Case Series Echocardiographic Findings in Vein of Galen Malformation Nora M. Doyle, MD, MPH, Joan M. Mastrobattista, MD, Mohinder K. Thapar, MD, M. Regina Lantin-Hermoso, MD Objective. Vein of Galen aneurysmal malformations (VGAMs) are rare congenital malformations thought to develop during weeks 6 to 11 of fetal life. Although they represent less than 1% of all cerebral vascular malformations, they constitute up to 30% of all pediatric vascular malformations. Vein of Galen aneurysmal malformations cause high-output heart failure in the fetus and neonate secondary to the decreased resistance and high blood flow in the lesion. We describe 2 cases, 1 prenatal and 1 postnatal, in which unusual aortic Doppler flow patterns and substantial brachiocephalic vessel dilation contributed to the discovery of a VGAM. Methods. Echocardiographic findings associated with VGAM malformations in 2 cases are described. Results. Unusual Doppler flow patterns and substantial brachiocephalic vessel dilation were seen in both cases. Pseudocoarctation of the aorta was also noted in both cases. Conclusions. The echocardiographic findings in fetal and neonatal VGAM may include pseudocoarctation of the aorta. Abnormal fetal cardiac findings should raise the practitioner s suspicion for cerebral malformations and vice versa. Key words: prenatal; postnatal; pseudocoarctation of aorta; vein of Galen aneurysmal malformation. Abbreviations MRI, magnetic resonance imaging; PDA, patent ductus arteriosus; VGAM, vein of Galen aneurysmal malformation Received July 27, 2004, from the Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences (N.M.D., J.M.M.), and Division of Pediatric Cardiology, Department of Pediatrics (M.K.T., M.R.L.-H.), University of Texas Houston Medical School, Houston, Texas USA; and Memorial Hermann Children s Hospital, Houston, Texas USA (M.R.L.-H.). Revision requested August 9, 2004. Revised manuscript accepted for publication August 24, 2004. We thank sonographers James Dozer, Raquel Lathem, Matt Demecs, and Jennifer Metcalf for care of the patients. Address correspondence and reprint requests to M. Regina Lantin-Hermoso, MD, Division of Pediatric Cardiology, Department of Pediatrics, University of Texas Houston Medical School, 6431 Fannin, MSB 3.126, Houston, TX 77025 USA. E-mail: m.r.lantin-hermoso@uth.tmc.edu Vein of Galen aneurysmal malformations (VGAMs) are rare congenital vascular abnormalities characterized by the absence of cerebral capillaries, resulting in a direct communication between the cerebral arteries and the deep draining veins of the brain. This gives rise to direct shunting of cerebral arterial flow into the draining vein, which then becomes markedly enlarged and aneurysmal. Compression of the developing brain by the enlarged vessel may lead to cerebral hypoplasia, atrophy, or hydrocephalus. 1 Intractable congestive heart failure, resulting from the decreased resistance and high blood flow in the lesion, may lead to in utero or neonatal death and is another serious complication from this entity. 2 Advances in sonographic and Doppler techniques have made antenatal diagnoses of VGAMs possible, and their intracranial sonographic characteristics have been well described. 3 5 However, there is a paucity of information regarding associated in utero or neonatal cardiac sonographic findings in VGAMs. We describe 2 distinct cases of VGAMs, 1 diag- 2005 by the American Institute of Ultrasound in Medicine J Ultrasound Med 2005; 24:93 98 0278-4297/04/$3.50
nosed in utero and the other after birth, in which unusual aortic Doppler flow patterns and substantial brachiocephalic vessel dilation led to the diagnosis of the cerebral vascular malformation. The purpose of this report is to highlight the perinatal cardiac sonographic findings in VGAMs, which may be very similar to those in fetuses and neonates with coarctation of the aorta. The pathophysiologic characteristics of fetal highoutput congestive heart failure will also be reviewed. Case Descriptions A 39-year-old primigravida was referred for evaluation after abnormal screening sonographic findings at 28 to 29 weeks gestation. Family history was notable for a maternal sibling with Turner syndrome who died at 9 months of age from complications after surgical correction of coarctation of the aorta. Level 3 sonography and fetal echocardiographic examination revealed a singleton intrauterine pregnancy in the breech