Pathogenesis+and+Treatment

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media type="youtube" key="s32_RM2947k" height="187" width="336" align="right"Morphological changes in the wall of the cerebral artery such as weakening of the arterial wall contributes to the formation of an intracranial cerebral aneurysm. Bulging of the cerebral artery occurs as the weakened arterial wall is unable to withstand the hemodynamic pressure along with other factors. Renal disease, hypertension, trauma and smoking coupled with the weakening of internal endothelial layer of the artery account for the major risk factors that contribute to the formation of cerebral aneurysm. Cerebral aneurysms affect 2-5% of the population and it occurs predominantly in adult females. Most of the aneurysms are acquired, not inherited as they rarely occur before the age of 20. There are different types of intracranial cerebral aneurysms, therefore, the symptoms as well as treatment varies according to the size and location of the aneurysm within the brain. Similarly, different diagnostic techniques such as MRI, CT Scan and Arteriography are used in order to diagnose a person with cerebral aneurysm. = = 1.1 Etiology > 1.1.1 Internal Elastic Laminae Degeneration and Arterial Wall Bulging > 1.1.2 Myointimal Hyperplasia > 1.1.3 Inflammation, Macrophage Infiltration and Rupture 2.1 Risk Factors > 2.1.1 Hypertension > 2.1.2 Smoking > 2.1.3 Gender 3.1 Types of Intracranial Cerebral Aneurysm > 3.1.1 Saccular > 3.1.2 Fusiform > 3.1.3 Mycotic > 3.1.4 Dissecting 4.1 Diagnosing Intracranial Cerebral Aneurysm > 4.1.1 Arteriography > 4.1.2 Computed Tomography Angiogram (CTA) > 4.1.3 Magnetic Resonance Angiogram (MRA) 5.1 Surgical Interventions > 5.1.1 Microsurgical Clipping > 5.1.2 Endovascular Coiling || =Etiology=
 * **Contents**

Many studies, usually in vivo, have been done in order to understand the mechanism underlying the formation of intracranial cerebral aneurysm. In these studies, cerebral aneurysms are induced in the cerebral arteries of animals (rats or cats) by combination of hypertension and the disruption of the collagen synthesis. It is suggested that the mismatch between the tensile strength of an artery to the hemodynamic stress to which it is exposed to is the main cause of formation of cerebral aneurysm.

Internal Elastic Laminae Degenration and Arterial Wall Bulging
The review by Frösen,J. //et al//. (2012) [1] and the experiments done by Jamous,Mohammad //et al//. suggest that morphological changes occur in the cerebral arteries that lead to the development of cerebral anueurysms. Due to increased hemodynamic stress i-e increased blood pressure, the internal elastic laminae of the artery degenerates decreasing the elasticity of the artery and making it unable to withstand further high hemodynamic pressure. The wall of the artery starts to distend due to the death of smooth muscle cells if high hemodynamic pressure persists in the blood circulation. This distension results in the bulging of the arterial wall.

Myointimal Hyperplasia
Myointimal hyperplasia is the body's response to vascular injury similar to "healing process". This phenomenon causes the poliferation of smooth muscle cell to regain the arterial elasticity, but coupled with increased hemodynamic stress, disorganization of new smooth muscle cells and macrophage infiltration promotes the further protrusion of arterial wall forming an unruptured cerebarl aneurysm.

Inflammation, Macrophage Infiltration and Rupture
The initial trigger for inflammatory cell infiltration into cerebral aneurysm is unknown. In experimental cerebral aneurysm in rodents, macrophage infiltration follows cerebral aneurysm formation and endothelial dysfunction. The magnitude of inflammatory cell infiltrations has been associated with cerebral aneurysm rupture (Kataoka //et al//.,1999 ; Frösen //et al//., 2004 ), stressing the role of inflammation in the degenerative processes of the arterial wall. According to Frösen //et al//. (2012) [1], breakdown of ethrocytes into heme that is accumulated in the arterial wall protrusion can also induce inflammatory response. Macrophage infiltration is caused due to oxidative stress and the macrophages produce effectors like TGF-Beta, reactive oxygen species (ROS), [|tumor necrosis factor alpha (TNF-alpha)], and interleukin-1 (IL-1) that trigger apoptotic cell death rupturing the aneurysm. =Risk Factors=

