CFD studies evaluating hemodynamic parameters at the known site of rupture.
\r\n\t• Role of technological innovation and corporate risk management
\r\n\t• Challenges for corporate governance while launching corporate environmental management among emerging economies
\r\n\t• Demonstrating the relationship between environmental risk management and sustainable management
\r\n\t• Contemplating strategic corporate environmental responsibility under the influence of cultural barriers
\r\n\t• Risk management in different countries – the international management dimension
\r\n\t• Global Standardization vs local adaptation of corporate environmental risk management in multinational corporations.
\r\n\t• Is there a transnational approach to environmental risk management?
\r\n\t• Approaches towards Risk management strategies in the short-term and long-term.
Intracranial aneurysm (IA), a pathological dilation of the vessel wall, is the result of hemodynamic forces on the wall of the intracranial artery. It is characterized by mild to moderate structural changes of the vessel wall, which may result in aneurysm rupture, leading to a severe form of hemorrhagic stroke [1].
\nIn the last 15 years, there has been increasing incidental detection of unruptured intracranial aneurysms (UIA) due to an increasing use of noninvasive radiological examinations, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) [2]. The increasing use of these noninvasive techniques for various non-specific complaints results in higher detection and increasing treatment of UIA. While 20% of individuals operated on for an IA in 1998 were carrying a UIA, in more recent years, the number has increased to more than 50% of all patients operated on for IA in the Department of Neurosurgery of the Jan Evangelista Purkyně, Masaryk Hospital in Ústí nad Labem, Czech Republic. Concurrently, there have been an increasing number of patients that we monitor for UIA who do not receive treatment. Should the aneurysm not rupture, which occurs in the majority of IA cases, very few become symptomatic in other ways. If it does rupture, it results in severe consequences including death, various levels of neurological disabilities, and cognitive or social difficulties.
\nThe decision on whether to treat an individual with a UIA is based on the balance between the risk of treatment and the risk of the natural history of the aneurysm. If the aneurysm does not rupture, the risk of other clinical symptoms is quite low. These symptoms may appear as compression of the nervous structures (the optic nerve may be compressed by an ophthalmic aneurysm, the oculomotor nerve by a posterior communicating artery aneurysm, or the brain stem may be compressed by a large basilar aneurysm). Other symptoms may result from embolization of thrombi from the sac of an aneurysm; this is, however, very rare [3]. The worst outcome is that patients may experience aneurysm rupture. Overall, this risk is low in most patients and therefore does not occur in the vast majority of them in their lifetime [4]. The risk of rupture is associated with many factors; some of them are inherent (higher risk of rupture in females, some nations, such as Japanese); other factors are modifiable (higher risks are associated with hypertension or smoking). The rupture leads to a severe form of hemorrhagic stroke or even death. The risk of death after rupture is somewhere between 26 and 36% of patients [5]. The improved care of patients with SAH in specialized neurovascular centers improves survival rates [6]. Alternatively, about 15% of patients die immediately after rupture or before they are transported to hospital. Approximately 20% of those that survive develop a global cognitive deficit [7].
\nContrarily the treatment, even in selected UIA, may carry the risk of severe complications may be as high as 16% of patients; the risk of mortality being 0–3.2% and the chance of not being discharged home almost 20% [8]. All the scoring systems used for analyzing the risk of rupture are based on data from large population studies. These factors include the size of the aneurysm, its location within the circle of Willis, its shape, etc. However, the size or the shape of the aneurysm is a result of forces that themselves lead to aneurysm initiation, its growth, and eventual rupture (or stability with no rupture). This is the result of the balance between hemodynamic forces and the quality of the blood vessel wall at the site of the aneurysm. Immediately when the hemodynamic forces overcome the strength of the aneurysm wall, it will rupture. Consequently an understanding of the hemodynamics within the cerebral blood vessels and the aneurysm itself may help with understanding its initiation, growth, and eventual rupture. The ability to model the hemodynamics within the aneurysm could also possibly assist with predicting their risk element and the direction to preventive treatment. It may also be possible to securely monitor aneurysms with a non-risky hemodynamic profile.
\nIn this chapter we aim to provide current information on aneurysm hemodynamic modeling, using CFD. We will focus on ruptured and unruptured aneurysms, the hemodynamic characteristics at the point of rupture and the difference between ruptured and unruptured IA. We will discuss the issue from the perspective of neurosurgery and its possible contribution to clinical practice. We will summarize our 8 years of experience with CFD modeling in intracranial aneurysms, as well as the current literature.
\nDuring physiological conditions, the cerebral blood vessels consist of three layers: (1) tunica intima with a basal membrane, endothelial cells, and the internal elastic lamina; (2) tunica media, which consists of circumferentially oriented smooth muscle cells inside a dense network of collagen and elastin fibers; and (3) tunica adventitia, which consists mostly of collagen providing strength for the vessel wall. Tunica intima and tunica media are separated by a layer of lamina elastica interna, which is the key structure and has to degrade for the intracranial aneurysm to develop [9]. Cerebral blood vessels differ from extracranial blood vessels in that they have a thicker internal elastic lamina, less elastin, and smooth muscle cells in the media; in addition, they have no lamina elastica externa and a thinner layer of adventitia. There is minimum perivascular tissue in the subarachnoid space. The bifurcations of cerebral blood vessels contain irregularities in the vessel wall. The bifurcations are the typical areas of aneurysm development [10, 11]. Due to the small diameter of intracranial blood vessels, the wall shear stress plays a significant role in the degeneration of blood vessels and development of IA. The small diameter of cerebral blood vessels is also influenced by pathological forces induced, for example, by hypertension, and these lead to the development of IA. On the other hand, it is not quite clear what is the character of hemodynamic forces that lead to the development and rupture of IA. Some hypotheses describe the pathological influence of low wall shear stress leading to blood flow stagnation and the accumulation of blood elements (erythrocytes, leukocytes, thrombocytes), causing degeneration of the vessel wall together with inflammatory changes [12]. Another theory is based on high wall shear stress (WSS) causing damage of the endothelium, remodeling of the blood vessel wall, and its eventual degradation. It seems that possibly both scenarios could play a role [13].
\nThe actual process of modeling hemodynamic parameters consists of several steps. Creating a 3D model is done by manual or semiautomatic segmentation (Figure 1). Angiographic examinations (3D angiography, CT angiography, or MR angiography) are used as the source data. Each radiological method has its own limitations (calcifications, flow artifacts, etc.). Several studies have tried to assess the relationship between different imaging examinations [14, 15]. In one such study, the authors compared the results of CFD obtained from CTA or DSA [14]. In conclusion, the authors state that, despite the quantitative differences in the individual hemodynamic parameters between the CTA and the DSA segmented group, the basic flow characteristics of both groups were identical.
