State of the Art. Diagnosis and Management of Vein of Galen Aneurysmal Malformations

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1 State of the Art Diagnosis and Management of Vein of Galen Aneurysmal Malformations Philippe Gailloud, MD Declan P. O Riordan, MD Ingrid Burger, BS Olivier Levrier, MD George Jallo, MD Rafael J. Tamargo, MD Kieran J. Murphy, MD Christoph U. Lehmann, MD confusion is associated with the word aneurysm itself. In its modern use, aneurysm is typically applied to purely arterial lesions, while enlarged venous structures are usually defined as varices or varicosities. This tendency is arbitrary since the word aneurysm is derived from the Greek aneurynein, that is, to dilate. The use of aneurysmal in VGAM is therefore not a misnomer, and speaking of a venous aneurysm is etymologically legitimate. The first reported case of a VGAM was published in Although rare, it has been estimated that VGAM represent approximately 30% of the pediatric vascular malformations. 3 Vein of Galen aneurysmal malformations (VGAM) are rare intracranial vascular anomalies typically found in children. The anatomic landmark of a VGAM is the presence of multiple arteriovenous shunts draining into a dilated median prosencephalic vein, an embryonic vessel normally absent at the adult stage. This article reviews the developmental anatomy, the clinical presentation, and the current management of VGAM. Journal of Perinatology (2005) 25, doi: /sj.jp ; published online 14 July 2005 INTRODUCTION A vein of Galen aneurysmal malformation (VGAM) is a rare intracranial vascular anomaly typically found in the pediatric population. The anatomic landmark of VGAM is the presence of multiple arteriovenous shunts draining into a dilated median cerebral venous collector. This median vein corresponds to a persistent embryonic channel, the median prosencephalic vein of Markowski (MProsV), which is normally absent at the adult stage. The true nature of this venous collector, wrongly identified with the vein of Galen in the past, was first recognized by Raybaud and Strother. 1 However, usage has consecrated a misnomer, and the lesion continues to be defined as a VGAM. Some additional Division of Interventional Neuroradiology (P.G., I.B., O.L., K.J.M.), The Johns Hopkins Hospital, Baltimore, MD, USA; Eudowood Neonatal Pulmonary Division (D.P.O., C.U.L.), The Johns Hopkins Hospital, Baltimore, MD, USA; Division of Pediatric Neurosurgery (G.J.), The Johns Hopkins Hospital, Baltimore, MD, USA; Division of Cerebrovascular Surgery (R.J.T.), The Johns Hopkins Hospital, Baltimore, MD, USA; and Division of Interventional Neuroradiology (O.L.), C.H.U Marseille, France. Address correspondence and reprint requests to Philippe Gailloud, MD, Division of Interventional Neuroradiology, The Johns Hopkins Medical Institutions, 600 N Wolfe Street, Baltimore, MD 21287, USA. 542 DEVELOPMENTAL ANATOMY Since the landmark publications of Raybaud and co-workers, 1,4 it has become clear that a basic appreciation of the embryologic mechanisms underlying the formation of the normal deep cerebral venous system is necessary to the understanding of VGAMs. The early development of the cerebral vascular system occurs in three stages. 5 In the prechoroidal stage I, a still thin mantle of differentiating neural cells is organized around the neural groove and, later, the neural tube. The neural cells are nourished by direct diffusion of the amniotic fluid. In the prechoroidal stage II, the neural mantle has thickened and diffusion from the inner aspect of the neural tube has to be supplemented by a cellular plexus newly formed around the neural tube and rich in vascular channels, the meninx primitiva. After closure of the anterior and posterior neuropores, the circulation of the fluid contained within the neural tube depends on dense vascular plexuses that are derived from the meninx primitiva and invaginate into the central cavity of the neural tube. These newly formed choroid plexuses define the choroidal stage. The blood supply to the developing brain is, at this stage, principally derived from the choroid plexuses via multiple choroidal arteries. The venous drainage is largely assumed by a large median venous structure, the MProsV of Markowski 6 (Figure 1). Later, as the cortical arterial network matures, the choroidal arteries almost completely lose their role in the brain vascularization. The internal cerebral veins develop and take over the drainage of the choroid plexuses. The internal cerebral veins terminate their course in the posterior aspect of the MProsV, which begins to involute. Only the posterior segment of the MProsV will persist as the great cerebral vein, or vein of Galen. The MProsV of Markowski is the embryonic channel forming the aneurysmal component typical of a VGAM. Since the arterial supply of a VGAM is mostly derived from choroidal arteries, all Journal of Perinatology 2005; 25: r 2005 Nature Publishing Group All rights reserved /05 $30

