Figure 4.

Pathogenesis of intracerebral giant artery aneurysm formation. Frame A demonstrates a model of the vasa vasorum and the 5-lipoxygenase pathway participation in leukocyte recruitment, arterial remodelling and, finally intracerebral arterial giant aneurysm formation. Macrophages reach the adventitia via vasa vasorum, that arise from the parent vessel themselves (see frames B-G). These adventitial macrophages express 5-lipoxygenase (5-LO) and, subsequently generate leukotrienes which in turn activate (1) T cells, (2) other macrophages, (3) proliferation of vasa vasorum and (4) monocytes and lead to an increased extravasation of leukocytes from the vasa vasorum to the adventita. These activated leukocytes release proinflammatory factors (such as metalloproteinases) that damage the media by degradation of the extracellular matrix (ECM) and the elastic lamina that lead to a focally weakened parent vessel wall from which subsequently the aneurysmal lumen may form (5) (13). We complement this biological cascade with the traditional clinical observation of subadventitial hematomas in so-called "partially thrombosed aneurysms": Repeated subadventitial bleeding from the vasa vasorum (6) lead to an onion-shaped intramural hematoma of different ages, which can be perceived in the example of a giant aneurysm of the basilar tip in a 60 year old woman (Frames B-E) who presented with a partial third cranial nerve palsy along with a contralateral moderate hemiparesis. Frames B and C were taken on admission and show the "partially thrombosed" aneurysm with "clots" of different ages represented by crescent-shaped signal alterations in the vessel wall. Frame D was taken one year later and demonstrate a new crescent-shaped peripheral hematoma in the outer vessel wall (arrow). Digital subtraction angiography (DSA) in 3D (Frame E) shows the lumen of the aneurysm, however, the greatest part (i.e. the subadventitial hematoma) of the aneurysm is not visualized, since DSA can only depict intraluminal portions of the vessels. Frames F and G schematically explain the increase in size as being due to recurrent hemorrhages into the aneurysm vessel wall from the vasa vasorum leading to onion-shaped thrombus formations within the adventita (12). (BA: basilar artery, PCA: posterior cerebral artery, SCA: superior cerebellar artery).