**2. Prevalence and incidence of aneurysms**

Although Unruptured Intracranial Aneurysms (UIA) are common [23, 24]. Their prevalence is subject to changes due to the improvements in invasive and noninvasive imaging techniques, the increasing knowledge about the related factors that determines screening in asymptomatic populations and the increase in the life expectancy. Historically, the methods used to address prevalence were retrospective or prospective autopsy studies in the decades from 1950's to the earliest 2000's [25] but non-invasive imaging studies have demonstrated higher prevalence and prevalence ratios compared to autopsy studies (PR 3•5, 95% CI 2•1–6•1)3. To study UIA, the Magnetic Resonance Angiography (MRA) is the most common method for detection in asymptomatic patients [26] and compared to Intra-Arterial Digital Subtraction Angiography (IA-DSA), systematic reviews have found no significant differences in the prevalence reported between these two imaging techniques (more details will be elucidated in the next section of this chapter). However, it's important to highlight that prevalence reported in non-invasive imaging studies can present limitations due to the interobserver agreement, training, experience, quality of equipment and expert's judgment [27].

The IA characteristics are also a major concern in prevalence studies; technical limitations in regard to location, size and morphology can decrease the sensitivity and specificity of the diagnostic methods. Both, large and relatively small [28] cohort's studies had shown that saccular morphology is the most common form of presentation and that among patients without history of subarachnoid hemorrhage (SAH) the distribution of IA in the internal carotid artery (ICA) and middle cerebral artery (MCA) are 24.8 and 22.7% [29] respectively, however in patients with previous history of SAH, the prevalence is higher in the MCA. In regard to the size, modern imaging techniques can easily detect aneurysms from 2 mm, which is extremely important to determine the risks of possible treatments or natural history, so far, the current evidence is that UIA > 5 mm, location in basilar artery apex and decrease in BMI over the follow-up period are related to speed up the 2.9% of aneurysm growth per year. However, irrespective of aneurysm size, the irregular shape and daughter sac are more likely to rupture [30, 31]. Although we know these are contributing factors, there is still a need to understand better the contribution of aneurysm related factors.

The prevalence of UIA among the general population is 3–5% [32] but there are several differences between populations that increase the risk for having a IA or a SAH. The risk factors commonly associated to IA development and rupture whether there's a previous history of SAH or not, are age > 30, female sex, African-American race, smoking, alcoholism, hypercholesterolemia, high blood pressure, first and second-degree relatives with SAH history, and other comorbidities as polycystic kidney disease, connective tissue disorders and brain tumors [33–36]. However,

lifelong follow-up studies of UIA suggested that only female sex and smoking status were significant risk factors for aSAH [37]. Across countries, compared to USA prevalence, China, Japan, European countries including (UK, Netherlands, Finland, Germany and Italy) had no significant differences in the prevalence ratios adjusted to age, sex and comorbidities [38–41]. Other studies in Iranian population [42] have shown a prevalence of 3.2% but more studies in non-Caucasian populations are still required to further understand the impact of genetics and cultural practices.

The incidence of aneurysmal SAH (aSAH) reports are questionable, first, in average 20% of the aSAH deaths occur suddenly, away from hospital or in emergency rooms [43]. Therefore, incidence can vary between countries with different autopsy rates and medical study protocols. In the case of Finland, the PHASES study showed a 3–6 times increased risk of aneurysm rupture in compared to other European nations and USA [44]. However, these findings can be a proof of how epidemiological studies need to improve their parameters more than a proof that Finnish people have more risk of aSAH. Finland has high rates of autopsy studies in sudden deaths [45] and all nonhospital deaths and moreover, longer life expectancy and pyramid shrinking due to the increasing of elderly population [46]. So, there's no currently strong evidence to conclude that aSAH in Finland cohorts is truly higher than the other countries included in the PHASES study.

In spite of this evidence, careful consideration must be taken when we think about the pros and cons to treat a patient based on their personal risk factors. Most of the large cohort's publications and meta-analysis have been done in populations where ethnicity diversity was limited, the impact of social stratus had not been assessed and criteria for collecting data and analysis was not standardized. Therefore, perfect epidemiological studies do not exist so, great efforts will be necessary to determine inclusion and exclusion criteria in future prospective cohorts.