2 Vein of Galen Aneurysmal Malformations Gailloud et al. Figure 2. A 5-day-old child with a VGAM. Left vertebral artery angiography, unsubtracted anteroposterior view, showing the size of the aneurysmal vein of Galen (asterisk) relative to the skull diameter. Figure 1. Two of the original illustrations from Markowski s monograph on the development of the cerebral venous system (6). (a) Drawing in the coronal plane of the fetal brain, showing the midline location of the median prosencephalic vein (v.m.pros.), and exposing its close topographic relationship to the choroid formations of the roof of the third ventricle (l.ch.ep.). (b) Sagittal drawing of the fetal brain, showing the median prosencephalc vein (v.m.pros.) joined in its posterior half by one of the newly formed internal cerebral veins (v.c.i.). the components of a VGAM are present during the choroidal stage. The MProsV can normally be identified from the 8th to the 11th weeks of gestation, a window during which the events leading to the development of a VGAM are believed to occur. The mechanism of formation of the arteriovenous shunts remains unknown. As a consequence of the shunts, the anterior segment of the MProsV, instead of regressing, progressively enlarges under the stress produced by high-pressure inflow form the choroidal feeders. A VGAM is a cluster of arteriovenous fistulas draining into a persistent and dilated MProsV of Markowski (Figure 2). ANGIOARCHITECTURE Arterial Anatomy Three groups of arterial feeders classically participate in the vascularization of a VGAM: (i) the anterior and posterior choroidal arteries, (ii) the pericallosal artery, and (iii) transmesencephalic branches arising from the basilar tip and the proximal posterior cerebral arteries. As mentioned above, most of these feeders are choroidal arteries. This is obviously true not only for the anterior and posterior choroidal arteries, but also for the pericallosal artery, which is a prominent choroidal branch in the embryo and has a choroidal role in the adult (posteriorsuperior choroidal artery). 7 Other less common feeders include the middle cerebral artery, the superior cerebellar arteries, and various meningeal branches. Venous Anatomy The large median venous collector that gives a VGAM its typical appearance is a persistent and dilated MProsV. The straight sinus is often hypoplastic or absent, and the drainage of the MProsV occurs through a falcine sinus located within the posterior aspect of the cerebral falx. From this point on, the blood follows a normal route through the transverse/sigmoid sinuses and the internal jugular veins. Many collateral pathways may be involved, and other embryonic variants such as persistent occipital and marginal sinuses are commonly observed. Journal of Perinatology 2005; 25:

3 Gailloud et al. Vein of Galen Aneurysmal Malformations The anatomy of the normal deep venous drainage in patients with VGAMs is debated. It is often admitted that, when a VGAM is present, deep veins draining normal brain tissue do not end into the Galenic system. However, the termination of normal internal cerebral veins into the venous component of a VGAM, already mentioned by Raybaud et al., 4 has recently been documented unequivocally. 8,9 The implications of such observations for the choice of a therapeutic strategy in the management of VGAMs are discussed later. Secondary Vascular Alterations Secondary changes induced by sustained increase of flow can be observed on both the arterial and venous sides of a VGAM. Enlarged arteries can show marked sinuosity and can be associated with arterial aneurysm and/or steno-occlusive disease. Likewise, the dural sinuses involved in VGAM drainage can become stenotic or occluded, with redistribution of venous flow into cortical veins. Outflow impairment may worsen intracranial venous hypertension and increase the risk of intracranial hemorrhage, in particular when it leads to the development of venous aneurysms or varices. At the same time, the presence of flow obstruction on the venous side, for example, a straight sinus stenosis, has been shown to limit, in certain cases, the hemodynamic consequences of the arteriovenous shunts and represent a favorable prognostic factor. 