Various hereditary and acquired risk factors are implicated in the pathogenesis of cerebral aneurysms. Family history of tow or more family members having cerebral aneurysms accounts for 10% of the unruptured cerebral aneurysms. Various diseases affecting the connective tissues contribute to the increased risk of forming cerebral aneursym because they weaken the vascular walls. For example, 10-15% patients that develop cerbral aneurysms suffer from polycystic kidney disease, an autosomal dominant disease. Similarly, significant hereditary factors include fribromuscular dysplasia, Marfan's disease, [|Osler-Weber-Rendu Sydrome] and Type IV Ehlers-Danlos syndrome. Although hereditary factors plays an important role in the development and growth of cerebral aneurysms, acquired factors such as atheroseclorosis, alcohol and drug use, hypercholestremia and trauma are researched widely as it is possible to control these factors by means of lifestyle modification and minimize the risk of forming a cerebral aneurysm. Some of the most important risk factors (acquired and genetic) for the pathogenesis of cerebral aneurysms are: hypertension, smoking and gender.

Hpertension
Increased blood pressure causes high hemodynamic stress for the cerebral arteries weakening of the vascular wall by disrupting the synthesis of elastin and collagen. Hypertension also increases the risk of cardiac disease and stroke. Moreover, it induces the expression of TNF- alpha promoting the growth of cerebral aneurysm.

Smoking
Smoking is proinflammatory; it induces inflammatory injury by increasing VCAM-1, MCP-1, and IL-8 expression in the subendothelial and medial layers of the arterial wall (Zou //et al//., 2009). Cigarette smoke also downregulates lysyl oxidase, an enzyme initiating cross-linkage between elastin and collagen, thereby causing endothelial dysfunction. The modifications on type IV collagen by cigarette smoke and lipid peroxidation products trigger macrophages which are involved in triggering apoptosis. [8]

Gender
Cerebral aneursyms are common in adult female because of variations in the levels of estrogen. Studies done by Harrod //et al//. , have shown that decreased estrogen levels promote the growth of cerebral aneurysms in women by causing enothelial dysfunction. Estrogen receptors are important modulators of vascular injury and estrogen itself acts as an anti-inflammatory inhibiting the activation and infiltration of macrophages. Tamura //et al//. has suggested that estrogen replacement therapy conteracted the effect of estrogen deficinecy. =Types of Intracranial Cerebral Aneurysm=

[[image:types_of_IA.gif width="259" height="236" align="right"]]
This type of aneurysm looks like a "sac" or "berry", hence the name saccular or berry aneurysms. It is the most common type of intracranial cerebral anuerysm and is located at the bifurcation of the major cerebral arteries known as the Circle of Willis. 85-95% of these aneurysms are found in the carotid system while 5-15% are found in vertebrobasilar circulation. [11]

Fusiform Aneurysm
Fusiform aneurysms are associated with athersclerosis and are bulge out on all side creating a dilated artery. This type of aneursym rarely ruptures and is more commonly found in the vertebrobasilar system.

Mycotic Aneurysm
These aneurysms are formed as a result to an infection in the vessel wall. 60% of the mycotic aneurysm develop due to //Streptococcus// and //Staphylococcus// infection and 3-15% of the patients that present mycotic aneurysms suffer from subacute bacterial endocarditis. [11]

Dissecting Aneurysm
A dissecting aneurysm can occur due to trauma, but can also happen spontaneously. It results from a tear within the inner layer of the arterial wall along the length of the artery. The leakage and accumulation of blood in the layers of the artery causes it to swell on one side of the arterial wall obstructing the blood flow through the artery. =Diagnosing Intracranial Aneurysm=

Most of the cerebral aneurysms are diagnosed accidentally; the clinical presentation of cerebral aneurysm depends on its size and location in the brain, but if a patient presents the classic symptoms of cerebral aneurysms such as "thunderclap" headache and seizures, then three different modalities: arteriography, computed tomography angiogram and magnetic resonance angiogram are used to diagnose cerebral aneurysms.