### **3. Unruptured intracranial aneurysms**

Diagnosis of unruptured intracranial aneurysms (UIA) in most of the cases is incidentally during evaluations of other conditions [44] because the vast majority are asymptomatic or have subtle manifestations. Only, 10 to 15.5% of patients have symptoms related to UIA [45]. These symptoms generally are associated to mass effect due to the aneurysm size and growth, rarely cranial neuropathy or even more rare with sentinel hemorrhage, due to minimal blood leaking with the consequent meningeal irritation [45]. Symptomatic UIA often present with neurological deficits as visual dysfunction, ocular nerve palsy, bilateral temporal hemianopsia and other neurological symptoms as headaches, embolic cerebral ischemia, poorly defined spells, and seizures [46, 47]. Patients with symptomatic UIA need more attention because this can be a manifestation about riskier distribution and morphological [45] characteristics of the aneurysm, and a warning sign of an impending rupture [48]. The diagnoses modality after incidental discovery of an UIA, is based on which imaging modality is more sensitive depending on aneurysms characteristics, patients related factors, medical history and moreover, methods available in each center. Therefore, there is no specific diagnoses algorithm for UIA. The decision of screening or further imaging after finding an incidental aneurysm is still on the specialist judgment. These considerations are discussed below:

It has been mentioned that most of the UIA are diagnosed incidentally, and some of the non-invasive imaging methods have also been mentioned in the "prevalence" section of this chapter. However, there are still different evidences about the rates of diagnosis and prevalence reported through these non-invasive imaging methods as the MRA or CTA and IA-DSA, the current gold standard [22, 49]. Many authors had

**185**

*Endovascular Treatment of Brain Aneurysms DOI: http://dx.doi.org/10.5772/intechopen.88964*

expensive costs of MRA or CTA makes them inaccessible.

available treatments will be discussed below.

**3.1 Conservative management**

suggested that the MRA and CTA to be the best methods for preliminary screening of IA [50, 51], the sensitivity and specificity of both methods are 87 and 95% for MRA and 90 and 86% for CTA [47]. But the effectiveness of the diagnoses can decrease depending on the IA characteristics; in UIA < 3 mm, MRA and CTA sensitivity plummet to 38 and 61%, respectively [52]. Moreover, the high rates of comorbidities in people with UIA product of common pathophysiology (like hypertension with the consequent kidney failure) or to the old age of patients can limit the use of the contrast dye in CTA for screening. Therefore, MRA is the most frequent tool for screening nowadays. Other non-invasive techniques like transcranial Doppler (TCD) have been explored, but whether power Doppler is done with or without contrast enhancement, it's sensitivity and specificity together are not superior to MRA and CTA [51]. Nevertheless, TCD can be a screening tool in countries were the

Sensitivity and specificity of imaging methods for diagnostic are important, but more considerations should be taken to study UIA characteristics. IADSA, provides the better spatial resolution than other techniques [44], but this method may not provide a good sense of aneurysm volume and can present difficulties when vessels are overlapped, and therefore 3D reconstructions are often needed to fully evaluated for intracranial aneurysms. Moreover, IADSA as an invasive method, can carry risks; 2.3% of patients can present transient neurological complications, 0.4% permanent neurological complications and 14.7% of non-neurological complications [52]. Novel imaging methods as the Optical coherence tomography (OCT) can be useful to assess key factors in aneurysm structure due to the power to increase 10 times image resolution compared to other current techniques [44] and furthermore, OCT has a nearlybiopsy resolution [53] and enhance resolution of birefringent tissues as artery laminas [54] which is major concern in pathophysiology, as mentioned before in this chapter. Furthermore, considerations need to be taken as to imaging modality if the patient has had previously treated aneurysms. MRA is not sensitive for patients with previously treated clipped aneurysms. For these patients CTA is preferred. MRA is still sensitive for previously coiled aneurysms. For patients treated with flow diverter stents either MRA with contrast or CTA can be used. If the patient had coils with any kind of stent, then MRA with contrast is the preferred modality. Taken together the results of imaging for UIA, the neuro-interventional team consider the possible treatments for each patient based on the risks and benefits between prevent treatment and natural history, however due to lack of evidence of the natural history in some categories of UIA is not uncommon to balance the pros and cos between prevent treatment and aSAH outcomes. Some of the current