4 ANATOMY OF THE SHUNTS AND VGAM CLASSIFICATIONS Two types of arteriovenous connections have been recognized in VGAMs. The simplest type (or choroidal type) consists in direct, high-flow shunts located within the wall of the venous aneurysm (Figure 3a and b). The second type (or mural type) involves the interposition of an arterial network between the feeders and the venous aneurysm itself (Figure 4a and b). This network is usually located in the quadrigeminal cistern and results in a less significant blood flow increase. The type of shunt present in a VGAM determines its clinical presentation (as described later), and has therefore been used to design various VGAM classifications. The classification proposed by Yasargil has the double advantage of clinical usefulness and simplicity. It also recognizes the existence, besides the pure forms of direct shunts (type I) and network-like shunts (type II), of a third configuration combining direct shunts and arterial network (type III). In addition, Yasargil included in his classification a type IV describing cerebral arteriovenous malformations (AVM) secondarily draining into an enlarged vein of Galen. Although type IV lesions represent a different entity, they can sometimes be difficult to distinguish from true VGAMs and offer similar therapeutic challenges. Type IV lesions are also referred to as vein of Galen aneurysmal dilatation (VGAD). 10 Figure 3. A 5-day-old child with a VGAM (mural type). (a) Left common carotid angiography, anteroposterior view, showing enlarged anterior choroidal artery (arrowhead) and anterior cerebral artery (arrow) as the principal feeders ending directly into the venous aneurysm. (b) Left common carotid angiography, lateral view, showing the termination of the anterior cerebral (arrow) and anterior choroidal (arrowhead) feeders as direct arteriovenous shunts. Note the drainage of the venous aneurysm into a persistent falcine sinus (asterisk). IMAGING Ultrasound Transfontanellar Doppler sonography is a noninvasive technique enabling bedside evaluation of the cerebrovascular system of neonates. 11 Although quick and convenient, its quality strongly 544 Journal of Perinatology 2005; 25:

4 Vein of Galen Aneurysmal Malformations Gailloud et al. the brain parenchyma and the cerebral ventricles. Transcranial Doppler (TCD) shows some promise in the evaluation of intracranial vascular malformation in the older child and the adult. Computed Tomography and Computed Tomography Angiography Until recently, the role of computed tomography (CT) was limited to the evaluation of indirect findings such as ventricular enlargement, brain atrophy, and parenchymal calcifications associated with severe intracranial venous hypertension. The newly introduced technique of CT angiography has, however, an enormous potential for the evaluation of cerebrovascular diseases affecting newborn babies and infants. 12,13 CT angiography consists of a spiral acquisition of the region of interest after intravenous administration of a bolus dose of iodinated contrast agent. A computer workstation then generates various two- and threedimensional representations of the acquired data, showing in particular the vascular bed and its osseous surroundings. Thanks to the development of multidetector technology, CT angiography only requires a few more minutes than the head CT routinely obtained in newborns with a suspicion of intracranial anomaly. CT angiography can be performed in awake or lightly sedated children with no or little degradation of image quality. Although not as precise as conventional catheter angiography, CT angiography is noninvasive and offers more detailed vascular information than sonographic and MR techniques. Figure 4. A 28-year-old woman with a VGAM (choroidal type). (a) Left vertebral angiography, anteroposterior view, showing an enlarged posterior-medial choroidal artery (arrow) feeding a complex arterial network (asterisk) that subsequently drains into the venous aneurysm. (b) Left vertebral angiography, lateral view, showing the large posteriomedial choroidal feeder (arrow) and the arterial network (asterisk). depends on operator experience. It can be repeated as often as needed without the anesthesiologic support required for CT or MR imaging. Doppler sonography is therefore an excellent tool for the evaluation of the critically ill neonate. Fine Doppler analysis of a VGAM can be performed not only for diagnostic purpose but also to monitor the hemodynamic repercussion of the treatment. Transfontanellar ultrasound provides additional information on Magnetic Resonance Imaging and Angiography Magnetic resonance (MR) imaging provides information about the VGAM and its surrounding structures. The size and configuration of the venous aneurysm can be appreciated, and an initial estimation of the number and type of feeders obtained. More importantly, MR imaging documents secondary repercussions of the VGAM, such as third ventricle or aqueduct compression, and cerebral atrophy. A clear appreciation of the degree of irreversible cerebral damage is essential for both therapeutic decision-making and prognosis evaluation. 