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

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Abstract

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.

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Acknowledgments

The authors thank Yumiko Shinohe deeply for her technical assistance. This study was supported by Grant-in-aid from the Ministry of Education, Science and Culture of Japan (No.011-0321).

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Authors and Affiliations

  1. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan

    Masaaki Hokari, Naoki Nakayama & Kiyohiro Houkin

  2. Department of Pathology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan

    Hiroshi Nishihara

Authors
  1. Masaaki Hokari
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  2. Naoki Nakayama
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  3. Hiroshi Nishihara
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  4. Kiyohiro Houkin
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Correspondence to Masaaki Hokari or Hiroshi Nishihara.

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Comments

Samuel L. Barnett, Dallas USA

In this study, the authors describe their findings that subintimal fibrin deposition and macrophage infiltration is a present in the majority of ruptured aneurysms. In the 28 ruptured aneurysms studied, histologic evidence of subintimal fibrin deposition was present in 92.9 % of the specimens and immunohistochemical evidence of chronic inflammation was present 100 % of the time. In contrast, these findings were only present in 16.7 and 33.3 % of unruptured aneurysms, respectively. This study provides further evidence that inflammatory changes probably play a significant role in aneurysm wall degeneration which may ultimately lead to rupture. We look forward to further studies from this group using electron microscopy to clarify the role of endothelial dysfunction in this process.

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Hokari, M., Nakayama, N., Nishihara, H. et al. Pathological findings of saccular cerebral aneurysms—impact of subintimal fibrin deposition on aneurysm rupture. Neurosurg Rev 38, 531–540 (2015). https://doi.org/10.1007/s10143-015-0628-0

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  • DOI: https://doi.org/10.1007/s10143-015-0628-0

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