Intracranial arterial aneurysm vasculopathies: targeting the outer vessel wall

Abstract

The pathogenesis of intracranial arterial aneurysms (AA) remains unclear, despite their clinical importance. An improved understanding of this disease is important in choosing therapeutic options. In addition to the "classical" berry-type aneurysm, there are various other types of intracranial AA such as infectious, dissecting or giant, partially-thrombosed aneurysms. From the clinician's perspective, the hypothesis that some of these intracranial AA might be due to abluminal factors has been proposed for several years. Indeed, this hypothesis and the empirical use of anti-inflammatory drugs in giant intracranial aneurysms have been confirmed by recent studies reporting that an enzyme involved in the inflammatory cascade (5-lipoxygenase or 5-LO) promotes the pathogenesis of specific aneurysms in humans. 5-LO generates different forms of leukotrienes which are potent mediators of inflammation. Adventitial inflammation leads to a weakening of the media from the abluminal part of the vessel wall due to the release of proinflammatory factors that invade the media, thereby degrading the extracellular matrix, the elastic lamina of the vascular wall, and, finally, the integrity of the vessel lumen. This in turn results in a dilation of the vessel and aneurysm formation. Moreover, neoangiogenesis of vasa vasorum is found in close proximity to 5-LO activated macrophages. In addition to this biological cascade, we argue that repeated subadventitial haemorrhages from the new vasa vasorum play an important role in aneurysm pathogenesis, due to a progressive increase in size mediated by the apposition of new layers of intramural haematoma within the vessel wall. Intracranial giant AA can therefore be regarded as a proliferative disease of the vessel wall induced by extravascular activity. Considering certain aneurysmal vasculopathies as an abluminal disease might alter current therapeutic strategies. Therapy should not only be aimed at the intraluminal repair of the artery, but also cross the vessel wall to reach the vasa vasorum. Drug-eluting stents placed proximal to the lesion and targeted to the origin of the vasa vasorum could be considered as a potential future option. "Intelligent" MRI contrast agents (i.e., macrophage marking) could be used to detect vasa vasorum proliferation and weakening of the vessel wall in vivo.

Partially Thrombosed Intracranial Aneurysms Presenting with Mass Effect: Long-Term Clinical and Imaging Follow-Up after Endovascular Treatment

“…Some propose that the vasa vasorum of the aneurysmal wall play a crucial role in the development and growth of aneurysms with intraluminal thrombus by proliferation, inflammation, and rupture. [25][26][27] These authors suggest that these aneurysms should be treated by targeting the outer vessel wall and not the aneurysmal lumen. Our study does not confirm this theory.…”

Partially Thrombosed Vertebral Artery Aneurysm With Wall Enhancement Treated by Stent-Assisted Coil Embolization -Case Report-

“…These``abluminal'' aneurysmal vasculopathies could be aggravated by``luminal'' aneurysmal vasculopathies. 8) Abluminal factors may also be related to hypercholesterolemia, atherosclerosis, and chronic inflammation. 4) A stepwise mechanism may account for progression of dolichoectatic aneurysms based on pathologic findings.…”

The Many Faces of Intracranial Arterial Dissections

“…perifocal edema and an onion skin appearance of the intramural hematoma suggesting blood of varying ages and subsequent growth over time) [20][21][22] (Figure 8). Treatment of these lesions is probably the greatest challenge of all dissecting processes since they may be regarded as a proliferative disease of the vessel wall with growth induced by extravascular activity.…”