14 Fetal Imaging VGAMs are now often detected in utero by fetal imaging. Although ultrasound remains the most widely available technique for in utero imaging, fetal MR imaging is increasingly used to investigate specific prenatal conditions (Figure 5). In addition to early detection and characterization of the VGAM itself, fetal MR imaging can document the presence of brain atrophy and cardiac insufficiency, both associated with poor prognosis. 14 Digital Subtraction Angiography Digital subtraction angiography (DSA) remains the gold standard technique for the evaluation of the cerebrovascular system. Only DSA offers precise evaluation of the VGAM angio-architecture and Journal of Perinatology 2005; 25:

5 Gailloud et al. Vein of Galen Aneurysmal Malformations Neonatal Period When symptomatic, newborn infants typically present with severe cardiorespiratory alterations at or shortly after birth. Infants diagnosed during the fetal period may already demonstrate signs of cardiac failure prior to delivery, including hydrops. In these children, the volume overload imposed by a VGAM with high-flow shunts (Yasargil type I) is such that it can rapidly induce cardiovascular and respiratory distress syndromes. The majority of cases (94%) diagnosed in the neonatal period will therefore present with high-output cardiac failure. 17 Severe pulmonary hypertension may be a complicating factor. In the past, the mortality rate for this group was close to 100%. Recent advances made in the management of these patients, in particular the use of endovascular techniques in a dedicated neonatal intensive care environment, have significantly altered this dismal prognosis. Figure 5. Detection of a VGAM in a 32-week-old fetus by maternal magnetic resonance imaging. Note that the size of the cardiac chambers can be evaluated. provides access for endovascular management of the lesion. DSA details the fine anatomy of the arterial feeders in terms of size, number, and origin, and detect associated vascular anomalies such as proximal high-flow arteriopathy. If the clinical condition of the newborn allows it, DSA should be delayed to the fifth month of life. 15 During the perinatal period, catheterization of the umbilical artery is the most convenient arterial approach, and can usually be used up to the third day of life. In some instances, an apparently thrombosed umbilical artery can be superficially dissected, and a catheter passed. The risk of femoral access in small children lies in possible limb ischemia with either acute or delayed repercussion, the latter potentially resulting in assymetric leg development. Ultrasound guidance facilitates difficult arterial puncture. Once access has been obtained, catheter angiography in children is generally remarkably straightforward. CLINICAL PRESENTATION In 1964, Gold et al. 16 typified the presentation of patients with VGAM in three clinical syndromes based on personal observations and previously published cases. These clinical pictures reflect a tight correlation between the age at presentation and the angioarchitecture and hemodynamic characteristics of the VGAM. Infancy Patients in this age group characteristically present with an increased head circumference, hydrocephalus, and/or seizures. A cerebral steal phenomenon may be the etiology for frequently associated psychomotor disturbances. Noncommunicating hydrocephalus results from direct compression of the aqueduct or posterior third ventricle by the venous aneurysm itself, as already noted by Jaeger et al. 2 in the first reported case of VGAM. Communicating hydrocephalus, on the other hand, has been classically ascribed to impaired cerebrospinal fluid reabsorption caused by subarachnoid blood. However, Zerah et al. 18 have highlighted the role of VGAM-induced intracranial venous hypertension in the development of hydrocephalus. Other signs and symptoms may include cranial bruit, dilated scalp veins (in particular in the periorbital region and the glabella), proptosis, and recurrent epistaxis. Infancy presentation is associated with Yasargil type II VGAMs. Older Child and Adult Older children tend to present with headache that may or may not be associated with subarachnoid hemorrhage. Gold et al. s 16 survey found that subarachnoid hemorrhage occurred in 10 of the 13 patients belonging to this age category. Although the discovery of VGAM at the adult age is still considered rare, late diagnosis in pauci- or asymptomatic patients may become more common with increased availability and use of MR imaging. In such a case, the VGAM is usually small and the degree of arteriovenous shunt limited. A small cerebral AVM draining into an enlarged but otherwise normal vein of Galen (Yasargil type IV) has to be considered in the differential diagnosis. MANAGEMENT The advent of endovascular therapy has radically changed the treatment and prognosis of VGAM patients The development 546 Journal of Perinatology 2005; 25:

6 Vein of Galen Aneurysmal Malformations Gailloud et al. of intensive care units and physicians specialized in the management of critically ill neonates bears an equally significant importance in the favorable outcomes achieved nowadays. The prenatal characterization of a VGAM now available through fetal sonography and MR imaging authorizes optimal monitoring and delivery conditions in specialized high-risk pregnancy units. Surgical options are reserved for particular situations that include the evacuation of intracranial hematomas and the treatment of hydrocephalus. Optimal management of patients with a VGAM is achieved only through the comprehensive, multidisciplinary approach offered by specialized tertiary care centers. Endovascular Treatment The endovascular approach to VGAM includes transarterial and transvenous percutaneous embolization techniques. In our institution, the transarterial approach is favored whenever possible. Arterial access is gained via the umbilical artery, if still patent, or via femoral puncture. Flow-guided or over-the-wire microcatheters are selected on a case-by-case basis, and navigated to the site of the arteriovenous shunts under fluoroscopic control. A cyanoacrylate glue (N-butyl-cyanoacrylate (NBCA)) is the embolic material of choice (Figure 6a c). 21 Prior to injection, NBCA is mixed with a radio-opaque agent (ethiodized oil). The glue composition influences its setting characteristics, and is chosen according to the hemodynamic and angio-architectural characteristics of the targeted arteriovenous shunt. A direct fistula requires very fastsetting glue, while a shunt with interposed arterio-arterial connections needs a slower, more penetrating glue composition. Detachable microcoils can be used as an alternative embolic agent. However, achieving complete obliteration of a feeder with detachable microcoils is a longer procedure, which requires more endovascular manipulations, and carries, in our opinion, an increased risk of vessel rupture. When used adequately, NBCA is fast and safe, and allows precise targeting of the arteriovenous shunt itself. The transvenous approach to a VGAM is performed via a femoral or jugular access followed by retrograde catheterization of the venous aneurysm. 22,23 When not feasible, direct puncture of the torcula via an occipital burr hole, or using sonographic guidance, 20 offers an alternate route. Both techniques ultimately involve partial obliteration or occlusion of the venous aneurysm with microcoils. Although some teams have obtained good results with the transvenous technique and advocate its use as a first-line option, 22 it is reserved, in our institution, to VGAMs that cannot be accessed transarterially. Occluding the venous aneurysm can potentially impair normal deep venous drainage pathways. 8,9 Catheterization of the venous aneurysm may also result in its perforation. 23 In addition, if transarterial embolization often leads to regression of the aneurysmal component of the lesion and of its associated mass effect, a similar result is less likely to occur with the transvenous approach in view of the persistent nature of the coil pack. It should be noted that, in selected cases, a transvenous approach may allow retrograde catheterization of direct arterial feeders and their subsequent obliteration with NBCA or microcoils. 23 The endovascular treatment of a VGAM often requires several successive procedures. Staged embolization sessions initially aimed at controlling cardiac failure help avoiding the occurrence of parenchymal bleedings secondary to a perfusion breakthrough phenomenon, or massive venous thrombosis potentially endangering the normal venous drainage. The transarterial approach is ideally suited for this stepwise strategy by allowing the operator to control the degree of devascularization by selecting the number of pedicles to be embolized. A balanced treatment, that is, a devascularization that is sufficient to relieve the cardiopulmonary stress and later avoid recurrence, but not too pronounced in order to avoid complete closure of the venous aneurysm, is more difficult to attain with a transvenous approach. 20 Ideally, when the hemodynamic conditions allow it, embolization should be deferred until 5 to 6 months of life. On the other hand, excessive delay may lead to permanent impairment of the cerebrospinal fluid hydrodynamic, after which even successful correction of the shunts would not result in hydrocephalus regression. 