**1.1 The incidence of intracranial atherosclerotic disease (ICAD)**

Intracranial atherosclerosis is one of the most important causes of stroke worldwide [1]. All major intracranial arteries are affected by atherosclerotic disease, and between 6 and 50% of all world ischemic strokes are the result of ICAD [2]. Intracranial arterial atherosclerotic stenosis (ICAS) represents the most advanced stage of ICAD, and thus nonstenotic ICAD is much more common than stenotic ICAD [3].

Regarding the incidence of ICAD, it varies especially by ethnicity. Population groups which are at high risk for ICAS include: Asians (30–50% of all new ischemic strokes) [4], Hispanics, and population of African descent; conversely, the risk is lower in Caucasians (8–10% of all new ischemic strokes) [5]. The reason for racial differences is still unclear. The main hypotheses include: low lipid levels and high blood pressure (susceptibility to intracranial and intracerebral vascular disease);

high lipids and high blood pressure (susceptibility to extracranial occlusive vascular lesions); and diabetes mellitus and metabolic syndrome (for ICAS) [2, 6, 7]. Other studies include inherited susceptibility of intracranial vessels to atherosclerosis [8], acquired differences in the prevalence of risk factors [5], differential responses to the same risk factors [9], and different genetic susceptibility [7]. It is also possible that misclassifying patients with adult-onset Moya-Moya disease (MMD) as having ICAD may partly explain the high prevalence of ICAD in Asians [10]. A genome-wide linkage analysis and an exome analysis identified the strongest susceptibility gene for MMD in East Asian people: ring finger 213 (RNF213) [10]. An important role in the emergence of these ethnic differences can be represented by the lifestyle: the pattern of ischemic stroke is changing in Asian patients; due to the westernized lifestyle, the number of extracranial cervical disease is rising [11].

#### **1.2 Prognosis of asymptomatic intracranial atherosclerotic disease (ICAD)**

Regarding the prevalence of asymptomatic ICAD in general population, information is still limited, in the absence of large clinical trials [12]. The atherosclerotic process develops silently over years, until its lesions suddenly become symptomatic. Accordingly, early diagnosis of ICAD may improve the therapeutic strategy, while the disease is still asymptomatic. However, the natural history of asymptomatic ICAD is not fully known, especially in Caucasians [3].

The natural history of asymptomatic versus symptomatic ICAD differs from that of extracranial carotid disease (ECAD). Patients with symptomatic ICAD have a low risk of stroke in the stenotic arterial territory, compared to patients with asymptomatic ECAD, while patients with symptomatic ICAD have a higher risk, especially those with clinically significant hemodynamic stenosis, early after stroke [13]. Therefore, recent studies suggest that the annual risk of stroke in asymptomatic patients with at least 50% stenosis of a major intracranial artery is less than 10% [14]. Furthermore, patients with severe intracranial stenosis (70–99%) have a higher risk of stroke than do patients with moderate intracranial stenosis (50–69%) [14].

Arenillas designed a population-based study [3], which comes to clarify the natural history and the prevalence of asymptomatic ICAD in Caucasians. Study subjects (1503) were randomly selected from a population of 600 000 inhabitants, from March 2007 until June 2010. The primary enrollment criteria were: age over 50 years, no past history of cerebrovascular or ischemic heart disease, and moderate-to-high vascular risk. Presence and severity of ICAS were determined through the medium of transcranial color-coded duplex (TCCS) and subsequent MR angiography (MRA) confirmation. Preliminary results showed a prevalence of asymptomatic ICAD of 9% in the first 157 studied subjects [3].

Several transcranial Doppler (TCD) studies in an asymptomatic Asian population have also been conducted. They have come to the conclusion that the prevalence of asymptomatic ICAS ranged from 5.9 to 24.5% [15].

#### **1.3 Risk factors for intracranial atherosclerotic disease (ICAD)**

Oh Young Bang reported various conditions and risk factors for ICAD, from risk factors associated with asymptomatic ICAD to risk factors for stroke recurrence [16]. ICAD risk could not be fully related to conventional risk factors for stroke; therefore, specialists are still investigating specific risk factors for ICAD [3].

**81**

*Diagnosis of Symptomatic Intracranial Atherosclerotic Disease*

**2. The mechanisms of ischemia in intracranial atherosclerotic disease** 

The main limitations of this classical approach are as follows:

1.It may be restricted to the most advanced stage of ICAD alone [3].

According to Arenillas [3], our traditional understanding of ICAD is based on the detection of hemodynamically relevant intracranial arterial stenosis (ICAS).