presentation at 29 weeks gestation, with an estimated fetal weight of 1649 g. The fetus had sinus tachycardia (fetal heart rate, 190 beats per minute), with 4-chambered cardiac anatomy and normally related great arteries. Moderate cardiomegaly was observed (cardiothoracic rate, 72%), with right atrial, right ventricular, and superior vena caval dilation (Figure 1). Figure 1. Fetal longitudinal right parasagittal view showing marked dilation of the superior vena cava (SVC), which measures nearly 3 times the diameter of the inferior vena cava (IVC). Moderate tricuspid insufficiency and right-toleft shunting was shown across the patent foramen ovale and patent ductus arteriosus (PDA), with the latter exhibiting a high-velocity flow (nearly 2 m/s by pulsed wave Doppler sonography). Doppler flow velocities across both atrioventricular and semilunar valves were increased (>0.8 and >1.4 m/s, respectively). The ascending aorta and innominate artery were dilated (Figure 2), with increased flow velocity shown across the latter of up to 1.8 m/s. The aortic isthmus and transverse arch appeared hypoplastic, with turbulent flow across the area of narrowing (Figure 3). Gated pulsed Doppler interrogation of the ascending aorta revealed normal antegrade flow throughout the cardiac cycle. However, in the transverse and descending aorta, just distal to the origin of the left common carotid and left subclavian arteries, respectively, antegrade systolic flow, followed by retrograde diastolic flow reversal, was shown (Figure 4). Because of these findings, a concern was raised regarding the possibility of fetal coarctation of the aorta. The right common carotid artery was followed intracranially. A large supratentorial cystic mass was seen (Figure 5). Power Doppler interrogation showed high-velocity vascular turbulence within it, consistent with a VGAM (Figure 6). Areas of echogenicity were seen within the cerebral tissue, and note was made of cerebral ventriculomegaly. There was no evidence of fetal ascites or pericardial effusion, and the remainder of the fetal anatomy appeared grossly normal. The above findings were most consistent with fetal high-output congestive heart failure and impending fetal hydrops secondary to the VGAM. Maternal digoxin therapy was initiated (0.25 mg orally once daily), and serial maternal electrocardiograms were obtained to monitor for digoxin effects or possible toxicity. Magnetic resonance imaging (MRI) of the fetal brain was performed to confirm the sonographic findings. It revealed a large VGAM, moderate to severe atrophy of the cerebral hemispheres, thinning of the corpus callosum, and lateral ventriculomegaly. Follow-up at 30 weeks gestation revealed normalization of the fetal heart rate to around 130 beats per minute, and maternal digoxin therapy was continued. Shortly before induction of labor at 39 weeks, a small amount of concentric pericardial effusion was noted (Figure 7). 94 J Ultrasound Med 2005; 24:93 98
Doyle et al The patient was delivered of a live-born male neonate who underwent intubation in the delivery room secondary to poor respiratory effort, cyanosis, and hypotonia (neurogenic central apnea). A postnatal echocardiogram confirmed prenatal findings. High-velocity flows ( 2 m/s) were noted across the aortic isthmus, which initially appeared relatively narrowed. The ascending aorta and innominate artery were dilated, and Doppler flow reversal was noted in the juxtaductal aorta, similar to the prenatal findings. A large PDA with bidirectional flow was noted, and this, along with the high-velocity tricuspid regurgitation jet, was evidence of substantial pulmonary hypertension. In the presence of a large bidirectional shunting PDA, the presence of aortic coarctation was difficult to rule out. However, the patient did not have any signs of aortic arch obstruction (bounding lower extremity pulses and no blood pressure differential between the upper and lower extremities). Serial echocardiographic evaluation, performed immediately after birth and on day 1 of life, eventually ruled out the presence of true coarctation. Brain MRI was performed, which confirmed the presence of a large VGAM with multiple arterial feeding vessels. Unfortunately, the presence of severe cerebral hemisphere atrophy was also confirmed. Because of the uniformly poor prognosis of such patients, 6 the family requested withdrawal of aggressive measures, and the neonate died on day 