\nThe process of obtaining patient-specific geometry from the CT or MR scan with high resolution includes accurate voxel segmentation of the vessel, generating surface mesh, and finally smoothing, generating volumetric mesh, and prescribing inlets and outlets with possible shortening and elongating of the outputs.
In the next step, a calculation is performed using the Navier-Stokes equations, which describe the flow of incompressible fluid with constant viscosity. The use of the numerical solution of the Navier-Stokes equations calculates with assumption of blood having laminar flow. Possible influences of phenomena not captured by this model are further investigated, such as the influence of turbulent flow or viscosity change depending on the shear stress [16, 17, 18, 19].
\nThese calculations characterize the flow, i.e., they provide information about fluid velocity and pressure on the vessel wall and the quantities derived there from such a stress tensor. Due to the uncertainty in the description of the area, as well as the specified boundary conditions, the inconsistency of these variables may be significant, but certain global-derived quantities—wall shear stress and oscillatory shear index (OSI)—are identical for a certain variation in the accuracy of numerical solutions [20]. WSS is defined as the pressure that acts in parallel with the blood vessel lumen. The OSI then describes the difference between the WSS vector and the blood flow during the cardiac cycle. When interpreting the data, we always need to bear in mind the approximations and assumptions during the process of CFD modeling.
\nThe development of intracranial aneurysm can be divided into three phases: initiation, growth, and stabilization. Only a small percentage of aneurysms are unstable, progressing, and eventually resulting in rupture. The growth, shape change, and rupture of the aneurysm are the situations that we try to understand by mathematical modeling and to estimate the risk of these critical phases of development.
\nOne way to determine the risk of intracranial aneurysms is to compare the hemodynamic characteristics between ruptured and unruptured aneurysms. We can either compare non-specific aneurysms based on the status of rupture or only compare ruptured and unruptured aneurysms either at specific locations (MCA, PCom, etc.) or the so-called “mirror” aneurysms (right and left PCom or MCA aneurysms) [21, 22].
\nTo date, several studies have been conducted to compare ruptured and unruptured aneurysms [22, 23]. Some of them were performed on a large number of aneurysms; others were focused on a small number of aneurysms at a specific location [22, 24, 25, 26]. The aim of these studies was to find differences between morphological and hemodynamic parameters, which would distinguish both groups. The characteristics of ruptured aneurysms could then help to identify the risky ones.
\nIn one of the largest studies on 119 aneurysms, the authors found differences in 4 morphological and 6 hemodynamic parameters between ruptured and unruptured intracranial aneurysms [27]. The multivariate logistic regression analysis revealed that the morphological factor of size ratio and two hemodynamic factors, WSS and OSI, were independent factors of rupture risk. In 2017, a meta-analysis was published which, based on 1257 aneurysms from 22 studies, evaluated differences in hemodynamic parameters between ruptured and unruptured aneurysms. It showed that in ruptured aneurysms, WSS is significantly lower than in unruptured ones [28]. The same result was shown on 106 ACM aneurysms [22]. Alternatively, the largest ever study comparing ruptured and unruptured aneurysms has shown that wall shear stress is higher than those in unruptured aneurysms [29].
\nPrevious results must therefore be given careful consideration as many factors have a significant influence on WSS. The meta-analysis itself shows, for example, the difference in WSS in aneurysms at different locations (the lowest is in the aneurysms of the apex of the basilar artery). One way to eliminate the influence of different localizations is to compare either the so-called mirror aneurysms (right and left IA MCA or PCom) or aneurysms of one localization in general (ACom, ICA, MCA, PCom, etc.).
\nAnother important factor affecting IA hemodynamics is their size [13, 30]. We compared hemodynamic factors in small and large aneurysms based on the largest diameter of 10 mm (small <10 mm, large >10 mm) as this is commonly used to differentiate between small and large aneurysms in clinical practice (publication in preparation). We have found that size significantly influences the WSS within the aneurysm, independent of its rupture status. WSS in small aneurysms was significantly smaller. The only similar study used a volume of the sac to differentiate small and large aneurysms [30]. However, in clinical practice, the volume of the sac is not assessed on a regular basis, and its use is less practical in clinics. Nonetheless the results of both studies emphasize the importance of aneurysm size assessment with respect to evaluation of hemodynamic factors; generally it is necessary to compare hemodynamic parameters in equally sized aneurysms. One possible way to circumvent this effect is to use the so-called WSS statistical maps to convert the results to the surface of the aneurysm sac [31].
\nSpecific limitations of studies comparing ruptured and unruptured aneurysms result from the fact that we already assess the condition given by rupture, not the aneurysm at risk, before rupture. Therefore, altered morphology of the aneurysm after rupture can lead to erroneous results or misinterpretations [32]. Another limitation in these studies is that we usually do not possess the individual boundary conditions for each aneurysm and need to use literature-based information.
\nThe study of hemodynamics in ruptured aneurysms provides a chance to link the hemodynamic parameters with rupture (Figure 2A–D). Most studies have focused on the aneurysm sac as a whole. However, the aneurysm sac in ruptured aneurysms may be divided into the site of the rupture and the surrounding part of the sac. In these rare cases when we are able to differentiate those two parts of the aneurysm sac, we can combine our knowledge with local hemodynamic parameters. There are two types of studies in which the authors were able to identify the point of rupture. Firstly, there are surgical series when the neurosurgeon perioperatively identifies the site of rupture (perioperative rupture, apparent wall rupture during inspection of the sac usually before clip deployment, etc.) [33, 34]. Secondly, there are mostly case reports when the rupture in the angiographic room occurs, and the leakage of blood from the sac is thus identifiable during the interventional procedure [35, 36].
\n(A–C) Development of WSS over time in an IA that eventually ruptured. The WSS gradually decreased between the years 2007 and 2011. (D) A ruptured ACom aneurysm. The point of rupture (*) was confirmed during surgery. It was associated with increased WSS. (E) A perioperative image showing a ruptured MCA aneurysm. The point of rupture is in the weak part of the aneurysm wall. (F) A perioperative image showing an unruptured MCA aneurysm with heterogenous wall, an atherosclerotic part with a thrombus inside (black asterisk) and a red thin wall (white asterisk). (G) A histological image showing in detail the vessel wall of the Willis’s circle without an aneurysm: the structure consists of the tunica intima with endothelial cells, which is separated from the tunica media by the internal elastic lamina (IEL), the tunica media with linear layer of smooth muscle cells, and the tunica adventitia, the outermost layer, which comprise mainly of collagen. (H) An UIA: moderate structural changes of the vessel wall, mainly fibrosis across the vessel wall without layers and the internal elastic lamina. (I) A ruptured IA: severe structural changes of the vessel wall. The wall is thinner, without tunica intima, and linear layer of smooth muscle cells, with the presence of organized thrombus (Masson trichrome staining in all three histological images).
