Comparative ultrastructural and stereological analyses of unruptured and ruptured saccular intracranial aneurysms

Background - Patients with intracranial aneurysms (IA) who have a high risk of rupture benefit from preventive treatment, but the ability to identify high risk IA is poor, with size being the main determinant. We characterized and quantified (ultra)structural differences between unruptured and ruptured aneurysm walls, to identify potential determinants of IA rupture. Methods- Six unruptured and six ruptured IA fundi were resected after microsurgical clipping and analyzed by correlative light microscopy (LM) and transmission electron microscopy (TEM). Quantitative analysis expressed as proportion of the vessel wall area was performed on LM samples and qualitative ultrastructural analysis on TEM samples. Results- Quantitative analysis revealed extensive internal elastic lamina (IEL) thickening in ruptured aneurysms (36.3% ±15), while thin and fragmented IEL is a common feature in unruptured IA (5.6%±7.1). The analysis also indicated extensive inflammation: Macrophages were more often found in ruptured IA (28.3% ±24) than in unruptured IA (2.7% ±5.5), as were leukocytes (12.85% ±10 in ruptured IA and 0% in unruptured IA). Vasa vasorum in ruptured IA contained vast numbers of inflammatory cells and extravasation of these cells into the vessel wall was observed, both in contrast to unruptured IA. Conclusions- Compared to unruptured IA, ruptured IA have significantly thicker IEL, and heavy inflammation throughout the vessel wall. Vasa vasorum might be a pathway by which inflammatory cells enter the vessel wall. Differences identified may be helpful in developing tools to identify rupture prone IA and thereby tailor treatment of patients with unruptured IA in the future. (Figure Presented).