Background: Intracranial atherosclerotic disease (ICAD) remains a major global cause of ischemic stroke—particularly in Asian, Black, and Hispanic populations—and is characterized by high recurrence rates despite advances in intensive medical management. Objectives: This review synthesizes current evidence on surgical and endovascular approaches for ICAD, including extracranial–intracranial bypass, encephaloduroarteriosynangiosis, angioplasty, and hybrid revascularization strategies. Methods: We performed a structured narrative literature search of PubMed and Scopus. Searches were conducted up to 1 October 2025 using combinations of subject headings and keywords, including “intracranial atherosclerotic disease”, “ICAD”, “intracranial stenosis”, “bypass”, “encephaloduroarteriosynangiosis”, “angioplasty”, “stenting”, “revascularization”, and “stroke”. We also scanned reference lists of key articles and relevant reviews. Non-English language articles were excluded. Results: While randomized trials such as SAMMPRIS, VISSIT, and CASSISS reaffirm intensive medical management as first-line therapy, emerging data suggest that surgical revascularization may benefit select patients with hemodynamic compromise refractory to medical therapy. Recent studies incorporating physiologic imaging—such as PET, SPECT, and perfusion MRI—have refined patient selection, reducing perioperative risk and improving long-term outcomes. Innovations in indirect revascularization, hybrid procedures, and intraoperative imaging continue to expand therapeutic possibilities. However, evidence remains heterogeneous, underscoring the need for well-powered randomized trials integrating modern surgical techniques, objective hemodynamic endpoints, and AI-enhanced imaging analytics. Conclusions: While intensive medical management remains the first-line standard of care, select patients with refractory, hemodynamically significant ICAD may benefit from direct, indirect, or hybrid surgical revascularization. Future directions emphasize personalized, physiology-based management frameworks that combine medical, surgical, and technological advances to optimize stroke prevention and long-term vascular outcomes in ICAD.

Introduction: Intracranial aneurysms (IAs) are focal dilatations of cerebral arteries that carry a significant risk of rupture and subarachnoid hemorrhage (aSAH). Advances in basic science have improved understanding of vascular wall biology, hemodynamic stress, inflammation, and genetic contribution to aneurysm rupture. Rapid progress in neurovascular therapeutics highlights the need to evaluate emerging molecular and pharmacologic strategies targeting IAs. Methodology: This narrative review synthesizes evidence from 2015 to 2025 on the cellular, molecular, and biomechanical mechanisms underlying IA pathophysiology. A structured search of PubMed, Scopus, and Embase identified studies examining molecular pathways, genetic determinants, and therapeutic approaches. Discussion: Aneurysm initiation involves endothelial responses to abnormal shear stress, activating NF-κB, MAPK, and calcium-dependent pathways that promote inflammation, smooth-muscle cell apoptosis, and extracellular matrix degradation. Pharmacologic candidates including MCP-1 antagonists, PPARγ agonists, and IL-6/STAT3 inhibitors reduce inflammatory remodeling, while doxycycline and cathepsin inhibitors preserve matrix integrity. Emerging strategies like microRNA modulation, tyrosine-kinase inhibition, and gene-based delivery offer potential for localized, durable stabilization with minimal systemic toxicity. Conclusions: Integrating surgical and biologic therapies may shift IA management from reactive repair to rupture prevention.