2 of life. Autopsy confirmed the VGAM with multiple arterial feeding vessels, severe cerebral hemisphere atrophy, a large PDA, and no aortic arch obstruction or true coarctation. Patient 2 was a 4-day-old, full-term, 2.8-kg female neonate, born at an outside facility. The mother had colonization of group B Streptococcus and received intrapartum therapy. Apgar scores were 9 and 9, at 1 and 5 minutes, respectively. However, over the first 48 hours of life, the neonate became tachypneic and dyspneic (respiratory rate, 90 breaths per minute), and a heart murmur was auscultated. A sepsis workup and antibiotics were initiated, and she was transferred to our facility for further evaluation. On admission, the infant had sinus tachycardia, with a heart rate of 180 beats per minute. She was tachypneic, with a respiratory rate of around 80 breaths per minute. A hyperdynamic left ventricular impulse with a prominent P2 component of the second heart sound and an S3, S4 summation Figure 2. Fetal longitudinal left parasagittal view showing marked dilation of the ascending aorta and right innominate and left common carotid arteries. Note is made of the relative hypoplasia of the transverse arch. A indicates right innominate artery; B, left common carotid artery; and C, left subclavian artery. gallop were auscultated. Additionally, a grade 2/6 systolic ejection murmur (aortic flow murmur) in the right upper sternal border radiating widely to the entire precordium and the neck was noted. The liver edge was palpable 3 cm below the right subcostal margin. Distal pulses were bounding with no brachiofemoral delay. The cranial sutures were splayed, and a loud cranial bruit was auscultated over the anterior fontanelle. An electrocardiogram revealed sinus tachycardia with right ventricular predominance. A chest roentgenogram documented moderated car- Figure 3. Fetal left parasagittal view of the aortic arch, with the Doppler gate positioned in the aortic isthmus, just distal to the left subclavian artery. Note is made of the high-velocity continuous diastolic flow in the descending aorta, of nearly 2.2 m/s. This Doppler pattern is similar to that observed in true coarctation of the aorta. J Ultrasound Med 2005; 24:93 98 95
Figure 4. Fetal long axis left parasagittal view with color Doppler interrogation showing flow reversal in the descending aorta. The flow in the descending aorta should have been antegrade (blue denotes flow away from the transducer). A indicates ascending aorta; B, right innominate artery; C, descending aorta; D, left common carotid artery; and E, left subclavian artery. Figure 5. Fetal head showing the dilated lateral ventricle and central VGAM. diomegaly with increased pulmonary vascularity. Transthoracic echocardiography showed 4- chambered anatomy with normally related great vessels and moderate cardiomegaly, along with superior vena cava, right atrial, and right ventricular dilation. Moderate tricuspid regurgitation predicting near systemic right ventricular and pulmonary arterial pressures was shown. The ascending aorta and the innominate artery were dilated. As in the first case, the aortic isthmus appeared relatively hypoplastic, with a juxtaductal configuration similar to classic coarctation. Pulsed Doppler interrogation once again showed normal pulsatile systolic antegrade flow in the ascending aorta, with retrograde flow across the transverse and proximal descending aorta during diastole. There was a large PDA with bidirectional flow. The abdominal aorta was pulsatile, but the Doppler flow pattern showed continuous systolic and diastolic flow, similar to what one would see in infantile coarctation. Subsequent echocardiographic evaluations revealed resolution of the findings, consistent with pulmonary hypertension, and aortic coarctation was ultimately ruled out. Brain MRI showed aneurysmal enlargement of the vein of Galen and posterior draining venous sinuses, but the cerebral parenchyma was otherwise grossly normal. The neonate was treated with digoxin, diuretics, and augmented caloric feedings. Over the next few days, her tachycardia and tachypnea and other symptoms of congestive heart failure became fairly well controlled. The infant subsequently awaited endovascular therapy. Discussion The vein of Galen originates from the median vein of the prosencephalon and results from the union of the 2 internal cerebral veins that eventually drain into the straight sinus. A VGAM occurs when the vein of Galen receives an arterial communication from 1 or more major intracranial arteries, whether directly or through an interposed angiomatous malformation. 