of the MProsV of Markowski, which at this point has begun to involute. Remnants of the caudal portion of the median prosencephalic vein then join the internal cerebral veins to form the vein of Galen.

When a VGAM develops, arteriovenous shunts form between the choroidal circulation and the MProsV of Markowski. The presence of these shunts keeps the MProsV of Markowski patent and promotes its enlargement, which forms the VGAM. It also prevents the normal formation of the vein of Galen. Raybaud and colleagues noted that the anterior choroidal arteries, posterior choroidal arteries, and anterior cerebral arteries drained directly into the VGAM. In addition, the circumferential, mesencephalic, meningeal, and, rarely, subependymal arteries anastomosed on the VGAM, although these are not usually a dominant feature of this malformation.

The deep cerebral venous anatomy of VGAMs is of particular importance and has been the subject of considerable debate. VGAMs may drain through a normal straight sinus and/or through a falcine sinus, a persistent embryonic sinus that joins to the posterior third of the superior sagittal sinus. Variations in drainage include hypoplastic or absent straight sinuses and multiple or sinuous falcine sinuses. The presence of a straight sinus does not preclude the existence of a VGAM. More important is the concept that, rather than being separate from the deep venous drainage system, a VGAM may maintain connections with the galenic system. This concept is critical in determining an endovascular treatment plan, because these drainage pathways may only be visible on follow-up imaging studies after endovascular treatment.

In contrast with the VGAM, adjacent parenchymal AVMs can cause aneurysmal dilatation of the vein of Galen. These dilatations are known as vein of Galen aneurysmal dilatations or varicosities and are different from VGAMs. Previously, no distinction existed between these 2 entities, which resulted in imprecise descriptions of the anatomic features and natural history of a VGAM.

Anatomy and embryology of the vein of Galen

In normal neurovascular development, the choroid plexus becomes responsible for fluid circulation within the neural tube after closure of the anterior and posterior neuropores between gestational weeks 6 and 10. At this stage, the telencephalon is supplied by multiple choroidal arteries that arise from the choroid plexus. Concurrently, the MProsV of Markowski develops on the roof of the diencephalon and is responsible for the venous drainage. Between gestational weeks 10 and 11, the arterial network of the cortex matures and the choroidal arteries lose their central role in cerebral vascularization. Paired internal cerebral veins develop and drain the choroid plexus. The internal cerebral veins terminate in the posterior portion of the MProsV of Markowski, which at this point has begun to involute. Remnants of the caudal portion of the median prosencephalic vein then join the internal cerebral veins to form the vein of Galen.

When a VGAM develops, arteriovenous shunts form between the choroidal circulation and the MProsV of Markowski. The presence of these shunts keeps the MProsV of Markowski patent and promotes its enlargement, which forms the VGAM. It also prevents the normal formation of the vein of Galen. Raybaud and colleagues noted that the anterior choroidal arteries, posterior choroidal arteries, and anterior cerebral arteries drained directly into the VGAM. In addition, the circumferential, mesencephalic, meningeal, and, rarely, subependymal arteries anastomosed on the VGAM, although these are not usually a dominant feature of this malformation.

The deep cerebral venous anatomy of VGAMs is of particular importance and has been the subject of considerable debate. VGAMs may drain through a normal straight sinus and/or through a falcine sinus, a persistent embryonic sinus that joins to the posterior third of the superior sagittal sinus. Variations in drainage include hypoplastic or absent straight sinuses and multiple or sinuous falcine sinuses. The presence of a straight sinus does not preclude the existence of a VGAM. More important is the concept that, rather than being separate from the deep venous drainage system, a VGAM may maintain connections with the galenic system. This concept is critical in determining an endovascular treatment plan, because these drainage pathways may only be visible on follow-up imaging studies after endovascular treatment.

In contrast with the VGAM, adjacent parenchymal AVMs can cause aneurysmal dilatation of the vein of Galen. These dilatations are known as vein of Galen aneurysmal dilatations or varicosities and are different from VGAMs. Previously, no distinction existed between these 2 entities, which resulted in imprecise descriptions of the anatomic features and natural history of a VGAM.

