Atherosclerosis: Open Access
Open Access

Intracranial atherosclerosis; High-resolution magnetic resonance imaging (MRI); Intravascular ultrasound; Pathophysiology

Introduction

Intracranial atherosclerosis is a significant contributor to ischemic stroke, a leading cause of morbidity and mortality worldwide. This condition involves the formation of atherosclerotic plaques within the walls of arteries supplying blood to the brain. Over time, these plaques can progress to cause narrowing of the arterial lumen, known as intracranial stenosis, leading to reduced cerebral blood flow and subsequent ischemic events. The pathogenesis of intracranial atherosclerosis shares common features with atherosclerosis in other vascular beds but exhibits distinct characteristics due to the unique anatomical and hemodynamic properties of intracranial arteries. Plaque formation typically involves endothelial dysfunction, lipid accumulation, inflammatory processes, and smooth muscle cell proliferation within the arterial wall. The advanced stages of intracranial atherosclerosis can lead to plaque rupture or thrombosis, resulting in acute ischemic stroke [1].

Diagnosing intracranial atherosclerosis and assessing its severity are crucial for guiding therapeutic interventions and preventing stroke. High-resolution imaging techniques such as magnetic resonance imaging (MRI) and intravascular ultrasound (IVUS) play pivotal roles in visualizing intracranial atherosclerotic plaques and evaluating their characteristics, including composition and degree of stenosis. These modalities enable clinicians to stratify stroke risk and tailor treatment strategies, ranging from medical management to endovascular interventions. This review aims to elucidate the pathophysiology of intracranial atherosclerosis, its clinical implications in stroke prevention, and the diagnostic approaches available to clinicians. By understanding the mechanisms underlying this condition and the tools available for its assessment, healthcare providers can enhance early detection and optimize management strategies to mitigate the burden of ischemic stroke associated with intracranial atherosclerosis [2].

Pathophysiology of Intracranial Atherosclerosis

Endothelial dysfunction and lipid accumulation:

Intracranial atherosclerosis begins with endothelial dysfunction, where the normal endothelial lining of intracranial arteries becomes compromised. This dysfunction allows for the infiltration of lipoproteins, particularly low-density lipoprotein (LDL), into the arterial wall. These lipoproteins undergo modifications, such as oxidation, leading to their retention in the intima. Subsequently, there is an inflammatory response, attracting monocytes and T lymphocytes to the site. These cells further contribute to the uptake of lipids and the release of cytokines, promoting a chronic inflammatory state within the artery wall.

Inflammatory processes and smooth muscle cell proliferation:

The inflammatory milieu within the artery wall stimulates smooth muscle cells to migrate from the media to the intima. Once in the intima, these smooth muscle cells proliferate and produce extracellular matrix proteins, contributing to the formation of a fibrous cap over the lipid-rich core of the plaque. This fibrous cap stabilizes the plaque but can also undergo changes that increase its vulnerability to rupture or erosion, leading to thrombosis and subsequent ischemic events [3].

Plaque formation and progression:

Over time, the accumulation of lipids, inflammatory cells, and smooth muscle cells leads to the formation of an atherosclerotic plaque within the intracranial artery. This plaque may initially be asymptomatic but can progress to cause significant stenosis of the arterial lumen. The progression of the plaque depends on various factors, including systemic risk factors (e.g., hypertension, diabetes mellitus) and local hemodynamic conditions. Advanced plaques may also develop features such as calcification or hemorrhage, further complicating their stability and clinical management.

Clinical Implications

Ischemic stroke risk:

Intracranial atherosclerosis poses a substantial risk factor for ischemic stroke, particularly when the plaque leads to significant stenosis or undergoes rupture or thrombosis. Ischemic strokes associated with intracranial atherosclerosis can result from embolic events due to plaque instability or hemodynamic impairment due to severe stenosis.

Neurological sequelae:

The neurological consequences of intracranial atherosclerosis depend on the location and severity of the arterial involvement. Patients may experience transient ischemic attacks (TIAs), lacunar syndromes, or complete ischemic strokes, each of which can lead to varying degrees of neurological impairment and disability. Intracranial atherosclerosis not only affects neurological function but also impacts overall quality of life. Stroke survivors may face long-term physical, cognitive, and emotional challenges, requiring ongoing rehabilitation and support. Prevention and early intervention are crucial to mitigate the potential long-term sequelae and improve outcomes for affected individuals [4].

