Sudhir Bhanu Jayanand, Keelara Arun Gowda, Venkat Easwer Harihara, Kazumata Ken, Sundararaman Ananthalakshmy
1Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala State, India.
2Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan; and.
Neurosurg Focus. 2021 Sep;51(3):E6. doi: 10.3171/2021.6.FOCUS21281.
Moyamoya angiopathy (MMA) affects the distal internal carotid artery and is designated as moyamoya disease (MMD) when predisposing conditions are absent, or moyamoya syndrome (MMS) when it occurs secondary to other causes. The authors aimed to investigate the reason for this anatomical site predilection of MMA. There is compelling evidence to suggest that MMA is a phenomenon that occurs due to stereotyped mechanobiological processes. Literature regarding MMD and MMS was systematically reviewed to decipher a common pattern relating to the development of MMA.
A systematic review was conducted to understand the pathogenesis of MMA in accordance with PRISMA guidelines. PubMed MEDLINE and Scopus were searched using "moyamoya" and "pathogenesis" as common keywords and specific keywords related to six identified key factors. Additionally, a literature search was performed for MMS using "moyamoya" and "pathogenesis" combined with reported associations. A progressive search of the literature was also performed using the keywords "matrix metalloprotease," "tissue inhibitor of matrix metalloprotease," "endothelial cell," "smooth muscle cell," "cytokines," "endothelin," and "transforming growth factor" to infer the missing links in molecular pathogenesis of MMA. Studies conforming to the inclusion criteria were reviewed.
The literature search yielded 44 published articles on MMD by using keywords classified under the six key factors, namely arterial tortuosity, vascular angles, wall shear stress, molecular factors, blood rheology/viscosity, and blood vessel wall strength, and 477 published articles on MMS associations. Information obtained from 51 articles that matched the inclusion criteria and additional information derived from the progressive search mentioned above were used to connect the key factors to derive a network pattern of pathogenesis.
Based on the available literature, the authors have proposed a unifying theory for the pathogenesis of MMA. The moyamoya phenomenon appears to be the culmination of an interplay of vascular anatomy, hemodynamics, rheology, blood vessel wall strength, and a plethora of intricately linked mechanobiological molecular mediators that ultimately results in the mechanical process of occlusion of the blood vessel, stimulating angiogenesis and collateral blood supply in an attempt to perfuse the compromised brain.
烟雾病血管病（MMA）累及颈内动脉远端，在无易感因素时被称为烟雾病（MMD），继发于其他原因时则称为烟雾病综合征（MMS）。作者旨在探究MMA出现这种解剖部位偏好的原因。有确凿证据表明，MMA是一种由刻板的机械生物学过程导致的现象。对有关MMD和MMS的文献进行了系统综述，以解读与MMA发生相关的共同模式。
按照PRISMA指南进行系统综述，以了解MMA的发病机制。在PubMed MEDLINE和Scopus数据库中检索时，使用“烟雾病”和“发病机制”作为常见关键词以及与六个已确定关键因素相关的特定关键词。此外，使用“烟雾病”和“发病机制”并结合已报道的关联对MMS进行文献检索。还使用关键词“基质金属蛋白酶”“基质金属蛋白酶组织抑制剂”“内皮细胞”“平滑肌细胞”“细胞因子”“内皮素”和“转化生长因子”对文献进行逐步检索，以推断MMA分子发病机制中缺失的环节。对符合纳入标准的研究进行了综述。
通过使用归类于六个关键因素（即动脉迂曲、血管角度、壁面剪应力、分子因素、血液流变学/粘度和血管壁强度）下的关键词，文献检索得出44篇关于MMD的已发表文章，以及477篇关于MMS关联的已发表文章。从符合纳入标准的51篇文章中获取的信息以及上述逐步检索得出的其他信息，被用于将关键因素联系起来，以推导出发病机制的网络模式。
基于现有文献，作者提出了一种关于MMA发病机制的统一理论。烟雾病现象似乎是血管解剖结构、血流动力学、流变学、血管壁强度以及大量错综复杂相互关联的机械生物学分子介质相互作用的结果，最终导致血管闭塞的机械过程，刺激血管生成和侧支血液供应，以试图为受损的大脑供血。