The site of rupture may show specific hemodynamic features (Figure 2D). So far there have been few studies with altogether a low number of patients (around 40 in total). The results are rather contradictory as it is apparent from the table; thus, it is difficult to make any straightforward general conclusions (Table 1).
\nAuthor, year | \nNo. of cases | \nIdentification of rupture | \nHemodynamics at the site of rupture | \n
---|---|---|---|
Kono et al., 2012 [33] | \n1 | \n3DRA | \nLow WSS at diastole and high pressure at systole | \n
Omodaka et al., 2012 [56] | \n6 | \nPeriop finding | \nLow WSS and high OSI | \n
Hodis et al., 2013 [36] | \n1 | \n2DA | \nJet flow, elevated WSS, and pressure at systole | \n
Fukazawa et al., 2015 [34] | \n12 | \nPeriop finding | \nLow WSS and slow flow | \n
Cebral et al., 2015 [57] | \n9 | \n3DRA and CT | \nHigh WSS | \n
Hejčl et al., 2017 [39] | \n1 | \nPeriop finding | \nJet flow and high WSS | \n
Wang et al., 2018 [58] | \n1 | \nPeriop finding | \nLow WSS and high OSI | \n
Suzuki et al. 2019 [59] | \n7 | \nPeriop finding | \nMax pressure areas, then decreased WSS | \n
CFD studies evaluating hemodynamic parameters at the known site of rupture.
It seems that the site of rupture is associated either with concentrated jet flow and high WSS (Figure 2D) or, on the other hand, a slow flow and low WSS. Both types of flow can lead to degeneration of the blood vessel wall but via a different mechanism [13]. Whereas low WSS and high OSI may lead to the activation of inflammatory cells and impairment of vessel wall structure, high WSS leads to the activation of cells in the vessel wall, leading to the growth of aneurysm sacs and rupture in small sacs or blebs. Reaching a certain size of the aneurysm sac during its growth leads to slowing the flow and recirculations, resulting in WSS decrease. In the IA itself, the highest WSS is usually around the neck and it decreases toward the apex. The low WSS can lead to degradation of the internal structure of the vessel wall and a further increase in the size of the sac. Most ruptures take place just in the apex of the aneurysm sac.
\nThe disadvantage of all studies evaluating local hemodynamic parameters relative to the rupture site is the same as in all studies evaluating ruptured aneurysms. As mentioned above ruptured aneurysms may have a different shape after rupture, which can influence the results of hemodynamic modeling parameters as compared to the pre-rupture situation [32, 37]. Studies in which a hemodynamic analysis was performed shortly before rupture avoid this limitation and may be helpful [35, 38]. These studies are rare, but their results are important, as they provide a hemodynamic characteristic within an extremely vulnerable aneurysm (which will soon rupture). Zhang et al. described three cases of large carotid aneurysms just before their rupture (2–5 days before SAK from aneurysm) and compared them with the same large eight unruptured ones [35]. They found that all ruptured aneurysms had an irregular shape and a higher aspect ratio (AR), and the WSS was lower than in the parent artery, as opposed to ruptured aneurysms. Additionally, in another study where the hemodynamic study of the basilar artery apex was performed 2 hours before the aneurysm rupture, the authors also found that in this aneurysm, WSS was lower than the parent artery [38]. However, the actual rupture site was associated with high WSS at the point of the blood jet into the sac. We found a similar flow characteristic in our case report where the site of rupture correlated with concentrated jet flow accompanied with high WSS and high normal pressure [39].
\nUnderstanding the changes in hemodynamics in ruptured aneurysms over time before the moment of rupture is of great importance; such studies are obviously quite rare [32, 40]. Our own study showed that a secondary aneurysm, a frequent rupture site, was observed in the aneurysm that subsequently ruptured (Figure 2A-C) [40]. WSS was reduced and the flow was slow at the rupture point. Over time, the area of low WSS increases in aneurysms that rupture (Sejkorová et al., in preparation). Such studies are vital for identifying the hemodynamic factors associated with the increased risk of rupture and may possibly be used in the future as an indicator for the active treatment of monitored UIA.
\nOne of the shortcomings of mathematical modeling is that we still know little about the relationship between hemodynamics and its influence of the biology of the vessel wall [41]. Understanding the balance between the flow and the biology of the aneurysm wall is the key factor in the life cycle intracranial aneurysms. The aneurysm wall ruptures when there is an imbalance between the aneurysm wall thickness and hemodynamic forces; both reciprocities are influenced. Modeling the relationship between histological changes and hemodynamic parameters is a logical way of research development (Figure 2E–I). The correlation of histological changes with mathematical models can help to verify the accuracy of mathematical models of hemodynamics, to improve understanding of the acquired data, and to transfer this methodology closer to practice in clinical neurosurgery. The correlation of histological changes and hemodynamics avoids errors related to CFD parameter evaluation in relation to, for example, aneurysm rupture; while the ruptured one was not ruptured prior to the event, the unruptured one could be ruptured in a few hours.
\nFrösen et al. classified four types of histological wall structures of aneurysms, based on disorganization of the vessel wall structure, myointimal hyperplasia or hypocellularity of the vessel wall, smooth muscle cell (SMC) proliferation, and the presence of organized thrombus [42]. The ruptured aneurysm wall is more often characterized by being disorganized, thinner, hypocellular, with an organized thrombus present (Figure 2I). Different types of wall structures can be found within one aneurysm sac. One of the first studies to correlate hemodynamic parameters with the pattern of the vessel wall has recently been published [43]. Quite surprisingly, the authors found that the high WSS and high-velocity flow were associated with the appearance of inflammatory changes in the aneurysm wall, while low flow areas were associated with degenerative changes in the aneurysm wall and loss of smooth muscle and pericytes. This finding is quite different from the previous studies, which did not correlate hemodynamics and histological characteristics. The correlation of histological changes and hemodynamics avoids the risk of error in comparing ruptured and unruptured aneurysms. There will most likely be a difference between an aneurysm that never ruptures and an aneurysm whose rupture is imminent. However it is not known which aneurysms we are analyzing.
