Produção Nacional
Revisado por pares
Pathogenesis, hemodynamics, and growth of intracranial aneurysms: Future directions
2016; Wiley; Volume: 300; Issue: 7 Linguagem: Inglês
10.1002/ar.23530
ISSN1932-8494
AutoresPatricia Bozzetto Ambrosi, Carlos Augusto Carvalho de Vasconcelos, J. Moret, Laurent Spelle, Marcelo Moraes Valênça,
Tópico(s)Acute Ischemic Stroke Management
ResumoTreatments using flow diversion or disrupting stents have increasingly gained attention due to being less invasive, and because of increased levels of safety, as well as being feasible and having high success rates (Tse et al., 2013; Chalouhi et al., 2015). This is especially true for large, dysplastic, and wide-neck aneurysms (Brinjikji et al., 2009; Huang et al., 2009; Byrne and Szikora, 2012). In addition, intravascular flow modifying stents are effective tools that act directly on the pathogenesis of intracranial aneurysms (McAuliffe and Wenderoth, 2012; Huang et al., 2013). An intracranial aneurysm is a vascular ectasia arising from the wall of intracranial arteries, predominantly in the cerebral arterial circle of Willis, in most cases of saccular form (Keedy, 2006) (Fig. 1). However, irrespective of its shape and location, an intracranial aneurysm is a disease within the vascular wall, particularly at the level of the endothelium of blood vessels. Endothelial cells respond physiologically to changes in blood flow patterns. Therefore, flow diverting stents are designed to act by promoting a temporary scaffold for proliferation of endothelial cells, with healing to the formation of a new vascular wall and stimulating aneurysmal thrombosis (Tremmel et al., 2010). Image tridimensional obtained from patient with ICA giant aneurysm during pre-assessment of vessels of circle arterial of Willis using 3D-DSA for stenting planning. One of our challenges is to understand the interplay of biological and hemodynamic processes involved in the formation and progression of intracranial aneurysms. Examples of incomplete understanding of interplay are initiation of aneurysms, their growth, the inflammatory and degenerative processes related to an aneurysm's rupture, and eventual recanalization (Sforza et al., 2009). Another interesting element regards to the behavior of intracranial aneurysms, which is unpredictable. Although aneurysms are dynamic, they often remain unnoticed until they are detected incidentally. Also, the true prevalence of intracranial aneurysms is not known, and the current consensus in clinical decisions is often to avoid subarachnoid hemorrhage (Turjman et al., 2014). Populational studies show that ∼85% of intracranial saccular aneurysms develop in the internal carotid circulation. More specifically, ∼35% appear on the complex anterior communicating artery, followed by carotid artery (∼30%) and middle cerebral artery (∼22%). They are less common in the posterior circulation at the top of the basilar artery and along its branches. Multiple aneurysms are found in about ∼30% of patients who already have at least one aneurysm (Keedy, 2006). A preponderance of intracranial aneurysms occurs in women, which increases with the number of aneurysms (Defillo et al., 2014). In samples of people aged 50 and over, this preponderance may approach a ratio of 1:2, or even greater. This trend seems to be associated with low levels of estrogen (Longstreth et al., 1994). Regarding the formation of an intracranial aneurysm, the current consensus is that origin is multifactorial, and there is no completely satisfactory theory. Evidence demonstrates a complex evolutionary process in which many factors may be involved. The possible co-factors involved are anatomy, vascular geometry, and abnormal flow patterns, with endogenous factors related to the vascular wall (weakness and vulnerability). However, the interplay of biological and hemodynamic factors is not well understood and therefore remains unclear. Recent experimental studies show that arterial vessels' caliber and its histological structure are regulated by blood flow variations (Sforza et al., 2009). Also, variations in the vessels and changes in bifurcation angles are involved in the genesis, development, and eventual rupture of aneurysms. As a result, increasing importance is placed on cerebral hemodynamic assessment as a predictor of the initiation and development of intracranial aneurysms. Analyses of cerebral hemodynamics suggest considerable variability in the arterial circle of Willis, which frequently includes asymmetries (Fig. 2). A complete circle of Willis was observed only in 20–25% of patients (Puchade-Orts et al., 1975), as illustrated in Figure 2 [Types S1 to S4]. Evidence suggests that anatomical variations observed in the cerebral arterial circle of Willis and related vessels may play a role in the genesis of intracranial aneurysms (Kayembe et al., 1984). Padget was among the first to compare the number of cases of embryological abnormalities with aneurysms and without aneurysms (Padget, 1945). Also, an asymmetrical circle of Willis, whether congenital or acquired, is a risk factor for the development of aneurysms, where hemodynamic stress produces degenerative changes leading to hyperdynamic flow (Milenkovic, 1981) (Fig. 2—Type A, H, AF and AH). Drawing showing usual symmetric (Types S1 to S4) and asymmetric types of of circle arterial of Willis (Types A, H, A/F, and A/H). S1 and S2 = both symmetric with possible variations of AcoA, S3 = symmetrical with possible variations of PCoA, A = dominance of A1, H/F = unilateral hypoplastic PcoA or unilateral PcoA fetal, A/H= combination of A and H. Recent studies lead to a proposal that a congenital absence of anastomosis capacity of the arterial circle of Willis is correlated with other cerebrovascular diseases, thus alluding to a mechanism of hypoperfusion in the development of chronic ischemic pathology or small vessel