1Faculty of Medical Science and Research, Sai Nath University, Ranchi, Jharkhand-835219, India
2Department of Pharmacy, Shubham University, Bhopal, Madhya Pradesh-462010, India
Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the internal carotid arteries and their proximal branches, leading to the formation of characteristic collateral vessels that appear as a "puff of smoke" on angiography. This comprehensive review examines the global perspectives on MMD, focusing on its genetic underpinnings, diverse clinical presentations across different populations, and recent advances in diagnostic and surgical management approaches. The disease shows significant geographical and ethnic variations, with the highest prevalence observed in East Asian populations, particularly in Japan and Korea. Recent genetic studies have identified multiple susceptibility loci, including RNF213, ACTA2, and GUCY1A3, which contribute to our understanding of disease pathogenesis. Clinical manifestations vary considerably between pediatric and adult populations, with children typically presenting with ischemic symptoms and adults more commonly experiencing hemorrhagic complications. Diagnostic approaches have evolved with advanced neuroimaging techniques, including high-resolution MRI and computational fluid dynamics modeling. Surgical management strategies, particularly direct and indirect revascularization procedures, have shown significant improvements in patient outcomes. This review synthesizes current knowledge on MMD from a global perspective, highlighting regional differences in disease characteristics and management approaches while identifying areas for future research and collaborative efforts.
Moyamoya disease represents one of the most intriguing cerebrovascular disorders in contemporary neurology, characterized by its unique angiographic appearance and complex pathophysiology. First described by Takeuchi and Shimizu in 1957, the term "moyamoya" derives from the Japanese phrase meaning "puff of smoke," aptly describing the characteristic collateral vessel network observed on cerebral angiography (Suzuki & Takaku, 1969). Kuroda et al. (2014) established that MMD is defined by bilateral stenosis or occlusion of the terminal portions of the internal carotid arteries and the proximal segments of the anterior and middle cerebral arteries, accompanied by abnormal vascular networks in the basal region of the brain. The global significance of MMD has become increasingly recognized as diagnostic capabilities have improved and awareness has expanded beyond its initial description in Asian populations. Scott & Smith (2009) demonstrated that while the disease was originally thought to be confined to East Asian populations, cases have now been reported worldwide, revealing important ethnic and geographical variations in disease presentation and progression. Baba et al. (2008) highlighted that the bimodal age distribution of MMD, with peaks in childhood and middle age, presents unique challenges for both diagnosis and management across different healthcare systems globally. The complexity of MMD extends beyond its clinical presentation to encompass significant genetic, environmental, and demographic factors that influence disease manifestation and outcomes. Recent advances in molecular genetics, neuroimaging technologies, and surgical techniques have revolutionized our understanding and management of this condition, necessitating a comprehensive global perspective on current knowledge and future directions.
2. Epidemiology and Global Distribution
2.1 Geographical and Ethnic Variations
The epidemiological landscape of MMD reveals striking geographical and ethnic disparities that provide crucial insights into disease pathogenesis and risk factors. Uchino et al. (2005) conducted comprehensive epidemiological studies demonstrating that the highest prevalence of MMD occurs in East Asian countries, with Japan reporting an incidence of approximately 0.35 per 100,000 population annually. Yeon et al. (2014) confirmed similar patterns in South Korea, where the incidence has been steadily increasing, potentially due to improved diagnostic awareness and techniques. In contrast, Western populations show significantly lower incidence rates, with North American and European studies reporting rates approximately 10-fold lower than those observed in Asian populations. Ahn et al. (2014) analyzed this discrepancy and suggested that genetic factors play a predominant role in determining population susceptibility. Miao et al. (2010) extended these observations to demonstrate that even among Asian populations living in Western countries, the incidence remains elevated compared to the native population, supporting the genetic basis of disease susceptibility.
2.2 Age and Gender Distribution
The demographic characteristics of MMD exhibit consistent patterns across different populations, despite variations in overall incidence. Hallemeier et al. (2006) established that MMD demonstrates a characteristic bimodal age distribution, with the first peak occurring in the first decade of life and a second peak in the fourth and fifth decades. Kim et al. (2012) further refined these observations, noting that pediatric cases predominantly present with ischemic manifestations, while adult cases more frequently exhibit hemorrhagic complications. Gender distribution patterns show a consistent female predominance across all populations studied. Kraemer et al. (2008) reported female-to-male ratios ranging from 1.8:1 to 2.2:1 in most populations, with this pattern being particularly pronounced in adult-onset cases. Liu et al. (2015) suggested that hormonal factors may contribute to this gender bias, particularly in relation to pregnancy-associated exacerbations of the disease.
3. Genetic Foundations and Molecular Pathogenesis
3.1 Major Genetic Susceptibility Loci
The genetic architecture of MMD has been extensively elucidated through genome-wide association studies and linkage analyses across diverse populations. Kamada et al. (2011) identified RNF213 as the major susceptibility gene for MMD in East Asian populations, with the R4810K variant showing strong association with disease development. Liu et al. (2011) confirmed that this variant is present in approximately 95% of familial MMD cases and 79% of sporadic cases in Japanese populations. However, the genetic landscape varies significantly across different ethnic groups. Cecchi et al. (2014) demonstrated that RNF213 variants are much less common in European and North American MMD patients, suggesting population-specific genetic risk factors. Guey et al. (2017) identified additional susceptibility loci, including variants in ACTA2 and GUCY1A3 genes, which appear to be more relevant in non-Asian populations.
Arnab Roy*, Deep Jyoti Shah, Abhinav Kumar, Abhijit Kumar, Shruti Kumari, Niraj Kumar, Abhinav Keshri, Vivek Prajapati, Mukti Oraon, Pinky Kumari, Divya Kumari, Vishal Kumar, Bharti Kumari, Manvi Kumari, Aliya Neshab, Bunty Verma, Rajni Mariyam Marandi, Nikhil Kumar Sharma, Global Perspectives on Moyamoya Disease: Genetic Origins, Clinical Diversity and Innovations in Diagnosis and Surgical Management, Int. J. Sci. R. Tech., 2025, 2 (10), 124-134. https://doi.org/10.5281/zenodo.17297689
10.5281/zenodo.17297689
