Ep 14: Vein of Galen Malformation

Learning Objectives

By the end of this episode, NICU Grads will be able to:
1. Review the anatomy/embryology of vein of Galen malformation (VOGM).
2. Understand the pathophysiology & clinical manifestations of VOGM
3. Describe the diagnostic approach and therapeutic management to VOGM
4. Review current trends in prognosis and morbidity of VOGM

Epidemiology

• Rare intracranial arteriovenous malformation
• Incidence: 1 in 25,000
• VOGM accounts for 1% of all pediatric congenital malformations, 30% of all vascular malformations

Normal Embryology/Physiology of Cerebral Vein Development

• Prior to ~ 11-12 weeks of gestation, internal cerebral veins drain into vein of Markowski (VOM).
• After 12 weeks gestation, VOM involutes and cerebral and basal veins drain into what becomes the VOG.
• VOG drains posteriorly into the straight sinus–> transverse sinus–>sigmoid sinus –> jugular vein.

Pathogenesis

• Not clearly understood
• MOA: Lack of involution of VOM
• This leads to persistence of the VOM that abnormally connects to cerebral arterials instead of connecting with capillaries, which help slow blood flow.
• Bypassing capillaries leads to rapid circulation, high pressure and venous load into the VOG, dilation of the VOM, and the eventual development of VOGM.

Clinical Presentation

• Timing~65% present in neonatal period
•  If VOGM is small, may present later in life
• Symptoms vary depending on size of aneurysm and degree of shunting
• Most common neonatal presentation of VOGM= signs of high-output heart failure
• Cardiac signs and symptoms
  • Usually presents in first few hours of age and tends to worsen during first 3 days of age
  • ↑ heart rate & ↑ circulation blood volume to compensate for systemic steal/shunting of blood from systemic circulation to VOGM
  • High output cardiac failure 
  • Coronary artery ischemia
  • Shock physiology with impaired end organ perfusion
  • Pulmonary hypertension type pathophysiology
    • Can be easily misdiagnosed as persistent pulmonary hypertension of the newborn (PPHN)
    • Differentiating features:
      • Evidence of pulmonary overcirculation on chest X-ray points to VOGM
      • Intracranial bruit points to VOGM
• Pulmonary
  • Respiratory distress
  • Pulmonary edema
• Renal & Hepatic signs and symptoms
  • ↓ systemic cardiac output + reverse aortic end diastolic flow
  • Prerenal kidney injury 
  • Hepatic Insufficiency 
• Neurologic signs and symptoms
  • Continuous intracranial bruit
  • Brain injury (parenchymal ischemic/hemorrhagic injuries)
  • Hydrocephalus
    • ~15% of cases
    • Not usually observed in neonatal period, possibly secondary to aqueductal obstruction or elevated venous pressure
  • Encephalomalacia
  • Seizures
  • Developmental delay
  • Headaches, focal neurologic deficits, and syncope (especially if small aneurysm and symptoms present later in life)
  • MOA= Result of both intracranial venous hypertension and arterial steal from the cerebral circulation
    • Inadequate venous drainage + impaired CSF resorption–> ↑ intracranial pressure + impaired cortical development
    • Intracranial arterial steal secondary to disrupted intracranial hydrostatic balance + diastolic run-off

Diagnosis & Evaluation

• Timing~44% present in neonatal period
• Prenatal
  • 50% dx in utero
• Postnatal
  • Head ultrasound–> follow hydrocephalus / ICP without having to repeat MRIs
  • MRI Brain –> dx confirmation and evaluation for cerebral sequelae 
  • STAT EEG 
  • Echocardiogram
  • Labs
    • Liver panel
    • Coagulation panel
    • BUN/Cr
  • Consults: Neurology, Neurosurgery, Interventional Neuroradiology, Cardiology
  • Calculate Bicêtre Score- clinical decision tool to assist in determining the appropriateness and timing of embolization

MANAGEMENT 

• Prenatal
  • Fetal evaluation at an advanced maternal-fetal care center to confirm diagnosis, evaluate extent of malformation and plan for postnatal management
  • Inadequate data to support a certain mode of delivery
• Postnatal