Arteriography[[image:PE-angio3.jpg align="right" caption="Angiogram showing aneurysm"]]
Arteriography is also known as angiography or an angiogram. It works like an X-ray and is used to detect aneurysm, arteriovenous malformation (AVM), arterial stenosis, tumor and clots. Cerebral arteriography is an invasive procedure in which a contrast dye containing iodine is delivered into the blood stream through a catheter. The catheter is usually inserted the upper femoral artery, a local anesthetic is applied to the leg/thigh area, and guided through the blood stream to the arteries of the neck where the dye is injected. After injecting the dye, X-ray films of the head is obtained and then interpreted by the radiologist. The X-ray can not pass through the contrast dye, thus making the arteries visible on the X-ray film. Since arteriography is a highly invasive procedure that can sometimes lead to the unintentional ruputre of aneurysm while performing the procedure, noninvasive procedures such as CTA and MRA are used.

Computed Tomography Angiogram (CTA)[[image:CTA.jpg width="312" height="103" align="right" caption="CTA showing giant middle cerebral aneurysm"]]
CTA is the most common noninvasive method used to detect cerebral aneurysms. In addition to detecting aneurysms, it is used to diagnose tumors, hemorrhages, head injuries, and bone abnormalities. CTA images show blood vessels, soft tissue and bones and the images can be 3D reconstructed so that the cerebral vessels can be rotated and viewed from all angles. Similar to arteriography, a contrast dye containing iodine is administered into the blood stream but through an intravenous (IV) line. CT scans of the head are then taken while the IV is still placed into the person's arm. The x-ray tube rotates and takes images of the head which are then produced as computerized scans for viewing the cerebral vessels.

Magnetic Resonance Angiogram (MRA) [[image:MRA2.gif width="137" height="92" align="right" caption="MRA showing saccular aneurysm"]]
MRA is a noninvasive diagnostic test that takes detailed images of the soft tissues of the body. Along with detecting cerebral aneurysms, MRA is also used to diagnose AVM and tumors. Unlike X-rays or CT, images are created by using a magnetic field, radio waves, and a computer. A contrast dye contai ning gadolinium instead of iodine is injected into the blood stream that helps the computer “see” the arteries and veins. [12]

=Surgical Interventions =

There is a 1% annual risk of rupture and it is depend on the size and location of the aneurysm. Usually 50% of the patients with ruptured aneurysms do not make it to the hospital and die within a few seconds/minutes of the rupture, therefore, it is necessary to treat the aneurysm before it ruptures. Generally aneurysms greater than 10mm in size are treated; but in the case of middle-aged, younger patients or patients with a family history of aneurysms, the aneursym should be treated when it is 7-9mm in size. The surgical interventions are decided by the neurosurgeon depending on the size, type and location of the aneurysm. Studies have shown that although both clipping and coiling are effective surgical procedure, coiling produces much better results than clipping.

Microsurgical Clippingmedia type="youtube" key="IZ9f1JjeRHo" height="154" width="280" align="right"
This procedure is also known as open craniotomy. A small area of the head is shaved and a piece of the skull is removed to expose the area of the brain containing the aneurysm. The aneurysm is observed through a high resolution dissecting microsscope and a titanium clip is placed along the neck of the aneurysm to stop the flow of the blood into the aneurysm. The surgery is highly effective in preventing the aneurysm from rupturing and sometimes even eliminate the aneurysm. Complications may arise if the clip is placed inccorectly or is sealing the artery partially. causing the blood flow to be reduced or stop leading to stroke.

Endovascular Coiling media type="youtube" key="5Ss-IOmFyeA" height="186" width="336" align="right"
This procedure involves sealing the aneurysm by placing platinum coils into the aneurysm. In order to place the coils into the aneurysm, a catheter is inserted into the upper femoral artery and guided to the aneurysm through the blood stream. The catheter serves as a guide to the aneurysm and the coil is deployed into the aneurysm. Several coils are then placed in order to totally block the aneurysm. Once the aneurysm is blocked, the catheter is retrieved. If the neck of the aneurysm is wide, a balloon embolization is used. In balloon embolization, an deflated balloon is placed along the neck of the aneurysm. When the catheter is in place, the balloon is inflated covering the whole neck of the aneurysm. The aneurysm is then filled with coils; the balloon is deflated and the removed along with the catheter. Although coiling is an extremely effective treatment, complication may arise if the coil does not seal the whole aneurysm or protrudes in the artery associated with the aneurysm stopping the flow of blood through that artery causing stroke.

=References=