7 Large arteriovenous shunts in the fetal or placental circulation, such as may occur in the presence of tumors with a large vascular supply (sacrococcygeal teratoma, neuroblastoma, or placental chorioangioma), or a VGAM may result in high-output fetal cardiac failure. The reduced afterload due to abnormal tumor vascularity or the low-resistance cranial circulation, along with high preload from the increased venous return from the shunt, results in an increased cardiac output and metabolism. 8 In both of our cases, the reduced afterload was shown by the retrograde diastolic runoff flow in the transverse and proximal descending aorta (Figures 3 and 4). The increased preload has its origin intracranially, evidenced by marked dilation of the superior but not the inferior vena cava (Figure 1). With progression of the disease process, cardiac failure may develop. The fetal ventricles dilate as they handle more than twice the estimated normal range of cardiac output. Because fetal cardiac output is highly dependent on heart rate, sinus tachycardia is a common finding. Tricuspid 96 J Ultrasound Med 2005; 24:93 98
Doyle et al regurgitation, cardiomegaly, and fetal hydrops may then ensue. Two-dimensional echocardiographic and Doppler findings in neonatal cerebral arteriovenous malformations, which are similar to those in neonates with coarctation of the aorta, have been described. 9 Although patient 2 had all the infantile findings reported by Starc et al, 9 we think that the fetal diagnosis of a VGAM on the basis of impending fetal hydrops and pseudocoarctation, as in patient 1, is unique. In rare instances, congenital cardiac anomalies, particularly sinus venosus atrial septal defects and true coarctation of the aorta, are associated with VGAMs. 10 The first patient s family history of Turner syndrome with coarctation of the aorta heightened the suspicion of true coarctation. As an isolated entity, coarctation of the aorta is difficult to diagnose in utero. Data have suggested that use of normal growth curves for the developing aortic arch may facilitate the prenatal diagnosis of aortic arch abnormalities, with an isthmus ascending aorta ratio of less than 0.81 being suggestive of coarctation. 11 The isthmal area of the fetus in case 1 appeared relatively narrowed compared with the markedly dilated ascending aorta, with an isthmus ascending aorta ratio of 0.69. It must therefore be noted that the aortic arch diameter nomograms may not apply to fetuses in whom ascending aorta dilation develops secondary to decreased afterload due to a low-resistance distal circulation, such as that which occurs in a VGAM. It has been reported that, in true coarctation, increased aortic compliance brings about dilation of the precoarctation aorta in systole, resulting in a persistence of stored upstream energy, manifested as a diastolic Doppler runoff when the precoarctation aortic walls contact. 12 We postulate that the same mechanism operates in VGAMs in utero and may perhaps be exaggerated by the highly compliant, low-resistance cerebral circulation. This may explain the Doppler flow observations described above, which may easily be mistaken for true coarctation. Information from the literature suggests that when a VGAM is large enough to be detected prenatally, as in our first case, then the likelihood of perinatal cardiac failure increases. 13 The fetus in case 1 had signs of volume overload and beginning cardiac decompensation (cardiomegaly, substantial tricuspid regurgitation, and sinus tachycardia) at 28 to 29 weeks gestation. The Figure 6. Fetal head with color Doppler image showing high flow in the VGAM. clinicians caring for the patient opted to begin digitalization in utero to improve the fetal hemodynamic status. Indeed, the follow-up fetal cardiac evaluation was reassuring. Unfortunately, the degree of cerebral parenchymal loss was so extensive that, despite the relative stability of the fetal and neonatal hemodynamic status, a poor outcome was inevitable. Persistent pulmonary hypertension of the neonate, as shown by case 2, is not an uncommon association in VGAM. 14 Bidirectional or pure right-to-left shunting through a PDA is pathognomonic for pulmonary hypertension. In its presence, coarctation of the aorta, especially if subtle, may be difficult to rule out. Serial Figure 7. Transverse 4-chamber view of the fetal heart showing cardiomegaly with marked right atrial and right ventricular dilation, along with a small concentric pericardial effusion. PE indicates pericardial effusion; RA, right atrium; and RV, right ventricle. J Ultrasound Med 2005; 24:93 98 97