\nIn a less elaborative way, CFD modeling can be correlated simply with the perioperative findings during surgery (Figures 2E, Fand3). The wall of many aneurysms can be heterogenous including thin red areas, calcifications, and the thick yellow atherosclerotic wall part. In one such study, red, thin aneurysm wall areas were more often associated with low WSS (Figure 3A1–3) [44]. A total of 39 areas were identified and directly visually inspected on the aneurysms walls. The study showed that red, thin aneurysm wall areas were more often associated with low WSS, high pressure, parallel WSS vectors, and curved streamlines (75%) [40]. On the other hand, the association of low WSS with high pressure, diverging WSS vectors, direct impact of streamlines, and high-velocity flow more frequently matched with yellow, atherosclerotic aneurysm walls (79%) (Figure 3B1–3). Although routinely used imaging techniques can provide information about morphology and anatomical relationships of the aneurysm with the surrounding structures, there is currently no way to predict the thickness of the aneurysm wall. CFD can potentially provide this kind of information, which would be valuable not only to assess rupture risk but also to improve the surgical strategy during clipping or coiling. The authors of this study hypothesize that direct, high-velocity impact of blood flow on a specific area of the aneurysm could trigger a remodeling of the wall, ultimately leading to a reactive thickening.
\n(Left panel) Red, thin areas on aneurysm wall are more often associated with low WSS. (A1) Right ICA aneurysm. (A2) Intraoperative microscopical view. (A3) CFD analysis. (Right panel) Yellow, atherosclerotic areas on aneurysm wall are more often associated with low WSS, high pressure, diverging WSS vectors, direct impact of streamlines with high-velocity flow (labeled with “1” in the figure). (B1) Anterior communicating artery aneurysm. (B2) Intraoperative endoscopic view. (B3) CFD analysis.
In our recent project, we evaluated histological changes in ruptured and unruptured intracranial aneurysms. According to our preliminary data on the first 30 samples of individuals with ruptured and unruptured IA together with some control samples from similar locations of the cadaver’s Willis’s circle, the wall was damaged by scarring, with the disappearance of the tunica intima and the internal elastic membrane, in patients with both ruptured and unruptured aneurysms (Figure 2G–I). In the classification according to Frösen et al., categories A to C were demonstrated for unruptured IA, i.e., minor to moderate structural changes, such as fibrosis and disorganization of SMC (Figure 2H). However, the wall of ruptured aneurysms was thin, hypocellular, and fibrotized, often with the presence of an organized thrombus (Figure 2I). In the classification according to Frösen, it corresponded to categories C and D, i.e., a significantly damaged wall.
\nThe correlation of vessel wall biology in intracranial aneurysms also has limitations:
Resection of only a part of the aneurysm sac. The entire aneurysm cannot be taken for histological evaluation. Due to the need to close at least the neck, but often also significant parts of the dome with an aneurysm clip, it is often possible to remove only the apex bag, even for larger aneurysms. Often small aneurysms are all hidden within a clip. On the other hand, large aneurysms often have a wall that is altered by atherosclerosis, weakened or calcified, and thus requires the application of, for example, several parallel clips and often a minimal residue of free sac to allow for sampling. A possible, at least partial, solution is the correlation of hemodynamics with the perioperative description of the aneurysm wall character (thinned wall, calcification, thickened atherosclerotic wall, etc.) by a neurosurgeon.
3D orientation of the histological sample against angiographic imaging. The problem is the orientation of the cut bag in 3D space or 3D neuroradiological mapping. The hemodynamic parameters are processed in a 3D image based on CTA or 3D DSA. However, after cutting off the tip of the bag, it is necessary to orient the specimen and mark it properly so that the histology of the vessel wall with hemodynamic results can be ideally correlated. So far, a methodological study has been published to address this topic. However, it is currently quite complicated to be applied in clinical practice.
Another disease that is also used to investigate the relationship between atherosclerosis and hemodynamics is the carotid plaque in the bifurcation of the common carotid artery (Figure 4) [45]. This model is more advantageous for several reasons. It can be removed completely without disturbing its structure and then prepared for histological examination in one piece. Due to the size of the plaque and a simple orientation in the 3D geometry of the carotid arteries, the spatial correlation of the plaque model relative to the 3D image of hemodynamic calculations is simple. Also mathematical calculations on the carotid arteries are significantly simpler due to the relatively flat shape of the vessels and the larger cross-sectional size of the arteries, which are thus less affected by minor inequalities and errors given by the neuroradiological images. Therefore, the histological studies of carotid plaques in correlation with hemodynamic characteristics in the common carotid bifurcation can be performed with fewer approximations and thus can contribute to the understanding of atherosclerosis and degenerative changes in the vascular wall.
\nCFD in a model of carotid stenosis. WSS (A) and streamlines (B).
The degeneration of the aneurysm wall progresses from the neck toward the dome. Aneurysm rupture usually occurs at the apex, which is also often a low shear stress region. According to a large meta-analysis by Zhou et al., the low shear stress (0–1.5 Pa) in the aneurysm sac is a characteristic of ruptured aneurysms [28]. It is assumed that wall shear stress of approximately 2.0 N/m2 (Pa) is most suitable for maintaining the integrity of the vessel wall. A shear stress of less than 1.5 N/m2 results in endothelial cell apoptosis [46]. Takao et al. found that the minimum WSS value for ruptured aneurysms was half that of ruptured aneurysms [26]. Thus, low WSS may be an indicator of an increased risk of intracranial aneurysm rupture. Furthermore, several authors have demonstrated that in ruptured aneurysms, the low WSS region is greater than in unruptured aneurysms [21, 25, 47]. Similar results were found in our study (Sejkorová et al., in preparation), in which we have shown that the area of low wall shear stress (LSA) grows over time in those aneurysms that eventually ruptured. The nature of the flow and its properties are influenced by the shape of the sac. Inside the narrow neck aneurysms, there may be a slow flow with recirculations, resulting in low shear stress leading to increased vascular degeneration. Hemodynamic changes within the aneurysm lead to the production of biological signals in endothelial cells and may result in microscopic changes in the vessel wall [48]. Nitric oxide is a key mediator of low WSS and shear stress oscillation. The low shear stress further promotes the expression of adhesion molecules such as VCAM-1 and ICAM-1. These promote adhesion of leukocytes leading to inflammation and vascular changes. Therefore low WSS seems to be associated with degeneration of cerebral aneurysm vessel wall resulting in rupture. But the situation is probably more complex as in another study in a large number of aneurysms, the authors found that ruptured aneurysms were characterized by concentrated blood stream and a higher shear stress compared to unruptured ones [29].
