Hemodynamic Effects of Developmental Venous Anomalies with and without Cavernous Malformations

Discussion

In view of the presence of some degree of altered perfusion around all the DVAs studied, our results indicate that the presence of a DVA is likely to be inherently associated with altered hemodynamics in the involved brain parenchyma. While supporting previous findings,^10,11 our results indicate that PWI is able to detect such perfusion alterations around most DVAs, not just anecdotal cases. The pattern of perfusion abnormalities in our study was also similar to that seen previously,^10,11 with higher relative CBV as well as MTT in the brain around the DVAs. A variable change in relative CBF (Fig 3) is also in accordance with that in previous studies.^10⇓–12

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Fig 3.

Axial contrast-enhanced T1-weighted image (A) demonstrates tributaries of the DVA in the right lentiform nucleus, seen as punctate enhancing foci. Corresponding rCBV (B), rCBF (C), and rMTT (D) maps demonstrate a zone of perfusion alteration around these tributaries incorporating otherwise normal-appearing brain tissue. Note that in this case, the alteration in rCBV and rMTT maps was more pronounced relative to the rCBF.

The pathogenesis of DVAs is not fully understood. Some investigators consider them to result from in utero thromboses of the developing venous system.^2,3,13,14 The dilated medullary veins converging onto a prominent collector channel in effect serve as a replacement of the normal venous system that would have otherwise existed in this part of the brain.² Consistent elevation of rMTT and rCBV seen in our study supports this model of DVA pathogenesis of a venous outflow, inherently less robust than normal venous drainage. Similar prolongation of MTT on PWI has been seen in the setting of other conditions affecting venous outflow, such as dural venous thrombosis or patients with Sturge-Weber syndrome.^15⇓–17 This increase in the MTT for DVAs, however, appears to be due to alterations in the CBV and CBF that follow a pattern distinct from that seen in other restrictive venous pathologies. As per the central volume theorem, MTT is simply a ratio of CBV and CBF.¹⁸ Prolongation of MTT in the presence of venous outflow restriction is usually the result of venous engorgement–induced increase in CBV, along with outflow restriction–induced reduction in CBF, as has been shown in diseases such as Sturge-Weber syndrome.^16,17

In contrast, in most of the DVAs studied by us and in previous reports, the increase in rMTT was seen in the setting of increased rCBV and a less pronounced increase in the rCBF. While the increased rCBV is easy to explain, elevation of rCBF around many DVAs is more difficult to explain solely on the basis of alterations in the venous development. Modest reactive vasodilation in arterioles has been demonstrated in response to venous dilation in animal studies.¹⁹ However, it is unlikely that such a reactive change is able to more than overcome the restrictive effects of the outflow restriction in the presence of venous outflow obstruction. The exact explanation for increased rCBF around DVAs remains unclear. However, it is possible that the developmental nature of the venous anomalies (as opposed to the acquired nature of venous obstruction in experimental models/pathologic venous obstruction) is somehow unique in that the etiologic factors responsible for formation of DVAs are also able to induce developmental changes in the arterial inflow that try to minimize stasis of blood in the affected brain by increasing the CBF in the face of increased CBV. A control cerebral blood flow indicator of close to 1 in brain parenchyma with normal venous drainage would argue against the possibility that these elevated relative CBF values are somehow representing artifacts.

Pathophysiologic implications of these results are also highlighted by the observed differences in the perfusion parameters of DVAs with and without CMs. A greater prolongation of MTT and a trend toward a lesser increase (or even decrease in individual cases) of rCBF in the CM group may be related to greater restrictive effects of DVAs in this group. Significant quantifiable differences in the perfusion parameters around developmental venous anomalies with and without associated cavernous malformations may reflect the role of hemodynamic factors in the development of these malformations. We hypothesize that in a large number of DVAs, the diminished venous capacity still has enough reserves to accommodate the physiologic needs, and such DVAs may remain completely asymptomatic. In other DVAs however, the restrictive effects on the venous drainage may be enough to cause local venous hypertension and thereby the propensity of these vessels to bleed and result in localized hemorrhage and subsequent CM formation. Given that the medullary veins composing the tributaries of the DVA are also known to have thinner walls, such veins may be more prone to bleed with this local venous hypertension.²⁰

DVAs generally fill later in the venous phase on catheter angiography. Our findings of prolonged rMTT are consistent with this observation because it has been previously demonstrated that the angiographic circulation time is proportional to the mean transit time.²¹ Previously, authors have also reported some complex DVAs demonstrating early venous drainage, attributing it to microshunts within the DVAs or possibly concomitant DVAs and arteriovenous malformations.^2,22,23 We did not have any patients with reduced rMTT as could be expected in these patients. While we did not have angiographic correlation for our patients, it is likely that given the rarity of such DVAs with microshunts,² our study failed to include any such patients.

Our study had limitations. The number of patients was relatively small, and our results may not be generalizable to all DVAs. While PWI cannot accurately measure the actual CBV and CBF, it does offer a robust method to evaluate the relative changes in the perfusion of the brain. This is supported by the fact that for brain parenchyma with normal venous drainage, relative perfusion values (cCBV, cCBF, and cMTT) were noted to be close to 1, as would be expected. It is possible that susceptibility effects of CMs can affect the relative perfusion values obtained in the surrounding brain parenchyma. While we cannot be certain of these additional susceptibility effects on the perfusion calculations, none of the ROIs were placed directly in the location of the CMs. In a similar manner, we took precautions not to place the ROIs directly on visible enhancing venous structures. Indeed, the correlation of the perfusions maps and the contrast-enhanced TIWI showed the perfusion alterations not to be restricted to the venous channels themselves but rather extending into the brain parenchyma in between the venous tributaries as well (Figs 1 and 3). However, it is possible that the elevated blood pool in the surrounding brain parenchyma could itself make the quantification of the perfusion parameters in this region less reliable. In a large number of individuals studied, the DVAs were either completely asymptomatic or the patient had symptoms that could not be directly ascribed to them. Similarly, acute hemorrhage was seen in only 1 DVA with an associated CM. It remains unknown whether DVAs with more pronounced symptoms or a greater propensity to bleed are associated with even greater hemodynamic perturbation.

CMs associated with DVAs are sometimes resected surgically. The decision to intervene, however, involves careful assessment of potential benefits and risks, including the risk of future expansion or hemorrhage of the CM. If the extent of altered hemodynamics in the surrounding brain tissue is associated with CM formation as indicated by our study, quantitative evaluation of such altered hemodynamics by using PWI may also provide a means for better assessment of future growth/hemorrhage of the CM. Future longitudinal studies will be needed to test this hypothesis.