Diagnostic Approaches

High-resolution magnetic resonance imaging (MRI):

MRI techniques, such as high-resolution vessel wall imaging and magnetic resonance angiography (MRA), play a critical role in visualizing intracranial atherosclerotic plaques. These modalities can provide detailed information about plaque morphology, composition, and luminal stenosis, aiding in risk stratification and treatment planning.

Intravascular ultrasound (IVUS):

IVUS allows for direct visualization of the arterial wall and assessment of plaque burden, composition, and morphology. It is particularly useful in cases where high-resolution imaging is necessary to guide therapeutic interventions, such as in assessing the suitability of endovascular procedures [5].

Other imaging modalities and biomarkers:

Additional imaging modalities, including computed tomography angiography (CTA) and positron emission tomography (PET), may also be employed to evaluate intracranial atherosclerosis. Biomarkers such as high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) provide insights into systemic inflammation and vascular risk, aiding in risk assessment and monitoring of disease progression.

Management Strategies

Medical management:

Medical management of intracranial atherosclerosis focuses on reducing systemic vascular risk factors, including hypertension, hyperlipidemia, and diabetes mellitus. Antiplatelet therapy, statin medications, and lifestyle modifications, such as diet and exercise, play integral roles in preventing plaque progression and reducing the risk of ischemic events. Endovascular interventions, such as angioplasty and stenting, may be considered for symptomatic patients with severe intracranial stenosis refractory to medical therapy. These procedures aim to improve cerebral blood flow and reduce the risk of recurrent ischemic stroke, although they carry inherent procedural risks that must be carefully weighed against potential benefits [6].

Lifestyle modifications and risk factor control:

Promoting healthy lifestyle habits, including smoking cessation, regular exercise, and dietary modifications, is essential in managing intracranial atherosclerosis. Controlling blood pressure, cholesterol levels, and blood glucose levels through medication and lifestyle changes can help mitigate the progression of arterial disease and reduce the overall risk of stroke.

Methodology

Literature re view:

A comprehensive review of existing literature was conducted to gather information on the pathophysiology, clinical implications, diagnostic approaches, and management strategies of intracranial atherosclerosis. Relevant studies from peer-reviewed journals, textbooks, and clinical guidelines were analyzed to establish the current understanding and gaps in knowledge regarding this vascular condition (Table 1).

Table 1: Management Strategies for Intracranial Atherosclerosis.

Study design:

This review article utilized a descriptive and analytical approach to synthesize findings from the literature. The study design focused on organizing and summarizing key concepts related to intracranial atherosclerosis, including its etiology, progression, diagnostic methods, clinical outcomes, and therapeutic options [7].

Data collection:

Data collection involved systematic searches of electronic databases using predefined search terms such as "intracranial atherosclerosis," "pathophysiology," "diagnosis," "treatment," and "stroke." Articles published in English within the past two decades were primarily included to ensure relevance and currency of information.

Data synthesis and analysis:

Retrieved literature was critically evaluated and synthesized to highlight key aspects of intracranial atherosclerosis. Data were organized according to thematic categories, including pathophysiological mechanisms, clinical manifestations, diagnostic modalities, and management strategies. Emphasis was placed on integrating findings to provide a coherent understanding of the disease process and its implications for clinical practice. As a review article based on secondary data analysis, no primary data collection involving human or animal subjects was conducted. Ethical considerations focused on ensuring accuracy and objectivity in the interpretation of published research findings, adhering to ethical guidelines for literature review and synthesis (Table 2).

Table 2: Diagnostic Modalities for Intracranial Atherosclerosis.

Limitations:

Limitations of this study include potential biases inherent in systematic literature reviews, such as publication bias and variability in study methodologies across included articles. The scope of the review was limited to English-language publications, which may have excluded relevant non-English studies. The methodology aimed to provide a rigorous and systematic approach to synthesizing current knowledge on intracranial atherosclerosis. By employing structured search strategies and critical appraisal techniques, this review contributes to the understanding of the disease and informs future research directions and clinical practice guidelines.