\nMathematical modeling performed in IA extends our knowledge on the pathophysiology of their initiation, growth, development, and rupture [13, 49]. At the same time, it is necessary to note that CFD modeling is usually based on many approximations and carries several limitations. In most studies, individual patient data are not available. This is particularly difficult to obtain in patients with ruptured aneurysms that require acute treatment, and there is usually no time for additional diagnostic examinations (TCD or PC-MR). The method that can partially reduce the disadvantage of missing individual data is to relate values in the aneurysm to the parent artery. Such value normalization reduces the impact of missing input data. Another limitation is that CFD represents mathematical models that are currently not able to describe all aspects of the biology of the cerebral aneurysms and cerebral blood vessels, their histology, atherosclerotic changes, pulsations, etc. Also during modeling, blood vessels are simplified as rigid tubes. The rheological properties of blood are simplified as incompressible Newtonian fluid.
\nAnother aspect associated with limitations in CFD modeling is the use of different mathematical modeling algorithms among various groups working on CFD. This has been clearly shown in the CFD rupture challenge—phase I and phase II [50, 51]. In the rupture challenge, two MCA aneurysms, one ruptured and one unruptured IA, were evaluated using CFD analysis, and the status of the aneurysm was supposed to be identified by the research groups. In the second phase, several research groups were supposed to describe the hemodynamic parameters in one IA. The vast differences among the research groups confirmed the fact that various algorithms may lead to significant differences in the hemodynamic analysis [52]. In future it will be necessary to somehow unify the methodology in order to get more universally applicable results.
\nAnother disadvantage of CFD modeling is the relatively complicated protocol with the need to include sophisticated and laborious calculations requiring supercomputers. Nonetheless, technological advances in imaging may provide hemodynamic modeling during regular MRI examinations [53]. If MRI allows precise evaluation of hemodynamic parameters in the future, it can be used even during initial MRI evaluation and during follow-ups without radiation burden.
\nThe rationale for studying hemodynamics of IA is the increasing detection of UIA with the need to decide whether to treat or watch the aneurysm. Studying and modeling hemodynamics within an aneurysm provides more information on the pathophysiology of IA. We can evaluate the hemodynamic parameter at one time point or follow the aneurysm with CFD assessments over time [40, 54]. The method has been mostly developed by endovascular surgeons with the goal to assess the effect of various treatment modalities, such as flow diverters, stents, scarification of the parent vessel, etc. The neurosurgeons would mostly need information on aneurysm hemodynamics with respect to the rupture risk in the assessment of UIA [40]. The neurosurgeons themselves may provide unique information on aneurysm wall quality: direction visualization of the aneurysm sac under the operating microscope (calcifications, wall weakening, atherosclerotic changes, thrombosis), identification of the site of rupture, aneurysm sac harvesting after clipping, etc. The aneurysm sac wall may then be assessed histologically. Some pilot studies have already been published [43]. Despite an increasing number of CFD studies, there are, to date, still no conclusions with respect to hemodynamics and growth or rupture that would be universally accepted.
\nFrom a clinical point of view, the CFD data need to be clinically useful and relevant, such as in a study that points out the relationship between the hemodynamic factors and the risk of endovascular treatment failure in patients treated for a basilar apex aneurysm [55]. The CFD parameters more often mentioned with respect to clinical use are WSS and character of flow. Many studies show that aneurysms with low WSS and complex flow tend to be associated with a higher risk of rupture [27, 28]. Further developments are still required in CFD research before it may be considered clinically relevant in providing useful information on UIA and its assessment, with respect to the risk of rupture.
\nSupported by Ministry of Health of the Czech Republic, grants nr. NV17-32872A and NV19-04-00270. All rights reserved.
\nImagine that you are in the trauma bay receiving a patient with a suspected high spinal cord injury due to a motor vehicle crash. Emergency medical responders sign out to you that the blood pressure has been fine on the way in, 110/60 mmHg with a heart rate in the 60s. As you complete your primary survey and get the patient on to your monitors you find the pressure has plummeted to 80/50 but rather than tachycardia the patient’s heart rate is only 45. The rhythm is sinus bradycardia, the hemoglobin on your initial lab is 14.4 g/dl and there is no clear source of blood loss.
\nAll too often neurogenic shock is an under-recognized but deadly cause of hypotension, bradycardia, and other complications related to spinal cord injury. In this chapter, we examine the definition, diagnosis, and treatment taking special care to differentiate it from spinal shock. We also briefly discuss autonomic dysreflexia and the role that neurogenic shock and autonomic dysreflexia can play in the rehabilitation setting.
\nSearches were conducted using the PubMed database for “neurogenic shock.” The Lewis Katz School of Medicine online textbook library was also referenced using the same search terms, as were hard copies of reference textbooks 10 and 11.
\nThe contemporary understanding of “neurogenic shock” was born with Alfred Blalock’s “classification of peripheral circulatory failure,” which he described in articles between 1927 and 1942. His “pure” types of shock included cardiogenic, hematogenic (better known as hypovolemic), neurogenic, and vasogenic (anaphylactic and septic) [1]. In descriptions of the neurogenic type, Blalock wrote: “the primary alteration is vasodilatation dependent on diminished constrictor tone as a result of influences acting through the nervous system,” a description that has persisted [2]. At the time, Blalock associated neurogenic shock with spinal cord injury, spinal anesthesia, and vasovagal syncope [2]. Though our definition of neurogenic shock has evolved since Blalock’s time, his classification system remains, and so do the challenges of defining, identifying, and managing neurogenic shock.
\nNeurogenic shock is considered distributive in nature and refers to the loss of vasomotor tone and the instability that subsequently follows due to an imbalance in the autonomic nervous system (ANS) [3, 4]. Loss of sympathetic tone leads to unopposed parasympathetic control, manifested by refractory hypotension and bradycardia [3]. Other aspects of neurogenic shock include temperature dysregulation, autonomic dysreflexia, and orthostatic hypotension [5]. Aside from bradycardia and hypotension, many patients develop autonomic dysreflexia defined as a profound autonomic response to what would typically be a mild stimulus such as bladder or bowel distension [6]. The presence of a focal neurological deficit is not required for diagnosis, and although this is most often encountered in the setting of an acute SCI, theoretically any damage resulting in the loss of cerebral control of the autonomic nervous system may place a patient at risk for neurogenic shock. Neurogenic and spinal shocks are distinct consequences of spinal cord injury and the terms should not be used interchangeably.
\nNeurogenic shock most often occurs after an acute injury above T6, with a possible incidence of 29% in the cervical SCI population and 19% in the thoracic SCI population [4]. The onset may be variable in relation to the timing of the injury, but in SCI patients it most commonly manifests within 2 h of the trauma [7]. In most patients it is transient and may last for 1–6 weeks after injury [5, 8].