15 Spontaneous thrombosis of a VGAM is occasionally reported. It remains a rare event (4% in Lasjaunias series 15 ), and its potential occurrence should not be used to delay adequate VGAM management. Surgical Options Thanks to the advent of endovascular therapy, surgical access to a VGAM is now only considered in case of failure of, or rarely as a complement to, embolization. Surgery is, on the other hand, indicated for the evacuation of intracranial hematomas and for the management of hydrocephalus, by endoscopic third ventriculostomy or shunt placement. Shunt placement is associated with a significant increase in morbidity and mortality in the VGAM population, 18 and should be considered only after treatment of the VGAM has failed to improve the hydrocephalus. The relatively new procedure of endoscopic third ventriculostomy may have less associated risks than conventional shunt placement. It can be performed in symptomatic children prior to endovascular intervention. Medical Management Prenatal detection of a VGAM, which occurs most commonly during the third trimester, facilitates the medical management of the newborn by allowing delivery in a specialized tertiary care center. Evidence of cardiac decompensation and hydrops, as well as encephalomalacia, may now be detected prenatally by ultrasonography and MR imaging. 14 Postnatal manifestations of a VGAM vary with the age of presentation. Neonates classically develop congestive heart failure due to tremendous left to right shunting through the low resistance vascular bed of the Journal of Perinatology 2005; 25:

7 Gailloud et al. Vein of Galen Aneurysmal Malformations Figure 6. A 5-day-old child with cardiorespiratory insufficiency. (a) Right common carotid artery angiography, anteroposterior view, showing a large right anterior choroidal artery (arrowhead) ending into the venous aneurysm. Note the diminutive caliber of the otherwise normal middle cerebral artery (arrow). (b) Superselective embolization of the anterior choroidal artery with N-butyl-cyanoacrylate glue. The glue is dark, while the path used by the microcatheter to access the lesion appears white. (c) Right common carotid artery angiography after embolization, showing significantly decreased flow to the VGAM, which now receives minor residual inflow from the distal segment of the anterior cerebral artery (arrow). 548 Journal of Perinatology 2005; 25:

8 Vein of Galen Aneurysmal Malformations Gailloud et al. VGAM. 24,25 Symptomatic infants may develop both volume and pressure overload on the right ventricle leading to cyanosis from shunting across the patent ductus arteriosus (PDA) and the atrial septum The development of suprasystemic pulmonary artery pressures carries a poor prognosis. 25 Echocardiography has a primary role in the newborn with a VGAM for assessing ventricular function and the degree of shunt across a PDA and atrial septum, for estimating pulmonary artery pressures, identifying associated anomalies (secundum atrial septal defect and coarctation), and ruling out congenital heart disease. 24,25,28 In addition, echocardiography may reveal reversal of aortic flow during diastole, indicating a steal phenomenon that decreases peripheral perfusion. Although cardiac failure and persistent pulmonary hypertension of the newborn (PPHN) are the most dramatic features of VGAMs in neonates, encephalomalacia, seizures, and multiorgan dysfunction due to poor perfusion are frequently associated. Medical stabilization of the symptomatic neonate with VGAM can be exceedingly difficult in the presence of cardiac failure with pulmonary hypertension. Optimal strategies have not been defined. For infants with acyanotic congestive heart failure, diuretic and inotrope therapy may be sufficient to stabilize the patient and allow deferring the endovascular treatment of the VGAM. Infants with coexisting pulmonary hypertension present a more difficult task. The presence of the right to left shunt at the atrial and ductal levels is exacerbated by the low total systemic vascular resistance largely due to the VGAM. Resistance through the VGAM may be low enough to induce a steal phenomenon manifesting as reversal of aortic flow during diastole causing subendocardial and peripheral ischemia. 24 Nitric oxide, the most effective therapy for traditional PPHN, will likely play a larger role in the future, but only a limited number of infants with VGAMs and pulmonary hypertension have been placed on nitric oxide so far and its benefits remain unknown. Other therapies include beta agonists (dopamine, dobutamine), prostaglandin infusions, phosphodiesterase inhibitors, digoxin, and the combination of vasodilation with low-dose beta agonist (sodium nitroprusside plus low-dose dopamine). 