Fetal and Neonatal MRI Predictors of Aggressive Early Clinical Course in Vein of Galen Malformation

DISCUSSION

Vein of Galen malformation is a rare congenital vascular anomaly with a complex and potentially devastating outcome. The presence of a cerebral arteriovenous shunt with resultant high cardiac output leads to multiple possible morbidities: severe pulmonary hypertension, increased cardiac preload, holodiastolic reversal of flow in the descending aorta with concomitant organ hypoperfusion, cerebral venous congestion and hypertension, and so forth. In severe cases, the persistent arteriovenous shunting may lead to multiorgan failure and progressive destruction of hemispheric white matter and cortical parenchyma.¹⁰ This severely affected cohort (NAR), representing approximately two-thirds of neonates with VOGM, continues to have a high mortality rate and a high rate of severe neurodevelopmental morbidity among survivors, despite advances in neuroendovascular management.⁷ However, other patients with VOGM of similar overall caliber do not decompensate physiologically, do not require intubation or cardiac support, are discharged home from the neonatal intensive care unit, and are treated electively at several months of age. This latter group (IT) has a mortality rate of ∼10%.

For the past 2 decades, the most widely used clinical scale for grading VOGM severity at presentation has been the Bicêtre neonatal evaluation score.¹¹ Low scores on this scale (<8), consistent with multiorgan presentation, have been used in many centers as a rationale for withholding all treatment efforts; high scores (>12) have been used as a rationale for watchful waiting; and midrange scores (8–12), as an indicator of the need for urgent embolization. However, it has become clear that with expert treatment, some neonates scoring in the <8 range can have good outcomes and most referral centers no longer use strict score cutoffs for assignation of care. Moreover, the Bicêtre score is based on clinical criteria and is, thus, post hoc. It cannot be calculated during the antenatal period; and even at birth, it is impossible to predict how a given patient will evolve. Thus, to direct clinical resources appropriately, to offer families a realistic assessment of likely clinical outcome, and to identify an appropriate cohort to whom novel therapies should be directed, a need for a mechanism for prognosticating fetal outcomes exists. The present study was conducted to assess whether select vascular parameters on fetal MR imaging could play this role.

Measurements can be reliably obtained on MR imaging of most relevant fetal and neonatal vascular architecture. We found that vascular parameters on neonatal MR imaging revealed widespread dilation of both arterial and venous structures in patients in the NAR cohort compared with those in the IT cohort; to the best of our knowledge, these measurements have not been systematically evaluated previously.

However, we reasoned that the point of greatest constriction to flow return from the malformation to the systemic circulation might serve as the single most efficient predictor of neonatal outcome. Indeed, we found that in both fetal and neonatal MR imaging, patients with lesser constriction at this critical point (ie, those with a large mediolateral diameter or cross-sectional area of the straight or falcine sinus at its shortest section) were at significantly greater risk of evolving to NAR; thus, dilation at this point was sharply predictive of mortality and the need for neonatal intervention. The rationale behind choosing the mediolateral axis for diameter measurement was because the falcine and straight sinuses are tightly tacked by the dural reflection on the rostral and caudal edges of the sinus (thus the choice of the section with the shortest height as the section of interest), while the lateral walls of the sinus are free and unattached. This degree of freedom allows the sinus to expand or contract in the lateral plane as a function of flow; thus, the mediolateral diameter serves as an anatomic marker of flow. These measurements were readily obtained from both fetal and neonatal MR imaging and can be reliably quantified in either the axial or coronal plane, as long as a cross-referenced sagittal sequence is available to identify the shortest section of the sinus. While other studies have suggested broadly that a dilated straight sinus was a poor prognosticator for patients with VOGM on both MR imaging and sonography, none of these studies detailed where or how to measure dilation, and no quantitative or systematic analysis was performed.^12,13 The specific measurement we put forward here has not been previously described. The utility of this technique in terms of readily differentiating cohorts with very low likelihood versus very high likelihood of evolution to NAR is illustrated in Table 6, even for a single MR imaging reader.

Most interesting, median prosencephalic varix size itself was not a predictor of clinical evolution to NAR versus IT, a finding in conflict with some earlier reports. Paladini et al¹² found that a VOGM varix volume of >20,000 mm³ was predictive of poor outcome and parenchymal injury. On the other hand, Saliou et al¹⁴ found that the size of the varix on prenatal MR imaging was not predictive of poor outcome, as others had reported.¹¹ We would note that Paladini et al grouped patients with VOGM who had neurologic sequelae, neonatal death, and termination of pregnancy into a single cohort, while in the present study, NAR assignation was determined by neonatal death or need for urgent neonatal embolization. In the same study, Saliou et al reported on middle cerebral artery “pseudofeeders” on fetal MR imaging as a risk factor for poor clinical prognosis, but we found making standardized assessments of middle cerebral artery branches in the Sylvian fissure to be very challenging, largely due to variable fetal positioning.

Quisling and Mickle¹⁵ performed transtorcular venous pressure measurements on a small cohort of patients. They found that patients with an enlarged straight or falcine sinus trended toward increased venous pressures. Additionally, 1 patient presented with a normal straight sinus and normal pressure; but across time, the straight sinus dilated and repeat measurement found elevated pressure. The relationship between straight or falcine sinus dilation and venous pressure is difficult to prove on the basis of that small study but does represent an interesting direction for further research.

The major limitation in this study is the small sample size (in keeping with the rarity of VOGM), along with incomplete measurements in some cases due to either image quality or lack of relevant MR imaging sequences. Even with these limitations, our central finding was quite robust.