cerebrovascular disease (Ryan et al., 2015). Another flow-related disease is the ligation of the carotid artery. This procedure was performed for the treatment of giant carotid siphon aneurysms as the technique of choice for a long period of time before the development of neuroendovascular therapy. However, this kind of procedure is associated with de novo intracranial aneurysm formation and flow-induced vascular remodeling (Gao et al., 1981). Carotid ligation experimental models demonstrate that compensatory cerebral blood flow increases after carotid occlusion, with secondary pathologic remodeling. For example, flow adaptive development throughout the arterial circle of Willis is associated with formation of an aneurysm in the contralateral carotid artery (Tutino et al., 2014). A probability is that the same principle may apply to the bifurcation of the carotid artery and its branches, which may be due to changes in hemodynamic parameters at this level. Flow studies show that the source point of an intracranial aneurysm is distal to the bifurcation or the gradient fields, which are higher (Alnaes et al., 2007). Therefore, hemodynamic stress and the turbulent blood flow associated with hyperdynamic flow patterns may cause excessive wear and vibration, resulting in structural fatigue and eventual rupture of the internal elastic lamina and, therefore, the formation of cerebral aneurysms. Patients with hyperdynamic flow patterns as a result of abnormally high flow conditions or other collateral pathways are therefore at-risk for accelerated degenerative changes in the vessel wall and the subsequent growth of an aneurysm (Wiebers, 2004). In this case, environmental factors such as hypertension, smoking, and connective tissue diseases probably play a contributory role, rather than being the cause. Studies have also looked into the possibility of changes in morphology in large vessels because the main-trunk and internal carotid arteries could be responsible for the formation of cerebral aneurysms (Sekhar et al., 1981). Experimental studies show that within the dome of an aneurysm, hemodynamic stress seems to be caused by sequential and repetitive turbulent flow. This type of abnormality is evident in the cavity of an aneurysm during systole. This abnormal flow becomes inverted during diastole, so these quick changes in the direction of flow continue to cause friction in the inner wall of the vessel and contribute to the formation and progression of an aneurysm (Gonzalez et al., 1992). Given all the facts and ideas that arise when trying to better figure out the local vascular and Willis polygon environment for the understanding of an aneurysm, some key points can help us: is there any correlation between the different pattern of geometries in the circle of Willis and the vessels related to certain subtypes of intracranial aneurysms? Perhaps certain anomalies or circle of Willis patterns justify screening and preventative treatment? Or is it that an aneurysm will not only be a local disease but a disease trigger point in all other hemodynamic spots that develop in the cerebral circulation or are acquired congenitally? Despite new fast and non-invasives methods that allowing to examining the use of cerebral hemodynamics, a detailed analysis would need for adequate interpretation and assessment of its abnormalities. In Figures 3 and 4, a pre-assessment of vessels of circle arterial of Willis using CTA before the endovascular treatment with tridimensional reformatting is showed whilst in the Figure 5, a pre-assessment using MR and TOF sequences for endovascular planning is also illustrated. Contrary to previous statements, the role of cerebral hemodynamics is not clear because there are some confounding elements as constitutional problems or disease characteristics and blood structure contribution, hemodynamic, mechanical vascular by gender and the formation of aneurysms. As has previously been shown, there is a sex-linked difference in anatomical variations and this is linked to the anatomical distribution of aneurysms (Ghods et al., 2012); we still do not know whether these two elements are connected. More controlled studies are needed. CTA of intracranial vessels—assessment of circle arterial of Willis—axial slice. CTA of intracranial vessels—assessment of circle arterial of Willis—coronal slice. Time of flight of circle arterial of Willis obtained from female patient with aneurysm of the ophthalmic segment within her left ICA for endovascular planning showing asymmetric type of circle of Willis. Finally, our current and future directions further elucidate the genesis and natural history of intracranial aneurysms and perhaps predict the response to treatment with stents flow diverters and to have a better understanding of the cerebral hemodynamics. This should also contribute to the understanding of the pathophysiology, in particular, to a more effective direction in the detection and prevention of intracranial aneurysms. We are grateful to Miss Kate Radford, Senior Graphic Artist of the Department of Medical Illustration at Leicester Royal Infirmary for her lovely and impressive art drawing which improved the realism of our subject matter. Patricia Bozzetto Ambrosi Interventional Neuroradiology Department Neuri-Beaujon, Clichy, Paris, France Postgraduate Program in Biological Sciences Federal University of Pernambuco, Recife, Brazil Carlos Augusto Carvalho DE Vasconcelos Department of Nutrition/LNED, Federal University of Pernambuco, Recife, Brazil Jacques Moret Interventional Neuroradiology Department, Neuri-Beaujon, Clichy, Paris, France Laurent Spelle Interventional Neuroradiology Department Neuri-Beaujon, Clichy, Paris, France Marcelo Moraes Valença Postgraduate Program in Biological Sciences Federal University of Pernambuco, Recife, Brazil
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