Pathological findings of saccular cerebral aneurysms—impact of subintimal fibrin deposition on aneurysm rupture

Although several studies have suggested that aneurysmal wall inflammation and laminar thrombus are associated with the rupture of saccular aneurysms, the mechanisms leading to the rupture remain obscure. We performed full exposure of aneurysms before clip application and attempted to keep the fibrin cap on the rupture point. Using these specimens in a nearly original state before surgery, we conducted a pathological analysis and studied the differences between ruptured and unruptured aneurysms to clarify the mechanism of aneurysmal wall degeneration. This study included ruptured (n = 28) and unruptured (n = 12) saccular aneurysms resected after clipping. All of the ruptured aneurysms were obtained within 24 h of onset. Immunostainings for markers of inflammatory cells (CD68) and classical histological staining techniques were performed. Clinical variables and pathological findings from ruptured and unruptured aneurysms were compared. Patients with ruptured or unruptured aneurysms did not differ by age, gender, size, location, and risk factors, such as hypertension, smoking, and hyperlipidemia. The absence or fragmentation of the internal elastica lamina, the myointimal hyperplasia, and the thinning of the aneurysmal wall were generally observed in both aneurysms. The existence of subintimal fibrin deposition, organized laminar thrombus, intramural hemorrhage, neovascularization, and monocyte infiltration are more frequently observed in ruptured aneurysms. Multivariate logistic regression analysis showed that ruptured aneurysm was associated with presence of subintimal fibrin deposition and monocyte infiltration. These findings suggest that subintimal fibrin deposition and chronic inflammation have a strong impact on degeneration of the aneurysmal wall leading to their rupture, and this finding may be caused by endothelial dysfunction.