Classification

Various classification systems have been proposed for VGAMs. The 2 most clinically used systems are those of Lasjaunias and Yaşargil. Lasjaunias and colleagues described 2 angiographic types of aneurysmal malformations: a primary or true vein of Galen malformation and a secondary type resulting from a deep AVM that drains into the vein of Galen. The primary type was further subdivided into a mural type and a choroidal type. The mural type has 1 or many direct arterial connections into the wall of the MProsV of Markowski. The choroidal type has many choroidal feeders that form a nidal network that drains into the MProsV of Markowski.

Yaşargil proposed 4 types of aneurysmal malformations based on the arterial feeder patterns of drainage into the vein of Galen :

1.

Type I is made up of 1 or more direct fistulas between the pericallosal and posterior cerebral arteries and the vein of Galen ( Fig. 1 ).

Fig. 1

( A ) Lateral view from an angiogram of a Yaşargil type I VGAM. The black arrow points to the direct arteriovenous shunt between choroidal arteries and the vein of Galen (median prosencephalic vein of Markowski). ( B ) Yaşargil type I VGAM. Direct arterial feeders from the anterior and posterior circulation drain into the enlarged MProsV of Markowski. In addition, a persistent falcine sinus drains blood from the VGAM into the superior sagittal sinus, which can cause the straight sinus to be hypoplastic (as in this figure) or completely absent.

(Part [ A ] Courtesy of Gailloud P, MD. The Johns Hopkins Hospital.)
2.

Type II consists of a thalamoperforator network that lies between the arterial feeders and the vein of Galen ( Fig. 2 ).

Fig. 2

( A ) Lateral view from an angiogram of a Yaşargil type II VGAM. The white asterisk overlies the arterioarterial posterior thalamoperforator network supplying the VGAM. ( B ) Yaşargil type II VGAM. Arterial feeders are seen entering an arterioarterial niduslike network, which subsequently drain into the enlarged MProsV of Markowski.

(Part ( A ) Courtesy of Gailloud P, MD. The Johns Hopkins Hospital.)
3.

Type III has multiple fistulous connections from different vessels having characteristics of type I and II malformations ( Fig. 3 ).

Fig. 3

( A ) Lateral view from an angiogram of a Yaşargil type III VGAM. The black arrows denote the direct arteriovenous shunts and the white asterisk overlies the arterioarterial network supplying the VGAM. ( B ) Yaşargil type III VGAM. Direct arterial feeders from the anterior and posterior circulation and feeders from the arterioarterial niduslike network drain into the enlarged MProsV of Markowski.

(Part ( A ) Courtesy of Gailloud P, MD. The Johns Hopkins Hospital.)
4.

Type IV have adjacent AVMs that drain into the vein of Galen and cause a secondary aneurysmal venous dilatation ( Fig. 4 ).

Fig. 4

( A ) Lateral view from an angiogram of a Yaşargil type IV VGAM. A corpus callosum AVM is present draining into an enlarged internal cerebral vein ( white arrow ) and a dilated vein of Galen ( white asterisk ). ( B ) Yaşargil type IV VGAM with a deep AVM draining into an enlarged vein of Galen. In contrast with Yaşargil types I to III, the venous system has otherwise developed normally.

(Part ( A ) Courtesy of Gailloud P, MD. The Johns Hopkins Hospital.)

Only a primary vein of Galen malformation (Lasjaunias classification) and types I to III malformations (Yaşargil classification) represent true VGAMs, in which the MProsV of Markowski is the pathologic vessel. Secondary vein of Galen malformations (Lasjaunias classification) and type IV malformations (Yaşargil classification) are AVMs that produce secondary dilatation of the vein of Galen.

Clinical features and pathophysiology

Patients with a VGAM most commonly present with cardiac and neurologic complications. The clinical presentation depends on the age of presentation. Neonates tend to present with high-output cardiac failure, pulmonary hypertension, and, in more severe cases, multiorgan system failure. Infants commonly present with hydrocephalus, seizures, or neurocognitive delay. Older children and adults usually present with headaches or intracranial hemorrhage. If cardiac failure presents outside the neonatal period, it is usually mild to moderate and can be medically controlled.