24,25 No clinical trials have been performed yet and no consensus has arisen for treatment strategies in the neonates with the worst cardiac failure. Older infants and children tend to present with hydrocephalus, developmental delay, megalencephaly, seizures, and/or dilated facial veins. Cardiac failure, when present, is milder and more amenable to treatment. Pulmonary hypertension has not been a prominent symptom in infants, although one case of prominent and ultimately fatal pulmonary hypertension has been reported in a 2-month-old child. 29 neonatal population. In 1964, the review of Gold et al. 16 reported mortality rates of 100% (9/9) for the neonates, 68% (13/19) for infants, and 45% (5/11) for older children/adults. The introduction of endovascular techniques has significantly modified this somber prognosis, in particular by helping control the cardiovascular repercussions of the arteriovenous shunts using a minimallyinvasive approach. 30 In addition, as pointed out by Friedman et al. 31 in 1993, improvement in endovascular techniques and materials as well as in the perinatal management of the patients (modern imaging, intensive care environment) has further improved the favorable outcome obtained by early endovascular techniques. In their early experience with 22 neonates in 1991, 32 these authors reported a 50% mortality rate and a 37% (four patients) incidence of severe mental retardation in survivors. In their more recent series of 11 neonates in 1993, 31 no mortality occurred and six (55%) of the patients were functionally normal at up to 30 months of follow-up. These numbers suggest an improvement in mortality, while improvement in morbidity for those who survive remains more difficult to assess due to measurements variability. Although each presents a limited number of children, several recently published series reflect the benefit of modern endovascular techniques. Mitchell et al. 20 treated five symptomatic neonates. One died of intractable cardiac failure (20%). In the remaining four others, control of cardiac failure was achieved by embolization without neurological deficit. On follow-up examination, one of the survivors showed moderate developmental delay (20%). In another series, Frawley et al. 24 treated nine neonates with symptomatic VGAMs, and obtained control of cardiac failure and a normal neurological function in six (66%). One patient died from intractable cardiac failure in the neonatal period, and two died later from severe hypoxic ischemic neurological injury (33% mortality). At follow-up (6 months to 4 years), five infants had no evidence of neurological abnormality or cardiac failure, and one child had mild developmental delay (11%). In 1996, Lasjaunias et al. 33 discussed the treatment and follow-up of a total of 78 neonates, infants, and children. Seven of these patients died (9% mortality). For the remaining 71 patients who were followed (median 4.4 years, range 1 to 10 years), 66% were neurologically normal, 14% had transient neurological symptoms, 11.5% had mild permanent deficits, and 8.5% had severe permanent deficits. Most recently, Fullerton et al. 34 presented a series of 27 patients, four of whom died (15% mortality) during hospitalization. Of the 23 patients followed (0.75 to 14 years, median 4.5 years follow-up), 61% had no or minor developmental delay and 64% had no or mild abnormalities on neurological examination. PROGNOSIS The prognosis of treated or untreated VGAM has been notably poor in the past, with reported mortality rates reaching 100% for the ETHICAL CONSIDERATIONS The management of patients with VGAMs presents clinicians with ethical challenges because they are rare, potentially fatal lesions Journal of Perinatology 2005; 25:

9 Gailloud et al. Vein of Galen Aneurysmal Malformations that occur in young children and require highly specialized and coordinated care. While endovascular techniques have greatly reduced the mortality associated with VGAM, there are certainly patients for whom this treatment is neither beneficial nor indicated. For example, treatment is clearly not indicated for an infant with intractable heart failure at birth and massive brain atrophy. At the opposite end of the spectrum, treatment is clearly indicated for an infant with normal brain imaging studies and hemodynamic stability for several months after birth. Ethical challenges arise when available medical information does not clearly indicate the benefit of treating versus not treating a lesion. While some authors have developed algorithms to aid therapeutic