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      High WSS or Low WSS? Complex Interactions of Hemodynamics with Intracranial Aneurysm Initiation, Growth, and Rupture: Toward a Unifying Hypothesis

      , , ,
      American Journal of Neuroradiology
      American Society of Neuroradiology (ASNR)

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          Abstract

          Increasing detection of unruptured intracranial aneurysms, catastrophic outcomes from subarachnoid hemorrhage, and risks and cost of treatment necessitate defining objective predictive parameters of aneurysm rupture risk. Image-based computational fluid dynamics models have suggested associations between hemodynamics and intracranial aneurysm rupture, albeit with conflicting findings regarding wall shear stress. We propose that the "high-versus-low wall shear stress" controversy is a manifestation of the complexity of aneurysm pathophysiology, and both high and low wall shear stress can drive intracranial aneurysm growth and rupture. Low wall shear stress and high oscillatory shear index trigger an inflammatory-cell-mediated pathway, which could be associated with the growth and rupture of large, atherosclerotic aneurysm phenotypes, while high wall shear stress combined with a positive wall shear stress gradient trigger a mural-cell-mediated pathway, which could be associated with the growth and rupture of small or secondary bleb aneurysm phenotypes. This hypothesis correlates disparate intracranial aneurysm pathophysiology with the results of computational fluid dynamics in search of more reliable risk predictors.

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          Most cited references32

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          Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association.

          The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). A formal literature search of MEDLINE (November 1, 2006, through May 1, 2010) was performed. Data were synthesized with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. The guideline draft was reviewed by 7 expert peer reviewers and by the members of the Stroke Council Leadership and Manuscript Oversight Committees. It is intended that this guideline be fully updated every 3 years. Evidence-based guidelines are presented for the care of patients presenting with aSAH. The focus of the guideline was subdivided into incidence, risk factors, prevention, natural history and outcome, diagnosis, prevention of rebleeding, surgical and endovascular repair of ruptured aneurysms, systems of care, anesthetic management during repair, management of vasospasm and delayed cerebral ischemia, management of hydrocephalus, management of seizures, and management of medical complications. aSAH is a serious medical condition in which outcome can be dramatically impacted by early, aggressive, expert care. The guidelines offer a framework for goal-directed treatment of the patient with aSAH.
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            Hemodynamic shear stress and its role in atherosclerosis.

            Adel Malek (1999)
            Atherosclerosis, the leading cause of death in the developed world and nearly the leading cause in the developing world, is associated with systemic risk factors including hypertension, smoking, hyperlipidemia, and diabetes mellitus, among others. Nonetheless, atherosclerosis remains a geometrically focal disease, preferentially affecting the outer edges of vessel bifurcations. In these predisposed areas, hemodynamic shear stress, the frictional force acting on the endothelial cell surface as a result of blood flow, is weaker than in protected regions. Studies have identified hemodynamic shear stress as an important determinant of endothelial function and phenotype. Arterial-level shear stress (>15 dyne/cm2) induces endothelial quiescence and an atheroprotective gene expression profile, while low shear stress (<4 dyne/cm2), which is prevalent at atherosclerosis-prone sites, stimulates an atherogenic phenotype. The functional regulation of the endothelium by local hemodynamic shear stress provides a model for understanding the focal propensity of atherosclerosis in the setting of systemic factors and may help guide future therapeutic strategies.
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              Saccular intracranial aneurysm: pathology and mechanisms.

              Saccular intracranial aneurysms (sIA) are pouch-like pathological dilatations of intracranial arteries that develop when the cerebral artery wall becomes too weak to resist hemodynamic pressure and distends. Some sIAs remain stable over time, but in others mural cells die, the matrix degenerates, and eventually the wall ruptures, causing life-threatening hemorrhage. The wall of unruptured sIAs is characterized by myointimal hyperplasia and organizing thrombus, whereas that of ruptured sIAs is characterized by a decellularized, degenerated matrix and a poorly organized luminal thrombus. Cell-mediated and humoral inflammatory reaction is seen in both, but inflammation is clearly associated with degenerated and ruptured walls. Inflammation, however, seems to be a reaction to the ongoing degenerative processes, rather than the cause. Current data suggest that the loss of mural cells and wall degeneration are related to impaired endothelial function and high oxidative stress, caused in part by luminal thrombosis. The aberrant flow conditions caused by sIA geometry are the likely cause of the endothelial dysfunction, which results in accumulation of cytotoxic and pro-inflammatory substances into the sIA wall, as well as thrombus formation. This may start the processes that eventually can lead to the decellularized and degenerated sIA wall that is prone to rupture.
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                Author and article information

                Journal
                American Journal of Neuroradiology
                AJNR Am J Neuroradiol
                American Society of Neuroradiology (ASNR)
                0195-6108
                1936-959X
                July 15 2014
                July 2014
                July 2014
                April 18 2013
                : 35
                : 7
                : 1254-1262
                Article
                10.3174/ajnr.A3558
                7966576
                23598838
                ee650d86-319a-4c9c-a90a-27ac6189a03a
                © 2013
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