First of all, having an aneurysm does not imply always the need to undergo surgical or endovascular treatment. Most of the UIA will never cause symptoms neither rupture or at least the probability of this events will not be over 1% per year. Therefore, many patients decide to take the risk of conservative management over the risks of preventive treatments. However, conservative management is not equal to doing nothing, this management bear intervention from the physician to educate well the patient about the risk factors that will increase the probabilities of rupture and an active participation of the patients to modify their risky habits. There is strong evidence that supports the conservative management when lifetime risk of

Nevertheless, in patients under conservative management, imaging follow-ups at 1 year intervals have been recommended with CTA or MRA [25] to assess aneurysm

morbidity and mortality is low [42] as represented in **Figure 1**.

#### *Endovascular Treatment of Brain Aneurysms DOI: http://dx.doi.org/10.5772/intechopen.88964*

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

higher than the other countries included in the PHASES study.

specialist judgment. These considerations are discussed below:

**3. Unruptured intracranial aneurysms**

In spite of this evidence, careful consideration must be taken when we think about the pros and cons to treat a patient based on their personal risk factors. Most of the large cohort's publications and meta-analysis have been done in populations where ethnicity diversity was limited, the impact of social stratus had not been assessed and criteria for collecting data and analysis was not standardized. Therefore, perfect epidemiological studies do not exist so, great efforts will be necessary to determine inclusion and exclusion criteria in future prospective cohorts.

Diagnosis of unruptured intracranial aneurysms (UIA) in most of the cases is incidentally during evaluations of other conditions [44] because the vast majority are asymptomatic or have subtle manifestations. Only, 10 to 15.5% of patients have symptoms related to UIA [45]. These symptoms generally are associated to mass effect due to the aneurysm size and growth, rarely cranial neuropathy or even more rare with sentinel hemorrhage, due to minimal blood leaking with the consequent meningeal irritation [45]. Symptomatic UIA often present with neurological deficits as visual dysfunction, ocular nerve palsy, bilateral temporal hemianopsia and other neurological symptoms as headaches, embolic cerebral ischemia, poorly defined spells, and seizures [46, 47]. Patients with symptomatic UIA need more attention because this can be a manifestation about riskier distribution and morphological [45] characteristics of the aneurysm, and a warning sign of an impending rupture [48]. The diagnoses modality after incidental discovery of an UIA, is based on which imaging modality is more sensitive depending on aneurysms characteristics, patients related factors, medical history and moreover, methods available in each center. Therefore, there is no specific diagnoses algorithm for UIA. The decision of screening or further imaging after finding an incidental aneurysm is still on the

It has been mentioned that most of the UIA are diagnosed incidentally, and some of the non-invasive imaging methods have also been mentioned in the "prevalence" section of this chapter. However, there are still different evidences about the rates of diagnosis and prevalence reported through these non-invasive imaging methods as the MRA or CTA and IA-DSA, the current gold standard [22, 49]. Many authors had

lifelong follow-up studies of UIA suggested that only female sex and smoking status were significant risk factors for aSAH [37]. Across countries, compared to USA prevalence, China, Japan, European countries including (UK, Netherlands, Finland, Germany and Italy) had no significant differences in the prevalence ratios adjusted to age, sex and comorbidities [38–41]. Other studies in Iranian population [42] have shown a prevalence of 3.2% but more studies in non-Caucasian populations are still required to further understand the impact of genetics and cultural practices. The incidence of aneurysmal SAH (aSAH) reports are questionable, first, in average 20% of the aSAH deaths occur suddenly, away from hospital or in emergency rooms [43]. Therefore, incidence can vary between countries with different autopsy rates and medical study protocols. In the case of Finland, the PHASES study showed a 3–6 times increased risk of aneurysm rupture in compared to other European nations and USA [44]. However, these findings can be a proof of how epidemiological studies need to improve their parameters more than a proof that Finnish people have more risk of aSAH. Finland has high rates of autopsy studies in sudden deaths [45] and all nonhospital deaths and moreover, longer life expectancy and pyramid shrinking due to the increasing of elderly population [46]. So, there's no currently strong evidence to conclude that aSAH in Finland cohorts is truly