\nConversely, spinal shock is the transient loss of reflexes and sensorimotor function that manifests acutely after injury to the spinal cord. It is a symptom of underlying spinal cord injury and the term “shock” in this situation does not refer to cardiovascular instability. Spinal shock is characterized by flaccid paralysis, anesthesia, and areflexia or hyporeflexia [3, 7]. Note that often enough the two may be present in the same patient but their natural course and treatment are distinct; furthermore there are often other potential causes for shock in the trauma patient (e.g. hypovolemic secondary to acute blood loss) clouding the diagnosis. It has been proposed that there are four phases of complete spinal shock resolution: hyporeflexia or areflexia (0–24 h), initial return of reflexes (1–3), early hyperreflexia (day 4 – 1 month) and spasticity (1–12 months) [7]. The total duration of spinal shock depends on the definition of its resolution. Resolution has been defined as the appearance of any reflex, the appearance of the bulbocavernosus reflex, return of reflex detrusor functions, or the return of deep tendon reflexes [7, 9]. Depending on which definition you use, spinal shock can last anywhere from days to months.
\nSpinal shock and neurogenic shock may occur at the same time in a patient, complicating management, but they are not synonymous (see Table 1). Perhaps the most significant distinction is the difference in their management. The mainstay of treatment of neurogenic shock is fluids and vasopressors. As a transient symptom of spinal cord injury, spinal shock is expected to resolve on its own, in a predictable manner. Once spinal shock resolves, the underlying injury may be more accurately assessed.
\n\n | Spinal shock | \nNeurogenic shock | \n
---|---|---|
Definition | \nTransient loss of reflexes and sensorimotor function below level of injury | \nLoss of sympathetic tone with unopposed parasympathetic control, leading to cardiovascular instability | \n
Blood pressure | \nHypotension | \nHypotension | \n
Heart rate | \nBradycardia | \nBradycardia | \n
Associated autonomic symptoms | \nDifficulty breathing, bowel and bladder dysfunction, priapism | \nAutonomic dysreflexia, orthostatic hypotension, temperature dysregulation | \n
Motor | \nFlaccid paralysis | \nVaries with injury | \n
Reflexes | \nAreflexia or hyporeflexia in early stage, hyperreflexia in later stage of resolution | \nVaries with injury | \n
Duration | \nDays to months | \nMost often 1–6 weeks | \n
Treatment | \nStabilization and treatment of underlying injury | \nFluids and vasopressors with appropriate temperature monitoring | \n
The autonomic nervous system constitutes the involuntary control of many crucial systems of the body. Described as a system of visceral sensory inputs and motor responses, it maintains homeostasis and responds to both internal and external stimuli by manipulating the balance between its main divisions, the sympathetic and parasympathetic systems [10]. Although much of the autonomic system includes spinal reflex arcs with visceral motor neurons originating in ganglia lying peripheral to the spinal cord, there is overarching control exerted by multiple systems in the brain (Figure 1) [5]. It is the loss of this input from above that produces the dysfunction of the system, leading to shock [3]. The ANS maintains control of vital functions in the heart, vasculature, lungs, liver, digestive and para-digestive organs, glands, and reproductive organs. Although there are many involved neuropeptides, norepinephrine is the most common effector molecule in the sympathetic division and exerts it influence on both alpha and beta receptors, as well as the adrenal gland [10].
\nOverview of sympathetic outflow. Panel 1 (top left): CNS control of the sympathetic nervous system originates in multiple brainstem areas and nuclei as well as the hypothalamus, which also receives input from the cortex and amygdala. The combined input creates a sympathetic outflow tract which descends the spinal cord to the intermediolateral gray matter. Panel 2 (bottom left): At multiple levels from T1 through the rostral lumbar spine the preganglionic neurons will exit through the ventral rami and then jump to the sympathetic chain where they may ascend, descend, or synapse at that level before exiting again as part of the spinal nerves. Panel 3 (right): Zoomed out view of the sympathetic chain with multiple Para-vertebral ganglia in which the preganglionic neurons may synapse. The exiting post ganglionic noradrenergic neurons provide direct sympathetic input to the heart, lungs, glands, vascular beds, and adrenal medulla. Note that some sympathetic neurons may exit and not synapse in the sympathetic chain but travel to pre-ganglionic neurons to synapse (such as the celiac and mesenteric ganglia) [10, 11]. Created with Biorender.com.
Estimating the true incidence of neurogenic shock is difficult for multiple reasons. The overall definition is reasonably broad, and a patient may experience multiple subtypes of shock at the same time. Furthermore, there may not be a simple direct imaging correlate that is easily elucidated (for example, one can see a significant anterior or lateral cord injury and correlate the physical symptoms to the level of the lesion, but isolating the level of injury in the intermediolateral gray matter and ruling out other causes of shock is more challenging). Studies of incidence after SCI have been widely variable, ranging from 14 to 44% depending on the criteria used [4]. Extrapolating from a range of papers, criteria have ranged from systolic blood pressures (SBP) <70 mmHg up to <100 mmHg, and heart rates (HR) <50 beats per minute (BPM) up to ≤90 BPM in various combinations [12]. Examples include SBP <90 mmHG or HR <50 BPM as a cutoff, more recently others have used SBP <100 mmHG and HR <80 BPM, and still others simultaneous SBP <90 mmHg and HR <80 BPM with some variability in terms of whether or not lab values accounting for hypovolemia were examined as a confounder [4]. In one cohort of patients with isolated spinal cord injury (the majority of which were related to blunt trauma), defining neurogenic shock as SBP <100 mmHg, HR <80 BPM or both, out of 490 cases the incidence of hypotension was 25.8% and of classic neurogenic shock (hypotension and bradycardia) was only 19.3% [13]. What is suggested but not thoroughly quantified in the literature is that the incidence is highest in cervical spine injury and somewhat less for upper thoracic injury (above T6) while SCI lower than T6 would be considered rarely associated with neurogenic shock [3]. There is also not a single consensus in regard to penetrating vs. blunt trauma as to which is more likely to lead to neurogenic shock. Considering that SCI accounts for only about 5% of major trauma cases, a lack of experience may play a role in limiting identification and definitive management even at centers of reasonably high volume [13].
