Association between Venous Angioarchitectural Features of Sporadic Brain Arteriovenous Malformations and Intracranial Hemorrhage

Discussion

Intracranial hemorrhage accounts for most of the morbidity and mortality caused by brain AVMs. Natural history studies have reported markedly different hemorrhage rates, ranging from 1% to 34% risk of rupture, with multiple previously identified risk factors affecting these rates.³ Among these, numerous angiographic characteristics of the venous components of these malformations have been noted to affect hemorrhage risk. While certain trends have been identified, disparate results have been reported concerning several venous features. The current study seeks to clarify the role of such venous characteristics by examining a large prospectively maintained series of patients that have been uniformly evaluated on the basis of consensus recommendations.¹

Deep venous drainage is the single characteristic most frequently associated with AVM hemorrhage.^{4⇓⇓⇓–8} The current study supports this widely reported finding, with exclusively deep drainage more commonly associated with hemorrhage than exclusively superficial or mixed superficial and deep venous drainage. This was the strongest predictor noted in this study. Of note, the subgroup of AVMs in our cohort with superficial nidus location and exclusively deep venous drainage (perhaps implying occlusion of previously extant superficial veins) had a particularly high frequency of hemorrhagic presentation (OR, 9.12; P = .002).

AVMs with fewer draining veins have shown higher rates of hemorrhage in prior studies.^{9⇓⇓⇓⇓⇓⇓⇓–17} Analysis has varied, with some studies looking at correlations of numbers of draining veins^{14⇓⇓–17} and other studies categorizing or dichotomizing numbers to compare hemorrhagic risks.^{9⇓⇓⇓–13} The current study found that lesions with a single draining vein were more likely to be associated with hemorrhage at the time of initial clinical presentation. This finding has face validity: Fewer draining veins mean fewer potential routes for egress of blood from an AVM, thus presumably increasing the likelihood of AVM pressurization and rupture when any given draining vein thromboses.

Venous ectasia has been examined in previous studies, and there is no consensus on the role of ectasia and the risk of hemorrhage. Some studies report increased risk of hemorrhage,^8,13,18,19 while other reports suggest no impact¹² or a protective role for ectasia.^11,20 This study found that venous ectasia is inversely related to intracerebral hemorrhage. This finding may reflect an adaptive mechanism whereby such dysmorphism supports either a greater efferent capacitance and/or more functional arterialization of the draining veins. Venous ectasia also appears to develop with time, with older patients more likely to demonstrate this feature than younger patients in our cohort.²¹ In our cohort, exceedingly few patients with ectasia have experienced repeat hemorrhage; we have described one of these patients elsewhere.²²

Similar to ectasia, stenosis or occlusion of draining veins has been examined in prior studies with no resulting consensus. Some studies report increased risk of hemorrhage,^{4,9,18,20,23,24} while other reports suggest no independent effect.^11,12,25 Venous stenosis offered no predictive value in the current study. Of course, cerebral veins that are completely thrombosed are not directly visible on DSA and only inconsistently identifiable on CT and MR imaging, thus limiting the utility of this measure.

Venous reflux is a less commonly discussed finding but has been suggested to identify lesions more likely to cause hemorrhage, presumably because reflux is an indicator of increased venous pressure.^18,26 However, venous reflux was inversely related to hemorrhage in univariable analysis in this study. This association did not persist in the multivariable model, suggesting interaction with other variables.

When considering numerous characteristics, there is potential for confounding variables. For example, multiple series have shown that smaller AVMs are more likely to bleed. However, small AVMs are also likely to have fewer draining veins, which also carry an increased association with hemorrhagic risk. Similarly, central lesions are more likely to rupture, but these lesions are also more likely to have deep draining veins. In the current analysis, age at diagnosis and the presence of venous reflux demonstrated statistical significance in univariable analysis, but their roles were not confirmed in the multivariable analysis. Size persisted as a significant predictor of intracerebral hemorrhage in multivariable analysis, though to a lesser degree than singular venous outflow or deep venous drainage.

While this study identifies an association of venous architectural features with intracranial hemorrhage, it has several limitations. This was a cross-sectional analysis of prospectively enrolled patients in a robustly designed data base, but it examined an outcome that occurred contemporaneously with or before enrollment. Hemorrhagic association was based solely on imaging features and did not account for clinical features. Furthermore, analysis allowed by this database did not permit differentiation between hemorrhage occurring acutely at the time of enrollment or evidence of prior hemorrhage noted on noninvasive imaging at the time of enrollment. Additionally, the analysis does not distinguish the hemorrhagic location (eg, intraparenchymal versus intraventricular). Furthermore, it is possible that hemorrhage may alter angioarchitectural features in such a way that they differ from what would be identified before the hemorrhage.

Further investigation is warranted for both clinical and angiographic features that can predict AVM hemorrhage, to most accurately stratify hemorrhagic risk and thereby identify patients most suitable for treatment. This is particularly important because of the publication of the A Randomized Trial of Unruptured Brain Arteriovenous Malformations study,²⁷ wherein a relatively short follow-up of previously unruptured AVMs demonstrated inferior outcomes for patients who received therapeutic interventions compared with patients who received conservative medical follow-up.