Intracranial atherosclerosis: current understanding and perspectives

Area of Science:

• Neurology
• Vascular Medicine
• Stroke Research

Background:

• Intracranial atherosclerotic disease (ICAD) is a major cause of stroke, comparable to extracranial carotid stenosis and nonvalvular atrial fibrillation.
• Recent clinical trials evaluating anticoagulation and stenting in ICAD patients failed to significantly reduce major vascular events.
• Understanding ICAD's diverse stroke mechanisms is crucial, unlike simpler mechanisms in other cerebrovascular diseases.

Purpose of the Study:

• To summarize recent advances in understanding ICAD risk factors and potential race-ethnic disparities.
• To analyze the reasons behind the failure of recent large clinical trials in ICAD.
• To propose a more nuanced approach for future ICAD clinical trials.

Main Methods:

• Review of recent clinical trial data and literature on intracranial atherosclerotic disease.
• Analysis of stroke mechanisms associated with ICAD, including in situ thrombotic occlusion, artery-to-artery embolism, hemodynamic insufficiency, and branch occlusion.
• Exploration of potential biomarkers for patient stratification in clinical trials.

Main Results:

• Optimal control of risk factors is paramount for reducing major vascular events in ICAD patients.
• Existing clinical trials may have been limited by a failure to account for the heterogeneity of ICAD stroke mechanisms.
• Race-ethnic differences in ICAD prevalence warrant further investigation.

Conclusions:

• Future ICAD clinical trials must consider the diverse stroke mechanisms and patient-specific features.
• Treatment strategies should be tailored based on clinical presentation, time since onset, and advanced biomarkers like diffusion-weighted imaging and plaque characteristics.
• Further research is needed to refine treatment approaches for intracranial atherosclerotic disease.