Cardiac Manifestations and Associated Systemic Complications

The high-flow, low-resistance arteriovenous connection that is present in a VGAM causes a compensatory increase in blood volume and cardiac output. As a result, cerebral blood flow can comprise as much as 80% of the cardiac output in these cases. In utero, the placenta is also a low-resistance system that competes with the VGAM for blood flow and limits the blood flow that passes through the VGAM. However, postpartum blood flow greatly increases through the VGAM.

There are several factors that lead to worsening cardiac function. Increased venous return because of the VGAM can lead to pulmonary hypertention. The presence of a patent ductus arteriosus (PDA) and/or patent foramen ovale increases the volume of venous return, which worsens pulmonary hypertension. In addition, these right-to-left shunts decrease coronary blood flow, which can result in myocardial ischemia. Diastolic flow reversal can occur in the descending aorta, which can lead to hepatic and renal insufficiency.

Neurologic Manifestations

Normal cerebral development requires normal fluid balance among the extracellular, intracellular, and intravascular spaces. When a VGAM is present, the efferent flow from the torcula is directed medially given the persistent occipital and marginal sinuses. In turn, flow is directed away from the dural sinuses, which can lead to hypoplastic or thrombosed jugular bulbs as well as enlarged facial veins. Venous congestion and intracranial venous hypertension can develop, which disrupt the fluid balance among the intracranial spaces, leading to impaired cortical development.

Cerebral atrophy and irreversible brain damage can occur as a result of persistent venous congestion. When they are detected in the antepartum or neonatal period, they are associated with a poor prognosis. In severe cases, there may be rapid parenchymal loss, which is known as melting brain. Infants and children who are initially neurologically normal can still experience progressive neurologic and cognitive decline manifested by the development of calcifications, subependymal atrophy, and epilepsy. Restoring a hemodynamic balance by correcting the venous hypertension after endovascular treatment can lead to regression of the cerebral calcifications. Neurologic deficits usually occur from vascular steal caused by high flow through the VGAM, whereas developmental retardation is caused by venous congestion.

Hydrocephalus and macrocrania are typical presenting signs of infants. Obstructive hydrocephalus can occur from compression of the cerebral aqueduct by the VGAM ( Fig. 5 A). However, the predominant cause seems to be communicating hydrocephalus that occurs from decreased cerebrospinal fluid (CSF) absorption as a result of the intracranial venous hypertension, caused by disruption of the hydrovenous equilibrium. In both cases, hydrocephalus is a secondary phenomenon that results from the VGAM.

Headaches and seizures are common presenting symptoms in older children with a VGAM. In addition, subarachnoid, and intraparenchymal hemorrhage can also be the cause of presentation in older children with a VGAM. Although the VGAM tends to be smaller with a more limited arteriovenous shunting in older patients, the angiomatous network supplying the VGAM can produce microaneurysms.

Diagnostic workup

Most patients with a VGAM are diagnosed in the neonatal period. A thorough evaluation of the neonate being managed for a suspected VGAM begins with a bedside clinical examination and a battery of diagnostic tests to determine the management strategy. The neonatal evaluation should include a complete clinical evaluation of the neonate including weight and head circumference. An echocardiogram provides baseline data for patients without cardiac insufficiency and helps quantify the severity of cardiac failure in symptomatic patients. Renal and liver function tests should be obtained to screen for renal and hepatic insufficiency, especially when cardiac insufficiency is present. A transfontanelle ultrasound can be performed at the bedside to assess the brain parenchyma, evaluate the VGAM, and assess the ventricular size. Magnetic resonance imaging (MRI) of the brain can help confirm the diagnosis of VGAM and detect cerebral changes such as infarcts, atrophy, and hydrocephalus (see Fig. 5 ). An electroencephalogram should be performed on patients in the intensive care unit setting to rule out seizure activity.

Computed tomography (CT) is a useful screening tool and is often the imaging modality that detects a mass in older patients ( Fig. 6 ). CT angiography is a useful, noninvasive imaging modality that provides a clear map of the arteries and veins. It has better spatial resolution and can be obtained faster than magnetic resonance angiography (MRA). Conventional angiography is the gold standard imaging modality to evaluate the VGAM angioarchitecture. However, it should be performed as part of a planned endovascular intervention rather than for diagnostic purposes because the VGAM can be initially evaluated by MRI/MRA.