Structural fragility and inflammatory response of ruptured cerebral aneurysms. A comparative study between ruptured...

Despite technical advances in endovascular and microsurgical treatment, patients with aneurysmal subarachnoid hemorrhage still have a high mortality and morbidity rate. To improve the treatment results in patients with aneurysms, we must better understand the pathophysiology of cerebral aneurysms and the mechanisms leading to their rupture. Therefore, we studied the pathological differences between unruptured and ruptured aneurysms.

Ruptured (n=44) and unruptured (n=27) aneurysms were obtained at surgery. The aneurysmal endothelium was scored from 0 (normal) to 5 (complete disruption) by using a scanning electron microscope. The aneurysmal wall was evaluated by immunohistochemical methods. The wall structure was scored from 1 (dense collagen and rich, smooth muscle cells) to 5 (hyaline-like structure). The degree of inflammatory cell invasion into the wall was also scored from 0 (very few cells) to 3 (many cells).

Ruptured aneurysms manifested significant endothelial damage (score of 3.7 versus 0.8; Mann-Whitney U test, P<10(-3)), significant structural changes of the wall (3.7 versus 1.7, P<10(-5)), and significant inflammatory cell invasion (2.2 versus 0.8, P<10(-4)) compared with unruptured aneurysms. There was a significant correlation between the score for wall structure and the score for inflammatory cell invasion (Rs=0. 63; Spearman rank correlation test, P<10(-5)). The pathophysiology of several symptomatic unruptured aneurysms was similar to that of ruptured aneurysms.

We conclude that the pathophysiology of unruptured, asymptomatic and ruptured aneurysms is different. The wall of ruptured aneurysms was found to be fragile, possibly because macrophage infiltration into the aneurysmal wall resulted in loss of smooth muscle cells and in degradation of matrix proteins.