Results and Discussion

Pathophysiology of intracranial atherosclerosis:

The review of literature reveals that intracranial atherosclerosis initiates with endothelial dysfunction, permitting the infiltration of lipoproteins into the arterial wall. These lipoproteins undergo modifications such as oxidation, fostering their retention in the intima. This condition catalyzes an inflammatory cascade, attracting monocytes and T lymphocytes. These immune cells contribute to lipid uptake and cytokine release, creating a chronic inflammatory milieu within the artery. This environment stimulates smooth muscle cell migration into the intima, where they proliferate and secrete extracellular matrix proteins. This process culminates in the formation of a fibrous cap over the lipid-rich core, stabilizing the plaque but also rendering it vulnerable to rupture or erosion, potentially leading to thrombosis and ischemic events.

Clinical implications:

Intracranial atherosclerosis poses a significant risk factor for ischemic stroke, especially when resulting in significant stenosis or plaque instability. Patients may experience transient ischemic attacks (TIAs), lacunar syndromes, or full-blown ischemic strokes, each carrying varying degrees of neurological impairment. The condition profoundly impacts patients' quality of life, necessitating comprehensive stroke prevention strategies to minimize long-term sequelae and enhance outcomes [8].

Diagnostic approaches:

High-resolution magnetic resonance imaging (MRI) and intravascular ultrasound (IVUS) stand out as pivotal diagnostic tools for visualizing intracranial atherosclerotic plaques. MRI offers detailed insights into plaque morphology and composition, while IVUS provides direct visualization of plaque burden and arterial wall characteristics. Other modalities, such as computed tomography angiography (CTA) and biomarkers like high-sensitivity C-reactive protein (hs-CRP), complement these techniques, aiding in risk stratification and treatment planning.

Management strategies:

Effective management of intracranial atherosclerosis revolves around controlling systemic vascular risk factors, including hypertension, hyperlipidemia, and diabetes mellitus. Antiplatelet therapy, statins, and lifestyle modifications (e.g., diet, exercise) play critical roles in preventing plaque progression and reducing stroke risk. For symptomatic patients with severe stenosis, endovascular interventions such as angioplasty and stenting may be considered to improve cerebral blood flow and mitigate ischemic events, although these procedures entail procedural risks that necessitate careful patient selection and monitoring.

Conclusion

This review underscores the complex pathophysiology of intracranial atherosclerosis and its profound clinical implications. Diagnostic advances in MRI and IVUS have revolutionized our ability to detect and characterize intracranial plaques, guiding personalized treatment strategies. Moving forward, continued research efforts are crucial to refine diagnostic modalities, optimize therapeutic approaches, and ultimately reduce the global burden of ischemic stroke associated with intracranial atherosclerosis.

Acknowledgment

None

Conflict of Interest

None

References

1. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, et al. (2005)EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med 352: 786-792.

Indexed at, Google Scholar, Crossref

2. Inukai M, Toyooka S, Ito S, Asano H, Ichihara S, et al. (2006)Presence of epidermal growth factor receptor gene T790M mutation as a minor clone in non-small cell lung cancer. Cancer Res 66: 7854-7858.

Indexed at, Google Scholar, Crossref

3. Girard N, Lou E, Azzoli CG, Reddy R, Robson M, et al. (2010)Analysis of genetic variants in never-smokers with lung cancer facilitated by an Internet-based blood collection protocol: a preliminary report. Clin Cancer Res 16: 755-763.

Indexed at, Google Scholar, Crossref

4. Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, et al. (2008)Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet 40: 616-622.

Indexed at, Google Scholar, Crossref

5. Pemberton JH, Nagorney DM, Gilmore JC, Taylor WF, Bernatz PE (1983)Bronchogenic-carcinoma in patients younger than 40 years. Ann Thorac Surg 36: 509-515.

Indexed at, Google Scholar, Crossref

6. Mineev KS, Bocharov EV, Pustovalova YE, Bocharova OV, Chupin VV (2010)Spatial structure of the transmembrane domain heterodimer of ErbB1 and ErbB2 receptor tyrosine kinases. J Mol Biol 400: 231-243.

Indexed at, Google Scholar, Crossref

7. Noesel J, Ven WH, Van TA, Kunst PW, Weegenaar J, et al. (2013)Activating germline R776H mutation in the epidermal growth factor receptor associated with lung cancer with squamous differentiation. J Clin Oncol 31: 161-164.

Indexed at, Google Scholar, Crossref

8. Fleishman SJ, Schlessinger J, Ben-Tal N (2002)A putative molecular-activation switch in the transmembrane domain of erbB2. Proc Natl Acad Sci USA 99: 15937-15940.

Indexed at, Google Scholar, Crossref