**184**

suggested that the MRA and CTA to be the best methods for preliminary screening of IA [50, 51], the sensitivity and specificity of both methods are 87 and 95% for MRA and 90 and 86% for CTA [47]. But the effectiveness of the diagnoses can decrease depending on the IA characteristics; in UIA < 3 mm, MRA and CTA sensitivity plummet to 38 and 61%, respectively [52]. Moreover, the high rates of comorbidities in people with UIA product of common pathophysiology (like hypertension with the consequent kidney failure) or to the old age of patients can limit the use of the contrast dye in CTA for screening. Therefore, MRA is the most frequent tool for screening nowadays. Other non-invasive techniques like transcranial Doppler (TCD) have been explored, but whether power Doppler is done with or without contrast enhancement, it's sensitivity and specificity together are not superior to MRA and CTA [51]. Nevertheless, TCD can be a screening tool in countries were the expensive costs of MRA or CTA makes them inaccessible.

Sensitivity and specificity of imaging methods for diagnostic are important, but more considerations should be taken to study UIA characteristics. IADSA, provides the better spatial resolution than other techniques [44], but this method may not provide a good sense of aneurysm volume and can present difficulties when vessels are overlapped, and therefore 3D reconstructions are often needed to fully evaluated for intracranial aneurysms. Moreover, IADSA as an invasive method, can carry risks; 2.3% of patients can present transient neurological complications, 0.4% permanent neurological complications and 14.7% of non-neurological complications [52]. Novel imaging methods as the Optical coherence tomography (OCT) can be useful to assess key factors in aneurysm structure due to the power to increase 10 times image resolution compared to other current techniques [44] and furthermore, OCT has a nearlybiopsy resolution [53] and enhance resolution of birefringent tissues as artery laminas [54] which is major concern in pathophysiology, as mentioned before in this chapter.

Furthermore, considerations need to be taken as to imaging modality if the patient has had previously treated aneurysms. MRA is not sensitive for patients with previously treated clipped aneurysms. For these patients CTA is preferred. MRA is still sensitive for previously coiled aneurysms. For patients treated with flow diverter stents either MRA with contrast or CTA can be used. If the patient had coils with any kind of stent, then MRA with contrast is the preferred modality.

Taken together the results of imaging for UIA, the neuro-interventional team consider the possible treatments for each patient based on the risks and benefits between prevent treatment and natural history, however due to lack of evidence of the natural history in some categories of UIA is not uncommon to balance the pros and cos between prevent treatment and aSAH outcomes. Some of the current available treatments will be discussed below.

#### **3.1 Conservative management**

First of all, having an aneurysm does not imply always the need to undergo surgical or endovascular treatment. Most of the UIA will never cause symptoms neither rupture or at least the probability of this events will not be over 1% per year. Therefore, many patients decide to take the risk of conservative management over the risks of preventive treatments. However, conservative management is not equal to doing nothing, this management bear intervention from the physician to educate well the patient about the risk factors that will increase the probabilities of rupture and an active participation of the patients to modify their risky habits. There is strong evidence that supports the conservative management when lifetime risk of morbidity and mortality is low [42] as represented in **Figure 1**.

Nevertheless, in patients under conservative management, imaging follow-ups at 1 year intervals have been recommended with CTA or MRA [25] to assess aneurysm

**Figure 1.** *Giant right vertebral aneurysm before and after coiling.*

growth, although it is unclear whether this frequency of time-interval is truly necessary. However, is not uncommon to have mixed factors in UIA patients, to make it clear, a systematic review showed that if hypertension and history of SAH are present (considering this both as major risk factors) in a patient under 70 years, with an <10 mm UIA in the anterior circulation, we will still be talking about a probability of risk of ~1% per year [24]. So, a standardized timing for imaging follow-ups according to each patients and aneurysm related factors does not exist, in part because aneurysm growing is discontinuous but the ELAPSS score (mentioned in **Figure 1**) can be helpful to determine the need of follow-up at 3 or 5 years based on the risk of aneurysm growth [55]. These patients who choose conservative management live with a small very definite risk of rupture. Recently, a study showed that patients with untreated UIA, may decrease their quality of life (QoL) and moreover, trigger mental disorder as anxiety and depression [56, 57] possibly due to the uncertainty of whether their aneurysm is going to burst and when.
