ISUIA: the old problem.

Key point:


  • To analyze the controversy concerning the risk of rupture of small intracranial aneurysms.

In the last post, we have concluded that when an unruptured intracranial aneurysm is identified we have to decide whether the "patient" (and not only the aneurysm) should be treated and whether it should be treated with endovascular or neurosurgical techniques. But for years our decision making has been influenced by results of the International Study of Unruptured Intracranial Aneurysms (ISUIA).

ISUIA Results

<7 mm no RF <7 mm with RF 7-12 mm 13-24 mm ≥ 25 mm
Cavernous carotid 0 0 0 3 6.4
AC/MC/IC 0 1.5 2.6 14.5 40
Post – P comm 2.5 3.4 14.5 18.4 50

5-year cumulative rupture rates according to size and location of unruptured aneurysm

ISUIA is a longitudinal prospective study, which found that larger aneurysms are more likely to rupture.

Is it true? 

The problem is that ISUIA study failed to resolve one of the fundamental clinical problems: the discrepancy between their reported extremely low rupture risk in asymptomatic aneurysms <7 mm at 0.7% per year compared to the large proportion of ruptured aneurysms in the same category. In fact, in contrast to the findings of the ISUIA, several studies showed that the majority of SAHs result from aneurysms <10 mm in size and a significant proportion of patients present with ruptured aneurysms <5 mm in diameter (Korja et al.). The high percentage of ruptured small IAs among ruptured IAs clearly indicates that small IAs can rupture without becoming large IAs. This thing suggests that there are some intrinsic differences between small and large IAs in morphological and hemodynamic features.

Varble et al. inquired whether small and large IAs might have different rupture risk profiles. They used a cutoff of 5 mm and they found that there are some different hemodynamic and clinical, but not morphological, rupture discriminants.

Shared and distinct rupture discriminants between small and large IAs

SHARED DISCRIMINANTS DISTINCT DISCRIMINANTS
a history of SAH low WSS predict large IA rupture
higher UI (surface irregularity) high OSI predict small IA rupture

WSS=wall shear stress; OSI=oscillatory shear index.

This previous study indicated that small and large IAs have different paths to rupture and demonstrated that 5 mm is the best cutoff.

"Different paths to rupture" does not mean "Different risk of rupture"
Hemodynamics: the big problem

Aneurysmal geometry and hemodynamics are mutually causal: Geometry instantaneously determines flow conditions, while flow drives aneurysm remodeling/growth through pathobiology, thereby determining future geometry (ie, enlargement and shape change). As this process continues, an intracranial aneurysm will either grow until homeostasis (stability) is reached or until its wall strength can no longer withstand the hemodynamic stress, in which case rupture occurs.

Triangular relationship among geometry, flow, and pathobiology.

Intracranial aneurysm growth and rupture are related to aberrant hemodynamics, chiefly through abnormal WSS, that cause destructive changes to outweigh eutrophic changes, making the aneurysm wall increasingly weaker and prone to rupture. It means that while the rupture episode itself is triggered by temporary pressure and/or frequency surge and wall failure, the predisposition of an intracranial aneurysm wall to rupture is due to biologic degradation, mediated by the interaction between hemodynamics and pathobiology with time. Pathobiological events induced by hemodynamic phenomena lead to formation of different aneurysmal phenotypes:

  • type I – small aneurysms with uniformly thin, smooth, hypocellular, translucent walls, through which reddish blood flow can be visualized at the time of surgical clipping;
  • type II – entirely thick walled large aneurysms (10 mm), with an irregular surface on which whitish/yellowish atherosclerotic plaques obstruct the visualization of blood;
  • type III – medium-sized aneurysms with a combination of thin and thick walled characteristics in different regions or with intermediate wall thickness.

In conclusion what is evident from these articles is that:

  • Growth and rupture of IAs are dynamic conditions, related to hemodynamic changes.
  • "Larger size = higher risk" is an old idea, because small aneurysms need to be carefully evaluated by relying on different indicators.

Reference

  • * Johnson AK, Heiferman DM, Lopes DK. Stent-assisted embolization of 100 middle cerebral artery aneurysms. J Neurosurg. 2013 May;118(5):950-5. doi: 10.3171/2013.1.JNS121298. Epub 2013 Feb 8.
  • Alreshidi M, Cote DJ, Dasenbrock HH, Acosta M, Can A, Doucette J, Simjian T, Hulou MM, Wheeler LA, Huang K, Zaidi HA, Du R, Aziz-Sultan MA, Mekary RA, Smith TR. Coiling Versus Microsurgical Clipping in the Treatment of Unruptured Middle Cerebral Artery Aneurysms: A Meta-Analysis. Neurosurgery. 2018 Feb 9. doi: 10.1093/neuros/nyx623. [Epub ahead of print]
  • Varble N, Tutino VM, Yu J, Sonig A, Siddiqui AH, Davies JM, Meng H. Shared and Distinct Rupture Discriminants of Small and Large Intracranial Aneurysms. Stroke. 2018 Apr;49(4):856-864. doi: 10.1161/STROKEAHA.117.019929. Epub 2018 Mar 13.
  • Meng H, Tutino VM, Xiang J, Siddiqui A. High WSS or low WSS? Complex interactions of hemodynamics with intracranial aneurysm initiation, growth, and rupture: toward a unifying hypothesis. AJNR Am J Neuroradiol. 2014;35:1254–1262. doi: 10.3174/ajnr.A3558.

Leave a Reply