echocardiographic examinations, showing eventual reversal of the shunt or a decrease in the size of the PDA with normalization of Doppler findings, along with continued clinical evaluation, are necessary to ultimately rule out true coarctation of the aorta. In summary, the echocardiographic findings in fetal and neonatal VGAMs include superior vena caval dilation with right atrial and right ventricular dilation due to an increased cardiac preload. The ascending aorta and the brachiocephalic vessels supplying the afferent flow to the VGAM will be markedly dilated due to the diminished afterload afforded by the highly compliant cerebral circulation. Retrograde diastolic flow in the transverse or proximal descending aorta just distal to the source of afferent blood flow is highly characteristic. Because of the demands for high cardiac output, fetal sympathetic tone is augmented, and sinus tachycardia is an invariable finding. High fetal cardiac output also results in increased Doppler flow velocities across all cardiac valves and great vessels, including the PDA. Anatomic and Doppler evidence of pseudocoarctation and persistent pulmonary hypertension of the neonate may also be shown. Although fetal hemodynamic impairment may be obviated by transplacental digitalization, the prognosis ultimately depends on the degree of cerebral involvement and associated fetal anomalies. References 1. de Koning TJ, Gooskens R, Veenhoven R, et al. Arteriovenous malformation of the vein of Galen in three neonates: emphasis on associated early ischemic brain damage. Eur J Pediatr 1997; 156:228 229. 2. Frawley GP, Dargaville PA, Mitchell PJ, Tress BM, Loughnan P. Clinical course and medical management of neonates with severe cardiac failure related to vein of Galen malformation. Arch Dis Child Fetal Neonatal Ed 2002; 87:F144 F149. 3. Vintzileos AM, Eisenfeld LI, Campbell WA, et al. Prenatal ultrasonic diagnosis of arteriovenous malformation of the vein of Galen. Am J Perinatol 1986; 3:209 211. 4. Mendelsohn DB, Hertzanu Y, Butterworth A. In utero diagnosis of a vein of Galen aneurysm by ultrasound. Neuroradiology 1984; 26:417 418. 5. Hirsch JH, Cyr D, Eberhardt H, Zunkel D. Ultrasonographic diagnosis of an aneurysm of the vein of Galen in utero by duplex scanning. J Ultrasound Med 1983; 2:231 233. 6. Fullerton HJ, Aminoff AR, Ferriero DM, Gupta N, Dowd CF. Neurodevelopment outcome after endovascular treatment of vein of Galen malformations. Neurology 2003; 61:1386 1390. 7. Truwit CL. Embryology of the cerebral vasculature. Neuroimaging Clin North Am 1994; 4:663 689. 8. Schmidt KG, Silverman NH, Harison MR, Callen PW. High-output cardiac failure in fetuses with large sacrococcygeal teratoma: diagnosis by echocardiography and ultrasound. J Pediatr 1989; 11:1023 1028. 9. Starc TJ, Krongrad E, Bierman FZ. Two-dimensional echocardiography and Doppler findings in cerebral arteriovenous malformation. Am J Cardiol 1989; 64:252 254. 10. McElhinney DB, Halbach VV, Silverman NH, Dowd CF, Hanley FL. Congenital cardiac anomalies with vein of Galen malformations in infants. Arch Dis Child 1998; 78:548 551. 11. Hornberger LK, Weintraub RG, Pesonen E, et al. Echocardiographic study of the morphology and growth of the aortic arch in the human fetus: observations related to the prenatal diagnosis of coarctation. Circulation 1992; 86:741 747. 12. De Groff CG, Orlando W, Shandas R. Insights into the effect of aortic compliance on Doppler diastolic flow patterns seen in coarctation of the aorta: a numeric study. J Am Soc Echocardiogr 2003; 16: 162 169. 13. Doren M, Tercanli S, Holzgreve W. Prenatal sonographic diagnosis of a vein of Galen aneurysm: relevance of associated malformations for timing and mode of delivery. Ultrasound Obstet Gynecol 1995; 6:287 289. 14. Hendson L, Emery DJ, Phillipos EZ, Bhargava R, Olley PM, Lemke RP. Persistent pulmonary hypertension of the newborn presenting as the primary manifestation of intracranial arteriovenous malformation of the vein of Galen. Am J Perinatol 2000; 17:405 410. 98 J Ultrasound Med 2005; 24:93 98