decision-making, 17 gray areas will persist regardless of medical progress. Normally, treatment decisions are reached by weighing the expected risks, benefits, and outcomes of an intervention compared to conservative management. Relying on such information in the case of VGAM therapy is, however, difficult since it does not exist in a robust form; the continuing modification of endovascular techniques coupled with the rarity of the disease has made obtaining strong data on mortality and morbidity rates difficult. Without strong data to guide management and evaluate prognosis F particularly neurodevelopmental outcome of children after endovascular treatment F it is difficult for clinicians to satisfactorily counsel families about the risks, benefits, and expected outcomes of intervention. This dilemma has two implications. First, it highlights the importance of collecting and analyzing patient information in order to bolster knowledge of VGAM treatment outcomes. Second, it requires that clinicians cultivate their ability to communicate clearly, honestly, and supportively with parents about the management options and prognosis for their children based upon available knowledge. Therapeutic decision-making should be a shared process between the clinician and the parents. In situations where there is uncertainty about treatment outcomes, decisions may be influenced less by medical knowledge than by social and cultural factors. Parents of sick infants are uniquely vulnerable and face a stressful decision process. Furthermore, parents may place quite different values on expected risks and benefits of treatment than their clinicians, leading to conflicting views regarding the best management of the childs condition. This may lead parents to decline consent for treatment even when the medical team feels that the child is a good candidate, or to push for treatment of a child who is a poor candidate. Resolution of such issues is difficult and demands a high level of communication among all members of the team and the family, with the common goal of doing what is in the best interest of the child. One framework that may be helpful for defining a child s best interest was put forth by the President s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research in a report entitled Deciding to Forego Life Extending Treatment. 35 This framework lays out the following five elements to consider: (i) the degree of suffering and potential for a therapy to provide relief, (ii) the severity of disability and potential to restore function, (iii) the life expectancy for a particular infant, (iv) the potential to lead a personally satisfying and enjoyable life, and (v) the potential for an infant to develop the ability to make his/her own life choices. The weight given to each of these elements may vary among different parents and clinicians. A good decision-making process, however, would include consideration and discussion of these elements by parents and clinicians, who could then arrive at a decision based in part upon this discussion. CONCLUSIONS VGAMs are congenital vascular malformations made of multiple arterial feeder establishing direct or indirect connections (shunts) with a large median venous collector. The latter is not the vein of Galen per se, but a persistent embryonic channel that normally participates in the formation of the vein of Galen, the median prosencephalic vein of Markowski. VGAMs classically present in the neonatal period with high-output cardiac insufficiency, or during infancy with hydrocephalus, seizures, and/or mental retardation. The prognosis of the disease has been notably dark, with death rates reaching 100% in the past. While prenatal documentation of brain atrophy and cardiac insufficiency remains associated with poor outcomes, the advent of endovascular management via a transarterial or transvenous route has profoundly modified the prognosis of children with a VGAM, both in terms of mortality and morbidity. References 1. Raybaud CA, Strother CM. Persisting abnormal embryonic vessels in intracranial arteriovenous malformations. Acta Radiol Suppl 1986;369: Jaeger JR, Forbes RP, Dandy WE. Bilateral congenital cerebral arteriovenous communication aneurysm. Trans Am Neurol Assoc 1937;63: Long DM, Seljeskog EL, Chou SN, French LA. Giant arteriovenous malformations of infancy and childhood. J Neurosurg 1974;40: Raybaud CA, Strother CM, Hald JK. Aneurysms of the vein of Galen: embryonic considerations and anatomical features relating to the pathogenesis of the malformation. Neuroradiology 1989;31: Raybaud CA. Development of the arterial supply to the brain tissue. In: Lasjaunias P, Berenstein A, editors. 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