\nCase Presentation: 70 y/o male presents by air to a level I trauma center following a bike accident wherein he was thrown down a hill. It is unclear if he was wearing a helmet. He was initially resuscitated by bystanders as he was in cardiac arrest, and then intubated in the field prior to arrival (GCS 3-T). At the time of arrival he is found to have bradycardia with HR 53 BPM and initial BP was 112/74 with mildly low body temp 96.3 F (35.7 C). He became more bradycardia and did not respond to atropine requiring another brief round of cardiopulmonary resuscitation. Although the initial hemoglobin on his arterial blood gas (ABG) was 13.3 g/dl, he was also transfused four units of packed red blood cells (PRBC’s). Computed Tomography (CT) of the head and cervical spine showed an occipital condyle fracture as well as a type III (low) dens fracture with 6 mm distraction and a c2 spinous process fracture (Figure 2). Pressor support with norepinephrine was initiated and preparations were made for trans-venous pacing in the event of refractory bradycardia. Magnetic resonance imaging (MRI) the following day confirmed a likely distraction injury with cord edema and hemorrhage (Figure 3). Interestingly, his hemoglobin by hospital day 1 had increased to 17.5 g/dl suggesting that his perceived response to transfusion may have been related to volume resuscitation and pressers rather than the PRBC’s. He continued to have issues with bradycardia but did not require trans-venous pacing. Considering his severe high cervical spine injury with resultant tetraparesis and complications he was transitioned to comfort directed care on hospital day 3.
\nCoronal (left pane) and sagittal (right pane) CT scan views of the cervical spine showing a type III odontoid fracture (yellow arrow), C1/C2 fracture distraction (long blue arrow) and C2 spinous process fracture (short blue arrow). Created with Biorender.com.
Sagittal STIR c-spine MRI (left pane) with noted intra-axial edema and hemorrhage at the base of the odontoid (red triangle and top axial slice), more inferior cord edema (yellow triangle and bottom axial slice), and significant posterior compartment paravertebral edema (yellow star). Created with Biorender.com.
Case Discussion: The case above illustrates the complexities in early identification of neurogenic shock as a distinct entity. Because the signs of neurogenic shock are somewhat variable in terms of timeframe from injury to onset, and in light of differences between individual patients and systems in regard to fluid resuscitation in the field, a high index of suspicion is necessary from the time of initial evaluation through the early hours and days of intensive care. Any patient presenting with a spinal cord injury should be considered to be at risk with those having higher level injuries at higher risk (Figure 1). The authors suggest that the American Spinal Injury Association Autonomic Standards Assessment Form [14] is a reasonable place to start and takes into account blood pressure, heart rate, sweating, temperature regulation, the bronchopulmonary system, and the lower urinary tract and bowel. Even with this tool, however, no specific definition of bradycardia/hypotension is forthcoming; thus it will need to be set by individuals and institutions. As there is no single accepted treatment cutoff for the bradycardia and hypotension, it may be important for systems to consider their patient population in relation to prior studies and establish parameters for automatic physician notification during hemodynamic monitoring with reasonable case reviews to establish the best local standard.
\nIt is agreed, however, that the profound systemic hypotension that characterizes neurogenic shock may lead to hypoperfusion of the spinal cord with subsequent ischemia and secondary injury [15]. To improve outcomes, prompt and aggressive treatment of hypotension should be undertaken in a monitored intensive care unit, with adequate cardiopulmonary and ventilatory support [8]. Medical treatment consists of sufficient fluid administration as well as vasopressor therapy for sustaining blood pressure and maintaining perfusion [4]. That being said, it should be noted that the data regarding pressor use in SCI may be conflicting in this regard, as a distinction needs to be made between pressor use in an attempt to stabilize or improve the motor and sensory loss related to SCI, and that to preclude hypotension and bradycardia related to neurogenic shock from causing complications such as systemic hypoperfusion and cardiac arrest among others. According to one author, up to 100% of patients suffering from neurogenic shock may also have bradycardia, with 71% reported as having severe bradycardia (HR < 46 BPM) and 16% progressing to cardiac arrest [16].
\nFluid resuscitation is the first line therapy for hypotension in the setting of neurogenic shock [17]. Maintenance of blood volume influences both blood pressure and blood flow around the site of injury [8]. If there is an inadequate response to fluid resuscitation, agents with α1 and β1 adrenergic receptor activity should ideally be used to increase sympathetic activation [15]. What is otherwise considered routine care such as suctioning, as well as abdominal changes such as elevated bladder and bowel pressures, are known to produce wide swings in heart rate and blood pressure that may be refractory to treatment [18]. These changes should be anticipated and prevented as much as possible.
\nBlood pressure can be further augmented through the administration of intravenous vasopressor agents. These include norepinephrine, epinephrine, dopamine, phenylephrine, as well as concurrent atropine in patients with significant bradycardia [15]. There are some prior reports of transitioning individuals that need extended treatment with a non-intravenous agent to propantheline, aminophylline, theophylline, and ephedrine although the evidence is extremely limited [16]. Enteral pseudoephedrine has also been used successfully as an adjunctive therapy [16].
\nCurrent management guidelines dictate that mean arterial pressure (MAP) should be maintained above 85–90 mmHg for the first 5–7 days of therapy [19]. This resuscitation target has been questioned due to the lack of quality evidence showing a positive effect on outcomes [8]. Additionally, maintenance for 5–7 days may be insufficient because certain individuals benefit from longer management [4]. One study has shown that vasopressor therapy achieving the MAP goal is more likely to cause complications than to improve neurological outcomes, with dopamine leading in complications [20]. As such, the risk of vasopressors should be balanced against their benefits in each individual patient, and there should be clear goals for use in regard to improvement of the sensory and motor deficits vs. cardiovascular stabilization.
\nA recent study suggests that maintenance of a spinal cord perfusion pressure (mean arterial pressure – cerebral spinal fluid pressure) above 50 mmHg is a stronger predictor of neurologic recovery than systemic MAP and may also be useful in guiding management [21]. More studies with high quality evidence are needed to establish reasonable treatment goals that are linked to improved patient outcome.
\nRehabilitation in patients with spinal cord injuries should be comprehensive, interdisciplinary, and patient-centered, with goals that are individualized and realistic. Interventions should not be delayed and complications need to be anticipated and promptly identified.
\nNeurogenic shock can persist for 1–6 weeks after the initial injury, certainly long enough to interfere with rehab in some cases [8, 22]. In additional to that, patients with spinal cord injuries are vulnerable to a number of cardiovascular complications which should be anticipated in the course of rehabilitation, and some with prolonged or severe bradycardia may require permanent pacemakers [16]. Cardiovascular complications are the leading causes of morbidity and mortality in patients in both the acute and chronic stages of spinal cord injury [17]. Common complications include autonomic dysreflexia, orthostatic hypotension, reduced cardiovascular reflexes and absence of cardiac pain during ischemia [18].
\nIndependent of neurogenic shock, autonomic dysreflexia (AD) is a potentially fatal complication that occurs in 48–90% of patients with injuries above T6 [17]. It is caused by the loss of supraspinal sympathetic modulation and is characterized by sudden episodes of hypertension, headache, and tachycardia with prevailing reflex bradycardia [23, 24]. Additional sympathetic features include piloerection and cool extremities due to vasoconstriction below the level of injury [23]. In contrast to the sympathetic response below the level of injury, a parasympathetic response may predominate above the level of injury. A compensatory baroreceptor response leads to reflex bradycardia. Other features include flushing, sweating, and nasal congestion [24].