2.It is unable to differentiate atherosclerosis from stenosis caused by other entities. The etiological differential diagnosis of the arterial stenosis includes atherosclerotic disease, embolus with partial recanalization, arterial dissection, vasculitis, and vasospasm. Thus, it is important to note that while anatomic diagnosis of arterial narrowing can be made with appropriate accuracy using conventional imaging techniques, identifying the cause of stenosis involves

3.It may not be able to provide information about the histopathologic composition and activity of the intracranial atherosclerotic plaque. The importance of this last point is based on the fact that symptomatic intracranial atherosclerotic plaques are characterized not only by a higher degree of luminal stenosis but also by a richer content in lipid, intraplaque hemorrhage, and inflammatory cell infiltration, all of which are well-known determinants of plaque instability

Stroke associated with ICAD occurs in association with four mechanisms:

large territorial lesions via sudden thrombotic occlusion [16].

b.Artery-to-artery embolism. This mechanism commonly causes multiple

c.Hemodynamic insufficiency/failure (with impaired collateral flow and cerebrovascular reserve). Severe narrowing or occlusion of the lumen may lead to hypoperfusion of the distal brain territory, especially in patients with inadequate collateral flow. The hypoperfusion through a stenotic intracranial artery

d.Branch occlusion disease (BOD) is one of the main stroke mechanisms of ICAD. This mechanism, specific to ICAD, consists in growing of the plaque over the ostia of penetrating arteries. It is defined by a milder degree of stenosis and comma-shaped infarcts extending to the basal surface of the parent artery.

Thus, even mild stenosis of intracranial atherosclerotic arteries (<50%) may be clinically relevant, and high-resolution magnetic resonance imaging (HR-MRI)

a.In situ thrombotic occlusion (with impaired anterograde flow). Plaque rupture reveals its thrombogenic core to clotting factors resulting a thrombus that can locally occlude the artery or even embolize distally. The term of "vulnerable plaques" refers to those ones with a large lipid core, the presence of intraplaque hemorrhage, or a thin or ruptured fibrous cap; this kind of plaques are liable to suffer anytime a rupture. Patients with unstable intracranial plaques may show

*DOI: http://dx.doi.org/10.5772/intechopen.90250*

iterative or multimodal imaging [3].

in the extracranial vasculature [3, 17].

cortico-subcortical infarcts [16].

causes watershed or border-zone strokes [16].

BOD has been related to cryptogenic strokes [16, 18].

**(ICAD)**

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

high lipids and high blood pressure (susceptibility to extracranial occlusive vascular lesions); and diabetes mellitus and metabolic syndrome (for ICAS) [2, 6, 7]. Other studies include inherited susceptibility of intracranial vessels to atherosclerosis [8], acquired differences in the prevalence of risk factors [5], differential responses to the same risk factors [9], and different genetic susceptibility [7]. It is also possible that misclassifying patients with adult-onset Moya-Moya disease (MMD) as having ICAD may partly explain the high prevalence of ICAD in Asians [10]. A genome-wide linkage analysis and an exome analysis identified the strongest susceptibility gene for MMD in East Asian people: ring finger 213 (RNF213) [10]. An important role in the emergence of these ethnic differences can be represented by the lifestyle: the pattern of ischemic stroke is changing in Asian patients; due to the westernized lifestyle, the number of extracranial cervical disease is

**1.2 Prognosis of asymptomatic intracranial atherosclerotic disease (ICAD)**

Regarding the prevalence of asymptomatic ICAD in general population, information is still limited, in the absence of large clinical trials [12]. The atherosclerotic process develops silently over years, until its lesions suddenly become symptomatic. Accordingly, early diagnosis of ICAD may improve the therapeutic strategy, while the disease is still asymptomatic. However, the natural history of asymptomatic ICAD is not fully known, especially in

The natural history of asymptomatic versus symptomatic ICAD differs from that of extracranial carotid disease (ECAD). Patients with symptomatic ICAD have a low risk of stroke in the stenotic arterial territory, compared to patients with asymptomatic ECAD, while patients with symptomatic ICAD have a higher risk, especially those with clinically significant hemodynamic stenosis, early after stroke [13]. Therefore, recent studies suggest that the annual risk of stroke in asymptomatic patients with at least 50% stenosis of a major intracranial artery is less than 10% [14]. Furthermore, patients with severe intracranial stenosis (70–99%) have a higher risk of stroke than do patients with moderate intracranial

Arenillas designed a population-based study [3], which comes to clarify the natural history and the prevalence of asymptomatic ICAD in Caucasians. Study subjects (1503) were randomly selected from a population of 600 000 inhabitants, from March 2007 until June 2010. The primary enrollment criteria were: age over 50 years, no past history of cerebrovascular or ischemic heart disease, and moderate-to-high vascular risk. Presence and severity of ICAS were determined through the medium of transcranial color-coded duplex (TCCS) and subsequent MR angiography (MRA) confirmation. Preliminary results showed a prevalence of

Several transcranial Doppler (TCD) studies in an asymptomatic Asian population have also been conducted. They have come to the conclusion that the preva-

Oh Young Bang reported various conditions and risk factors for ICAD, from risk factors associated with asymptomatic ICAD to risk factors for stroke recurrence [16]. ICAD risk could not be fully related to conventional risk factors for stroke; therefore, specialists are still investigating specific risk factors for ICAD [3].

asymptomatic ICAD of 9% in the first 157 studied subjects [3].

**1.3 Risk factors for intracranial atherosclerotic disease (ICAD)**

lence of asymptomatic ICAS ranged from 5.9 to 24.5% [15].

**80**

rising [11].

Caucasians [3].

stenosis (50–69%) [14].