• Timing and approach of treatment depends on age of patient, severity of congestive heart failure and structure of lesion 
• Main therapy goal is to:
  1. Reducing the effects of the shunt by balancing pulmonary and systemic perfusion
  2. Minimize congestive heart failure
  3. Achieve hemodynamic stability to allow for embolization
  4. Embolize arterial feeders to the malformation
• Utilize Bicêtre Score to determine the appropriateness and timing of embolization
• Best possible score of 21, and the lower the score is the sicker the patient is. 
  • <8      No treatment
    • Represents severe compromise in cardiac output and end organ effects
    • Presence of prenatal neurologic sequelae or cardiac enlargement 
    • Prenatal findings believed to be incompatible with life with 100% mortality in some case
    • Comfort care candidate
  • 8-12    Emergent embolization
    • Arterial >>>>> Venous
      • UAC (first 3 days) or femoral artery approach
      • Venous embolization is technically easier but higher risk of deep venous thrombosis and less hemodynamic control. 
    • Goal is for hemodynamic normalization and NOT anatomic correction
      • 30-50% stepwise reduction each time to avoid the massive hemodynamic shifts associated with occlusion of a VOGM
    • 2-3 embolizations, 4-6 weeks apart
    • Complete by 1 year of age
  • >12     Embolization after 5 months old
    • Cardiac
      • Diuretics: ↓ preload
      • Fluid restriction: ↓ preload
      • Inotropes: improve contractility, cardiac output
    • Pulmonary
      • iNO for pHTN
    • Renal/Hepatic
      • Monitor rine output, BUN/Cr, LFTs
    • Neurologic
      • Monitor developmental milestone, head circumferenc, head ultrasound if concern for hydrocephalus 
      • Embolization
        • If cardiac failure is medically-controlled with diuretics, embolization can be deferred until 3 to 5 months of age to balance the risk of embolization with the risk of delayed cerebral maturation
      • Ventriculoperitoneal shunt (VPS)??? 
        • There are case reports and case series showing worsening of clinical outcome from shunt.  
        • But why does it make things worse?  
          • VPS may reverse the pressure gradient between the ventricles and brain parenchyma and thus, might give temporary immediate relief. However, long term it actually worsens venous congestion and brain edema in the case of VOGM.
        • Treating the VOGM with embolization many times can ameliorate increased cranial pressure resulting in <50% needing a VPS.

PROGNOSIS 

• Outcome dependent on severity of congestive heart failure, degree of brain injury and whether pt received embolization
• Embolization has dramatically improved survival rates and reduced neurologic morbidity.
• Despite therapeutic techniques, morbidity and mortality remain high. 
  • 1/3 survive with good outcome, 1/3 survive with fair outcome, 1/3 die
• Moderate to severe neurodevelopmental delay associated with VOGM varies from 17% to 26%.

References

1. Berenstein A, Fifi JT, Niimi Y, Presti S, Ortiz R, Ghatan S, Rosenn B, Sorscher M, Molofsky W. Vein of Galen malformations in neonates: new management paradigms for improving outcomes. Neurosurgery. 2012 May;70(5):1207-13; discussion 1213-4. doi: 10.1227/NEU.0b013e3182417be3.
2. Madhuban, Andjenie et al. “Vein of Galen Aneurysmal Malformation in Neonates Presenting With Congestive Heart Failure.” Child neurology open vol. 3 2329048X15624704. 4 Apr. 2016, doi:10.1177/2329048X15624704
3. Wong, F., Mitchell, P., Tress, B. et al. Hemodynamic disturbances associated with endovascular embolization in newborn infants with vein of Galen malformation. J Perinatol26, 273–278 (2006).doi.org/10.1038/sj.jp.7211479
4. Puvabanditsin S, Mehta R, Palomares K, et al. Vein of Galen malformation in a neonate: A case report and review of endovascular management. World J Clin Pediatr. 2017;6(1):103-109. Published 2017 Feb 8. doi:10.5409/wjcp.v6.i1.103
5. Hansen D, Kan PT, Reddy GD, Mohan AC, Jea A, Lam S. Pediatric knowledge update: Approach to the management of vein of Galen aneurysmal malformations in neonates. Surg Neurol Int 13-May-2016;7.
6. Brain AVM (arteriovenous malformation), Mayo Foundation for Medical Education and Research (MFMER), May 2019, www.mayoclinic.org/diseases-conditions/brain-avm/symptoms-causes/syc-20350260.
7. Richard J. Martin, Avroy A. Fanaroff, Michele C. Walsh. (2015). Fanaroff and Martin’s neonatal-perinatal medicine: diseases of the fetus and infant. Philadelphia, PA: Elsevier/Saunders.
8. Brodsky, Dara, and Camilia Martin. Brodsky and Martin’s Neonatology Review Series. 3rd ed., Lulu, 2020.
9. Brodsky, Dara. Neonatology Review: Q&A. 3rd ed., Lulu, 2016.
10. Chess, Patricia. Avery’s Neonatology Board Review: Certification and Clinical Refresher. 1 ed., Elsevier, 2019.
11. Polin, Richard A., and Mervin C. Yoder. Workbook in Practical Neonatology. 5th ed., Saunders, 2014.

Credits

• Written and Produced by: Neena Jube-Desai MD, MBA FAAP
• Cover Art by: Neena Jube-Desai MD, MBA FAAP
• Host: Neena Jube-Desai MD, MBA FAAP
• Editor: Neena Jube-Desai MD, MBA FAAP
• Guest: Ashley Lucke, MD, FAAP