\nStimuli that may induce an AD response include bladder distension, detrusor sphincter dyssynergia, kidney or bladder stones, or other painful stimuli such as ingrown toenails, pressure ulcers, infections, fecal impaction, musculoskeletal pain, and menstrual cramps [24]. Sequelae of untreated hypertension in the setting of autonomic dysreflexia include stroke, intracranial hemorrhage, seizures, cardiac arrest, hypertensive encephalopathy, and death [25]. An increase of 20–40 mmHg in systolic blood pressure in people with spinal cord injury should raise suspicion for AD, though the exact definition is not consistent across studies [25].
\nPrimary treatment of AD includes sitting patients upright and lowering their legs, as well as removing or loosening tight clothing or accessories [26]. After that it becomes necessary to identify triggering noxious stimuli and address them. A distended bladder should be emptied with a catheter, a rectal exam may identify impaction, skin should be examined for pressure ulcers and more serious causes need to be suspected because they may not be obvious [26]. Medications that can be administered to help stabilize AD include the calcium channel blocker nifedipine, nitrates, and vasodilatory agents such as hydralazine [18, 23], although hypotension needs to be anticipated and patients will require appropriate hemodynamic monitoring.
\nAnother cardiovascular consequence of spinal cord injury related both to neurogenic shock and autonomic dysreflexia is orthostatic hypotension (OH). It is defined by the American Autonomic Society as a reduction in systolic or diastolic blood pressure of ≥20/10 mmHg, within 3 min of standing upright [27]. Symptoms occur as a result of reduced cerebral perfusion pressure and include light-headedness, dizziness, syncope, pallor, nausea, fatigue, and sweating. Nevertheless, many patients do not report symptoms despite meeting the definition of OH, and some report symptoms in spite of not fully meeting that definition. Pharmacologic therapy may be used to treat OH but should be done carefully because of the already labile blood pressure in patients with spinal cord injury. The most common treatments are compression stockings, abdominal binders, midodrine, or fludrocortisone [23, 27].
\nAdditional autonomic complications that occur after injury are the reduction of cardiovascular reflexes and the absence of cardiac pain. Cardiovascular reflexes regulate blood pressure, intravascular volume, and temperature [18]. The sensation of pain related to cardiac ischemia may be altered because cardiac pain fibers that travel with sympathetic afferent fibers (visceral sensory fibers) are disrupted in cervical or thoracic injuries above T4 [28]. As a consequence, spinal cord injury patients may have atypical presentations of cardiac ischemia including referred pain.
\nOther major components that are critical in spinal cord injury rehabilitation are bowel and bladder training, respiratory care, mobilization, as well as physical and occupational therapy. Not only should rehabilitation address the medical aspects of patient care, but the psychological impacts of spinal cord injury as well. A comprehensive approach treating the whole individual gives patients a better chance at achieving optimal functional recovery.
\nNeurogenic shock is a feared and difficult to treat complication of disruption of the sympathetic nervous system which most often occurs in the setting of a spinal cord injury. The refractory hypotension and bradycardia may be extremely dangerous for the patient, and may lead to cerebral anoxia, cardiac arrest, and more. Although there is no single accepted blood pressure and heart rate cutoff to define neurogenic shock, the signs are reasonably well established and definitive treatment is in line with current critical care management standards. Beyond the short term, neurogenic shock as well as autonomic dysreflexia, which may commonly accompany spinal injuries at the same level, can complicate the rehabilitation process. Hopefully future prospective studies will adopt standard ways of isolating and confirming neurogenic shock and establish treatment paradigms that improve patient outcomes.
\nThe authors report no conflict of interest.
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El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis",institutionString:null,institution:{name:"Al Azhar University",country:{name:"Egypt"}}},{id:"113313",title:"Dr.",name:"Abdel-Aal",middleName:null,surname:"Mantawy",slug:"abdel-aal-mantawy",fullName:"Abdel-Aal Mantawy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ain Shams University",country:{name:"Egypt"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5684},{group:"region",caption:"Middle and South America",value:2,count:5166},{group:"region",caption:"Africa",value:3,count:1682},{group:"region",caption:"Asia",value:4,count:10211},{group:"region",caption:"Australia and Oceania",value:5,count:887},{group:"region",caption:"Europe",value:6,count:15616}],offset:12,limit:12,total:1689},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{hasNoEditors:"0",sort:"dateEndThirdStepPublish",topicId:"9"},books:[{type:"book",id:"10260",title:"E-Service",subtitle:null,isOpenForSubmission:!0,hash:"11dab65781b3c4347022c56477311f46",slug:null,bookSignature:"Dr. Kyeong Kang",coverURL:"https://cdn.intechopen.com/books/images_new/10260.jpg",editedByType:null,editors:[{id:"2114",title:"Dr.",name:"Kyeong",surname:"Kang",slug:"kyeong-kang",fullName:"Kyeong Kang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9226",title:"Intelligent User Interfaces",subtitle:null,isOpenForSubmission:!0,hash:"2540a73b78f2f13158366ac0ab9d62a1",slug:null,bookSignature:"Dr. Rüdiger Heimgärtner",coverURL:"https://cdn.intechopen.com/books/images_new/9226.jpg",editedByType:null,editors:[{id:"135236",title:"Dr.",name:"Rüdiger",surname:"Heimgärtner",slug:"rudiger-heimgartner",fullName:"Rüdiger Heimgärtner"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9980",title:"Vision Sensors",subtitle:null,isOpenForSubmission:!0,hash:"fc472f04a4214bf13db3f693a2c7c323",slug:null,bookSignature:"Dr. Vasanth Iyer",coverURL:"https://cdn.intechopen.com/books/images_new/9980.jpg",editedByType:null,editors:[{id:"301000",title:"Dr.",name:"Vasanth",surname:"Iyer",slug:"vasanth-iyer",fullName:"Vasanth Iyer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10517",title:"Swarm Intelligence",subtitle:null,isOpenForSubmission:!0,hash:"c184136bf5b833b19f7e12ace5531773",slug:null,bookSignature:"Dr. Mehmet Emin Aydin",coverURL:"https://cdn.intechopen.com/books/images_new/10517.jpg",editedByType:null,editors:[{id:"148497",title:"Dr.",name:"Mehmet",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10576",title:"Factoring Ethics in Technology, Policy Making and Regulation",subtitle:null,isOpenForSubmission:!0,hash:"eff20787f4c5417ea12367e8a6d72e92",slug:null,bookSignature:"Prof. Ali G. 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